Central congenital hypothyroidism due to TSHB gene mutation: 25-year follow-up

Area of Science:

• Genetics
• Endocrinology
• Neonatal Medicine

Background:

• Isolated central congenital hypothyroidism (iCCH) is often diagnosed late, leading to potential neurocognitive deficits.
• Thyroid-stimulating hormone (TSH) gene mutations are a known cause of iCCH.
• Neonatal hyperbilirubinemia can sometimes mask or delay diagnosis of hypothyroidism.

Purpose of the Study:

• To report a case of iCCH diagnosed in a neonate presenting with prolonged unconjugated hyperbilirubinemia.
• To highlight the importance of early diagnosis and treatment of iCCH.
• To demonstrate the long-term outcomes of timely levothyroxine initiation.

Main Methods:

• Clinical presentation and diagnostic workup of a term neonate with suspected hypothyroidism.
• Thyroid function tests, anterior pituitary hormone assessment, and pituitary MRI.
• Genetic analysis of the TSHB gene to identify causative mutations.

Main Results:

• A female neonate presented with prolonged unconjugated hyperbilirubinemia and clinical suspicion of hypothyroidism.
• Genetic analysis revealed a deletion in the TSHB gene (c.108-109 in exon 2).
• Timely initiation of levothyroxine therapy on day 11 of life averted neurocognitive sequelae, with the patient remaining well on follow-up for 25 years.

Conclusions:

• TSHB gene mutations can cause iCCH, sometimes presenting with atypical initial findings like hyperbilirubinemia.
• Early diagnosis and prompt levothyroxine treatment are critical for preventing neurocognitive impairment in infants with iCCH.
• Genetic confirmation of TSHB mutations aids in understanding disease severity and prognosis, emphasizing the benefits of early intervention.