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New insights in thyroid diagnosis and treatment

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Published: 02 December 2023
Volume 25 , pages 1–3, ( 2024 )

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Fabian Pitoia ORCID: orcid.org/0000-0002-2742-7085 1 &
Pierpaolo Trimboli ORCID: orcid.org/0000-0002-2125-4937 2 , 3

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The prevalence of thyroid disease continues to rise. As a consequence, the research in the thyroid field has significantly increased over time. Thus, clinicians, and endocrinologists first, have to be aware of the important continuous progress achieved, in particular of thyroid cancer, to better manage their patients. This themed issue, titled “New Insights in Thyroid Diagnosis and Treatment,” delves deep into contemporary hot topics in thyroid field. These papers included in the present issue are focused on several aspects in this area, such as imaging, molecular analysis, machine learning and radiomics, nuclear medicine, clinical, and laboratory. Seven papers centers around thyroid cancer. Three papers review imaging modalities for thyroid nodule/cancer assessment. Two papers report a comprehensive review of metabolic issues involving thyroid gland. Finally, a large overview about genetics of Graves’ disease is reported in another study. Clinicians will find this issue very interesting.

Overview of the 2022 WHO Classification of Thyroid Neoplasms

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Salivary gland pathologies: evolution in classification and association with unique genetic alterations

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The global prevalence of thyroid disease is alarmingly high and continues to rise, imposing a substantial burden on healthcare professionals. Among thyroid diseases, thyroid nodules (TNs) represent the most frequent with an estimated prevalence reaching approximately 60%, as ascertained through high-resolution thyroid ultrasound [ 1 ]. However, it is noteworthy that a limited proportion of patients diagnosed with thyroid diseases experience oncological or clinically severe thyroid disorders. For instance, only a minority of thyroid nodules (TNs), approximately 5%, ultimately will be malignant [ 1 , 2 ]. Although there are a number of studies suggesting that there might be environmental risk factors contributing to a larger diagnosis of thyroid cancer, most of the diagnosis can be attributable to the widespread use of ultrasonography, the generalized imaging screening of the thyroid gland, and the higher access to health care [ 2 , 3 , 4 , 5 ]. According to the National Cancer Institute from the United States of America, the incidence of these tumors has tripled over the last decades, with a low and stable mortality rate. Indeed, more than 60% of its incidence has been attributed to tumors smaller than 1 cm [ 6 ]. With this premises, clinicians, and endocrinologists first, have to be aware of significant continuous progress in the field of thyroid disease and in particular of thyroid cancer.

This themed issue, titled “New Insights in Thyroid Diagnosis and Treatment,“ delves deep into contemporary hot topics in thyroid field encompassing imaging, molecular, machine learning and radiomics, nuclear medicine, clinical, and laboratory aspects.

The central theme of seven papers featured in this issue is centered on thyroid cancer. Specifically, Smulever et al. delve into the contemporary subject of active surveillance (AS) of small papillary thyroid carcinoma (PTC). Several international institutions have been launched their protocols, despite ongoing debates surrounding the subject and the necessity for additional prospective evidence. A wealth of global experience underscores a notable trend among these tumors, characterized by minimal changes in size during the active surveillance period. These growth patterns frequently lean towards slow progression or even size reduction. The authors of this review propose a systematic framework for implementing active surveillance, underscoring the pivotal role of meticulous patient selection. A comprehensive update on the current state of molecular testing for thyroid nodules is reported by Ferraz C. Biopsy of TNs often faces the challenge of indeterminate samples (e.g., Bethesda III-IV). While, historically, these cases often led to surgical interventions with only a 20–30% of malignancy postoperatively, molecular tests have emerged as a beacon of hope. This review provides endocrinologists with a usable guide in this field.

Major guidelines underscore the significance of post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. The management of differentiated thyroid cancer (DTC) assessed with the initial risk of recurrence and the dynamic risk assessment to define additional treatments and the understanding of the meaning of the different responses to treatment and their impact in the long-term follow up is clearly discussed by Jerkovich et al. Additionally, in this special issue we find a thorough analysis of those patients with intermediate risk of recurrence. This topic is reported in a comprehensive overview by Padovani et al. with a particular focus on the nuanced criteria that should guide decisions regarding adjuvant therapy in the current era of personalized medicine. As result of that review, unlike their low- and high-risk counterparts, the literature available for intermediate-risk DTC is fraught with contradictions, and a consensus on adjuvant therapy remains elusive. Another paper from authors representing the Latin American Thyroid Society present the challenges for the management of radioiodine (RAI) refractory DTC in Latin America. Identifying RAI-refractoriness is often straightforward in specialized centers, but the timing for starting multikinase inhibitors (MKI), the availability of genomic testing, and the prescription of MKI and selective kinase inhibitors vary globally in Latin America. Access to MKI remains a hurdle across all Latin American countries, extending to new selective tyrosine kinase inhibitors requiring genomic testing, which is not widely accessible. As precision medicine advances, it reveals significant disparities, and despite efforts to enhance coverage and reimbursement, molecular-based precision medicine remains beyond reach for most of these countries. The authors call for attention in order to take urgent measures to bridge the gap between the current state-of-the-art care for RAI-refractory thyroid cancer and the existing situation in Latin America. The landscape of genetic alterations of differentiated thyroid cancer (DTC) in the pediatric population is explored by Alina de Sousa et al. Although an infrequent tumor occurring at this age and, despite its aggressive presentation, pediatric DTC exhibits an exceptional good prognosis when compared to its adult counterpart, being seldomly radioiodine refractory. This manuscript contributes to the elucidation of the global molecular landscape of pediatric thyroid cancer, highlighting prevalent alterations that serve as pivotal oncogenic drivers. Piccardo et al. perform a systematic review of the literature on the prognostic value of pre-ablative thyroglobulin levels (pa-Tg). The results of the retrieved studies provide compelling evidence of paTg’s prognostic value in pediatric DTC. Notably, pa-Tg cutoff values were identified as valuable markers. These findings are very useful for clinical practice. Both thyroid autoimmunity and thyroid malignancy are common clinical conditions, and there are clues that a common mechanism exists. This topic is investigated in another review by Valsecchi et al. This manuscript raises important insights that can help physicians to better personalize DTC patient’s clinical management. Additionally, Cunha Leite et al. helps us to understand the concomitant scenario of thyroid autoimmunity and thyroid cancer. Both conditions exhibit shared molecular signatures involving the programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) axis, suggesting a common underlying mechanism, and further investigation is warranted to elucidate the molecular link between these conditions for improved patient management.

Three papers included in the present issue are focused on imaging modalities for thyroid nodule/cancer assessment. One comprehensive narrative review by Bojunga et al. provides an overview of thyroid ultrasound (US) and its adjunctive techniques for the evaluation of thyroid nodules. The most relevant data about elastography, superb microvascular imaging, contrast-enhanced ultrasound, and multiparametric ultrasound, is summarized to expand the diagnostic spectrum and enrich the diagnostic toolkit. In addition, it is debated the potential role of artificial intelligence. An overview about machine learning and radiomics in nuclear medicine is also presented by Dondi et al. The fusion of these innovative technologies with nuclear medicine modalities has begun to unlock previously uncharted diagnostic possibilities. This systematic review unveiled a trove of seventeen studies where radiomics and ML flexed their diagnostic muscles across a spectrum of thyroid disease scenarios. From the assessment of thyroid incidentalomas at 18 F-FDG PET to the evaluation of cytologically indeterminate thyroid nodules and the classification of various thyroid diseases, these technologies showcased their versatility and potential. Imperiale et al. perform a comprehensive summary of most advanced molecular imaging modalities for the management of medullary thyroid carcinoma is included in this issue. This paper can guide endocrinologists and other thyroidologists towards a rationale for the use of these procedures also including theragnostic opportunities to personalize treatment.

Two papers report comprehensive review of metabolic issues involving thyroid. The matter of relationship between thyroid cancer and insulin is intriguing. A narrative review by Brenta et al. is focused on the topic of insulin resistance as the potential mediator of incidence and progression of differentiated thyroid carcinoma. A unanimous suggestion emerged from this paper – there exists a positive association with thyroid cancer. Similarly, in the realm of diabetes, support for a link with thyroid cancer was evident in four out of five publications. A nuanced narrative unfolded in the seven studies probing antidiabetic agents, with a noteworthy indication that metformin might hold promise in benefitting thyroid cancer outcomes. In another paper, the implication of microbiota in the thyroid field in fully explored by Virili et al. This systematic review of published reviews, summarizes the conclusion of 38 reviews, and then achieves very high interest. The conclusions are relevant for clinicians and advice for further studies in this emerging topic.

One large overview about genetics of Graves’ disease is reported in another paper by Grixti et al. Numerous genetic studies were reviewed and discoveries over years were outlined, starting with historic candidate gene studies and then exploring more recent ones. In addition, emerging evidences achieved were discussed. Clinicians have to be aware of these aspects to be capable to implement future targeted clinical therapies of Graves’.

In conclusion, the contents of the current REMD issue stand as a valuable resource for clinicians and clinical investigators specializing in thyroid disorders. The diverse array of papers presented not only deepens our understanding of critical aspects within this field but also serves as a catalyst for further exploration and advancements in thyroid disorder research. The collective insights offered in this issue contribute significantly to the ongoing dialogue, fostering a rich foundation for informed clinical practice and future investigative pursuits.

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No datasets were generated or analysed during the current study.

Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The diagnosis and management of thyroid nodules: a review. JAMA. 2018;319(9):914–24.

Article PubMed Google Scholar

Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid Cancer. Thyroid. 2016;26(1):1–133.

Article PubMed PubMed Central Google Scholar

Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017;317(13):1338–48.

Udelsman R, Zhang Y. The epidemic of thyroid cancer in the United States: the role of endocrinologists and ultrasounds. Thyroid. 2014;24(3):472–9.

Morris LG, Sikora AG, Tosteson TD, Davies L. The increasing incidence of thyroid cancer: the influence of access to care. Thyroid. 2013;23(7):885–91.

Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140:317–22.

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Head Thyroid Section, Division of Endocrinology, Hospital de Cl?nicas, University of Buenos Aires, Viamonte, Argentina

Fabian Pitoia

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Pierpaolo Trimboli

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Pitoia, F., Trimboli, P. New insights in thyroid diagnosis and treatment. Rev Endocr Metab Disord 25 , 1–3 (2024). https://doi.org/10.1007/s11154-023-09859-5

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Accepted : 27 November 2023

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DOI : https://doi.org/10.1007/s11154-023-09859-5

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The one-hundred most-cited articles focused on thyroid research: a bibliometric analysis

Affiliations.

1 Department of Radiology, Breast and Thyroid Cancer Center, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
2 Department of Radiology, Kangdong Seong-Sim Hospital, Hallym University College of Medicine, Seoul, South Korea - [email protected].
3 Department of Radiology, Ilsong Memorial Head and Neck-Thyroid Cancer Hospital, College of Medicine, Hallym University, Seoul, South Korea.
4 Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
5 Department of Radiology, Kangdong Seong-Sim Hospital, Hallym University College of Medicine, Seoul, South Korea.
6 Department of Otorhinolaryngology-Head and Neck Surgery, Ilsong Memorial Head and Neck-Thyroid Cancer Hospital, College of Medicine, Hallym University, Seoul, South Korea.
PMID: 28548477
DOI: 10.23736/S0391-1977.17.02629-3

Introduction: The number of citations that an article has received reflects its impact on a particular research area.

Evidence acquisition: We determined the one-hundred most-cited articles in thyroid research via the Institute for Scientific Information Web of Knowledge database, using the search term. The following parameters were used to analyze the characteristics of the 100 most-cited articles: publication year, journal (including subject category and impact factor), number of citations and annual citations, authors, department, institution, country, type of study, and topic.

Evidence synthesis: The number of citations for the 100 most-cited articles ranged from 2521 to 412 (mean, 643.4) and the number of annual citations ranged from 392.9 to 7.1 (mean, 38.0). The majority of articles were published in 2000-2009 (32%), published in endocrinology journals (29%), originated in the USA (70%), were clinical observation study (31%), and dealt with nodular thyroid disease (32%). Department of Internal Medicine, Johns Hopkins University School of Medicine and Department of Internal Medicine, Ohio State University College of Medicine (N.=6 each) were the leading institutions and Mazzaferri EL (N.=7) was the most prolific author.

Conclusions: Our study presents a detailed list and analysis of the 100 most-cited thyroid research articles, which provides a unique insight into the historical development in this field.

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Published: 24 November 2012

The thyroid gland and the process of aging; what is new?

Adam Gesing 1 ,
Andrzej Lewiński 2 , 3 &
Małgorzata Karbownik-Lewińska 1 , 2

Thyroid Research volume 5 , Article number: 16 ( 2012 ) Cite this article

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The endocrine system and particular endocrine organs, including the thyroid, undergo important functional changes during aging. The prevalence of thyroid disorders increases with age and numerous morphological and physiological changes of the thyroid gland during the process of aging are well-known. It is to be stressed that the clinical course of thyroid diseases in the elderly differs essentially from that observed in younger individuals, because symptoms are more subtle and are often attributed to normal aging. Subclinical hypo- and hyperthyroidism, as well as thyroid neoplasms, require special attention in elderly subjects. Intriguingly, decreased thyroid function, as well as thyrotropin (TSH) levels – progressively shifting to higher values with age – may contribute to the increased lifespan.

This short review focuses on recent findings concerning the alterations in thyroid function during aging, including these which may potentially lead to extended longevity, both in humans and animals.

Introduction

The endocrine system and particular endocrine organs, including the thyroid gland, undergo – similarly to other organ systems – crucial functional changes with aging. Numerous morphological and physiological changes of the thyroid during the process of aging are well-known [ 1 – 3 ]. A specificity of thyroid diseases in the elderly, differing essentially from that observed in younger subjects, relies on the presence of more subtle symptoms which are often attributed to normal aging. Therefore, subclinical hypo- and hyperthyroidism, as well as thyroid neoplasms, the prevalence of which increases with age, require special attention in elderly subjects. Interestingly, altered thyroid function may contribute to the extended longevity. The present review focuses on the newest findings concerning the alterations in thyroid function during the process of aging.

Thyroid dysfunction with aging

The process of aging affects both the prevalence and clinical presentation of hypo- and hyperthyroidism. Importantly, subclinical disturbances of thyroid function are more frequent than overt diseases in general population, as well as in elderly people [ 4 , 5 ]. Consistently, the prevalence of subclinical hypothyroidism, which is characterized by normal free thyroxine (FT 4 ) and elevated thyrotropin (TSH) levels, increases with aging [ 6 – 12 ] and ranges from 3 to 16% in individuals aged 60 years and older [ 13 ].

Although it is known that overt thyroid disorders negatively affect physical and cognitive function in elderly people – for example, overt hypothyroidism is associated with the impairment of attention, concentration, memory, perceptual functions, language, and executive functions [ 14 ], subclinical hypothyroidism is not associated with impairment of physical and cognitive function or depression in individuals aged 65 years and older, as compared to euthyroidism [ 15 ]. Also Park et al. [ 16 ] have demonstrated that subclinical hypothyroidism in elderly subjects is neither associated with cognitive impairment, depression, poor quality of life nor with metabolic disturbances. On the other hand, other studies demonstrated the presence of – at least – mild cognitive impairment in people with subclinical hypothyroidism at mean age under 65 years (reviewed in [ 17 ]). Furthermore, as reported by de Jongh et al. [ 15 ], subclinical hypothyroidism was also not associated with the increased overall mortality risk. Similar findings were shown by Rodondi et al. [ 18 ] who analyzed data from numerous large prospective cohorts and demonstrated that total mortality was not increased in subjects with subclinical hypothyroidism, although the risk of coronary heart disease (CHD) events and of CHD mortality increased with TSH levels 10 mIU/l or higher. Nevertheless, it should be emphasized that this analysis regarded numerous different populations (cohorts) which consisted of not only elderly people and that the effect in question, i.e. of increasing TSH level on CHD incidents was not influenced by age [ 18 ].

Undoubtedly, there are obvious indications for treatment of overt hypothyroidism. On the other hand, indications for treatment of subclinical hypothyroidism are still controversial. Despite improvement of lipid profile due to treatment of subclinical hypothyroidism, there is no clear evidence that this beneficial effect can be associated with decreased cardiovascular or all-cause mortality in elderly patients [ 19 ]. Furthermore, Parle et al. [ 20 ] have reported that L-thyroxine replacement therapy does not improve cognitive function in elderly individuals with subclinical hypothyroidism. When the natural history of subclinical hypothyroidism was evaluated in the elderly, the final results depended on the presence or absence of thyroid antibodies and on that to what extent TSH concentration was increased. Thus, a quite high rate of reversion of subclinical hypothyroidism to euthyroid status in adults aged at least 65 years with lower baseline TSH levels and antithyroid peroxidase antibody (TPOAb) negativity was observed [ 21 ]. In turn, higher TSH level and TPOAb positivity were independently associated with lower chance of reversion to euthyroidism [ 21 ]. Moreover, TSH levels ≥ 10 mIU/l were independently associated with progression to overt hypothyroidism [ 21 ]. Similar findings, showing that higher baseline TSH levels are associated with progression from subclinical to overt hypothyroidism and that higher TSH level (> 8 mIU/l) is a predictive value for development of overt hypothyroidism, were recently reported by Imaizumi et al. [ 22 ]. On the other hand, there is strong evidence that thyroid hypofunction may contribute to increased lifespan (see further in the text). Therefore, taking into account all mentioned observations, the replacement therapy with L-thyroxine is not uniformly recommended in elderly people with subclinical hypothyroidism.

In turn, subclinical hyperthyroidism, characterized by serum TSH levels below lower limit of the reference range and normal serum FT 4 levels, is observed in about 8% of individuals aged 65 years and older [ 23 ]. Subclinical hyperthyroidism may be associated in older adults with decreased bone mineral density and fractures [ 24 ], or cognitive impairment [ 23 ] (reviewed in [ 25 ]). Furthermore, subclinical hyperthyroidism is associated with increased risk of total, as well as CHD mortality and atrial fibrillation (AF) incidents [ 26 ]. The highest risks of CHD mortality and AF are observed in the case of TSH levels lower than 0.1 mIU/l [ 26 ]. Unexpectedly, de Jongh et al. [ 15 ] have reported that subclinical hyperthyroidism is not associated with impairment of physical and cognitive function or depression in elderly people, aged 65 years and older. These authors have also demonstrated that subclinical hyperthyroidism is not associated with the increased overall mortality risk [ 15 ]. Such results are quite difficult to explain. Presumably, that ambiguity in observations may result from differences in the number of individuals enrolled in particular studies or from follow-up duration. Interestingly, Rosario [ 27 ] has recently shown that progression of subclinical hyperthyroidism to overt hyperthyroidism in elderly patients is an uncommon observation. Nevertheless, since subclinical hyperthyroidism (and obviously, overt hyperthyroidism with increased T 4 level) may lead to increased risk of total, as well as CHD mortality, patients older than 65 years, with low TSH levels – particularly in case of toxic multinodular goitre or a solitary autonomous thyroid nodule – require proper medical treatment (e.g. [ 11 ]).

It should also be stressed that during aging, gender-specific alterations in TSH and free thyroid hormone levels were observed [ 28 ]. Namely, with increasing age in males there were decreases in free thyroid hormones but not in TSH concentrations. In turn, in females, the free thyroid hormone levels were not changed with aging but TSH level increased in age-dependent manner [ 28 ].

Most recent results indicate that even in euthyroid older men with normal levels of TSH, differences in FT 4 levels within the normal range predict specific health outcomes relevant to aging. For example, higher FT 4 within the normal range was independently associated with frailty in euthyroid men aged ≥70 years [ 12 ]. Moreover, higher FT 4 levels within the normal range were associated with lower hip bone mineral density, increasing bone loss and fracture risk in postmenopausal women [ 29 ]. Therefore, it seems that further studies are required to explain whether higher FT 4 levels contribute causally (or not) to the above mentioned poorer health outcomes. Moreover, it is of interest to clarify whether FT 4 levels in the low-normal range could be considered as potential biomarkers for healthy aging [ 12 ].

Although numerous studies demonstrate that the increased TSH level resulting from subclinical hypothyroidism further rises with aging [ 6 – 12 ], other findings suggest that aging is associated – in the absence of any thyroid disease – with lower TSH levels [ 30 – 35 ]. It has been known that TSH secretion in response to thyrotropin-releasing hormone (TRH) is reduced in aging individuals, and serum TSH level is usually lower in older than in young people in response to decreased thyroid hormone concentrations, suggesting a certain level of insensitivity of thyrotrophic cells in anterior pituitary, occurring with age; moreover, nocturnal surge of TSH is – to various degree – lost in the elderly (reviewed in [ 1 ]). On the other hand, Bremner et al. [ 10 ] have recently reported that the TSH increase – observed by other authors during aging – seems to be a consequence of age-related alteration in the TSH set point or reduced TSH bioactivity. Interestingly, the largest TSH increase is observed in people with the lowest TSH at baseline, and, in turn, people with higher baseline TSH levels had proportionally smaller increases in TSH concentrations [ 10 ]. It is worth adding that TRH and FT 4 serum levels do not differ between young, middle-aged and elderly subjects [ 34 ].

Thyroid dysfunction and longevity

As it has been mentioned above, the alterations in levels of hormones related to pituitary-thyroid axis are associated with the process of aging and, thus, may impact longevity. However, a direction of these changes, which may lead to increased lifespan, still seems to be not fully determined [ 6 – 12 , 30 – 35 ].

One should emphasize that the most striking findings concerning potential contribution of TSH and thyroid hormones to lifespan regulation, were obtained in the studies performed on centenarians (and almost centenarians). In 2009, Atzmon et al. [ 7 ] published the results of studies on thyroid disease-free population of Ashkenazi Jews, characterized by exceptional longevity (centenarians). They have observed higher serum TSH level in these subjects as compared to the control group consisted of younger unrelated Ashkenazi Jews, as well as to another control group obtained from The National Health and Nutrition Examination Survey (NHANES) program of studies [ 7 ]. Therefore, these findings appear to support previous observations, indicating that serum TSH shifts progressively to higher levels with age (e.g., [ 36 ]). Moreover, the authors have observed an inverse correlation between FT 4 and TSH levels in centenarians and Ashkenazi controls, and finally, they have distinctly concluded that increased serum TSH is associated with extreme longevity [ 7 ]. In another study, a role of genetic background, potentially responsible for the above-mentioned changes, was assessed [ 37 ]. It turned out that two (2) single nucleotide polymorphisms (SNPs) in TSH receptor (TSHR) gene, namely rs10149689 and rs12050077, were associated with increased TSH level in the Ashkenazi Jewish centenarians and their offspring [ 37 ].

The above-mentioned inverse correlation between FT4 and TSH in centenarians may suggest a potential role of decreased thyroid function in lifespan regulation, leading to remarkable longevity. Such a hypothesis seems to have been confirmed by the findings obtained in the Leiden Longevity Study, demonstrating the associations between low thyroid activity and exceptional familial longevity [ 38 ].

In turn, Corsonello et al. [ 39 ] have demonstrated that age is associated with a decrease in free triiodothyronine (FT 3 ) and FT 4 but not with increased TSH levels. Moreover, children and nieces/nephews of centenarians had lower FT 3 , FT 4 and TSH levels as compared to the age-matched subjects [ 39 ]. It may, at least partially, confirm an important role of low thyroid function in the regulation of lifespan.

It should be stressed that reduced thyroid function with low levels of T 4 is associated with extended longevity also in animals [ 40 – 42 ]. For example, a very severe thyroid hypofunction with reduced core body temperature, as observed in Ames dwarf (df/df) and Snell mice (characterized by mutations at the Prop-1 and Pit-1 gene, respectively, and demonstrating a lack of growth hormone (GH), prolactin and TSH), is considered to substantially contribute to remarkable longevity in these rodents [ 40 ]. Furthermore, severe hypothyroid Ames dwarfs and mice with targeted disruption of the growth hormone receptor/growth hormone binding protein gene (GH receptor knockout; GHRKO) with mild thyroid hypofunction, have decreased thyroid follicle size which may explain decreased thyroid hormone levels in these mutants [ 43 ].

Concluding, the findings in animals are consistent with the results obtained in humans and may confirm a relevant role of thyroid hypofunction in lifespan extension.

Thyroid cancerogenesis and aging processes

The prevalence of thyroid nodules and thyroid neoplasms is increased in the elderly. Among elderly people, males are at higher risk of cancer and thyroid cancer is more aggressive in men than in women [ 44 ].

Papillary thyroid carcinoma (PTC) is the most common endocrine malignant neoplasm in the older individuals. Women are affected by PTC two to three times more often than men [ 45 ]. Nevertheless, female-to-male ratio seems to decline with the process of aging [ 45 ]. Importantly, the mortality rate of PTC is usually higher in the elderly [ 46 ]. Presumably, it is a consequence of increased mitotic activity of these tumors and increased likelihood of distant metastases [ 46 ]. It is known that in general population patients with aggressive variants of PTC have higher risk for the metastatic disease development [ 47 ]. The potential role of NDRG2 gene expression in the development and progression of PTC is also raised [ 48 ]. It is worth recalling that mutated BRAF gene is an independent predicting factor of poor outcome in PTC and is related to advanced age [ 49 ].

Follicular thyroid carcinoma (FTC) occurs also often in older people and is the second most common and the second least aggressive thyroid cancer. This cancer is more likely to metastasize hematogenously to distant sites, resulting in a worse prognosis in comparison with PTC [ 44 ].

Medullary thyroid carcinoma (MTC), which derives from the parafollicular cells (C cells) of the thyroid gland, constitutes up to 5% of all thyroid malignancies. Its sporadic form, more frequent than is familial MTC, occurs more commonly in the older population [ 50 ].

Rapidly growing and typically very aggressive anaplastic (undifferentiated) thyroid carcinoma (ATC) is rare. However, one should strongly emphasize that its prevalence is considerably higher in older than in younger people. By the time of diagnosis, most patients have widespread local invasion and distant metastases. Age appears to be a strong predictor of poor prognosis in ATC [ 44 ].

Conclusions

The process of aging strongly affects entire endocrine system. Consistently, thyroid gland is also impacted by aging. One should emphasize that thyroid diseases-associated symptoms in the elderly people are very similar to symptoms of the normal aging. Therefore, broadening the knowledge on alterations in thyroid function, which may be observed during aging, appears to be very important and constitutes a challenge for thyroid researchers, given that some specific thyroid dysfunctions may contribute to lifespan extension.

Lewiński A, Sewerynek E, Karbownik M: Aging processes and the thyroid gland. In Aging and Age-Related Diseases: The Basics . Edited by: Karasek M. New York: Nova Science Publishers, Inc; 2006:131–172.

Google Scholar

Faggiano A, Del Prete M, Marciello F, Marotta V, Ramundo V, Colao A: Thyroid diseases in elderly. Minerva Endocrinol 2011, 36: 211–231.

CAS PubMed Google Scholar

Papaleontiou M, Haymart MR: Approach to and treatment of thyroid disorders in the elderly. Med Clin North Am 2012, 96: 297–310. 10.1016/j.mcna.2012.01.013

Article CAS PubMed Central PubMed Google Scholar

Cooper DS: Thyroid disease in the oldest old: the exception to the rule. JAMA 2004, 292: 2651–2654. 10.1001/jama.292.21.2651

Article CAS PubMed Google Scholar

Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ: Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004, 291: 228–238. 10.1001/jama.291.2.228

Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N: Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008, 148: 832–845.

Article PubMed Google Scholar

Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I: Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009, 94: 1251–1254. 10.1210/jc.2008-2325

Boucai L, Surks MI: Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice. Clin Endocrinol 2009, 70: 788–793. 10.1111/j.1365-2265.2008.03390.x

Article Google Scholar

Surks MI, Boucai L: Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab 2010, 95: 496–502. 10.1210/jc.2009-1845

Bremner AP, Feddema P, Leedman PJ, Brown SJ, Beilby JP, Lim EM, Wilson SG, O’Leary PC, Walsh JP: Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab 2012, 97: 1554–1562. 10.1210/jc.2011-3020

Cooper DS, Biondi B: Subclinical thyroid disease. Lancet 2012, 379: 1142–1154. 10.1016/S0140-6736(11)60276-6

Yeap BB: Hormones and health outcomes in aging men. Exp Gerontol 2012. in press, http://dx.doi.org/10.1016/j.exger.2012.07.012

Biondi B, Cooper DS: The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008, 29: 76–131.

Kramer C, von Muhlen D, Kritz-Silverstein D, Barrett-Connor E: Treated hypothyroidism, cognitive function, and depressed mood in old age: the Rancho Bernardo Study. Eur J Endocrinol 2009, 161: 917–921. 10.1530/EJE-09-0606

de Jongh RT, Lips P, van Schoor NM, Rijs KJ, Deeg DJ, Comijs HC, Kramer MH, Vandenbroucke JP, Dekkers OM: Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals. Eur J Endocrinol 2011, 165: 545–554. 10.1530/EJE-11-0430

Park YJ, Lee EJ, Lee YJ, Choi SH, Park JH, Lee SB, Lim S, Lee WW, Jang HC, Cho BY, Woo JI, Kim KW: Subclinical hypothyroidism (SCH) is not associated with metabolic derangement, cognitive impairment, depression or poor quality of life (QoL) in elderly subjects. Arch Gerontol Geriatr 2010, 50: e68-e73. 10.1016/j.archger.2009.05.015

Begin ME, Langlois MF, Lorrain D, Cunnane SC: Thyroid function and cognition during aging. Curr Gerontol Geriatr Res 2008. 10.1155/2008/474868

Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J, Thyroid Studies Collaboration: Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010, 304: 1365–1374. 10.1001/jama.2010.1361

Bensenor IM, Olmos RD, Lotufo PA: Hypothyroidism in the elderly: diagnosis and management. Clin Interv Aging 2012, 7: 97–111.

Parle J, Roberts L, Wilson S, Pattison H, Roalfe A, Haque MS, Heath C, Sheppard M, Franklyn J, Hobbs FD: A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study. J Clin Endocrinol Metab 2010, 95: 3623–3632. 10.1210/jc.2009-2571

Somwaru LL, Rariy CM, Arnold AM, Cappola AR: The natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study. J Clin Endocrinol Metab 2012, 97: 1962–1969. 10.1210/jc.2011-3047

Imaizumi M, Sera N, Ueki I, Horie I, Ando T, Usa T, Ichimaru S, Nakashima E, Hida A, Soda M, Tominaga T, Ashizawa K, Maeda R, Nagataki S, Akahoshi M: Risk for progression to overt hypothyroidism in an elderly Japanese population with subclinical hypothyroidism. Thyroid 2011, 21: 1177–1182. 10.1089/thy.2010.0411

Ceresini G, Lauretani F, Maggio M, Ceda GP, Morganti S, Usberti E, Chezzi C, Valcavi R, Bandinelli S, Guralnik JM, Cappola AR, Valenti G, Ferrucci L: Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J Am Geriatr Soc 2009, 57: 89–93. 10.1111/j.1532-5415.2008.02080.x

Article PubMed Central PubMed Google Scholar

Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, Lipscombe LL: Levothyroxine dose and risk of fractures in older adults: nested case–control study. BMJ 2011, 342: d2238. 10.1136/bmj.d2238

Mitrou P, Raptis SA, Dimitriadis G: Thyroid disease in older people. Maturitas 2011, 70: 5–9. 10.1016/j.maturitas.2011.05.016

Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, Iervasi G, Asvold BO, Sgarbi JA, Völzke H, Gencer B, Maciel RM, Mollinaro S, Bremner A, Luben RN, Maisonneuve P, Cornuz J, Newman AB, Khaw KT, Westendorp RG, Franklyn JA, Vittinghoff E, Walsh JP, Rodondi N, Thyroid Studies Collaboration: Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012, 172: 799–809. 10.1001/archinternmed.2012.402

Rosario PW: Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0.1 and 0.4 mIU/l: a prospective study. Clin Endocrinol 2010, 72: 685–688. 10.1111/j.1365-2265.2009.03696.x

Article CAS Google Scholar

Suzuki S, Nishio S, Takeda T, Komatsu M: Gender-specific regulation of response to thyroid hormone in aging. Thyroid Res 2012, 5: 1. 10.1186/1756-6614-5-1

Murphy E, Gluer CC, Reid DM, Felsenberg D, Roux C, Eastell R, Williams GR: Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of non-vertebral fractures in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab 2010, 95: 3173–3181. 10.1210/jc.2009-2630

Mariotti S, Franceschi C, Cossarizza A, Pinchera A: The aging thyroid. Endocr Rev 1995, 16: 686–715.

Chahal HS, Drake WM: The endocrine system and ageing. J Pathol 2007, 211: 173–180. 10.1002/path.2110

Ferrari E, Cravello L, Falvo F, Barili L, Solerte SB, Fioravanti M, Magri F: Neuroendocrine features in extreme longevity. Exp Gerontol 2008, 43: 88–94. 10.1016/j.exger.2007.06.010

Sell MA, Schott M, Tharandt L, Cissewski K, Scherbaum WA, Willenberg HS: Functional central hypothyroidism in the elderly. Aging Clin Exp Res 2008, 20: 207–210.

Mazzoccoli G, Pazienza V, Piepoli A, Muscarella LA, Inglese M, De Cata A, Giuliani F, Tarquini R: Hypothalamus-hypophysis-thyroid axis function in healthy aging. J Biol Regul Homeost Agents 2010, 24: 433–439.

Over R, Mannan S, Nsouli-Marktabi H, Burman KD, Jonklaas J: Age and the thyrotropin response to hypothyroxinemia. J Clin Endocrinol Metab 2010, 95: 3675–3683. 10.1210/jc.2010-0281

Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002, 87: 489–499. 10.1210/jc.87.2.489

Atzmon G, Barzilai N, Surks MI, Gabriely I: Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. J Clin Endocrinol Metab 2009, 94: 4768–4775. 10.1210/jc.2009-0808

Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, Beekman M, Frölich M, de Craen AJ, Westendorp RG, van Heemst D: Familial longevity is associated with decreased thyroid function. J Clin Endocrinol Metab 2010, 95: 4979–4984. 10.1210/jc.2010-0875

Corsonello A, Montesanto A, Berardelli M, De Rango F, Dato S, Mari V, Mazzei B, Lattanzio F, Passarino G: A cross-section analysis of FT3 age-related changes in a group of old and oldest-old subjects, including centenarians’ relatives, shows that a down-regulated thyroid function has a familial component and is related to longevity. Age Ageing 2010, 39: 723–727. 10.1093/ageing/afq116

Brown-Borg HM: Hormonal regulation of longevity in mammals. Ageing Res Rev 2007, 6: 28–45. 10.1016/j.arr.2007.02.005

Buffenstein R, Pinto M: Endocrine function in naturally long-living small mammals. Mol Cell Endocrinol 2009, 299: 101–111. 10.1016/j.mce.2008.04.021

Edrey YH, Park TJ, Kang H, Biney A, Buffenstein R: Endocrine function and neurobiology of the longest-living rodent, the naked mole-rat. Exp Gerontol 2011, 46: 116–123. 10.1016/j.exger.2010.09.005

Gesing A, Bartke A, Masternak MM, Lewiński A, Karbownik-Lewińska M: Decreased thyroid follicle size in dwarf mice may suggest the role of growth hormone signaling in thyroid growth regulation. Thyroid Res 2012, 5: 7. 10.1186/1756-6614-5-7

Rukhman N, Silverberg A: Thyroid cancer in older men. Aging Male 2011, 14: 91–98. 10.3109/13685538.2010.529195

Kilfoy BA, Devesa SS, Ward MH, Zhang Y, Rosenberg PS, Holford TR, Anderson WF: Gender is an age-specific effect modifier for papillary cancers of the thyroid gland. Cancer Epidemiol Biomarkers Prev 2009, 18: 1092–1100. 10.1158/1055-9965.EPI-08-0976

Toniato A, Bernardi C, Piotto A, Rubello D, Pelizzo MR: Features of papillary thyroid carcinoma in patients older than 75 years. Updates Surg 2011, 63: 115–118. 10.1007/s13304-011-0060-0

Chrisoulidou A, Boudina M, Tzemailas A, Doumala E, Iliadou PK, Patakiouta F, Pazaitou-Panayiotou K: Histological subtype is the most important determinant of survival in metastatic papillary thyroid cancer. Thyroid Res 2011, 4: 12. 10.1186/1756-6614-4-12

Mordalska A, Latek J, Ferenc T, Pomorski L, Gałecka E, Zygmunt A, Lewinski A: Evaluation of NDRG2 gene expression in primary papillary thyroid carcinoma and in metastases of this neoplasm to regional lymph nodes. Thyroid Res 2010, 3: 6. 10.1186/1756-6614-3-6

Ito Y, Higashiyama T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A: Risk factors for recurrence to the lymph node in papillary thyroid carcinoma patients without preoperatively detectable lateral node metastasis: validity of prophylactic modified radical neck dissection. World J Surg 2007, 31: 2085–2091. 10.1007/s00268-007-9224-y

Habra M, Sarlis NJ: Thyroid and aging. Rev Endocr Metab Disord 2005, 6: 145–154. 10.1007/s11154-005-1494-9

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Acknowledgements

Preparation of this review was supported by funds (2011/V/1 and 2011/VII/7) from the Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.

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Gesing, A., Lewiński, A. & Karbownik-Lewińska, M. The thyroid gland and the process of aging; what is new?. Thyroid Res 5 , 16 (2012). https://doi.org/10.1186/1756-6614-5-16

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Histiocytic lesion masquerading as papillary carcinoma thyroid-A case report

Kumar, Bipin; Chadha, Prerna; Singh, Tanwi; Kumar, Deepak 1

Department of Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

1 Department of Radio-Diagnosis, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

For correspondence: Dr. Prerna Chadha, Department of Pathology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna - 800 014, Bihar, India. E-mail: [email protected]

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Langerhans cell histiocytosis (LCH) is a rare clonal neoplasm derived from Langerhans-type cells that express CD 1a, langerin, and S 100 on immunohistochemistry. LCH usually involves multiple sites and multiple systems or multiple sites in a single system. Solitary LCH commonly involves the bones (especially the skull), lymph nodes, skin, and lungs. Solitary LCH of the thyroid is an extremely rare disease with a few reported cases in the indexed literature and poses a diagnostic dilemma for both the clinician and pathologist. Histopathology along with ancillary tests forms the gold standard for diagnosis. Surgical resection alone offers a good prognosis once multisystemic involvement has been ruled out. Herein is reported one such case of solitary LCH in a young male patient who remains disease-free after 2 years of follow-up.

INTRODUCTION

Langerhans cell histiocytosis (LCH) is defined as a clonal neoplasm derived from Langerhans-type cells that express CD 1a, langerin, and S 100 on immunohistochemistry. [ 1 ] LCH usually involves multiple sites and multiple systems or multiple sites in a single system. Solitary LCH commonly involves the bones (especially the skull), lymph nodes, skin, and lungs. Solitary LCH of the thyroid is a rare disease. [ 2 ] Herein we report one such case in a pediatric patient.

CASE REPORT

An 18-year-old male patient presented with a midline neck swelling of 6 months duration. The swelling was insidious in onset, painless, and gradually progressed to its present size. The patient did not give any history suggestive of hyper or hypothyroidism. There was no history of any lack of appetite or loss of weight. No other relevant medical history was present. On local examination, there was a diffuse enlargement of the thyroid (moving with deglutition). Both the right and left lobes measured approximately 5 × 5 cm in size. No cervical lymph nodes were palpable. The lab workup at our hospital showed a hemoglobin value of 14.6 g/dL and a total leukocyte count of 11,000/μL. The thyroid function tests, liver function tests, and kidney function tests were within normal limits. Ultrasound of the neck showed diffuse enlargement of the thyroid with altered echoes. Contrast-enhanced CT scan (CECT) showed a diffusely enlarged thyroid involving both lobes with heterogeneous attenuation. There was no evidence of any lymphadenopathy or infiltration into the trachea or surrounding tissues [ Figure 1 ]. Ultrasound of the abdomen did not reveal any organomegaly.

Cytopathological findings

Fine needle aspiration was performed that yielded hypercellular smears and showed a singly dispersed and loosely cohesive population of large cells having ovoid to convoluted nuclei, many of which showed a prominent nuclear grooving. Admixed lymphohistiocytic cells and some eosinophils were also seen. The report was suggestive of papillary carcinoma thyroid with a background of thyroiditis [ Figure 2 ]. Total thyroidectomy with nodal excision was performed and the histopathological findings are as below.

Histopathological findings

Sections showed a nodular proliferation of sheets and groups of round to oval pale neoplastic cells with intervening normal-appearing thyroid follicles. These cells had moderate pale eosinophilic cytoplasm with ovoid to convoluted nuclei having delicate chromatin and grooved nuclei. Admixed lymphocytes, some eosinophils, and occasional multinucleate giant cells were also seen. Focal areas showed infiltration of thyroid follicular epithelium with the presence of these cells in the follicular lumina [ Figure 3a - c ]. No papillae formation, significant atypia, nuclear psedoinclusions, or mitoses were seen. On immunohistochemistry (IHC), the neoplastic cells expressed S 100 (cytoplasmic and nuclear), CD 1a (diffuse and strong membranous), and CD 68 (focal) [ Figure 3d - f ] while being negative for pancytokeratin and TTF-1. A diagnosis of LCH of the thyroid gland was rendered and the aspirate slides were reviewed.

Further workup for the patient in the form of a whole body bone scan, skull X-ray, high-resolution CT scan (HRCT) of the chest along with bone marrow examination was performed, all of which ruled out multisystemic involvement. Hence, a final diagnosis of a single system, unifocal involvement of the thyroid gland by LCH was made. The patient remains symptom-free after 2 years of follow-up, with no evidence of any systemic disease.

LCH is a rare neoplastic proliferation of Langerhans-type cells with an incidence rate of 5 cases per 1 million population. [ 1 ] LCH commonly presents in the pediatric population; however, it may also affect adults. It can present as a multisystemic disease, multiple sites within a single system, or can even be localized to a single site. Solitary involvement of the thyroid is extremely rare and there is scarce literature available in published English literature pertaining to it. Patten et al . [ 2 ] reported only 13 cases with a solitary thyroid involvement of LCH amongst a total of 66 cases. It often presents a diagnostic dilemma for both the clinician and the pathologist due to its rarity. [ 3 , 4 ] Fine needle aspiration cytology (FNAC) of the thyroid is an important modality for diagnosing thyroid lesions. However, LCH thyroid is often misdiagnosed on aspirate with a varied differential diagnosis, encompassing both benign and malignant diseases. [ 2 , 4 , 5 ] It may uncommonly be associated with primary thyroid malignancies. [ 6 ]

In our case too, the diagnosis rendered on fine needle aspirate cytology was Papillary carcinoma based on the cellularity, poorly cohesive clusters of cells, and nuclear grooving. The lymphohistiocytic cells and a few eosinophils in the background were attributed to lymphocytic thyroiditis, which can be an associated finding. The diagnostic criteria defined by the Histiocyte Society emphasize the morphologic identification of the characteristic LCH cells along with positive staining of the lesional cells with CD1a and/or Langerin (CD207). [ 7 ] Electron microscopy reveals Birbeck granules on ultrastructural examination.

Histopathological and immunohistochemical examinations performed on the thyroidectomy specimen in this case aided in the final diagnosis of this case. LCH thyroid usually has a multisystemic involvement at presentation commonly seen in adult patients. [ 2 ] Our case represents the 14 th case of solitary thyroid involvement with LCH and the 2 nd case reported in the pediatric age group so far.

Further workup and imaging to rule out a multisystemic involvement are imperative for deciding the therapy. Surgical resection with or without adjuvant chemoradiation is the management of choice for a single-system unifocal disease, which has a good prognosis. [ 8 ] Most cases of thyroid LCH respond well to therapy with low rates of recurrence. [ 9 ] Our patient underwent no further treatment after thyroidectomy and remains symptom-free after 2 years and 11 months of follow-up.

Solitary Langerhans cell histiocytosis of the thyroid is a rare neoplasm posing a diagnostic dilemma for both the clinician and the pathologist. The key to recognizing the disease lies in the knowledge of its existence with a high index of suspicion. Cytopathological examination revealing histiocytes with nuclear grooving and indentation along with eosinophils and lack of significant atypia should caution the pathologist before making a diagnosis of epithelial malignancy. Histopathological examination with immunohistochemistry aids in the definitive diagnosis. This case represents one such example and contributes to the scarce literature pertaining to solitary thyroid LCH, which has a good prognosis. Extensive workup and investigations are however required to rule out the possibility of a multisystemic disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest.

There are no conflicts of interest.

Acknowledgments

The authors thank the technical staff of the laboratory medicine department for their skillful assistance.

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v.9(1); 2020 Feb

Hyperthyroidism

Hyperthyroidism is a condition where the thyroid gland produces and secretes inappropriately high amounts of thyroid hormone which can lead to thyrotoxicosis. The prevalence of hyperthyroidism in the United States is approximately 1.2%. There are many different causes of hyperthyroidism, and the most common causes include Graves’ disease (GD), toxic multinodular goiter and toxic adenoma. The diagnosis can be made based on clinical findings and confirmed with biochemical tests and imaging techniques including ultrasound and radioactive iodine uptake scans. This condition impacts many different systems of the body including the integument, musculoskeletal, immune, ophthalmic, reproductive, gastrointestinal and cardiovascular systems. It is important to recognize common cardiovascular manifestations such as hypertension and tachycardia and to treat these patients with beta blockers. Early treatment of cardiovascular manifestations along with treatment of the hyperthyroidism can prevent significant cardiovascular events. Management options for hyperthyroidism include anti-thyroid medications, radioactive iodine, and surgery. Anti-thyroid medications are often used temporarily to treat thyrotoxicosis in preparation for more definitive treatment with radioactive iodine or surgery, but in select cases, patients can remain on antithyroid medications long-term. Radioactive iodine is a successful treatment for hyperthyroidism but should not be used in GD with ophthalmic manifestations. Recent studies have shown an increased concern for the development of secondary cancers as a result of radioactive iodine treatment. In the small percentage of patients who are not successfully treated with radioactive iodine, they can undergo re-treatment or surgery. Surgery includes a total thyroidectomy for GD and toxic multinodular goiters and a thyroid lobectomy for toxic adenomas. Surgery should be considered for those who have a concurrent cancer, in pregnancy, for compressive symptoms and in GD with ophthalmic manifestations. Surgery is cost effective with a high-volume surgeon. Preoperatively, patients should be on anti-thyroid medications to establish a euthyroid state and on beta blockers for any cardiovascular manifestations. Thyroid storm is a rare but life-threatening condition that can occur with thyrotoxicosis that must be treated with a multidisciplinary approach and ultimately, definitive treatment of the hyperthyroidism.

Introduction

Hyperthyroidism is defined as an inappropriately high synthesis and/or secretion of thyroid hormones from the thyroid gland. Thyrotoxicosis is the clinical condition where the effect of excess thyroid hormone on the tissues causes systemic clinical manifestations ( 1 ). The prevalence of hyperthyroidism in the United States is 1.2% with overt hyperthyroidism accounting for 0.5% and subclinical hyperthyroidism accounting for 0.7% ( 1 - 3 ). In this review, we will discuss the causes of hyperthyroidism, the clinical manifestations and how to diagnose it, and the different management options for the most common types of hyperthyroidism, including thyroid storm (TS), a rare but serious complication of hyperthyroidism.

The most common causes of hyperthyroidism are Graves’ disease (GD), followed by toxic multinodular goiters (TMNG) and toxic adenomas (TA). GD is an autoimmune condition that occurs with the loss of immunotolerance causing thyrotropin receptor antibodies (TRAb) to form, bind and subsequently stimulate the thyroid stimulating hormone (TSH) receptors. This causes increased thyroid hormone synthesis and secretion ( 4 ). Non-toxic nodular goiters can sporadically develop and become autonomous overtime causing hyperthyroidism ( 5 ). These conditions demonstrate autonomous hormone production, which can be from mutations of genes that regulate thyroid hormone synthesis or the TSH receptor causing familial and sporadic non-autoimmune hyperthyroidism ( 6 ). The prevalence of TAs and TMNGs increases with age and iodine deficiency ( 1 ).

Other causes of hyperthyroidism include iodine-induced, TSH-producing pituitary tumors, trophoblastic and germ cell tumors, struma ovarii, thyroid cancer, silent or painless thyroiditis from pregnancy or medications such as lithium or tyrosine kinase inhibitors, painful thyroiditis from infections, amiodarone-induced thyroiditis, and exogenous thyroid hormone intake ( 1 , 4 , 7 , 8 ). Hyperthyroidism in pregnancy can be overt hyperthyroidism, most commonly from GD ( 4 ), or subacute thyroiditis in the post-partum period. This type of thyrotoxicosis is usually self-limited followed by a period of hypothyroidism and then recovery of thyroid function ( 9 ). Therefore, anti-thyroid medications and radioactive iodine (RAI) treatment are not recommended. Painless or postpartum thyroiditis can recur in subsequent pregnancies so these patients should have continued monitoring. Painful thyroiditis is typically from an infection and is self-limited. Treatment can include beta blockers for symptoms associated with any thyrotoxicosis, non-steroidal anti-inflammatories and steroids for severe cases.

Amiodarone-induced thyroiditis can present as either type I or type II ( 4 ). Type I occurs from underlying TMNG or GD that are exposed to high iodine content from amiodarone causing excess thyroid hormone production. Treatment includes anti-thyroid medications and potassium perchlorate. Type II is a destructive thyroiditis from the toxicity of amiodarone on thyroid cells. It is usually self-limited, may not require discontinuation of amiodarone, and treatment includes steroids or surgery for refractory disease.

Presentation and diagnosis

Biochemical.

TSH is the most sensitive and specific first-line biochemical test to examine thyroid function ( 10 ). Confirmatory testing with free T4 and total serum T3 can be done for high suspicion of thyrotoxicosis or to further evaluate an abnormal TSH level. Some laboratory protocols add on a free T4 and total T3 when the initial TSH is low to avoid subsequent phlebotomy. Overt hyperthyroidism will show low TSH and high T3/T4 levels while subclinical hyperthyroidism will show low TSH with normal T3/T4 levels. GD will usually have positive TRAbs ( 1 ).

A ratio of the total T3 to total T4 can be calculated to help distinguish the etiology of thyrotoxicosis. Overt hyperthyroidism will produce more T3, creating a high T3:T4 ratio. Thyroiditis will have higher T4 levels creating a low T3:T4 ratio ( 11 ). Exogenous ingestion of thyroid hormone will present with low thyroglobulin levels, which is released from the thyroid gland with thyroid hormones, and a low T3:T4 ratio.

Other more rare etiologies can cause abnormal thyroid function tests. Euthyroid hyperthyroxinemia can occur in certain circumstances when the free T4 and total T3 are high, without a low TSH, due to abnormal protein binding (pregnancy, estrogen therapy, hepatitis, acute intermittent porphyria, medications or drug abuse, and high altitudes) ( 12 ). High doses of biotin can interfere with assays and cause falsely elevated T4 levels because biotin competes with biotinylated analogues in the binding assay. Patients should stop biotin for at least 2 days before having TSH and T4 tested ( 1 ).

While thyroid function tests can confirm a diagnosis of hyperthyroidism, it doesn’t necessarily clarify the etiology. A clinical diagnosis of GD can be made if the thyroid gland is diffusely enlarged, there is moderate to severe thyrotoxicosis, and Graves’ ophthalmopathy (GO) is present. If the clinical diagnosis is not clear due to lack of GO, a TRAb level can be obtained and a positive TRAb confirms the diagnosis. If the TRAb is negative or unclear, a RAI uptake (RAIU) scan can be done to distinguish GD from other etiologies ( 1 ). Studies have shown that in the United States, testing TRAb over RAIU reduces costs and gives a faster diagnosis ( 13 ). Patients with autoimmune causes of their hyperthyroidism often will have thyroid peroxidase antibodies as well.

The clinical manifestations of hyperthyroidism can be diverse as thyroid hormones can have an impact on a variety of systemic symptoms. The cellular effects of T3 binding to alpha and beta receptors increases thermogenesis and basal metabolic rates. This can result in constitutional symptoms of weight loss, fatigue and heat intolerance. Skin changes can occur including warm, moist skin with thinning of hair and pretibial myxedema in GD. Musculoskeletal manifestations include weakness, increased bone resorption, osteoporosis and increased risk of fracture. Patients can develop lymphadenopathy, gynecomastia in men or oligomenorrhea in women. Gastrointestinal (GI) manifestations include dysphagia, hyperdefecation and hunger ( 7 ). Ophthalmologic findings include lid retraction and infiltrative GO can be seen in patients with GD ( 1 , 14 ). Older age, smoking, longer duration of symptoms and female gender are risk factors associated with GO ( 15 ).

Significant cardiovascular manifestations are common in hyperthyroidism and it is important to recognize and treat them appropriately ( 7 ). The most common cardiovascular manifestations of hyperthyroidism are hypertension (HTN) and tachycardia. Approximately, 10% of the total population has HTN from secondary causes including endocrine etiology, and HTN may be the first presentation of a primary endocrine pathology ( 8 ). The pathophysiology of HTN with hyperthyroidism is multifaceted. Under normal conditions, the tissue effects of T3 are important for homeostasis. Problems occur when T3 is in excess because it directly increases cardiac contractility and ( 8 , 16 ) dilates arterioles, which decreases systemic vascular resistance and arterial filling. In turn, this stimulates renin release and activation of the angiotensin-aldosterone axis ( 17 ). Additionally, thyroid hormone targets certain ion channels including calcium/calmodulin-dependent kinase IV which plays a role in endothelial nitric oxide synthase activity contributing to control of vascular tone and blood pressure regulation ( 8 , 18 , 19 ). Thus, thyrotoxicosis is associated with arterial stiffness ( 20 ). Thyroid hormone excess also causes higher levels of atrial natriuretic peptide, brain natriuretic peptide, endothelin-1, vasodilating polypeptide adrenomedullin, and erythropoietin which all effect hemodynamics ( 8 , 16 , 21 , 22 ).

The clinical presentation will be HTN, tachycardia, and increased cardiac output which is similar in presentation to increased adrenergic activity, yet catecholamines may be low or normal in hyperthyroidism ( 22 , 23 ). Atrial fibrillation and congestive heart failure (CHF) can occur as well. Older age, higher T4 levels, male gender and toxic nodules are associated with a risk of atrial fibrillation. Early studies show that heart failure develops in 6–16% of patients with hyperthyroidism, but even higher rates are expected if there is underlying cardiovascular disease ( 8 ). Atrial fibrillation is an independent risk factor for developing heart failure ( 24 ). These cardiovascular manifestations can be reversible following treatment of hyperthyroidism and achieving a euthyroid state ( 24 , 25 ).

Treatment of cardiovascular manifestations should be in conjunction with treatment of the hyperthyroidism. Studies show that patients with untreated or insufficiently treated hyperthyroidism, compared to those who are treated, are at significantly higher risk of adverse cardiovascular events. Timely treatment and careful monitoring of hyperthyroid patients can help to reduce this risk ( 26 ). The recommended treatment for patients with hyperthyroidism is to block the cardiovascular effects with beta blockers. If there is a contraindication to beta blockers, angiotensin-converting enzyme (ACE)-inhibitors or calcium-channel blockers can be used ( 8 , 27 ).

There is evidence that subclinical hyperthyroidism can increase the risk of cardiovascular events, yet it has not necessarily been proven to be associated with HTN. Nonetheless, many authors recommend treatment of subclinical hyperthyroidism to prevent cardiovascular risk, among other reasons ( 8 , 28 ).

Once biochemical and clinical features have been identified, imaging modalities such as ultrasound and RAIU scans play an important role in diagnosis and treatment planning. A RAIU scan can distinguish between GD and TAs or TMNGs. In GD, the scan will show diffuse RAIU throughout the gland. A TMNG will show irregular patterns of uptake and a TA will show a localized area of uptake with no uptake in the remaining gland ( 4 ). In certain conditions when there is an acute release of excess thyroid hormone but no ongoing overproduction, there will be no RAIU. These conditions include painless thyroiditis, amiodarone-induced thyroiditis, subacute thyroiditis, palpation (surgical manipulation) thyroiditis, iatrogenic thyrotoxicosis, factitious ingestion of thyroid hormone, struma ovarii, and metastatic disease from follicular thyroid cancer ( 1 ).

Ultrasound with the use of color flow doppler can be an alternative method to help with the diagnosis, especially when a RAIU scan is contraindicated (pregnancy, breast feeding, allergies). In expert hands, the thyroidal blood flow can be measured and can help distinguish between GD which will show diffuse increased blood flow, thyroiditis which may show patchy areas of increased flow ( 29 , 30 ), or a toxic nodule which will show nodular disease with a normal thyroid in the background.

The treatment options for hyperthyroidism are based on the cause and include medical management with beta blockers or anti-thyroid medication, RAI and surgery. For GD, the most recent 2016 American Thyroid Association (ATA) Guidelines consider RAI, anti-thyroid medications or surgery all reasonable effective options. For TAs and TMNGs, RAI and surgery are typically recommended with anti-thyroid medications used only for short-term management ( 1 ). Each treatment modality has advantages and disadvantages that need to be considered. These options are preference-sensitive meaning that the patient and provider must discuss the tradeoffs for each individual ( 31 ).

Anti-thyroid and other medications

Generally, anti-thyroid medications are used as a bridging therapy to establish euthyroidism in preparation for a definitive treatment such as RAI or surgery ( 7 ). Patients that wish to avoid the risks of surgery or RAI may choose long-term anti-thyroid medications. However, the risks of anti-thyroid medication include potential serious side effects, risk of relapse or persistent hyperthyroidism, lack of definitive treatment, and a longer interval to establish a euthyroid state.

The primary anti-thyroid medications are propylthiouracil (PTU) and methimazole. They don’t demonstrate peak efficacy for 4–6 weeks, so most patients need beta blockers for immediate symptomatic relief of thyrotoxicosis. Beta blockers are recommended in all patients with symptomatic thyrotoxicosis, elderly patients, and those with tachycardia or co-existing cardiovascular disease ( 1 ). Beta blockers are contraindicated in patients with bronchospastic asthma, and in such cases ACE-inhibitors or calcium-channel blockers (diltiazem, verapamil) can be used ( 8 , 27 ). Beta blockers inhibit the conversion of T4 to T3 while controlling tachycardia and tremor. Propranolol is the most commonly used medication and is dosed at 10–40 mg 4 times a day ( 7 ).

Methimazole is recommended as first-line treatment, except during pregnancy when PTU is preferred due to the teratogenic effects of methimazole. Methimazole is generally preferred due to better efficacy ( 32 ), longer half-life and duration of action ( 4 , 33 ) allowing for once a day dosing, and less side effects compared to PTU. Methimazole is started at 10–30 mg daily and PTU is started at 100 mg 3 times daily ( 7 ). Methimazole inhibits the early step in thyroid hormone synthesis by inhibiting thyroid peroxidase ( 34 ), and also may inhibit thyroglobulin synthesis ( 35 ). PTU inhibits new hormone synthesis but also decreases the conversion of T4 to T3 in the periphery ( 34 ).

When starting anti-thyroid medications, it is recommended to obtain a baseline set of labs to check complete blood count and liver enzymes due to the potential side effects, which are overall rare. Common minor side effects include fever, rash, pruritus, hair loss, lymphadenopathy, headache, myalgias and arthralgias. More severe side effects include agranulocytosis, hepatotoxicity, vasculitis, lupus-like syndrome, and neuritis ( 7 , 34 ). It is recommended to check a free T4 and T3 at 2–6 weeks after initial therapy and adjust dosing according to the levels. It is not recommended to check TSH because it may remain suppressed for months ( 1 , 7 ). Once euthyroidism is achieved, the dose can be decreased by 30–50% with continued monitoring every 4–6 weeks ( 1 ). Additional white blood cell counts should be obtained in any febrile patients, and a liver panel should be sent in any patients who develop jaundice, pruritic rash, dark urine, light stools, joint or abdominal pain. There are no recommendations for routine monitoring of these labs once established on anti-thyroid medications, so it is provider preference ( 1 ).

Anti-thyroid medications should be discontinued after 12–18 months if a patient is considered in remission with normal TSH and TRAb (in the case of GD) ( 1 , 4 , 34 ). Remission can be defined by normal thyroid function tests after 1 year. Approximately, half of patients taking anti-thyroid medications will enter remission but this can vary from 30% to 70% depending on clinical and geographical population factors ( 34 , 36 ). Once a patient is able to stop their anti-thyroid medication, the ATA guidelines recommend thyroid function tests to be monitored every 2–3 months for the 1 st 6 months, every 4–6 months for the next 6 months and then every 6–12 months ( 1 ).

Patients need to be educated about symptoms of hyperthyroid returning in relapse, which can happen years later ( 1 ). Higher doses of anti-thyroid medications and longer courses of treatment do not increase the chance of remission, but only increase side effects, so this practice is not recommended ( 1 , 37 , 38 ). In GD, TRAb levels prior to discontinuing the medication may predict which patients can be successfully weaned. Those more likely to relapse are younger, have severe disease with large goiters, high T3/T4 levels, persistent suppression of TSH ( 4 , 39 ), high baseline levels of TRAb ( 40 ) or persistent elevated TRAbs and should be considered for definitive treatment with RAI or surgery ( 1 , 41 ). Continued low dose anti-thyroid medical treatment can be considered in mild disease or with contraindications to definitive treatment. A recent analysis of patients who relapsed after medical treatment compared follow up RAI ablation versus continued medical therapy and found the medical therapy group had less GO, less persistent thyroid disfunction, and less weight gain ( 42 ). In select patients, the authors of some studies have found long-term anti-thyroid medication treatment to be safe ( 43 ).

Advantages of RAI include avoidance of surgical risk and potential avoidance of hormone replacement therapy. Yet, the disadvantages include a risk of treatment failure and persistent hyperthyroidism requiring either re-treatment with more RAI or subsequent surgery and a longer interval to reach a euthyroid or hypothyroid state ( 44 ). RAI treatment should be considered in the elderly, those with significant co-morbidities, contraindications for surgery, previous neck radiation, small goiters, and limited access to high volume surgeons ( 1 ). It is contraindicated in pregnancy or those planning a pregnancy and in those who cannot comply with radiation safety guidelines. RAI should be used with extreme caution in GD as it can exacerbate GO ( 45 , 46 ). RAI treatment with steroids can be considered in the absence of GO and in mild GO in non-smokers, but it should be avoided in moderate to severe GO ( 1 ).

Clinical exacerbation of hyperthyroidism and even TS can occur with RAI, especially in the elderly and those who have comorbidities that may increase the risk of thyrotoxicosis ( 47 , 48 ) including cardiovascular disease, atrial fibrillation, heart failure, pulmonary HTN, diabetes, renal failure, infection, trauma, or cerebrovascular disease. These patients should be given beta blockers ( 1 , 21 , 49 ) and be considered for methimazole treatment before and after RAI treatment. In individuals who will benefit from pre-treatment with methimazole, the recommendation is to give it prior to RAI but discontinue it 2–3 days prior to RAI treatment, and then resume 3–7 days after RAI treatment with a taper while thyroid function tests should simultaneously normalize. Young healthy individuals who are clinically well compensated should be able to tolerate RAI without pre-treatment ( 1 ). In patients who are not pre-treated, thyroid levels should stabilize or decrease in the first month after RAI ( 50 ).

A typical average dose of RAI is 10–15 mCi. The dose can be given in a fixed dose or calculated based on the RAIU by the thyroid gland and the size of the gland with comparable successful treatment outcomes ( 51 ). A pregnancy test should be done prior to treating. Dosing must be carefully considered in patients on dialysis and with jejunostomy or gastric feeding tubes. It is recommended to avoid high iodine diets and foods for 1 week prior to treatment ( 1 ).

After RAI treatment, it is recommended to recheck thyroid function tests within 1–2 months. Monitoring should be continued every 4–6 weeks for at least 6 months or until achievement of hypothyroidism with a stable dose of thyroid hormone replacement. Most patients respond to treatment in 4–8 weeks, meaning clinical symptoms improve and thyroid function tests are normalized or even show a hypothyroid state. Starting thyroid hormone replacement depends on thyroid function tests and clinical symptoms. Patients are biochemically hypothyroid when their free T4 is below normal. Thus, thyroid hormone replacement therapy can be instituted at that time with further adjustments based on continued free T4 monitoring. TSH levels may be suppressed for months, so this lab should not be used to determine the timing of initiation of thyroid hormone replacement ( 7 ). Beta blockers can be tapered and other medical therapy can be stopped after successful RAI treatment.

The success rate of RAI varies depending on the definition of success, the etiology of hyperthyroidism and the dose given. Thankfully, RAI treatment for the 3 most common causes of hyperthyroidism is generally successful. One study evaluated RAI treatment in GD, TA, and TMNG. The authors reported successful RAI treatment, defined as subsequent hypothyroid or euthyroid state, to be 87.1% in GD, 93.7% in TA and 81.1% in TMNG ( 52 ). For patients with GD who are unresponsive to RAI, have persistent enlarged glands, higher T4 levels or continued symptoms of hyperthyroidism, re-treatment with a higher dose of RAI can be considered at 6 months (3 months in select patients) ( 1 ). The goal of re-treatment should be hypothyroidism ( 1 ) and some authors recommend re-treatment with a higher dose of RAI ( 53 ). One single-institution study found a RAI failure rate of 23% and reported certain predictors of failure to be more severe tachycardia at presentation, more severe laboratory abnormalities, and low doses of RAI <13 mCi ( 54 ). This was consistent with other literature regarding dosing ( 53 ). Providers often lack selection criteria between RAI and surgery for follow-up treatment after failed RAI, other than the known contraindications for either ( 55 ). Often times patients are referred to surgeons after RAI has failed, however surgery after fibrosis caused by RAI can be more challenging.

RAI and cancer risk

Postoperative RAI for thyroid cancer has been shown to increase the risk of second primary malignancies, including bone, leukemia, soft tissue sarcomas, salivary gland and GI tract as these doses are usually >100 mCi ( 56 , 57 ). Studies have been inconclusive for the risk of developing site-specific cancers after treatment with RAI for hyperthyroidism ( 56 , 58 - 60 ). Doses of RAI are much less (10–15 mCi) for hyperthyroidism compared to postoperative cancer treatment, and absorption of radiation varies in different organs ( 1 , 56 ). However, given the significant retained uptake within the thyroid gland in hyperthyroidism, the total body radiation exposure may actually be higher in treatment for hyperthyroidism versus cancer.

In 1998, the Cooperative Thyrotoxicosis Therapy Follow-up Study Group determined RAI did not contribute to an increased risk of total cancer mortality and was safe ( 61 ). More recent studies however, have shown mixed results. Some authors report a higher incidence of stomach, kidney and breast cancers in those who underwent RAI ablation for hyperthyroidism ( 58 ). Others show no increase in overall cancer risk, but suspect trends towards increased risk in thyroid, kidney, stomach and respiratory tract cancers. The Cooperative Thyrotoxicosis Therapy Follow-up Study Group has been extended an additional 24 years to examine the radiation dose-response relationships for site-specific cancer death within the group of hyperthyroid patients who were treated with RAI ( 56 ), and this study does now confirm an increased risk of secondary cancers (including breast) due to RAI treatment for hyperthyroidism. This study included patients with hyperthyroidism in 25 United States medical centers and 1 United Kingdom center between 1946 and 1964 ( 56 , 62 ) with a total 18,805 patients analyzed. The average administered RAI activity was 10.1 mCi for GD and 17.6 mCi for TMNG. The authors found that the relative risk of death from solid organ cancers (including breast) increases with greater doses of RAI. In summary they found if patients are treated for hyperthyroidism at age 40, 1 in 31–52 patients would develop a secondary cancer, and of those treated at age 50, 1 in 32–55 would develop a secondary cancer ( 56 ). This study may shift the decision-making process going forward with regards to definitive treatment, especially as the number of high-volume endocrine surgeons continues to increase ( 63 ).

Advantages of surgery for hyperthyroidism allow for nearly 100% cure rates, identification of incidental cancers, and rapid achievement of euthyroid or hypothyroid states ( 1 ). Disadvantages are perioperative and postoperative risks of thyroid surgery including bleeding, hypocalcemia, recurrent laryngeal nerve injuries, and the potential need for lifelong thyroid hormone replacement. Surgery should be considered if there are compressive symptoms, suspicion for or known thyroid cancer, concurrent hyperparathyroidism, large or substernal goiters, low RAIU, in pregnancy planning, pregnancy in the 2 nd trimester, GD with GO, or the need for fast definitive therapy in thyrotoxicosis ( 44 ).

Surgery, when done by a high-volume surgeon, is the most cost-effective definitive treatment for GD ( 64 ), TA, and TMNG with failure rates <1% ( 1 ). Total thyroidectomy is recommended for GD and TMNG. TAs on the other hand, should undergo ultrasound evaluation to assess the entire thyroid gland. If feasible, a lobectomy can be done for isolated TAs ( 1 ). This offers the advantage of potentially avoiding hormone replacement therapy. Preoperatively, patients should be on anti-thyroid medications to establish a euthyroid state. Beta blockade should be initiated for higher risk individuals including elderly, severe thyrotoxicosis, and existing cardiovascular disease ( 4 ). In the setting of GD (not TA or TMND), inorganic iodide administration preoperatively in the form of saturated potassium iodide solutions (SSKI) or potassium iodide-iodine (Lugol’s solution) is also recommended ( 7 ). It will decrease blood flow to the thyroid, decrease intraoperative blood loss and has been shown to improve the safety of surgery with decreased rates of transient hypoparathyroidism and hoarseness from transient recurrent laryngeal nerve injury ( 65 ).

The main risks of surgery include anesthesia, bleeding, hypocalcemia with hypoparathyroidism, and recurrent laryngeal nerve injury. These risks, however, remain very low with high-volume surgeons, which some authors define as >100 thyroid surgeries per year ( 66 , 67 ). Risk of recurrent laryngeal nerve injury remains <1% and transient hypocalcemia <10% ( 44 ). In GD, preoperative vitamin D deficiency, female gender, and perioperative parathyroid autotransplantation have been shown to be predictors for post-thyroidectomy hypocalcemia ( 68 , 69 ). Therefore, the authors recommend preoperative and postoperative supplementation with calcium carbonate and activated vitamin D if needed, to decrease rates of postoperative hypocalcemia ( 70 ). Additional advantages of surgery may apply to those of lower socioeconomic status and those with weight concerns. One study has shown that in their institution’s population of patients, those with a lower socioeconomic status had more features of GD to make surgery more favorable ( 71 ). Another study found that patients who undergo surgery as first line treatment for hyperthyroidism are less likely to become obese or gain weight postoperatively ( 72 ).

Postoperatively, anti-thyroid medications and iodide solutions can be stopped and beta blockers should be weaned off. For patients undergoing a total thyroidectomy, thyroid hormone replacement should be started on a weight based or body mass index (BMI) based calculation, typically between 1.2–1.8 µg/kg/day ( 73 ). For both total thyroidectomy and lobectomy, TSH should be measured by 6–8 weeks postoperatively to assess remaining thyroid function or the dosing of thyroid hormone replacement. About 75% of patients will require subsequent dose adjustments before they are euthyroid ( 74 ). Patients can experience undesirable symptoms of hyper or hypothyroidism during this dose adjustment period, and therefore it is important to achieve a euthyroid state in these patients as soon as possible. Recent studies are identifying algorithms using machine learning and TSH values that can assist in these subsequent dose changes ( 75 ). TSH should be measured every 1–2 months until stable, and then every year.

When thyroid nodules are found in patients with GD, they should be managed according to guidelines and recommendations for euthyroid cases ( 76 , 77 ). There is an increased risk of cancer in GD, typically of papillary variant. This may be due to increasingly sensitive preoperative evaluation modalities or increased incidental findings of microcarcinoma in surgical specimens. Nonetheless, a recent international meta-analysis found that the incidence is likely at least 2 times higher than the previous reported rate of 2% ( 78 ). If a nodule is suspicious or proven to be cancer, the recommended treatment for the hyperthyroidism is surgery. In summary, surgical treatment for GD, TA and TMNG is a safe option for surgical candidates with high-volume surgeons.

Thyroid storm

TS is a rare, potentially life-threatening condition that occurs in thyrotoxicosis leading to multiple organ system decompensation that is usually triggered by severe stress ( 79 ) with a mortality rate ranging 8–25% ( 80 ). Clinical presentation of TS includes thyrotoxicosis with a goiter most commonly from GD, fever, cardiopulmonary dysfunction (tachycardia, CHF), central nervous system (CNS) manifestations (finger tremor, restlessness, psychosis, lethargy, coma), and GI-hepatic dysfunction (nausea, emesis, diarrhea, abdominal pain, jaundice) ( 79 ). Many different triggers have been identified, with the most common being non-compliance with anti-thyroid medications or infection ( 79 , 81 ). Other predisposing conditions causing major systemic stress include trauma, non-thyroid surgery, direct pressure from thyroid surgery or strangulation ( 82 ), RAI therapy ( 1 ), acute illness such as sepsis or diabetic ketoacidosis ( 83 ), and pregnancy or child birth ( 4 ).

Diagnosis of TS is clinical and not always clear, but several diagnostic aids are available. Burch-Wartofsky scores (BWS) identify criteria with a scoring system that allocates points for various system dysfunctions including thermoregulatory, CNS, GI-hepatic and cardiovascular. A score of <25 points is low suspicion for TS, a score of 25–44 points allocates impending TS and a threshold of ≥45 points is highly suggestive of TS ( 80 , 84 ). The Japanese Thyroid Association recognizes different diagnostic criteria formulated from a retrospective study by Akamizu et al. that suggested TS1 and TS2 diagnostic criteria. It differs from BWS in that thyrotoxicosis was a prerequisite for diagnosis and they did not use a scoring system, but rather a combination of clinical features for diagnosis: thyrotoxicosis with different combinations of CNS manifestations, fever, tachycardia or CHF, and GI-hepatic dysfunction ( 79 ). Comparisons of the diagnostic criteria may suggest the TS1/TS2 criteria is not as sensitive as BWS for diagnosing TS ( 80 ).

Treatment of TS requires multiple modalities. According to the BWS scores, patients in the intermediate category of 25–44 points should be monitored closely and treated based on provider discretion. Patients with 45 points or more should absolutely be treated. Treatment strategies should include blocking thyroid hormone synthesis and secretion, blocking the peripheral effects of thyroid hormone, reversing systemic hemodynamic decompensation, treating the precipitating stressor and definitive therapy ( 1 , 84 ). Several ways to decrease thyroid hormone include PTU as it blocks the synthesis of new hormone and the conversion from T4 to T3 in the periphery ( 34 , 85 ), glucocorticoids ( 86 ), and beta blockers, specifically propranolol ( 87 ). Lugol’s solution or SSKI should be given to further rapidly decrease both T3 and T4 levels ( 88 ). ATA guidelines recommend the following dosing: PTU 500–1,000 mg load and then 250 mg every 4 hours. Propranolol 60–80 mg every 4 hours. Hydrocortisone 300 mg intravenous load and then 200 mg every 8 hours. SSKI is given orally as 5 drops (0.25 mL or 250 mg) every 6 hours ( 1 ). In a worst case scenario when patients are unresponsive to the above treatment, plasma pheresis can be done. Decompensated hemodynamics in critically ill patients with TS can initiate many of the secondary clinical features seen and thus, optimizing cardiovascular function and hemodynamics with aggressive volume resuscitation is of utmost importance ( 80 ). Cooling blankets and acetaminophen can be administered for fever. Respiratory, nutritional and intensive care unit support should be given if needed. Definitive treatment includes surgery or RAI, but patients should be recovered from the acute decompensation of TS and be as close to euthyroid as possible before initiating this definitive treatment ( 4 ).

Conclusions

In summary, hyperthyroidism is a complex pathology with many etiologies in which multiple diagnostic modalities can be utilized to identify the best treatment. The treatment of choice is preference-sensitive and should involve a shared decision-making process between the patient and provider. Thus, patient education is important so that each individual understands their options and can choose the treatment that best addresses their concerns. Successful treatment of hyperthyroidism has been reported in many studies. Although future research could close some of the gaps that exist in terms of long-term outcomes, patients and providers should be optimistic for good outcomes with the treatment modalities currently available.

Acknowledgments

Funding: None.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/ .

Conflicts of Interest: The authors have no conflicts of interest to declare.

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Error bars indicate 95% CIs.

eTable 1. SIR for second primary malignant tumors after papillary thyroid cancer

eTable 2. SIR for second primary malignant tumors for localizations after papillary thyroid cancer

eTable 3. Age and latency period between the first and second tumors (Mean±SE)

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Taha A , Taha-Mehlitz S , Nadyrov EA, et al. Second Primary Cancer Among Patients With Papillary Thyroid Carcinoma Following the Chernobyl Disaster. JAMA Netw Open. 2023;6(8):e2329559. doi:10.1001/jamanetworkopen.2023.29559

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Second Primary Cancer Among Patients With Papillary Thyroid Carcinoma Following the Chernobyl Disaster

1 Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland
2 Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St Clara Hospital and University Hospital Basel, Basel, Switzerland
3 Department of Pathology, Gomel State Medical University, Gomel, Belarus
4 Laboratory of Epidemiology, Republican Research Center for Radiation Medicine and Human Ecology, Gomel, Belarus
5 Cancer Registry, State Establishment, N.N. Alexandrov National Cancer Center of Belarus, Lesnoy, Belarus
6 School of Life Sciences, University of Sussex, Brighton, England, United Kingdom
7 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
8 Department of Surgical Oncology and Colorectal Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina
9 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Question What is the risk of second primary cancers in patients with papillary thyroid carcinoma after the Chernobyl disaster?

Findings This cohort study of 30 568 patients with papillary thyroid carcinoma over a 31-year time frame found that the standardized incidence ratio was statistically significant for all cancer types, including solid malignant tumors and leukemias. Statistically significant risks of secondary tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal gland as well as Kaposi sarcoma were found.

Meaning This study suggests that nuclear disasters can have substantial long-term effects requiring intense monitoring of survivors of such disasters.

Importance To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.

Objective To study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.

Design, Setting, and Participants This was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.

Main Outcomes and Measures For analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.

Results Of the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.

Conclusions and Relevance This cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.

Nearly 36 years after the Chernobyl nuclear power plant accident, there are still many unanswered concerns about the socioeconomic, environmental, and health effects of the disaster. Information from the Belarussian Cancer Registry (BCR), which recently became available for the first time, sheds light on several key Chernobyl disaster effects.

When Chernobyl nuclear power plant station No. 4 melted down on April 26, 1986, a substantial amount of radionuclides were released into the environment, causing radioactive contamination of the territories of Belarus as well as portions of Ukraine and the Russian Federation. The population’s radiation dose was mostly contributed to by 2 radionuclides: long-lived caesium-137 and short-lived iodine-131. 1

By the method of radioecological modeling, the average doses of thyroid radiation were reconstructed for more than 9.5 million people in 19 age categories who in 1986 lived in 23 325 settlements of the Republic of Belarus. According to studies, nearly all of Belarus’s population was exposed to iodine-131 to various degrees, based on their age at the time of exposure and where they resided. 2

In 1992, Kazakov et al 3 provided data on the geographical distribution of thyroid cancer cases across Belarus. They showcased that after the accident, there was a statistically significant increase in the number of cases of thyroid cancer among children. According to the publication, the number of cases among children in Belarus in 1991 was 27.5 times higher than in 1986 (2 cases in 1986 vs 55 cases in 1991).

To our knowledge, the only reported health consequence associated with exposure to radioactive isotope iodine-131 after the accident was, and remains to this day, thyroid cancer in those who were a child at the time of exposure. 4 In the adult population, the risk of thyroid cancer has been established only in Chernobyl emergency workers. 5 However, using the BCR, Mahoney et al 6 showed an increase in thyroid cancer rates among both sexes of all age groups. It is assumed that the high prevalence of preexisting iodine deficiency combined with exposure to iodine-131 contributed to a potential carcinogenic effect on the thyroid gland. Because there are no known thyroid radiation doses in the study population, it is impossible to determine the risk of thyroid cancer with any degree of accuracy. Over a 10-year period, there were 21.1% more thyroid cancer cases overall in the general population. In 2020, Belarus age-standardized (world) incidence was 9.0 thyroid cancer cases per 100 000 people (2.6 for men and 14.8 for women). 7 , 8 In general, the accumulated risk from exposure to ionizing radiation still continues to influence the annual increase of cases of diseases to date. 4 The incidence in the cohort of irradiated people 18 to 50 years old has stabilized but has not decreased, remaining 5 to 6 times higher than before the Chernobyl accident. 7 , 8 In Belarus, after the Chernobyl disaster, papillary thyroid carcinoma (PTC) accounted for 97% of all histological cancer variants. 9 Along with the current concern over a nuclear conflict and/or a nuclear power plant accident in a conflict zone, the current cohort study was conducted with the aim of revealing the rate of second primary malignant tumors after PTC following the Chernobyl accident to fill the knowledge gap and promote better understanding to deal with the effects of a similar event.

Data from the BCR were used in this investigation. In the Republic of Belarus, cancer control and oncological care for the population is ensured by an extensive network of 12 oncological institutions for adult solid cancer treatment. Childhood cancer is treated at the Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology. Additionally, there are 2 specialized clinics for hematological pathologies. Thus, all oncological patients are treated and observed in specialized clinics, which are joined with the BCR. Every patient is observed for their entire lifespan with regular examinations by oncologists. Outcomes are tracked by polyclinics, the Census Bureau, and the Ministry of Internal Affairs. Due to this organization of the public health system, the BCR covers almost the entire population of the Republic of Belarus and tracks every patient. The BCR is the most complete information data resource on newly diagnosed and previously registered cancer in the country’s territory.

This study was approved by the ethical committee of the Republican Research Centre for Radiation Medicine and Human Ecology in Gomel, Belarus, which enables regulated access for research of anonymous data from the BCR and for which no informed consent is required. The study was performed according to the Declaration of Helsinki and followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guidelines. 10

Personal data were extracted from the BCR. Patients with primary thyroid cancer were included in the cohort. They were observed until the second cancer appeared, the time of death, the time of loss of observation, or the end of the study (December 31, 2021). Synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). Second primary cancers with latency between 2 diagnoses of more than 1 year were considered metachronous, and expected numbers for them were calculated based on multiplication of person-years of observation by incidence rate. Expected numbers for synchronous cancers were calculated by multiplication of incidence rate of second tumor by number of thyroid cancer cases. If more than 2 cancers were present, patients were observed until the diagnosis of the second tumor and the subsequent following one (for example, in case of 3 cancers, person-years were calculated until the second and third, and both cancers were considered as observed numbers).

Standardized incidence ratios (SIRs) were calculated to assess the probability of a second primary malignant tumor. The SIRs were calculated by indirect standardization using 1-year time and 5-year age intervals (ie, 0-4, 5-9, … 75-79, ≥85 years), considering sex and place of residence. The formulas for calculating SIR are presented in the eMethods in Supplement 1 . 11 , 12 The calculations were made according to the method previously described by Curtis et al. 13 Statistical analyses for demographic indicators were conducted using Prism, version 8.4.2 (GraphPad). Statistical tests were 2-sided, with P < .05 considered statistically significant.

In total, 30 568 patients with primary PTC were included, and 2820 second cancers were found. In women, 2204 secondary cancers occurred, and 616 occurred in men. A general overview of the distribution of second cancers according to sex is shown in Figure 1 . The mean (SD) age of patients at the time of the primary cancer for both sexes was 53.9 (0.2) years and 61.5 (0.2) years at the time of secondary cancer ( Figure 2 ).

As summarized in eTable 1 in Supplement 1 , cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.

Women had a statistically significant higher risk than men for second primary malignant tumors of the lip, oral cavity, and pharynx (SIR, 1.72; 95% CI, 1.16-2.46). In contrast, the SIR was not statistically significant for men. However, both groups together showed a considerable increased risk of developing a second tumor at these sites (SIR, 1.45; 95% CI, 1.12-1.86).

An increased risk of developing a second primary malignant tumor of the digestive organs was found in women (SIR, 1.31; 95% CI, 1.20-1.44) and in men (SIR, 1.34; 95% CI, 1.13-1.57). There was also a statistically significant increased risk for both sexes overall (SIR, 1.32; 95% CI, 1.22-1.43).

An increase in the risks of second primary malignant tumors of the respiratory organs and intrathoracic organs was detected in women (SIR, 2.23; 95% CI, 1.84-2.69). For both sexes, there was a statistically significant increased risk overall (SIR, 1.49; 95% CI, 1.29-1.71).

Only women had an increased risk of developing a second primary malignant tumor of the mesothelium and soft tissues (SIR, 2.44; 95% CI, 1.78-3.25); in contrast, SIR was not statistically significant for men. However, for both sexes overall there was an increase in the SIR (2.43; 95% CI, 1.05-4.80).

For second primary malignant tumors of the female and male reproductive systems and breasts, there was an increased risk of female breast cancer (SIR, 1.72; 95% CI, 1.58-1.86). Women also had an increased risk of cancers of the reproductive system (SIR, 1.12; 95% CI, 1.01-1.24), as did men (SIR, 1.95; 95% CI, 1.64-2.31).

The SIRs for urinary tract tumors showed increased risks in women (2.47; 95% CI, 2.16-2.82) and men (2.04; 95% CI, 1.64-2.52). The only malignant tumor among all of the individuals in this group with statistically significant increased risk was kidney cancer (SIR, 2.79; 95% CI, 2.46-3.15).

Second primary malignant tumors of lymphoid, hematopoietic, and associated tissue had the highest risk for second primary malignant tumors. Overall, this risk was elevated (SIR, 2.24; 95% CI, 1.97-2.54). The SIR values for individual types of tumors are summarized in eTable 2 in Supplement 1 .

Overall, there was an increased risk of melanoma (SIR, 2.21; 95% CI, 1.79-2.71). In both men (SIR, 3.16; 95% CI, 1.87-4.99) and women (SIR, 2.07; 95% CI, 1.63-2.59) this risk remained elevated. Women had an increased risk for Kaposi sarcoma (SIR, 6.26; 95% CI, 1.29-18.28) and minor neoplasm of other connective and soft tissue (SIR, 2.90; 95% CI, 1.84-4.34), while in men this risk was not statistically significantly elevated.

The overall SIR for malignant neoplasm of the eye and adnexa was elevated (SIR, 2.26; 95% CI, 1.24-3.79). In men the risk was not elevated; however, there was increased risk in women for individual localized cancers in these sites. Only women were at risk for meningeal neoplasms (SIR, 3.65; 95% CI, 1.19-8.52). Men (SIR, 2.27; 95% CI, 1.13-4.06) and both sexes combined (SIR, 1.43; 95% CI, 1.01-1.98) had a higher chance of developing brain cancer. Overall, there was a statistically significant difference (SIR, 4.00; 95% CI, 1.09-10.24) for developing a spinal cord and cranial nerve malignant neoplasm.

Only women had an increased risk for malignant neoplasm of other endocrine glands and related structures (SIR, 17.77; 95% CI, 3.66-51.92). Overall, there was a statistically significant increased risk for adrenal tumors (SIR, 3.17; 95% CI, 1.03-7.40) and malignant neoplasm of other endocrine glands and related structures (SIR, 14.69; 95% CI, 3.03-42.92).

As summarized in eTable 3 in Supplement 1 , the mean (SD) age of the first tumor for all malignant neoplasms overall was 53.9 (0.2) years. Women presented slightly earlier in life than men (mean [SD] age, 53.3 [0.3] years vs 56.2 [0.5] years). Overall, the mean (SD) age at diagnosis for solid tumors was 54.0 (0.3) years (women, 53.3 [0.3] years; men, 56.4 [0.5] years) and for all leukemias was 53.4 (1.2) years (women, 53.5 [1.3] years; men, 53.1 [3.2] years).

Overall, the mean (SD) age at second tumor diagnosis was 61.5 (0.2) years (women, 61.2 [0.3] years; men, 62.6 [0.5] years). For all solid tumors, the mean (SD) age at diagnosis was 61.6 (0.2) years (women, 61.2 [0.3] years; men, 62.8 [0.5] years). Mean (SD) age was similar at diagnosis for all leukemias (overall, 60.6 [1.2] years; women, 61.4 [1.3] years; men, 58.3 [2.9] years). For individual sites for the second tumor, the most advanced mean (SD) age for both sexes were for tumors of ill-defined sites, secondary and unspecified sites (67.7 [1.6] years), and digestive organs (65.0 [0.5] years).

For individual sites, the latency period in mean (SD) years was longest for both sexes for tumors of the digestive organs (8.9 [0.3] years) and tumors of ill-defined, secondary, and unspecified sites (8.0 [1.3] years); tumors of the endocrine glands (1.7 [0.9] years) and tumors of respiratory and intrathoracic organs (5.6 [0.4] years) had the shortest latency period ( Figure 2 ).

This study presents a comprehensive report of the risk of developing a second primary malignant tumor among adult patients with PTC in the overall time frame of 31 years after the Chernobyl disaster. After treatment of thyroid cancer in the years following the Chernobyl accident, second primary malignant tumors were found to have a statistically significant increased risk of development. Previous publications have reported an increased risk of both solid tumors and leukemia. 14 - 19 Prior to the current study, only 2 reports were found on the development of a second primary malignant tumor after thyroid cancer. 20 , 21 In a cohort of 6559 patients with post-Chernobyl PTC, an increased risk was demonstrated in patients with solid secondary malignant tumors in general and in the colon, female breast, and urinary system. 21 Additionally, an increased risk was found in patients with leukemia, which most likely reflects radiation exposure to the bone marrow. All patients were children at the time of the Chernobyl accident. Accordingly, PTC was detected at a median age of 29 (range, 23-36) years.

This analysis has demonstrated an increased risk of second primary tumors, with some differences between sexes, as the risk for second tumors of all sites, including solid cancers and all leukemias, was statistically significant for both sexes. In women, there was a statistically significant elevated risk of second primary malignant tumors of the breast after PTC (603 cases; 27.4% of all second tumors), as well as a statistically significant elevated risk of second primary malignant tumors of the parotid gland, oropharynx, larynx, trachea, and bronchi. These results correspond to previous studies for US and Asian populations. 22 , 23 It is interesting that women were shown to be at higher risk for these tumor types, as smoking was thought to raise the risk of some cancers in men, such as tumors of the oral cavity, oropharynx, larynx, trachea, bronchi, and lungs.

The present study also showed an increased risk for second primary malignant tumors of the digestive organs in women, including colon and rectal cancer. Additionally, men showed a higher risk of gastrointestinal tumors, including colon cancer. There have been reports of an increased risk of small and large bowel cancers; however, the individuals in these investigations had various postoperative treatments (radiation therapy, radioisotopes, as well as other forms of treatment). Moreover, different histological types of thyroid cancer were examined in addition to PTC. 14 , 19 , 23 In a cohort of children exposed to iodine-131 at the time of the Chernobyl accident, only 1 report showed an increased risk of second colon cancer. 21 The results of the present study on secondary tumors after PTC were not shown earlier for such a large population.

The current analysis also found that the group of soft tissue tumors, the risks for mesothelioma, and Kaposi sarcoma were increased, which to our knowledge has not been previously described. Also, the risk of secondary tumors of the eye and adnexa, meninges, and the adrenal gland have not been previously described in women. For malignant tumors of the lymphoid, hematopoietic, and related tissue, increased risks are shown in both sexes. Furthermore, and to our knowledge, the increased risk for Hodgkin lymphoma has not been previously described.

It is known that the radioiodine treatment of PTC increases the risk of second primary malignant tumors, especially bone cancer, kidney cancer, hematological cancers, and prostate cancer, as shown in numerous studies. 14 , 16 , 22 , 24 , 25 Tumors of the salivary glands had the highest risk followed by bone and joint tumors and chronic myeloid leukemia. Interestingly, the incidence of colorectal cancer was found to be lower in survivors of thyroid cancer compared with the general population. 19

The main limitation of this study is that the cumulative radiation dose that the individuals absorbed is not considered for the lack of such data. To obtain these doses by radioecological modeling methods, additional data sources would be needed (thyroid gland and thyroid gland mass; measurements of the dose rate of iodine-131 in soil, grass samples, and food; and other variables and data points). Considering all of these difficulties, we could not analyze the contribution of radiation doses to the development of second primary malignant tumors in individual patients.

Furthermore, to minimize immortal bias, we calculated expected numbers of synchronous cancers by multiplication of incidence rates. We supposed that synchronous cancer is diagnosed more often due to more accurate patient examination because of first tumor. Thus, we did not know which tumor was the first. Therefore, the number of person-years could not be accurately determined and, as such, the probability of occurrence of synchronous tumors was defined as the product of the multiplication of the first and second tumors.

The results of this cohort study indicate a statistically significant elevated incidence of solid secondary tumors over a 31-year time frame for the first time, to our knowledge. Statistically significant risks of secondary tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal gland as well as Kaposi sarcoma were also described, to our knowledge, for the first time in a population-based investigation including patients with PTC following the Chernobyl accident. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage. This study shows that nuclear disasters can have substantial long-term effects requiring intense monitoring of victims of such disasters.

Accepted for Publication: July 9, 2023.

Published: August 17, 2023. doi:10.1001/jamanetworkopen.2023.29559

Corresponding Author: Ralph A. Schmid, Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Guoxue Alley 37, Chengdu, Sichuan, China ( [email protected] ).

Author Contributions: Dr Levin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Taha and Taha-Mehlitz contributed equally and share first authorship.

Concept and design: Taha, Taha-Mehlitz, Melling, Cattin, Schmid.

Acquisition, analysis, or interpretation of data: Taha, Nadyrov, Zinovkin, Veyalkin, Levin, Pranjol, Honaker, Cattin, Schmid.

Drafting of the manuscript: Taha, Veyalkin, Levin, Honaker, Cattin, Schmid.

Critical review of the manuscript for important intellectual content: Taha, Taha-Mehlitz, Nadyrov, Zinovkin, Pranjol, Melling, Honaker, Cattin, Schmid.

Statistical analysis: Taha, Nadyrov, Zinovkin, Veyalkin, Levin.

Administrative, technical, or material support: Taha, Taha-Mehlitz, Honaker, Cattin.

Supervision: Cattin, Schmid.

Conflict of Interest Disclosures: None reported.

Data Sharing Statement: See Supplement 2 .

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Second Primary Cancer Among Patients With Papillary Thyroid Carcinoma Following the Chernobyl Disaster

Thyroid gland articles within Scientific Reports

Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis

Differential diagnosis of thyroid nodule capsules using random forest guided selection of image features

Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE)

Using deep learning to identify the recurrent laryngeal nerve during thyroidectomy

Lymph node metastasis around the entrance point to recurrent laryngeal nerve in papillary thyroid carcinoma

The control mechanisms of heart rate dynamics in a new heart rate nonlinear time series model

Effectiveness of hemostatic agents in thyroid surgery for the prevention of postoperative bleeding

The Influence of Energy Depletion by Metformin or Hypocaloric Diet on Thyroid Iodine Uptake in Healthy Volunteers: a Randomized Trial

Maternal predator odour exposure programs metabolic responses in adult offspring

Retinal S-opsin dominance in Ansell’s mole-rats ( Fukomys anselli ) is a consequence of naturally low serum thyroxine

An extremely high dietary iodide supply forestalls severe hypothyroidism in Na + /I − symporter (NIS) knockout mice

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