Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Biallelic variants in the TSHB gene cause isolated TSH deficiency, leading to central congenital hypothyroidism (CCH).
• CCH is characterized by low free thyroxine and inappropriately low TSH, potentially missed by neonatal screening.
• This condition has an estimated incidence of 1 in 65,000 births.

Purpose of the Study:

• To report a case of CCH with a novel TSHB variant.
• To highlight the importance of consistent thyroxine replacement in managing CCH and preventing pituitary hyperplasia.
• To demonstrate the reversibility of pituitary hyperplasia with improved treatment adherence.

Main Methods:

• Case report of a patient diagnosed with CCH as a neonate.
• Genetic testing of the TSHB gene identifying compound heterozygosity for a novel and a previously reported variant.
• Clinical follow-up assessing pituitary hyperplasia and hypothyroidism management.

Main Results:

• The patient had a novel TSHB variant (c.217A>C, p.(Thr73Pro)) and a previously reported variant (c.373delT, p.(Cys125Valfs*10)).
• Recurrence of pituitary hyperplasia and symptomatic hypothyroidism occurred due to poor compliance with thyroxine replacement.
• Improved compliance led to the resolution of pituitary hyperplasia without further intervention.

Conclusions:

• Novel TSHB variants can cause CCH.
• Consistent thyroxine replacement is essential for treating hypothyroidism and preventing pituitary hyperplasia in CCH.
• Pituitary hyperplasia is reversible with sustained adherence to thyroxine therapy.