McCune-Albright syndrome (MAS) is a disorder characterized by the triad of café-au-lait skin pigmentation,
polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product,
G(s)alpha. The term gsp oncogene has been assigned to these mutations due to their association with certain
neoplasms. The aim of this study was to estimate the prevalence of GH excess in MAS, characterize the clinical and endocrine manifestations, and describe the response to treatment. Fifty-eight patients with MAS were screened, and 22 with stigmata of
acromegaly and/or elevated GH or
IGF-I underwent oral
glucose tolerance testing. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral
glucose tolerance test, and underwent a TRH test, serial GH sampling from 2000-0800 h, and magnetic resonance imaging of the sella. We found that vision and hearing deficits were more common in patients with GH excess (4 of 12, 33%) than those without (2 of 56, 4%). Of interest, patients with a history of
precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH, 11 of 12 (92%) had
hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels.
Pituitary adenoma was detected in 4 of 12 (33%) patients. All patients with elevated
IGF-I levels were treated with
cabergoline (7 patients), long-acting
octreotide (LAO; 8 patients), or a combination of
cabergoline and LAO (4 patients). In six of the seven patients (86%) treated with
cabergoline, serum
IGF-I decreased, but not to the normal range. In the eight patients treated with LAO alone,
IGF-I decreased, and, in four, returned to the normal range. The remaining 4 patients were treated with a combination of
cabergoline and LAO. For them, symptoms of GH excess diminished, and
IGF-I decreased further, but did not enter the normal range. GH excess is common in MAS and results in a distinct clinical phenotype characterized by inappropriately normal stature, TRH responsiveness,
prolactin cosecretion, small or absent
pituitary tumors, a consistent but inadequate response to treatment with
cabergoline, and an intermediate response to LAO.