Effect of sulpiride-induced hyperprolactinemia on serum testosterone response to HCG in normal men.

In six normal volunteers hyperprolactinemia was induced by sulpiride (150 mg/day) for 10 days. Both before and during sulpiride hCG was injected; the higher testosterone response to hCG, when PRL levels were enhanced, suggests a possible stimulatory role of PRL on Leydig cells.

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.

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.

Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hyperprolactinemic patients.

To further evaluate the potency and time course of the PRL-lowering effect of single oral doses of cabergoline, two doses of the drug were given to 51 hyperprolactinemic patients who also received 2.5 mg bromocriptine according to a randomized cross-over design. One group (n = 26) received 0.3 mg, and the other (n = 25) received 0.6 mg. Both cabergoline doses induced a significant fall in serum PRL levels, which lasted, on the average, from 3 h to 5 days after 0.3 mg and from 3 h to 14 days after 0.6 mg; the mean maximum decrease after 0.3 mg was -65 +/-4% (+/- SEM), significantly (P less than 0.05) less than that after bromocriptine (group mean, -73 +/- 4%), and it was -76 +/- 3% after 0.6 mg, not significantly different from that induced by bromocriptine (group mean, -71 +/- 4%). The effect of 0.6 mg cabergoline was significantly greater than that of 0.3 mg (P less than 0.01). In a second study designed to evaluate the possible therapeutic use of the new drug, 0.3 or 0.6 mg cabergoline was administered orally once weekly for 9 weeks to 2 groups of 15 and 16 hyperprolactinemic patients, respectively. Serum PRL levels fell significantly by the first week and reached a plateau after 2 doses in the 0.6 mg cabergoline-treated group and after 5 doses in the 0.3 mg-treated group; the absolute PRL decrease was greater in the former. Ten patients in each group achieved normal serum PRL levels, and a marked decrease (greater than 50% of pretreatment values) occurred in all patients treated with 0.6 mg and in 13 treated with 0.3 mg weekly. Resumption of menses occurred during the treatment period in 15 of the 17 premenopausal women with amenorrhea. Six patients who had poor responses had better responses when given higher drug doses for 4 weeks, and serum PRL levels became normal in the 3 receiving 0.6 mg twice weekly. These data confirm that cabergoline is a long-acting oral dopaminergic drug and suggest that it may be a useful agent for the treatment of patients with hyperprolactinemia.

Cabergoline: long-acting oral treatment of hyperprolactinemic disorders.

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.

Long-lasting prolactin-lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients.

The new long-acting ergoline derivative cabergoline was given orally in a single dose of 300 micrograms to 15 hyperprolactinemic patients (including 4 acromegalic patients, 2 of whom were dopamine responsive). Serum PRL and GH levels were determined before and 3, 4, and 6 h and 1, 2, 3, 4, 5, 6, and 7 days after treatment. A control test with a single oral dose of 2.5 mg bromocriptine was also performed; serum PRL and GH levels were measured at the same time intervals for 2 days. Cabergoline induced a marked fall in serum PRL which began within 3 h and continued for 7 days. The maximal decrease ranged between -49.2% and -55.2% and occurred after 2-5 days. This maximal effect was only slightly less than that 6 h after bromocriptine treatment (-63.8%). After cabergoline treatment, serum GH levels did not change significantly in either nonacromegalic or acromegalic patients, whereas the two dopamine-responsive acromegalic patients had a marked GH fall after bromocriptine. A moderate blood pressure decrease, more evident in the standing position, occurred after both cabergoline and bromocriptine treatments. The only symptomatic side-effect was orthostatic hypotension after cabergoline in an elderly woman. These data indicate that cabergoline has potent and prolonged dopaminergic activity and may prove suitable for once weekly treatment of hyperprolactinemic patients.

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.

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.

Changes in radioiodine turnover in patients with autonomous thyroid adenoma treated with percutaneous ethanol injection.

UNLABELLED: In 24 patients with autonomous thyroid adenoma, we studied the hormonal pattern (free thyroxine, free triiodothyronine and thyroid stimulating hormone) and markers of radioiodine turnover before and after nodule ablation with percutaneous ethanol injection. METHODS: The hormonal pattern was studied before treatment and at various intervals after nodule ablation. Changes in radioiodine turnover were studied measuring 131I protein-bound iodine and the biologic half-life of radioiodine in the thyroid (calculated from thyroid uptake at 24 and 48 hr) before and after ethanol treatment. RESULTS: The hormonal pattern was normalized by treatment in all patients and remained normal for the follow-up period. Before treatment, protein-bound 131I was elevated in all patients but 4; after treatment, it normalized in 15 patients with the disappearance of the adenoma on scintigraphy. In the remaining 9 patients with only partial nodule destruction on scintigraphy, protein-bound 131I remained elevated although markedly reduced. Biologic half-life was shortened in 18 of 24 patients before treatment; after treatment, it was normal in 18 of 24 patients (13 of 15 with complete nodule ablation and 5 of 9 with partial ablation). CONCLUSION: Ethanol treatment normalized the hormonal pattern in all patients. Measures of radioiodine turnover were better markers of residual disease in that they normalized in almost all patients with complete nodule ablation, whereas they remained abnormal in a high proportion of patients with incomplete ablation. Thyroid hormones remained normal over a follow-up period of 3-7 yr in all patients.

Dosimetry study in patients with autonomous thyroid nodule who are candidates for radioiodine therapy.

UNLABELLED: A dosimetry study was performed on 26 patients with an autonomous thyroid nodule and suppressed serum thyroid-stimulating hormone, to determine the dose to extranodular tissue when the nodule receives 300 Gy for 131I therapy. METHODS: Parameters of radioiodine turnover to be used in the dosimetry formula were separately obtained for the nodule and the contralateral lobe, as a measurable example of the extranodular tissue, using 55 MBq 123I and a computer-assisted gamma camera. The biologic half-life of 123I was then converted into the effective half-life of 131I, and the volumes of the nodule and the lobe were obtained by scintigraphy or sonography. RESULTS: The mean dose to the contralateral lobe from uptake and irradiation by the nodule was calculated to be 32 Gy, and that to the ipsilateral lobe was estimated to be 34 Gy. CONCLUSION: During radioiodine therapy for autonomous thyroid nodules, the extranodular tissue receives a higher dose than is generally assumed, which explains the relatively high rate of post-treatment hypothyroidism reported in the literature.

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.

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.

[Percutaneous ethanol injections in the treatment of autonomous thyroid nodules. 4 years' experience]. / L'iniezione percutanea di etanolo (PEI) nella terapia dei noduli tiroidei autonomi. Esperienza dopo quattro anni.

We treated with PEI 81 patients carriers of autonomous thyroid nodule, 65 toxic and 16 non toxic, all with undetectable serum TSH and suppressed extranodular tissue on scintigraphy. The treatment schedule was: 1-2 sessions per week, 1-8 ml per session, 3-13 sessions in total, In relation to the size and the therapeutic response. The signs of hyperthyroidism disappeared in all cases. Complete cure was obtained in 51 patients; hormonal remission was obtained in 24 patients; partial compensation was obtained in six patients. No recurrences were observed, but two dysphonias lasting three months were reported. PEI seems to be an alternative to surgery and 131I for the ablation of toxic nodules with a volume less than 30 ml.

Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decision-making process in primary hyperparathyroid disease.

PURPOSE: Ultrasound (US) and scintigraphy are used most frequently of all the available imaging techniques for the preoperative evaluation of patients with possible primary hyperparathyroid disease. The aim of this study was to assess the value of dual-phase Tc-99m MIBI scintigraphy compared with US in the detection of adenomatous or hyperplastic glands and in the surgical decision-making process for patients with a biochemical diagnosis of primary hyperparathyroid disease. METHODS: Ninety-seven patients with increased levels of parathyroid hormone and calcium, and at least 6 months' follow-up after US and scintigraphy, were examined retrospectively to assess the influence of the diagnostic work-up on the therapeutic decision of the referring clinicians and to evaluate the sensitivity of these diagnostic tools in the surgically treated patients. Forty-eight patients underwent surgery. RESULTS: Parathyroid adenomas were found in 43 patients and hyperplasia in 1, whereas 4 patients had no evidence at surgery. The sensitivity and specificity rates were 84.4% and 95.9% for scintigraphy, and 66.6% and 98.6% for US, respectively. Of the 49 nonsurgically treated patients, 35 had negative results with both MIBI and US; only 3 had positive findings with both imaging methods. Patients treated conservatively had significantly lower parathyroid hormone and serum calcium levels than did the patients who had surgery. CONCLUSIONS: The data suggest that the high sensitivity of dual-phase MIBI scintigraphy can improve the detection of hyperfunctioning parathyroid glands. Furthermore, despite the controversy surrounding the use of imaging methods in the preoperative assessment of primary hyperparathyroid disease, these data suggest that the decision of the clinician to order surgery for a patient with a moderate increase of serum PTH level may be influenced by the results of the imaging methods.

Asymptomatic parathyroid adenoma manifested by intratumoral hemorrhage.

A 48-year-old woman whose past history was unrevealing presented with sudden swelling of the neck with pain and dysphonia. Neck ultrasonography suggested the possibility of hemorrhage in a parathyroid adenoma. Surgical exploration revealed a hemorrhagic parathyroid adenoma of the chief cell type. This event is exceedingly rare, but should be considered in the differential diagnosis of suddenly appearing masses of the neck region.

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.

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.