Abstract
BACKGROUND: Persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH), a rare autosomal dominant disorder caused by gain-of-function thyroid-stimulating hormone receptor (TSHR) pathogenic variants, manifests with protean clinical features that frequently elude timely detection. We present a pediatric case of genetically confirmed PSNAH harboring a de novo TSHR mutation, in which diagnostic delays triggered life-threatening multiorgan complications. CASE DESCRIPTION: We report a 34-month-old boy presenting with acute-onset dyspnea, severe mitral regurgitation, ventriculomegaly, and cerebellar tonsillar herniation. Biochemical profiling demonstrated severe hyperthyroidism: extremely low levels of thyrotropin (TSH 0.01 µIU/mL), elevated free triiodothyronine (fT3 >30.8 pmol/L; normal 3.5-6.5), free thyroxine (fT4 73.39 pmol/L; normal 11.5-22.7), total T3 (9.78 nmo/L; normal 1.6-4.1), and total T4 (288.7 nmol/L; normal 94-193.1). Genetic testing identified a de novo heterozygous TSHR mutation (c.1868C>T, p.Ala623Val). Multidisciplinary management included methimazole, metoprolol, diuretics, and staged procedures: emergent ventriculoperitoneal shunting preceding mitral valvuloplasty with chordal reconstruction under cardiopulmonary bypass. Postoperative echocardiography confirmed normalization of left ventricular end-diastolic dimension (LVEDD) at 30-day follow-up, though biochemical euthyroidism remained elusive post-9-month antithyroid therapy. CONCLUSIONS: PSNAH may manifest as a multisystem disorder with thyrotoxicosis-associated valvular heart disease as a sentinel presentation. Prenatal thyrotropin receptor hyperactivity and delayed treatment initiation induce structural valvulopathy and cerebellar tonsillar herniation. Early pharmacologic intervention coupled with valve-sparing surgery can restore valvular integrity. The necessity for further neurosurgical intervention in the subsequent management of cerebellar tonsillar herniation requires further longitudinal follow-up.