Amniotic fluid thyrotropin (TSH) following maternal administration of thyrotropin releasing hormone

Cord blood and amniotic fluid thyrotropin (TSH), T4, T3, and rT3 concentrations were measured in 49 women who received 400 micrograms thyrotropin releasing hormone (TRH) iv during labor and in 16 control women who received saline. Cord blood serum TSH concentrations were elevated for as long as 4 hours after TRH administration and peak values (38.0 +/- 4.2 microU/ml) were observed from 61-120 minutes after TSH as compared to control values of 5.0 +/- 0.3 microU/ml. The elevations in fetal TSH concentration stimulated the fetal thyroid, resulting in a progressive increase in cord blood T4 and T3 but not rT3 concentrations. These TRH induced elevations in fetal cord blood TSH concentrations were not accompanied by increases in unconcentrated and 4 fold concentrated amniotic fluid TSH concentrations which were almost always below 0.6 microU/ml, the limit of assay sensitivity. Unconcentrated amniotic fluid T4 concentrations were barely detectable and no variation was observed between the TRH treated and saline treated mothers; amniotic fluid T3 was not detectable in any of the groups; and amniotic fluid rT3 concentrations ranged between 46.4 and 55.6 ng/dl and did not differ between groups. These findings suggest that term amniotic fluid TSH values do not reflect transient but marked elevations in fetal serum TSH concentrations and that amniotic fluid TSH determination is probably not useful in the detection of primary fetal hypothyroidism. It is possible, but unlikely, that long-term and even greater elevations in fetal serum TSH concentrations would result in increased amniotic fluid TSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma medroxyprogesterone acetate levels following intramuscular or oral administration in patients with endometrial adenocarcinoma.

The concentration of medroxyprogesterone acetate (MPA) in plasma samples taken 24 h after intramuscular or oral administration of 100 mg daily doses of the drug to patients with endometrial adenocarcinoma was measured by radioimmunoassay. In general, a plasma level of about 4 ng/ml was found 24 h after the dose, independent of the route of drug administration. However, in three of the patients to whom intramuscular MPA was given, considerably higher values were found. A maximal plasma level was achieved three hours after ingestion of 100 mg MPA. This was followed by a rapid decline to 20-25% of the peak value after about 12 h. A rather small day-to-day intraindividual variation was found in daily blood samples taken just before administration of the next dose. However, considerable differences were found between individuals and it is concluded that this variation in plasma levels may be reflected in the clinical efficacy of the treatment. Thus further studies in which plasma values and clinical effectiveness are correlated seem to be indicated.     

Prolactin and thyrotropin responses to thyrotropin-releasing hormone during the peripartal period

To investigate the changes in pituitary responsiveness to hypothalamic releasing hormones during the periparturitional period, women undergoing labor and vaginal delivery were stimulated with thyrotropin-releasing hormone. The percentage of incremental changes in prolactin and thyroid-stimulating hormone were significantly lower in pregnant women at term than in nonpregnant control subjects. Evidence of augmented release of prolactin was disclosed after the onset of active labor. The percent increases in prolactin and thyroid-stimulating hormone were significantly higher at 24 hours post partum than at term. Administration of thyrotropin-releasing hormone to the gravid patient in active labor caused a brisk response in fetal thyroid-stimulating hormone, although the increase in fetal prolactin remained low. These findings suggest that the changes in serum triiodothyronine (T3) significantly influence the release of prolactin and thyroid-stimulating hormone in response to thyrotropin-releasing hormone during the periparturitional period.     

Prolactin and thyrotropin after stimulation by thyrotropin releasing hormone a study under long-term administration of oral contraceptives (author's transl)]

The longtime application of oral contraceptives is assumed to elevate serum prolactin levels under non-stimulated conditions. We therefore examined whether oral contraceptives also will augment prolactin secretion after stimulation, e.g. by thyrotropin releasing hormone (TRH). After TRH stimulation the time sequence of secretion both of prolactin (HPRL) and thyroid stimulating hormone (TSH) was determined. Three groups of women were tested in a non-randomized study: group 1 without any hormonal medication (= controls), group 2 taking an oral contraceptives containing cyproterone acetate, group 3 using an oral contraceptive containing d-norgestrel. HPRL secretion was similar in all three groups, the same held true for TSH. A possible correlation between the secretion of HPRL and TSH was examined in the control group. No such correlation was found. The secretion patterns of both hormones also were different. In addition, the basic levels of both HPRL and TSH did not seem to influence the response after stimulation.     

Prolactin response to thyrotropin-releasing hormone in women with infertility and/or randomly elevated serum prolactin levels

Infertile women with normal serum prolactin (PRL) levels have been known to establish a pregnancy after the use of bromocriptine, a dopamine agonist. These data imply that there may be a group of women with a slight but significant increase in PRL secretion that may have resulted in their infertility. This study evaluates the thyrotropin-releasing hormone (TRH)-induced PRL and thyroid-stimulating hormone (TSH) response in normal women (NL, n = 6), women with anovulation and/or inphase endometrial biopsies (AN/IN, n = 12), and women with histologic evidence of luteal phase deficiency (LPD, n = 12). Most of these women were found to have elevated serum PRL values on random testing. There was a statistically significant increase in PRL response at all time intervals after TRH between the NL and AN/IN groups compared with the group with LPD on the basis of repeated measures analysis (P = 0.0013). There was no statistical difference in the TSH response between these three groups. Although the PRL response was statistically different, individual PRL response patterns were not diagnostic. It appears from these data that there is an increased PRL secretion in infertile women who have histological evidence of a LPD.     

Depressed follicle-stimulating hormone, luteinizing hormone, and prolactin responses to the luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and metoclopramide test in endurance runners in the hard-training season

The responses of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to luteinizing hormone-releasing hormone (LH-RH) and the responses of prolactin (PRL) to thyrotropin-releasing hormone (TRH) and metoclopramide (MC) were measured in the late luteal phase of the cycle in 12 endurance runners and 11 control women and in 12 joggers and 7 control women. LH-RH (100 micrograms) and TRH (200 micrograms) were injected intravenously at the beginning of the test, and MC (10 mg) was injected 60 minutes later. Blood samples were obtained before and 20, 60, 80, and 120 minutes after the beginning of the test. Runners had significantly lower serum concentrations of estradiol and progesterone than control subjects, whereas the concentrations of FSH, LH, and PRL were similar at the beginning of the study. Compared with their controls, the runners had significantly lower FSH (P less than 0.05) and LH responses at 20 minutes (P less than 0.05) and lower LH responses at 80 minutes (P less than 0.01) to LH-RH and lower PRL responses to MC 20 minutes after MC injection (P less than 0.05). Joggers and their control subjects had similar LH, FSH, and PRL responses to these pharmacologic stimuli. It is concluded that decreased ovarian activity explains, at least partly, the lowered responses of FSH and LH to LH-RH and the lowered response of PRL to MC in endurance runners.     

Plasma hormone concentrations in induced abortion with local prostaglandin administration in the 1st trimester

Abortion was performed by curettage on 71 women with pregnancies between the 7th and the 13th week of gestation seven to eight hours after intracervical application of a tylose gel containing 3mg prostaglandin F2 alpha. Prior to the application of the prostaglandin and immediately before the surgical intervention a sonographic examination for determining the vitality of the pregnancy was carried out.--Plasma progesteron, estradiol and HPL levels were determined radioimmunologically prior to the application of prostaglandin, at four-hour intervals on the day of intervention, and 24, 48 and 72 hours after the intervention. In 22 women a complete or an incomplete abortion occurred; in two cases a blighted ovum was observed; 47 pregnancies, according to sonographic examination, remained intact until curettage. After seven to eight hours duration of the effect of the prostaglandin gel, progesterone levels were found to be reduced to 60.5 per cent and 17-beta-estradiol to 31.4 per cent of the initial values, whereas the HPL values fell below the specificity of the testing procedure (12.5 ng/ml). Comparative investigations of the pregnancies which, according to sonographic findings, remained intact until curettage and those which were aborted after the application of prostaglandin did not, in spite of low plasma progesterone and estradiol levels in the abortive group, reveal any statistically significant differences. The abortive effect--even with local application--of the prostaglandins was confirmed. Conclusions regarding the effective mechanism of the prostaglandins upon the fetoplacental unit and the function of the corpus luteum remain subject to speculation.     

Seral,uterine and fetal salicylate concentrations after oral administration

Salicylate concentrations in serum, endometrium, myometrium and fetus were determined 3 h after an oral dose of 1 000 mg of acetylsalicylic acid. The material consisted of 19 females (11 for legal abortion and 8 for operative treatment of fibroids). Tissue salicylate concentrations were at a level at which prostaglandin synthetase is inhibited.     

Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans.

It is well known that peripheral prolactin levels are significantly higher in menarcheal women than in men. Higher levels of prolactin in menarcheal women are related to exposure to higher levels of estrogen in women than in men. Increased exposure to androgens in men has also been proposed as a possible reason to account for lower prolactin levels in men; however, this suggestion has not been conclusively proven. The current study sought to evaluate the cross-gender effects of male and female hormones on basal levels and the pituitary store of prolactin in humans. Four groups of individuals were involved: normal men and women, male and female transsexuals primed with female hormones and testosterone, respectively for at least 6 months. A metoclopramide challenge test was carried out on each subject of each group. Subjects were rested for 1 h, with an indwelling catheter in the antecubital vein, before a blood sample was collected for estimation of basal hormone levels. Following an oral ingestion of 10 mg of metoclopramide, blood samples were collected at 15, 30, 60, 90, 120, 150 and 180 min. Prolactin, estradiol and testosterone concentrations were measured by radioimmunoassay. Basal levels as well as metoclopramide-induced releases of prolactin (as measured by area under the curve) in normal women were significantly higher (p less than 0.05) than corresponding levels in normal men. Following long-term priming with female hormones, the pattern of response to metoclopramide in male transsexuals was dramatically changed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinology of pregnancy. I. Denominations of concentrations of triiodothyronine, thyroxine, effective thyroxine, thyreotrophin and growth hormone in normal pregnancy, labour and in cord blood

Concentrations and activities of the following agents were estimated: triiodothyronine (T3), thyroxine (T4), effective thyroxine (ETR), thyreotrophin (TSH), and growth hormone (HGH). Blood samples were collected in pregnancy, labour and from the umbilical cord of the newborns. It was demonstrated that in normal pregnancy the concentrations of T3, ETR, and TSH did not differ significantly from the values considered as normal in non-pregnant women. The concentration of T4 was distinctly higher in the course of pregnancy (139 to 157 nmol/l versus 110 nmol/l in non-pregnant subjects). The HGH concentration increased during pregnancy from 5.6 to 14.3 micrograms/l. The cord blood demonstrated comparable values of ETR and HGH and in half of the cases of TSH also with those observed in the mothers. In the other one half of the cases, TSH activity was fourtimes higher than the material value. The T3 and T4 were lower than values in the mothers. The results presented are the normal values for further planned investigations of endocrinology of pregnancy, especially for studies into course of pregnancy in women who work in noxious conditions.     

Plasma ACTH levels and beta-endorphin-like immunoreactivity following administration of luteinizing hormone-releasing hormone in Nelson's syndrome

The effect of LH-RH (25 micrograms as a single i.v. bolus) on plasma corticotropin (ACTH) levels and beta-endorphin-like immunoreactivity was studied at 30 and 60 min in eight women with Nelson's syndrome. Plasma ACTH concentrations increased in three of them, while beta-endorphin-like immunoreactivity, measured in six cases, rose significantly at 30 min in all the patients under investigation. In the control group containing seven women with Nelson's syndrome, placebo (0.9% sodium chloride) administration did not induce any significant changes in ACTH concentrations or in beta-endorphin-like immunoreactivity. Our results suggest that a paradoxical stimulatory influence of LH-RH on pituitary Nelson's adenomas may play an important role in the adenoma hormonal activity and, perhaps, growth. Such an effect could be responsible for a rapid development of some pituitary neoplasms during pregnancy.     

Amenorrhea following the administration of oral contraceptives

It is estimated that about 2.2% of women experience amenorrhea and anovulatory cycles after discontinuing use of oral contraceptives (OCs), although exact figures are lacking due to differences of definition and problems of diagnosis. Several possible mechanisms to explain the occurrence of postpill amenorrhea have been suggested, including endometrial atrophy and fibrosis, changes in the ovaries similar to those found in Stein-Levanthal syndrome, hypothalamic disorder, late menarche, irregular cycles, and periods of amenorrhea before or during OC use. Previous pregnancies, duration of pill use, and formulation utilized are apparently not related to occurrence of post-pill amenorrhea. Clinical diagnosis requires detection of ovulation by means of basal body temperature, cervical mucus changes, and vaginal smears. If amenorrhea persists after administration of a progestagen to induce bleeding, more complete examinations must be done to exclude pituitary tumor, Cushing's syndrome, thyroid problems, and possible precocious menopause or anorexia nervosa. X-rays, administration of thyroid or suprarenal hormones, gonadotropins, or estrogens, an endometrial biopsy, or laparoscopy may be necessary. Generally all test values are normal except that levels of estrogens, follicle stimulating hormone, and luteinizing hormone are usually reduced. Treatment of post-pill amenorrhea can take various forms. About 5% of cases appear to resolve spontaneouusly; efforts should therefore be made to detect ovulation through basal body temperature, cervical mucus and vaginal smears. Corticosteroids including prednisone and dexametasone may administrered, or if estrogen levels are low and the patient fails to respond to progestagens with withdrawal bleeding, clomiphene may be used. Human menopausal gonadotropin or human chorionic gonadotropin can be in patients with low estrogen levels who do not respond to clomiphene. Ergocriptine derivatives may be used in cases with associated galactorrhea due to basal hyperprolactinemia. Palliative treatment with OCs may be used in patients who wish to avoid pregnancy. The prognosis is always poor in the presence of galactorrhea or if progestagen administration is not followed by withdrawal bleeding or estrogen levels are low. Treatment is usually futile in cases of polycystic ovaries that have sclerosed. The most significant feature of such amenorrhea is its role in infertility. If the patient wishes to become pregnant after some period of OC use, it is advisable to interrupt treatment periodically until 1-2 normal menstrual cycles have reappeared, especially in young patients who had irregular cycles before initiating hormonal contraception.     

Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea.

The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen.     

Prolactin molecular heterogeneity. Response to thyrotropin-releasing hormone stimulation of concanavalin A-bound and -unbound immunoassayable prolactin during human pregnancy

Since the milieu of pregnancy stimulates physiologic hyperprolactinemia, we questioned whether prolactin secreted during normal pregnancy contains a large-molecular weight component that binds to concanavalin A and whether this large-molecular weight prolactin contributes to the thyrotropin-releasing hormone (TRH)-releasable pool. Serum was collected from pregnant patients (n = 28) undergoing TRH stimulation tests. This serum was passed through a concanavalin A column and eluted with 0.2M alpha-methylmannoside. Concanavalin A-bound prolactin, as determined by radioimmunoassay, ranged from 10% to 30% of the total immunoassayable prolactin. An increase in the basal serum concentration of both concanavalin A-bound and -unbound prolactin occurred as pregnancy progressed. However, throughout gestation, only the concanavalin A-unbound prolactin increased after TRH stimulation. The concanavalin A-bound prolactin was found to have a molecular weight of 60,000 by means of Sephadex G-100 permeation chromatography.     

Serum prolactin and thyroid stimulating hormone levels following thyreotropin releasing hormone stimulation in preeclamptic patients.

Serum prolactin and thyroid stimulating hormone (TSH) levels were measured following administration of thyreotropin releasing hormone (THR) in 17 preeclamptic patients and 18 normal pregnant controls. From the 31st to the 35th pregnancy week the preeclamptic patients showed increased basal serum prolactin and TSH levels compared to controls, but later in pregnancy the differences disappeared. Following TRH stimulation, the serum prolactin and TSH responses were similar in women with and without preeclampsia. A possible role of prolactin in the development of preeclampsia is discussed.     

Effects of estrogen replacement therapy on pituitary size, prolactin and thyroid-stimulating hormone concentrations in menopausal women.

There are few studies in the literature investigating pituitary size at an age consistent with the menopause and the influence of estrogen replacement therapy on pituitary height. We therefore evaluated the effect of estrogen on pituitary size, prolactin and thyroid-stimulating hormone (TSH) levels in menopausal women. Sixty-nine women were evaluated, 47 using estrogen and 22 controls. The measure of pituitary height was obtained from magnetic resonance imaging. Hormone evaluation did not show a statistically significant difference in mean (+/-standard deviation) prolactin level between the group using estrogen (7.6 +/- 6.4 ng/ml) and controls (5.1 +/- 3.4 ng/ml; p = 0.15), yet mean TSH level was significantly higher in the treated group (1.9 +/- 1.5 vs. 1.2 +/- 0.9 microU/ml; p = 0.03). Mean pituitary height in the estrogen-treated group (5.2 +/- 1.4 mm) was greater than in the controls (4.4 +/- 1.4 mm; p = 0.04). However, when such potential confounders as age, prolactin and TSH levels, treatment and duration of estrogen exposure were considered, the magnitude of difference did not attain significance. In conclusion, estrogen may play a role in pituitary size, since a mean difference in pituitary height, estimated as 0.78 mm, was detected between the groups in favor of the estrogen-treated group. This suggestion can be investigated in further studies.