Search

Background Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. We studied the possible protective effect of testosterone and triptorelin to inhibit gonadal activity in men and women receiving cyclophosphamide, respectively. Study Design Nonrandomized trial. Setting & Participants 28 consecutive patients, 11 men and 17 women, from a university medical center with various forms of glomerulonephritis, treated with cyclophosphamide. Intervention Men received cyclophosphamide plus testosterone; women were divided into 2 groups: 13 patients (group A) received cyclophosphamide plus triptorelin; 4 (group B) received only cyclophosphamide. Outcomes & Measurements Serum follicle-stimulating hormone (FSH) and serum luteinizing hormone levels and, in addition, sperm counts and testosterone levels in men and estradiol levels in women were measured before and after treatment with cyclophosphamide. Results All 10 men became azoospermic or severely oligospermic during treatment; after 12 months, all except 1 had a normal sperm count and FSH levels were normal. In women during cyclophosphamide therapy, amenorrhea occurred in all patients. After cessation of therapy, all women in group A started to menstruate regularly, and at the end of follow-up, ovulatory cycles were demonstrated in all women. Hormone levels showed no significant changes throughout the observation period. Six women conceived, and the pregnancies were brought to term successfully without complications. In group B, all 4 women developed sustained amenorrhea; serum FSH and luteinizing hormone levels at the end of therapy and follow-up were significantly higher with respect to baseline; estradiol levels at the end of follow-up were significantly lower compared with baseline and corresponding values in group A. Limitations The substudy in men is uncontrolled, the substudy in women is nonrandomized. Conclusions The study suggests a protective effect of testosterone and triptorelin against cyclophosphamide-induced gonadal damage in men and women with various forms of kidney disease, respectively.

Children suffering from thalassaemia major are reported to have growth delay and bone alterations even when well transfused and chelated. In the present study we evaluated bone and collagen turnover (bone Gla-protein, BGP; carboxyterminal telopeptide of type I collagen, ICTP; aminoterminal propeptide of type III procollagen, PIIINP, respectively) and bone mineral density (BMD) in 5 pre-pubertal GH deficient thalassaemic children before and during rec-GH treatment (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex-matched control group. Before treatment, serum BGP and ICTP levels were significantly lower (p0.0001) in children with thalassaemia (9.3+/-0.7 ng/ml and 5.3+/-0.5 ng/ml, respectively) than in healthy controls (18.9+/-0.9 ng/ml and 14.4+/-0.6 ng/ml, respectively), while serum PIIINP levels did not significantly differ in the two groups (6.7+/-0.7 ng/ml vs 6.7+/-0.7 ng/ml). Mean lumbar BMD values of patients (0.62+/-0.05 g/cm2) were significantly lower (p0.05) than those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values were similar in the two groups (patients: 0.70+/-0.08 g/cm2 vs controls: 0.74+/-0.01 g/cm2). One-year GH therapy significantly increased height velocity (from 2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p0.0001) and IGF-I levels (from 61.6+/-15.4 to 342+/-38.5 ng/ml, p0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml, 6th month: 10.8+/-0.6 ng/ml, 12th month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml, 6th month: 7.9+/-0.8 ng/ml, 12th month: 10.9+/-1.7 ng/ml) and PIIINP levels (basal: 6.7+/-0.7 ng/ml, 6th month: 9.9+/-1.0 ng/ml, 12th month: 9.6+/-1.4 ng/ml) significantly increased (p0.05), while no significant effects were observed on lumbar and femoral BMD values. Although the GH-induced stimulation of bone turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH therapy was not sufficient to completely normalize these parameters, which remained significantly lower than in healthy controls. In conclusion, our study shows that pre-pubertal GH deficient children with thalassaemia major have reduced bone turnover (both bone formation and resorption) and lumbar BMD values, thus indicating that bone metabolism should be monitored and improved even in well-transfused patients. One-year GH treatment is able to increase, but not normalize, bone turnover, this effect being insufficient to improve BMD values. More prolonged periods of GH therapy are probably requested to positively affect both bone turnover and BMD values in GH deficient thalassaemic patients, as occurs in children and adults with GH deficiency.

This study investigated hormonal parameters of gonadal function in severely obese men before and 1 year after undergoing biliopancreatic diversion (BPD).This observational 1-year postoperative study conducted at medical and surgical clinics at an academic medical center in Italy followed 20 severely obese men age 21 to 63 years, with a mean (+/- standard deviation) body mass index (BMI) of 47.3 +/- 13.1. The following parameters were evaluated: body composition, using body impedance analysis (BIA), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, estradiol 17beta, and leptin.At a mean 12 +/- 1 months after surgery, the patients showed a significant decrease in weight, from 132.1 +/- 36.9 before surgery to 93.5 +/- 20 kg (P.0001), and BMI, from 47.3 +/- 13.1 before surgery to 33.5 +/- 7 (P.0001). LH increased from 2.42 +/- 1.59 to 4.97 +/- 2.6 mIU/ml (P.0001), FSH increased from 2.85 +/- 1.85 to 4.9 +/- 4.2 mIU/mL (P = .021), and total testosterone increased from subnormal presurgical values to within normal range (2.81 +/- 1.08 to 9.12 +/- 1.37 ng/mL; P.0001), whereas estradiol 17beta decreased from elevated basal levels of 44.0 +/- 29 to 16.7 +/- 6.9 pg/mL (P.0001). The basal leptin level dropped from 33.0 +/- 9.23 to 16.6 +/- 5.12 ng/mL (P.0001), reflecting the decrease in body fat. Subjective improvement in sexual performance was reported by 80% of patients.Severe obesity is coupled with some significant alterations of the gonadotropin-testicular axis and estradiol 17beta and leptin blood levels. These derangements were substantially corrected by 1 year after BPD.

Background: The aim of the study is to evaluate the importance of age on the mid- and long-term results and complications after biliopancreatic diversion (BPD). Methods: Our study comprises 132 morbidly obese patients who underwent Scopinaro BPD from February 1995 to April 2001, with follow-up from 24 to 96 months. The patients, 53 males (40%) and 79 females (60%), with mean preoperative BMI 50.2 (35.4-81.5), and mean age 42 (20-65), were divided in 4 groups. Group A age 20-35, 43 patients; Group B age 36-45, 33 patients; Group C age 46-55, 31 patients and Group D age >55, 25 patients. Incidence of long-term specific complications after BPD were analyzed, including protein malnutrition, reversals, anastomotic ulcer, and incisional hernia. Results: Mean postoperative BMI was similar in all Groups. After 60 months the following BMI values were observed. Group A 30.8, Group B 34.9, Group C 35.9, Group D 32. Incidence of long-term complications were not significantly different (χ2) in the 4 Groups, and were respectively: protein malnutrition 6.9%, 12.1%, 6.4%, 16.0%; anastomotic ulcer 11.6%, 9%, 6.4%, 16.0%; reversal 2.3%, 9.0%, 1.32%, 8.0%; ventral hernia 34.8%, 45.4%, 54.8%, 32.0%. Conclusions: From the preliminary results, it appeared that the incidence of the complications was higher in group D (>55 years old), whereas group C (46-55 years old) showed a lower complication rate. However, the prevalence of complications in all groups was not statistically different on χ2 analysis. No age limit for bariatric surgery could be determined from the age ranges studied.

Growth was monitored in 133 male and 150 female North Sardinian prepubertal patients with homozygous beta-thalassemia in order to ascertain the incidence of GH deficiency (GHD) and the effects of long-term recombinant GH (recGH) treatment on growth velocity and bone maturation. A significant reduction in growth velocity and a fall in IGF-I levels was observed in 19 male and 16 female patients (12.3%). Their peak GH responses to GHRH (5.45+/-0.78 and 4.99+/-0.86 ng/ml) and clonidine administration (4.21+/-0.32 and 4.15+/-0.27 ng/ml in males and females, respectively) were markedly reduced with respect to control subjects (p0.01). No statistically significant correlation was found between chronological age, number of blood units received, plasma ferritin levels and plasma IGF-I levels as well as with peak GH response to stimulation. Thalassemic patients with GHD had plasma ferritin levels (1382.44+/-160.34 and 1255.23+/-139.81 ng/ml in males and females, respectively) significantly lower than those recorded in the other patients (2848.94+/-283.61 and 3077.82+/-220.51 ng/ml). Patients with GHD were treated with recGH for an average period of 59 months (range 26-124). Treatment was able to restore growth and to increase significantly plasma IGF-I levels. Growth velocity at the end of the first yr of treatment was 6.78+/-1.21 and 6.11+/-0.85 cm/yr in males and females, respectively. Growth velocity values and plasma IGF-I levels remained significantly higher than basal values throughout the period of treatment. However, treatment was unable to normalize bone maturation since bone age values were always reduced with respect to chronological age. No incidence of side effects was observed. These data indicate that GHD, when present, is one but not the sole cause of delayed bone maturation and height deficiency in thalassemia.

Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations.To study the possible protective effect of testosterone used to inhibit germinal cell activity in men who are receiving cyclophosphamide.Randomized, clinical trial.University medical center.15 patients with the nephrotic syndrome who were treated with cyclophosphamide for 6 to 8 months.Five patients received daily oral cyclophosphamide, five received cyclophosphamide in monthly bolus injections, and five received monthly intravenous boluses of cyclophosphamide plus testosterone (100 mg intramuscularly every 15 days).Sperm counts, serum follicle-stimulating hormone levels, and serum luteinizing hormone levels were measured before, during, and after treatment with cyclophosphamide alone or cyclophosphamide plus testosterone.The 10 patients who did not receive testosterone became azoospermic during cyclophosphamide therapy. In only 1 of the 10 patients did the sperm count return to normal 6 months after discontinuation of therapy. Follicle-stimulating hormone levels were elevated in these patients (mean +/- SE, 19.20 +/- 1.28 IU/L in patients receiving oral cyclophosphamide and 16.04 +/- 2.22 IU/L in patients receiving intravenous cyclophosphamide alone). All 5 patients who received testosterone became azoospermic or severely oligospermic during treatment but had a normal sperm count 6 months after the discontinuation of therapy. In these patients, the mean sperm count was 45.78 +/- 3.89 x 10(6)/mL and follicle-stimulating hormone levels were normal (5.08 +/- 0.56 IU/L).Testosterone given to men before and during an 8-month cycle of cyclophosphamide therapy for the nephrotic syndrome may preserve fertility.

The efficacy and tolerability of a slow-release preparation of bromocriptine (Parlodel SRO) were compared to those of conventional bromocriptine (Parlodel R) in a double blind, double dummy study of 12 hyperprolactinemic women (plasma PRL 81.3 +/- 4.73, ng/ml mean +/- SEM). For 2 weeks, the patients received 2.5 mg b.i.d. Parlodel R or 5 mg once daily Parlodel SRO; for the following 2 weeks, the dose of the drugs was doubled. The patients were then treated, in an open study, with 2.5-10 mg daily Parlodel SRO for 6 months. Both preparations caused a prompt and sharp PRL fall. Hormone levels remained inhibited over the whole month of observation with both preparations. Daily PRL profiles were very close with either drug although morning PRl levels were slightly higher during Parlodel SRO than during Parlodel R administration. Doubling the doses of the two drugs did not result in further significant lowering of PRL values. During the 6-month study with Parlodel SRO, plasma PRL further decreased and normalized in 11 of 12 patients. Clinical improvement occurred in the majority of cases. Tolerability of Parlodel SRO appeared to be better, though without statistically significant differences, than that of Parlodel R. Side effects were less important with the former compound in their number, severity and duration. In conclusion, thanks to its favourable pharmacological profile, Parlodel SRO appears to be a valuable alternative to regular bromocriptine in the management of hyperprolactinemia.

The administration of apomorphine and piribedil, two dopaminergic agents, significantly reduced thyrotropin (TSH) and prolactin levels in six female patients with primary hypothyroidism. These data provide further evidence for an inhibitory role of dopaminergic stimulation on TSH secretion.

SUMMARY The effects of a 5 day course of Piribedil, a dopaminergic agonist, on prolactin release evoked by mechanical breast emptying in puerperal women, was investigated. A daily dose of 75 mg. caused a significant decrease in the prolactin response to mechanical breast stimulation. Piribedil also proved clinically useful in inhibiting lactation. The role of dopaminergic mechanisms in the regulation of prolactin release induced by mechanical breast emptying are discussed.

In 12 healthy male volunteers we studied the effect of nomifensine, an inhibitor of endogenous catecholamine reuptake, on insulin-induced prolactin and growth hormone (GH) secretion. The effect of the drug on TRH-induced prolactin secretion was also studied. Nomifansine was able to suppress completely the insulin-stimulated prolaction secretion, whereas no effect on GH secretion was observed. TRH-induced prolactin secretion was uninfluenced by the drug.

To investigate the role of Angiotensin II in the release of ACTH, the response of adrenocorticotrophic hormone to hypoglycaemia was studied before and during treatment with an angiotensin converting enzyme inhibitor, enalapril, in 15 male patients with essential hypertension. Plasma levels of ACTH were measured before and 60, 90 and 120 min after an i.v. bolus of normal saline, as placebo, and, 3 days later, after an i.v. bolus of regular insulin (0.15 U/Kg b.w.). Enalapril treatment was then started and both placebo and hypoglycaemic tests were repeated 15 days thereafter. No changes in ACTH plasma levels were observed after acute normal saline either before or during enalapril treatment. On the contrary, hypoglycaemia induced a sharp increase of ACTH before enalapril (from 19.5 +/- 4.1 to 74.4 +/- 13.0 pg/ml, p less than 0.01 60 min after insulin) but not during ACE inhibition (from 26.1 +/- 6.2 to 34.6 +/- 5.9 pg/ml, NS, at min 60 of the study). The present data confirm our previous observation on the reduction of the hypoglycaemic-induced ACTH release during ACE inhibition with captopril and support the hypothesis that circulating Ang II may exert a facilitating role on adrenocorticotrophic hormone release.

SUMMARY The effect of acute oral administration of metergoline on serum thyrotrophin and prolactin levels in six patients with primary hypothyroidism was studied. Metergoline 4mg by mouth caused a significant decrease in the concentration of serum thyrotrophin and prolactin in all subjects. There was no consistent change in serum thyroxine and triiodothyronine concentrations during the experiment. These findings suggest that metergoline inhibits prolactin and thyrotrophin secretion by a direct action on the hypothalamus or pituitary gland.

Serum prolactin levels were measured in 50 patients with oligospermia and in 20 control subjects under fasting conditions and following the administration of levodopa, pyridoxine, metoclopramide, and synthetic thyrotropin-releasing hormone. Four patients (8%) under fasting conditions had prolactin levels slightly above the normal range. However, no significant differences in prolactin behavior were detected between patients with hyperprolactinemia, patients with normal prolactin levels, and control subjects. The four patients with hyperprolactinemia were treated with metergoline, an ergoline derivative. Metergoline administration promptly reduced the prolactin levels. Spermatogenesis was restored in three patients after 4 to 5 months of treatment.

The authors investigated the effect of a single 75-mg oral dose of pirenzepine, a drug which selectively blocks the muscarinic receptors and does not cross the blood-brain barrier, on the function of the HPA axis. A significant decrease in basal cortisol values following the administration of the drug was observed in comparison with a placebo test. Moreover, the adrenal response to exogenous adrenocorticotropin (ACTH) administration was unchanged following a 5-day course of the drug, ruling out direct action of pirenzepine at the adrenal level. These data suggest that cholinergic muscarinic hypothalamic and/or pituitary systems may be involved in the regulation of ACTH-cortisol secretion.

Serum growth hormone (GH) response to insulin and glucagon administration was studied in 12 male and 12 female volunteers under control conditions, and under treatment with pimozide and metoclopramide. In addition, serum prolactin levels were measured during the treatment period. Pimozide and metoclopramide administration had no effect on the GH response to insulin and glucagon. In contrast, serum prolactin levels increased markedly during the treatment period. Dopaminergic blockade is unable to affect GH secretion in response to insulin and glucagon administration in man.

Serum prolactin, TSH and GH levels were measured in thirty healthy volunteers in fasting conditions and following oral administration of 200 mg nomifensine. In addition, the effect of the drug on serum prolactin and TSH response to synthetic TRH was studied in twenty normal subjects. Inhibition of endogenous catecholamine reuptake by nomifensine significantly inhibited prolactin release whereas it had no effect on TSH and GH levels. Nomifensine administration had no appreciable effect on the TRH-induced release of TSH and prolactin.

Serum GH levels were measured in 12 multitrans- patients, whereas no effect was observed in the normal subjects, fused patients with β-thalassaemia and in 12 normal subjects ofcomparable age under control conditions and after the administration of synthetic TRH and synthetic LRH. TRH administration induced a paradoxical rise in GH levels in 8 out of 12 patients, whereas no effect was observed in the normal subjects. Synthetic LRH administration was devoid of any effect on serum GH in both patients and controls. (J Clin Endocrinol Metab 54:1271, 1982)

Plasma atrial natriuretic factor (ANF), blood pressure, age, plasma renin activity and creatinine were measured in 50 normal volunteers, 141 essential hypertensives, 35 patients with chronic renal failure who had never been dialysed and 27 patients with end-stage renal failure on constant haemodialysis. Plasma ANF was correlated positively with age in the normal group (r = 0.52, P less than 0.01) and with blood pressure in the essential hypertensives (r = 0.50, P less than 0.001), and negatively with renin in the normal and end-stage renal failure patients (r = -0.47, r = -0.34; P less than 0.01, P less than 0.05, respectively). When patients without left ventricular hypertrophy were matched for age and blood pressure, plasma ANF was significantly different between the essential hypertensives and the normal and end-stage renal failure patients (16 +/- 1, 38 +/- 6 and 148 +/- 24 pmol/l, respectively; P less than 0.001). Cardiac factors are therefore not the only determinant of circulating plasma ANF in humans with chronic renal failure.

In order to investigate whether the variations in prolactin (PRL) secretion found in patients with liver cirrhosis are related to the derangement of neurotransmitter metabolism, serum PRL levels were measured in 8 patients with hepatic encephalopathy (a condition where neurotransmission is severely deranged), in 10 patients with liver cirrhosis but without encephalopathy and in 10 control subjects under control conditions and in response to nomifensine, levodopa and synthetic TRH administration. Inhibition of endogenous catecholamine reuptake by nomifensine was able to significantly reduce PRL levels in normal subjects and in patients with liver cirrhosis, whereas only one out of 8 patients with hepatic encephalopathy showed a reduction in PRL levels. On the contrary, levodopa administration was able to reduce PRL secretion in all the subjects studied. PRL release by TRH was greater in patients with liver disease than in controls. The results seem to indicate that the derangement in neurotransmitter metabolism which occurs in liver cirrhosis is one, but not the sole cause of alterations of PRL secretion in liver cirrhosis. The failure of nomifensine to depress PRL is an early finding in the course of encephalopathy and may be of diagnostic value.

Auricular electroacupuncture (EA) increased plasma ACTH and β-endorphin levels significantly in 10 patients receiving EA as an analgesic aid during surgery. Pre-treatment with iv hydrocortisone (200 mg) completely suppressed both ACTH and β-endorphin release in response to EA without significantly affecting EA anaesthesia in 6 other patients and in a patient with Addison's disease.

In 20 patients with duodenal ulcer we measured serum prolactin levels following acute and long-term cimetidine administration. In addition, in 20 healthy volunteers we studied the effect of pre-treatment with bromocriptine, metergoline, nomifensine and cyproheptadine on cimetidine-induced prolactin release. Intravenous cimetidine stimulated prolactin secretion in patients and in normal subjects. In the latter, bromocriptine and metergoline pre-administration blunted the release of prolactin in response to iv cimetidine whereas nomifensine and cyproheptadine were ineffective. Long-term treatment with cimetidine (1.2 g daily for 3 months) had no effect on prolactin secretion in the 20 patients studied. No incidence of gynaecomastia, galactorrhoea or disorders of the menstual cycle was observed.

The effect of atenolol on serum thyroid hormones levels is controversial. To get more information on this problem we studied the effect of propranolol and atenolol on plasma thyroid hormone concentrations in 20 thyrotoxic patients. Propranolol but not atenolol caused a significant decrease in T3 levels whereas no significant changes wee observed in T4 levels after both propranolol and atenolol administration.

Endocrine function was evaluated in 20 prepubertal patients with homozygous beta-thalassemia treated with frequent transfusions and long term iron chelation therapy. FSH, LH, PRL, and TSH secretion were evaluated by LRH and TRH testing and L-dopa and ACTH were used to assess GH and adrenocortical reserve. No statistically significant differences were found between FSH, LH, PRL, GH, and cortisol secretion in the patients and in normal subjects. There was a relatively high incidence (35%) of primary thyroid impairment since 1 patient had primary hypothyroidism and 6 others had evidence of subclinical hypothyroidism as manifested by increased TSH responses to TRH. However, no statistically significant correlations were found between either serum ferritin levels, total blood transfusions received, and thyroid function.

The Authors investigated anterior pituitary function in hypertensive patients in basal conditions and following a 15-day course of treatment with Captopril, a drug which blocks the generation of Angiotensin II (Angio II). No differences were observed for any of the pituitary hormones except ACTH, whose response to hypoglycemia was significantly blunted by the pharmacological treatment. A possible role of Angio. II in modulating some aspects of pituitary function is proposed.

Fluoxetine hydrochloride, a specific inhibitor of serotonin reuptake, was given orally to five adult males to study its effect on fasting and insulin-stimulated release of PRL. A 3- day course of fluoxetine (30 mg daily) had no demonstrable effect on fasting PRL levels. Fluoxetine significantly enhanced insulin-induced PRL release. These data suggest that serotoninergic pathways have little or no part in the control of spontaneous PRL secretion in man, whereas they may play a role in insulin-stimulated PRL release.

The effect of pirenzepine, a muscarinic receptor blocker which does not cross the blood brain barrier, on basal and TRH-stimulated prolactin (PRL) secretion in normal subjects was studied. Administration of 75 mg oral pirenzepine had no effects on prolactin levels in male subjects whereas it significantly reduced prolactin in females. No effect on TRH induced prolactin secretion was observed.

Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR®, Sandoz), 25-100 mg (mostly 50 mg) im every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p