Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-induced hypoglycemia test was used to study the hypothalamic-pituitary function of nine normal control subjects and 49 patients with amenorrhea. There were 10 patients with secondary amenorrhea due to hypothalamic dysfunction, eight with hypothalamic failure, eight with primary amenorrhea due to hypogonadotropic hypogonadism, 19 with a prolactin-secreting pituitary adenoma, and four with Sheehan's syndrome. After the administration of insulin (0.15 unit/kg), a significant increase in plasma levels of prolactin, growth hormone, and cortisol occurred in all normal subjects. Of the 10 patients with hypothalamic dysfunction, two had a blunted prolactin response, six had an abnormal growth hormone response, and all had a normal cortisol response. Of those with hypothalamic failure, abnormal responses for prolactin were seen in two patients, for growth hormone in four patients, and all had a normal increase in cortisol. Five of the eight patients with primary amenorrhea had a blunted response for prolactin, six for growth hormone, and there were no abnormalities for plasma cortisol. All 19 patients with pituitary adenomas had a blunted increase in prolactin, 16 had an abnormal growth hormone response, and two had an abnormal cortisol response. Prolactin, growth hormone, and cortisol responses were blunted in all patients with Sheehan's syndrome. These results demonstrate that the release of growth hormone subsequent to insulin-induced hypoglycemia is the most common abnormality seen in women with amenorrhea. The high frequency of abnormal release of prolactin indicates that serum prolactin should be measured when this test is performed. In addition, patients with prolactin-secreting adenomas and those with Sheehan's syndrome should be given an insulin tolerance test before treatment is instituted, so that patients with secondary adrenal insufficiency can be identified.
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PMID:Pituitary response to insulin-induced hypoglycemia in patients with amenorrhea of different etiologies. 636 9

The treatment of hyperprolactinemia with dopaminergic agents is directly correlated with the improvement of the knowledge about hypothalamic control of prolactin secretion. Since 1963 it is wellknown that the hypothalamus acts on this activity of the pituitary gland with a tonic inhibition. A prolactin inhibiting factor (PIF) was suspected for this control and the tubero-infundibular dopaminergic system was considered to modulate the secretion of PIF. In fact a lot of experience demonstrated a direct control of dopamine on pituitary gland itself (fig. 1). Ergot alkaloids are the most useful dopaminergic drugs. They derive from 6 methyl 9 ergoline (fig. 2) and, in the main group of 12 ergocryptine molecules, alpha-ergocryptine and ergocornine are the most potent (fig. 3). Bromocryptine (2 alpha-bromoergocryptine, BEC) is a compound (fig. 4) with a magnification of the effect on prolactin secretion and loss of uterotonic and vasoconstrictive effects. This drug acts directly on normal pituitary cells and on adenomas in vitro. The inhibition of secretion is first seen, followed by inhibition of synthesis. Transplanted tumors (MtTW15) are sensible to ergocornine but not to BEC. The oral administration of the drug is followed by an increase in serum concentration (fig. 5) maximum at 3 hours. The decrease of prolactin is progressive and prolonged until the 7th hour. Some similarities between the structure of dopamine and bromocryptine may explain the effect of the drug (fig. 6). Hyperprolactinemia constitutes a frequent clinical syndrome with amenorrhea-galactorrhea and sterility. The cause is a pituitary tumor composed of prolactin secreting cells. All the clinical and biological manifestations are due to high prolactin secretion and the surgical ablation of the adenoma is followed by complete cure. This result is obtained frequently in microadenomas. The medical treatment of hyperprolactinemia with BEC was initiated in 71 by Lutterbeck. Since that time a lot of clinical experiences give the same kind of results: Improvement in 100% of galactorrhea, 90% of amenorrhea and 80% of fertility. These results are now wellknown and the secondary effects of the drug are quite limited. The development of pregnancy in a patient suspected of a pituitary adenoma is a major problem which is now clearly solved. In a survey of the literature Nillius found 146 patients in this situation with only 5.6% of complication. Our experience with 18 patients is confirmative. Moreover we found after delivery a decrease of serum prolactin (fig. 7).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Dopaminergic agents in the treatment of hyperprolactinemia]. 636 1

Two patients are described who were suffering from primary hypothyroidism and who developed a pituitary microadenoma and macroadenoma with suprasellar extension, respectively, diagnosed by CT scan of the pituitary. Both patients originally presented with amenorrhea and galactorrhea. In addition to low serum T4 and T3 levels and an elevated TSH level, they also had hyperprolactinemia. The TRH test performed in one of the patients showed an exaggerated response of both TSH and PRL to TRH. Correction of hypothyroidism by prolonged (months) treatment with levothyroxine resulted in normalization of thyroid function tests as well as hyperprolactinemia and in regression of the pituitary tumor. It was concluded that primary hypothyroidism was the cause of the pituitary adenoma and the amenorrhea/galactorrhea syndrome. It is recommended that routine thyroid function tests be obtained for patients with hyperprolactinemia. Demonstrable primary hypothyroidism should be corrected for prolonged periods of time by levothyroxine therapy, and CT scanning of the pituitary should be repeated before any other treatment such as bromocriptine or surgery is attempted.
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PMID:Regression of a pituitary adenoma following levothyroxine therapy of primary hypothyroidism. 641 99

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma.
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PMID:Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics. 642 60

The clinical use of bromocriptine was investigated in 50 hyper- and 30 normoprolactinaemic women attending an infertility clinic and presenting with anovulatory cycles, oligomenorrhoea or amenorrhoea and the complaint that they had failed to become pregnant. The results confirmed that bromocriptine is effective in the treatment of hyperprolactinaemic states. Bromocriptine supresses prolactin secretion irrespective of the underlying pathologic process. Hyperprolactinaemia in humans is frequently associated with anovulation. Serum prolactin values showed no close correlation with the degree of menstrual abnormalities or galactorrhoea. Basal FSH and LH levels and the gonadotropin response to LH-RH were essentially normal in hyperprolactinaemia. Circulating E2 levels were largely subnormal suggesting an inhibitory effect of prolactin on ovarian E2 production. Prolactin levels over 100 ng/ml are suggestive of pituitary adenoma.
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PMID:Hyperprolactinaemia and female infertility. 644 Jan 15

A 43-yr-old woman, who had previously had a subtotal thyroidectomy, presented with hyperthyroidism and amenorrhea-galactorrhea due to a pituitary adenoma secreting TSH, TSH-alpha, and PRL. Her serum T4 concentration was 14 micrograms/dl; T3, 5.7 ng/ml, and TSH, 19-33 microU/ml. Serum TSH was not altered by TRH stimulation or T3 suppression. Basal plasma PRL levels were 19-27 ng/ml and plasma PRL doubled after TRH stimulation. A 900-mg pituitary tumor, removed by transphenoidal surgery, was studied in cell culture. After dispersion, tumor cells were maintained on an extracellular matrix produced by bovine corneal endothelial cells in a defined serum-free medium. The hormones released in the culture medium were analyzed by high pressure gel chromatography. Three fractions of tumor TSH were found, with respective apparent mol wts of 45,000 (11%), 28,000 (70%), and 20,000 (19%). Tumoral PRL eluted as a single peak of apparent mol wt of 24,000. Pharmacological studies of TSH, TSH-alpha, and PRL release using thyroid hormones (T3), dopamine agonist (bromocriptine), TRH, and cholera toxin yielded the following results: 1) T3 after 3 days of incubation produced a dose-dependent inhibition of TSH, TSH-alpha, and PRL release. Maximal inhibition (81%) was obtained at 10(-9) M and half-maximal inhibition at 4-6 X 10(-11) M. 2) Bromocriptine produced rapid and partial inhibition of hormone release. Maximal inhibition (51%) was obtained at 10(-8) M and half-maximal inhibition at 5 X 10(-10) M. 3) TRH at 10(-8) M concentration significantly stimulated PRL release but it had no effect on TSH release. 4) Adenylate cyclase activation by 10(-11) M cholera toxin increased TSH (152%), TSH-alpha (150%), and PRL (220%). Immunohistochemical analysis of serial 2 micron sections of the tumor showed that: 1) TSH-alpha immunoreactive cells were the most numerous, 2) TSH-beta positive cells were always positive for TSH-alpha, 3) PRL immunoreactivity was found either uniquely in some cells and colocalized with TSH-alpha immunoreactivity in other cells. However, by electron microscopy, the tumor cells were thyrotrophs. These data indicate that in this patient's tumor: 1) cells secreting TSH were responsive in vitro to near physiological concentrations of thyroid hormones. 2) The colocalization of PRL and TSH-alpha immunoreactivities in some cells raises the possibility either of fusion of differentiated pituitary cells synthesizing distinct hormones or of transformation of less differentiated multipotential pituitary cells.
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PMID:A human pituitary adenoma secreting thyrotropin and prolactin: immunohistochemical, biochemical, and cell culture studies. 648 Aug 9

A prolactin-secreting pituitary adenoma containing amyloid substance was studied by light and electron microscopy. The tumor was found in a 32-year-old woman who presented with a short history of amenorrhea and galactorrhea. Pituitary adenoma containing amyloid substance is a very rare entity, and the implications of this association are discussed. Previous reports, suggesting that mesenchymal cells or hormone-secreting tumor cells in pituitary adenomas produce amyloid substances, are reviewed.
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PMID:Prolactinoma of pituitary with associated amyloid-like substances. Case report. 663 2

A case-control study was conducted to determine whether use of oral contraceptives (OCs) is associated with an increased risk of prolactin-secreting pituitary adenomas. Two hundred twelve women with such adenomas (140 of which were surgically confirmed) were recruited from four clinical centers and interviewed and matched by age and race to neighborhood control subjects. In addition, 119 hyperprolactinemic patients with amenorrhea and/or galactorrhea (A/G) who had normal or equivocal tomograms and 205 normoprolactinemic women with A/G were also interviewed and matched to neighborhood control subjects. No increase in relative odds (RO) for any of these groups of patients was found for use of OCs (pituitary adenoma cases versus controls RO = 1.33, 95% confidence intervals [CI] = 0.81 to 2.22; equivocal cases versus controls RO = 1.35, 95% CI = 0.69 to 2.70; secondary A/G cases versus controls RO = 0.67, 95% CI = 0.37 to 1.18). History of infertility (RO = 25.5, 95% CI = 8.49 to 76.6), of menstrual problems or A/G (RO = 4.47, 95% CI = 2.21 to 9.05), and of nulliparity (RO = 4.36, 95% CI = 2.10 to 9.04) were each associated with a significantly increased risk of pituitary adenomas. The results of this study do not indicate any increase in risk of pituitary adenomas as a result of using OCs.
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PMID:Pituitary adenomas and oral contraceptives: a multicenter case-control study. 668 10

Serial measurements of serum prolactin (PRL), chorionic gonadotropin (hCG), estradiol and progesterone were performed during 16 normal pregnancies. The same hormone analyses were performed in a woman with the galactorrhea-amenorrhea syndrome and a pituitary adenoma during two pregnancies, with and without continued treatment with bromocriptine throughout gestation. The study indicates that marked differences in circulating PRL levels do not influence the fetoplacental hormone levels. Furthermore, tumor expansion may possibly be prevented and successful breast-feeding can be achieved after treatment with bromocriptine throughout gestation.
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PMID:Normal and abnormal prolactin levels during human pregnancy. Lack of influence on fetoplacental endocrine function. 673 Sep 28

Of 17 patients with longstanding amenorrhea and hyperprolactinemia (3-15 years, mean 7.7 years), 8 developed their amenorrhea after the use of oral contraceptives (Group 1) and 9 became amenorrheic spontaneously (Group 2). There were no differences between the groups with respect to the basal serum levels of (FSH) follicle stimulating hormone; (LH) luteinizing hormone; (LPE) low polar estrogens (estradiol-17 beta and estrone); and prolactin. Tomography revealed pituitary adenoma in 4 patients; 1 developed symptoms of her tumor during pregnancy and they subsided following delivery. The others with tumors are checked twice/year and have not yet received treatment. The patients with no detectable tumors were treated with bromocriptine starting with 1.25x 3 daily. The peripheral serum levels of prolactin, FSH, LH, LPE, and progesterone were determined once a week and if the prolactin levels remained high, the bromocriptine dosage was increased. All patients began to menstruate once the prolactin returned to normal levels (below 25 mcg/l). Those patients who desired to become pregnant (N=6) subsequently did. 3 were delivered by cesarean section, 1 had a normal delivery, and 2 are still pregnant. There were no differences between Group 1 and 2 in the dose required or in the duration of treatment before menstruation started. 3 cases of galactorrhea were found.
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PMID:Hyperprolactinemia in cases of infertility and amenorrhea. 677 90


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