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Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia.

The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.

Adenoma, Acidophil

[Dynamics of hormonal modifications induced by bromocryptin during hyperprolactinemia].

In a group of 16 females and 2 males with hypogonadism and hyperprolactinemia, bromocriptine was found to suppress prolactin (PRL) high levels within one day without further significant lowering during a 3 weeks longitudinal survey. The usually effective dosage was 5 mg per day. On the contrary, sex hormones did not vary initially and increased secondarily only in those patients resuming gonadal activity. The changes were either cyclical or heterogenous when the first cycle was anovulatory. This latter situation could sometimes but not always be attributed to persistent hyperprolactinemia. Menstruation resumed in 11 patients. Persistance of hypogonadism in the remainder could be explained by incomplete PRL reduction in one case and probability of previous hypothalamo-pituitary damage in six. The latter hypothesis was based in part on impaired gonadotropins responses to LH RH which were not modified by the treatment.

Adolescent

[Primary dysmenorrhoea and hyperprolactinemia (author's transl)].

Between 5 and 10% of all young girls and women suffer of severe primary dysmenorrhoea which interfers monthly with their activities. In this type of primary dysmenorrhoea we found hyperprolactinemia in 13 of 15 women who were examined. All 15 patients had a pituitary tumour ruled out and were treated with Bromo-ergocryptine (parlodel). Eight patients became free of symptoms and five were well improved. The possible correlation of hyperprolactinemia to premenstrual tension and severe primary dysmenorrhoea is discussed.

Adolescent

Sellar enlargement with hyperprolactinemia and a Rathke's pouch cyst.

A woman with secondary amenorrhea was found to have hyperprolactinemia without clinical galactorrhea. Radiological findings of an enlarged sella turcica with displacement of the pituitary stalk were considered consistent with a prolactin macroadenoma. Treatment with bromocriptine corrected the amenorrhea and hyperprolactinemia, and the patient inadvertently became pregnant. However, no complications to the mother or fetus occurred during pregnancy or postpartum. On transsphenoidal surgery three months postpartum, the unexpected presence of a large Rathke's pouch cyst with a microadenomatous or nodular hyperplasia type of prolactin-secreting tumor was observed to account for the preoperative clinical and radiological findings.

Adult

Pituitary gonadotropin response in women with idiopathic hyperprolactinemia.

Inappropriate lactation and idiopathic hyperprolactinemia are frequently associated with amenorrhea. In these individuals, peripheral levels of follicle-stimulating hormone (hFSH) are usually normal, and luteinizing hormone (hLH) levels are often found in the low-normal range. The present study was undertaken to evaluate the functional capacity of the pituitary by the response of hFSH and hLH to synthetic gonadotropin-releasing hormone (Gn-RH). Six women with amenorrhea, inappropriate breast secretion, and idiopathic hyperprolactinemia (prolactin levels ranged from 45 to 355 ng/ml) were given 100 mug of Gn-RH intramuscularly. Serum hFSH and hLH levels were assessed in samples obtained at 15-minute intervals over the next 2-hour period. Initial hFSH levels were normal in all women, with a mean of 242 +/- 72 ng/ml. The absolute increase after Gn-RH administration averaged 486 +/- 193 ng/ml. Serum hLH was below normal in three of the six women, and normal in the remaining three women initially. The absolute increase averaged 1308 +/- 315 ng/ml. The greatest percentage increase in hLH was found in the women with the subnormal basal titers. In these women, hLH rose from a mean of 22 ng/ml to a mean of 1092 ng/ml. These data demonstate an exaggerated increase in hFSH and hLH levels after exogenous Gn-RH administration. This suggests that the amenorrhea associated with elevated serum prolactin levels is principally of hypothalamic origin.

Amenorrhea

Amenorrhea, hyperprolactinemia and pituitary enlargement secondary to primary hypothyroidism. Successful treatment with thyroid replacement.

A 22-year-old nulliparous woman presented with primary amenorrhea, primary hypothyroidism, hyperprolactinemia, and radiologic evidence of pituitary enlargement. Investigation demonstrated limited reserves of ACTH and growth hormone. Circulating concentrations of TSH and prolactin were elevated; they increased in response to thyrotropin releasing hormone and decreased following L-dopa administration. After treatment with L-tri-iodothyronine, serum TSH and prolactin levels fell markedly, reserves of growth hormone and ACTH returned to normal, menstrual periods began, and the patient conceived. She experienced an uncomplicated prenatal, intrapartum, and postpartum course. It is thought that this patient represents a distinct clinical entity: a syndrome of amenorrhea, hyperprolactinemia, and pituitary enlargement, all secondary to primary thyroid failure. This syndrome should be distinguished from the Forbes-Albright syndrome, as it is reversible with thyroid replacement therapy. Recognition of this syndrome may thus spare the patient unnecessary, and potentially dangerous, pituitary surgery or irradiation.

Adult

Nonpuerperal galactorrhea and hyperprolactinemia. Clinical findings, endocrine features and therapeutic responses in 56 cases.

The clinical and endocrine features, and the responses to different treatment modalities, were examined in 56 patients with galactorrhea and/or hyperprolactinemia after a two month to six year follow-up period. A pituitary adenoma was diagnosed in 17 patients. A prolactin-cell adenoma was identified histologically in eight patients. Other etiologic factors were myxedema (two patients), phenothiazine ingestion (six patients) and breast manipulation (four patients). In 27 patients, including three with abnormalities of the sella turcica, no causal factor was found, and their condition was labelled as dysfunctional in origin. Symptoms were preceded by childbirth in 11 patients and by estrogen-progestin contraception in 22; pituitary adenomas were discovered in both groups in approximately the same frequency (30%) as in the over-all study group. Aside from roentgenographic studies, as well as visual field perimetry in a few cases, a serum prolactin level above 100 ng/ml was the only indicator of a pituitary prolactin-cell adenoma. Prolactin-suppression tests (L-DOPA and 2alpha-Br-ergocryptine) were found to be of no value in discriminating between tumoral and dysfunctional conditions. No significant alterations in prolactin levels occurred after water loading irrespective of basal levels or the nature of the pathologic process. Selective pituitary tumor excision (eight patients) was followed by rapid normalization of prolactin levels and disappearance of clinical abnormalities. Conversely, after pituitary irradiation (eight patients), improvement tended to be slower. Treatment of infertility in those patients without an apparent organic lesion was more successful with 2alpha-Br-ergocryptine (three of three) than with clomiphene (two of seven). Pregnancies following the administration of drugs or after surgical treatment were uneventful. Since follow-up resulted in the early diagnosis of pituitary tumors from seven to 56 months after initial investigation, and since no diagnostic tools are currently available which help to discriminate between tumoral and dysfunctional conditions before abnormalities become evident on roentgenograms, prolonged observation of these patients remains essential.

Adenoma

Treatment of hyperprolactinemia-anovulation syndrome.

Twelve patients with amenorrhea-galactorrhea and hyperprolactinemia are presented. The mean serum prolactin level was 175 ng/ml (range, 37 to 575 ng/ml). Basal gonadotropin levels were normal in all patients. Serum estradiol levels were normal in three women and reduced in nine. The response to luteinizing hormone-releasing hormone was normal in 10 patients and the response to clomiphene citrate was reduced in all women. Radiologic evaluations of the sella turcica and neurologic examinations were performed in all cases. Patients were treated with bromocryptine (2-bromo-alpha-ergocryptine, CB-154), 2.5 to 10 mg/day, for 5 to 35 weeks. In 10 patients normalization of the menstrual cycle was restored, and 9 patients were ovulatory. The galactorrhea ceased or was improved in all cases. Four patients who were treated for infertility became pregnant after one to three treatment cycles. In all cases prolactin levels were normalized (mean level, 10 ng/ml). Side effects were slight and were experienced only on initiation of therapy. The role of prolactin and the significance of normalization of plasma prolactin levels are discussed. Lowering prolactin secretion with bromocryptine allows resumption of normal gonadal function.

Adult

Value of luteinizing hormone-releasing hormone testing in bromocriptine treatment of amenorrhea and hyperprolactinemia in patients with pituitary tumors.

The results of bromocriptine treatment in 13 patients with radiologically evident pituitary tumors are described. A menorrhea was present in all patients, hyperprolactinemia in 12 of the 13 patients, and acromegaly in 3 patients. Five patients have previously been treated surgically and by radiotherapy because of suprasellar extension of the adenoma. Plasma prolactin levels after one single dose of 2.5 mg of bromocriptine were found to have no predictive value as to the dosage needed for treatment, whereas the plasma gonadotropin response after the administration of luteinizing hormone-releasing hormone appeared to be predictive with respect to the return of ovulation during bromocriptine therapy.

Adenoma

Pituitary tumors associated with hyperprolactinemia and polycystic ovarian disease.

Galactorrhea and hyperprolactinemia, or both, have been described in some patients with polycystic ovarian disease. Three patients who had had previous bilateral wedge resection of the ovaries and who manifested persistent amenorrhea were found to have elevated levels of serum prolactin (180 to 540 ng/ml) 5 to 10 years later. All three patients initially demonstrated moderate hirsutism and failed to experience withdrawal bleeding after administration of progesterone or clomiphene citrate. Polytomographic evidence suggestive of an intrasellar tumor was present when elevated serum prolactin levels were noted. (Routine sellar roentgenograms prior to wedge resection had been reported as normal.) Two of the three patients underwent transsphenoidal surgery with removal of an 8-mm diameter chromophobe adenoma in each instance. Although serum prolactin levels decreased to 32 and 102 ng/ml, respectively, amenorrhea has persisted with gradual cessation of galactorrhea over a 1- to 2-year follow-up period. Our experience with the reported three cases supports the conclusion that in some cases an association may exist between polycystic ovarian disease and prolactin-producing adenomas.

Adult

Hyperprolactinemia in sarcoidosis: incidence and utility in predicting hypothalamic involvement.

Patients with sarcoidosis have been reported frequently to have elevated concentrations of serum prolactin. On this basis, it was suggested that the hypothalamus might be a common site of involvement by sarcoidosis and that measurement of serum prolactin concentrations might serve as a sensitive indicator of hypothalamic disease. We measured serum prolactin concentrations in a group of 61 patients with sarcoidosis. Hyperprolactinemia was detected in only 2 of the entire group and was not observed in any of the 9 patients with central nervous system involvement. Because radioimmunoassayable prolactin concentrations are infrequently elevated in patients with disseminated sarcoidosis, even when pitutitary hypofunction is apparent, it is concluded that the measurement of serum prolactin is not a reliable method for screening these patients for pituitary or hypothalamic disease.

Adolescent

Hyperprolactinemia-induced precocious puberty in the female rat: ovarian site of action.

Hyperprolactinemia induced in immature female rats by chronic treatment with sulpiride, a dopaminergic receptor blocker, resulted in advancement of the onset of puberty. While serum PRL levels increased promptly after initiation of the treatment and remained elevated throughout the entire period studied (day 22 to first diestrus after vaginal opening), gonadotropin levels did not appear to be altered and increased abruptly only at the time of the first preovulatory surge. Except for a decrease during the first diestrus, serum TSH and GH were not consistently altered by sulpiride. After 5 days of treatment, serum progesterone levels, but not those of androgens, were increased in hyperprolactinemic (HP) rats. Uterine weight, taken as an index of estrogen secretion, was unambiguously increased in HP rats, the first significant difference being observed 5 days after initiation of the sulpiride treatment (day 27). Ovarian estrogen and progesterone responsiveness of normal animals to gonadotropins, as determined by in vitro release of the steroids after incubation with hCG, increased with age. The response was dramatically enhanced in HP rats, its magnitude increasing markedly as the animals approached puberty. Androgen response to hCG was, however, similar in HP and control rats. In vitro release of adrenal progesterone, but not that of estrogen or androgens, was slightly enhanced in HP rats. When sulpiride treatment was terminated on the first day of diestrus after vaginal opening, the animals continued to show estrous cycles. By contrast, maintenance of the treatment for several days after vaginal opening resulted in a condition of constant diestrus. The results suggest that one of the mechanisms by which PRL induces precocious puberty in the female rat is by sensitizing the ovaries to the low circulating gonadotropin levels observed during the prepubertal period. In addition, PRL also seems to stimulate progesterone secretion by the adrenal glands.

Androgens

Normal pregnancies after treatment of hyperprolactinemia with bromoergocryptine, despite suspected pituitary tumors.

Bromocryptine treatment was administered to 15 patients with amenorrhea and galactorrhea (AG) and to 1 patient with amenorrhea. All of them had increased plasma PRL levels. Of these 16 patients, 4 had a normal sella turcica (ST; group STO), 4 had a slight enlargement (group ST+), and 7 had a clear enlargement of ST (ST++) but no evidence of suprasellar extension. Ovulation was restored in 15 patients by bromocryptine treatment only. In one patient, ovulation resumed only after human pituitary gonadotropin treatment in combination with bromocryptine. There was no correlation between basal prolactinemia, PRL stimulability or suppressibility, the size of ST, or the efficiency of bromocryptine treatment. Every patient with normal LH response to either LRH or clomiphene or both resumed ovulation. Ovulation resumed in 3 patients among the 4 with abnormal LH response to either LRH or clomiphene or both. Among the 14 who desired pregnancy, 13 became pregnant. To date, 12 patients (ST++, 5; ST+, 3; STO, 4) have delivered normal babies. The courses of pregnancy were normal. During pregnancy, no change of ST was noted on lateral and frontal skull x-ray performed in every patient at trimonthly intervals. There was no change in the sellar index in 10 patients after pregnancy, as compared to the pretreatment status. In the presence of a pituitary adenoma or in patients with hyperprolactinemia and amenorrhea and galactorrhea, bromocryptine treatment may cure sterility without pituitary complication during pregnancy.

Adult

Pituitary function testing in amenorrhea-galactorrhea-hyperprolactinemia.

Fifteen patients, age 16 to 55, presented with amenorrhea-galactorrhea-hyperprolactinemia. Pituitary function was evaluated by bolus injections of insulin, luteinizing hormone-releasing hormone (LHRH), and thyrotropin-releasing hormone (TRH) in 13 and by LHRH and TRH in 2. Responses to growth hormone (GH), thyroid-stimulating hormone (TSH), cortisol (F), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured. GH, TSH, and F responses were normal in most cases. LH responses were decreased (P less than 0.025) in patients with abnormal sellar tomography, whereas FSH responses tended to decrease with elevated prolactin levels. Prolactin responses were absent in five of the seven cases which could be evaluated. The clinical value of such testing appears to be limited to an individualized basis, although some prognosis of ovulatory response to bromocriptine therapy may be obtained from the gonadotropin response.

Adolescent

Hyperprolactinemia in multiple endocrine adenomatosis, type 1.

Three cases are described in which hyperprolactinemia occurred as a feature of multiple endocrine adenomatosis, type 1 (MEA-1); enlargement of the sella turcica varied from gross to absent, and serum prolactin (PRL) levels ranged from 21 to 1,000 ng/ml in these cases. Since PRL-secreting pituitary tumors may occur with variable presentation in MEA-1, periodic measurements of serum PRL levels should be carried out to detect this abnormality.

Adult

Hyperprolactinemia and polycystic ovarian syndrome.

Prolactin and pituitary gonadotropin levels were studied in eight patients with polycystic ovarian syndrome. All women were of reproductive age and had had menstrual disorders since menarche. Three patients had hyperprolactinemia with or without galactorrhea and tomograms of the sella turcica revealed pituitary microadenomas. The remaining five patients with normal baseline prolactin levels had a prolactin stimulation test which used 25 mg of thorazine per os, and a prolactin suppression test using l-dopa 500 mg per os. Analysis of the results of these tests and a comparison with tests performed in five normal individuals used as controls showed significantly different responses in the two groups of women. The preliminary information obtained indicates that an abnormal prolactin secretion status may exist in the polycystic ovarian syndrome.

Adolescent