GnRH-TRH and arg-GnRH-TRH test in females with normoprolactinemic galactorrhea

In 8 patients aged from 17 to 48 years (average age 32,6 years) with normoprolactinemic galactorrhea a stimulation test with GnRH-TRH or arginine-GnRH-TRH was performed. The basal and stimulated serum levels of LH, FSH, PRL, TSH, HGH and total thyroxine (T4), the thyroxine binding capacity (TBC) and the free thyroxine index (FT4-I) were determined. -In a few cases there were disturbances of both the basal and the stimulated serum levels of the hormones. -Both the menstrual disorders which were seen in all patients with galactorrhea and the hormonal disturbances are discussed in context of an hypothetical increase of the PRL receptor sensibility in face of normal PRL serum levels or as a hint at a transient hyperprolactinemia.     

Effect of mestranol and chlormadinone acetate on TSH, T4, TBC and FT4 index in Turner syndrome

In 19 patients with Turner's syndrome aged from 12 to 24 years (average age 17.0 years) the influence of mestranol and chlormadinone acetate on both basal and TRH stimulated TSH secretion, total thyroxine (T4), thyroxine binding capacity (TBC) and free thyroxine index (FT4-I) by means of sequential stimulation test (0.5 g arginine hydrochloride/kg body weight, 25 micrograms GnRH and 200 micrograms TRH) was investigated. These investigations were performed before hormonal substitution, during third to 5th cycles of treatment and 4 month after finishing treatment. TSH and T4 serum levels were determined by RIA, TBC by radio reagent assay. The FT4 index was calculated. Mean basal TSH levels both before, during and after hormonal treatment did not differ. Netto TSH level increase were somewhat higher in 8 of the 19 patients during hormonal treatment. TBC and T4 significantly increased under treatment. The rise of FT4 in a few patients under treatment could not be ensured statistically. After finishing treatment the levels of thyroid parameters decreased.     

Basal and TRH stimulated TSH secretion and determination of total thyroxine (T4). Thyroxine-binding capacity and free thyroxine index (FT4-I) in patients with chronic uremia

In 11 patients with chronic uremia both the basal and TRH stimulated TSH levels and T4, TBC and FT4-I were determined. The investigations were repeated in 2 cases after renal transplantation. TSH and T4 in serum were determined by RIA, TBC by radio reagent assay. FT4-I was calculated. In 8 patients the basal TSH levels were in the normo- and in 3 in the hypothyreotropic range. In 9 patients the response to TRH was adequate. There were deviations from the physiological range in 7 patients for T4 and in 6 for FT4-I.     

Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test.

Systematic pituitary evaluation was performed in four patients suspected of having Sheehan's syndrome. A sequential pituitary stimulation test, consisting of insulin-induced hypoglycemia followed by stimulation of gonadotropin-(GnRH) and thyroid-releasing hormone (TRH), a metyrapone test, and adrenocorticotropic hormone (ACTH) stimulation test, was performed. All four patients failed to develop a normal increase in serum growth hormone, cortisol, and prolactin (PRL) following insulin-induced hypoglycemia. All patients demonstrated a blunted PRL, follicle-stimulating hormone, and luteinizing hormone response to the combination of GnRH and TRH. Although thyroid stimulating hormone (TSH) response was impaired in all patients, two patients had normal T3 resin uptake and thyroxine, demonstrating minimal TSH reserve maintaining normal baseline free thyroxine index. Metyrapone administration was followed by no increase in 11-deoxycortisol or 17-ketogenic steroids, thereby adding no additional information to the hypoglycemia stimulation. ACTH infusion revealed normal adrenal cortisol response. In conclusion, in patients with suspected postpartum hypopituitarism, a complete pituitary function investigation can be done in a short time by using the described pituitary sequential stimulation test.     

Studies on the binding capacity of thyroxin-binding globulin (TBC), total thyroxin (T4), free thyroxin index (FT4-I) and the ETR-test in gestosis and placental insufficiency]

Total serum thyroxine (T4), thyroxine binding capacity (TBC), free thyroxine index (FT4-I) and effective thyroxine ratio (ETR) were measured in 53 toxemias of pregnancy and in 5 cases with placental insufficiency. Total serum thyroxine, ETR and FT4-I were found in physiological ranges of the normal pregnancy, the TBC-index was decreased. Between the 19. and 34. week of pregnancy, the decrease of the TBC-index was smaller than after the 34. week of pregnancy.     

Effect of ethinyl estradiol sulfonate/norethisterone acetate on TSH, T4, TBC and the FT4 index in pubertal girls

In 13 healthy tall girls the influence of the hormonal treatment with depotestrogen ethinylestradiolsulfonate and norethisterone acetate on basal and TRH stimulated TSH secretion, total thyroxine (T4), thyroxine binding capacity (TBC) and free thyroxine index (FT4 index) was investigated. The investigations were performed before treatment, during the 8th to 11th cycles of treatment, and in the 4th month after finishing the therapy. TSH and T4 serum levels were determined by RIA, TBC by radio agent assay, the FT4 index was calculated. The mean basal TSH levels before, during and after therapy showed no significant differences. During hormonal therapy T4, TBC and FT4 were significant higher (p less than 0.05) than before and after therapy.     

Hyperprolactinemia: comparison of thyrotropic-releasing hormone and tomography

A group of 95 women with unexplained hyperprolactinemia (over 20 ng/mL) underwent radiologic examination of the sella turcica with hypocycloidal polytomography (N = 58), computed axial tomography (N = 8), or both (N = 29). All patients also underwent a thyrotropin-releasing hormone (TRH) stimulation test, with serum prolactin (PRL) measurement before and 20 and 30 minutes after a 500-micrograms intravenous bolus of TRH. Their PRL responses were compared with those of two control groups, nine normal women in the follicular phase of the menstrual cycle, and 13 women in the first five months of gestation with pregnancy-related hyperprolactinemia. Both control groups exhibited PRL increases with 95% confidence limits at least 200% above baseline levels. In all, 12 patients from the study group also had a normal PRL response (more than a 200% increase) to TRH, and none of these women had tomographic findings consistent with a pituitary tumor. The remaining 83 women all had diminished or absent PRL increases after TRH administration; 46 (55%) of these patients had radiographic evidence of an adenoma, whereas 37 (45%) had no clear signs of a tumor on either polytomography or computed axial tomography. No patient with a baseline PRL level in excess of 60 ng/mL had a normal PRL response to TRH. The results of the study indicate that 1) in patients with PRL between 20 and 60 ng/mL, a normal TRH test can be relied upon to avoid the expense and radiation of tomography (computed axial tomography or polytomography), 2) there is no benefit to be obtained in performing a TRH test in patients with a baseline PRL level over 60 ng/mL, and 3) about 45% of patients with hyperprolactinemia and an abnormal TRH test have a normal computed tomography or polytomography. These patients may have a small adenoma, and thus warrant closer follow-up than patients with a normal TRH test.     

Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women

Seventy-one hyperprolactinemic women were analyzed for medical history, gonadotropin and ovarian hormonal levels, and prolactin (PRL) responsiveness to benserazide. Sellar tomography was then performed on a yearly basis for 3 years in all women, computerized coronal and sagittal tomography in 54 of them. Under basal conditions, 30 women had roentgenographic evidence of pituitary adenoma; at the end of the follow-up period, such evidence was seen in 44. Amenorrhea, steady PRL levels, a low LH/FSH ratio, a longer duration of the disease, and low serum progesterone levels were more common in women with a final diagnosis of pituitary adenoma than in those with a persistently normal sella. The benserazide test for PRL release had yielded abnormal results since the beginning in all the 44 women with final roentgenographic evidence of pituitary adenoma, and in about half of the patients with persistently normal aspect of the sella; autoantibodies towards the pituitary gland, the thyroid gland, and gastric parietal cells were found in 3, 2, and 3 patients, respectively. No autoantibodies towards the adrenal gland or the islets of Langerhans were ever found in any cases. These data show that a fair proportion of hyperprolactinemic women have a (micro)adenoma, which becomes apparent over a relatively short period of time. Amenorrhea and steadily raised PRL levels are more common in these women. The benserazide test seems to be adequate for predicting which women will eventually develop a roentgenographically detectable adenoma. Autoimmunity does not seem to be involved in the pathogenesis of hyperprolactinemia and/or pituitary adenoma.     

Prolactin response to thyrotropin-releasing hormone (TRH) in patients with hypothalamic-pituitary disease

The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) was evaluated in 686 patients over a 4-year period. Of the 170 control subjects tested, none had a blunted PRL response to TRH. Eighty patients with prolactinomas documented by surgery were tested. Ninety-five percent (76 of 80) of these patients had an abnormally blunted PRL response to TRH. Of the 87 patients with a prolactinoma who did not undergo surgery, 98% (85 of 87) had a blunted PRL response to TRH. Many patients with other pituitary and hypothalamic diseases (pituitary tumors other than prolactinomas [Cushing's disease, acromegaly, chromophobe adenoma], craniopharyngioma) also had an abnormal PRL response to TRH (79 of 153, 52%). In the majority of patients with hyperprolactinemia due to dopamine antagonist medications, TRH stimulation did not produce a normal rise in PRL. The TRH test may be helpful in confirming the diagnosis of prolactinoma, but it is not a decisive factor in the diagnosis or management of this entity.     

Behavior of the hypothalamo-hypophyseal unit to stimulation with arginine, GnRH and TRH in patients with chronic uremia

In 11 women aged from 20 to 47 years (average age 33,1 years) with chronic uremia, treated by hemodialysis, a sequential stimulation test (SST) with 0.5 g arginine hydrochloride per kg body weight, 25 micrograms GnRH and 200 micrograms TRH was performed to examine the responsibility of the hypothalamo-pituitary unit. For evaluation of basal and stimulated secretion of PRL, LH, FSH, TSH, and HGH the corresponding serum levels were determined by RIA. 10 of the 11 women showed a galactorrhoea. No correlation between levels of PRL and creatinine could be found. Menstrual disorders in women with chronic uremia are discussed in the context of basal LH serum levels nearly always unphysiologically increased. In a few cases disturbances of basal secretion of TSH and HGH, respectively, could be observed.     

Prolactin responsiveness to TRH in amenorrheic women with and without galactorrhea.

Sixty women were given intravenous injection of 200 microgram TRH to assess its diagnostic potential as a stimulus to PRL release. Following the administration of TRH, there was a prompt increase in serum PRL to 614.6%, to 296%, to 282.1%, and 34% in normal women, amenorrheic patients, non tumoral galactorrheic cases, and patients with pituitary tumors respectively. The TRH response above baseline of PRL levels was statistically significant in all groups, but the women with pituitary tumors which showed a blunted response. The per cent of increment of PRL levels after TRH was similar in amenorrheic women regardless the presence or not of galactorrhea; this increase was significantly greater than in patients with pituitary tumors (p less than 0.01). The per cent of increment above baseline of PRL was significantly greater in menstruating women than in amenorrheic patients (p less than 0.001). In basis of present data: 1) there is a diminished PRL secretion after TRH in amenorrheic women regardless the presence of galactorrhea or hyperprolactinemia; 2) a blunted response to TRH in hyperprolactinemic women may be indicative of a pituitary tumor.     

Study on serum TSH and its response to TRH measured by a high sensitive immunoradiometric assay during and after pregnancy

With a new highly sensitive immunoradiometric assay (IRMA), serum thyrotropin (TSH) concentrations were determined in 213 healthy pregnant women. Serum free thyroxine (FT4) and human chorionic gonadotropin (HCG) levels were also measured in the same individuals. The mean serum TSH value in the 1st trimester was 0.8 microU/ml and significantly lower than those of the other three periods and non-pregnant women. Seventeen of 77 (22.1%) and 2 of 128 (1.6%) subjects in the 1st and 3rd trimester, respectively, had an undetectable serum TSH value (less than 0.1 microU/ml) with normal or slightly elevated serum FT4 levels and these pregnant women had no clinical signs or symptoms of thyrotoxicosis. Significant positive correlations were found between serum FT4 and HCG in the 1st and 3rd trimester. In 13 subjects whose serum basal TSH values had been less than 0.1 microU/ml, the thyrotropin-releasing hormone (TRH) stimulation test was performed. Two of 4 subjects in the 1st trimester and one of 8 subjects in the 2nd trimester did not respond to TRH and their serum TSH values before TRH administration were less than 0.1 microU/ml. Although the exact mechanism of blunted TSH response to TRH is not clear, the feedback suppression of serum TSH by slightly elevated serum FT4 concentrations may occur early in pregnancy. However, in the 3rd trimester serum FT4 values fell below the reference range without an elevation of serum TSH. Other factors regulating the secretion of TSH during pregnancy can be postulated.     

An endocrinological study of hyperprolactinemia and its treatment (author's transl)

Twenty-six cases of women with pituitary adenoma and seven cases of women with functional hyperprolactinemia were studied to evaluate the effects of neurosurgery and Bromocriptine treatment. In the patients with pituitary adenoma, the mean serum PRL level was significantly higher than that in the functional cases. Among the patients with pituitary adenoma, the serum PRL levels were roughly correlated to the size of the tumors. Basal serum LH, FSH and 17 beta-estradiol levels were lower in the patients with pituitary macroadenoma than in those with microadenoma. Neurosurgery was performed on fourteen patients of pituitary adenoma. Of ten cases with visual disturbance, it was necessary to use Bromocriptine to reduce the serum PRL to the normal level after operation. In the treatment of sixteen patients with microadenoma, Bromocriptine alone was used for eight of them and surgery was performed on four. As a result, there was a significant lowering of the serum PRL level and induction of regular menses in ten patients. Regular menses were induced by means of Bromocriptine treatment in all of the patients with functional hyperprolactinemia. Our data indicate that neurosurgery, either selective or combined with Bromocriptine, can normalize PRL levels and induce regular menses in patients with hyperprolactinemia.     

Prolactin hyperstimulation in response to thyrotropin-releasing hormone in patients with endometriosis

In order to clarify the role of hyperprolactinemia as a possible cause of infertility in patients with endometriosis, baseline serum prolactin (PRL) concentrations and the PRL response to thyrotropin-releasing hormone (TRH) stimulation were measured in 14 infertile women with endometriosis and in 13 normal, fertile women. Baseline PRL concentrations were 2-fold greater in the endometriosis group than in normal subjects, but the mean values did not differ significantly. Following TRH administration, a significant increase in peak PRL concentrations was observed in patients with endometriosis (211.5 +/- 34.9 ng/ml) when compared with corresponding values in control subjects (117.1 +/- 14.9 ng/ml, P less than 0.05). This hypersecretory state was selective for PRL because no significant differences between the baseline and TRH-stimulated thyroid-stimulating hormone (TSH) concentrations or total serum thyroxine concentrations were observed. In summary, some infertile women with endometriosis exhibit a greater capacity for PRL secretion than normal women. These results suggest that relative hyperprolactinemia may be responsible for the infertility associated with endometriosis, and that PRL suppression may be indicated in these patients.     

Evaluation of dynamic pituitary function testing in patients with hyperprolactinemia on diagnosis of pituitary prolactin-secreting adenoma (author's transl)

Thirty hyperprolactinemic women were divided into four group according to radiological and computed tomographic findings of sella turcica as follows; sulpiride-induced (N = 7), functional (N = 6), microadenoma (N = 9) and macroadenoma (N = 8). It was measured the serum basal level of pituitary LH, FSH, PRL, TSH and GH, and the responsiveness to LH-RH, TRH, insulin administration, respectively. These values were compared to that during bromocriptine treatment (5mg/day, 2 weeks). Before and during treatment with bromocriptine, there were not significant changes of basal level of LH, FSH and TSH, and also the responsiveness to LH-RH administration in four group. In pretreatment period, PRL responsiveness to TRH was good in sulpiride-induced and functional groups, but decreased in microadenoma and macroadenoma groups. During bromocriptine treatment period, basal PRL level was significantly suppressed in three groups except sulpiride-induced group, and PRL responsiveness to TRH was good in three groups except macroadenoma group. These findings ae concluded as follows: 1) Mechanism of the disturbance of ovulation in hyperprolactinemia does not closely related to pituitary gonadotroph dysfunction. 2) Decreased PRL responsiveness to TRH (maximal fold increase: under 40%) is of diagnostic value of pituitary adenomas. 3) Difference of PRL responsiveness to TRH during treatment with bromocriptine is distinguishing the microadenoma from macroadenoma.     

Stimulation test of the adenohypophysis with arginine, gonadotropin-releasing hormone (GRH), and thyrotropin-releasing hormone (TRH) in 45, XO patients with Turner's syndrome (author's transl)

Pituitary stimulation tests with arginine, gonadotropin-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were performed in five 45, XO patients with Turner's syndrome. Their ages ranged from 12--17 years. Serum levels of LH, FSH, PRL, HGH, and TSH were measured by RIA. The hypothalamo-pituitary system appeared normal in the patients with Turner's syndrome.     

Isolated prolactin deficiency: a case report.

A 36-year-old woman, with lifelong oligomenorrhea and immeasurable serum PRL levels, conceived and had normal deliveries after ovulation induction with CC. Alactogenesis followed both deliveries. Evaluation of other pituitary hormones were within normal limits, and attempted stimulation of PRL levels by TRH was unsuccessful. The clinical significance of isolated hypoprolactinemia is discussed.     

Arginine-GnRH-TRH test in patients with primary hypothalamic amenorrhea

In 8 patients with hypothalamic primary amenorrhea aged from 16 to 23 years (average age 19,4 years) a sequential stimulations test was performed with 0,5 g arginine hydrochloride per kg body weight, 25 micrograms gonadotropin-releasing hormone (GnRH) and 200 micrograms thyreotropin-releasing hormone (TRH). The response of the lactotropic, gonadotropic, thyreotropic and somatotropic cells of the pituitary was investigated. Serum levels of PRL, LH, FSH, TSH and HGH were determined by RIA. In all women hypoplastic ovaries were found by laparoscopy. In 7 patients tissue biopsies showed primordial follicles or primordial and secondary follicles, respectively. Investigations point to, that in hypothalamic primary amenorrhea at first the function of the gonadotropic and lactotropic cells of the pituitary is injured. The somatotropic cells could not be stimulated in 3 of 8 patients, the function of hypothalamo-pituitary-thyroid-axis in the stimulations test was normal in all women.     

Effect of mestranol and chlormadinone acetate on basal and TRH-stimulated PRL secretion in Turner's syndrome

In 19 patients aged from 12 to 24 years (average age 17.0 years) with Turner's syndrome the influence of mestranol and chlormadinone acetate on both basal and TRH stimulated PRL secretion was investigated by means of sequential stimulation test (0.5 g arginine hydrochloride/kg body weight, 25 micrograms GnRH and 200 micrograms TRH). This test was performed before, during the third until 5th cycle of treatment and 4 month after the end of therapy. PRL levels were determined by RIA. In most patients under treatment both basal and stimulated PRL showed an increase within the normal range. Hyperprolactinemic levels could be observed on one patient only.     

Subclinical hypothyroidism in infertile women: the importance of continuous monitoring and the role of the thyrotropin-releasing hormone stimulation test.

The aim of our study was to assess the prevalence of subclinical hypothyroidism (SH) after administering a thyrotropin-releasing hormone (TRH) stimulation test among women with normal serum thyroid-stimulating hormone (TSH) levels and various causes of infertility. Eighty-seven infertile women (39 with ovulation disorders and 48 with other causes of infertility) had a TRH stimulation test on day 3 - 7 of their cycle. Exaggerated TSH response (>30 mIU/l at 20, 40 or 60 min) following intravenous injection of 400 microg TRH was defined as SH. The TRH test was performed 2 - 4 months after the first visit to the clinic. We found that the prevalence of SH was significantly higher among women with ovulation disorders (20.5%) than among women with normal ovulation (8.3%). In addition, we found that although basal TSH levels were normal at recruitment, 2 - 4 months later these levels were abnormally high in 8% of the women. All these women had an abnormal TRH test. We recommend performing TRH stimulation testing in women suffering from ovulation disorders who have normal basal TSH levels, followed by repeat assessments of thyroid function to enable treatment with thyroxine in cases with abnormal results.