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Context: Thyroid ultrasound screening is recommended in children with PTEN hamartoma tumor syndrome (PHTS) due to increased risk of thyroid neoplasia, but the natural history of thyroid disease in children with PHTS is unclear.Objective: Determine the prevalence and natural history of thyroid disease in children with PHTS.Methods: Retrospective cohort study (1998-2019) in an academic pediatric hospital of individuals with genetically confirmed PHTS diagnosed before age 19 years. Clinical, thyroid ultrasound, and laboratory characteristics are described. Primary outcomes were the prevalence of thyroid nodules ≥10 mm diameter and time course and risk factors for nodule development assessed by Cox regression analysis. Secondary outcomes included thyroid nodule requiring biopsy, other ultrasound findings, and prevalence of autoimmune thyroid disease.Results: Among 64 subjects with PHTS, 50 underwent thyroid ultrasound. A thyroid nodule ≥10 mm was diagnosed in 22/50 (44%) subjects at median (range) age 13.3 (7.0-22.9) years. Nodules were diagnosed earlier in females than in males (10.8 [7.0-17.9] vs 14.2 [9.9-22.9] years, P = .009). In multivariate analysis, risk of thyroid nodules was significantly associated with female sex (hazard ratio 2.90, 95% CI 1.16-7.27, P = .02) and inversely associated with the presence of neurologic findings of PHTS (HR 0.27, 95% CI 0.10-0.69, P = .007). Abnormal-appearing lymph nodes with echogenic foci were observed by ultrasound in 20% of subjects, but these were not associated with malignancy. Autoimmune thyroid disease was present in 10/33 (30.3%) of subjects in whom it was assessed.Conclusion: Thyroid disease is common in children with PHTS. This study supports current consensus recommendations for ultrasound screening. [ABSTRACT FROM AUTHOR]

Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests. [ABSTRACT FROM AUTHOR]

Background: In 2004, the U.S. Preventive Services Task Force found insufficient evidence to recommend thyroid screening. Purpose: To update the 2004 U.S. Preventive Services Task Force review on the benefits and harms of screening and treatment of subclinical and undiagnosed overt hypothyroidism and hyperthyroidism in adults without goiter or thyroid nodules. Data Sources: MEDLINE and Cochrane databases through July 2014. Study Selection: Randomized, controlled trials and observational studies of screening and treatment. Data Extraction: One investigator abstracted data, and a second investigator confirmed; 2 investigators independently assessed study quality. Data Synthesis: No study directly assessed benefits and harms of screening versus no screening. For subclinical hypothyroidism (based on thyroid-stimulating hormone levels of 4.1 to 11.0 mIU/ L), 1 fair-quality cohort study found that treatment of subclinical hypothyroidism was associated with decreased risk for coronary heart disease events versus no treatment. No study found that treatment was associated with improved quality of life, cognitive function, blood pressure, or body mass index versus no treatment. Effects of treatment versus no treatment showed potential beneficial effects on lipid levels, but effects were inconsistent, not statistically significant in most studies, and of uncertain clinical significance (difference, -0.7 to 0 mmol/L [-28 to 0 mg/dL] for total cholesterol levels and -0.6 to 0.1 mmol/L [-22 to 2 mg/dL] for low-density lipoprotein cholesterol levels). Treatment harms were poorly studied and sparsely reported. Two poor-quality studies evaluated treatment of subclinical hyperthyroidism but examined intermediate outcomes. No study evaluated treatment versus no treatment of screen-detected, undiagnosed overt thyroid dysfunction. Limitation: English-language articles only, no treatment study performed in the United States, and small trials with short duration that used different dosage protocols. Conclusion: More research is needed to determine the clinical benefits associated with thyroid screening. [ABSTRACT FROM AUTHOR]

Purpose. We sought to investigate the utility of classification and regression trees (CART) classifier to differentiate benign from malignant nodules in patients referred for thyroid surgery. Methods. Clinical and demographic data of 271 patients referred to the Sadoughi Hospital during 2006-2011 were collected. In a two-step approach, a CART classifier was employed to differentiate patients with a high versus low risk of thyroid malignancy. The first step served as the screening procedure and was tailored to produce as few false negatives as possible. The second step identified those with the lowest risk of malignancy, chosen from a high risk population. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the optimal tree were calculated. Results. In the first step, age, sex, and nodule size contributed to the optimal tree. Ultrasonographic features were employed in the second step with hypoechogenicity and/or microcalcifications yielding the highest discriminatory ability. The combined tree produced a sensitivity and specificity of 80.0% (95% CI: 29.9-98.9) and 94.1% (95% CI: 78.9-99.0), respectively. NPV and PPV were 66.7% (41.1-85.6) and 97.0% (82.5-99.8), respectively. Conclusion. CART classifier reliably identifies patients with a low risk of malignancy who can avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

Introduction. The aim of this study was to evaluate the serum levels of resistin and insulin-like growth factor-1 (IGF-1) and and also the potential relationship between thyroid function and levels of resistin and IGF-1 in hypothyroid and hyperthyroid patients. Methods. Fifteen cases of hypothyroid (HT), 16 of subclinically hypothyroid (SCHT), 15 of hyperthyroid (HrT), 15 of subclinically hyperthyroid (SCHrT), and 17 healthy individuals have been included in the study. Serumresistin levels were measured using enzyme-linked immunosorbent assay and IGF-1 and thyroid stimulating hormone (TSH) levels by chemiluminescence method. Results. Resistin levels in total HT group were significantly higher than in controls (12.66 ± 6.04 and 8.45 ± 2.90 ng/mL, resp.). In SCHrT subgroup resistin levels were significantly higher than those of controls (14.88 ± 7.73 and 8.45 ± 2.90 ng/mL, resp.). IGF-1 levels were significantly lower in total HT than in total HrT and control groups (117.22 ± 52.03, 155.17 ± 51.67, and 184.00 ± 49.73 ng/mL, resp.). Furthermore IGF-1 levels in HT subgroup were significantly lower compared to controls (123.70 ± 44.03 and 184 ± 49.73 ng/mL, resp.). In SCHT subgroup IGF-1 levels were significantly lower than those of control and SCHrT groups (111.11 ± 59.35, 184.00 ± 49.73, and 166.60 ± 47.87 ng/mL, resp.). There were significant correlations between IGF-1 and TSH in HT subgroup and between resistin and TSH in total HrT group. Conclusion. It was concluded that increased resistin levels are directly related to thyroid dysfunction, and GH/IGF-1 axis is influenced in clinically or subclinically hypothyroidism patients. [ABSTRACT FROM AUTHOR]

There is much concern expressed in the literature regarding the lack of predictive power of the thyroid fine needle aspiration/biopsy ( TFNAB) approach to defining the nature of clinically detected thyroid nodules. This has been exacerbated in the past decade or more by the routine use of ultrasonography ( US) in examining the thyroid as well as the introduction of molecular testing in the realm of thyroid pathology. Some have even gone so far as to suggest replacing the TFNAB with molecular signature testing to reduce the degree of uncertainty for a specific cytological diagnosis. This review addresses those concerns with a re-emphasis on understanding the basic keys to successfully evaluating a patient with a thyroid nodule by routine TFNAB examination. These keys include bringing to bear an experienced group of physicians in an integrated team approach, a sharpened focus on the TFNAB cytological categories and a grounded understanding of the predictive ability of molecular testing in a given patient when the cytological interpretation creates too much uncertainty in the minds of the patients and clinicians in attempting to reach a decision on how to manage a thyroid nodule. With this practical approach in mind, the false-negative and false-positive rates of 'negative (benign)' and 'positive (malignant)' thyroid aspirates should be no more than 1%; and the prevalence of an 'indeterminate' aspirate - the area in TFNAB attracting the most attention for improvement with novel biomarkers - should be 10% or less. Thus, physicians should be capable of managing at least 90% of patients undergoing TFNAB in a confident manner without further testing beyond the routine, future re-examination of the patient's nodule to re-assess for any change in its nature or its impact on the patient's quality of life. The other 10% can then be considered for molecular testing in a manner tailored to those individuals truly in need of a more sophisticated - and expensive - approach to the characterization of their thyroid nodules. As the era of US has matured - just as with the era of serum PSA testing for prostate cancer in men - we have experienced a paradigm shift: Given the incidence of thyroid nodules in the U.S. adult population in comparison with the risk of dying of thyroid malignancy, the main role of TFNAB is to reduce the need for surgical intervention. [ABSTRACT FROM AUTHOR]

We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08±2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level. [ABSTRACT FROM AUTHOR]

To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. The project participants hope that the adoption of this flexible framework will facilitate communication among cytopathologists, endocrinologists, surgeons, radiologists, and other health care providers; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies. [ABSTRACT FROM AUTHOR]

Objective: The article studied the knowledge and practice patterns of primary care providers and internal medicine residents in their initial evaluation of thyroid nodules and determined whether their practice is in accordance with published guidelines by the American Thyroid Association and American Association of Clinical Endocrinologists. Method: A survey was distributed to primary care physicians (PCPs) and internal medicine residents at a community hospital in Baltimore and a chart review was conducted at the Diabetes and Endocrine Center in the same hospital. Results: A total of 47 physicians (70%) responded to the survey, 16 PCPs and 33 residents. Most responders (96%) will always obtain a TSH, and of these, 21% of PCP and 25% of residents will obtain a TSH without any other laboratory work-up. Fifty percent of the physicians (PCP, 75%; resident, 39%) will always obtain a thyroid ultrasound (p=0.043). Most physicians (97%) will refer for a fine-needle aspiration (FNA) biopsy of a nodule >1 cm. Sixty-two percent of the physicians will not put a euthyroid patient on levothyroxine suppression therapy. Many physicians (48%) are not aware of the AACE and ATA thyroid nodule guidelines. Most physicians (65%) have not read the guidelines. Of the 113 charts reviewed, TSH was obtained alone in 40% and with other laboratory tests in 74%. Thyroid ultrasound was done in 67%. Only one patient was on levothyroxine for levothyroxine suppression therapy. Discussion: Although many physicians were not aware of the guidelines, and a small number of physicians have read them, many PCP and residents responded in concordance with the guidelines in obtaining TSH, an ultrasound, performing FNA biopsy, and not providing levothyroxine suppressive therapy in euthyroid patients. No differences were found between the responses of PCP and residents except for obtaining an ultrasound. Chart review data also showed that majority of tests ordered for non-toxic thyroid nodule evaluation were in agreement with the guidelines. Limitations include lowsurvey response rate among PCPs and that results are from one community hospital. Conclusion: Our findings from the survey and chart review conclude that majority of primary care physicians were initiating the appropriate work up of thyroid nodules prior to referral to a specialist. [ABSTRACT FROM AUTHOR]

The article discusses the significance of autoantibodies in diagnosing thyroid disorders in the U.S. It states that thyrotropin receptor antibodies (TRAb) may help predict hypothyroidism. In relevance, thyroid antibody tests may assess in equivocal situations such as normal radioiodine study in hyperthyroidism or evaluating the cause of hypothyroidism when infiltrative disorders are suspected. It highlights a study which examines the importance of thyroid peroxidase antibody (TPOAb) in determining thyroid-related disorders.

This article discusses various issues related to the sclassification of congenital primary hypothyroidism. Neonatal screening for congenital hypothyroidism, which allows for early diagnosis and treatment and the avoidance of mental retardation, is widely performed throughout the world. Recent studies using thyroid scintigraphy have indicated that thyroid dysgenesis represents a smaller percentage of congenital hypothyroidism cases, and in many the thyroid gland is in the proper position and is normal in size or enlarged. In 1987 the American Academy of Pediatrics and the American Thyroid Association jointly issued recommended guidelines for congenital hypothyroidism newborn screening. In the great majority of instances, congenital primary hypothyroidism is a disease requiring a lifetime of therapy and maximum effort should be taken to make a specific diagnosis in the immediate neonatal period. Early anatomic and functional diagnosis allows for more effective treatment and family counseling and sets the stage for a more accurate classification to elucidate genetic and pathophysiologic variations of this heterogeneous disorder.

Reports that the American Association of Clinical Endocrinologists has launched an educational program that encourages all Americans with elevated cholesterol levels to check their necks for an enlarged thyroid gland and ask their physicians about getting tested for thyroid disease. Recognized link between high cholesterol and hypothyroidism.