Normal Serum Prolactin Research Articles

Validity of hypothalamic-pituitary testing in hyperprolactinemia: Prolactin responses to insulin hypoglycemia and arginine

The release of prolactin (PRL) following insulin tolerance testing (ITT) and arginine infusion was studied in four groups of women: normal volunteers, amenorrheic women with normal PRL levels, and hyperprolactinemic women with without roentgenographic evidence of pituitary adenoma. Women with normal serum PRL concentrations were found to have an increase in peripheral PRL after both testing modalities. Hyperprolactinemic women, whether or not there was evidence of a pituitary adenoma, did not appear to have a PRL response to either of these tests. Based on the percent change of PRL over basal values, there was a significant difference between the euprolactinemic and hyperprolactinemic groups (p < 0.01 for insulin and p < 0.05 for arginine). Our data indicate that in women with hyperprolactinemia neither ITT nor arginine-induced PRL release can be utilized to discriminate between the presence and absence of an adenoma. This poor PRL response to ITT and arginine in the hyperprolactinemic patients could be the result of hypothalamic dysfunction. (Am. J. Obstet. Gynecol. 141:556, 1981

Diurnal variation of prolactin secretion differentiates pituitary tumors from the primary empty sella syndrome

In an attempt to find an endocrine function test that might be useful in differentiating the primary empty sella syndrome from a pituitary tumor, we evaluated 24-hour prolactin levels in seven patients with the primary empty sella syndrome, 16 patients with pituitary tumors and 37 normal subjects. All eight patients with the primary empty sella syndrome had normal 24-hour mean prolactin levels and normal diurnal variation of prolactin release whereas in each patient with a pituitary tumor nocturnal prolactin secretion was blunted. In light of these findings and those of other investigators, we do not perform routine invasive study of the pituitary in patients with (1) a typical clinical presentation of the empty sella syndrome, (2) no endocrinopathies, (3) a normal computerized axial tomography scan, when indicated, and (4) normal serum prolactin levels with intact diurnal variation.

The use of thyrotropin-releasing hormone in distinguishing prolactin-secreting pituitary adenoma

In order to differentiate between a prolactin-secreting adenoma and a nonneoplastic etiology for galactorrhea, a single stimulatory dose of 500 μg of thyrotropin-releasing hormone (TRH) was employed to assess the prolactin (PRL) response of 50 women. The results were compared to those obtained in 19 control subjects (10 with subsequent surgical removal of a PRL-secreting adenoma and nine women stimulated in the early follicular phase). All patients were grouped according to normal or elevated serum PRL, and normal, equivocal, or abnormal findings by tomography of the sella turcica. Patients with a normal baseline PRL had a normal PRL response to TRH of at least 200% above baseline. This normal response was independent of findings by tomography of the sella turcica. A highly significant difference in response (p < 0.001) was illustrated by all patients with elevated PRL and abnormal tomograms, and in some patients with elevated PRL and normal or equivocal tomograms. These responses were identical to those of the control patients who had histologic evidence of a PRL-secreting adenoma. The findings indicate that a PRL-secreting adenoma in patients with galactorrhea can be identified on the basis of the PRL response to TRH stimulation.

Prolactin-secreting pituitary adenomas in women. IV. Pituitary function in amenorrhea associated with normal or abnormal serum prolactin and sellar polytomography.

An analysis of anterior pituitary function with respect to abnormal or normal serum prolactin (hPRL) concentrations (normal, <20 ng/ml) and sellar polytomography was performed in 84 amenorrheic women to determine whether those with hyperprolactinemia and abnormal sellar polytomograms could be distinguished from amenorrheic patients without elevated hPRL levels or abnormal tomograms. Patients were categorized as follows: group A, normal hPRL levels (mean α SEM, 9 α 1 ng/ml) and normal sella; group B, normal hPRL levels (11 α 1 ng/ml) and abnormal sella; group C, hyperprolactinemia (52 α 9 ng/ml) and normal sella; and group D, hyperprolactinemia (251 α 83 ng/ml) and abnormal sella. Group D was comprised entirely of patients with histologically confirmed pituitary adenomas. Anterior pituitary function tests included the hPRL responses to TRH (200 exg, iv) and L-dopa (250 mg, orally), LH and FSH responses to gonadotropin-releasing hormone (GnRH; 100 eg, iv) and GH and cortisol responses to insulin-induced hyp...

Hypoglycemia in Pregnancy

Severe symptomatic hypoglycemia (serum glucose level, 24 mg/dL) developed in a 23-year-old, 147.3-cm-tall woman during her late second and third trimesters of pregnancy. Endocrine studies disclosed insulin levels less than 2 microU/mL; growth hormone level less than 3 ng/mL; and cortisol level less than 1 microgram/dL. Hydrocortisone therapy corrected her hypoglycemia, and she was delivered of a healthy female infant. Postpartum, her evaluation included normal thyroid function studies, a normal thyroid-stimulating hormone response to protirelin (thyrotropin-releasing hormone), normal serum and urine gonadotropin levels, normal serum prolactin, normal sella turcica tomograms, and a normal EMI brain scan. Urine 17-hydroxycorticosteroids increased during a four-day cosyntropin infusion, but failed to rise after metyrapone administration. The growth hormone level failed to rise after stimulation with levodopa and propranolol administration. The patient was believed to have idiopathic partial hypopituitarism, with hypoglycemia being due to adrenocorticotropic hormone (ACTH) and growth hormone deficiency and the drain of maternal glucose by the fetus. It is suggested that pregnant women with symptomatic hypoglycemia be treated with glucocorticoids while awaiting the results of their endocrine evaluation.

Blunted prolactin response to hypoglycemia in patients with hypothalamic-pituitary disease and in subjects receiving estrogen

The prolactin response to hypoglycemia was evaluated in 22 control subjects and 8 patients with hypothalamic-pituitary disease but normal basal serum prolactin levels. Eighteen of the 22 control subjects demonstrated at least a twofold prolactin rise in response to hypoglycemia. In contrast to the control subjects, none of the 8 patients demon-strated a prolactin response to hypoglycemia. This blunted prolactin response to hypoglycemia was the only endocrine abnormality in 3 of these 8 patients. In an attempt to better determine the sensitivity of the prolactin response to hypoglycemia as an index of early pituitary disease, the effect of a short course of estrogen on the prolactin response to hypoglycemia was examined. Estrogen was selected because of its known acute stimulatory effect on pituitary mitosis and chronic effects that lead to pituitary tumor formation in rodents. Accordingly, diethylstilbestrol (DES) 5 mg t.i.d. was administered orally to 6 normal men for 3 days, a period known to stimulate pituitary mitotic activity in rodents. Diethylstilbestrol treatment caused significant elevation of the baseline prolactin (8 ± 2 versus 18 ± 3 ng/ml, p < 0.05); however, the prolactin response to hypoglycemia was blunted (8 ± 2–30 ± 10 ng/ml, p < 0.05, before DES; 18 ± 3–20 ± 5 ng/ml after DES, p > 0.05). This estrogen-induced blunted prolactin response to hypoglycemia resembled the blunted prolactin response to hypoglycemia found in patients with hypothalamic-pituitary disease.

Estrogenic Response in Women with Amenorrhea during Treatment with Human Menopausal Gonadotropin with and without the Simultaneous Administration of Bromocriptine

In an attempt to determine whether prolactin influences estrogen biosynthesis in the ovary, the estrogenic responses of women with amenorrhea under treatment with human menopausal gonadotropin (hMG), with and without the simultaneous administration of the prolactin inhibitor bromocriptine, were investigated in a total of 20 treatment cycles. In five of the six women studied, the addition of bromocriptine produced a urinary excretion of estrogenic compounds 79% higher than that produced by treatment with hMG alone. In one woman with a slightly increased serum prolactin level, the addition of bromocriptine necessitated halving the total hMG dosage. One woman with low endogenous levels of follicle-stimulating hormone (FSH) and a limited response to gonadotropin-releasing hormone showed no increased estrogen excretion after bromocriptine administration over that produced by hMG alone. These results suggest that (1) both elevated and normal serum prolactin levels can have a direct inhibitory effect on the ovary and (2) FSH may be necessary for the formation of prolactin receptors in the ovary.

Hyperprolactinemia: a possible cause of sexual impotence in male patients undergoing chronic hemodialysis.

Hyperprolactinemia is known to cause impotence in patients with normal renal function and elevated serum prolactin levels (SPLs) have also been reported in uremia. This study was undertaken to examine a possible role of elevated SPLs in the impotence of male patients undergoing chronic hemodialysis (CHD). SPLs in 16 male patients undergoing CHD were evaluated using a homologous double-antibody radioimmunoassay with prolactin isohormones isolated from human amniotic fluid. Patients were divided in 2 groups: 6 patients were sexually impotent and 10 sexually potent. Patients with emotional disturbances or marital conflicts known to cause impotence were excluded from the study. The SPLs of the impotent patients were found to be significantly elevated in comparison to the levels of the potent patients (136.7 +/- 28.2 vs. 37.3 +/- 2.7 ng/ml, p less than 0.001). Furthermore, in 2 patients who were successfully treated with bromocriptine to suppress hyperprolactinemia, recovery of sexual potency was noted. Thus, sexual impotence in male CHD patients seems to be associated with marked hyperprolactinemia. It is suggested that elevated SPLs may be an important cause of impotence among CHD patients.

Possible role of prolactin and pineal prolactin-regulating substances in pineal-mediated gonadal atrophy in hamsters.

Homoplastic anterior pituitaries were transplanted beneath the renal capsule of adult male, Syrian golden hamsters and the effects studied on the gonadal and accessory organ atrophy following bilateral optic enucleation or placement in reduced (L/D = 10/14 h) photoperiods. In all cases, control hamsters, bearing kidney fragments transplanted beneath their renal capsules, showed gonadal atrophy and reduced blood levels of prolactin and LH at 8--10 weeks following light deprivation. On the other hand, hamsters, bearing three or four homoplastic pituitary grafts, showed complete maintenance of gonadal and accessory weights as well as normal or supranormal serum prolactin levels. Prolactin, but not LH, levels were maintained in hypophysectomized male hamsters bearing pituitary homografts. These results point out the significant role played by prolactin, and possibly that of pineal prolactin-regulating factors, in pineal-mediated gonadal atrophy.

Comparison of serum prolactin, plain radiography, and hypocycloidal tomography of the sella turcica in patients with galactorrhea

Hypocycloidal tomography of the sella turcica is being used with increasing frequency in patients with galactorrhea in order to establish the diagnosis of pituitary adenoma. In 201 patients with galactorrhea, serum prolactin (PRL) levels were correlated with anteroposterior (AP)-lateral plain radiographs and hypocycloidal tomography of the sella turcica. Plain films were normal in 167 and abnormal in 34 patients. Of the 167 patients with normal AP-lateral plain films, 80 had normal tomograms and normal serum prolactin levels while 80 patients had normal tomograms and elevated serum PRL levels (21 to 256 ng/ml). The remaining seven of the 167 patients had normal plain films with abnormal tomograms and elevated serum PRL levels (28 to 176 ng/ml). All patients with abnormal plain radiographs had abnormal tomograms and had either elevated or normal serum PRL levels. In view of these findings, sella tomography is only necessary in patients with normal plain radiographs and elevated serum PRL levels.

Prolactin-Secreting Tumors in Men: Surgical Cure

Two men presented with decreasing libido and impotence. Endocrine evaluation showed that they both had low levels of serum testosterone and a prolactin-secreting adenoma. Transsphenoidal removal of their tumors resulted in normalization of serum prolactin and testosterone concentrations and normalization of sexual function. These patients represent the first two nonacromegalic men with prolactin-secreting tumors and hypogonadism in whom surgical resection of their tumors resulted in a complete clinical and biochemical remission. We discuss the effects of elevated prolactin on male sexual function.

Pituitary function following surgery for prolactinomas.

Preoperative and postoperative endocrine function studies were performed in 18 patients with prolactin-secreting tumors defined by hyperprolactinemia and abnormal sellar tomography. Preoperative testing showed decreased prolactin response to thyrotropin-releasing hormone (TRH); 9 of 18 patients had low basal serum LH and 11 of 15 patients had low urinary LH. In most patients follicle-stimulating hormone (FSH) was normal (serum, 13/18 and urine, 13/13). Five of 9 patients tested with luteinizing hormone-re-leasing hormone (LH-RH) had an exaggerated LH response and the rest were normal. The changes in gonadotropin secretion did not correlate with tumor size. In contrast, only patients with suprasellar extension showed deficiencies of thyroid hormone, or insulin-stimulated growth hormone (GH) or cortisol. Following surgery, 10 of 18 patients had normal serum prolactin. However, the prolactin response to TRH remained abnormal in 10 of 11 patients tested. Serum LH increased to normal in all patients whose prolactin values reverted to normal postoperatively. The GH values following provocative testing were higher postoperatively in the group as a whole and normalized in the patients with low GH values preoperatively. Clinical response did not correlate with tumor size; 3 of 5 patients with microadenomas recovered normal menses, while 5 of 8 patients with larger tumors resumed menses. Several of our findings may bear on the pathophysiology associated with these tumors. First, the TRH test results suggest that disordered prolactin secretion may persist after tumor removal. Second, the hypogonadotropic state in these individuals seems to represent a hypothalamic rather than a pituitary defect, ie, the defect is observed in patients with small tumors, and pituitary responsiveness to LH-RH is normal or exaggerated. The resolution of clinical hypogonadism and disordered LH secretion after surgery is consistent with a direct effect of prolactin on the hypothalamic control of LH secretion.

Bromocriptine in the treatment of the premenstrual syndrome.

Therapeutic trials with bromocriptine in the premenstrual syndrome are based on the hypothesis that this condition is characterised by an increased luteal phase prolactin secretion, believed to be of importance in the aetiology and pathogenesis of the syndrome. Reviewing the literature does not substantiate this original hypothesis. Women with the premenstrual syndrome seem to have normal serum prolactin levels as well as normal thyrotrophin releasing hormone induced increments. This does not necessarily mean that bromocriptine is ineffective in the treatment of the syndrome, but knowledge of the pathophysiology of the premenstrual syndrome does not explain any therapeutic effect of the drug. This review covers 6 controlled trials of bromocriptine in 119 women with the syndrome. Although the studies do not give a uniform picture, the following view emerges: medication should be cyclical, begin around mid-cycle and continue until the onset of the menstrual flow. Despite rather frequent side effects, the dosage should not be less than 2.5mg twice daily, since there is no evidence of any therapeutic effect of smaller dosages. The efficacy of such therapy is not uniformly accepted, although a beneficial effect on premenstrual mastodynia is convincingly supported.

Oestrogen-gonadotrophin feedback abnormalities in hyperprolactinaemic amenorrhoea demonstrated by the response to clomiphene administration.

Clomiphene was administered to 16 patients with elevated serum prolactin levels in doses of 100, 200 and 300 mg/day for five days in succeeding months and total urinary oestrogens estimated on days 0, 5, 8, 12 and 15 following commencement of treatment. The responses were compared with six patients who were amenorrhoeic but had normal serum prolactin levels and absent positive feedback to oestrogen. The increased outputs of oestrogens were similar in the two groups. In the hyperprolactinaemic group 5 out of 16 subjects showed evidence of ovulation whilst the remainder showed a secondary failure of response. Six subjects who failed to ovulate were treated with clomiphene and human chorionic gonadotrophin (HCG) and ovulations were induced in 31 out of 34 treatment cycles but no pregnancies were achieved. The responses to clomiphene therapy in the hyperprolactinaemic subjects were compared to the assessment of positive feedback mechanisms by means of oestrogen provocation and oestrogen amplification tests and good correlation was obtained. Only those with evidence of positive feedback to these tests were likely to ovulate on clomiphene.

Vaginography for enterovaginal fistula

though the patient was not clinically masculinized, the preoperatively elevated testosterone levels along with their return to normal following removal of the tumor support the thesis that the solid granulosa cell tumor described was predominandy testosterone producing. Granulosa cell tumors are often associated with menstrual irregularities, ranging from hypermenorrhea to oligomenorrhea and amenorrhea. It has been suggested that the latter are due to suppression of LH and FSH by the increased levels of testosterone. In this case FSH was suppressed while LH was within the normal range. Following the removal of the tumor, menses resumed and FSH returned to normal. This suggests a partial suppression of the hypothalamic pituitary axis by testosterone. Although menstrual irregularities are often associated with granulosa cell tumors, galactorrhea has not been described in this setting. This patient had galactorrhea and normal serum prolactin values preand postoperatively. A number of patients with galactorrhea, however. have normal serum prolactin concentrations. 2 None of the other known etiologic factors leading to galactorrhea was present in this case. The cessation <)f this patient's galactorrhea following the removal of the granulosa cell tumor and return of plasma testosterone to normal suggests the existence of a causal relationship between the elevated testosterone levels and her galactorrhea. The exact nature of this relationship remains ro be defined.

Response of amenorrheic patients with normal serum prolactin to chlorpromazine during administration of human menopausal gonadotropin

To study the effects of graded amounts of estrogens on prolactin (PRL) secretion, PRL response to chlorpromazine (CPZ) during administration of human menopausal gonadotropin (hMG) was determined. A control CPZ test was done prior to initiation of hMG therapy and the test was repeated when endogenous estrogen secretion reached the physiologic range (350 to 400 pg. per milliliter) which stimulates luteinizing hormone surge in the normal ovulatory menstrual cycle. Six euprolactinemic women with secondary amenorrhea were studied. Studies showed that there was no significant change in the mean serum prolactin concentrations during control and repeat CPZ testing procedure (5.8 ± 2 and 10.8 ± 2 ng. per milliliter, p < 0.1). The maximal response of PRL to CPZ was significantly higher during hMG-induced high estrogenic state than during control testing (69.9 and 32.3 ng. per milliliter, p < 0.01). This finding suggests that endogenous estrogen may play a role in the regulation of serum prolactin concentration during the menstrual cycle.

283 NEONATAL HYPOGLYCEMIA ASSOCIATED WITH ANTERIOR HYPOPITUITARISM

We have observed the association of profound hypoglycemia and anterior hypopituitarism in four newborns. All presented with hypoglycemia during the first 30 hours of life, which reached levels less than 10 mg.%. Rates of 20-30 mg./kg./min. of 20% dextrose were required to maintain glucose levels above 30 mg.%. All infants were products of complicated pregnancies and deliveries and had APGAR scores of five or less at one and five minutes. Measurements of anterior pituitary function including serum TSH, T4, ACTH, cortisol and growth hormone, in addition to metapyrone and cosyntropin stimulation, revealed anterior panhypopituitarism in three infants and isolated ACTH deficiency in the other. Posterior pituitary function was normal in all cases. Unresponsiveness of TSH to intravenous thyrotropin releasing hormone (TRH) and normal serum prolactin levels further support anterior pituitary dysfunction in contrast to a hypothalamic etiology. Autopsy on one infant revealed no anterior pituitary tissue. The three surviving patients are all doing well on appropriate hormone replacement. Micropenis was present in the one male and all infants showed a widening of the midfacies. This unappreciated cause of early neonatal hypoglycemia may be related to birth hypoxia or anatomic malformation of the anterior pituitary and its rudiments. These may be more susceptible to events at birth than previously appreciated and consequently this system should be more agressively evaluated in newborns.

Endocrine Function in the Prader-Willi Syndrome

Five males and 2 females with the Prader-Willi Syndrome, aged 10-26 years, had low levels of circulating LH with a subnormal response to 100 and 500 mcg of gonadotrophin releasing hormone (Gn-RH) IV. Serum FSH response to Gn-RH was absent in 3, but normal in only one. Gonadotrophin response to Gn-RH increased in 4 patients during oral clomiphene (200 mg daily) given one to 6 weeks. This suggests that the pituitary gonadotrophes can function normally and that the deficiency is hypothalamic. Five males received 2000 u HCG twice weekly IM for up to 6 weeks. In 2 there was no response; in the remainder the rise in plasma testosterone was subnormal. Six of 7 patients had exaggerated TSH responses to 200 mcg thyrotrophin releasing hormone IV. All had normal thyroid function and serum prolactin and no evidence of thyroiditis. While gonadotrophin deficiency is present, primary gonadal failure may also be a feature of the hypogonadism.

The borderline pituitary fossa in patients with amenorrhoea and/or galactorrhoea

A retrospective clinicoradiological study of 80 patients with amenorrhoea and/or galactorrhoea showed: 1. Of 60 patients, in whom prolactin levels were estimated, 28 (47%) had hyperprolactinaemia (serum prolactin levels greater than 20 ng/ml). 2. Hyperprolactinaemia was present in 85% of patients with amenorrhoea and galactorrhoea, 35% of those with galactorrhoea only, and 12.5% of those with only amenorrhoea. 3. Pituitary adenomas were surgically removed from six patients; all but one had prolactin levels over 100 ng/ml. The level was 53 ng/ml in the sixth patient. 4. There is a considerable degree of observer variation in the interpretation of borderline sellar changes. 5. Minor abnormalities of the pituitary fossa were noted in 64% of patients with hyperprolactinaemia and 36% of those with normal prolactin levels. 6. The highest incidence of perfectly normal sellae was among patients with either amenorrhoea or galactorrhoea and normal serum prolactin.

Pluridirectional tomography in the evaluation of pituitary tumors

A series of 110 patients with suspected pituitary tumors was recently evaluated by endocrinologic and neuroradiologic studies. Of the 77 patients in this series who underwent surgery, 74 had confirmed pituitary adenomas, two had suprasella tumors of the influndibulum, and one had an empty sella not previously diagnosed at pneumoencephalography. All 17 patients with normal plain skull films but abnormal thin section tomography who underwent surgery had documented pituitary tumors. This includes six patients who presented with amenorrhea and/or galactorrhea and normal baseline serum prolactin levels; the only abnormality was found on tomography of the sella. In the preoperative evaluation of these patients, pluridirectional tomography of the sella was the most sensitive indicator of intrasellar pathology.