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Context: There are differences in diagnosis, treatment, and outcomes for thyroid between racial and ethnic groups that contribute to disparities. Identifying these differences and their causes are the key to understanding and reducing disparities in presentation and outcomes in endocrine disorders., Evidence Acquisition: The present study reviews original studies identifying and exploring differences between benign and malignant thyroid diseases. A PubMed, Web of Science, and Scopus search was conducted for English-language studies using the terms "thyroid," "thyroid disease," "thyroid cancer," "race," "ethnicity," and "disparities" from inception to December 31, 2022., Evidence Synthesis: Many racial and ethnic disparities in the diagnosis, presentation, treatment, and outcomes of thyroid disease were found. Non-White patients are more likely to have a later time to referral, to present with more advanced disease, to have more aggressive forms of thyroid cancer, and are less likely to receive the appropriate treatment than White patients. Overall and disease-specific survival rates are lower in Black and Hispanic populations when compared to White patients., Conclusions: Extensive disparities exist in thyroid disease diagnosis, treatment, and outcomes that may have been overlooked. Further work is needed to identify the causes of these disparities to begin to work toward equity in the care of thyroid disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There have been documented racial and ethnic disparities in the care and clinical outcomes of patients with thyroid disease., Context: Key to improving disparities in thyroid care is understanding the context for racial and ethnic disparities, which includes acknowledging and addressing social determinants of health. Thyroid disease diagnosis, treatment, and survivorship care are impacted by patient- and system-level factors, including socioeconomic status and economic stability, language, education, health literacy, and health care systems and health policy. The relationship between these factors and downstream clinical outcomes is intricate and complex, underscoring the need for a multifaceted approach to mitigate these disparities., Conclusion: Understanding the factors that contribute to disparities in thyroid disease is critically important. There is a need for future targeted and multilevel interventions to address these disparities, while considering societal, health care, clinician, and patient perspectives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves' disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves' disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Amiodarone is a class III antiarrhythmic drug containing 37% iodine by weight, with a structure similar to that of thyroid hormones. Deiodination of amiodarone releases large amounts of iodine that can impair thyroid function, causing either hypothyroidism or thyrotoxicosis in susceptible individuals reflecting ~20% of patients administered the drug. Not only the excess iodine, but also the amiodarone (or its metabolite, desethylamiodarone) itself may cause thyroid dysfunction by direct cytotoxicity on thyroid cells. We present an overview of the epidemiology and pathophysiology of amiodarone-induced thyroid disorders, with a focus on the various forms of clinical presentation and recommendations for personalized management of each form., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia., Objective: The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids., Data Sources: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018., Study Selection: Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism., Data Extraction: Pairs of independent reviewers extracted data and appraised studies., Data Synthesis: Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration., Conclusions: Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Cardiovascular outcomes in mild thyroid dysfunction (treatment controversial) and moderate or severe dysfunction (treatment standard) remain uncertain., Objective: To examine cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and events., Design: In the Atherosclerosis Risk in Communities Study, we measured concentrations of thyrotropin, free thyroxine, and total triiodothyronine (T3) in stored serum samples originally collected in 1990-1992. We used multivariable linear regression to assess cross-sectional associations of thyroid function with cardiovascular risk factors and Cox regression to assess prospective associations with cardiovascular events. Follow-up occurred through 31 December 2014., Setting: General community., Participants: Black and white men and women from the United States, without prior myocardial infarction (MI), stroke, or heart failure., Main Outcomes and Measures: Cross-sectional outcomes were blood pressure, glycemic markers, and blood lipids. Prospective outcomes were adjudicated fatal and nonfatal MI and stroke., Results: Among 11,359 participants (57 ± 6 years, 58% women), thyroid function was more strongly associated with blood lipids than blood pressure or glycemic measures. Mean adjusted differences in low-density lipoprotein cholesterol were +15.1 (95% confidence interval: 10.5 to 19.7) and +3.2 (0.0 to 6.4) mg/dL in those with moderate/severe and mild chemical hypothyroidism, relative to euthyroidism; an opposite pattern was seen in hyperthyroidism. Similar differences were seen in triglycerides and non-high-density lipoprotein cholesterol. With a 22.5-year median follow-up, 1102 MIs and 838 strokes occurred, with similar outcomes among baseline thyroid function groups and by T3 concentrations., Conclusions: Hypothyroidism is associated with hyperlipidemia, but the magnitude is small in mild chemical hypothyroidism, and cardiovascular outcomes are similar between thyroid function groups., (Copyright © 2017 Endocrine Society)

Context: The broad spectrum of thyroid disease severity--from subclinical hypothyroidism to myxedema coma, subclinical thyrotoxicosis to thyroid storm, and microscopic papillary to anaplastic cancers--has always demanded that clinicians individualize their management of thyroid patients. Deepening knowledge of thyroid pathophysiology along with advances in diagnostic, prognostic, and therapeutic technologies applicable to thyroid diseases position this field to ride the wave of precision medicine in the decade ahead.

Context: Increased thyroid cancer incidence is at least partially attributed to increased detection and shows considerable regional variation., Objective: We investigated whether regional variation in cancer incidence was associated with variations in thyroid disease management., Design: We conducted a retrospective population-based cohort study that involved linking data from the Belgian Health Insurance database and the Belgian Cancer Registry to compare thyroid-related procedures between regions with high and low cancer incidence., Main Outcome Measures: Primary outcome measures were rates of TSH testing, imaging, fine-needle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes were proportions of subjects with thyrotoxicosis and nodular disease treated with surgery, of subjects treated with surgery preceded by FNAC or with synchronous lymph node dissection, and of thyroid cancer diagnosis after surgery., Results: The rate of TSH testing was similar, but the rate of imaging was lower in the low incidence region. The rate of FNAC was similar, whereas the rate of surgery was lower in the low incidence region (34 [95% CI 33; 35 ] vs 80 [95% CI 79; 81 ] per 100,000 person years in the high incidence region; P < .05). In the low incidence region compared to the high incidence region, surgery represented a less chosen therapy for euthyroid nodular disease patients (47% [95% CI 46; 48] vs 69% [95% CI 68; 70]; P < .05), proportionally more surgery was preceded by FNAC, more cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had more preoperative FNAC and synchronous lymph node dissection., Conclusion: Regional variation in thyroid cancer incidence, most marked for low-risk disease, is associated with different usage of thyroid imaging and surgery, supporting variable detection as a key determinant in geographic variation.

Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement., Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U.S. population-based studies. Search strategies combining Medical Subject Headings terms and keyword terms and phrases defined two concepts: 1) racial, ethnic, and sex differences including specific populations; and 2) the specific endocrine disorder or condition. The search identified systematic reviews, meta-analyses, large cohort and population-based studies, and original studies focusing on the prevalence and determinants of disparities in endocrine disorders. consensus process: The writing group focused on population differences in the highly prevalent endocrine diseases of type 2 diabetes mellitus and related conditions (prediabetes and diabetic complications), gestational diabetes, metabolic syndrome with a focus on obesity and dyslipidemia, thyroid disorders, osteoporosis, and vitamin D deficiency. Authors reviewed and synthesized evidence in their areas of expertise. The final statement incorporated responses to several levels of review: 1) comments of the SSTF and the Advocacy and Public Outreach Core Committee; and 2) suggestions offered by the Council and members of The Endocrine Society., Conclusions: Several themes emerged in the statement, including a need for basic science, population-based, translational and health services studies to explore underlying mechanisms contributing to endocrine health disparities. Compared to non-Hispanic whites, non-Hispanic blacks have worse outcomes and higher mortality from certain disorders despite having a lower (e.g. macrovascular complications of diabetes mellitus and osteoporotic fractures) or similar (e.g. thyroid cancer) incidence of these disorders. Obesity is an important contributor to diabetes risk in minority populations and to sex disparities in thyroid cancer, suggesting that population interventions targeting weight loss may favorably impact a number of endocrine disorders. There are important implications regarding the definition of obesity in different race/ethnic groups, including potential underestimation of disease risk in Asian-Americans and overestimation in non-Hispanic black women. Ethnic-specific cut-points for central obesity should be determined so that clinicians can adequately assess metabolic risk. There is little evidence that genetic differences contribute significantly to race/ethnic disparities in the endocrine disorders examined. Multilevel interventions have reduced disparities in diabetes care, and these successes can be modeled to design similar interventions for other endocrine diseases.

Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org)., Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence., Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes., Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

This has been an exciting year in thyroid research. In this article, we summarize the new developments in selected areas of thyroid research by reporting on key papers published during the period June 2009 to June 2010. We selected those papers that, in our opinion, have significant clinical or translational impact. Selection criteria were applied for inclusion of papers for the Year in Thyroid lecture at the 92nd Annual Meeting of The Endocrine Society in San Diego, June, 2010. Papers relating to translational and clinical discovery in thyroidology were reviewed. Papers were chosen if they provided new insight into the understanding of thyroid disease and advanced clinical science, or advanced the diagnosis of disease, or proposed new therapy, or provided new data on important clinical questions in thyroidology. Here we review and discuss these papers and show how they provide new insights into clinical thyroidology.

Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. It has become clear that previously accepted reference ranges are no longer valid as a result of both the development of more highly sensitive TSH assays and the appreciation that reference populations previously considered normal were contaminated with individuals with various degrees of thyroid dysfunction that served to increase mean TSH levels for the group. Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter. The remainder with higher values are outliers, most of whom are likely to have underlying Hashimoto thyroiditis or other causes of elevated TSH. Importantly, data indicating that African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.

It has been suggested that intercellular adhesion molecule-1 (ICAM-1) may play an important role in the initiation, localization, and perpetuation of autoimmune thyroid diseases (AITD). In an effort to clarify its role, we have investigated the expression of ICAM-1 on thyroid epithelial cells (TEC) of patients with AITD, patients with nontoxic goiter (NTG), and normal subjects (PN) by flow cytometric analysis under basal conditions and after modulation with cytokines, before and after 8 weeks of thyroid tissue xenotransplantation in nude athymic mice (which lyses all passenger lymphocytes), and in severe combined immunodeficient (SCID) mice where these cells survive. Before xenografting, ICAM-1 was expressed on 56% of TEC from Hashimoto's thyroiditis (n = 5), 54% of Graves' disease (n = 6), 15% of NTG (n = 5), and 12% of PN TEC. After the xenografts had been 8 weeks in nude mice, ICAM-1 expression decreased markedly in AITD TEC [from 56% to 10% in Hashimoto's thyroiditis (P < 0.001) and from 54% to 8% in Graves' disease (P < 0.01)], but did not change significantly in NTG or PN. After the xenografts had been 8 weeks in SCID mice, the expression of ICAM-1 was significantly higher on TEC of AITD compared with the same tissue in nude mice. When the SCID mice engrafted with AITD tissue were treated with the anti-CD4+ T (helper) cell agent FK-506, the expression of ICAM-1 was reduced significantly compared with that in the original tissue or that in nontreated mice engrafted with the same tissue. The proportion of TEC that were ICAM-1 positive was up-regulated in all cases by certain cytokines (e.g. interferon-gamma and tumor necrosis factor-alpha applied alone or in combination). We also detected the presence of ICAM-1 in AITD frozen tissues using an immunohistochemical technique. These data suggest a role for ICAM-1 in human AITD. However, the expression of ICAM-1 appears to be a secondary phenomenon in response to the immune assault, rather than a primary event. Our results support the idea that TEC may act as passive captives to immunological events in human AITD.

Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.

Serum levels of procollagen III N-peptide (PIIINP) and hyaluronic acid (HA) reflect secretion of procollagen III and HA from fibroblasts, a cell type sensitive to thyroid hormones. Serum PIIINP and HA concentrations were measured in different thyroid function states, the former by two different assays, one detecting intact and aggregated PIIINP (PIIINP assay) and another detecting low mol wt degradation products of PIIINP as well (Fab-PIIINP assay). Two thirds of 28 hyperthyroid patients had elevated serum PIIINP values (mean, 192% in the PIIINP assay and 243% in the Fab-PIIINP assay) compared to age- and sex-matched controls (P less than 0.001). Normalization was seen after medical treatment (n = 16). In contrast, serum HA levels increased from 49 +/- 30 to 68 +/- 37 ng/mL (P less than 0.01) when a euthyroid state was achieved. Hypothyroid patients (n = 23) had increased serum HA levels (mean, 162%; P less than 0.05), which normalized after L-T4 treatment (71 +/- 50 before and 41 +/- 20 ng/mL after treatment (n = 16; P less than 0.02). L-T4 treatment also increased serum PIIINP levels significantly. Subjects with familial dysalbuminemic hyperthyroxinemia (n = 8), representing a situation with elevated circulating levels of T4 due to enhanced protein binding, and patients with nontoxic goiter with serum TSH levels ranging from 3.6-0.05 mU/L had normal serum levels of PIIINP and HA. Our data suggest that the secretion of procollagen III and that of HA from fibroblasts are influenced differently by thyroid hormones, since the secretion of procollagen III seems enhanced by thyroid hormones, whereas the secretion of HA seems reduced. Neither euthyroidism with enhanced serum T4 levels (familial dysalbuminemic hyperthyroxinemia) nor euthyroidism with reduced serum TSH levels (nontoxic goiter) seems associated with alterations at the connective tissue level.

A chemiluminescent TSH assay (detection limit, less than 0.01 mU/L) allows for accurate measurement of subnormal TSH concentrations. We retrospectively analyzed serum TSH and the free T4 (fT4) index of 460 consecutive endocrine clinic visits to determine the usefulness of TSH measurements alone in the assessment of thyroid function. Additionally, case histories were presented nonconsecutively to one of us (TSH alone or TSH with fT4) to determine if knowledge of the fT4 level would alter management. Of hypothyroid patients on replacement therapy (n = 127), 60% had concordant fT4 and TSH, 14% had subnormal TSH with normal fT4, 18% had high TSH with normal fT4, and 4% normal TSH with high fT4; only 4% were managed differently when the fT4 level was known in addition to TSH. Of the patients receiving suppressive therapy with TSH levels above 0.05 mU/L (n = 81), only 4% were managed differently when fT4 was known; 4% had high fT4. With TSH levels below 0.05 mU/L (n = 64), knowledge of fT4 was felt to be necessary for management in all cases; 53% had high fT4. Twenty-three of 46 (50%) patients being treated for hyperthyroidism had discordant TSH and fT4, including 7 patients with low TSH and low fT4. Two of 21 (10%) patients screened with pituitary/hypothalamic disease had discordant TSH and fT4, and 4 of 9 (44%) patients treated with L-T4 for secondary hypothyroidism had subnormal TSH. Knowledge of fT4 was felt to be necessary in all these cases. We conclude that TSH alone is sufficient for screening and monitoring L-T4 replacement or suppression therapy if TSH levels are above 0.05 mU/L. These patients account for the majority of visits to our endocrine clinic. TSH alone is misleading in pituitary disease and during the treatment of hyperthyroidism. fT4 is needed if TSH levels are less than 0.05 mU/L to assess the degree of hyperthyroidism.

Between 1961 and 1979, 349 patients with autonomously functioning thyroid nodules (AFTN) were seen. There were 287 nontoxic and 62 toxic lesions. Toxic lesions were seen in 56.5% of AFTN patients over 60 yr of age but in only 12.5% of the younger patients. The female to male ratio was 14.9:1 for nontoxic AFTN patients but only 5.9:1 for toxic AFTN patients. The proportion of toxic AFTN in patients less than 20 yr old (13.8%) was not significantly different from that in patients 20--60 yr old (12.7%). T3 toxicosis was observed in 46% of those patients with hyperthyroidism. All but 4 of the toxic AFTN measured 3 cm in diameter or larger. AFTN 3 cm or larger were more than twice as common in patients 40 yr or older than in younger patients. Of 159 untreated nontoxic AFTN patients, 14 became toxic within 1--6 yr. One patient in 5 with a nontoxic AFTN 3 cm or larger developed toxicity.