DIVERGENCE BETWEEN GROWTH-HORMONE RESPONSES TO INSULIN-INDUCED HYPOGLYCEMIA AND GROWTH HORMONE-RELEASING HORMONE IN PATIENTS WITH NONFUNCTIONING PITUITARY MACROADENOMAS AND HYPERPROLACTINEMIA

OBJECTIVE The GH responses to the insulin tolerance test (ITT) and gro wth hormone-releasing hormone (GHRH) may yield different results in pa tients with pituitary lesions. The GH responses to these stimuli were compared in patients with untreated non-functioning pituitary macroade nomas, who represent an important cause of GH deficiency. DESIGN Analy sis of peak on to ITT and to 100 mu g GHRH in relation to an elevated PRL level (> 200 mIU/l for males and > 600 mIU/l for females) as an in dication of hypothalamic-pituitary dysregulation, as well as in relati on to other anterior pituitary hormone deficiencies. A peak GH < 5 mu g/l in either test indicated GH deficiency. PATIENTS Twenty females an d 14 males (median age 52 (23-77) years) evaluated preoperatively in a university hospital setting. RESULTS In the whole group the median pe ak GH to GHRH (3.6 (0.9-26.3) mu g/l) was higher than to ITT (1.6 (0.2 -7.8) mu g/l, P < 0.001). This difference was seen only in 19 patients with concomitant hyperprolactinaemia (P < 0.001). When hyperprolactin aemia was present, an insufficient GH peak was demonstrated by ITT in 16 cases and by GHRH stimulation in 7 cases (P < 0.01). The frequency of an insufficient GH peak by ITT (13 cases) and by GHRH (14 cases) wa s similar in the normoprolactinaemic patients. In addition, 9 of 10 pa tients with an impaired response to ITT and a normal response to GHRH were hyperprolactinaemic compared to 7 of 19 patients with GH deficien cy as assessed by both stimuli (P < 0.02). Peak GH to ITT was lower in 24 patients with, compared to 10 patients without, other hormonal def iciencies (1.4 (0.2-5.6) vs 3.0 (1.0-7.8) mu g/l, P < 0.02), but was n ot related to elevated PRL. In contrast, GHRH-stimulated GH was higher in hyperprolactinaemic than in normoprolactinaemic patients (5.9 (1.6 -26.3) vs 2.9 (0.9-5.4) mu g/l, P < 0.001) and was not related to the presence of other pituitary hormone deficiencies. Analysis of covarian ce confirmed that peak GH to ITT was negatively associated with the pr esence of other pituitary hormone deficiencies (P < 0.01), whereas pea k GH to GHRH was positively related to an elevated PRL level (P < 0.02 ). nasal GH was positively correlated with PRL (R(s) = 0.36, P < 0.05) . CONCLUSIONS This study demonstrates that ITT and GHRH tests cannot b e used interchangeably in diagnosing GH deficiency in patients with no n-functioning pituitary macroadenoma and hyperprolactinaemia. If the I TT is considered to be the reference test, GH deficiency as assessed b y GHRH can be missed in patients with hyperprolactinaemia. This dispar ity is probably due to a different mechanism of action of these stimul i. Hyperprolactinaemia may be associated with a diminished somatostati n tone, leading to a higher basal and GHRH-stimulated GH, without havi ng an effect on peak GH to ITT.