Growth hormone releasing hormone priming increases growth hormone secretion in patients with Cushing's syndrome

Summary OBJECTIVE In patients with Cushing's syndrome, decreased growth hormone (GH) secretion is observed though the basic mechanism is unknown. In states of chronic deficiency of hypothalamic growth hormone releasing hormone (GHRH) release, a blunted GH response to exogenous GHRH has been reported; such impairment can be partially normalized by repetitive GHRH administration (priming). In order to clarify whether a deficit in hypothalamic release of GHRH is the basis of the decreased GH secretion in patients with Cushing's syndrome, GHRH plus pyridostigmine tests were undertaken, both before and after GHRH priming. DESIGN GHRH (200 μg/day as a single s.c. injection) was given daily over 7 days. Two pyridostigmine (120 mg p.o.) plus GHRH (100 μg i.v.) tests were performed before and after priming to assess GH response. PATIENTS Eight patients (seven women, one man), with untreated Cushing's syndrome (six Cushing's disease, one autonomous bilateral adrenal hyperplasia, one adrenal adenoma), were studied. MEASUREMENTS Plasma GH levels were measured by immunoradiometric assay. RESULTS GHRH plus pyridostigmine‐induced GH release was impaired in patients with untreated Cushing's syndrome (mean peak 52 ± 14 mU/l, area under the curve (AUC) 472 ± 96). Repetitive administration of GHRH over 7 days partially restored the GH response to the second pyridostigmine‐GHRH test (mean peak 150±21 mU/l. AUC 1016±104), both P < 005. All of the eight Cushing's syndrome patients studied presented a higher GHRH plus pyridostigmine‐induced GH secretion after priming. CONCLUSIONS Repetitive administration of GHRH increases the pyridostigmine‐GHRH‐induced GH secretion in patients with Cushing's syndrome. This suggests that impaired hypothalamic release of GHRH is a contributing factor to the decreased GH secretion observed in chronic hypercortisolism.