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Changes in the catecholamine metabolism in the adrenal medulla of male hamsters with experimental hyperprolactinemia.

1. Prolactin (PRL) can play a role as a physiological modulator of adrenal medulla function in several rodents. 2. We have examined the effects of hyperprolactinemia induced by ectopic pituitary grafts in Syrian hamsters on the adrenal medulla contents of catecholamines (CA) and their metabolites, as well as on the activities of several enzymes involved in the metabolism of these amines. 3. Increases in the peripheral levels of PRL in these animals were associated with decreases in adrenal medulla weight and increases in adrenal medulla contents of norepinephrine, epinephrine and vanilmandelic acid, the main degradative metabolite of CA, while adrenal medulla contents of the O-methylated derivatives of CA, normetanephrine and metanephrine, were unaltered. 4. These changes were correlated with increases in the adrenal medulla activity of monoamine oxidase, while the activities of tyrosine hydroxylase, phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase were unaltered. 5. These results indicate that PRL is able to act on the adrenal medulla of hamsters by increasing the ability of these cells to metabolize CA via oxidative deamination.

Adrenal Medulla↗

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay.

OBJECTIVE: To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. DESIGN AND METHODS: Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p<0.05) normalisation of PRL following PEG. RESULTS: PRL recovery was similar in volunteer and hyperprolactinemic samples (mean+/-SD 101+/-13% and 101+/-19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. CONCLUSIONS: Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived.

Chromatography, Gel↗

Renal epithelioid angiomyolipoma associated with hyperprolactinemia.

We report a unique case of a 42-year-old woman with a renal epithelioid angiomyolipoma associated with elevated serum prolactin levels and presenting with galactorrhea. Magnetic resonance imaging of the brain showed no pituitary abnormality, and abdominal imaging demonstrated a large right renal mass. Pathologic analysis of the radical nephrectomy specimen revealed an epithelioid angiomyolipoma. She had an uneventful postoperative recovery with complete normalization of her serum prolactin level and resolution of galactorrhea. To our knowledge, the association between epithelioid angiomyolipoma and hyperprolactinemia has never before been reported.

Adult↗

[Macroprolactin as etiology of hyperprolactinemia. Method for detection and clinical characterization of the entity in 39 patients].

The presence of serum macroprolactin is a relatively frequent situation that can lead to expensive explorations and ineffective treatments. The precipitation with polyethylene glycols permits its detection rapidly, trustworthily, and inexpensively. The objective of the present work has been to assess the incidence of macroprolactin in patients with hyperprolactinemia through its identification with polyethylene glycols, as well as the clinical and radiological findings, and the response in these patients to the treatment. For it the clinical history of all the cases in which there was detected macroprolactinemia, some of them with several years of previous follow-up, was reviewed exhaustively. Of the 1505 patients in which prolactin level was determined, 195 (13%) showed values higher than 40 microg/l. In 39 (20%) of them the presence of macroprolactin was detected. After observing the evolution of these patients, spontaneously or under treatment with dopaminergic agonists, a clear relationship of causality between the presence of macroprolactin and the clinical manifestations was not found, except in a case of galactorrhea. In 27 cases nuclear magnetic resonance was done; in 4 of them a picture was observed compatible with small microadenoma or microcyst and in no patient a macroadenoma was detected. We conclude that the macroprolactinemia is a relatively frequent and easily detected entity through precipitation with polyethylene glycols. It has a limited relation with the clinical findings and there should always be sought other possible causes of this situation. It is an apparently benign situation and its identification can avoid unnecessary explorations and treatments.

Adolescent↗

New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Animals↗

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

17-alpha-Hydroxyprogesterone↗

Effects of sulpiride-induced hyperprolactinemia on human ovarian follicles during the late follicular phase.

The effect of hyperprolactinemia during the midfollicular through the late follicular phase of the menstrual cycle on follicular development and follicular fluid hormone concentrations was studied. Fourteen women underwent laparotomy in the late follicular phase for gynecologic reasons; 6 were treated with sulpiride daily from the midfollicular to the late follicular phase (sulpiride group) and 8 received no treatment (control group). Daily administration of sulpiride (150 mg orally) significantly elevated serum prolactin (PRL) levels in all six women. In the small follicles (less than or equal to 8 mm in diameter), follicular fluid 17 beta-estradiol (E2) concentration was significantly lower (P less than 0.01), and testosterone (T) concentration was higher (P less than 0.05) in the sulpiride group. In the large follicles (greater than or equal to 9 mm in diameter), however, follicular fluid E2 and T concentrations showed no significant differences between the sulpiride and control groups. In the sulpiride group, the mean diameters of the follicles were significantly smaller than in the control group (P less than 0.01). These observations suggest that PRL exerts a suppressive effect on the smaller but not the larger follicles during the late follicular phase.

Adult↗

Transient hyperprolactinemia during cycle stimulation and its influence on oocyte retrieval and fertilization rates.

Prolactin (PRL) has been shown to have inhibitory effect on follicle-stimulating hormone induced aromatase activity and estrogen biosynthesis in human granulosa cells cultured in vitro. To investigate the validity of the hypothesis that transient hyperprolactinemia during controlled ovarian hyperstimulation might influence follicular steroidogenesis and oocyte maturation, we measured serum PRL, estradiol, and progesterone before aspiration of oocytes in women undergoing ovarian stimulation (n = 108) in in vitro fertilization-embryo transfer. No correlation was detected between PRL and total number oocytes, number mature oocytes, fertilization rate, cleavage rate, and pregnancy rate. Transient elevation of PRL was a common finding in patients (57%) but was not associated with a poor clinical outcome.

Clomiphene↗

Transient hyperprolactinemia is associated with a midcycle luteinizing hormone surge.

This study demonstrates that LH surge cycles in IVF patients were associated with significantly higher serum PRL concentrations than cycles in which a spontaneous LH surge did not occur. Our findings support the hypothesis of concomitant LH and PRL release at the time of the midcycle gonadotropin surge, as well as that of estrogen sensitization of pituitary lactotropes, and suggest a possible mechanism for transient midcycle hyperprolactinemia.

Chorionic Gonadotropin↗

The effect of two dopaminergic drugs on menstrual function and psychological state in hyperprolactinemia.

OBJECTIVE: To investigate the effect of dopaminergic drugs on the well being in hyperprolactinemic patients. DESIGN: A psychometric test for well being, the SCL-90, was applied at baseline and in the 24th week of a double-blind randomized prospective study comparing the effectiveness and safety of the new dopamine d2 agonist CV 205-502 with bromocriptine. SETTING: Outpatient department of a university clinic for obstetrics and gynecology. PATIENTS: Twenty-four women with hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before, and 11 were known to react unfavorably to bromocriptine. RESULTS: The effectiveness of CV 205-502 was identical to bromocriptine: its tolerability appeared to be better, especially in the initial phase of treatment. At baseline, the mean scores of the SCL-90 were significantly elevated over the reference values. Sixteen patients had normal scores. The elevations were caused by 8 patients with scores in the range found in psychiatric disease (211 +/- 30 [SD] [CV 205-502] and 182 +/- 32 [bromocriptine]). They were depressed, anxious, and hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130 +/- 23.5) in the SCL-90 than the patients treated with bromocriptine (149.5 +/- 20). CONCLUSION: The markedly increased well being in patients treated with CV 205-502 cannot be explained by its better tolerability and is probably caused by a specific central activity of CV 205-502. Further research into the antidepressive properties of this compound is warranted.

Adult↗

Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases.

Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.

Adenoma↗

Primary amenorrhea associated with hyperprolactinemia: four cases with normal sellar architecture and absence of galactorrhea.

Hyperprolactinemia is an uncommon cause of primary amenorrhea. The diagnosis should be sought even in the absence of galactorrhea and sellar abnormality, particularly when thelarche and pubarche have occurred. Reduction of serum PRL levels followed by menarche can be anticipated within a few months of starting bromocriptine therapy in the majority of cases.

Adolescent↗

Pattern of development of hyperprolactinemia after initiation of haloperidol therapy.

OBJECTIVE: To determine the time it takes for prolactin (PRL) levels to increase after initiation of therapy with haloperidol (a neuroleptic medication) and the pattern and extent of the increase. METHODS: Seventeen individuals scheduled to be given treatment with neuroleptic drugs were enrolled. Baseline blood specimens were collected for PRL and TSH levels. Follow-up samples for PRL determinations were obtained every 3 days for 18 days after initiation of haloperidol therapy. RESULTS: There were 17 subjects: 14 women and three men. Two of the subjects were found to have hyperprolactinemia due to hypothyroidism and were excluded from the basic study. The 15 remaining subjects all had normal baseline PRL levels and normal TSH values. The PRL levels in all 15 showed a similar pattern: a rapid increase in PRL levels in the first 6-9 days, followed by a plateau that remained, with minor fluctuations, throughout the study. The highest mean peak level of PRL was 37.4 ng/mL and the maximum was 77 ng/mL. The two individuals with hypothyroidism had somewhat elevated baseline PRL levels; although they showed the same initial pattern of increase after haloperidol administration, their PRL levels reached values well above 100 ng/mL. CONCLUSION: There is a distinct pattern of response of PRL to haloperidol. The PRL level increases for 6-9 days, then plateaus, the peak being between 30 and 50 ng/mL, and always remains below 77 ng/mL. In our study, levels that continued to increase, or increased above 77 ng/mL, indicated the presence of hypothyroidism. The patterns and levels of the increase were uninfluenced by the therapeutic dose of the medication given. Given that the patients in our study with elevated levels of TSH had such high levels of PRL, all patients should have TSH determinations at the initiation of therapy with neuroleptic medications such as haloperidol.

Adult↗

Cushing's disease and hyperprolactinemia due to a mixed ACTH- and prolactin-secreting pituitary macroadenoma.

A 36-year-old man with depression, Cushingoid features and hypogonadism was found to have simultaneous pituitary-dependent Cushing's disease and marked elevation of serum prolactin (PRL). CT-scan revealed a macroadenoma with suprasellar extension. Transphenoidal surgery cured the patient's Cushing's disease, but failed to correct his hyperprolactinemia, which was controlled by subsequent bromocriptine therapy. Immunostaining of the pituitary tumor was positive for PRL as well as for ACTH, and ACTH-related peptides beta-lipotropin and beta-endorphin in two distinct tumor cell lines. This pituitary tumor is one of the few mixed PRL- and ACTH-secreting tumors documented by immunostaining. It is the second reported in a macroadenoma, in which PRL-secreting tumoral cells are much more abundant than ACTH-secreting cells.

Adenoma↗

Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.

Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory regulator of pituitary hormone secretion. Mice with a disrupted D2 dopamine receptor gene had chronic hyperprolactinemia and developed anterior lobe lactotroph hyperplasia without evidence of adenomatous transformation. Unexpectedly, the mutant mice had no hyperplasia of the intermediate lobe melanotrophs. Aged female D2 receptor -/- mice developed uterine adenomyosis in response to prolonged prolactin exposure. These data reveal a critical role of hypothalamic dopamine in controlling pituitary growth and support a multistep mechanism for the induction and perpetuation of lactotroph hyperplasia, involving the lack of dopamine signaling, a low androgen/estrogen ratio, and a final autocrine or paracrine "feed-forward" stimulation of mitogenesis, probably by prolactin itself.

Animals↗

Melperone treatment in an organic delusional syndrome induced by hyperprolactinemia: a case report.

A young female with organic delusional syndrome induced by hyperprolactinemia was admitted to the Psychiatry Clinic of Ankara Social Security Hospital. The most striking characteristic of her history was either worsening of the endocrinologic clinical outcome under conventional neuroleptic treatment or worsening of clinical psychiatric outcome under bromocriptine therapy. A new atypical neuroleptic, melperone, suggested to minimally affect plasma prolactin levels, was started. Her psychotic complaints significantly subsided and she was devoid of any symptomatological change regarding her endocrinological status. These results were discussed.

Adult↗

Acromegaly with moderate hyperprolactinemia caused by an intrasellar macroadenoma.

BACKGROUND: A 31-year-old woman presented 12 months after discontinuing the oral contraceptive pill with progressive headache to her primary-care physician. She had previously presented with irregular menses to her obstetrician-gynecologist 4 months after discontinuing the oral contraceptive pill. Her serum prolactin levels were 153 microg/l and a pituitary MRI revealed a 13 mm intrasellar mass consistent with an adenoma. The patient was given 0.5 mg cabergoline twice weekly, and after 6 weeks her prolactin levels fell to 31 microg/l. After 6 months, however, she complained of persistent frontal headache and a repeat MRI revealed that the adenoma had increased in size to 16 mm. The patient was referred to an endocrinologist for further evaluation. INVESTIGATIONS: Serum insulin-like growth factor 1 levels and growth hormone levels measured 2 h after ingestion of 75 g of oral glucose. DIAGNOSIS: Acromegaly and hyperprolactinemia caused by a mixed-cell adenoma, secreting growth hormone and prolactin. MANAGEMENT: Trans-sphenoidal surgery followed by medical therapy with 20 mg intramuscular octreotide-LAR monthly.

Acromegaly↗