Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and testicular steroidogenesis in male hypercholesterolemic patients.

To evaluate the influence of an hydrophilic statin, pravastatin, on adrenal and testicular steroidogenesis and spermatogenesis, eight male hypercholesterolemic patients were studied. All patients observed a hypocholesterolemic diet and received placebo for 4 weeks followed by pravastatin (20 mg/die) for 6 months. Before, during (4th-5th week) and at the end (23th-24th week) of active treatment, CRH (1 microgram i.v.), ACTH (Synacthen 250 micrograms i.v.) and human CG (HCG 3000 IU i.m.) tests were performed in addition to semen analysis. Pravastatin significantly reduced total cholesterol (20.3%), calculated LDL-cholesterol (24.6%) and apolipoprotein B (10.5%, increased apolipoprotein A1 (16.1%) and did not influence plasma HDL-cholesterol and triglycerides. Basal plasma cortisol, aldosterone, androstenedione, testosterone and oestradiol did not change under active treatment. Pravastatin administration affected neither adrenal hormone responses to CRH and ACTH or testicular response to HCG nor spermatogenesis in respect of motility, morphology and sperm count. In conclusion, long-term pravastatin treatment, at doses effective in improving lipid profile, did not influence testicular reproductive and endocrine function and did not interfere with basal and stimulated adrenal activity of male hypercholesterolemic patients.

17-Hydroxyprogesterone response to ACTH in bilateral and monolateral adrenal incidentalomas.

The aim of our study was to assess the frequency of 21-hydroxylase deficiency, a cause of congenital adrenal hyperplasia (CAH), in incidentally discovered asymptomatic adrenal masses (incidentalomas) and to compare the prevalence of this enzymatic disorder in monolateral (M) and bilateral (B) forms. Twenty-seven patients with incidentalomas (12 M and 15 B) and 16 sex and age-matched controls (C) received synthetic adrenocorticotropin (ACTH, 250 micrograms i.v.). Plasma 17-OHprogesterone (17-OHP) and cortisol were collected in basal conditions and after 30, 60, 90 minutes. Basal plasma 17-OHP in C [1.25 +/- 0.15 (0.61) ng/ml, mean +/- SE (SD)] was not significantly different from that in patients with M [0.85 +/- 0.13 (0.44) ng/ml] or B [0.94 +/- 0.23 (0.90) ng/ml] incidentalomas. After ACTH, 17-OHP levels significantly (p < 0.05) increased in C, in M and B incidentalomas. However, the rise in plasma 17-OHP in C both in terms of peak [2.5 +/- 0.28 (1.1) ng/ml] and of AUC values [174 +/- 16 (64) ng/ml/min] was significantly lower than that observed in M [peak 6.32 +/- 1.66 (5.7) ng/ml, p < 0.01; AUC 410 +/- 111 (385.5) ng/ml/min, p < 0.01] and in B [peak 8.84 +/- 1.98 (7.65) ng/ml, p < 0.001; AUC 613 +/- 149 (579.3), ng/ml/min, p < 0.001] incidentalomas. Individual data indicated that while 17-OHP response to ACTH in C never reached 5 ng/ml (cut-off for normal response), 16 out of 27 patients with incidentalomas (59.2%) exceeded this value. Moreover, the abnormal response was more frequently observed in B (66.6%) than in M (50%) incidentalomas. Basal and stimulated plasma cortisol did not differ among the three groups. In conclusion, our data indicate that in adrenal incidentalomas the endocrine pattern of 21-hydroxylase deficiency is very common and that this enzymatic defect is more frequent in bilateral than in monolateral lesions.

Effects of erythropoietin administration on prolactin secretion in normal subjects.

To evaluate the acute effect of human erythropoietin (r-HuEPO) on basal and stimulated prolactin (PRL) secretion, 18 normal subjects (12 females, 6 males) were studied. The PRL response to thyrotropin-releasing hormone (TRH; 200 micrograms intravenously, n = 7), metoclopramide (MCP, 20 mg intravenously, n = 5) and fenfluramine (FF, 60 mg os, n = 6) was tested in presence of saline or r-HuEPO (30 U/kg intravenously). The drug neither modified basal PRL levels nor affected the normal PRL release to TRH, MCP and FF. Our results indicate that, in normal subjects, the acute administration of therapeutic doses of r-HuEPO does not interfere with PRL secretion both after a direct pituitary stimulus and after stimuli involving dopaminergic and serotoninergic pathways.

The inter-relationship between insulin resistance and hypertension.

Insulin resistance and compensatory hyperinsulinaemia commonly occur in patients with untreated essential hypertension. The coexistence of insulin resistance and hypertension can be viewed as a cause-effect relationship (insulin resistance as a cause of hypertension or vice versa) or as a noncausal association. Insulin can increase blood pressure via several mechanisms: increased renal sodium reabsorption, activation of the sympathetic nervous system, alteration of transmembrane ion transport, and hypertrophy of resistance vessels. Conversely, hypertension can cause insulin resistance by altering the delivery of insulin and glucose to skeletal muscle cells, resulting in impaired glucose uptake. For example, hypertension can impair vasodilation of skeletal muscle as a result of vascular structural changes and rarefaction, and increased response to vasoconstrictor stimuli. Also, the prevalence of muscle type 2b fibres (fast twitch fibres) may contribute to the development of insulin resistance. The common pathogenetic mechanism for both insulin resistance and hypertension could be activation of the sympathetic nervous system. This results in vasoconstriction, and may contribute to the genesis of vascular structural changes and increase the number of fast twitch fibres. Finally, hypertension and insulin resistance can be viewed as a noncausal association, according to the following hypotheses: 1) they may represent 2 independent consequences of the same metabolic disorder (intracellular free calcium accumulation), or 2) insulin resistance is a genetic marker and/or a pathogenetic mechanism of multiple metabolic abnormalities frequently associated with hypertension.