Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance due to a mutation in the TRbeta gene...

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Resistance to thyroid hormone (RTH) is a rare genetic disorder characterized by decreased target tissue response to thyroid hormones.
• Mutations in the thyroid hormone receptor beta (TRbeta) gene are the most common cause of RTH, leading to variable clinical manifestations.
• Understanding the genetic basis and clinical spectrum of RTH is crucial for diagnosis and management.

Observation:

• Two unusual cases of RTH were observed within a single family, linked to a specific TRbeta gene mutation (M313T).
• The male infant presented with neonatal thyrotoxicosis, poor weight gain, and elevated free T4 with inappropriately normal TSH, responding to propylthiouracil (PTU).
• The mother exhibited secondary infertility and thyrotoxic features, with RTH symptoms fluctuating during pregnancies.

Findings:

• The study identified a novel TRbeta gene mutation (M313T) associated with RTH, presenting with both thyrotoxic and hypermetabolic features in infancy.
• Propylthiouracil (PTU) treatment demonstrated efficacy in managing hyperthyroid symptoms and improving fertility in the affected mother.
• The male infant, initially treated with PTU, became clinically euthyroid and developmentally normal after treatment discontinuation.

Implications:

• These cases expand the clinical spectrum of RTH, particularly highlighting its association with hypermetabolic states in infancy and secondary infertility.
• The findings underscore the importance of genetic testing for TRbeta mutations in patients with unexplained thyroid dysfunction and related symptoms.
• This research provides insights into the variable expressivity of RTH mutations and the potential therapeutic role of antithyroid drugs in specific contexts.