Extrahypothalamic Growth-Hormone-Releasing Factor (GRF) Secretion Is a Rare Cause of Acromegaly: Plasma GRF Levels in 177 Acromegalic Patients*

Abstract

To assess the frequency with which acromegaly is caused by ectopic secretion of GRF, we collected plasma samples from 177 unselected acromegalic patients. The samples together with those of three acromegalic patients with previously diagnosed tumors secreting GRF and of normal subjects were assayed in 3 independent GRF RIAs. Plasma immunoreactive GRF (IR-GRF) levels in normal subjects were either undetectable or detectable at levels up to 62.5 pg/ml. In none of the 177 specimens from acromegalic patients were IR-GRF values detectable in all assays, and in the most sensitive assay, the levels were similar to those in normal subjects, with the highest level measuring 82 pg/ml. In contrast, plasma IR-GRF found in the 3 patients with tumors that secreted GRF ranged from 2.0-24.4 ng/ml. These data suggest that extrahypothalamic GRF secretion is a rare cause of acromegaly. However, it is important that this rare cause of acromegaly be diagnosed before the patient has unnecessary surgery and/or irradiation directed at the pituitary. We recommend that plasma IR-GRF be measured in each new acromegalic patient.

Pathophysiology and clinical aspects of the ectopic GH‐releasing hormone syndrome

“…Since high levels of plasma GHRH have been detected in all the acromegalic patients with ectopic GHRH syndrome in which they were measured (see below), the best method of inferring the prevalence of the syndrome in the general population is to measure GHRH levels in a group of unselected patients with acromegaly. In such a study, Thorner et al (1984), using three different radioimmunoassays for GHRH, did not find any patient with elevated plasma GHRH concentration among 177 consecutive acromegalic patients, suggesting that the incidence of the ectopic GHRH syndrome probably does not exceed 0 . 5% of all cases of acromegaly.…”

Paraneoplastic syndromes secondary to neuroendocrine tumours

“…This PNS is more commonly related to GHRH-hypersecretion and rarely to GH itself; however, its rarity may be related to the fact that clinical presentation is usually subtle, and GHRH measurement is not widely available (Biermasz et al 2007). NETs most commonly associated with GHRH hypersecretion are carcinoids, PICTs, SCLCs and phaeochromocytomas, with w70 cases having been described (Thorner et al 1984, Faglia et al 1992, Biermasz et al 2007, Vieira et al 2007). However, GHRH tumoral immunoreactivity without clinically obvious acromegaly is found in up to 17% of gastroenteropancreatic NETs (Dayal et al 1986).…”

Acromegaly and Gigantism

“…In children and young adults, maximal GH secretion occurs within 1 hour after the onset of deep sleep (stage III or IV) (Finkelstein et al, 1972;Mendelson, 1982;Takahashi et al, 1968). Two hypothalamic hormones regulate GH secretion; Growth hormone releasing hormone (GHRH) provides the primary drive for GH synthesis and secretion by inducing GH gene transcription and hormone release and does not induce other anterior pituitary hormones (Barinaga et al, 1983;Thorner et al, 1984). GHRH is needed for normal pulsatile GH secretion (Painson et al, 1991;Wehrenberg et al, 1982].…”

“…Pituitary carcinomas are another exceedingly rare cause of acromegaly. Infrequently acromegaly occurs as a result of a hypothalamic tumor secreting GHRH, ectopic secretion of GHRH from a peripheral neuroendocrine tumour (Thorner et al, 1984) or from excessive hypothalamic GHRH secretion (Asa et al, 1984). Several genetic disorders including multiple endocrine neoplasia type 1 (MEN1) syndrome, McCune Albright syndrome, familial acromegaly and Carney's syndrome are also characterized with growth hormone excess.…”