Our data reinforce the crucial role of DIO2 in the brain as a protective enzyme rescuing from peripheral TH deficiency [5], and once again demonstrate that the circulating TH levels do not necessarily reflect the brain T3 availability [8] and that the local TH signalling is physiologically and functionally more relevant than circulating TH levels. The gene discussed is TH; the disease is hyperinsulinemic hypoglycemia, familial, 4.