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We investigated the effect of an orally administered, long-acting, beta-adrenergic blocking agent, penbutolol, on the circadian rhythm of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) levels in hospital patients with essential hypertension validated by a chronobiological inferential statistic method. After a wash-out period of three weeks, a group of 8 hypertensive patients (5 women and 3 men, 27 to 41 years old) underwent automatic BP and HR monitoring, and blood sampling for 24 hours in a hospital room before and after 4 weeks of treatment with penbutolol (40-mg tablet once a day at 9 a.m.). In basal conditions, a statistically significant mean circadian rhythm was demonstrated for HR, diastolic BP, PRA, PA, and PC. Systolic and diastolic BP were lowered by penbutolol, with only a minor decrease of HR. The treatment eliminated also the mean circadian rhythm of BP and HR. Penbutolol induced both a remarkable reduction of PRA with disappearance of the related circadian rhythm and a significant decrease in PA levels with maintenance of their circadian rhythmicity. The circadian secretory patterns of PC were similar before and after therapy. In conclusion, long-term treatment with penbutolol appears not only to set BP, PRA and PA values to lower levels, but also to decrease the within-day variation of BP, HR, and PRA. In addition, penbutolol does not influence the 24 h-secretion of PC.

The effects of iv somatostatin (somatotrophin release inhibiting factor (SRIF) on growth hormone (GH) and prolactin (Prl) response to dermorphin (D) were tested in 6 healthy men. In all subjects D induced a significant increase in GH and Prl levels, as expected. SRIF completely blocked the GH-releasing activity of D, whereas it only reduced the Prl-releasing activity. The results confirm that D is a potent stimulant for GH and Prl release in man, and furthermore demonstrate that the action of D on GH secretion can be completely overridden by SRIF.

We have recently shown that dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) stimulates prolactin (PRL) and growth hormone (GH) secretion in humans. In 11 patients with a PRL-secreting pituitary adenoma (eight microprolactinomas and three macroprolactinomas with suprasellar extension), diagnosed by pituitary dynamic function tests, and radiological evidence with confirmation at surgery, the PRL and GH responses to D were studied to evaluate the effect of pathological hyperprolactinemia on the opioid-induced secretion of GH and PRL. No PRL response to D was observed in all 11 patients. Plasma GH increased after D in all patients, except in three patients bearing a macroprolactinoma. This study shows that the effect of D on PRL and GH secretion can be dissociated in patients with PRL-secreting pituitary adenoma, perhaps for a different derangement in the hypothalamic-pituitary mechanism(s) underlying the opioidergic regulation of GH and PRL secretion. In addition our data indicate that D can be employed as a useful opioid probe in humans.

The aim of this study was to investigate further the influence of dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on the functional activity of the pituitary-adrenocortical system in man. Six normal men were treated with oral metyrapone to stimulate the secretion of ACTH, beta-lipotropin, and beta-endorphin. In these subjects, significant suppression of metyrapone-evoked release of ACTH and related peptides occurred during D infusion (5.5 micrograms/kg X min for 30 min) compared with that during saline infusion. These results indicate that D can induce a significant decline in plasma levels of ACTH, beta-lipotropin, and beta-endorphin, the major circulating peptides from the C-terminal part of proopiocortin, and suggest that opioid peptides may be involved in the control of the functional activity of pituitary-adrenocortical activity in man.

Empty sella syndrome is an anatomical entity in which the pituitary fossa is enlarged and partially filled with cerebrospinal fluid owing to the arachnoid herniation, while the pituitary gland is compressed against the posterior rim of the fossa. This condition can be due to an inherent weakness of the diaphragm sella and/or to an increase in intracranial pressure which promote the herniation of the arachnoid membrane into the pituitary fossa (primary empty sella) or it can results following surgery, radiation or vascular and tumorous pituitary diseases (secondary empty sella). Empty sella can be associated with neuroradiological and endocrine symptoms. This study reports the clinical, endocrine, and roentgenographic features in 20 patients with primary empty sella syndrome. Disturbances of hypothalamic-pituitary function were detected in 6 patients (hyperprolactinemia, hypopituitarism, central diabetes insipidus, hypothalamic hypothyroidism). Three patients exhibited hypergonadotropic hypogonadism. This report supports the following conclusions: a) there is no correlation between size of pituitary fossa, type an extension of arachnoid herniation and the degree of hypothalamic-pituitary dysfunction; b) endocrine alterations are frequent in the empty sella syndrome; c) the association of empty sella and primary diabetes insipidus is not a very rare event.