Elevated basal growth hormone levels and growth hormone response to TRH in alcoholic patients with cirrhosis.

Basal plasma growth hormone (GH) and GH responses after the administration of thyrotropin releasing hormone (TRH) were studied in 9 male alcoholic patients with cirrhosis. Basal GH was significantly higher in cirrhotic patients than in normal men. Intravenous injection of synthetic TRH (400 microgram) caused a significant increase in plasma GH in 7 out of the 9 cirrhotic patients examined, while it did not increase GH levels in normal subjects.

Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation.

Growth hormone (GH) response to clonidine and growth hormone-releasing hormone (GHRH) stimulation, together with baseline somatomedin C (SmC) levels, were examined in parallel in a group of 21 patients with anorexia nervosa (AN) and in 10 controls. In addition, the Hamilton Rating Scale for Depression (HRS) was administered to the patients. Clonidine (2.5 micrograms/kg body weight, iv) induced GH elevations that were not significantly different between patients and controls. In contrast, GHRH (1 microgram/kg body weight, iv) produced a significantly higher GH response in anorectics than in controls. The ratio between GH responses (area under the curve, or AUC) to GHRH and to clonidine was significantly higher in patients than in controls. Baseline SmC levels (6 patients) were significantly lower in anorectics than in controls. Minor depressive symptomatology was present in all patients. When viewed in relation to the GH hyperresponsiveness to GHRH, the apparent normality of the response to clonidine in anorectics reflects the existence of an actual alpha 2-adrenoceptor subsensitivity. As clonidine reportedly acts via release of endogenous GHRH, an excessive, rather than a normal, GH response to clonidine was to be anticipated.

Stimulation of insulin secretion in man by oral glycerol administration.

The effects of an orally administered glycerol load (1 g/Kg body weight) on blood glucose, plasma FFA, and plasma insulin levels have been determined in eight normal fasting or glucose loaded (1 g/Kg body weight) volunteers. Blood glucose levels were not affected by glycerol loading while glicemia followed the same pattern of a glucose tolerance test in the group treated with glucose plus glycerol. Plasma FFA were significantly lowered only 90 min after glycerol loading while they had markedly and persistently decreased by glycerol plus glucose per os. Finally, though glicemia did not change, insulinemia was markedly increased by glycereol, 90 min after loading; moreover, plasma IRI was significantly higher in the group treated with glycerol plus glucose than in the group treated with glucose alone. These data suggest that the release of insulin may be stimulated by a very small increment of blood glucose, which derives from glycerol.

Effects of naloxone and coffee on anterior pituitary hormones.

Both naloxone, a specific opiate antagonist, and caffeine and other components of coffee powders show influences on opiate receptors and on the secretion of some pituitary hormones. In order to study the possible effect of naloxone and coffee on the secretion pattern of hypophyseal hormones in man, experiments were performed in normal volunteers using either naloxone or coffee alone or both substances. Five healthy normal males, aged 25-30 years, received on three separate occasions and in random order: (i) coffee (4 cups of Italian style "espresso" coffee); or (ii) naloxone 12 micrograms/kg i.v.; or (iii) coffee plus naloxone simultaneously. The results show that naloxone given alone did not modify basal plasma PRL, GH, TSH, FSH or cortisol levels but significantly increased basal LH concentrations. On the other hand, the absorption of four cups of coffee did not modify the values of any of the hormones studied. The combination of the two drugs (coffee + naloxone) did not alter the response of the hormones studied to naloxone alone. It was concluded that coffee drinking, at least in these experimental conditions, does not appear to have any influence on anterior pituitary hormone secretion. Naloxone, on the other hand, is able to stimulate LH secretion even at very low doses.

Multicentre clinical study with flunoxaprofen in osteoarthritis: preliminary data on 154 patients.

Flunoxaprofen S-(+)-2 [p-fluorophenyl]-alpha-methyl-5-benzoxazole acetic acid, a new propionic acid derivative, was studied to investigate its long-term effectiveness and tolerability in the management of osteoarthritis (OA). To the study were admitted 154 patients suffering from radiologically proven OA of the large joints; 37% of them were hospitalized. The patients received flunoxaprofen 100 mg twice daily for a period of 45-60 days. The variables investigated were: pain at rest, pain on passive motion and pain on active motion with or without load, quality of sleep, articular flexion. In addition, the usual clinical and laboratory controls were carried out (arterial blood pressure, hepatic and renal function tests, haematological examinations). The assessments were made before and at 15, 30, 45 and 60 days of treatment. The results obtained show significant improvements for all variables considered and a very good tolerability of the drug concerning either laboratory controls or adverse reactions.

Failure of inhibition by TRH of L-Dopa stimulated GH secretion in patients with alcoholic cirrhosis of the liver.

We have investigated the effects of a single oral dose of L-Dopa (500 mg) or of an i.v. infusion of TRH (1 mg dissolved in 400 ml of saline solution) or both administered together, on GH release in men with alcoholic cirrhosis of the liver, and compared them with responses in normal subjects. The results obtained in normal subjects confirm that TRH does not modify plasma GH levels, L-Dopa elevates GH concentrations, while the administration of these two drugs together significantly inhibits GH release induced by oral L-Dopa. In contrast, in patients with alcoholic cirrhosis of the liver, the following results were obtained: 1 TRH infusion significantly increased plasma GH levels which were steadily elevated throughout the experiment; 2 oral administration of L-Dopa provoked a significant rise in blood GH over the basal values similar to that observed in normal subjects; 3 when TRH and L-Dopa are administered at the same time a GH increase like that observed after L-Dopa alone was obtained. These results clearly demonstrate that in patients with alcoholic cirrhosis of the liver the normal inhibitory effect of TRH on L-Dopa induced GH release is completely lost.

Effect of pinealectomy on arterial blood pressure and food and water intake in the rat.

Pinealectomy in the rat induces a significant increase of the arterial blood pressure within 15 days from the surgical procedure; this hypertension is still present 30 and 60 days after pinealectomy while after 90 days it returns to the normal range. Histological examination of the kidneys of pinealectomized hypertensive rats shows wall thickening and lumen narrowing of the arterioles, adventitial and periadventitial fibrosis, dense glomeruli. The vascular lesions are not diffuse but patchily distributed. Body weight is higher in pinealectomized rats compared with normal and sham-operated animals: this difference becomes significant about 40 days after pinealectomy and gradually decreases until it disappears at the end of the third month. Food and water intake is higher in pinealectomized rats up to the 7th week; during the 8th week they return to the normal range.

Suppression of clonidine-induced release of growth hormone by thyrotropin releasing hormone in humans.

A single oral dose of clonidine (0.15 mg), a selective alpha-adrenergic stimulating agent, was able to increase plasma growth hormone (GH) levels (above 5 ng/ml) in 6 out of 7 normal men tested. This GH increase was independent of the hypotensive effect of the drug and was observed without any modification of plasma prolactin, thyroid stimulating hormone, gonadotropins and glycemia. When oral clonidine administration was associated to a slow thyrotropin releasing hormone (TRH) infusion (1 mg dissolved in 400 ml of 0.9% saline solution, at a constant rate during 150 min) the plasma GH response was significantly inhibited when compared with that observed after clonidine alone. These results suggest that in normal subjects TRH is capable of blocking the effect of an alpha-adrenergic stimulus which is conceivably acting at the level of central nervous system.

Enhanced TSH stimulating effect of TRH by sulpiride in man.

Sulpiride, a specific dopaminergic blocker, was administered im to 6 normal male volunteers (100 mg) alone or in association with L-DOPA (500 mg per os, 90 min before sulpiride) or with TRH (400 micrograms iv in bolus, 30 min after sulpiride) and blood samples were obtained for TSH radioimmunoassay at various intervals before and after the treatments. Sulpiride alone produced a slight increase of plasma TSH levels which was inhibited by L-DOPA pre-treatment. The previous administration of sulpiride resulted in a marked increase of the TSH response to TRH. It is suggested that dopamine and TRH may interact to modulate pituitary secretion of both TSH and prolactin, though the hypophyseal thyrotrophs and lactotrophs show a different sensitivity to the common stimulatory and inhibitory substances.

Inhibitory effect of cimetidine on L-dopa-stimulated growth hormone release in normal man.

Some evidence suggests the existence of a histaminergic influence on GH secretion in animals and man. We used cimetidine, a specific H2-receptor antagonist, to study the possible interference of H2-receptor blockade on plasma GH release by L-dopa and on PRL inhibition by L-dopa in normal man. Seven healthy normal male volunteers aged 23-36 years received a single oral dose of L-dopa (500 mg) or an i.v. bolus of cimetidine (300 mg) or both (L-dopa 30 min before cimetidine). Blood samples were taken at various times over 2 h and plasma GH and PRL levels measured. Cimetidine alone did not alter basal plasma GH values; L-dopa elicited the well-known GH releasing effect with peak values at 75 min (15.65 +/- 2.8 ng/ml); cimetidine injected 30 min after L-dopa ingestion significantly blunted the GH response to L-dopa and peak values (4.7 +/- 1.6 ng/ml) were delayed to 105 min. Cimetidine provoked a rapid rise in plasma PRL with the peak value of 15 +/- 3 ng/ml at 15 min, followed by a return to near basal values in 90-120 min. L-Dopa completely inhibited the PRL response to cimetidine. We conclude that there is an inhibitory influence of the H2-receptor antagonist cimetidine on GH release by L-dopa. This, together with the action of cimetidine on PRL secretion (with or without L-dopa), suggests a possible antidopaminergic effect of H2-receptor blockade at the level of the central nervous system.

Inhibitory influence of thyrotropin releasing hormone administration on growth hormone response to low doses of growth hormone-releasing hormone in normal man.

Literature data show that TRH may have either stimulatory or inhibitory actions on GH release according to pathophysiological conditions of the subject. In view of this dual effect of TRH, we studied the possible interaction of TRH and GRF on GH secretion. Six healthy male volunteers received iv in different occasions and in random order: 1) GRF 0.05 micrograms/Kg; 2) GRF 0.1 micrograms/Kg; 3) GRF 1 microgram/Kg; 4) GRF 0.05 micrograms/Kg + TRH 400 micrograms, simultaneously; 5) GRF 0.05 micrograms/Kg + TRH 20 micrograms, simultaneously; 6) GRF 1 microgram/Kg + TRH 400 micrograms, simultaneously, 7) the vehicle as control treatment. Blood samples were obtained at several time intervals and plasma GH, PRL and TSH were measured by RIA methods. Plasma GH significantly increased in all subjects after all the tested doses of GRF and after the combination of the highest and of the lowest doses of GRF + TRH (treatments 6 and 5). GH responses increased progressively with the dose of GRF administered, even if a clear dose-response relationship could not be demonstrated, owing to the considerable interindividual variability in the responsiveness. The administration of GRF 0.05 micrograms/Kg increased significantly plasma GH levels vs control treatment. The simultaneous administration of a low effective dose of GRF (0.05 micrograms/kg) plus a high dose of TRH (400 micrograms) was able to significantly inhibit the GH secretion elicited by GRF 0.05 micrograms/Kg alone. The other GRF + TRH combinations tested (treatments 5 and 6) did not modify the GH response to the same doses of GRF given alone. Plasma PRL and TSH did not change either after GRF at any dose or after the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic heroin addiction on pituitary-thyroid function in man.

Pituitary-thyroid function has been studied in heroin addicts. Data have been obtained in 10 male addicts, aged 18-24 years, with histories of addiction to heroin alone lasting from 8 months to 4 years, and in 9 controls matched for sex and age. Basal plasma levels of TSH, T4 and T3 were measured. A TRH stimulation test was done, injecting 500 micrograms of TRH iv as a bolus and assaying TSH levels before the injection and at 30 min intervals up to 2 h afterwards. The results revealed no difference between addicts and controls in basal levels of TSH, T4 and T3. The TRH stimulation test induced a blunted TSH rise in 50% of the cases. The possible mechanism of action of heroin on pituitary-thyroid axis is discussed.

Growth hormone response to thyrotropin-releasing hormone and gonadotropin-releasing hormone stimulation in heroin addicts.

Previous endocrine investigations have demonstrated the presence of multiple impairments of pituitary-target gland function in heroin addicts suggesting a possible hypothalamic involvement. Since the response of the pituitary to nonspecific stimuli is considered an expression of hypothalamic dysfunction, indicating a disconnection between the central nervous system and the anterior pituitary, we thought it worthwhile to study the GH response to stimulation with thyrotropin-releasing hormone (TRH) or gonadotropin-releasing hormone (GnRH) in heroin addicts. 23 male heroin addicts, aged 18-40 years, with histories of addiction to heroin alone from 8 months to 4 years, and daily i.v. heroin intakes between 200 and 2,500 mg of the drug (containing 18% pure heroin) were studied. 8 patients received TRH 500 micrograms, GnRH 150 micrograms and 5 saline only, intravenously, and GH levels were assayed radioimmunologically in bloods taken 30 min before, at the moment of stimulation and 15, 30, 60, 90 and 120 min thereafter. The results show normal base GH levels. Stimulation with TRH and GnRH induced marked GH hypersecretion in 8 of the 18 patients examined. These results suggest that the hypothalamo-pituitary function may be impaired in heroin addiction.

Glucose-insulin metabolism in chronic schizophrenia.

The present study deals with possible connections between the schizophrenic syndrome and alterations of the glucose-insulin metabolism. Data have been obtained in 18 patients, 9 males and 9 females, aged 22-62 years, suffering from chronic schizophrenia of 5-29 years duration. The patients were treated with Haloperidol for 30 days, 6 mg, i.m.p.d. to a total dose of 180 mg. The glucose metabolism was examined through a GTT (with a glucose load of 100 gr. per os), and an Insulin Tolerance Test (with 0.1 U/kg body weight). The insulin levels were examined under glucose load by the radioimmunological assay of Hales and Randle. The glycemic levels were examined under glucose load by an oxidative method. The psychopathological features were controlled by a Wittenborn Rating Scale. The metabolic and psychological examinations were done twice before the beginning of therapy, at 46 hrs. interval, then at 10-20-30 days of therapy. The results are probative for the presence of a chemical diabetes in a significantly high percent of patients. The significance of possible neurotransmitter impairments acting at both the biochemical and psychological levels is discussed.