Hyperprolactinaemia does not always mean 'hyperprolactinaemia'!

The presence of macroprolactinaemia was investigated in the symptom-free hyperprolactinaemia cases to reveal its incidence. The serum prolactin (PRL) fractions in 21 female patients with hyperprolactinaemia without any clinical symptoms were analyzed with PEG (polyethylene glycol precipitation) procedure. In 14 of these 21 cases, hyperprolactinaemia was detected with a high fraction of macroprolactin. In cases with asymptomatic hyperprolactinaemia, it is more appropriate to employ the PEG precipitation test to detect the disorder. High levels of serum prolactin, do not essentially indicate the presence of a prolactinoma but may only indicate macroprolactinaemia.     

Hyperprolactinaemia and the regular menstrual cycle in asymptomatic women: should it be treated during therapy for infertility?

It is known that hyperprolactinaemia can cause galactorrhoea and irregular cycles or even amenorrhoea. High serum prolactin (PRL) can disturb follicular maturation and corpus luteum function. Treatment of hyperprolactinaemia in patients with resulting bleeding anomalies is established, but the question is how to manage normal cyclic hyperprolactinaemic women? Studies have shown that in a subgroup of asymptomatic patients the serum contains mainly high molecular weight form (big big PRL), which has a low bioactivity, called macroprolactinaemia. It is evident that macroprolactin does not affect the control of pituitary PRL secretion via the short loop feedback mechanism or the secretion of gonadotrophins as does monomeric PRL. Identification of macroprolactinaemia is therefore clinically important to prevent unnecessary examinations and inappropriate treatment. Prolactinoma can be associated with macroprolactinaemia. Performance of pituitary imaging in asymptomatic patients with hyperprolactinaemia may therefore be justified, but further studies are needed to evaluate the relation of costs and benefit. An unsolved problem is the differentiation between inactive and PRL-secreting tumours. Caution should be exercised concerning medical treatment in unstimulated patients and also in patients during ovarian stimulation alone or in combination with intrauterine insemination or in-vitro fertilization. The potential clinical significance of hyperprolactinaemia/macroprolactinaemia in asymptomatic women must be further evaluated.     

Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia

The role of macroprolactinemia in women with hyperprolactinemia is currently controversial and can lead to clinical dilemmas, depending upon the origin of macroprolactin, the presence of hyperprolactinemic symptoms and monomeric prolactin (PRL) levels. Macroprolactinemia is mostly considered an extrapituitary phenomenon of mild and asymptomatic hyperprolactinemia associated with normal concentrations of monomeric PRL and a predominance of macroprolactin confined to the vascular system, which is biologically inactive. Patients can therefore be reassured that macroprolactinemia should be considered a benign clinical condition, resistant to antiprolactinemic drugs, and that no diagnostic investigations or prolonged follow-up should be necessary. However, a significant proportion of macroprolactinemic patients appears to suffer from hyperprolactinemia-related symptoms and radiological pituitary findings commonly associated with true hyperprolactinemia. The symptoms of hyperprolactinemia are correlated to the levels of monomeric PRL excess, which may be explained as coincidental, by dissociation of macroprolactin, or by physiological, pharmacological and pathological causes. The excess of monomeric PRL levels in such cases is of primarily importance and the diagnosis of macroprolactinemia is misleading or inadequate. However, macroprolactinemia of pituitary origin associated with radiological findings of pituitary adenomas may rarely occur with similar hyperprolactinemic manifestations, exclusively due to bioactivity of macroprolactin. Therefore, in such cases with hyperprolactinemic signs and pituitary findings, macroprolactinemia should be considered a pathological biochemical condition of hyperprolactinemia. Accordingly, individualized diagnostic investigations with the introduction of dopamine agonists, or other treatment with prolonged follow-up, should be mandatory. The review analyses the laboratory and clinical significance of macroprolactinemia in hyperprolactinemic women suggesting clinically useful diagnostic and treatment strategies.     

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.     

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.     

Hyperprolactinaemic Amenorrhoea in Hong Kong

In a retrospective study of 595 patients attending the Menstrual Disorder Clinic from January, 1978 to December, 1981, 92 patients (15.5%) had raised serum prolactin (PRL) levels (greater than 25 ng/ml) on 2 or more separate occasions with a mean (+/- S.E.M.) value of 67.1 +/- 2.5 ng/ml. Galactorrhoea was found in 27.2% of the hyperprolactinaemic patients. Primary amenorrhoea was observed in 1 patient (1.1%) with serum PRL level of 68 ng/ml. Secondary amenorrhoea of longer than 6 months' duration occurred in 61 patients (66.3%) with mean PRL level 84.2 +/- 3.3 ng/ml. The 30 patients (32.6%) with irregular menstruation had a mean PRL level of 47.2 +/- 3.3 ng/ml. Investigations revealed that 43 patients (46.7%) had idiopathic hyperprolactinaemia, 14 patients (15.4%) had drug induced hyperprolactinaemia and 1 patient (1.1%) had hypothyroidism; 18 patients (19.5%) had suspected pituitary microadenoma and 16 patients (17.2%) had abnormal radiographic findings. Bromocriptine treatment was given to 38 patients, 13 with abnormal tomographic findings (mean serum PRL greater than 100ng/ml); 18 with suspected pituitary microadenoma (mean serum PRL 94 +/- 2.7 ng/ml) and 7 with idiopathic hyperprolactinaemia (mean serum PRL 65 +/- 4.7 ng/ml). All patients (38/38) responded to treatment with restoration of menstruation and cessation of galactorrhoea within 1 to 3 months. Mean PRL level was 21.6 +/- 5.2 ng/ml at the time of response. Thirteen patients subsequently became pregnant and all delivered healthy babies.     

Long-term effects of time, medical treatment and pregnancy in 176 hyperprolactinemic women.

The changes in plasma prolactin (PRL) concentrations were studied in 176 hyperprolactinemic women over periods of 6-180 months, to evaluate the independent effects of time, drugs and pregnancy on the evolution of prolactinemia. CT scans showed pituitary adenoma in 87 (9 macroadenoma), the clinical presentations for 110 patients there amenorrhea, for 37 abnormal cycles and 29 had anovulatory sterility as an isolated symptom. 107 women underwent 191 cycles of dopaminergic treatment and 73 had pregnancies (86), either spontaneously or as a consequence of the treatment. Changes in prolactin induced by medical treatment and pregnancy were recorded and the spontaneous changes in prolactin in 38 patients (17 with adenoma) were followed over periods of 6-72 months. Final mean PRL concentrations were lower than basal though not significantly, in both 'functional' (54.4 vs. 79.2 ng/ml) and prolactinoma patients (87.3 vs. 116.4 ng/ml). Separate calculation of changes in prolactin after the course of medical treatment, pregnancies or 'just waiting' periods showed mean PRL concentrations to be significantly lower only for 'functional' patients after pregnancy. On the other hand, PRL variations in individual patients revealed that: (1) spontaneously, PRL rarely becomes lower over a few years; (2) dopaminergic treatment was associated with normalization of PRL in 13% of women; and (3) pregnancy normalized prolactin concentrations in 29% of the patients. Chi-square analysis of the PRL-lowering frequencies in functional patients showed a high cure rate for pregnancy (P less than 0.0001) and a lesser but still significant effect of drugs (P less than 0.025).     

Serum prolactin and ovarian function after discontinuation of drug treatment for hyperprolactinaemia: a study with bromocriptine and metergoline

Serum prolactin (PRL) was estimated for up to 2 months after discontinuation of therapy with either bromocriptine (n = 33; 15 with idiopathic disease, 12 with pituitary microadenoma, and six with macroadenoma) or metergoline (n = 23; 11 with idiopathic disease, and 12 with microadenoma) that had been administered for 8-30 months. Only five patients treated with bromocriptine and two treated with metergoline had PRL levels that remained normal or below 50% of pretreatment values. Among the patients followed-up for up to 12 months, four showed a fall in PRL at 3-4 months, but this was followed by a rise in one patient. Five patients showing persistently lower or normal PRL after drug withdrawal were retested with thyrotrophin-releasing hormone; the two responsive women also had a normal response before treatment. Of 10 patients followed for 9 months, three had persistently normal PRL levels. Amenorrhoea and anovulation recurred, with some delay, in all the patients showing PRL rebound except one. Medical treatment of hyperprolactinaemia only rarely results in permanent benefit.     

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.     

Serum prolactin and gonadotrophin levels before and after luteinizing hormone-releasing hormone in the investigation of amenorrhoea.

An intravenous luteinizing hormone-releasing hormone (LRH) test was performed in 287 women with amenorrhoea. Prolactin, progesterone and oestrogens in serum were also measured. Twenty-four women with premature ovarian failure and 9 with gonadal dysgenesis had raised basal follicle-stimulating hormone (FSH) levels. Neither the basal luteinizing hormone (LH) level nor the gonadotrophin responses after LRH gave a better separation of this group of women with irreversible ovarian failure. Measurement of prolactin levels were valuable in that 15 of 42 patients with hyperprolactinaemia had a radiologically abnormal pituitary fossa, whereas pituitary fossa abnormalities were found in only 11 of 245 normoprolactinaemic women. It was thought that 181 women had functional amenorrhoea; 54 per cent of these women had developed amenorrhoea in relation to weight loss and 32 per cent in relation to discontinuation of oral contraceptives. A strong correlation was found between the body weight and the basal gonadotrophin levels. The basal LH levels were correlated with serum oestrogen levels, the basal FSH level and the LH response to LRH. Most of the patients with low basal LH values had developed amenorrhoea in relation to self-imposed weight-loss. The responses to LRH were often impaired in the underweight patients but became normal after weight gain. The polycystic ovary syndrome (PCO) could not be diagnosed by measuring either basal or LRH-stimulated gonatrophin levels. Single FSH and prolactin determinations in serum seemed to be the only indispensible hormone assays in the routine clinical evaluation of amenorrhoea.     

Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.     

Effects of pregnancy, delivery and lactation in hyperprolactinemia with prolactin producing pituitary adenoma

The effects of pregnancy, delivery and lactation on changes in serum prolactin (PRL) values were investigated in patients with hyperprolactinemia. Thirty-seven patients with hyperprolactinemia who wished to become pregnant were treated by transsphenoidal surgery, bromocriptine therapy, or a combination of the two. In 33 patients whose pre-pregnancy serum PRL concentration exceeded 30ng/ml, only in two did serum PRL return to the normal range below 30ng/ml after pregnancy, delivery and lactation. However, the serum PRL concentration was decreased in 28 patients. When classified according to the pre-pregnancy serum PRL concentrations, PRL less than or equal to 100 (Group A), 100 less than PRL less than or equal to 200 (Group B) and 200 less than PRL (Group C), patients with the greatest pre-pregnancy serum PRL concentration showed the greatest reduction. The ratios of post-pregnancy serum PRL to pre-pregnancy PRL in group A, B and C were 91.4 +/- 22.1%, 81.5 +/- 7.0% and 65.0 +/- 6.5% (Mean +/- SE), respectively. Group C with the highest pre-pregnancy serum PRL concentration consisted almost entirely of patients with macroadenoma. Thus, the reduction in serum PRL after pregnancy, delivery and lactation was considered to be the result of a decrease in the size of the adenoma due to adenoma enlargement over the sella turcica through the estrogen effects during pregnancy, and from impairment of pituitary circulation.     

Pregnancy outcome in pituitary tumors

Objective  To observe the maternal and perinatal outcome in pituitary tumor (macro- and micro-adenoma) during pregnancy. Methods  A retrospective analysis of a total of 19 cases of pituitary tumor group 1 (10 macroadenoma), and group 2 (9 microadenoma), during pregnancy over last 3 years in our unit were evaluated for pregnancy outcome, comparing maternal and perinatal outcome in the two groups using statistical analysis (Chi square test and Fischer exact t test). Results  The mean age was 27.1 years in group 1 (macroadenoma), 29.2 years in group, parity was 0.2 and 0.55, respectively, in the two groups. Mean pituitary size 14.85 cm³ in group 1 and 0.22 cm³ in group 2. While there was no significant difference in infertility, menstrual disorder in the two groups, galactorrhea, headache, seizures and blurring of vision were more common in macroadenoma group. More patients required medications (cabergoline/bromocriptine) in group 1 with significantly more women had worsening of their symptoms (raised intracranial tension, seizures) in group 1 than in group 2. Mean gestation and birthweight were better in group 2 (37.6 vs. 36.1 weeks and 2,849 vs. 2,401 g). While vaginal delivery could be achieved in 88.8% women in microadenoma group (group 2), 80% women required cesarean delivery in macroadenoma group (group 1), a highly significant difference (P value 0.005), there were no perinatal death in any group. Conclusion  Pituitary tumor during pregnancy if properly treated is associated with excellent maternal and perinatal outcome but macroadenoma is associated with lower gestation, birth weight and increased cesarean delivery rate.     

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.     

Long-term follow-up of 246 hyperprolactinemic patients

BACKGROUND: We wanted to evaluate the very long-term effects of bromocriptine on prolactin (PRL) levels and pituitary tumor size in a large cohort of hyperprolactinemic patients. METHODS: We conducted a retrospective cohort study in the Department of Endocrinology from Necker Hospital in Paris, France. Two hundred and forty-six patients consulted primarily for menstrual disorders, with diagnosis of hyperprolactinemia. Patients were followed-up for 99.9+/-3.6 months. One hundred and ninety-one were treated with bromocriptine, 32 underwent surgery, and 23 received no treatment. RESULTS: The mean initial plasma PRL level was 135.0+/-20.2 ng/ml. Presence of an adenoma was detected in 60% of our patients and comprised a microadenoma in 64% of cases. Compared to oligomenorrheic women, amenorrheic patients had significantly higher levels of PRL and larger pituitary tumor size. In the bromocriptine group, PRL levels decreased from 99.6+/-7.9 to 20.0+/-1.5 ng/ml (p=0.00001). The medical treatment was associated with disappearance of the adenoma in 45% of the women and with stabilization of pituitary tumor size in 40% of patients. Surgery led to disappearance of the adenoma in almost all cases, but failed to definitively cure hyperprolactinemia. CONCLUSION: In this large-scale retrospective study, the medical treatment of mild hyperprolactinemia was shown to be effective and sufficient after 9 years of follow-up.     

Dysfunction of dopaminergic regulation of prolactin in patients with functioning and nonfunctioning pituitary adenomas and craniopharyngiomas

The response to domperidone (a dopamine blocking agent) of serum prolactin (PRL) levels was compared in 3 patients with amenorrhea-galactorrhea without evidence of a pituitary tumor, 23 patients with prolactinomas (10 cases with histologic confirmation), 7 patients with histologically verified large nonfunctioning pituitary adenomas with normal or moderately elevated basal PRL levels, and 6 patients with histologically verified craniopharyngiomas (3 with normal basal PRL levels and 3 with elevated PRL levels). The response was compared with that of 10 patients with postpartum hyperprolactinemia and 14 normal women. Ten milligrams of intravenous domperidone induced a rapid rise in PRL that was maximal at 30 to 45 minutes in normal, postpartum, and amenorrhea-galactorrhea patients who had no sign of tumor. In contrast, domperidone failed to induce significant changes in PRL in cases of prolactinoma, nonfunctioning pituitary adenomas, and craniopharyngioma with or without elevated basal PRL levels. The results suggest that dopaminergic control on PRL secretion was impaired in all tumor cases. The mechanisms of this abnormal dopaminergic control, however, may be different. Whereas dopamine control in cases of prolactinoma is altered at the level of pituitary dopamine receptors, alternative explanations must be found for those tumors with normal basal PRL levels and lack of response to domperidone.     

Outcome of Treatment with Bromocriptine in Patients with Hyperprolactinaemia

Results in 136 hyperprolactinaemic women who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea are reported. There was radiographic evidence of pituitary microadenoma in 21 (15.4%) patients and 5 (3.7%) had macroadenoma. Four patients were taking antidepressants, 2 antihypertensive drugs and 7 had taken oral contraceptives for a period of 6 months to 5 years. The remaining patients had no obvious cause for elevated prolactin levels. Patients with pituitary adenoma had a significantly higher (p less than 0.001) baseline serum prolactin level (182 +/- 4.6 ng/ml) than those with no adenoma (59.2 +/- 4.2 ng/ml). All patients in the study were treated with bromocriptine (2.5-10 mg) to normalize serum prolactin or to achieve a pregnancy. The patients without an adenoma required a significantly smaller dose of bromocriptine (2.5-5.0 mg) (p less than 0.005) than those with an adenoma. Galactorrhoea disappeared in all 64 patients within 2-4 months of treatment, sixty-six (71%) of the 93 patients who desired pregnancy achieved it within 3 to 8 months of bromocriptine therapy; 32 of these patients received additional treatment with clomiphene and human chorionic gonadotrophins for induction of ovulation. In the remaining 70 patients menstruation became regular and ovulation was evident in 40% of them. There was no significant difference in the pregnancy rate between the patients with or without pituitary adenoma. Similarly, presence of galactorrhoea or a high level of prolactin did not influence the pregnancy rate. No complications were observed during pregnancy related to pituitary adenomas; 8 (12%) pregnancies ended in first trimester abortion. No lethal congenital fetal abnormalities were observed in the patients treated with bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Integrity of central dopaminergic system in women with postpartum hyperprolactinemia

In order to elucidate the role of elevated prolactin (PRL) on the central dopaminergic systems, the suppressive effects of PRL were studied after the administration of l-dopa and l-dopa plus carbidopa on consecutive days to the following three groups: 10 normoprolactinemic subjects, six nonnursing normal puerperal women, and seven hyperprolactinemic women without any evidence of pituitary tumor. In the normoprolactinemic subjects (basal PRL 13 ± 2 ng/ml mean ± SE), the suppressive effects of l-dopa alone and l-dopa plus carbidopa were similar (48% ± 4% and 58% ± 6%, respectively). In puerperal hyperprolactinemic subjects, the basal PRL (116.8 ± 16.4 ng/ml) was suppressed 77% ± 2% after administration of l-dopa and 51% ± 7% after l-dopa plus carbidopa, significantly different from that of l-dopa alone (p < 0.005), but similar to that observed in normal subjects. In the patients with idiopathic hyperprolactinemia, the baseline PRL (131 ± 38 ng/ml) decreased 56.3% after the administration of l-dopa. In the presence of peripheral dopa decarboxylase inhibition, the administration of l-dopa decreased plasma PRL values 30%, a drop significantly different from that of l-dopa alone (p < 0.02). Women with idiopathic hyperprolactinemia exhibit reduced central dopaminergic inhibition of PRL secretion similar to that in patients with pituitary tumor; whereas the response to central dopaminergic inhibition in postpartum women with comparable baseline PRL levels is similar to that in normoprolactinemic subjects. This indicates that hyperprolactinemia per se is not associated with a state of reduced central dopaminergic inhibition. The increased pituitary sensitivity to l-dopa observed in puerperal women may be due to alterations in PRL receptors or vascularity.     

Pituitary response profile following metoclopramide administration in women with different forms of hyperprolactinemia

Aims: To test the hypothesis that macroprolactinemia is an extra-pituitary phenomenon by showing that the pituitary production of prolactin in patients with hyperprolactinemia due to macroprolactin is comparable to that in normoprolactinemic women and different from that in women with monomeric hyperprolactinemia.

Methods: Twenty-five women were studied: eight with macroprolactin hyperprolactinemia, eight with monomeric hyperprolactinemia, and nine controls. Prolactin levels were measured before and after precipitation with polyethylene glycol at baseline and at 5, 10,15, 30, and 60?min after metoclopramide administration (10?mg i.v.) in the three groups.

Results: The response profile of total and monomeric prolactin following the administration of metoclopramide was similar in women with monomeric hyperprolactinemia and normoprolactinemia but different in women with macroprolactinemia. The areas under the curve for total and monomeric prolactin were higher in patients with macroprolactinemia than in the other two groups (p?Discussion: Our findings support the hypothesis that prolactin secretion is comparable in women with macroprolactinemia and in normoprolactinemic women. The dynamics of the secretion suggest that the formation of prolactin complexes is an extra-pituitary process.     

Depressed prolactin levels in diabetic women with anovulation

The circulating levels of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol-17 beta were determined by radioimmunoassay in 76 normal healthy women in the follicular phase of the menstrual cycle, 54 consecutive anovulatory non-diabetic women and 20 consecutive diabetic women with anovulation. An elevated plasma PRL concentration was found in 1/20 (5%) of the diabetic women and in 17/54 (32%) of the non-diabetic anovulatory women (p less than 0.05). Plasma concentrations of estradiol-17 beta and gonadotropins in diabetics did not differ (p greater than 0.05) from those found in non-diabetic women with anovulation. Diabetic women with secondary amenorrhea had significantly (p less than 0.05) lower plasma concentrations of PRL and estradiol-17 beta than non-diabetic women with amenorrhea and normal controls. Furthermore, this group of diabetic women had lower median plasma LH concentrations than the non-diabetics with secondary amenorrhea and normal controls, but this difference was not significant (p greater than 0.05). These data indicate that diabetic patients with anovulation have hypothalamic and/or pituitary defects. Furthermore, the low prolactin and LH levels despite a low estradiol-17 beta concentration may suggest an increased hypothalamic dopamine activity in patients with diabetes mellitus and secondary amenorrhea.