A paradoxical GH response to TRH may also be observed in nonacromegalic conditions (eg, depression, anorexia nervosa, untreated primary congenital hypothyroidism) where it has been hypothesized to reflect dysregulation of the normal dopaminergic or somatostatin-mediated inhibitory effects on GH release, supporting the argument that although a somatotrope-autonomous role for IGSF1 is possible, additional hypothalamic dysfunction may also contribute to GH excess (53, 54). This evidence concerns the gene IGSF1 and primary congenital hypothyroidism.