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Objective: To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet., Design: A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study., Subjects: In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMI >or=28 kg/m(2)) were randomized to treatment with orlistat (n=346) or placebo (n=350)., Measurements: Body weight, anthropometry, lipid and glycemic control parameters and blood pressure., Results: After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lost >or=10% of their initial weight (P=0.04). A significantly greater number of patients receiving orlistat treatment maintained this >or=10% weight loss compared to those receiving placebo (28.1 vs 13.8%; P<0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18 mmol/l; P<0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%; P<0.001)., Conclusion: A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.

Objective: To investigate the relationships between alexithymia and emotional eating in obese women with or without Binge Eating Disorder (BED)., Research Methods and Procedures: One hundred sixty-nine obese women completed self-report questionnaires, including the Beck Depression Inventory, the State Trait Anxiety Inventory, the Stress Perceived Scale, the Dutch Eating Behaviour Questionnaire, and the Toronto Alexithymia Scale. The presence of BED, screened using the Questionnaire of Eating and Weight Patterns, was confirmed by interview., Results: Forty obese women were identified as having BED. BED subjects and non-BED subjects were comparable in age, body mass index, educational level, and socioeconomic class. According to the Dutch Eating Behaviour Questionnaire, BED subjects exhibited higher depression, anxiety, perceived stress, alexithymia scores, and emotional and external eating scores than non-BED subjects. Emotional eating and perceived stress emerged as significant predictors of BED. The relationships between alexithymia and emotional eating in obese subjects differed between the two groups according to the presence of BED. Alexithymia was the predictor of emotional eating in BED subjects, whereas perceived stress and depression were the predictors in non-BED subjects., Discussion: This study pointed out different relationships among mood, alexithymia, and emotional eating in obese subjects with or without BED. Alexithymia was linked to emotional eating in BED. These data suggest the involvement of alexithymia in eating disorders among obese women.

Ovarian virilizing tumors are rare and can lead to assessment difficulties because of their small size. A 41-yr-old female was referred for evaluation of hirsutism that had increased within the previous 3 yr. Menstrual cycle length was normal. Plasma testosterone was 3.9 ng/ml (normal range, 0.2-0.8 ng/ml), was not suppressible by 2 mg dexamethasone (4.3 ng/ml), and was increased (6.3 ng/ml) after three daily injections of hCG (5000 IU). Abdominal computed tomography scan showed an adrenal nodule (13 x 6 mm) that remained unchanged after 3 months. Ultrasound examination of the pelvis was normal. Ovarian and adrenal venous catheterization did not yield additional information. Topographic assessment was made by intraoperative measurement of testosterone in the samples taken from each ovarian vein (competitive chemiluminescent immunoassay ADVIA Centaur; right ovarian vein, 105 ng/ml; left ovarian vein, 5 ng/ml; peripheral blood, 7 ng/ml). Right annexectomy resulted in normalization of testosterone levels (0.22 ng/ml). Histopathological examination found a Leydig cell tumor of hilar type (1.5 cm). This observation illustrates the usefulness of intraoperative measurement of testosterone by a rapid automated technique for topographic assessment of ovarian virilizing tumor in premenopausal women.

We report the case of a female patient in whom gluten-induced enteropathy was revealed at the age of 68 years by resistance to treatment with levothyroxine and alfacalcidol. This case report shows that malabsorption without major digestive symptoms led to reduction of absorption of levothyroxine (LT(4)) and alfacalcidol, although the patient had normal free thyroxine (T(4)) levels (which increased by 45.8% after a loading dose of 250 microg of levothyroxine), high thyrotropin (TSH) and slightly elevated 1.25 dihydroxy-vitamin D(3) levels, low free triiodothyronine (T(3)) and calcium levels were found. Malabsorption had additional effects by reducing T(3) and calcium levels. Because minor forms of gluten-induced enteropathy are not rare in patients with thyroid autoimmune diseases, the cost-effectiveness of using antigliadin antibodies as a first-line test (instead of an LT(4) loading test) in patients requiring daily doses of levothyroxine above 2 microg per kg of body weight, whatever their age may be, is discussed.

Uncoupling protein-2 (UCP2) is a mitochondrial protein expressed in a wide range of human tissues. By uncoupling respiration from ATP synthesis, UCP2 might be involved in the control of energy expenditure. We have investigated UCP2 gene expression in human adipose tissue. In eight subjects, we found a positive correlation (r = 0.91, P < 0.002) between subcutaneous and visceral fat depots UCP2 messenger RNA (mRNA) levels, suggesting that UCP2 mRNA level in subcutaneous adipose tissue is a good index of UCP2 gene expression in whole body adipose tissues. The effect of a 25-day very-low-calorie diet un UCP2 mRNA level and resting metabolic rate was investigated in eight obese premenopausal women. There was no difference in UCP2 mRNA levels before and during the diet. After 25 days of hypocaloric diet, a positive correlation was found between adipose tissue UCP2 mRNA level and resting metabolic rate adjusted for lean body mass (r = 0.82, P < 0.01). These results show that very-low-calorie diet, unlike short-term fasting, is not associated with an induction in UCP2 mRNA expression, and that adipose tissue UCP2 mRNA levels may be related to variations in resting energy expenditure in humans.

The aim of this study was to determine those hormonal alterations in the gonadotropin-ovarian axis that are related to eating behavior in oligomenorrheic patients. We studied 74 oligomenorrheic women aged 26.2 +/- 0.8 years, divided into group IA (N = 13) with eating disorders, group IB (N = 61) without eating disorders and 18 normally cycling controls aged 29.2 +/- 1.6 years (group II). No subject had ovarian failure, pituitary disease, thyroid dysfunction or was taking any drug. Blood samples were taken on days 3-6 after the last menses. Luteinizing hormone (LH) was measured in two plasma pools, each made up of three samples taken at 30-min intervals, starting at 15.00 h (LH-15h) and 09.00 h (LH-9h), which allowed the mean LH (mLH) and variability in LH (V-LH: percentage increase from the lower to the higher of the two LH values) to be calculated. Follicle-stimulating hormone (FSH), sex steroids, and gonadotropin-releasing hormone-stimulated LH (sLH) and -FSH (sFSH) were also evaluated. Eating behavior was evaluated with the EAT questionnaire; the EAT 26 score, the dieting score (DS) and bulimia score (BS) were calculated. Dietary intake was evaluated in 35 group IB patients based on food diaries analyzed with the REGAL program, to evaluate daily calorie intake (Cal) and calories provided by carbohydrates (Carb), lipids (Lip) and proteins (Prot). Comparisons between groups were done by analysis of variance (followed by the Fisher PLSD test) and the Kruskal-Wallis test. Groups IA, IB and II did not differ regarding age, body mass index, LH-9h, LH-15h, mLH, FSH, sLH, sFSH, estradiol or dehydroepiandrosterone sulfate; group IA had a higher V-LH than group II (p < 0.02) and a higher testosterone level than groups IB and II (p < 0.05). Positive correlations were found between V-LH and DS (p < 0.01) and BS (p < 0.05), and between testosterone and BS (p < 0.02) and DS (p < 0.05). The V-LH was negatively correlated with Cal and Carb, and testosterone was positively correlated with Cal and Lip. In patients referred for oligomenorrhea, it is concluded that testosterone levels and variability of LH levels are related to eating behavior.

The aim of the study was to evaluate the short term and long-term effects of long acting repeatable bromocriptine (= Parlodel-LAR*) in patients with macroprolactinomas. Twenty-nine patients (15 men and 14 women) aged 42 +/- 2.7 (M +/- SEM) years were injected with Parlodel-LAR* every 4 weeks during 3.3 +/- 0.3 years. The starting dose was 50 mg/injection, then it was increased to 100 mg in 11 patients and 150 mg in 9 patients. PRL levels decreased in all but one patient 4 weeks after the first injection (270 +/- 59 vs 934 +/- 210 ng/ml, p < 0.001), then became less than 20 ng/ml in 20/29 (69%) patients and finally became undetectable or low in 13/29 (45%) patients. Visual field defects were present in 12/29 patients before treatment. In 11/12 patients, treatment with Parlodel-LAR* resulted in an improvement and complete correction of visual field defects was observed in 8/12 patients. Adenoma size (2.5 +/- 0.2 cm before treatment) was reduced by at least 20% in 24/29 (83%) patients. Disappearance of adenoma was observed on CT scan in 8/29 (28%) patients after 28.7 +/- 5.3 months of treatment. Minor side effects occurred in 20 patients after the first injection then disappeared in 18 patients within the following 6 months of treatment. One patient had rhinorrhea after 3 months of treatment. Treatment with Parlodel-LAR* results in beneficial short-term effects (with rapid correction of recent onset visual field defects) and long-term effects (which can include complete disappearance of adenoma on CT scan evaluation) in patients with macroprolactinomas.

Objectives: Determine whether ovulation in dystrophic ovaries treated with GnRH agonist followed by GnRH pulses is due to the GnRH pulse or is patient-dependent. SITE. Endocrinology department, CHU Purpan, Toulouse, France., Methods: Fifteen infertile patients, age range 22 to 35 years, with ovarian dystrophy were given GnRH agonist (Decapeptyl, 3.75 mg IM on day 3 of the cycle). In 5 patients, an IV pulse of GnRH was then given (6 micrograms/90 min)., Statistical Analysis: Mann-Whitney U test, corrected chi 2 test., Results: Ovulation was achieved in 8/15 cases (3/5 with and 5/10 without pulsatile GnRH p = NS) and 3 pregnancies (without pulsatile GnRH). Before treatment LH was higher in patients who had an ovulation., Conclusion: Ovulation can be achieved after GnRH agonist treatment in patients with dystrophic ovaries, with or without pulsatile GnRH, particularly if the initial LH levels are high.

We studied the luteinizing hormone (LH) secretory pattern in three patients, aged 30, 23 and 43 years, with gynecomastia due to Leydig cell tumor of the testis, before and 6 months after unilateral orchidectomy. The results were compared to those of 11 normal fertile controls aged 20-35 years. Blood sampling was done at 20-min intervals from 22.00 h to 10.00 h. The LH data were analyzed with the Cluster analysis algorithm with "optimal parameters for LH male data" to determine the pulse interval and pulse amplitude. The Expfit program was applied to LH pulses to calculate the apparent half-life of immunoreactive LH. Before surgery, when compared to controls, the patients had a low to normal testosterone/estradiol ratio (0.053, 0.110, 0.046 vs 0.148 +/- 0.038) and mean LH levels (1.96, 3.7, 2.55 vs 4.0 +/- 1.9 IU/l), decreased pulse amplitude (2.65, 3.01, 2.21 vs 3.31 +/- 1.41 IU/l) and reduced apparent half-life of LH (74, 69, 78 vs 97 +/- 16 min). After removal of the Leydig cell tumor, the testosterone/estradiol ratio returned to the normal range (0.141, 0.177, 0.093) while an increase in mean LH levels (5.75, 7.90, 4.88 IU/l), LH pulse amplitude (3.07, 6.05, 2.86 IU/l) and apparent half-life of LH (138, 106, 104 min) was observed in all three patients. Our data indicate that endogenous hyperestrogenism in patients with Leydig cell tumor of the testis results in an inhibition of LH secretion, and suggests that such inhibition could result from a reduction in pulse amplitude and apparent half-life.

The plasma membrane Na+/H+ exchanger is a ubiquitous system which plays a role in the regulation of intracellular pH and the control of cell growth. In order to assess the potential role of this system in the pathogenesis of diabetic nephropathy, we investigate 42 normotensive insulin-dependent diabetic patients with or without microalbuminuria. We tested the platelet Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of cells suspended in sodium propionate. Urinary albumin excretion (UAE) was assayed by radioimmunoassay on a 24 h sample; the glomerular filtration rate (GFR) and the renal plasma flow were determined by 99 m Tc-DTPA and 1231 l-hippuran respectively. Thirty patients (group 1) had EUA > 30 mg/24 h (m +/- sd: 11 +/- 7 mg/24 h), 12 patients (group 2) had microalbuminuria (62 +/- 30 Mg/24 h, range from 35 to 136 mg/24 h). The platelet Na+/H+ exchange rate was significantly increased in patients of group 2: 0.34 +/- 0.01 versus 0.26 +/- 0.06 s-1 x 10(-2) (p < 0.005). There was no significant difference between these two groups regarding blood pressure (116 +/- 14/71 +/- 7 versus 119 +/- 12/73 +/- 5 mmHg), age, diabetes duration, glycated hemoglobin or fructosamine levels. On the whole population, we found a significant positive correlation between the platelet Na+/H+ exchange rate and the UAE (r = 0.57, p < 0.001) and with the glomerular filtration fraction (r = 0.43, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of the study was to evaluate the loss of nocturnal (N) decline in blood pressure (BP) in type II treated hypertensive diabetics. The study concerned 36 hypertensive diabetics 59 +/- 10 years old, 20 men and 16 women, with poor metabolic control (HbA1C: 9.6 +/- 3%), without dysautonomia; 14 had macroproteinuria and/or microalbuminuria (mu alb) (< 30 micrograms/min). An ambulatory BP monitoring (Spacelabs 90207) was performed in all patients. Left ventricular mass index (LVMI) and E/A were determined by Doppler-echocardiography. Two groups (G) were individualized: G1 (n = 17), with a normal circadian rhythm (diurnal and N.BP significantly different); G2 (n = 19) with a loss of N decline in systolic (S) and diastolic (D) BP or both; and compared to non diabetic treated hypertensive controls (G3). There was no difference neither in LVMI (125 +/- 43 g/m2), E/A (0.7), 24 h-mean (M) BP in the three groups, nor in HbA1C levels and mu alb occurrence in G1 and G2. Mean N.SBP and mean N.DBP were more closely related to LVMI in G2 than in G1 and G3. [table: see text] Half of these hypertensive diabetics, with bad metabolic control, have an altered circadian BP pattern; the prognostic value of nocturnal BP, related to LVMI despite the antihypertensive treatment, is suggested.

In order to assess the potential role of the plasma membrane sodium-proton (Na+/H+) exchanger in the pathogenesis of diabetic nephropathy, we investigated 32 insulin dependent (type 1) diabetic patients and 21 control subjects. We tested the Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of platelets suspended in sodium propionate. Patients with diabetic nephropathy had significantly increased rates of Na+/H+ exchange (0.31 +/- 0.06 s-1 x 10(-2)) when compared to those without nephropathy (0.24 +/- 0.07, p less than 0.05) or to a control group (0.23 +/- 05, p less than 0.05). Nine patients who were classified as hypertensive had a highly significant increase in the Na+/H+ exchange rates when compared to 23 non-hypertensive diabetic patients: 0.33 +/- 0.04 versus 0.24 +/- 0.06 (p less than 0.001). There was no significant correlation between the Na+/H+ exchange rates and age, diabetes duration, glycated hemoglobin or fructosamine levels on the day of the test. In summary, the data presented here demonstrate an increase in the Na+/H+ exchange rate in insulin-dependent diabetic patients with nephropathy and hypertension.

Objective: To assess the efficacy and tolerability of monthly injections of the long-acting repeatable bromocriptine in patients with macroprolactinomas., Design: Open and prospective trial., Setting: This multicenter trial was carried out in seven university hospitals., Patients: Forty-two patients with prolactin (PRL)-secreting macroadenomas., Interventions: Fifty to 200 mg of the drug were administered intragluteally every 28 days for 6 to 24 months., Main Outcome Measures: The efficacy was assessed by repetitive plasma PRL measurements, visual field determinations, and computed tomography scan examinations., Results: After the first 50-mg injection, the mean percentage decrease of PRL levels was 71% from baseline on day 14; between days 1 and 28, PRL levels were suppressed to normal in nine cases, and a clear tumor shrinkage was documented in 21% of the patients. Normalization of PRL secretion was obtained in 62%, and a clear-cut reduction in tumor size in 50% of the patients after 6 months of treatment., Conclusions: The long-acting repeatable form of bromocriptine was a well tolerated and quickly effective treatment in most of these patients with macroprolactinomas.

LH nocturnal pulsatility and bioactivity to immunoreactivity (B/I) ratio were determined in 16 patients with anorexia nervosa-related hypothalamic amenorrhea and low sex steroid levels, and in 12 normal women in the midfollicular phase. The patients were subdivided into 2 groups: IA (N = 7) without, and IB (N = 9) with documented recent weight gain. Blood samples were taken from each subject at 10-min intervals from 00.00 to 06.00 h. Immunoreactive LH data were analysed with cluster analysis algorithm. A pool of aliquots from all the samples was used to evaluate bioactive LH, immunoreactive LH and LH B/I ratio in each subject. LH pulse frequency was lower in Group IA than in controls, whereas it did not differ significantly between Group IB and controls. LH pulse amplitude was lower in Group IA, and higher in Group IB than in controls. LH B/I ratio was below the control range in 3/16 patients. In conclusion, persistent hypothalamic amenorrhea does not require a permanent inhibition of the GnRH pulse generator; transient inhibition of pulsatility and qualitative abnormalities of gonadotropins could be involved in the mechanism, at least in some patients.

The authors report the results of a prospective study designed to assess changes in vertebral and femoral bone density during the first two years of replacement therapy in 10 patients with hypothyroidism (4 men, 6 women). During the first year, bone density measured by dual photon absorptiometry fell significantly in the lumbar vertebrae (-5.4%), neck of the femur (-7%) and the trochanteric region (-7.3%). This bone loss was accompanied by an early increase in serum osteocalcin levels, urinary calcium/urinary creatinine ratio and in Sex Hormone Binding Globulin. During the second year, there was complete recovery of values of vertebral and trochanteric bone density, while density of the neck of the femur remained significantly lower than initial values. None of the patients showed any evidence of overdose during the period of monitoring of clinical and laboratory (free T4, total and free T3, ultra-sensitive TSH) parameters. This transitory bone loss could be indicative of a state of tissue hyperthyroidism and/or "hypersensitivity" of hypothyroid bone to the action of thyroid hormones. Its influence on the subsequent risk of fracture remains unclear. In the current state of knowledge, measurement of vertebral and femoral bone density appears to be indicated in patients given long term treatment which suppresses TSH, or requiring replacement therapy for severe hypothyroidism. Any demineralisation prior to treatment could justify the temporary prescription of an antiosteoclastic agent.

Objective: Since LH secretion occurs as a series of pulses, relationships between mean LH levels and LH pulse characteristics are to be expected. The aim of this study was to determine whether such relationships are similar in normal women and anovulatory patients., Design: We studied the correlations between mean LH levels and the products amplitude x frequency and area x frequency of LH pulses in normal women and in patients with disorders of ovulation. Blood samples were taken from each subject every 10 minutes during 6 hours on the 8th day after the last menses., Patients: The patients were divided into three groups: patients with polycystic ovary syndrome (n = 11), patients with idiopathic anovulation (n = 14) and patients with short luteal phase (n = 13). Their results were compared to those of 12 normal women., Measurements: LH was evaluated with an immunoradiometric assay. LH data were analysed with a 3 standard deviation threshold criterion for significant peaks, and with cluster analysis algorithm using 1, 2.5 and 5% false positive error rates and 'optimal parameters' (which give less than 5% false positive and false negative error rates in LH male data)., Results: Highly significant correlations between amplitude x frequency, area x frequency and mean LH were found in normals and patients with short luteal phase; no significant correlation was found in patients with polycystic ovary syndrome, while significant correlations were found in patients with idiopathic anovulation only with some of our criteria for peak detection., Conclusion: The differences that we found between the groups suggest that when commonly used methods are employed to determine LH pulse characteristics, most of the significant LH pulses are taken into account in normals and patients with short luteal phase, but not in anovulatory patients, especially in patients with polycystic ovary syndrome. This method using two correlations appears to be a simple and useful way to show the differences in the mechanisms by which mean LH levels are achieved in normal subjects and patients.

Oral yohimbine administration (0.2 mg/kg) induced lipid mobilization (increase in plasma non-esterified fatty acids, NEFA) in fasting non-obese women (body mass index BMI = 20.2 +/- 0.5, age 35.5 +/- 2.7 years) without significant action on plasma glucose, insulin levels, heart rate or blood pressure during the time-course of the experiment (240 min). Plasma norpinephrine (but not epinephrine) concentrations were increased (100 percent) after oral yohimbine administration. Oral administration of propranolol (40 mg, 60 min before yohimbine) reduced the lipid-mobilizing action of yohimbine (70 percent) during the 60 min following its administration and then totally suppressed its effect until the end of the experimental period (180 min). In fasting obese women (BMI = 36.4 +/- 2.1, age 37 +/- 3.6 years), yohimbine provoked an increase in plasma NEFA levels which was not markedly different from that observed in non-obese subjects. It had no significant effect on plasma glucose, insulin levels, heart rate or blood pressure. Plasma norepinephrine increased in the same proportions. The lipid-mobilizing effect of yohimbine in women is mainly attributable to the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta-adrenergic agonism. In the standard fasting conditions (12 hours) the blockade of the antilipolytic fat cell alpha 2-adrenoceptors seems to be a minor component of the lipomobilizing effect of yohimbine. Morever, when compared with non-obese women, the lipomobilizing effect of yohimbine is not enhanced in obese women.

We investigated 51 patients with idiopathic oligospermia and 10 control subjects. Blood samples were collected every 20 minutes from 10 P.M. to 10 A.M. and luteinizing hormone (LH) pulsatility was analyzed. A pool of all samples obtained from each subject was used to measure bioactive LH in an in vitro mouse Leydig cell bioassay and immunoactive LH in an immunoradiometric assay. Mean immunoactive LH pulse frequency was higher and mean bioactive to immunoactive LH ratio was lower in infertile men than in controls. There was a significant negative correlation between bioactive LH to immunoreactive LH ratio and LH pulse frequency. These data indicate that the defect in the gonadal axis in oligospermic men resides not in the hypothalamic-pituitary function but rather in the testis itself.

Fifty-two postmenopausal women (mean age 60 +/- 5 years) with low BMD (less than -2SD of young adult values) but who had not experienced previous crush fracture were treated with 50 mg of sodium fluoride (NaF), 1 g of calcium and 400 IU of vitamin D2 per day for 2 years. Repeated vertebral and femoral BMD measurements were made and compared with those of a control group consisting of 16 untreated women. Serum alkaline phosphatase and osteocalcin, blood and urinary fluoride levels were measured regularly to determine their predictive value on bone response. 18 of 52 (35%) of the treated patients experienced side effects (29% gastric, 4% lower extremity pain syndrome) but only in 6 cases (12%) was it necessary to discontinue treatment. In neither of the two groups was any fracture recorded (vertebral or otherwise). Among the 43 women who were treated for at least 2 years, 21 (49%) were considered to have responded (i.e., with an increase of vertebral BMD greater than 0.043 g/cm2). There was a mean linear increase in BMD in this group of 0.0041 g/cm2 per month (i.e., 5.5% per year). On the other hand in the non-responder group and in the control group, vertebral BMD either remained stable or decreased. However no difference was detected between the two groups (treated and controls) at the femoral site after 2 years; both groups showed a significant decrease in BMD. The responders had a lower initial osteocalcin level and treatment led to a relatively greater increase in osteocalcin.(ABSTRACT TRUNCATED AT 250 WORDS)

In this prospective multicenter trial, 61 patients presenting with a macroprolactinoma were studied over a 1 month-period following a single 50 mg intragluteal injection of the long-acting repeatable (L.A.R.) form of bromocriptine. The effects of the drug were evaluated mainly by repetitive plasma prolactin measurements on days 1, 3, 7, 14 and 28 after injection, and by repeated visual-field and computed tomography scanning examinations. Normalization of PRL levels was obtained in 23% of patients during the first month following injection. In 6 patients (9.8%), PRL values remained within normal range on day 28 after injection. In these latter patients, PRL levels were significantly lower than in the patients whose PRL values were not normal on day 28 (312 +/- 111 vs 2454 +/- 484 ng/ml [m +/- SEM]). The mean lowest PRL levels were achieved on day 3. The mean percent maximal decrease in PRL levels ranged between 70 and 72% from days 3 to 14 but constantly remained below 50% in 6 patients. An improvement in visual field was observed by day 7 in 45% of patients presenting initially with visual field defects. In particular, in half of the patients with bilateral quadranopsia or hemianopsia, such visual impairments had disappeared after 1 month of treatment. Computed tomography scanning examinations showed in 11% of the patients a more than 20% reduction in tumor mass by day 7 following injection. On day 28, the percent reduction in tumor size was 20-40% in 28% and above 40% in 10% of the patients. Most adverse effects (digestive symptoms, dizziness, postural hypotension) were observed during the first 24 hours of treatment. Local and systemic tolerability was in general good. In macroprolactinoma patients, a single 50 mg injection of bromocriptine LAR was thus able to achieve in the short-term a clear cut reduction in tumor size in 2/5 patients and normalization of PRL levels in 1/10 of patients. A study of the effects of monthly administration of bromocriptine LAR is currently under progress to assess the long-term efficacy of this drug.

Thyroid function and lipid tests were measured in 29 premenopausal women with subclinical hypothyroidism. This group was compared with 41 euthyroid women matched for age and metabolic parameters. In basal condition there was no difference in thyroid hormone levels between the two groups except for TSH concentration (P less than 0.01). Total cholesterol, triglycerides and apolipoprotein (apo A1, A2, B) of women with subclinical hypothyroidism were not different from controls. HDL cholesterol was significantly decreased in subclinical hypothyroidism compared to the controls (P less than 0.01). With thyroxine therapy, normalization of serum TSH was associated with (1) no significant change in total cholesterol and triglycerides, (2) an increase of HDL cholesterol (P less than 0.01) and apoprotein A1 (P less than 0.05) levels. Total cholesterol/HDL cholesterol ratio was increased in subclinical hypothyroidism (P less than 0.01). During L-thyroxine therapy this ratio returned to normal value. Decreased HDL cholesterol concentration might cause coronary heart disease reported in women with subclinical hypothyroidism.

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]yohimbine binding) were investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension due to autonomic neuropathy as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One-minute standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). Since platelet alpha 2-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet alpha 2-adrenoceptors in high affinity state could explain the occurrence of orthostatic hypotension in insulin-dependent diabetic patients. Multiple pathophysiological mechanisms underly orthostatic hypotension in insulin-dependent diabetic patients and include anomalies both in the sympathetic nervous system and in alpha 2-adrenoceptor coupling.

The purpose of this study was to evaluate prospectively the evolution of femoral and vertebral bone mineral density (BMD) in hypothyroid subjects treated with replacement doses (mean +/- SD dose of L-thyroxine = 135 +/- 32 micrograms/day) as compared to an untreated group. Vertebral bone density was also measured in other patients who had been treated for at least 2 years with either suppressive (mean dose = 154 +/- 36 micrograms/day, n = 28) or replacement doses (mean dose = 104 +/- 52 micrograms/day, n = 21) according to the thyrotrophin response (TSH) to the thyrotrophin releasing hormone (TRH) administration. In primary hypothyroid patients, a mean decrease of 5.4% (P less than 0.01) for vertebral BMD, 7.3% (P less than 0.01) for trochanter and 7% (P less than 0.001) for femoral neck was observed after 1 year of treatment. This loss was unrelated either to age or to menopausal status (ANOVA). A clinical and hormonal state of euthyroidism was reached since the 3rd month of treatment. Fasting urinary calcium/creatinine excretion was increased significantly (P less than 0.05) at the 3rd month, and plasma osteocalcin (OC) increased significantly from the 3rd month onwards (P less than 0.05) up to the 12th month (P less than 0.025). In the cross-sectional study, vertebral BMD was not significantly different from age-matched normal values in patients receiving either substitutive or suppressive doses of LT4. These results suggest that in the case of primary hypothyroidism even appropriate thyroid replacement therapy could lead during the first year of treatment to a significant reduction in vertebral and femoral BMD. However, the fact that an increased fracture rate has not been documented in long-term treated patients, and the results of our cross-sectional study, suggest that this bone mass reduction could be transient and reversible due to new bone formation at the end of the resorptive sequence.

The purpose of the study was to evaluate the interest of ambulatory blood pressure (BP) recording (ABPR) in the management of arterial hypertension (AH) with dysautonomia. The study concerned 8 hypertensive patients (pts), 5 men, 3 females 52 +/- 10 years old, with orthostatic hypotension (OH): BP was 162 +/- 19/87 +/- 16 mmHg and 129 +/- 15/76 +/- 8 mmHg in lying and standing position respectively. In two cases AH was associated with a central degenerative disorder whereas the six other pts had a diabetic dysautonomia: bad metabolic control (HBA1c 14.4 +/- 2.7%), and incipient or over nephropathy (4 pts). ABPR was performed in all pts during 24 hours (space-labs system). In these hypertensive pts with OH, the mean 24 hour-BP was surprisingly normal at 128 +/- 11/76 +/- 6 mmHg. ABPR demonstrated the loss of nocturnal decline in BP: diurnal and nocturnal BP were respectively 125 +/- 13/74 +/- 6 mmHg and 133 +/- 16/78 +/- 10 mmHg (NS). 6 of 8 pts had an increase in BP at night resulting for the population (n = 8) in a nocturnal increase (%) of + 5.6%, this pattern widely differs from controls--13%. The decrease in heart rate during sleep was blunted but significant from 89 +/- 9 b/min to 81 +/- 9 b/min (p 0.01). Diurnal and nocturnal BP variability (V), assessed by variation coefficient were not significantly different: SBP-V was 10.3 +/- 6.4% day and 12.3 +/- 4.2% night, DBP-V 7.5 +/- 6.3% day and 12.5 +/- 3.1% night.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]-yohimbine binding) have been investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One min standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and Kd) calculated by [3H]-yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state determined by inhibition experiments of [3H]-yohimbine binding by UK14,304 (a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). These results indicate that orthostatic hypotension in insulin-dependent diabetic patients is marked by a lack of noradrenaline increase in standing position and by a decrease in platelet alpha 2-adrenoceptors in high affinity state. Thus we suggest that orthostatic hypotension of diabetes mellitus is the result of sympathetic nerves injuries and of abnormalities in alpha 2-adrenoceptors coupling.

The follicle stimulating activity (FSA) and interstitial cell stimulating activity (ICSA) of highly purified human chorionic gonadotropin (hCG), its alpha and beta subunits, and hCG generated by subunit recombination were determined by ovarian weight and ventral prostate weight bioassays. Whereas highly purified hCG exhibited both FA and ICSA, its separated subunits were essentially devoid of both activities. ICSA and FSA, indistinguishable from that of the highly purified hCG, were restored by recombination of the hCG subunits. These observations are consistent with the hypothesis that the FSA and ICSA found in highly purified hCG preparations are properties of the hCG molecule.

Transsphenoidal microsurgery was performed in four patients with a pituitary microadenoma who presented Cushing's disease. Preoperative features were the following: 1) Clinical and laboratory signs of hypercortisolism 2) No radiological evidence of an adrenal tumor 3) Normal or increased ACTH plasma levels 4) Sellar tomograms suggesting the presence of a pituitary microadenoma in only one case. Postoperative outcome after 3 to 30 months follow-up showed persistence or even improved reactivity of the various pituitary functions and especially the early occurence of corticotropin deficiency in all 4 patients. This isolated deficiency regressed spontaneously after 6 and 12 months (2/4 cases). Twenty-four hour studies of ACTH and cortisol profiles and dexamethasone suppression as well as response to metyrapone confirmed the resumption of physiological corticotropin regulation.

Thyrotrophin releasing factor (TRF) was given intravenously in doses of 0-5 mg and 20 mg to six patients with Parkinsonism treated with L-dopa. Plasma thyrotrophin (TSH), prolactin, lutenizing hormone (LH), follicle stimulating hormone (FSH), thyroxine (T4) and triiodothyronine (T3) were measured before and after TRF infusion. The observation that FSH and LH did not change in response to either dose of TRF confirmed specificity of the effects TRF for certain anterior pituitary functions. The plasma TSH and prolactin levels achieved after 20 mg TRF were considerably greater and were maintained longer than those after 0-5 mg TRF. However, despite a seven fold increase in the overall TSH response, the T4 and T3 responses to 20 mg TRF were not significantly greater than those to 0-5 mg TRF. The explanation for this discrepancy between immunoreactive TSH levels and apparent biologic effect is unclear.

The course of mean arterial pressure was compared in two series concerning 18 primary or tumoral hyperaldosteronism and 8 idiopathic ones. Identification of the nature of the hyperaldosteronism should not yet motivate a decision on principle, surgical in case of tumor, medical in an idiopathic case. In the latter case cooperation and tolerance of medical treatment, severity of hypertension also come into consideration. A positive spirolactone test, a hypertension course of less than six years were in our experience a good indication of successful surgery, as opposed to a normal unilateral renal biopsy. In case of operation, the removal protocol should adapt to the peroperative findings; 80% adrenalectomy is the most common procedure, except in the case of isolated adenoma of more than 10 mm diameter.

A computerised study has been carried out on the general features of a clinical, biological and histological nature occurring in 124 varicocoele cases that were operated. These features were furthermore studied in correlation with the degree of varicocoele in existence and whether characteristics were found in isolation or in association with one another. The authors conclude that there were significant correlations between the degree of varicocoele present and the hormonal and histological findings. They advance a theory about the transport of testosterone in the spermatic cord which can explain the low level of testosterone found in the blood in these varicocoeles.

In connection with systematic studies of steroid and peptide hormone interactions during follicular growth, we have measured ovarian weight responses to graded doses of highly purified human chorionic gonadotropin (hCG), human interstitial cell stimulating hormone (hICSH)in hypophysectomized immature female rats (HIFR) treated with diethylstilbestrol in silastic capules (desc) implanted subcutaneously. Our results are consistent with earlier reports of enhancement of ovarian weight responses to hCG and FSH. Contrary to results of similar experiments reported by others, we have found that estrogen treatment of HIFR enhanced ovarian weight response to ICSH. In addition, we report for the first time that small doses of hCG and hICSH inhibit ovarian weight responses to estrogen in HIFR. Our observations on effects of small doses of hCG and hICSH and the long-known fact that ovarian interstitial cells are stimulated in HIFR given similar doses of these hormones lead us to hypothesize that ovarian interstitial cell stimulation is involved in the control of follicular maturation.

Inhibition by antiestradiol serum of ovarian weight gain and follicular growth in hypophysectomized immature rats given FSH and hCG suggested that gonadotrophin induced endogenous estrogen secretion plays a role in the ovarian augmentation reaction. We have studied the effects of a chemical estrogen antagonist, cis-clomiphene, on ovarian weight response to gonadotrophins in hypophysectomized immature female rats. We found that this antiestrogen inhibits the ovarian response to FSH and hCG. To our knowledge, this is the first demonstration of a direct effect of a chemical antiestrogen on the ovary, a result consistent with a role for intraovarian estrogen in follicular growth.

Endometrial progesterone concentrations have been determined during the menstrual cycle and compared to plasma progesterone and estradiol-17 beta concentration. There is a good relationship between endometrial and plasma progesterone concentrations but none between endometrial progesterone and estradiol-17 beta concentration.

The discovery that LH/RH was secreted in a pulsatile manner has made it possible to use the substance therapeutically in certain endocrine conditions of female sterility. 29 patients had sterility because of ovarian dysfunction. 3 of these were polycystic ovaries, 13 unexplained malfunction of ovulation and 30 hypothalamic in cause. They were treated with LH/RH intravenously. The dose used with each pulse was 6-18 micrograms. The patients were treated for between 18 and 30 days. In the 9 pregnancies that occurred (30%) one was in a patient with polycystic ovaries, 8 (70%) were in patients with hypothalamic ovarian failure. In each case the dose of LH/RH had been administered either at a level of less than 10 micrograms/pulse throughout the follicular phase with an injection of 5000 IU of HCG after ovulation or throughout the whole cycle. 77% of the pregnancies were obtained during the two first cycles of treatment. This work shows that hypothalamic female sterility is the proper indication for treatment using LH/RH. The protocol of dosage should be as economical as possible by administering 5-10 micrograms pulses intravenously up to the time that ovulation has been achieved. This takes note of the difficulties of obtaining supplies of the substance.

Thirteen patients aged 1 to 59 years hospitalized for diabetes insipidus (DI) were investigated by computed tomography (CT). Apart from one craniopharyngioma, CT revealed in 8 out of 12 cases several modifications in the hypothalamic-pituitary region. In this group, CT demonstrated a small, round, isodense mass in the chiasmatic cistern that enhanced after contrast medium injection. Coronal and sagittal reconstructions helped pinpoint the lesion in the infundibulum and pituitary stalk, and, in one case, in the supraoptic nuclei. These findings, and the noninvasiveness of CT, make this technique one of the most accurate means of radiological investigation of DI and also of determining the efficacy of therapy.

Levels of testosterone, free testosterone, oestrogen, LH, FSH, prolactin were measured in 39 dialysed men. A LHRH stimulation test was performed. This study was analysed in function of the underlying renal disease, the duration of hemodialysis, and serum ferritin levels. In chronic glomerulonephritis serum gonadotrophins concentrations were significantly higher than in chronic interstitial nephritis or polycystic disease. A correlation between prolactin and ferritin was found, which may reflect the pituitary iron overload. Free testosterone levels were significantly lower in patients with gynecomastia (23-29 patients). In fact, the most direct relationship that we found with gynecomastia in dialysed men was with the free testosterone/oestrogen ratio.

Since Sherwood's report in 1979, contradictory findings have been published with regards to the treatment of primary hyperparathyroidism with cimetidine. We studied 16 patients with primary hyperparathyroidism treated with 1,200 mg of Cimetidine and followed-up clinically and biochemically. A decrease in serum calcium and urinary CAMP was observed after the fourth week of cimetidine therapy with no significant change in parathormone levels. In none of the cases did Cimetidine seem to provide a treatment of hyperparathyroidism, a condition which remains curable with surgery.

Three patients with karyotype XYY who had presented with deep vein thrombosis and leg ulcers (plus pulmonary embolism in two of them) were investigated for: (1) androgens (plasma testosterone measurement, testosterone oestradiol binding globulin (TeBG) assay, GnRH 50 micrograms test), and (2) haemostasis by fibrinolysis tests (euglobulin lysis time and area, antigenic plasminogen activator assay before and after 10 min venostasis). Full evaluation of haemostasis failed to demonstrate the presence of circulating anticoagulant or of antithrombin III, protein C and protein S deficiencies. One patient had neither hormonal nor fibrinolytic abnormality. The other two patients shared some clinical features with male hypogonadism (gynoid morphotype in both, hypotrophy of the testes in one, gynaecomastia in the other). They also had hormonal disorders ("over-response" to the GnRH test in one case, elevated TeGB in the other case) and abnormalities of fibrinolysis (poor response to venostasis, high baseline level of plasminogen activator). Response to venostasis became normal after 3 months of treatment with percutaneous dihydrosterone 125 mg per day in the two patients with initially poor response. The mechanism of venous pathology in XYY subjects is discussed. A genetic defect not involving the fibrinolysis system is possible since fibrinolysis was normal in one patient; however, abnormal fibrinolysis may have been responsible for the venous pathology in the other 2 patients. The role played by abnormalities of fibrinolysis in the pathogenesis of deep vein thrombosis and leg ulcers is recalled, and the possible implication of these abnormalities in patients with XYY karyotype is emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary hyperparathyroidism is rarely diagnosed during pregnancy. The authors report a case occurring in a patient of 32 years of age, which was diagnosed in the fourth month of pregnancy because of the appearance of acute hypercalcemia. The outcome was good after a parathyroid adenoma had been removed. There was no hypocalcemia after the operation in the mother and when the child was born at term its calcium levels were normal. A review of the literature shows how the diagnosis can be made of primary hyperparathyroidism in pregnancy and how the discovery of the condition has evolved and that surgery should be carried out in the second trimester of the pregnancy to lessen the maternal and fetal morbidity.