Key Points Question Can the diagnosis of benign disease or cancer in thyroid nodules with indeterminate cytology be established by molecular testing instead of diagnostic surgery? Findings This prospective, blinded, multicenter cohort study of a multigene genomic classifier (ThyroSeq v3) test included 257 indeterminate cytology thyroid nodules with informative test results. It demonstrated a high sensitivity (94%) and reasonably high specificity (82%), with 61% of the nodules yielding a negative test result and only 3% residual cancer risk in these nodules. Meanings Up to 61% of patients with indeterminate cytology thyroid nodules may avoid diagnostic surgery by undergoing multigene genomic classifier testing.

Our data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.

Objective Thyroid eye disease (TED) is a debilitating condition that frequently manifests in patients suffering from Graves’ disease (GD). This study aims to analyse the prevalence of TED among GD patients, with a focus on geographical region‐specific rates. Methods Medline and Embase were searched for articles examining TED prevalence on April 2020, and articles were retrieved and sieved. Statistical analysis was performed after Freeman‐Tukey double arcsine transformation. Thereafter, results were pooled with random effects by DerSimonian and Laird model. Results Fifty‐seven articles involving 26,804 patients were included in the review. The overall pooled prevalence of TED was 40% (CI: 0.32 to 0.48) and by continent was 38% (CI: 0.31 to 0.46) for Europe, 44% (CI: 0.32 to 0.56) for Asia, 27% (CI: 0.06 to 0.56) for North America and 58% (CI: 0.55 to 0.61) for Oceania. The prevalence of TED in Southeast Asia was 35% (CI: 0.24 to 0.47) and Middle East 48% (CI: 0.19 to 0.78). Subgroup analysis showed regions with predominantly Caucasians (37%; CI: 0.28 to 0.46) had a lower prevalence of TED compared to Asians (45%; CI: 0.33 to 0.58). The pooled prevalence of lid retraction was 57% (CI: 0.39 to 0.74), proptosis 57% (CI: 0.48 to 0.65), diplopia 36% (CI: 0.24 to 0.48) and ocular hypertension 13% (CI: 0.06 to 0.19). Conclusion A substantial proportion of patients with GD have TED and often manifest as lid retraction, proptosis and diplopia. Early detection through active screening might help to mitigate the progression of TED and its associated complications.

Familial non-medullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancers. Out of all FNMTC cases, only 5% in the syndromic form has well-studied driver germline mutations. These associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex type 1, Werner syndrome and DICER1 syndrome. It is important for the clinician to recognize these phenotypes so that genetic counseling and testing can be initiated to enable surveillance for associated malignancies and genetic testing of family members. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. To date, 4 susceptibility genes have been identified (SRGAP1 gene (12q14), TITF-1/NKX2.1 gene (14q13), FOXE1 gene (9q22.33) and HABP2 gene (10q25.3)), out of which only the FOXE1 and the HABP2 genes have been validated by separate study groups. The causal genes located at the other 7 FNMTCassociated chromosomal loci (TCO (19q13.2), fPTC/ PRN (1q21), FTEN (8p23.1-p22), NMTC1 (2q21), MNG1 (14q32), 6q22, 8q24) have yet to be identified. Increasingly, gene regulatory mechanisms (miRNA and enhancer elements) are recognized to affect gene expression and FNMTC tumorigenesis. With newer sequencing technique, along with functional studies, there has been progress in the understanding of the genetic basis of FNMTC. In our review, we summarize the FNMTC studies to date and provide an update on the recently reported susceptibility genes including novel germline SEC23B variant in Cowden syndrome, SRGAP1 gene, FOXE1 gene and HABP2 genes in non-syndromic FNMTC.

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The incidence of clinical AFF in this context is 0.4% (1/253; 95% confidence interval [CI] 0.1%-2.2%), and the incidence of atypical femoral stress reaction based on imaging review is 4.5% (3/66; 95% CI 1.6%-12.5%). Clinicians should be aware of the clinical prodrome (which may or may not be present) and antecedent imaging changes associated with AFF. 2017;22:438-444 Among patients with metastatic bone disease treated with denosumab, cases of clinical and subclinical atypical femoral fracture (AFF) are rare. The one detected case of clinical fracture went unrecognized despite prodromic symptoms. Clinicians should be aware of (a) the potential prodrome of anterior thigh/groin pain and (b) subclinical imaging changes in the lateral femur, both of which may precede clinical AFF.

Objective American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery. Methods We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence. Results Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2–17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6–4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease. Conclusion In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.

Chernobyl demonstrated that iodine-131 (131I) released in a nuclear accident can cause malignant thyroid nodules to develop in children within a 300 mile radius of the incident. Timely potassium iodide (KI) administration can prevent the development of thyroid cancer and the American Thyroid Association (ATA) and a number of United States governmental agencies recommend KI prophylaxis. Current pre-distribution of KI by the United States government and other governments with nuclear reactors is probably ineffective. Thus we undertook a thorough scientific review, regarding emergency response to 131I exposures. We propose: (1) pre-distribution of KI to at risk populations; (2) prompt administration, within 2 hours of the incident; (3) utilization of a lowest effective KI dose; (4) distribution extension to at least 300 miles from the epicenter of a potential nuclear incident; (5) education of the public about dietary iodide sources; (6) continued post-hoc analysis of the long-term impact of nuclear accidents; and (7) support for global iodine sufficiency programs. Approximately two billion people are at risk for iodine deficiency disorder (IDD), the world’s leading cause of preventable brain damage. Iodide deficient individuals are at greater risk of developing thyroid cancer after 131I exposure. There are virtually no studies of KI prophylaxis in infants, children and adolescents, our target population. Because of their sensitivity to these side effects, we have suggested that we should extrapolate from the lowest effective adult dose, 15–30 mg or 1–2 mg per 10 pounds for children. We encourage global health agencies (private and governmental) to consider these critical recommendations.