biostudies-literatureUnknown14(6)Ravi RAutoimmune hypothyroidism occurs rarely before 3 years of age. Two siblings were diagnosed with autoimmune hypothyroidism at age 5 and 16 months, presenting with classic symptoms of hypothyroidism, abnormal thyroid function tests (TSH: 200 and 660 mU/L; reference range (RR): 0.73-8.4 mU/L; Free T4: 5.9 and <1.3 pmol/L; RR: 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.European thyroid journale250260https://www.ebi.ac.uk/biostudies/studies/S-EPMC12687928biostudies-literatureVery-early-onset autoimmune hypothyroidism: a report of two cases with STAT3 gain-of-function variant.PMC12687928Kero JMakkonen KNiinikoski HToppari JNiskanen AReeve MPRavi RfalseVery-early-onset autoimmune hypothyroidism: a report of two cases with STAT3 gain-of-function variant.Autoimmune hypothyroidism occurs rarely before 3 years of age. Two siblings were diagnosed with autoimmune hypothyroidism at age 5 and 16 months, presenting with classic symptoms of hypothyroidism, abnormal thyroid function tests (TSH: 200 and 660 mU/L; reference range (RR): 0.73-8.4 mU/L; Free T4: 5.9 and <1.3 pmol/L; RR: 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.2025-01-01T00:00:00Z2025 Dec2026-06-06T00:09:57.832Z2026-05-23T03:13:49.712ZS-EPMC126879284126329610.1530/ETJ-25-0260