Frequent TSH Receptor Genetic Alterations with Variable Signaling Impairment in a Large Series of Children with Nonautoimmune Isolated Hyperthyrotropinemia

Abstract

Nonpolymorphic alterations in the TSHR gene are commonly associated with isolated NAHT in young patients, thus configuring partial TSH resistance as the most frequent inheritable cause of isolated NAHT. The identification of TSHR defects may thus be helpful for a tailored management of subclinical hypothyroidism. We provide further evidence that besides the well-known defects in G(s) signaling, TSHR genetic alternations found in NAHT may frequently impair the G(q/11) pathway.