BACKGROUND.
The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine-needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic-histologic correlation, source of errors, and clinical management.

METHODS.
Patient cytology data were retrieved by a retrospective search of thyroid FNA in the institutional databases. Cytologic diagnoses were classified as unsatisfactory, benign, atypical cellular lesion (ACL), follicular neoplasm (FN), suspicious for malignancy, and positive for malignancy. Samples with a histologic discrepancy were re-evaluated, and clinical follow-up information was recorded.

RESULTS.
Of of 4703 FNA samples, 10.4% were classified as unsatisfactory, 64.6% were classified as benign, 3.2% were classified as ACL, 11.6% were classified as FN, 2.6% were classified as suspicious, and 7.6% were classified as malignant. Five hundred twelve patients had at least 1 repeat FNA, mainly for results in the unsatisfactory and ACL categories. One thousand fifty-two patients had surgical follow-up, including 14.9% of patients with unsatisfactory FNA results, 9.8% of patients with benign results, 40.6% of patients with ACL results, 63.1% of patients with FN results, 86.1% of patients with suspicious results, and 79.3% of patients with malignant results. The rates for histologically confirmed malignancy in these categories were 10.9%, 7.3%, 13.5%, 32.2%, 64.7%, and 98.6%, respectively. The cytologic-histologic diagnostic discrepancy rate was 15.3%. Sources of errors included diagnoses on inadequate specimens, sample errors, and overlapping cytologic features between hyperplastic nodules and follicular adenoma. The sensitivity and specificity of thyroid FNA for the diagnosis of malignancy were 94% and 98.5%, respectively.

CONCLUSIONS.
The current results indicated that FNA provides an accurate diagnosis of thyroid malignancy. The 6 diagnostic categories were beneficial for triaging patients for either clinical follow-up or surgical management. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.22955

Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations.

Proliferative thyroid diseases are more prevalent in females than in males. Upon the onset of puberty, the incidence of thyroid cancer increases in females only and declines again after menopause. Estrogen is a potent growth factor both for benign and malignant thyroid cells that may explain the sex difference in the prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting effect through a classical genomic and a non-genomic pathway, mediated via a membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase signaling pathways MAPK and PI3K. In papillary thyroid carcinomas, these pathways may be activated either by a chromosomal rearrangement of the tyrosine receptor kinase TRKA, by RET/PTC genes, or by a BRAF mutation and, in addition, in females they may be stimulated by high levels of estrogen. Furthermore, estrogen is involved in the regulation of angiogenesis and metastasis that are critical for the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed knowledge on this regulation is still missing for thyroid cancer.

/pdf/estrogen-and-its-role-in-thyroid-cancer-1xd55rpcf4.pdf

Estrogen and its role in thyroid cancer

Background
Clinical hypo- and hyperthyroidism are recognized causes of reversible dementia but prior studies relating thyroid stimulating hormone (TSH) levels to cognitive performance in clinically euthyroid persons have yielded inconsistent results.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/414403/ioi80052_1514_1520.pdf

Thyroid function and the risk of Alzheimer disease: the Framingham Study.

Context: TSH is the main factor involved in the control of proliferation of thyrocytes. Recently, a strong relationship between serum TSH and risk of thyroid malignancy has been reported. Objectives: The aim was to review published papers about the relationship between serum TSH and frequency of differentiated thyroid cancer. Evidence Acquisition: PubMed was used to identify studies focused on the relationship between TSH and differentiated thyroid cancer. Evidence Synthesis: In patients with nodular thyroid disease, the risk of thyroid malignancy increases with serum TSH, and even within normal ranges, higher TSH values are associated with a higher frequency and more advanced stage of thyroid cancer. The likelihood of papillary thyroid carcinoma is reduced when TSH is lower, as in thyroid autonomy, and increased when TSH is higher, as in thyroid autoimmunity. Treatment with l-thyroxine (LT4), which reduces serum TSH, is associated with significantly lower risk of developing clinically detectable thyroid ...

/pdf/serum-tsh-and-risk-of-papillary-thyroid-cancer-in-nodular-1u0v4bh21b.pdf

Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease.

Thyroid diseases are more prevalent in women, particularly between puberty and menopause. It is wellknown that estrogen (E) has indirect effects on the thyroid economy. Direct effects of this steroid hormone on thyroid cells have been described more recently; so, the aim of the present paper was to review the evidences of these effects on thyroid function and growth regulation, and its mechanisms. The expression and ratios of the two E receptors, α and β, that mediate the genomic effects of E on normal and abnormal thyroid tissue were also reviewed, as well as nongenomic, distinct molecular pathways. Several evidences support the hypothesis that E has a direct role in thyroid follicular cells; understanding its influence on the growth and function of the thyroid in normal and abnormal conditions can potentially provide new targets for the treatment of thyroid diseases.

/pdf/role-of-estrogen-in-thyroid-function-and-growth-regulation-4225jabhr0.pdf

Role of Estrogen in Thyroid Function and Growth Regulation

Fine-needle aspiration biopsy represents the most reliable test for cytologic evaluation of thyroid nodules. However, inadequate samples may occur leading to a repetition of the procedure with the consequence of patients' discomfort and poor compliance. In this paper, we present results from biopsy of thyroid nodules obtained by combining: (1) ultrasound (US) guidance, (2) no-aspiration technique, and (3) on-site review of specimens. A total of 465 nodules were biopsied in 307 patients. Solitary nodules and multinodular goiter were present in 36.8% and 63.1% of patients, respectively. After collection, each sample was smeared in duplicates, one of which was stained with hematoxylin and checked on-site by a cytopathologist. In cases of inadequate smears, biopsies were immediately repeated. All slides were then processed for final cytologic results, which were reported as benign in 427 nodules (91.8%), malignant in 12 nodules (2.5%), with follicular proliferation or suspicious for malignancy in 23 nodules (...

Ultrasound-guided fine-needle capillary biopsy of thyroid nodules, coupled with on-site cytologic review, improves results.

Objective: Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. Design: We immunohistochemically evaluated both ER-α and ER-β immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). Main Outcome: ER-α IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-β IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-β IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-β IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. Conclusions: This st...

Estrogen Receptor (ER)-β, But Not ER-α, Is Present in Thyroid Vessels: Immunohistochemical Evaluations in Multinodular Goiter and Papillary Thyroid Carcinoma

Objective: Estrogen receptors are present in thyroid follicular cells in normal and neoplastic tissue. We evaluated changes in total thyroid volume and volume of thyroid nodules in postmenopausal women given either hormone therapy (HT) or no treatment in a 1-year observational follow-up. Design: We studied 33 women receiving HT and 76 women receiving no treatment, comparing total thyroid volume, thyroid nodule volume, and serum concentrations of thyroid-stimulating hormone and estradiol at baseline and 1 year of follow-up. Results: Serum thyroid-stimulating hormone concentrations were not different between groups either at baseline or at 1 year. Estradiol rose significantly in the HT group. The final percent changes in total thyroid volume were comparable between groups (HT, 1.59 ± 2.56%; no treatment, 1.20 ± 2.28%). At baseline, nodules were detected in 17 (51.5%) and 33 (43.4%) of women in the HT and no treatment groups, respectively, with no statistically significant difference between groups. The final number of nodules was unchanged or reduced in 88.2% and 81.1% and increased in 11.8% and 18.9% of women in the HT and no treatment groups, respectively, with no differences between groups. Baseline volumes of thyroid nodules were 0.8 ± 0.4 and 1.4 ± 0.4 mL in women in the HT and no treatment groups, respectively (P = 0.4). After 1 year the volume of thyroid nodules was unchanged or reduced in 47.1% and 52.8% and increased in 52.9% and 47.2% of women in the HT and no treatment groups, respectively, with no differences between groups. Conclusions: Estrogen administration for 1 year did not affect thyroid volume or the number and volume of thyroid nodules in postmenopausal women.

Effect of estrogen therapy for 1 year on thyroid volume and thyroid nodules in postmenopausal women.

Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women >60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects >70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.

Thyroid disease in the elderly: sex-related differences in clinical expression.

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Papers

Ultrasound-guided fine-needle capillary biopsy of thyroid nodules, coupled with on-site cytologic review, improves results.

Estrogen Receptor (ER)-β, But Not ER-α, Is Present in Thyroid Vessels: Immunohistochemical Evaluations in Multinodular Goiter and Papillary Thyroid Carcinoma

Effect of estrogen therapy for 1 year on thyroid volume and thyroid nodules in postmenopausal women.

Thyroid disease in the elderly: sex-related differences in clinical expression.