EFFECTS OF OESTROGENS ON PROLACTIN AND THYROTROPHIN RESPONSES TO TRH IN WOMEN DURING THE MENSTRUAL CYCLE AND UNDER ORAL CONTRACEPTIVE TREATMENT

The effects of physiological and pharmacological variations of oestrogens on prolactin and thyrotrophin (TSH) secretion have been studied during the menstrual cycle and under oral contraceptive treatment. Ten women were tested for prolactin and TSH responses to 200 μg TRH in the early follicular (days 4-6), periovulatory (days 14-15) and luteal phases (days 22-26) of the same menstrual cycle. Circulating plasma prolactin levels did not significantly vary in three phases, but TSH basal levels were lower in the luteal than in the follicular and periovulatory periods. The prolactin response to TRH was significantly enhanced in the periovulatory phase, while the TSH response was slightly decreased. Seven women on sequential contraceptives exhibited increased basal and TRH-induced prolactin secretion during the oestrogen treatment, with an unaltered TSH secretion throughout therapy. Treatment with combined contraceptives did not alter either basal or TRH-induced prolactin secretion in eight women, but basal TSH secretion and its response to TRH were both reduced. These data show that oestrogens may produce different regulatory effects on prolactin and TSH secretion, particularly in the pituitary sensitivity to TRH stimulation. Physiological variations of oestrogen secretion such as those observed during the menstrual cycle can likewise modify prolactin levels. These results could provide some support for a regulatory role for prolactin in the menstrual cycle.     

PROLACTIN, TSH, LH AND FSH RESPONSES TO A COMBINED LHRH/TRH TEST AT DIFFERENT STAGES OF THE MENSTRUAL CYCLE

A combined test with LHRH and TRH was investigated in the normal female subject during the menstrual cycle. LH and FSH responses were not affected by raised prolactin or TSH levels after TRH.
No correlation was seen between either basal levels or responses of prolactin and TSH after TRH, and no difference in responses on days 4 or 24 were observed. The increments in prolactin and TSH were significantly greater in female than in male subjects.
Although FSH responses to LHRH+TRH were not significantly different, LH responses on day 24 were greater than on day 4. A significant linear correlation between FSH and LH responses to LHRH was seen.
The results indicate that prolactin and TSH responses to TRH are greater in female than male subjects and that changes in LH and FSH after LHRH do affect these responses. Normal ranges for hormone responses after LHRH and TRH are defined.     

Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolactin; response to LH-releasing hormone and thyrotropin-releasing hormone.

Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of 1/4 ad libitum food intake (chronically strved), 7 days complete food removal and 2 weeks of 1/4 ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group of rats. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups of rats, FSH and PRL rose in acutely but not in chronically starved rats, and GH was not elevated in any group. The increases in serum LH, FSH, TSH and prolactin in response to LHRH + TRH injection in acutely or chronically starved rats were equal to or greater than in the ad libitum fed controls. These data indicate that severe reductions in food intake result in decreased release of at least 5 anterior pituitary hormones, and this is due primarily to reduced hypothalamic stimulation rather than to inability of the pituitary to secrete hormones.     

The hormonal status of patients with benign prostatic hypertrophy: FSH, LH, TSH and prolactin responses to releasing hormones.

In order to determine whether the benign prostatic hypertrophy (BPH) adenoma is responsible for low serum LH levels in patients with this disease, we measured FSH, LH and prolactin in sera collected from patients before and 0.8–2.2 years after retro-pubic prostatectomy, but found no change in their levels. Pituitary stimulation tests were therefore conducted to evaluate the pituitary hormone reserve in normal elderly men, and BPH patients before and after removal of the BPH adenoma. Blood was drawn 20 min before and during the administration of 100 μg LHRH and 200 μg TRH, as a single intravenous injection, and after 20, 60 and 120 min. Serum FSH, LH, TSH and prolactin were estimated by radioimmunoassays. Prior to prostatectomy, patients with BPH had significantly lower levels of serum LH, but not FSH, TSH or prolactin, as compared to normal men 20 min before the test. Serum LH in the BPH group after prostatectomy (1–2.75 years) was not statistically different from that of normal age-matched men, but the mean level more closely resembled that of the untreated BPH group. Although there were no significant differences in serum levels of FSH or prolactin between subject groups during stimulation, levels of LH and TSH in untreated BPH patients' serum were significantly lower than those of normal men. The BPH patients after prostatectomy resembled the normal men under these circumstances, and the serum levels of TSH in these ex-BPH patients were significantly higher than in untreated BPH patients. Similarly, the maximum LH and TSH responses to the hypothalamic releasing hormones were also significantly lower in the BPH patients as compared to normal age-matched men, and evidently return to normal 1–2.75 years after prostatectomy. No statistically significant differences were observed in the FSH and prolactin responses to LHRH and TRH between groups. The results suggest that a factor originating from the BPH adenoma, such as 5α-dihydrotestosterone, may be responsible for the suppression of pituitary LH and TSH responses to LHRH and TRH, respectively. It also appears that the pituitary of BPH patients does not regain its full secretory potential after the BPH adenoma has been removed, or that an additional factor may regulate pituitary LH secretion in the untreated and ex-BPH patients at the hypothalamic level.     

PITUITARY FUNCTION TESTS IN SHEEHAN'S SYNDROME

Fourteen patients with a typical history of Sheehan's syndrome underwent pituitary function tests with simultaneous injections of 100 μg LH-RH, 200 μg TRH and 0·05–0·1 units of soluble insulin per kg body weight. Serum prolactin levels remained unchanged in all of eleven subjects given TRH. GH levels did not rise after hypoglycaemia in five subjects. In contrast serum LH and FSH rose significantly in twelve out of fourteen subjects given LHRH and serum TSH rose significantly in five out of seven subjects given TRH. It is concluded that pituitary function is relatively preserved for LH and FSH but not for prolactin and GH in Sheehan's syndrome. It is further suggested that absence of a rise in prolactin following TRH stimulation may provide the most sensitive test of pituitary hypofunction in postpartum haemorrhage.     

THE TSH, FSH AND PROLACTIN RESPONSES TO CONTINUOUS INFUSIONS OF TRH AND THE EFFECTS OF OESTROGEN ADMINISTRATION IN NORMAL MALES

Four normal males received a constant infusion of 0.9% NaCl for 1 hr followed immediately by 500 μg of TRH infused over the same period. A rise in serum TSH was observed in all subjects while in three there was also a significant FSH response. The prolactin response, unlike that of TSH, was markedly pulsatile indicating that different mechanisms exist for the release of these two hormones from the pituitary after TRH. Circulating levels of LH were unaffected. Ethinyl oestradiol, 30 μg daily for 3 days, was administered to two of the subjects and the infusions were repeated. Both basal FSH and LH levels were depressed, as was the FSH response to the infusion of TRH. By contrast, however, the TSH response to thyrotrophin releasing hormone was enhanced after oestrogen. In one subject the basal prolactin levels were significantly higher while in both there was an augmented prolactin response to TRH, the pulsatile pattern of release being maintained.     

Enzymatic dissociation and short-term culture of isolated rat anterior pituitary cells for studies on the control of hormone secretion.

A convenient procedure has been developed for preparing a suspension of isolated rat anterior pituitary cells which retains responsiveness to secretagogues. Rat anterior pituitaries were dispersed with collagenase and hyaluronidase followed by mechanical dispersion by means of a Pasteur pipette. Immediately after dispersion, the cells showed only slight responses to secretagogues, whereas after short-term culture (20-22 h) in the presence of sera, the cells recovered their ability to respond to synthetic LH-releasing hormone (LHRH) and synthetic thyrotropin-releasing hormone (TRH). During a 3-h incubation, cells prepared from pituitaries of male rats released LH and FSH, or TSH and prolactin (PRL) in amounts directly related to the dose of synthetic LHRH or TRH, respectively. The minimum effective concentrations of hypophysiotropic hormones lay between 10(-10) and 10(-9)M, although it was observed that cells originating from female rats usually gave quicker and larger responses to LHRH. No significant net increase in the total hormonal content (cells + medium) of radioimmunoassayable LH or FSH in response to LHRH, or of TSH or PRL in response to TRH, was observed during the 3-h incubation period. The cells released significant amounts of PRL, TSH, and to a lesser extent, LH, in response to 1-5 X 10-3M N6,O2'-dibutyryl cyclic AMP, accompanied by remarkable elevation in total content (cells + medium) of PRL and TSH but not of LH. The response of the cells to theophylline or high [K+] was similar to that usually observed in previous hemipituitary experiments. These results demonstrate the viability of this in vitro cell system and its suitability for further study of the regulation of the secretion of pituitary hormones.     

Early effects of cranial irradiation on hypothalamic-pituitary function

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.     

Selectivity of melatonin pituitary inhibition for luteinizing hormone-releasing hormone

The pineal indole melatonin suppresses the neonatal rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to LH-releasing hormone (LHRH), as shown in previous studies from this laboratory. We show in this study that the melatonin inhibition is a selective effect and is not due to general inhibition of pituitary function. The effects of the indole on the responses to thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) and on basal pituitary hormone secretion were examined with cells in culture. Neonatal rat anterior pituitary cells dissociated with collagenase and hyaluronidase were cultured overnight and distributed to 35-mm dishes at the time of use. For examination of melatonin effects on the response to releasing hormones, the cells were incubated for 3 h in control medium or medium containing LHRH (10-9-10-6 M), TRH (10-10-10-6 M), or SRIF (10-9-10-6 M), either alone or in the presence of melatonin (10-8 or 10-6 M). For examination of basal hormone secretion, the cells were incubated for 1.5, 3, 6, 15, or 24 h in either medium alone or medium containing melatonin (10-6 M). Medium and cell lysate concentrations of LH, FSH, thyroid-stimulating hormone (TSh), prolactin (PRL) and growth hormone (GH) were determined by double antibody RIA. As previously, melatonin (10-8 M) significantly suppressed LH and FSH release by all concentrations of LHRH. This concentration of the indole produced maximal suppression of both LH and FSH responses to LHRH. By contrast, melatonin at a 100-fold greater concentration (10-6 M) had no effect on TRH stimulation of TSH or PRL release or on SRIF inhibition of GH release. Similarly, melatonin had no effect on basal release of TSH, PRL, or GH at the times examined. These findings show that melatonin inhibition of the gonadotroph response to LHRH is a selective effect.     

The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases

OBJECTIVE: The combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone-releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children. DESIGN: A retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function. PATIENTS: One hundred and twenty-six children, 82 boys and 44 girls, aged 2-17 years, who had undergone pituitary function testing were studied. RESULTS: The TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60-140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism. The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients > or =13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7-3.6) and 2.6 IU/l (2.2-5.2) respectively. The three hypopituitary patients in this study with chronological age > or =13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients > or =13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02). CONCLUSION: TRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic-pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.     

The effects of chronic treatment with LHRH on gonadotrophin secretion and pituitary responsiveness to LHRH in women with secondary hypogonadism

Twenty women with secondary hypogonadism and four normal women in the early follicular phase of the cycle were treated for 7 days with 10, 50 or 100 micrograms synthetic LHRH administered intramuscularly at 4 h intervals. Concentrations of pituitary and ovarian hormones in plasma were measured at intervals during the treatment period. The episodic pattern of LH secretion and the gonadotrophin responses to acute stimulation with LHRH were evaluated before and after treatment. In normal women the concentrations of gonadotrophins and the LH response to LHRH remained unchanged, whilst the FSH response to LHRH was reduced after treatment. Concentrations of oestradiol rose progressively in response to treatment, indicating follicular development. In hypogonadal subjects with unimpaired pituitary function, treatment with LHRH induced a marked but transient increase in the concentrations of LH and FSH in plasma and a progressive rise in that of oestradiol. The concentration of progesterone was increased in four of the 11 subjects. However, the amplitude of LH pulses and the responses of FSH and LH to LHRH after treatment were suppressed below pretreatment values. Women with hypogonadotrophic hypogonadism and diminished pituitary responses to LHRH exhibited a sustained increase in the concentrations of LH, FSH and oestradiol in plasma to normal follicular phase levels. The amplitude of LH pulses and the LH response to LHRH were increased after treatment but did not reach normal values. The FSH response to LHRH was further reduced after treatment. Treatment of similar subjects with 10 micrograms LHRH induced a small increase in the concentration of gonadotrophins but not of ovarian steroids. These data demonstrate that the effect of chronic treatment with LHRH on women with secondary hypogonadism depends on the level of endogenous gonadotrophins. The dose of LHRH used in hypogonadal women receiving treatment by intermittent injection may require adjusting according to the level of gonadotrophin secretion if an optimal response is to be obtained.     

Dissociation of prolactin responsiveness to TRH and chlorpromazine in women with isolated gonadotropin deficiency.

The hormonal response to luteinizing hormone releasing hormone (LHRH) thyrotropin releasing hormone (TRH) and chlorpromazine has been evaluated in eleven female subjects with the syndrome of isolated bihormonal gonadotropin deficiency (IGD). Following LHRH, all subjects had elevations of both LH and FSH, but the gonadotropin responses were attenuated relative to those observed in normal female subjects studied in the early proliferative phase of the cycle. Similarly, peak TSH levels after TRH were significantly less in subjects with IGD relative to normal controls. Basal prolactin levels were low in the patient group. Prolactin levels following TRH increased at least two-fold in control subjects and in the group with IGD. Conversely, chlorpromazine failed to induce elevations of prolactin in eight of nine females with IGD.     

Anterior pituitary function before and after treatment in twenty-three patients with isolated adrenocorticotropic hormone (ACTH) deficiency reported in Japan (author's transl)

Anterior pituitary function in 23 patients (16 men and 7 women, aged 27 to 68) with isolated ACTH deficiency was analyzed. Four were our own cases while the other 19 cases were ascertained by questionnaire. Both the baseline TSH levels and the peak TSH responses to TRH were high before treatment in more than half the cases but were normalized after treatment. This abnormality was found in patients younger than 50. The peak prolactin responses to TRH were excessive before and after treatment in three-fourths of the cases but decreased after treatment. The peak HGH responses to ITT were excessive in 3 patients before treatment an increased after treatment in 5 out of 6 cases. The peak LH and FSH responses to LH-RH were low or high in 20-30% of cases, but these abnormal responses were reduced to half after treatment. These results demonstrate that many disorders of the anterior pituitary function were found in patients with isolated ACTH deficiency but that these disorders became normal after treatment.     

Carpenter's syndrome with empty sella and abnormal LRH and TRH response

Two sisters with Carpenter's syndrome and empty sella have been evaluated for pituitary function. The TRH injection brought a normal response of TSH and prolactin. There were no change in FSH and LH, but a paradoxical increase of growth hormone and cortisol. The injection of LRH brought a normal response of FSH and LH, no change in TSH and cortisol values and a paradoxical increase in prolactin and growth hormone.     

Longitudinal study of patients with idiopathic isolated TSH deficiency: possible progression of pituitary dysfunction in lymphocytic adenohypophysitis

The relationship between isolated TSH deficiency and hypophysitis was studied. Six patients (five women and one man) with idiopathic isolated TSH deficiency were longitudinally investigated with an interval of 31 to 60 months. Clinical symptoms, laboratory results and endocrine function were investigated as well as pituitary magnetic resonance imaging (MRI) at the start and the end of the study. Clinically, initial symptoms due to hypothyroidism were ameliorated by the thyroid hormone replacement in all patients. Oligomenorrhea newly appeared during the study in three patients, although no other symptoms appeared. Serum fT3 and fT4 levels were within the reference ranges, and serum TSH level and its response to TRH stimulation remained low in all patients. Peak plasma GH level during GRH stimulation was significantly (p<0.03) decreased, at the end of the study as compared with the start. Peak plasma FSH level to LHRH stimulation was significantly (p<0.03) decreased as well as basal FSH level. In contrast, peak of prolactin during TRH stimulation was significantly (p<0.03) increased at the end of the study as compared with the start as well as basal prolactin level. Endocrine features at the end of the study were compatible with those of lymphocytic adenohypophysitis (LAH). MRI of the pituitary gland showed empty sella in one patient and slight swelling in two patients. These findings remained unchanged during the study period. One patient underwent pituitary biopsy, with histological examination showing atypical form of LAH. LAH can cause idiopathic isolated TSH deficiency and can functionally progress to combine dysfunction of the pituitary gland.     

Sex hormones in amenorrheic women with alcoholic liver disease

Urinary excretion of estrogens and plasma concentrations of estrone, estradiol, LH, FSH, PRL, progesterone, testosterone, and sex hormone binding globulin were measured in nine chronic alcoholic women with cirrhosis or alcoholic fatty liver. They were aged 24-40 yr and all had secondary amenorrhea which had lasted for at least 3 months. The response of pituitary gonadotropin secretion to administration of LHRH and estradiol benzoate and of PRL secretion to TRH were also investigated. Urinary excretion of estrogens in the alcoholic women with liver disease was similar to that in normal postmenopausal women and less than half that in normal women of the same age in the midfollicular phase of the menstrual cycle. Plasma estradiol levels in the alcoholic women were lower than in the menstruating women but higher than in the postmenopausal women, whereas their plasma estrone levels were higher than in the menstruating women. Plasma concentrations of progesterone and testosterone in the alcoholic women did not differ from those in the postmenopausal women but were lower than in the menstruating women. In spite of the relative estrogen deficiency plasma LH and FSH levels were not elevated in the alcoholic women. The responses of LH and FSH to LHRH were similar in the patients and in the menstruating women. Intramuscular administration of estradiol benzoate did not increase plasma LH and FSH concentrations in the alcoholic women. Hyperprolactinemia was not found and there were no differences in the PRL responses to TRH between the patients and the control groups. In conclusion, disturbed regulation of gonadotropin secretion is an important factor in the genesis of estrogen deficiency and amenorrhea in alcoholic women with liver disease, although ovarian function may also be directly impaired.     

PITUITARY RESPONSIVENESS TO GONADOTROPHIN-RELEASING AND THYROTROPHIN-RELEASING HORMONES IN EPILEPTIC PATIENTS RECEIVING CARBAMAZEPINE OR PHENYTOIN

Pituitary responsiveness to gonadotrophin-releasing (LHRH) and thyrotrophin-releasing (TRH) hormones was studied in 19 epileptic patients receiving long-term carbamazepine or phenytoin therapy and 14 normal control subjects. Baseline prolactin levels were normal in the patients; 2h after LHRH-TRH the prolactin levels in women on carbamazepine were significantly higher than in the controls, but apart from this, no other differences were found. Baseline LH levels were raised in male patients and the response to LHRH-TRH was exaggerated in all patients on carbamazepine. FSH levels were normal throughout. The exaggerated LH response is consistent with primary hypogonadism caused by enhanced sex hormone metabolism, secondary to hepatic enzyme induction by the antiepileptic drugs.     

Ovarian steroid modulation of gonadotropin secretion and pituitary responsiveness to luteinizing hormone-releasing hormone in the female hamster.

The significance of ovarian estradiol (E2) and progesterone secretion in the regulation of pituitary LH and FSH secretion and pituitary responses to LHRH was investigated in the hamster. Cycling females showed increased LH and FSH responses to LHRH on the morning of proestrus as compared to the responses observed on diestrus day 2. Pituitary responsiveness to LHRH declined on the evening of proestrus, after the preovulatory LH/FSH release. The secondary increase in serum FSH concentration on the morning of estrus was accompanied by a selective increase in the pituitary FHS response to exogenous LHRH. Hamsters ovariectomized (ovx) on diestrus day 2 exhibited daily afternoon LH surges but not FSH surges for at least 10 days after ovx. The magnitude of the LH surges in ovx hamsters was approximately 30-50% of that observed in proestrous females. The pituitary LH response to exogenous LHRH in ovx animals was about 25% as great as in proestrus hamsters. Serum FSH concentrations in ovx females increased by only 30% after LHRH injection, while similar treatment with LHRH resulted in 3- to 4-fold increments in serum FSH in proestrous hamsters. Implantation of E2 capsules in ovx hamsters resulted in increased gonadotropin responses to exogenous LHRH. Serum LH concentrations in the E2-implanted, LHRH-injected animals were as great as those observed after LHRH injection in proestrous females. Administration of LHRH, LH, or progesterone on the morning of proestrus failed to detectably alter the timing or magnitude of the proestrus afternoon FSH surge. The present results suggest that the increasing serum titers of estrogen on diestrus and early proestrus result in increased pituitary sensitivity to LHRH, and this increased sensitivity probably contributes to the magnitude of the preovulatory LH surge. The increases in LH and progesterone which occur during the afternoon do not seem to be responsible for triggering the proestrous FSH surge.     

Pituitary-thyroid function in spironolactone treated hypertensive women.

Four weeks high dose spironolactone treatment (Aldactone Searle, 100 mg q. i. d.) significantly enhanced the TSH (delta max. 8.5 +/- 4.1 vs. 4.6 +/- 3.1 microunits/ml, P less than 0.05) and T3 (delta max. 32 +/- 27 vs. 11 +/- 16 ng/100 ml, P less than 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P greater than 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.     

Impaired LH release following exogenous estrogen administration in patients with amenorrhea-galactorrhea syndrome.

Serum gonadotropin levels were determined in 10 patients with the amenorrhea-galactorrhea syndrome before and following acute iv administration of synthetic LH-releasing hormone (LHRH) or conjugated estrogens, in order to clarify the hypothalamic derangements in the gonadotropin secretion in patients with hyperprolactinemia. The basal prolactin (PRL) levels were elevated in all the patients, and blunted responses to 500 mug of iv synthetic thyrotropin-releasing hormone (TRH) injection were found in 9 out of the 10 patients. The basal levels of LH and FSH were subnormal in 2 and 3 patients, respectively, while those in the remaining patients were normal or slightly elevated. Normal or excessive responses of gonadotropins to 100 mug of iv LHRH were observed in most patients, 9 for LH and 10 for FSH out of 10 patients. In 10 normal cyclic women at the mid-follicular phase (D7-9) and 10 hypothalamic amenorrhea patients without galactorrhea, LH release was found 48 to 72 h after the iv injection of 20 mg conjugated estrogens (Premarin). This LH release following Premarin injection was completely abolished in the patients with amenorrhea-galactorrhea. These data seem to indicate that in patients with hyperprolactinemia, tonic secretion of gonadotropin is maintained fairly well, while of the positive feedback effect of Premarin on the release of LH is impaired. It is suggested that impaired LH release may be partly responsible for anovulation and amenorrhea in patients with hyperprolactinemia.