Changes in prolactin levels with the menopause: the effects of estrogen/androgen and calcitonin treatment.

Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and at 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women p = 0.0001 and p = 0.0000 after 18 and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentrations together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged. Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in postmenopausal women.

The effect of intranasal salmon calcitonin on biochemical parameters of bone turnover in postmenopausal women.

This study aims to evaluate the effect of intranasal salmon calcitonin on variables of bone metabolism in 12 postmenopausal women during 24 months of treatment. A treatment regime of 100 U of intranasal salmon calcitonin on alternate days and 1500 mg daily of oral elementary calcium was applied. The control group consisted of 35 postmenopausal women distributed according to time since menopause. Biochemical and hormonal evaluations of calcium metabolism were performed at the start of treatment and after 6, 12, 18 and 24 months of treatment. Mean serum osteocalcin concentration was unchanged during the 1st year of treatment but was significantly elevated during the 2nd year (p = 0.03 and p = 0.005 after 18 and 24 months, respectively) when compared to levels at 12 months. Similar elevation of osteocalcin levels was observed in untreated women during the first 12 postmenopausal months. Mean 24-h hydroxyproline excretion decreased during the first 12 months of therapy but increased in the subsequent 6 months. The observed rise in serum osteocalcin concentration and urinary hydroxyproline excretion during the 2nd year of treatment with calcitonin was accompanied by a significant rise in serum calcitonin level. No significant differences in serum calcium, phosphorus, alkaline phosphatase or parathormone concentration, or urinary calcium excretion, were observed between treated and untreated women during the 24-month period. This study shows that 12 months' treatment with intranasal salmon calcitonin decreases bone resorption in early postmenopausal women, while bone formation remains unchanged. Longer treatment with intranasal salmon calcitonin, however, seems to be ineffective, most probably due to secondary resistance to calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes.

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documented. Although it has recently been shown that residual insulin secretion determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH and blood glucose profiles, insulin-like growth factor I (IGF-I) concentrations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects before and after 7 days treatment with recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-peptide negative (CpN, n = 12) patients without endogenous pancreatic beta-cell activity and C-peptide positive (CpP, (n = 9) patients with endogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH treatment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24-h GH concentrations in all groups studied which was statistically significant only in CpP diabetics. Mean pretreatment serum IGF-I concentrations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatment was however, significantly lower in CpN patients than in CpP and control subjects. GRF-induced GH response before and after rhGH treatment was significantly greater in diabetics than in controls. The response of GH to GRF in CpN diabetics was however, almost unchanged after treatment whereas it became lower in CpP diabetics and controls. The dose of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dose of rhGH failed to induce significant increase in GH levels in diabetics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I levels nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role of portal insulin in GH-induced hepatic IGF-I secretion.

The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion.

Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin-dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of improved blood glucose on growth hormone and cortisol secretion in insulin-dependent diabetes mellitus.

Growth hormone and cortisol secretion were studied in 25 patients with insulin-dependent diabetes before (Study 1) and 2 weeks after improved glucoregulation (Study 2). Blood samples for serum growth hormone (GH) and blood glucose determination were collected at hourly intervals whilst blood samples for cortisol and C-peptide were collected every 6 h during the 24-h period in Study 1 and Study 2. Glycaemic control was significantly improved in Study 2 compared to that in Study 1 (8.5 vs 13.3 mmol/l; P less than 0.001). With improved control, growth hormone levels rose by 21% (5.7 vs 4.7 mU/l; P less than 0.05). Throughout both study periods growth hormone levels were higher in patients with no residual C-peptide secretion (10 CpN patients) compared with patients with residual beta-cell function (15 CpP patients) (7.1 vs 3.2 mU/l in Study 1; 8.9 vs 4.2 mU/l in Study 2; P less than 0.001). Characteristic shapes of the 24-h blood glucose profile curves during both study periods were significantly different between the CpN and CpP group. Plasma cortisol decreased in both groups with improved metabolic control (P less than 0.001) but the observed different diurnal pattern did not change. These results demonstrate the importance of residual endogenous insulin secretion in determining growth hormone secretion in insulin-dependent diabetes and have important implications for glycaemic control and risk of microvascular complications.

Effects of improved blood glucose on insulin-induced hypoglycaemia, TRH, GnRH and exercise tests in insulin-dependent diabetes.

In order to evaluate effects of metabolic control on pituitary function in insulin-dependent diabetes exercise, hypoglycaemia (insulin tolerance test), thyrotrophin releasing hormone and gonadotrophin releasing hormone, tests were performed on 25 patients before (Study 1) and after 2 weeks of improved metabolic control (Study 2). Patients were sub-divided into C-peptide negative (CpN, 10 patients with no residual C-peptide secretion) and C-peptide positive (CpP, 15 patients with residual beta-cell function) groups for analysis of results. Exercise induced higher growth hormone responses in CpN patients independent of metabolic control (P less than 0.001). Thyrotrophin releasing hormone induced higher growth hormone responses in CpN patients; this response was threefold greater after improved control (P less than 0.005). Growth hormone and cortisol response to hypoglycaemia and thyroid stimulating hormone and prolactin secretion in response to thyrotrophin releasing hormone were unaffected by residual beta-cell function or metabolic control. Luteinizing hormone response to gonadotrophin releasing hormone in CpN patients was impaired and lower after improved control (P less than 0.002). The results indicate an association between residual pancreatic insulin secretory and hypothalamic/pituitary function, possibly reflecting central neurosecretion of insulin.

The effect of residual beta cell activity on menstruation and the reproductive hormone profile of insulin-dependent diabetics.

To investigate the cause of secondary amenorrhoea in insulin-dependent diabetes gonadotrophins, sex steroid hormone levels and residual beta cell activity (C-peptide index) were estimated in a group of 43 women with IDDM. Among 26 women with residual insulin secretion, the C-peptide positive (CpP) group, 5 had secondary amenorrhoea (CpP-Am); among 17 women without endogenous beta cell activity, the C-peptide negative (CpN) group 6 had secondary amenorrhoea (CpN-Am). In this study two different types of secondary amenorrhoea in insulin-dependent diabetics were observed. All CpP-Am women have the classical hormone profile of the polycystic ovary syndrome (increased (LH/FSH ratio, increased serum testosterone, decreased SHBG) together with a history of oligomenorrhoea and excess weight before the onset of diabetes. On the other hand, all CpN-Am women had decreased LH levels as well as low LH/FSH ratio and testosterone levels. These results strongly suggest that a lack of residual pancreatic beta cell activity influences hypothalamus-pituitary function in insulin-dependent diabetes. It might be concluded that PCOS is independent of diabetes while low LH amenorrhoea seems to be the consequence of diabetes and is strongly associated with a lack of residual insulin secretion.

Metoclopramide effect on serum prolactin LH and FSH in patients with polycystic ovary syndrome.

In order to investigate the DA activity in polycystic ovary syndrome (PCOS) we studied the response of LH, FSH and PRL to a dopamine receptor antagonist metoclopramide (MCP-10 mg iv) in 12 PCO subjects (7 with normal and 5 with elevated levels of prolactin). The prolactin and LH responses to metoclopramide were compared to those obtained in 6 normal cycling women. Although a significant increase in PRL levels was documented after MCP administration in all PCO patients and normal cycling women (p less than 0.01), the highest increment in PRL levels was observed in normoprolactinemic PCO subjects. In contrast a blunted PRL response was observed in hyperprolactinemic PCO patients. There was a negative correlation between basal PRL levels and the maximum net increase in PRL after MCP. In both groups of PCO subjects MCP administration caused initial decrease in LH levels followed by an increase after 4 h. In hyperprolactinemic PCO patients this observed MCP effect on LH was more pronounced and significantly different in comparison with normoprolactinemic PCO patients (p less than 0.01). MCP administration did not cause significant acute alterations in LH levels in normal cycling women and no significant FSH changes in either PCO or control subjects. A relative dopamine deficiency might cause hypersecretion of PRL and LH in patients with PCOS and hyperprolactinemia.

Acute effects of L-dopa and bromocriptine on serum PRL, LH and FSH levels in patients with hyperprolactinemic and normoprolactinemic polycystic ovary syndrome.

We have investigated the importance of the dopaminergic control of gonadotropin secretion by studying LH, FSH and PRL responses to L-dopa and bromocriptine in patients with polycystic ovary syndrome (PCOS). Both L-dopa and bromocriptine administration were followed by a statistically significant decrease in LH in the hyperprolactinemic PCO patients (compared to the normoprolactinemic subgroup - p less than 0.01 and control group - p less than 0.05); the decline was proportional to the basal level of LH. A significant positive correlation between basal LH levels and maximum net decrease of LH was observed after administration of both agents (p less than 0.01). Although both subgroups of PCO patients showed a similar decrease in PRL levels it was statistically significant only in the normoprolactinemic patients (p less than 0.01). Prolactin sensitivity to the inhibitory effect of bromocriptine and L-dopa showed a significant correlation with the basal PRL level (p less than 0.01). The response of serum FSH was variable and not significant. These results suggest that a reduction of an inhibitory influence of hypothalamic dopamine might be a cause of inappropriately elevated LH and PRL levels found in patients with polycystic ovary syndrome and hyperprolactinemia.

Pancreatic beta cell function in polycystic ovary syndrome: its relationship to body weight, serum testosterone and serum prolactin levels.

Circulating levels of insulin and C-peptide in response to oral glucose administration (75 g) were measured in 25 PCOS patients (13 were obese and 12 non-obese) without acanthosis nigricans and in 12 non-obese normal cycling women of similar age. Fasting levels of insulin and C-peptide as well as the sums of their levels in response to glucose were significantly greater in PCO patients than in controls despite similar glucose responses. Obese PCO patients had greater basal levels, maximum increments and sums of insulin and C-peptide levels than non-obese PCO patients and controls. PCO patients with increased basal total testosterone levels had significantly greater mean fasting insulin levels (p less than 0.005) than those with normal testosterone levels but their responses to glucose were not significantly different. Hyperprolactinaemic PCO patients had neither basal level nor sums of insulin and C-peptide levels in response to glucose greater than normoprolactinaemic PCO patients. In all PCO patients BMI correlated significantly with insulin (p less than 0.05) and C-peptide levels (p less than 0.001). Total serum testosterone levels correlated significantly with fasting levels and the sum of C-peptide levels in response to glucose. The correlations of total serum testosterone levels with fasting and the sum of insulin levels in response to glucose were also positive but not significant. These results clearly indicate that in PCOS there is a significant degree of hyperinsulinaemia which is mainly related to obesity.

Blunted prolactin response to metoclopramide in insulin-dependent diabetic patients with secondary amenorrhoea.

In order to investigate the dopaminergic activity in diabetic women with secondary amenorrhoea we studied the response of prolactin to a dopamine receptor antagonist metoclopramide (MTC - 10 mg i.v.) in three groups of women: 5 insulin-dependent diabetic women with secondary amenorrhoea, 5 insulin-dependent diabetics with normal menstrual cycles and 6 non-diabetic women with regular cycles. Patients with diabetes and secondary amenorrhoea had significantly lower basal LH levels (P less than 0.001) and FSH levels (P less than 0.005) than normally cycling diabetic women. Basal and metoclopramide stimulated prolactin levels were lower in diabetic women with secondary amenorrhoea compared to normally cycling diabetics and control subjects. Evaluation of C-peptide levels in peripheral blood revealed that all amenorrheic diabetics had no endogenous beta cell function while diabetic women with normal cycles (except 1 patient) had preserved residual pancreatic beta cell secretion.

Testosterone levels after bromocriptine treatment in patients undergoing long-term hemodialysis.

Seventeen out of 34 male patients undergoing long-term hemodialysis had increased basal plasma prolactin levels (mean = 1344 +/- 1158.76 mU/L). Seven of these 17 patients having the greatest degree of erectile impotence were treated with 3.5 to 7.5 mg/day of bromocriptine. After a 4-week treatment period, basal plasma prolactin levels in all seven patients were within normal limits (mean = 210.2 +/- 66.97 mU/L). The treated patients reported an improvement in both libido and potency. At the same time, an increase in plasma testosterone levels was observed, while plasma LH and FSH levels were essentially unchanged.

Renovascular hypertension associated with bilateral aldosteronoma.

The authors present a 35-year-old male patient with renovascular hypertension caused by the stenosis of both renal arteries of the right kidney. Two years after the diagnosis of hypertension was made, an endarterectomy was performed but a successful correction of the upper stenotic artery was not achieved. During the next 2 years the hypertensive disease was uncontrollable with antihypertensive medications and gradually entered into a malignant phase. In addition to the atrophy of the right kidney, an adenoma of the left adrenal gland was revealed (19.75 g) which was operated on. Left adrenalectomy had only a transitory benefit on blood pressure level. Five months later an adenoma of the right adrenal gland was diagnosed and together with the ischaemic right kidney was operated on (right adrenalectomy and nephrectomy) which definitely cured the hypertension. The chronological sequence of events and the course of the disease in the patient point to the possibility that long-standing hyper-reninaemia, due to renal ischaemia, may cause the development of multiple bilateral adrenocortical adenomas and that secondary aldosteronism may transform into primary.