Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.