Central congenital hypothyroidism caused by TSHB gene mutation: a case report

We present a case of central congenital hypothyroidism that was diagnosed clinically in the second month of life, after a false negative neonatal screening test.

A 44-day-old infant presented to the Emergency Department with cyanosis and hypotonia. Examination revealed macroglossia, perioral cyanosis, jaundice, holosystolic murmur, and umbilical hernia. There was a history of early neonatal hospitalization due to feeding difficulties and hypoglycemia; neonatal endocrine-metabolic screening was negative for all tested diseases, including congenital hypothyroidism (whole blood TSH <6.0 mUI/L). Due to desaturation and bradycardia, the child was admitted to the Pediatric Intensive Care Unit, requiring intubation, mechanical ventilation and, later, a tracheostomy. Metabolic studies showed no abnormalities. Thyroid function tests revealed undetectable TSH and very low free T3 and free T4 levels. Whole exome sequencing revealed a likely pathogenic variant in homozygosity in the TSHB gene, associated with central congenital hypothyroidism. Levothyroxine was initiated, with rapid normalization of free T4 levels and marked clinical improvement.

Clinical signs of congenital hypothyroidism are becoming increasingly uncommon, due to early screening, diagnosis and treatment; it is still crucial to recognize them, since central congenital hypothyroidism can be missed during routine neonatal screening. This case underscores the importance of starting hormone replacement therapy as early as possible to reduce systemic and cognitive complications.