Endocrine Abstracts

JOINT2084

Introduction: Extra-thyroidal abnormalities are common in congenital hypothyroidism (CH). This study aimed to investigate the frequency of extra-thyroidal abnormalities in CH cases and the relationship between extra-thyroidal disease and the genetic causes of CH.

Methods: Patients with CH were screened for non-thyroid congenital anomalies, and a thyroid genetic panel was analyzed using next-generation sequencing. The panel included the following genes: NKX2-5, PAX8, PHEX, POR, SERPINA7, SLC16A2, SLC26A4, SLC26A7, SLC5A5, ALB, DIO1, DIO2, DIO3, DUOX1, DUOX2, DUOXA2, FOXE1, GLIS3, GNAS, IGSF1, SLC6A4, TG, THRA, TPO, TRH, TRHR, TSHB, TSHR, TTR, ZNF607, THRB. Patients’ data were obtained retrospectively from hospital records.

Results: The study included 77 patients (29 females and 48 males) diagnosed with CH. Among CH patients, 5 had central and 72 had primary hypothyroidism. The most common etiology was dyshormonogenesis (89.6%). Fifty-one variants were detected in 43 of the 77 patients who requested a genetic panel for CH etiology. TG variants were found in 10 patients, ALB in 8 patients, TSHR in 8 patients, TSHB in 5 patients, TPO in 4 patients, THRA in 4 patients, POR in 3 patients, SLC26A4 in 2 patients, PAX8 in 2 patients, DUOX2, GNAS, PHEX, SLC16A2, THRB variants in 1 patient each. The genetic panel detected pathogenic variants in 10 patients (13%), likely pathogenic variants in 14 patients (18.2%), variants of uncertain significance in 19 patients (24.7%), and no variants in 34 patients (44.2%). L-thyroxine treatment was discontinued in 14% (6 patients) of patients in whom a genetic variant was detected. In contrast, the withdrawal rate was 47.1% (16 patients) in cases without variants (P = 0.002). In the screening for anomalies accompanying CH, 26 patients (33%) had congenital anomalies. Cardiac anomalies were found in 8 patients, genitourinary anomalies in 7, central anomalies in 7, dysmorphic features in 5, musculoskeletal anomalies in 3, gastrointestinal anomalies in 1, and ocular anomalies in 2. Multiple system anomalies were observed in four patients. Genetic variants were reported in 16 of 26 patients with congenital anomalies, whereas 10 patients with extra-thyroidal anomalies had no genetic variants.

Conclusion: This study has showed that about one third of CH patients had non-thyroidal abnormalities, most commonly cardiac abnormalities. Identifying genetic mutations that cause CH may help elucidate the phenotype-genotype relationship of extra-thyroidal disorders and contribute to early diagnosis and feasible and appropriate treatment for these patients.