Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment: report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma.

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.

Hormonal changes related to eating behavior in oligomenorrheic women.

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.

Treatment with long acting repeatable bromocriptine (Parlodel-LAR*) in patients with macroprolactinomas: long-term study in 29 patients.

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.

[Use of a gonadoliberin agonist with or without gonadoliberin pulses for ovulation induction in ovarian dystrophies]. / Utilisation d'un agoniste de la gonadolibérine suivie ou non de gonadolibérine pulsatile pour l'induction d'ovulation dans les dystrophies ovariennes.

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.

Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis.

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.

A long-acting repeatable form of bromocriptine as long-term treatment of prolactin-secreting macroadenomas: a multicenter study.

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.

[Transitory bone loss during substitution treatment for hypothyroidism. Results of a two year prospective study]. / Perte osseuse transitoire au cours du traitement substitutif de l'hypothyroïdie. Résultats d'une étude prospective de deux ans.

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.

LH pulsatility and in vitro bioactivity in women with anorexia nervosa-related hypothalamic amenorrhea.

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.

Correlations between mean LH levels and LH pulse characteristics: differences between normal and anovulatory women.

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.

Luteinizing hormone pulse frequency and in vitro bioactivity in male idiopathic infertility.

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.

[Short-term effect of delayed-action injectable bromocriptine in macroprolactinoma. French multicenter study]. / Effets à court terme de la bromocriptine injectable retard dans les macroprolactinomes. Etude multicentrique française.

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.

Preventive effects of transdermal administration of 17 beta-estradiol on postmenopausal bone loss: a 2-year prospective study.

A 2-year prospective study was conducted on 44 early postmenopausal women to assess the effect of transdermal estradiol (TTS-E2) on vertebral bone mass. Twenty treated women and 24 untreated were studied. Treatment consisted of TTS-E2 (0.05 mg/day, 3 weeks a month) and an oral gestagen (10 days per month). At 24 months, bone mineral density, measured by Dual Photon Absorptiometry (DPA), decreased significantly in untreated women (-4.3%) (p less than 0.001), while treated women had a net gain of +5.4% (p less than 0.001). Bone turnover parameters (serum osteocalcin, urinary calcium/creatinine ratio) were significantly (p less than 0.05) reduced from the 2nd month of treatment onwards. Serum estradiol levels were sustained during the treatment and were in the range of an early follicular phase (approximately 45 pg/ml). These findings suggest that low doses of transdermal estradiol sufficient to relieve menopausal symptoms, and which, due to the association with progestogen, result in regular withdrawal bleeding, are effective in preventing postmenopausal bone loss.

Sensitivity of dual-photon absorptiometry in spinal osteoporosis.

Lumbar spine bone mass and density were measured with Dual photon absorptiometry (DPA) in 60 patients with crush fractures and 60 age-matched normal women. Short-term reproducibility of bone mineral density (BMD) was 1.3% in normal women and 2.5% in osteoporotic women; long-term reproducibility in normal women was 2.2%. The reproducibility of bone mineral content (BMC) seemed to be poorer than that of BMD. In this study, aortic calcifications had no effect on BMD, and one or two crush fractures in the L2-L4 region increased BMD by an average of 3% (0-10%). Lumbar spine DPA provided high sensitivity for these younger crush fracture osteoporotic patients (x = 65 years). The sensitivity at 95% specificity was 74% for BMD and 73% for BMC. This sensitivity is substantially better than that reported for DPA instruments giving higher variances or for quantitative computed tomography.

Ovarian cystadenoma with stromal cell hyperplasia and postmenopausal virilization: a case report.

A 73-yr-old woman had noted progressive virilization. The plasma testosterone levels were elevated (340 ng/dl) and the pelvic ultrasound examination revealed an enlarged left ovary. At laparotomy, a large cystic tumor replaced the left ovary. The plasma testosterone became normal after the removal of the tumor. On anatomical analysis, the tumor was an ovarian cystadenoma with hyperplasia of stromal cells in the periphery of the tumor.

[Cimetidine treatment of primary hyperparathyroidism]. / Traitement par la cimétidine de l'hyperparathyroidie primitive.

Since Sherwood's report in 1979, contradictory findings have been published with regarding 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.

[Treatment with LH-RH in female sterility]. / Traitement par le LH-RH dans les stérilités féminines.

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.

Obesity and postmenopausal bone loss: the influence of obesity on vertebral density and bone turnover in postmenopausal women.

This study was undertaken to evaluate the effect of obesity on the postmenopausal bone mass. Bone mineral density, measured by dual photon absorptiometry of the lumbar spine, serum osteocalcin (OC), fasting urinary calcium to creatinine (Ca:Cr), serum estradiol (E2) dehydroepiandrosterone (DHA) and testosterone (T) were measured in 176 women aged 45-71 years. Women were divided into four groups according to their menopausal status and their weight: 49 perimenopausal, 28 obese perimenopausal, 49 obese postmenopausal. Within each population (perimenopausal and postmenopausal), mean age was the same, only weight was significantly different (p less than 0.0001). For the two groups of postmenopausal women mean interval since menopause (YSM) was the same (5.8 +/- 3 and 5.4 +/- 5 yr). Comparison between groups revealed a significant effect of menopausal status and obesity on BMD and bone turnover. As compared to perimenopausal women, BMD was lower, OC and Ca: Cr higher only in nonobese-postmenopausal women. E2, T, DHA did not differ between the two groups of postmenopausal women. The results of this study suggest that even moderate obesity can play a protective role on postmenopausal bone loss.

[Post-phlebitic leg ulcers and XYY karyotype: fibrinolysis and androgenic function tests. Apropos of 3 cases]. / Ulcères de jambe post-phlébitiques et caryotype XYY: tests de fibrinolyse et fonction androgénique. A propos de 3 cas.

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)