Endocrine Abstracts

JOINT613

Background: Goiterous hypothyroidism, characterized by thyroid enlargement and impaired hormone production, arises from diverse genetic mutations affecting thyroid development and function. Advances in genetic analysis have expanded understanding of its molecular underpinnings, aiding early diagnosis and tailored interventions.

Objectives: To summarize the genetic markers associated with goitrous hypothyroidism and their clinical implications, focusing on recent findings and their impact on patient outcomes.

Methods: A systematic review of studies (1998–2024) was conducted to identify genetic markers, mechanisms, and clinical outcomes in goiterous hypothyroidism. Data from next-generation sequencing (NGS), linkage analyses, and case studies were analyzed for phenotypic correlations.

Results: 1. Genetic Markers:.

• Thyroglobulin (TG) mutations (e.g., p.R277X, p.Val501Gly) impair hormone synthesis, contributing to congenital hypothyroidism (CH) and goiter (Caputo et al., 2007).

• Mutations in SLC5A5/NIS and DUOXA2 genes are linked to goitrous hypothyroidism, with severe phenotypes requiring long-term management (Stoupa et al., 2020; Jung et al., 2020).

• Oligogenic inheritance patterns were identified in congenital cases, emphasizing complex genetic contributions (Oliver-Petit et al., 2021).

2. Mechanisms and Clinical Impact:.

• Missense mutations in TG and TPO disrupt intracellular transport and hormone synthesis, causing thyroid enlargement (Hishinuma et al., 1998; Lee et al., 2013).

• Genome-wide studies identified loci on chromosomes 3q26.1-q26.3 and 14, linked to familial and autoimmune thyroid diseases (Takahashi et al., 2001; Tomer et al., 1998).

3. Therapeutic Outcomes:.

• Early hormone replacement therapy improved growth and cognitive outcomes in CH cases, while genetic insights informed precision medicine approaches (Li et al., 2021; Vincenzi et al., 2023).

• Novel interventions, such as combined selenium and myoinositol, showed promise in reducing thyroid antibodies in autoimmune thyroiditis (Ferrari et al., 2021).

Conclusion: Mutations in TG, TPO, DUOXA2, and other key genes shape the genetic landscape of goitrous hypothyroidism. Early diagnosis through advanced genetic tools enables tailored treatments, improving patient outcomes. Future research should focus on genotype-phenotype correlations and novel therapeutic strategies to enhance care for affected individuals.