Very-early-onset autoimmune hypothyroidism: a report of two cases with STAT3 gain-of-function variant

Abstract

<p>Autoimmune hypothyroidism occurs rarely before three years of age. Two siblings were diagnosed with autoimmune hypothyroidism at age five and 16 months, presenting with classic symptoms of hypothyroidism, abnormal thyroid function tests (TSH 200 and 660 mU/L; reference 0.73-8.4 mU/L; Free T4 5.9 and <1.3 pmol/L; reference 11.9-25.6 pmol/L), and high thyroid peroxidase antibody levels. Thyroxine medication alleviated their symptoms. Apart from mild infections, the siblings exhibited no other major disorders. Whole exome sequencing identified a pathogenic STAT3 gain-of-function variant, most commonly associated with infantile-onset multi-organ autoimmune disorder. Genetic testing for early-onset hypothyroidism may reveal specific etiologies, impacting follow-up and treatment.<br></p>