Brief report: melatonin-related hypogonadotropic hypogonadism.
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Biomedical subjects
Publications and source records attributed to S M Webb.
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Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long-acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way.
OBJECTIVE: We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. DESIGN: We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. PATIENTS: We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. MEASUREMENTS: Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. RESULTS: Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. CONCLUSIONS: In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.
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The results of the treatment of acromegaly in 56 patients have been reviewed. Transsphenoidal pituitary adenomectomy (TPA) represented the most effective therapy, as it resulted in a cure rate of 64.7%, with 8.8% of complications and 14.7% of endocrine insufficiencies secondary to surgery. When radiotherapy was administered after surgery (when the latter had not been curative), the overall rate of cure increased to 73.5%. By contrast, the patients treated only with radiotherapy had a markedly lower cure rate (44.4%), with a higher rate of endocrine insufficiency (55%). The occurrence of extrasellar extension shown in preoperative pituitary computed tomography did not correlate with a worse postoperative cure rate; by contrast, the invasive character of the adenoma represented a reduction in the postoperative cure rate. It was concluded that TPA is the treatment of choice in acromegaly, independently of the tumor size.
Diurnal profiles of the content of immunoreactive somatostatin (IRS) in the male and female rat pineal, Harderian gland and retina have been studied. Supplementary experiments have been performed to elucidate a possible effect of infradian cycles, namely estrous and seasonal cycles, and continuous dark on IRS concentration. Results demonstrate that the IRS content in the rat pineal gland, Harderian gland and retina is submitted to diurnal variations, but not under all studied conditions. A sexual dimorphism exists between male and female animals: male rats showed higher IRS content in pineal (103.8 +/- 4.7 vs 32.3 +/- 1.8 pg IRS/gland), but lower in retina (1,362.1 +/- 82.7 vs 2,176 +/- 102.2 +/- pg IRS/mg of protein) and Harderian gland (10.3 +/- 0.8 vs 30.6 +/- 3.5 pg IRS/mg of protein). Additionally, seasonal differences appeared: in male and female animals pineal IRS content was lower in spring than in November. This decrease also appeared in female retina IRS concentration. Estrous cycle did not seem to change IRS content in the three studied tissues. Finally, pineal IRS rhythm persisted after continuous dark for a week. These results demonstrate, in the rat, sexual differences in the IRS content of the various tissues studied and suggest a physiological role for somatostatin, possibly related to seasonal adaptation.
Hyperandrogenism in women is usually accompanied by a disruption of the hypothalamic-pituitary-ovarian axis; however, the precise effect of chronically elevated androgens on this axis is poorly understood. We report a postmenopausal woman with a virilizing ovarian tumour in whom the effects of chronic testosterone secretion on the hypothalamic-pituitary axis was investigated. A 56-year-old woman was evaluated for hirsutism and hyperandrogenism of recent onset. Peripheral serum testosterone was high (19.4 nmol/l), while gonadotropins were below normal for a postmenopausal woman, FSH (19.7 IU/l) being higher than LH (10.3 IU/l). Four LH and 1 FSH pulse were detected over 4 h. A left intraovarian testosterone secreting tumour, shown by catheterization of the ovarian veins and containing imperfect crystalloids of Reinke, was excised. Postoperatively, peripheral testosterone became undetectable, while gonadotropins rose to normal postmenopausal values. This patient's LH/FSH ratio was less than 1, in contrast with other situations of chronic hyperandrogenism. This could be explained by the concomitant hypoestrogenic state, and/or the theoretical absence of inhibin. The interest of this case resides in that it constitutes an appropriate model for studying the effects of testosterone on LH and FSH secretion in the absence of the other two classically involved modulators, namely oestrogens and inhibin.
A methodology was developed to support a comprehensive health services research project undertaken to monitor and evaluate the practice of in vitro fertilization (IVF) and related procedures, such as GIFT, in Western Australia (WA) from 1983 to 1987. The project included demographic, clinical and economic assessments of the new technology. The study subjects were the 1,240 couples who began IVF treatment between January 1, 1983 and December 30, 1986. Information was collected on all 2,982 treatment cycles commenced by June 30, 1987, and on the 273 births that resulted from these treatment cycles. Where relevant, comparisons were based on information obtained from the Australian Bureau of Statistics (ABS) census, the WA Midwives' Notification System and the WA Hospital Morbidity Data System. The need for long-term follow-up studies of children and participants is identified, as is the need for randomized clinical trials to evaluate more fully the success of the procedures where bilateral tubal blockage is not the indication for the treatment.
A female is reported with a pituitary tumor secreting growth hormone which remained active and induced invalidating headache in spite of previous treatment with surgery and radiotherapy. Treatment with the sustained action somatostatin analogue, SMS 201-995, was started and headache was improved in a matter of minutes, even if normalization of hormone hypersecretion was not demonstrated. The pathophysiological mechanisms possibly implicated in the improvement are discussed, and this therapeutic option in patients with headache unresponsive to common analgesics is emphasized.
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Gastrin and somatostatin-like immunoreactivity (SLI) levels were studied by means of radioimmunoassay in peripheral venous blood of healthy volunteers and patients suffering from gastric adenocarcinoma or duodenal and gastric ulcers. Gastrin and SLI levels were also evaluated in patients in blood drawn from gastric veins during surgery. The elevations of gastrin and SLI levels were found in patients with gastric cancer as compared with healthy people and patients suffering from ulcers. The impairment of the negative feedback between gastrin and somatostatin secretions in patients with gastric cancer was suggested.
Regional distribution of immunoreactive somatostatin (IRS) and melatonin were investigated in the bovine pineal gland. The total IRS and melatonin content ranged from 0.26 to 2.28 pmol, and from 19.4 to 42.7 pmol, respectively, per bovine pineal. Reverse phase liquid chromatography of pineal extracts demonstrated that more than 90% of IRS coeluted with synthetic somatostatin-14 and somatostatin-28. While the IRS content was shown to vary considerably throughout the gland, with a constant and marked maximal concentration at the proximal end of the pineal, the maximal melatonin concentration appeared in the central part of the gland, coinciding with the total protein distribution. The existence of the highest levels of pineal IRS near the habenular commissure, where the afferent fibers of the central pinealopetal innervation enter the gland, suggests that pineal somatostatin may be, at least in part, of neural origin.
Plasma melatonin circadian profiles were investigated in a group of 4 patients with anorexia nervosa and 4 healthy regularly cycling women. There were no differences in the mean age of both groups, whereas the anorexia nervosa patients had lower mean body weight (37.8 +/- 2.0 vs 57.0 +/- 4.9 kg) and body mass index (13.9 +/- 1.1 vs 20.8 +/- 2.0). Samples were collected every 2 h and plasma melatonin was measured by using a RIA with an iodinated tracer. Anorexia nervosa patients exhibited higher diurnal (60.7 +/- 1.8 vs 25.4 +/- 1.72 pmol/l, P less than 0.02) and nocturnal (419.2 +/- 37.4 vs 108.0 +/- 33.6 pmol/l), P less than 0.001) mean plasma melatonin concentrations. There were no differences in the time peak for nocturnal melatonin secretion in both groups, detected at 02.00 h. In anorexia nervosa, the melatonin circadian profile paralleled that observed in the control group, indicating that the increased melatonin values for anorexia nervosa were probably due to an enhanced secretory pineal function rather than an impaired melatonin metabolism. These results suggest a participation of the pineal gland in the pathophysiology of anorexia nervosa.
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Immunoreactive somatostatin (IRS) has been previously demonstrated in the pineal gland of different rodent species, and we observed a 24-hr rhythm in rats. Recent data suggest that the peptide may represent a neurotransmitter in the so-called peptidergic nerves of the central, pinealopetal innervation of the epiphysis, which may modulate the activity and secretion of the gland. We investigated whether 24-hr changes of pineal IRS content occurred in Syrian hamsters, gerbils, and mice. Adult males, kept in a 14:10 LD photoperiod, were decapitated at 4-hr intervals throughout a 24-hr period. Pineals and median eminences were analyzed for IRS by radioimmunoassay. No significant changes in the median eminence content of IRS with time was observed. As previously described in rats, a statistically significant rhythm of IRS was observed in the pineal of hamsters and mice, with a peak at 2000 hr (mice 51.7 +/- 5 pg/pineal; hamsters 26.3 +/- 4.6) and a nadir at 2400 hr (mice 30.8 +/- 1.4) or 0400 hr (hamsters 8.6 +/- 1). However, in the gerbil pineal IRS content remained unchanged throughout the period of study. Since the three species examined have very different melatonin cycles, it is suggested that the melatonin and IRS rhythms are unrelated and independently regulated events within the pineal gland.
Harderian glands of Syrian hamsters contained measurable levels of immunoreactive somatostatin. After an extraction procedure, serial dilutions of tissue were assayed and showed parallelism in the displacement curve with dilutions of purified somatostatin standard in the radioimmunoassay. Somatostatin concentrations were higher in female hamsters (10.0 +/- 2.1 ng/mg protein) than in males (2.6 +/- 0.4 ng/mg protein). Castrated males had somatostatin values in the range of females (12.4 +/- 2.3 ng/mg protein) at 1 month after gonadectomy. Testosterone implants prevented the rise of Harderian gland somatostatin in castrated males. Gonadectomized males had lower somatostatin content in the gland than did control males (1.0 +/- 0.2 ng/mg protein) at 2 months after castration. Somatostatin values in females were unaffected by gonadectomy, but there were variations during the oestrous cycle, with a nadir detected at dioestrus-1 and maximal values coincident with the day of the ovulation.
Seven women with prolactin-secreting pituitary microadenomas and three with persistent hyperprolactinemia after surgical adenomectomies were evaluated with computed tomography to assess the effect of pregnancy on the volume of pituitary prolactinomas and hyperfunctioning pituitary tissue. In one patient a microadenoma enlarged to become a macroadenoma. Tumor enlargement occurred in the remaining six patients with microadenomas. None of the patients with previously resected adenomas exhibited hypertrophy of residual pituitary tissue or tumor recurrence after pregnancy.
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