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Biomedical subjects

A Paracchi

Publications and source records attributed to A Paracchi.

At least 37 records · Page 2Linked to original sources

Effects of ibopamine on serum prolactin and growth hormone levels in hyperprolactinemic and acromegalic subjects.

The effects of oral doses (100, 200, and 400 mg) of a dopamine derivative, ibopamine, on serum prolactin (PRL) and growth hormone (GH) levels were evaluated in hyperprolactinemic patients, some of whom also were acromegalic. There was dose-related lowering of PRL levels. The highest dose was as effective as 500 mg L-dopa, although the duration of action was shorter, with a decrease to below 50% of basal PRL values in all patients. Serum GH did not rise in nonacromegalic subjects, but it fell after 400 mg ibopamine in the L-dopa-sensitive acromegalic patients. These data suggest, but do not prove, that ibopamine is able to directly stimulate pituitary dopamine receptors.

Acromegaly↗

Prolactin response to the dopamine antagonists sulpiride and domperidone. Further evidence for pituitary dopamine deficiency in hyperprolactinemic disorders of different etiology.

The PRL response to the dopamine antagonists sulpiride (100 mg i.m.) or domperidone (2 or 8 mg i.v.) was evaluated in healthy controls and in 148 patients with different hyperprolactinemic disorders (50 with idiopathic hyperprolactinemia, 58 with microprolactinoma, 19 with macroprolactinoma, 2 with empty sella, 8 with acromegaly, 7 with organic lesions of the hypothalamus, and 4 with idiopathic hypopituitarism of presumed hypothalamic origin). Mean PRL response to both drugs was significantly lower in all groups of patients than in controls, and significantly higher in subjects with idiopathic hyperprolactinemia than in those with pituitary adenomas or hypothalamic disease. Absent or impaired PRL responses were found in 38% of idiopathic patients, in 91.5% of microprolactinomas and in all of the patients with either macroprolactinoma, acromegaly, or hypothalamic disorders. Since the PRL response to dopamine antagonists depends on the presence of an endogenous dopaminergic tone, it is suggested that these figures reflect the incidence of major dopamine deficiency at pituitary lactotrophs in different hyperprolactinemic states. These data suggest that the pathophysiology of hyperprolactinemia in many patients with idiopathic disease is different from that of microprolactinoma. However, the finding of a normal PRL response to sulpiride in some subjects with radiologically or surgically proven microprolactinoma indicates that this test has no diagnostic value in the individual case.

Adolescent↗

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.

Adrenergic alpha-Antagonists↗

Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin.

TSH concentration was measured in plasma before and after TRH administration (200 micrograms, iv) in 89 patients with documented hypothyroidism consequent to various hypothalamic-pituitary disorders. Basal plasma TSH was less than 1.0 microI/ml in 34.8%, between 1.0-3.6 microU/ml in 40.5% and slightly elevated (3.7-9.7 microU/ml) in 24.7% of the cases. The plasma TSH response to TRH was absent in 13.5%, impaired in 16.8%, normal in 47.2%, and exaggerated in 22.5% of the cases, with delayed and/or prolonged pattern of response in 65% of the cases. The dilution curves of several plasmas drawn before and after TRH were parallel to those obtained with TSH standard preparation. After gel filtration, the elution pattern of TRH-stimulated plasmas from 4 patients did not show any major difference from that of pooled plasmas from normal subjects given TRH or from that of patients with primary hypothyroidism. Plasma TSH values determined by cytochemical bioassay on both basal and TRH-stimulated samples of 5 patients were markedly lower than those obtained by RIA. The serum T3 response to TRH was absent or low in 40 out of 53 patients in whom it was evaluated. The administration of T3 (100 micrograms/day for 3 days) or dexamethasone (3 mg/day for 5 days) respectively suppressed or reduced both basal and TRH-induced plasma TSH levels. Two patients became hypothyroid shortly after pituitary surgery in spite of basal and TRH-induced plasma TSH levels similar to or higher than those before surgery. Though thyroid atrophy due to chronic understimulation could explain the low T3 response to TRH in secondary hypothyroidism, it is difficult to reconcile thyroid understimulation with normal or increased plasma TSH unless the immunoreactive material has low biological activity. Present data suggest that several patients with hypothyroidism consequent to hypothalamic-pituitary diseases secrete a material which is immunologically similar to pituitary standard TSH and responds to stimulatory and suppressive agents in a manner similar to normal TSH but has low or absent biological activity. Thus, hypothyroidism due to insufficient TSH stimulation can be termed central hypothyroidism and can be due 1) to pituitary insufficiency (secondary hypothyroidism), 2) to a hypothalamic defect (tertiary hypothyroidism), or 3) to the secretion of biologically inactive TSH.

Biological Assay↗

Evaluation of the results of trans-sphenoidal surgery in acromegaly by assessment of the growth hormone response to thyrotrophin-releasing hormone.

Eighteen acromegalic patients GH-responsive to TRH were reinvestigated following trans-sphenoidal surgery and radiotherapy. Basal serum GH decreased below 10 microgram/1 in thirteen cases; nine of them became GH-unresponsive to TRH 1 month after operation, and another one following conventional pituitary irradiation. Four of these ten patients also showed a normal GH response to L-Dopa after treatment, and five responded normally to insulin-induced hypoglycaemia; two patients had a normal GH secretory pattern after both these stimuli. No recurrences were observed over a follow-up period of 15-80 months among the ten patients who became GH-unresponsive to TRH following operation, while one of the three subjects still responsive to TRH in spite of normalized basal serum GH concentration relapsed 10 months after surgery. Three patients with normalized TRH test following operation were repeatedly reinvestigated over a 3-6 years period and always found unresponsive. The present study shows that the 'paradoxical' GH responses to TRH and L-Dopa frequently disappear after surgery, that complete normalization of GH secretory pattern may rarely be attained, and that the disappearance of GH response to TRH probably indicates satisfactory treatment of acromegaly. These data suggest that the 'paradoxical' GH responses frequently found in acromegaly are dependent on the adenoma per se and not on hypothalamic dysfunction.

Acromegaly↗

Effects of short-term clofibrate administration on glucose tolerance and insulin secretion in patients with chemical diabetes or hypertriglyceridemia.

The effect of 1-wk administration of clofibrate on plasma glucose and insulin (IRI) before and during oral glucose tolerance tests (OGTT), as well as on serum lipids, uric acid, growth hormone (GH), and cortisol, were evaluated in 18 nondiabetic patients with hypertriglyceridemia and in 28 patients with chemical diabetes. Fasting plasma glucose, OGTT-glucose, and IRI areas were significantly decreased in both groups of patients, though the effects on glucose metabolism were much more marked in diabetics; 30-min IRI relative increase was unchanged; fasting plasma IRI was reduced in diabetics only. Glucose utilization during insulin tolerance tests carried out in 6 diabetics was significantly enhanced after treatment. Serum triglycerides (TG) and cholesterol (Chol) were significantly decreased in both groups of patients, as were serum free fatty acids and uric acid in diabetics; plasma GH and cortisol did not change. Significant correlations were found in diabetics between the postclofibrate decrease in OGTT-glucose area and the following: pretreatment values of serum Chol (r + 0.42, p less than 0.05) and of 30-min IRI absolute and relative increase (r + 0.44 and + 0.38, respectively, p less than 0.05); postclofibrate decreases in serum TG (r + 0.40, p less than 0.05), in fasting plasma glucose (r + 0.73, p less than 0.001), and in OGTT-IRI area (r + 0.57, p less than 0.01). These data suggest that the improvement in glucose metabolism observed during short-term clofibrate administration may be due to increased insulin sensitivity.

Adolescent↗

Effect of two serotonin antagonists on prolactin and thyrotrophin secretion in man.

The effects of serotoninergic blockade on prolactin and thyrotrophin secretion in man was evaluated by determining the basal and TRH-stimulated serum prolactin and TSH concentrations in normal volunteers before and after a 3 days course of cyproheptadine or methergoline administration. Cyproheptadine, a serotonin antagonist with antihistaminic, anticholinergic and antidopaminergic properties as well, did not affect prolactin secretion, while it reduced the serum TSH response to TRH; methergoline, a specific blocker of central serotonin receptors, decreased basal and TRH-induced serum prolactin levels, without affecting TSH secretion. These results support the existence of serotoninergic stimulatory influences on human prolactin release, while suggesting that human TSH secretion is not modulated by serotoninergic inputs.

Cyproheptadine↗

Failure of oral 5-hydroxytryptohan administration to affect prolactin secretion in man.

Oral 5-hydroxytryptopahn (5-HTP) administration, either 200 mg acutely or 50 mg q.i.d. fr 3 days plus 200 mg acutely, failed to modify either basal or TRH-stimulated prolactin secretion in normal subjects. This is at variance with the stimulatory action of intravenous tryptophan on human prolactin release. However, it is doubtful that 5-HTP at the dose used may increase brain serotonin concentration; moreover, the hydroxlated amino acid is also taken up by catecholaminergic neurons, from which noradrenaline and dopamine may then be released. It is concluded that the failure of 5-HTP to affect prolactin secretion in man is not a proof against the existence of serotoninergic stimulatory influences on human prolactin release.

5-Hydroxytryptophan↗

Influence of L-prolyl-L-leucyl-glycine amide on growth hormone secretion in normal and acromegalic subjects.

Melanocyte Release-Inhibiting Peptide (MRIP-I) did not affect circulating levels of ACTH, LH, FSH, TSH,ORL, betaMSH and insulin when iv infused (5.0 mg in 5 min plus 0.4 mg/min for 70-115 min), while it significantly reduced serum GH response to hypoglycemia in normal subjects and lowered serum GH levels in acromegalics. There was no correlation between the fall in serum GH after MRIP and after dopaminergic drugs in acromegaly. These data are compatible with either a direct suppressive action exerted by MRIP-I at pituitary level or an extra-pituitary effect not involving dopaminergic pathways. It can be spec-lated that since labelled MRIP-I accumualtes in the pineal and melatonin blunts GH response to hypoglycemia, the pineal gland might be involved in the MRIP-I-induced suppression of GH secretion.

Acromegaly↗

Some aspects of hypothalamic-pituitary function in patients with anorexia nervosa.

The secretion of lutenizing hormone (LH), follicle-stimulating hormone (FSH), thyrotrophin (TSH) and prolactin (PRL, was studied in 17 women suffering from anorexia nervosa. The mean basal serum LH was reduced (8.4 +/- 0.8 SE mIU/ml; P less than 0.001 vs normal controls), while LH increase after gonadotrophin-releasing hormone (LH-RH) appeared to be normal in 9 cases and impaired in 6 cases. The mean basal FSH did not significantly differ from normal subjects (3.9 +/- 0.5 mIU/ml), while LH-RH administration elicited an exaggerated increase in 7 cases and a normal increase in 8 cases: the mean FSH response was significantly higher than in controls (P less than 0.02). Plasma oestradiol-17beta was reduced (20.4 +/- 0.4 pg/ml; P less than 0.001) while the serum testosterone levels were normal (0.73 +/- 0.09 ng/ml). Clomiphene administration induced an increase in gonadotrophins in only 1 out of 7 patients. The mean serum TSH concentration was normal (2.3 +/- 0.4 muU/ml), while serum thyroxine and triiodothyronine and free thyroxine index, thought generally in the normal range, were significantly lower than values obtained in a control group (6.1 +/- 0.4 mug/100 ml, P less than 0.005; 102.3 +/- 7.7 ng/100 ml, P less than 0.005; 3.8 +/- 0.3, P less than 0.05). Though the mean serum TSH increase after thyrotrophin-releasing hormone (TRH) was normal (12.0 +/- 2.3 muU/ml), there were 4 impaired and 1 exaggerated increases, and 8 patients showed a delayed and frequently prolonged response. The increase in serum T3 after TRH appeared lower than in normal subjects (36.3 +/- 1.8 ng/100 ml, P less than 0.001). Serum PRL levels in basal conditions were higher than in the controls (19.4 +/- 4.1 ng/ml, P less than 0.001) while the increase in PRL after TRH was exaggerated in only 2 patients. The present data suggest that the primary failure in gonadotrophin secretion in anorexia nervosa occurs at hypothalamic level; moreover the data on TSH and PRL secretion also point to the existence of a hypothalamic disorder in this disease.

Adolescent↗

Treatment of acromegaly by transsphenoidal microsurgery.

The preoperative outlook and surgical results are evaluated in 29 acromegalic patients, employing the usual serum growth hormone (GH) screening techniques in association with GH response to the thyrotropin releasing hormone (TRH) test. Results obtained by transsphenoidal microsurgical technique in adenomas of different size and sellar morphology are reported. Overall results clearly favor selective microsurgery in early diagnosed and operated tumors (microadenomas), while a less than radical approach does not hold much promise of functional normalization in larger adenomas. In nonnormalized cases the efficacy of radiotherapy is stressed. The TRH test results were a good indication for radiation therapy even in those cases in which GH normalized after surgery by common assay methods.

Acromegaly↗

Triiodothyronine response to thyrotrophin releasing hormone in patients with hypothalamic-pituitary disorders.

The serum triiodothyronine concentration was evaluated before and after thyrotrophin releasing hormone in fifty-six patients with hypothalamic-pituitary disorders (thirty-four had secondary hypothyroidism, twenty-two were euthyroid) and in twenty-four normal controls. Basal serum T3 was low in fifteen hypothyroid subjects and normal in the remainders. After TRH, serum T3 did not increase normally in twenty-five hypothyroid and in ten euthyroid patients; even the patients with normal or supranormal plasma TSH increase had significantly lower T3 responses than normal controls (P less than 0-0001 for hypothyroid, P less than 0-01 for euthyroid subjects). The finding of low T3 response to TRH in some euthyroid patients with hypothalamic-pituitary disorders can perhaps identify cases of preclinical secondary hypothyroidism, probably due to low biological activity of released TSH.

Clinical Trials as Topic↗