Serum free thyroid hormones in T3-toxicosis: a study of 35 patients.

Few data are available on serum free thyroid hormone concentration in patients with T3-toxicosis. In this study total and free T4 and T3 and TBG were evaluated in 35 subjects with T3-toxicosis, including 12 with untreated Graves' disease, 5 Graves' patients on methimazole treatment, 13 with autonomous adenoma, 3 with multinodular goiter, and 2 with subacute thyroiditis. T4, T3, free T4 (FT4), free T3 (FT3) as well as calculated T4/TBG and T3/TBG ratios were significantly higher in patients than in 37 healthy controls. Serum FT4 levels above the normal range were found in 19 subjects with T3-toxicosis (9 with untreated and one with methimazole-treated Graves' disease, 6 with autonomous adenoma, 1 with multinodular goiter and 2 with subacute thyroiditis). These data, together with the few previous reports, indicate that high FT4 levels are present in about half of the patients with so called T3-toxicosis, and that this occurs more frequently in diffuse than nodular goiter. It is suggested that the term T3-toxicosis be used only for those subjects with normal total and free T4.

Oral glucose tolerance and insulin response after one week's clonidine treatment in hypertensive patients.

Acute clonidine administration is known to induce a significant rise in plasma glucose in man. In order to evaluate the possible effect of prolonged drug treatment on glucose metabolism, paired OGTTs were performed in 12 hypertensive patients (6 with normal and 6 with abnormal glucose tolerance) in basal conditions and following 1-week's administration of clonidine (0.15 mg every 8 h) Basal plasma glucose and serum insulin concentration as well as glucose tolerance and insulin response to oral glucose did not change in either group after treatment. Although the mechanism(s) mediating the transient hyperglycemic action of clonidine are not fully understood, the present findings indicate that this drug does not exert diabetogenic effects during chronic treatment, and suggest that homeostatic mechanisms may counteract the acute effect of clonidine on glucose metabolism.

Effect of loperamide, a peripheral opiate agonist, on circulating glucose, free fatty acids, insulin, C-peptide and pituitary hormones in healthy man.

The effect of acute oral administration of loperamide (4, 8 and 16 mg), a peripheral opiate agonist used in the treatment of diarrhoea, on several metabolic and endocrine variables has been evaluated in healthy volunteers in comparison with placebo. Plasma glucose was significantly raised by all three doses, whereas serum IRI and C-peptide were decreased and serum FFA was significantly increased only after loperamide 8 and 16 mg; serum PRL, GH, LH and FSH did not change. The data suggest that opiates may be involved in the regulation of glycaemia, probably by modifying islet hormone secretion by acting at a peripheral site, since loperamide does not cross the blood-brain barrier. Although the precise mechanism of these actions is unknown, it is suggested that the effects of loperamide are mediated either by stimulation of opiate receptors per se, or by suppression of acetylcholine release from cholinergic nerve endings. The lack of change in pituitary hormone secretion by loperamide is in agreement with previous observations indicating that opiate effects on PRL, GH and gonadotropins occur at the level of the central nervous system.

Metabolic effects of prazosin.

The effects of oral administration of 2 mg prazosin on several metabolic and endocrine variables were evaluated in 12 patients with hypertension (6 with normal and 6 with abnormal glucose tolerance). Prazosin was followed by a rise in plasma glucose and serum free fatty acids (FFA) in both normal and diabetic subjects; there was a trend upward in serum albumin (IRI), but growth hormone (GH), prolactin (PRL), and gastrin did not change. Although these results are in general agreement with metabolic effects of other alpha adrenergic blockers already reported, the rise in plasma glucose is at variance with studies performed with phentolamine.

Effect of four dopamine receptor antagonists on gastrin secretion in healthy subjects.

The effect of 1 week of oral treatment with four antidopaminergic drugs--metoclopramide, sulpiride, haloperidol, and pimozide--on fasting and meal-stimulated serum gastrin levels has been evaluated in healthy subjects. All of the four drugs significantly reduced the gastrin response to a meal, whereas basal concentration was unaffected. It is suggested that this action is mediated by central nervous system dopamine receptor blockade, which might act either via nervous or humoral mechanisms to inhibit gastrin release.

Gastric acid and gastrin secretion after administration of the anti-inflammatory drug, sulindac, in man.

The effects of oral administration of the anti-inflammatory drug, (Z)-5-fluoro-2-methyl-1-[p-(methylsulfinyl)-benzylidene]-indene-3-acetic acid (sulindac, Clinoril) 400 mg/d for 8 days, on basal and submaximal (3 micrograms/kg b.2. i.m.) and maximal (6 micrograms/kg b.w.) pentagastrin-stimulated gastric acid secretion as well as on serum gastrin concentration have been evaluated in female patients affected with osteoarthrosis. No significant changes in either gastric acid or gastrin secretion were induced by the treatment. Serum gastrin levels were also unaltered after acute administration of 200 mg sulindac. These results confirm and extend previous observations suggesting that the drug does not exert major actions on the stomach.

Effect of two antiserotoninergic drugs, methysergide and metergoline, on gastric acid secretion and gastrin release in healthy man.

The effects of acute oral administration of the antiserotoninergic drugs methysergide (3 mg) and metergoline (4 mg) on basal, submaximal (0.6 micrograms/kg i. m.) and maximal (6 micrograms/kg) pentagastrin-stimulated gastric acid secretion, as well as on basal and food-induced gastrin release, have been evaluated in healthy volunteers. Methysergide significantly increased basal and submaximal pentagastrin-stimulated gastric acid secretion, and metergoline significantly inhibited gastric acidity in all experiments. Basal and stimulated serum gastrin concentrations were not modified by either drug. The effect of methysergide on gastric acid secretion was opposed to that of serotonin and was probably dependent on its antiserotoninergic action, but the decrease in gastric acidity caused by metergoline is not easily explained. Although the effect is similar to that of a dopamine infusion, it does not depend on dopamine infusion, it does not depend on dopamine receptor stimulation, since it was not influenced by pretreatment with metoclopramide. It is suggested that it might be due to the weak anticholinergic and/or antihistaminic properties of metergoline.

Prolactin release by intravenous cimetidine in man: evidence for a suprapituitary locus on action.

In an attempt to identify the sites at which cimetidine stimulates prolactin release, the drug was administered intravenously (6 mg/kg body weight) to healthy subjects under basal conditions, during dopamine infusion (1 microgram/Kg-min for 120 min) and after pretreatment with L-dopa plus carbidopa (250 plus 25 mg every 6 for 1 day). The serum prolactin response to cimetidine was abolished by dopamine infusion and almost completely suppressed by L-dopa plus carbidopa administration. These findings suggest that the drug acts on the central nervous system to stimulate prolactin release. Although the mechanism of this action is unclear, it does not seem to depend on an antidopaminergic effect and may be related to blackade of brain H2 histamine receptors.

Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes.

The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.

Effect of bromocriptine administration on gastric acid and gastrin secretion in man.

The effects of acute oral administration of the dopaminergic drug, bromocriptin (5 mg), on basal and submaximal (1 and 3 microgram per kg bw given sc) and maximal (6 mug per kg bw) pentagastrin-stimulated gastric acid secretion and on basal and meal-induced gastrin release have been evaluated in healthy volunteers. Although basal and maximal pentagastrin-stimulated acid output did not change, the response to submaximal pentagastrin doses was significantly increased. Basal and stimulated serum gastrin concentrations were not modified, nor was fasting serum gastrin during chronic bromocriptine treatment (10 mg per day for 90 days) in acromegalic patients. As dopamine infusion is known to reduce basal and pentagastrin-induced gastric acid secretion, the presently reported effect of bromocriptine is not dependent on dopamine receptor stimulation. It is suggested that it might be due to alpha-adrenergic and/or serotoninergic antagonism, both actions being properties of bromocriptine. Alternatively, since bromocriptine, at variance with iv infused dopamine, crosses the blood-brain barrier, the effect of this drug on gastric function might depend on interference by centrally mediated actions on those directly exerted at the gastric level.

Stimulation of prolactin release by intravenous cimetidine: a dose-response study.

The PRL response to iv cimetidine was tested in 8 healthy males and 8 females at 4 different dose levels (0.75, 1.5, 3.0 and 6.0 mg/kg bw). Serum PRL levels were significantly increased in comparison with a placebo study by the second cimetidine dose in both sexes. The PRL response was significantly higher in females than in males at all but the lowest dose tested. A significant correlation between the cimetidine dose and the PRL response was observed. There was no significant modifications in serum GH, LH, FSH, IRI and glucose. Present findings demonstrate that the stimulation of PRL release by iv cimetidine is quite specific and dose-dependent.

Inhibition of prolactin release by serotonin antagonists in hyperprolactinemic subjects.

Metergoline (4 mg) and methysergide (3 mg), two serotonin antagonists known to inhibit prolactin secretion in normal subjects, and the dopaminergic agonist, bromocriptine (2.5 mg) were orally administered in hyperprolactinemic patients. Mean serum prolactin concentration was significantly decreased between 120 and 240 min following the ingestion of all three drugs in comparison with a placebo; a consistent reduction to below 50% of basal values occurred in 10 of 14 patients after metergoline, in 5 of 10 after methysergide, and in 11 of 14 after bromocriptine administration. These data indicate that serotonin antagonists may acutely lower serum prolactin levels in hyperprolactinemic patients similarly to bromocriptine, though their mechanism of action is most likely different.

Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man.

The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.

Effect of short-term clofibrate on glucose metabolism and insulin secretion in patients with mild maturity-onset diabetes mellitus.

The effect of 1 week clofibrate administration on glucose and insulin responses to oral glucose and to intravenous tolbutamide was evaluated in 21 patients with mild maturity-onset diabetes (fasting plasma glucose 108-152 mg/100 ml). After treatment, oral glucose tolerance and hypoglycaemic effect of tolbutamide were significantly improved; plasma insulin response was reduced after glucose and unmodified after tolbutamide; fasting plasma glucose was also significantly reduced. These findings did not correlate with the observed fall in serum lipids. Short-term clofibrate improves glucose metabolism in mild diabetes irrespective of its effects on lipid metabolism. It is suggested that the drug's action may be mediated by reduced insulin resistance.

Failure of lysine-acetylsalicylate and phenylbutazone to affect gastrin secretion in healthy adults.

The effect of acute parenteral and chronic oral administration of lysine-acetylsalicylate and phenylbutazone on fasting and meal-stimulated serum gastrin levels was investigated in healthy volunteers. No significant changes in gastrin secretion were induced by any treatment. The results confirm and extend previous observations suggesting that the ulcerogenic properties of salicylates and phenylbutazone are not related to increased gastrin secretion.