MODULATION BY GLUCOCORTICOIDS OF GROWTH-HORMONE SECRETION IN PATIENTSWITH DIFFERENT PITUITARY-TUMORS

The acute administration of glucocorticoids is a new stimulus of growt h hormone (GH) secretion in man. In order to ascertain its point of ac tion, and also the suitability of this new test as a diagnostic tool i n GH pathological states, 33 subjects were studied. Eight of them were normal controls, and 25 were patients with tumors affecting the hypot halamopituitary area. A glucocorticoid stimulus, dexamethasone 4 mg i. v. was administered at 0 min and GH levels (means +/- SEM, mu g/l) wer e measured during the following 5 h. In addition, GH-releasing hormone (GHRH) and clonidine were employed as either pituitary or hypothalami c GH stimuli. Dexamethasone administration to normal subjects did not alter GH levels in the first 2 h of the test. Afterwards, a GH peak wa s observed around the third hour, GH levels returning to basal ones th ereafter. The dexamethasone-induced GH peak(6.7 +/- 1.5) and area unde r the curve(526 +/- 137) were lower than after GHRH (14.0 +/- 4.5 and 1,070 +/- 369, respectively). In the 14 acromegalic patients studied, the GHRH-induced GH net increase was similar to that observed in contr ols, while the placebo did not alter GH basal levels. An absence of hy pothalamic control was evident because clonidine did not stimulate GH release. On the other hand, and contrary to normal subjects, dexametha sone strongly inhibited GH secretion, the values being significantly l ower when calculated either as mean GH peak, or maximum GH increment ( Delta). The Delta GH was -2.5 +/- 3.1 after placebo, +3.7 +/- 4.5 afte r clonidine, +17.0 +/- 3.3 after GHRH and -13.4 +/- 4.5 following dexa methasone administration. In 4 patients harboring pituitary prolactino mas, dexamethasone stimulated GH secretion in 1 subject with a microad enoma but was devoid of action in the 3 marcoprolactinoma patients, wh ich had suprasellar extension and absent clonidine-induced GH secretio n. Similarly, in 4 out of 5 patients with nonsecreting pituitary adeno mas that had a functional pituitary stalk section (suprasellar extensi on, mild prolactin levels and no GH response to hypothalamic stimulus) , dexamethasone was ineffective, while it stimulated GH secretion in t he other patient of this group with a normal hypothalamopituitary conn ection. In addition, in 2 other patients with hypothalamic germinoma a nd well-preserved GH response to GHRH, dexamethasone was devoid of act ion. These results indicate that GH stimulation by glucocorticoid is o nly observed in normal subjects and requires a normal hypothalamopitui tary connection. On the contrary, in acromegaly, glucocorticoids induc ed, instead, an inhibition of GH secretion. In conclusion, glucocortic oid stimulatory action over GH secretion seems to be exerted at the hy pothalamic level. On the contrary, in acromegalic patients a 'paradoxi cal' inhibition of GH secretion is observed after glucocorticoid injec tion. Acute administration of glucocorticoids may be a suitable test i n the diagnosis and follow-up of GH pathological states.