Evidence from rodents and humans suggests that leptin is necessary for the normal biosynthesis and secretion of thyrotropin-releasing hormone and that complete leptin deficiency is associated with a moderate degree of hypothalamic hypothyroidism characterized by low free thyroxine and high serum thyroid-stimulating hormone, which is bio-inactive (Gibson et al. 2004). The gene discussed is LEP; the disease is hyperinsulinemic hypoglycemia, familial, 4.