Studies of Benign and Malignant Thyroid Disease

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

Project 1 Background: Long-term management of intermediate- and high-risk differentiated thyroid cancer (DTC) involves thyrotropin (TSH) suppression with thyroid hormone to prevent potential stimulation of TSH receptors on DTC cells, leading to tumor growth. However, the current guidelines recommending TSH suppression are based on low- to moderate-quality evidence. Methods: We performed a systematic review and meta-analysis of studies evaluating the role of TSH suppression in intermediate- and high-risk DTC patients (≥18 years) treated as per regional guideline-based therapy with a follow-up duration of 5 years (PROSPERO #252396). TSH suppression was defined as "below normal reference range" or, when known, <0.5 mIU/L. Primary outcome measures included (i) composite of progression-free survival (PFS), disease-free survival (DFS), and relapse-free survival (RLFS), and (ii) composite of disease-specific survival (DSS), and overall survival (OS). Secondary outcome included a composite of cardiac or skeletal adverse events. All outcomes and comparisons were represented as TSH suppression versus TSH non-suppression. Randomized controlled trials, cohort studies, and case-control studies were included for analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effects model. Results: Abstract screening was performed on 6,369 studies. After the exclusion of irrelevant studies and full-text screening, nine studies were selected for the final meta-analysis. Based on seven studies (3,591 patients), the composite outcome of PFS, DFS, and RLFS was not significantly different between TSH suppression and non-suppression groups (HR: 0.75; 95% CI: 0.48-1.17; I2 = 76%). Similarly, a DSS and OS composite outcome assessment based on four studies (3,616 patients) did not favor TSH suppression (HR: 0.69; 95% CI: 0.31-1.52; I2 = 88%). Even after excluding studies of lower quality, the primary outcomes were not significantly different between the TSH suppression and nonsuppression cohorts. The secondary outcome, obtained from two studies (1,294 patients), was significantly higher in the TSH-suppressed groups (HR: 1.82; 95% CI: 1.30-2.55; I2 = 0%). Significant study heterogeneity was noted for primary outcomes. Conclusion: TSH suppression in intermediate- and high-risk DTC may not improve survival outcomes but may increase the risk of secondary complications. However, the limited evidence and study heterogeneity warrant a cautious interpretation of our findings. Project 2 Background: Familial non-medullary thyroid carcinoma (FNMTC) accounts for approximately 9% of differentiated thyroid cancer (DTC). There is conflicting data on the FNMTC aggressiveness compared with sporadic DTC (sDTC), leading to usually more extensive therapy applied for FNMTC, given its autosomal dominant genetic background. This study aimed to compare the progression-free survival (PFS) in patients with FNMTC and sDTC treated with standard therapy. Methods: This longitudinal retrospective cohort study included patients with FNMTC, defined as at least two first-degree relatives affected by DTC. FNMTC patients were matched with sDTC in a 1:3 ratio based on age, sex, American Thyroid Association recurrence risk stratification (ATA-R), extent of initial surgery, and diagnosis date. The primary outcome was PFS. Kaplan-Meier curves were used to compare PFS between the groups, and the Cox proportional hazards model was used to assess confounders. Results: From 95 affected FNMTC patients, 30 were excluded due to lack of follow-up data. The study population consisted of 65 FNMTC and 170 sDTC patients, with a median follow-up of 4.73 (2.87-10.27) years for FNMTC and 5.83 (2.33-10.79) years for sDTC (p = 0.76). There was 100% matching for ATA-R, sex, surgery type, and year of surgery and a satisfactory matching for age (43.12 ± 15.11 vs. 42.76 ± 12.46 years, p = 0.85). FNMTC exhibited a smaller tumor size (1.20 ± 0.96 vs. 1.89 ± 1.51 cm, p < 0.01) and fewer positive lymph nodes (range 0-13 vs. 0-38, p = 0.009) at presentation. The rate of repeated neck surgeries for persistent/recurrent disease was comparable between the groups: 13.8% (9/65) for FNMTC vs. 17.7% (30/170) for sDTC (p = 0.48). There was no difference in radioactive iodine (RAI) therapy dosage between the groups (104 [100-149] vs. 106 [76-160] mCi, p = 0.82). During follow-up, 15.4% of FNMTC and 18.2% of sDTC patients experienced disease progression (p = 0.61). PFS was non-different between groups (p = 0.56) and was associated with ATA-R (high vs. low hazard ratio [HR]: 9.2, confidence interval [CI]: 2.67-31.85, p < 0.001) and sex (male vs. female, HR: 2.5, CI: 1.11-5.6, p = 0.026). Conclusions: No difference in PFS between FNMTC and sDTC patients suggests comparable responsiveness to standard therapy. Therefore, the management of FNMTC should align with the standard of care for DTC to avoid overtreatment of FNMTC.