Thyroid nodules are common, with as many as two-thirds of adults harboring nodules detectable by ultrasound and about 5% by palpation.^1,2 Ultrasound has proven useful in estimating the likelihood of malignant tumors and selecting nodules for fine-needle aspiration (FNA) biopsy.^3-7 More than 600 000 thyroid FNAs are performed every year in the United States alone, and the number has been increasing annually by 16%.^8,9 Thyroid FNA cytology can accurately classify most nodules as benign and a minority as malignant, but the results remain indeterminate in about 20% (range, 10%-38%) of nodules when cytological features lack specific characteristics needed for a definitive diagnosis.¹⁰ Further, the proportion of indeterminate cytology results appears to be rising.¹¹

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.

Context: Although response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI.Objective: This study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI.Design and Setting: This was a retrospective study, which took place at a referral center.Patients: A total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk.Main Outcome Measure: Main outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24–510).Results: Recurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2–5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment.Conclusions: 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.

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 FNMTC-associated 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.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.