MON-380 - Congenital Central Hypothyroidism Due to A Homozygous TSHB Pathogenic Variant

Congenital central hypothyroidism is a rare disorder characterized by insufficient thyroid hormone production due to impaired pituitary or hypothalamic function. Reliance on thyroid-stimulating hormone (TSH) for diagnosis and treatment monitoring can lead to mismanagement and prolonged undertreatment. We present a case of congenital central hypothyroidism caused by a homozygous pathogenic TSHB variant that was unrecognized. A 46-year-old woman with hypothyroidism diagnosed in childhood was referred for evaluation of persistently suppressed TSH with low free thyroxine (FT4). She had been treated with levothyroxine dosed according to her TSH, which was consistently undetectable. Review of historical records revealed an undetectable TSH as early as the year 2000, though pituitary hormone evaluation was not performed at that time. A pituitary MRI in 2024 demonstrated no concern for structural abnormalities. Family history was limited as patient is adopted. Genetic testing was pursued and identified a homozygous pathogenic frameshift variant in TSHB (c.373del, p.C125Vfs*10), confirming the diagnosis of congenital central hypothyroidism. She was counseled on appropriate management of central hypothyroidism, emphasizing FT4-based monitoring rather than TSH. Levothyroxine was titrated appropriately, resulting in normalization of FT4 levels and clinical stability. This case underscores the importance of recognizing central hypothyroidism and avoiding TSH-based dosing of levothyroxine. This case also highlights a key limitation of newborn screening programs that rely solely on TSH measurement. In congenital central hypothyroidism due to TSHB pathogenic variants, TSH fails to rise despite low thyroid hormone levels, allowing affected neonates to pass TSH-based screening undetected. Increased awareness is essential to prevent mismanagement of central hypothyroidism and its potential complications.

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