V. Popovic et al., MODULATION BY GLUCOCORTICOIDS OF GROWTH-HORMONE SECRETION IN PATIENTSWITH DIFFERENT PITUITARY-TUMORS, Neuroendocrinology, 58(4), 1993, pp. 465-472
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.