Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans.

In order to determine whether an alpha1-adrenergic mechanism is involved in the secretion of Growth Hormone (GH) in humans, we studied the effect of the alpha1-adrenergic-stimulating agent methoxamine on serum GH levels in twelve normal males (age range 22-32 years). Intravenous infusion of methoxamine (dose: 6 microg/kg/min; duration: 150 min) significantly reduced serum GH levels at time 120 and 150, and on integrated concentrations. These data suggest that alpha1-adrenergic receptors inhibit tonic GH secretion in humans.

An inhibition of the hypothalamic somatostatinergic tone is not the cause of the enhanced growth hormone response to growth hormone-releasing hormone in patients with liver cirrhosis.

Animal models of liver cirrhosis (LC) display a reduced hypothalamic somatostatinergic tone. To test whether a similar mechanism could explain the enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH), which is seen in human LC, we studied the effect of the cholinesterase inhibitor pyridostigmine (PD), which is able to reduce the release of hypothalamic somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD were unable to increase GH secretion, this would constitute evidence of an already inhibited endogenous somatostatinergic tone. If proved, this in turn could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally) plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7 ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in patients with LC suggests that in this condition the enhanced GH response to GHRH is not due to a completely inhibited endogenous somatostatinergic tone. SS appears instead to maintain its modulator role on GH secretion in human LC, in contrast with what observed in animal models.

Successful treatment of retrograde ejaculation with the alpha1-adrenergic agonist methoxamine: case study.

We treated two patients affected by retrograde ejaculation (RE) with the pure alpha1-adrenergic agonist methoxamine; the drug was self-administered intramuscularly by the patients 30 min prior to intercourse or masturbation. A previous trial with oral imipramine had been ineffective in both patients. Sperm count increased substantially, particularly in the first patient who had insulin-dependent diabetes and was seeking fertility. In this patient, total ejaculated sperm increased from 22 millions to 488 and 419.5 millions on two different occasions, with good motility; two clinical pregnancies were obtained in the partner of this patient after 3 and 4 months of treatment, respectively. The second patient did not desire fertility. In both patients, no side effects were seen except for slight piloerection; blood pressure values increased slightly, and heart rate was unchanged. We conclude that self-administered methoxamine can be a useful, noninvasive and inexpensive treatment of RE, when oral agents are ineffective.

Seroprevalence of Helicobacter pylori in children with type 1 diabetes mellitus in Sardinia.

A few studies have reported an increased prevalence of Helicobacterpylori (HP) infection in diabetic subjects, which may be one of the causes of gastrointestinal symptoms and chronic atrophic gastritis frequently seen in diabetes of long duration. We determined the prevalence of HP infection in children and adolescents with Type 1 diabetes mellitus (T1DM) in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of T1DM. HP IgG and IgA titres were measured in 138 patients with T1DM and 138 age-matched healthy controls. The percentage of infected subjects did not differ between T1DM patients (29.7%) and controls (32.6%). Globally, infected subjects were more than 1 yr older (13.0 +/- 2.7 yr) than non-infected ones (11.8 +/- 2.9 yr), independently of the presence of T1DM; in most HP-positive subjects infection was asymptomatic, and only 2 subjects in each group reported clinically relevant symptoms. HP-positive and HP-negative diabetic patients had the same duration of the disease (5.6 +/- 3.5 vs 5.5 +/- 3.6 yr) and received very similar doses of insulin (0.94 +/- 0.27 vs 0.96 +/- 0.4 IU/kg/d), whereas mean HbA1c was significantly lower in HP-positive patients (7.8 +/- 1.6% vs 8.6 +/- 1.7%,p=0.02). We conclude that the prevalence of HP infection is not higher in Sardinian children with T1DM as compared to controls of similar age, and the overall clinical impact of HP infection in terms of gastrointestinal symptoms and diabetic control seems to be low.

The effect of acute bladder filling on plasmatic antidiuretic hormone production in healthy adult volunteers.

OBJECTIVE: To assess the existence of a vesical hypothalamic reflex by evaluating the changes of plasmatic ADH levels during acute bladder filling in healthy adult volunteers. MATERIALS AND METHODS: Twenty normal male subjects aged between 19 and 40 years (average age 31.6 years) were evaluated. All subjects signed informed consent. The subjects had no pathologic blood and urine examination, no cardiovascular, hepatic, renal disease, they were no smokers and they did not take drugs which may interfere with plasmatic ADH levels. A blood sampling at rest condition (time 0) and successively during cystometry in the presence of first sensation, normal and strong desire was carried out. Plasmatic ADH was measured on extracted samples by radioimmunoassay. A one-factor repeated measures analysis of variance was employed to verify the effect of time on ADH levels. The Greenhouse-Geisser and Huynh-Feldt adjustments were adopted to protect against the case of violation of homogeneity of covariance. RESULTS: Statistical analysis did not show significant differences of plasmatic ADH levels between rest condition and bladder filling. CONCLUSIONS: We exclude the existence of a vesical hypothalamic reflex and we suppose that extravesical factors may interfere with the plasmatic ADH production during the night.

Prevalence of silent celiac disease in patients with autoimmune thyroiditis from Northern Sardinia.

Celiac disease (CD) is frequently associated with other autoimmune diseases such as Type 1 diabetes mellitus, autoimmune thyroiditis (AT), and Addison's disease. The frequency of these associations varies with the populations studied. We conducted this study to ascertain the prevalence of CD in patients with AT from Sardinia, an area with a very high prevalence of CD. To this aim, 297 consecutive patients with AT (as defined by elevated antithyroid antibody levels and a positive ultrasound scan) were studied. Immunoglobulin A and G-class antigliadin antibodies were assayed in serum; if either or both were positive, antiendomysium antibodies were determined. If two markers were positive, serum ferritin, folate, and vitamin B12 levels were measured and jejunal biopsy was suggested. Thirteen out of the 14 patients who showed at least two positive markers consented to jejunal biopsy and all of them showed histological features of CD. The prevalence of CD in AT patients was 4-fold greater than that observed in the general population (4.37 vs 1.06%, p<0.0001). Ferritin was low in 6 and vitamin B12 in 2 out of 13 patients; serum folates were normal in all patients. Molecular typing of HLA class II alleles showed an increased frequency of the extended haplotype DRB1*0301/DQA1*0501/DQB1*0201. None of our patients had a history of gastrointestinal symptoms. We confirm the increased prevalence of silent CD in patients with AT. Patients with AT ought to be regarded as a high-risk group for CD and should be screened routinely for it; if negative, screening tests should be repeated at regular intervals.

The effect of noise on serum and urinary magnesium and catecholamines in humans.

We have studied whether a short-term exposure to loud noise was able to modify urinary catecholamine excretion and serum concentration and urinary excretion of magnesium and other related electrolytes. In 25 healthy volunteers, blood and urine concentrations of magnesium, calcium, phosphorus and creatinine, and urinary catecholamines were measured before and after exposure to noise in an industrial plant. Samples were collected at 08:00 h on the day of the experiment and soon after noise exposure (at 20:00 h). Two further urine samples were collected the following day and 2 days after the experiment, always at 08:00 h in the morning. The sound energy average level was 98 dB(A), but peak levels reached 108 dB(A). Urinary catecholamines were determined by high-performance liquid chromatography. Serum magnesium and calcium were significantly increased after exposure to noise, whereas phosphorus displayed a similar but non-significant trend (P = 0.065). Multivariate analysis of variance (ANOVA) showed significant differences both among subjects (P < 0.001) and after exposure (P < 0.001). Adrenaline, noradrenaline and dopamine values were not significantly different after exposure to noise (P > 0.05). Urinary magnesium levels were significantly different across time (P = 0.017). Urinary calcium levels were not significantly different across time (P = 0.36). Urinary phosphate values were increased after exposure to noise (P = 0.007); urinary creatinine was not changed after exposure (P > 0.05). Our study shows that noise induces significant increases of serum calcium and magnesium, with a borderline increase of serum phosphorus; this in turn is reflected in a significantly increased urinary excretion of magnesium and phosphate after exposure, which lasts for the following 2 days. Urinary calcium and creatinine were not modified by noise. The difference in catecholamine values did not reach statistical significance. Thus, we failed to substantiate a significant correlation between catecholamine secretion and magnesium metabolism, as others had suggested.

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine.

OBJECTIVE: To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine. PATIENTS AND METHODS: The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night). RESULTS: Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004). CONCLUSIONS: We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.

Acute thyroiditis in a child: misleading result of fine-needle aspiration biopsy.

We report a case of acute thyroiditis in a 6-year-old girl, whose initial borderline clinical and sonographic data, coupled with the absence of leucocytes and bacteria on the fine-needle aspiration biopsy, led to the reversal of the initial diagnostic impression of acute thyroiditis and the institution of an inappropriate glucocorticoid treatment. Since both diseases are rare in the paediatric age group and therapy is completely different, we conclude that in borderline cases careful clinical observation and the response to the initial antibiotic therapy should be considered more reliable than any single morphologic or microbiologic result. We also suggest that acute bacterial thyroiditis could be usefully classified into two forms, suppurative and non-suppurative.

The prevalence of coeliac disease in infertility.

An increased incidence of reproductive problems, including infertility, miscarriage, low birth weight newborns, and shorter duration of breast-feeding, are known to exist in women with coeliac disease; some of these conditions are improved by a gluten-free diet. We have tried to ascertain the prevalence of coeliac disease in 99 couples who were being evaluated for infertility, compared with the known prevalence of silent disease in the population of Northern Sardinia, in which it is endemic. Of all women, four tested positive for at least two out of three markers: immunoglobulin A (IgA) antigliadin, immunoglobulin (IgG) antigliadin, and anti-endomysium antibodies, and underwent a jejunal biopsy; three had histological evidence of coeliac disease. One male partner was positive for two markers, and had a diagnostic jejunal biopsy. The prevalence of coeliac disease in infertile women seems higher (three out of 99, 3. 03%) in the study group than in the general population (17 out of 1607, 1.06%), and particularly in the subgroup with unexplained infertility (two out of 25, 8%, P < 0.03). Screening for coeliac disease should be part of the diagnostic work-up of infertile women, particularly when no apparent cause can be ascertained after standard evaluation.

Opioid-receptor blockade blunts growth hormone (GH) secretion induced by GH-releasing hormone in the human male.

OBJECTIVE: To investigate the existence of an opioid stimulatory tone on growth hormone (GH) secretion in the human male. DESIGN: Seven healthy male volunteers, aged 19-30, were studied in the Endocrine Unit of the University of Sassari. GH-releasing hormone (GHRH), 100 micrograms as an intravenous (IV) bolus, as administered with and without preadministration of IV naloxone, 2 mg as a bolus followed by a constant infusion of 2 mg/h. Blood samples were taken for 120 minutes after GHRH administration. RESULTS: Naloxone significantly blunted the GH response to GHRH, measured either as mean peak value (at times 30 to 90) or as integrated concentrations. CONCLUSIONS: Naloxone is able to decrease the effect of a maximal dose of GHRH, thus suggesting the existence of an opioid stimulatory tone on GH secretion.

Pulsatile gonadotrophin secretion in hypothyroid women of reproductive age.

Hypothyroid women may have various disturbances of the reproductive system. Although menstrual cycle disturbances and infertility have been reported in hypothyroidism, gonadotrophin levels have usually been found in the normal range. We have investigated whether female hypothyroid patients of reproductive age have any alteration in the pulsatile secretory pattern of gonadotrophin secretion. LH and FSH were assayed on days 2-5 of the menstrual cycle in blood samples taken every 10 min for 8 h from six hypothyroid women and six age-matched control subjects. Pulsatility was analysed using the Cluster and Detect programs. There was no significant difference in the number of peaks identified (3.7 +/- 0.8 vs 3.7 +/- 0.8 for LH, and 3.7 +/- 0.8 vs 4.2 +/- 0.5 for ESH), the mean duration of peaks (LH: 68.0 +/- 6.9 vs 72.7 +/- 5.1 min; FSH: 81.9 +/- 8.1 vs 71.2 +/- 10.3 min), the area under the peaks (LH: 91.5 +/- 20.4 vs 148.2 +/- 55.1 IU/l per min; FSH: 71.5 +/- 4.5 vs 62.7 +/- 15.0 IU/l per min), and the incremental amplitude from baseline (LH: 2.2 +/- 0.4 vs 3.0 +/- 0.8 IU/l; FSH: 1.4 +/- 0.2 vs 2.1 +/- 0.5 IU/ l). However, the absolute pulse amplitude was greater in hypothyroid patients (LH: 14.5 +/- 1.4 vs 8.3 +/- 1.3 IU/l, P < 0.01; FSH: 9.0 +/- 1.5 vs 5.8 +/- 1.2 IU/l, P = 0.04), as were the integrated concentrations (LH: 6.6 +/- 0.7 vs 3.2 +/- 0.4 IU/l per min, P < 0.01; FSH: 4.3 +/- 0.4 vs 2.1 +/- 0.5 IU/l per min, P < 0.01). Oestradiol values were comparable in the two groups (42.7 +/- 0.4 vs 43.5 +/- 9.7 pg/ml). These results indicate that in hypothyroid women there is an increased baseline level with a normal pulsatility of the gonadotrophin secretion. Similar oestrogen levels in both groups, and normal or near-normal cycles in our patients suggest either a decreased biological potency of the gonadotrophins or a mild ovarian resistance.

[Effect of imipramine hydrochloride on urinary function and serum parameters in enuretic children: preliminary study]. / Action de l'Hydrochloride d'Imipramine sur la fonction urinaire et sur les paramètres sériques chez les enfants énurétiques: étude préliminaire.

We still do not know whether Imipramine works exactly as an antidiuretic. The aim of this study was to investigate any existing urinary or serum factor differences between 9 children with primary nocturnal enuresis and six age and sex matched controls and to see if therapy with Imipramine could modify these parameters. All subjects underwent an evaluation of daily and nightly urinary volume, daily fluid intake, morning plasma and urine osmolality, plasma aldosterone, electrolytes, blood urea nitrogen and plasma glucose. The results, using a one-way ANOVA, would suggest the following: 1) enuretic children have a higher 24 urinary volume with a reduced osmolality compared to controls; 2) Aldosterone does not seem to be involved in the pathogenesis of enuresis; 3) Imipramine HCL therapy does reduce the volume of urine lost in diapers, and its efficiency can be documented objectively; 4) Imipramine HCL's mechanism appears to be related to an increased renal water resorption.

Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog.

Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli; in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opiods induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline; (b) a met-enkephalin analog G-DAMME 250 micrograms IV as a bolus at time 0'; (c) hGH 2 IU as an IV bolus at time -180'; (d) G-DAMME as above, preceded by hGH as above. In our study, G-DAMME stimulated GH secretion both basally (peak 17.9 +/- 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 +/- 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded.

[Single-blind study of the effect of doxazosin mesylate in benign prostatic hypertrophy]. / Etude en simple aveugle de l'efficacité du Mesylate de Doxazosin dans l'hypertrophie bénigne de prostate.

The purpose of this single blind study was to verify the efficiency of Doxazosin Mesylate, an alpha-1 adrenergic blocker, in patients with benign prostatic hyperplasia (BPH). This study involved 20 patients non placebo responders. The duration of treatment was 45 days with administration of Doxazosin Mesylate increased every 15 days from 1 to 2 mg and from 2 to 4 mg respectively. At the end of each dosage cycle the following investigations were performed: a) peak urinary flow, b) residual urinary volume, c) funneling of the prostatic urethra by means of permictional transrectal echography, d) Boyarsky's score. The analysis of these data, applying a two way analysis of variance (ANOVA), showed that Doxazosin Mesylate resulted in improvements in both urodynamic and symptomatic parameters. The statistical analysis proved also that there was a good correlation between the dosage of the drug up until 2 mg and the results from each parameter considered.

Calcium ion and pituitary hormones: effect of calcium channel blockers on stimulated secretion of pituitary hormones.

The effects of two calcium channel blockers nifedipine (20 mg sublingual), and verapamil (10 mg i.v.) on growth hormone (GH), thyrotropin (TSH), prolactin (PRL) and gonadotropin (LH and FSH) secretion induced by growth hormone releasing hormone (GHRH), hypoglycemia, thyrotropin releasing hormone (TRH), metoclopramide and gonadotropin releasing hormone (GnRH), were studied in a group of normal volunteers (27 men and 8 women). Neither nifedipine nor verapamil had any effect on PRL, TSH or gonadotropin release. Verapamil did not cause variations in GH secretion following GHRH and insulin-induced hypoglycemia, whereas nifedipine significantly reduced the elevation in GH induced by GHRH; however the GHRH-mediated GH rise still remained within the normal range in all subjects. Our results suggest that neither nifedipine nor verapamil have important effects on stimulated pituitary hormone secretion, at least under conditions of acute administration.

Interaction of glucose and pyridostigmine on the secretion of growth hormone (GH) induced by GH-releasing hormone (GHRH).

In order to investigate the mechanisms by which hyperglycaemia induces an inhibition of GHRH-induced GH release, we gave the following treatments to seven normal men: a) GHRH 100 micrograms iv; b) pyridostigmine (PD) 120 mg po 60 min before GHRH; c) glucose 250 mg/kg iv as a bolus (10 min before GHRH) plus 10 mg/kg/min until the end of the test; d) glucose pyridostigmine and GHRH as above. Glucose significantly reduced GHRH-stimulated GH levels, whereas PD significantly enhanced them. When PD and glucose were given together, the effect on GHRH-stimulated GH secretion was not different from the algebraic sum of the single effects of the two substances. Thus glucose seems to be able to exert its inhibition, at least partially, also when pyridostigmine is coadministered.

Opioids stimulate growth hormone (GH) release in man independently of GH-releasing hormone.

The Met-enkephalin analog DAMME [D-Ala2,MePhe4-Met-enkephalin-(o)-o1, FK 33-824] can stimulate GH secretion in man. In this study we investigated the effects of the guanyl derivative of DAMME (G-DAMME) on the serum GH response to an analog of GHRH in normal men. GHRH-(1-29)NH2 and G-DAMME each induced a rise in serum GH, and the increase was greater when both were given together. Since the GHRH-(1-29)NH2 dose (100 micrograms) used was a maximally stimulatory one, these results suggest that the enhancing effect of G-DAMME on GHRH-induced GH release may be mediated through inhibition of somatostatin release.