Extrasellar prolactinomas: successful management of 24 patients using bromocriptine

24 patients with an extrasellar prolactinoma (mean prolactin 4,722 ng/ml), 8 of whom had previously had surgery, received 5-40 mg bromocriptine daily for 13-252 weeks. The mean prolactin level had fallen 89% at 2 days, 95% at 6 weeks, and 15 patients achieved normal values. Tumor shrinkage occurred in all 9 patients rescanned within 2 weeks and later was documented in 23; in 18 the extrasellar tumour disappeared. 12 patients had visual abnormalities; 7, including 2 who had been completely blind, improved within 1 week. 2 patients had normal prolactin levels after withdrawal of bromocriptine, 1 following radiotherapy and the other during two uncomplicated pregnancies. Bromocriptine is safe and effective. We conclude that medical treatment should always precede surgery unless pituitary apoplexy causes sudden deterioration of vision. Most patients will subsequently require radiotherapy or surgery for permanent cure.     

A case of large prolactinoma supposed to be cured by bromocriptine therapy

The authors reported a patient with a large prolactinoma (PRL 1,716 ng/ml) who was treated with bromocriptine for two years and followed up for a subsequent 36 months. After the start of the therapy, the tumor size was dramatically reduced, and finally the disappearance of the tumor was confirmed by high resolution coronal CT. The serum prolactin level and pituitary function were normalized. The tumor has not regrown and the blood prolactin level has remained normal for 36 months since the discontinuation of bromocriptine administration. This is a very rare case report on the eradicative effect of bromocriptine on such a large prolactinoma. Another characteristic of this case was that the prolactin reserve was maintained not only before the therapy but also during the early stage of the therapy.     

Giant Prolactinoma and Effectiveness of Medical Management

ObjectiveTo review our experience with long-term cabergoline and bromocriptine therapy in the treatment of giant prolactinomas.MethodsPatients with giant prolactinomas diagnosed and treated at our center in Mumbai, India, between January 2005 and January 2009 were included. Diagnostic criteria for giant prolactinoma included tumor diameter greater than 40 mm, serum prolactin concentration higher than 1000 ng/mL, and invasive tumor growth pattern with mass effects. Cabergoline was started at a dosage of 0.5 mg weekly and progressively increased as necessary up to 3.5 mg weekly. Patients were followed up with hormone measurements, sellar magnetic resonance imaging, and vision examinations.ResultsThe study group included 10 patients (5 male and 5 female), aged 17 to 50 years (mean, 36.1 years), treated for giant prolactinoma. In 8 patients, cabergoline was first-line therapy. Two patients had previously been prescribed bromocriptine, and this regimen was maintained. Mean serum prolactin concentration before treatment was 10789 ± 14278 ng/mL (range, 1256-43 163 ng/mL; reference range, 5-17 ng/mL). Following treatment, levels normalized in 7 patients within 2 to 18 months (mean, 8.8 months) and decreased in 1 patient to a level 3 to 4 times that of normal. Tumor diameter, which measured from 4 to 7 cm at diagnosis, showed a mean maximal decrease of 49.28 ± 18.27%; response was first noted about 6 months after treatment was begun. Seven patients had visual field defects at diagnosis; vision returned to normal in 3 and improved in 4. Testosterone levels, initially low in all male patients, normalized in 3.ConclusionCabergoline should be first-line therapy for aggressive prolactinomas, even in those patients who present with visual field defects. (Endocr Pract. 2010; 16:42-46)     

The combination therapy with bromocriptine and cyproheptadine in patients with acromegaly

The therapeutic efficacy of the combination of cyproheptadine and bromocriptine was studied in 15 patients with active acromegaly showing incomplete GH suppression in response to bromocriptine therapy alone. The mean basal plasma GH was 31.3 +/- 5.5 micrograms/L, and it decreased to 19.0 +/- 3.9 micrograms/L during the single bromocriptine therapy (10 to 20 mg for 2 to 21 months). When cyproheptadine (12 to 16 mg for 8 to 52 months) was added to bromocriptine therapy, plasma GH decreased further (9.4 +/- 3.0 micrograms/L: vs pretreatment, P less than 0.001; vs bromocriptine treatment, P less than 0.005), and GH normalization was obtained in 8 patients. The plasma somatomedin-C levels in these 8 patients (0.3-1.8 U/ml) were within the normal range during the combination therapy. Plasma GH responses to TRH or GHRH were markedly suppressed in 6 patients during the combination therapy compared to pretreatment or during bromocriptine treatment. In addition, a clear reduction in the tumor size was observed in 4 of 7 previously untreated patients during the combination therapy. In conclusion, cyproheptadine has therapeutic efficacy in acromegalic patients who showed incomplete GH suppression in response to treatment with bromocriptine alone. Following the cyproheptadine and bromocriptine combination therapy tumor shrinkage was observed in some patients.     

Hyperprolactinemia and sexual function in men

Male hyperprolactinemia (HPRL) is known to induce different types of sexual dysfunctions. In order to determine the incidence of HPRL among patients referred for sexual dysfunction, serum prolactin (PRL) was assayed in 1053 clinically idiopathic cases. Among 850 cases complaining of erectile impotence, 10 with marked HPRL (1.1%, PRL above 35 ng/ml) were found, of whom 6 cases were associated with a pituitary adenoma. 17 mild HPRL (2%, PRL 20-35 ng/ml) were also found. Among 124 cases with premature ejaculation, 13 (10%) mild HPRL were found. Serum PRL was normal in 51 cases complaining of an ejaculation without orgasm, and 27 patients exclusively complaining of reduced sexual desire. Our results lay stress on the fact that serum PRL must be assayed in every case of clinically idiopathic erectile impotence. Indeed, 5 of the 10 marked HPRL patients would have been misdiagnosed if we had only assayed this hormone when plasma testosterone was below the normal range. Moreover, in order to shed some light on the mechanisms by which HPRL disturbs male sexual function, the sexual behaviour of 17 markedly HPRL males was compared to their serum levels of PRL and testosterone, first before treatment, then at regular intervals during treatment. Our main conclusion is that impotence cannot be totally explained by a decrease in plasma testosterone, because this steroid hormone was within the normal range 7 of the 16 impotent patients. Moreover, when serum PRL was lowered by bromocriptine, 6 patients recovered their potency before plasma testosterone clearly increased, and in 3 of those patients before it reached the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Positive Prolactin Response to Bromocriptine in 2 Patients with Cabergoline-Resistant Prolactinomas

ObjectiveTo describe a positive prolactin response to bromocriptine treatment in 2 patients with cabergolineresistant prolactinomas.MethodsWe report the patients’ clinical presentations, laboratory test results, imaging findings, and clinical courses.ResultsPatient 1 had a 5-mm pituitary microadenoma that was initially diagnosed at age 30 years. After initial diagnosis, she was treated with transvaginal bromocriptine for 9 years and then subsequently went untreated for 2 years. After developing symptoms of amenorrhea, decreased libido, and hyperprolactinemia, oral cabergoline, 0.5 mg twice weekly, was initiated. Her prolactin concentration remained elevated at 80 ng/mL while taking cabergoline. Her prolactin concentration decreased to 13 ng/mL after her regimen was switched to bromocriptine, 5 mg daily. Patient 2 had a 17-mm pituitary macroadenoma that was initially diagnosed at age 15 years. Oral cabergoline was started at 0.5 mg twice weekly and increased to 1 mg 3 times weekly when prolactin levels continued to rise to 340 ng/mL over 18 months. After visual field defects developed, transsphenoidal surgery was performed. One year after surgery, magnetic resonance imaging showed a 6-to 7-mm pituitary adenoma, and there was a gradual rise in serum prolactin. Her serum prolactin concentration continued to rise to 212 ng/mL with increasing tumor size over 3 years. Cabergoline was discontinued and oral bromocriptine was initiated at a dosage of 10 mg daily. After 4.5 months of bromocriptine therapy, her serum prolactin concentration decreased to 133 ng/mL. However, after 2 months, the macroadenoma continued to increase in size and a visual field defect developed, so another transsphenoidal operation was performed.ConclusionsAlthough cabergoline is generally preferred to bromocriptine for the treatment of patients with prolactinomas because of its better tolerance profile and greater effectiveness, in patients with cabergoline-resistant prolactinomas, a bromocriptine trial should be considered a safe, relatively inexpensive, and well-tolerated alternative. (Endocr Pract. 2011;17:e55-e58)     

Prolactin regulation of cryptic prolactin receptors in cultured rat mammary tumor cells

Rat mammary tumors contain a unique class of cryptic cell-surface prolactin receptors that can be unmasked by depleting the cells of energy. These cryptic receptors, which are found in mammary tumors and nonlactating normal mammary cells but not in differentiated mammary tissue, are continuously inserted and rapidly removed from the cell surface. In this report we demonstrate that prolactin regulates the level of cryptic receptors. Treatment of primary cultures of rat mammary tumor cells with prolactin at concentrations between 0.1 and 0.5 ng/ml caused cryptic receptor levels to increase within 24 h, and this increase was maintained for up to 6 days. At prolactin concentrations of 10-50 ng/ml, receptor levels were the same as in cells incubated without hormone, while a decrease in the steady-state level of cryptic receptors was induced within 24 h by 100-500 ng prolactin/ml. Concentrations of 1,000-5,000 ng prolactin/ml caused a rapid, dose-dependent down regulation of cryptic receptor sites. Down regulation at 5,000 ng prolactin/ml was (1) complete (84 +/- 5% reduction) in 1 h; (2) specific for lactogenic hormones; (3) completely reversed within 10 h after prolactin removal; (4) energy dependent; and (5) not blocked by the cytoskeleton active agents cytochalasin B and colchicine or by NH4Cl, which inhibits hormone degradation. We conclude that rat mammary tumor cells have the capacity to auto-regulate cryptic prolactin receptors, a property that supports our notion that such receptors play a role in regulating prolactin responsiveness. The observed pattern of cryptic receptor autoregulation in response to prolactin concentration and time of exposure suggests that a pool of cryptic sites provides these cells with the capacity to respond to prolactin concentrations from pg to microgram/ml, a range well beyond the Kd for the receptor itself. Since prolactin receptors in mammary tumors are not down regulated unless prolactin concentrations are well beyond the saturation point, these cells may have a selective growth advantage over cells in normal mammary tissue.     

Opiate system involvement in the control of LH secretion in diabetic and normoglycemic male rats

The effect of Naltrexone (Nalt), a specific opiate receptor blocker, on LH secretion was studied at frequent intervals during the first hour following treatment. Nalt was injected i.v. by one bolus (1 mg/rat) to diabetic and normoglycemic rats. Blood samples (0.8 ml) were withdrawn at short intervals after injection, through an indwelling cannula. The diabetic rats responded by secretion of LH, which was lower, but not significantly, than that of normal rats, (peak levels 0.74 +/- 0.17 and 0.97 +/- 0.21 ng/ml respectively). After 45 min., LH levels were in the same range as baseline level in the diabetic group; but were still significantly elevated in the control rats. Thus, it can be concluded that in normal rats, as well as in diabetics, LH secretion as a response to Nalt was episodic in spite of Nalt's long half life time. In order to explain the rapid fall in LH levels after Nalt administration, normal rats were injected with a second bolus of Nalt, 2 hours after the first. The second bolus caused only a blunted response of LH secretion. In another experiment, administration of morphine (1 mg/rat) 2 hours after pretreatment with Nalt did not stimulate the prolactin secretion which normally follows morphine treatment. These results indicate that the rapid decrease of LH levels after Nalt treatment in normal rats is not due to absence of the drug in the system. It is suggested that other neural mechanisms, such as the dopaminergic system, are activated during Nalt influence.     

Prolactin enhances production of interferon-gamma,interleukin-12, and interleukin-10, but not of tumor necrosis factor-alpha,in a stimulus-specific manner

Prolactin, an anterior pituitary hormone, has been shown to have a role in immunomodulation. Some reports have shown the importance of prolactin in activating lymphocytes and macrophages, while in hyperprolactinemia patients, prolactin was found to decrease lymphocyte activation and natural killer function. In the present work, at physiological (15ng/ml) and stress-induced levels (30ng/ml) of prolactin, interferon-gamma (IFN-gamma) and interleukin (IL)-12 p70 levels, but not of IL-10 and tumor necrosis factor-alpha (TNF-alpha), increased significantly (p<0.05-0.006) in phytohemeagglutinin (PHA)+lipopolysaccharide (LPS)-stimulated whole blood. However, no such effect was observed at high concentrations of prolactin (100-300ng/ml). In addition, 15ng/ml of prolactin reversed hydrocortisone suppressive effect on IFN-gamma, IL-12 p70, and IL-10 production in PHA+LPS-stimulated whole blood. On the other hand, in LPS-stimulated whole blood, prolactin enhanced significantly (p=0.027) the production levels of IL-10, but not of IFN-gamma, IL-12 p70, and TNF-alpha, in non-concentration-dependent manner. These results suggest that prolactin modulates cytokine response during antigenic response, and this modulation is stimulus specific.     

Bioactivity of plasma prolactin in ovariectomized, diethylstilbestrol-treated Long-Evans and Holtzman rats after thyrotropin-releasing hormone or bromocriptine administration

The objective of this study was to determine the effects of thyrotropin-releasing hormone (TRH) and bromocriptine on plasma levels of biologically active prolactin in ovariectomized, diethylstilbestrol (DES)-treated rats. Female Long-Evans and Holtzman rats were ovariectomized and each was given a subcutaneous implant of diethylstilbestrol (DES). One week later, groups of DES-treated rats were fitted with indwelling intra-atrial catheters, and 2 days later blood samples were withdrawn before and at 1, 2, 5, 10, and 20 min after intravenous administration of TRH (250, 500, or 1000 ng/rat). Blood samples were obtained from other groups at 4 weeks of DES treatment by orbital sinus puncture under ether anesthesia before and at 30, 60, and 120 min after bromocriptine administration (2.5 mg/rat sc). Plasma was assayed for prolactin by conventional radioimmunoassay (RIA) and by Nb2 lymphoma bioassay (BA). Holtzman rats released significantly more prolactin following TRH than did Long-Evans rats when the RIA was used to measure prolactin. However, when the BA was used to assay prolactin in the same samples, the Long-Evans rats released more prolactin than did the Holtzman rats. In addition, the ratio of the BA to RIA values was significantly increased in both strains following TRH, but the greatest increase was observed in the Long-Evans rats, in which the ratio was 4.5 at the peak of the TRH-induced rise in plasma prolactin. Gel filtration chromatography of plasma obtained at 5 min after TRH treatment in Long-Evans rats revealed large molecular forms of prolactin with BA to RIA ratios of 4-5. In addition, monomeric prolactin had a BA to RIA ratio of 2. Bromocriptine treatment reduced prolactin levels in both strains, but the effect was more rapid in Holtzman than in Long-Evans rats. In addition, bromocriptine treatment of Holtzman, but not Long-Evans, rats significantly reduced the BA to RIA ratio of plasma prolactin. The results indicate that TRH and bromocriptine affect the release of biologically active prolactin to a greater extent than prolactin detected by antibody in the RIA, and that Long-Evans and Holtzman rats respond to these secretagogues differently with regard to BA to RIA comparisons.     

血清泌乳素水平对泌乳素瘤患者的临床价值研究

目的:分析术前血清泌乳素水平对泌乳素瘤患者的临床价值。方法:选择2011年1月至2016年12月于青岛大学附属医院行垂体腺瘤切除术且术前测得泌乳素(prolactin,PRL)水平、术后行病理免疫组化染色的垂体腺瘤164例,通过Spearman相关分析PRL水平与肿瘤大小的相关性,通过Kappa值判断PRL水平与病理诊断的一致性。采用ROC曲线获得PRL水平最佳临床诊断临界值。结果:(1)164例垂体瘤患者中,病理诊断单激素PRL瘤25例,主要表现为男性性功能低下及头痛、头晕,女性月经紊乱、闭经、泌乳;(2)术前PRL水平与年龄、性别无显著相关性(P均0.05),与肿瘤大小呈中度正相关(r=0.530,P0.05);(3)以正常范围上限值(23.3 ng/m L)为基线,分别以PRL23.3 ng/mL(1倍)、46.6 ng/m L(2倍)、69.9 ng/ml(3倍)、100 ng/mL、150 ng/m L、200 ng/mL为诊断标准,与病理免疫组化的一致性分析显示PRL69.9ng/m L作为诊断标准时符合率和Kappa系数最高,分别为82.3%和0.533;(4)以病理免疫组化作为诊断金标准作泌乳素瘤ROC曲线,以血清PRL为69.785 ng/m L作为诊断标准时,曲线下面积最大,此时符合率和Kappa系数分别为82.3%和0.553,灵敏度49.1%,特异度98.3%。结论:泌乳素瘤血清学诊断与病理免疫组化诊断一致性较高,血清PRL水平69.9 ng/mL(3倍于正常上限值)是诊断泌乳素瘤的最佳参考值。     

Effect of suppressing prolactin in the mouse on liveweight, food intake and ovulation rate

The involvement, if any, of prolactin in the relationship between appetite and ovulation rate was studied in mice. Injections of 0, 50, 100 or 150 micrograms of bromocriptine were given twice-daily to 46-day-old virgin mice for a minimum of 15 days. Between days 5 and 12 of treatment, mice receiving either 50, 100 or 150 micrograms of bromocriptine consumed 3.1, 4.3 and 6.2 g more food, respectively, than did mice in the control group. Liveweights and liveweight gain, however, were unaffected by bromocriptine injections. From day 0 to 12 of treatment mice grew 0.16, 0.15, 0.21 and 0.16 g/day in the 0, 50, 100 and 150 micrograms bromocriptine groups, respectively, (P greater than 0.05). Plasma prolactin concentrations were suppressed, but ovulation rates were similar in the 50, 100 and 150 micrograms bromocriptine groups compared with the control (median prolactin concentrations and mean ovulation rates were 32.9, 32.5 and 31.6 ng/ml and 14.4, 15.1 and 15.7 ova, respectively, compared with 217.2 ng/ml and 14.9 ova in the control). The results do not support the hypothesis that prolactin directly mediates a relationship between appetite and ovulation rate in the post-pubertal mouse.     

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.     

Long-term Treatment of Galactorrhoea and Hypogonadism with Bromocriptine

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.     

溴隐亭不同给药方案治疗高泌乳素血症女性性腺激素促排卵临床研究

目的:研究溴隐亭不同给药方案在治疗高泌乳素血症(HPRL)女性不育症中的临床疗效,关注其对女性促性腺激素诱导排卵的影响。方法:本研究共纳入60例就诊于我院的确诊为高泌乳素血症不孕不育患者,随机分为两组。分为研究组与对照组:研究组采取先口服溴隐亭调整血清泌乳素水平至正常后予以促性腺激素诱导排卵;对照组采取促性腺激素与溴隐亭同步治疗方案。结果:观察两组患者的促排卵周期数、平均用药天数、雌二醇水平及妊娠率,两组治疗前后的血清泌乳素都显著改善(P0.05);但是两组之间相比,采取溴隐亭药物治疗后诱导排卵的研究组在促排卵、雌二醇水平和妊娠率方面具有显著优势(P0.05)。结论:采用溴隐亭治疗高泌乳素血症患者,调整至正常后再使用促卵泡激素药物促排卵治疗不孕不育具为较优的治疗方案。     

Plasma luteinizing hormone and prolactin in normothermic and hyperthermic ovariectomized ewes

The effect of bromocriptine on concentrations of luteinizing hormone (LH) and prolactin (PRL) as well as the rhythmicity of episodic profiles of plasma LH were investigated in twelve ovariectomized ewes exposed to 3-day trials during which ambient temperature/humidity conditions maintained either normothermia or induced an average of 1.4°C increase of rectal temperature (hyperthermia). In 24 of 48 trials, ewes received twice daily subcutaneous injections of 1 mg bromocriptine beginning at 1900 hr on day 1. Plasma PRL and LH were measured at 10-min intervals for 4 hr on days 2 and 3. Bromocriptine significantly decreased plasma PRL (65 ± 6 vs 5 ± 1 ng/ml), mean plasma LH (11.0 ± 0.2 vs 6.5 ± 0.2 ng/ml) and tended (P < 0.1) to decrease LH rhythmicity. In hyperthermic placebo-treated ewes, plasma PRL was increased (65 ± 6 vs 212 ± 20 ng/ml) and mean LH was decreased (11.0 ± 0.2 vs 8.2 ± 0.2 vg/ml) compared to normothermic, placebo-treated ewes, but there was no effect of hyperthermia on LH rhythmicity. Bromocriptine treatment of hyperthermic ewes decreased mean PRL (212 ± 20 vs 32 ± 9 ng/ml) on both days of sampling although mean levels were significantly higher on day 2 than on day 3(54 ± 14 vs 10 ± 6 ng/ml). Perhaps because mean LH was already inhibited in hyperthermic ewes, bromocriptine did not further decrease mean LH (8.2 ± 0.2 vs 6.6 ± 0.2 ng/ml), but LH rhythmicity was decreased (P < 0.01). There was no significant difference in mean LH between normothermic ewes receiving bromocriptine and hyperthermic ewes receiving bromocriptine (6.5 ± 0.2 vs 6.6 ± 0.2 ng/ml). These results indicate that bromocriptine inhibits PRL and LH secretion in normothermic ewes. In hyperthermic ewes, the inhibitory effect of bromoriptine on PRL was even more pronounced, but the effect on LH release was minimal perhaps because LH was already inhibited by hyperthermia.     

Suppression of luteal function in dogs by luteinizing hormone antiserum and by bromocriptine

Beagle bitches were treated with equine anti-LH serum (ALHS) or the dopamine agonist bromocriptine at selected times during the 2-month luteal phase of the ovarian cycle or pregnancy. After a single injection of ALHS (10 ml, i.m.) at Day 42 of pregnancy (N = 2) or the ovarian cycle (N = 3), progesterone was reduced (P less than 0.05) to 7-24% of preinjection values within 1-2 days, and by 4-8 days returned to levels not different from those in control bitches treated with normal horse serum. Injections of bromocriptine (0.1 mg/kg, i.m.) daily for 6 days caused abrupt declines in progesterone which lasted 6-8 days in bitches treated at Day 8 or 22 of pregnancy (N = 5). In bitches treated at Day 42 of pregnancy (N = 3) or in non-pregnant cycles (N = 4) the bromocriptine treatment caused declines (P less than 0.05) in progesterone which were permanent, extensive (less than 2 ng/ml), and therefore abortive. The declines in progesterone in response to immunoneutralization of LH and to prolactin-lowering doses of a dopamine agonist demonstrate that normal luteal function in dogs requires both LH and prolactin.     

Prolactin is involved in the systemic inflammatory response in myocardial infarction

Prolactin may contribute to an atherogenic phenotype. Furthermore, previous studies have shown that prolactin levels increase in situations of acute stress and inflammation. We therefore aimed to investigate the relationship between prolactin, acute stress and inflammation in patients with myocardial infarction. We performed a case-control study in 40 patients with myocardial infarction and 39 controls, aged 41-84 years. Blood for assessment of prolactin and high sensitive C-reactive protein (hsCRP) was drawn at inclusion, that is, during the acute phase of the event, and 2-3 weeks later. Unexpectedly, prolactin levels at inclusion did not differ between cases and controls (7.0 ng/ml and 6.0 ng/ml, respectively, p=0.28). 2-3 weeks later prolactin levels in cases had not decreased. However, univariate regression analysis indicated that hsCRP is associated with prolactin levels (regression coefficient β 0.11; [95% CI 0.01; 0.21]; p=0.03) in cases during the acute phase of myocardial infarction. Our findings may suggest that prolactin is involved in the systemic inflammatory response, which takes place during myocardial infarction; however, this association may not be strong enough to induce higher prolactin levels in patients with myocardial infarction.     

Bromocriptine in management of large pituitary tumours.

Bromocriptine has an accepted place in the management of small pituitary tumours that secrete either prolactin or growth hormone. The treatment of large tumours with extrasellar extensions is more difficult, however: though surgery is the standard treatment, it is often unsuccessful in returning excessive hormone secretion to normal and may cause hypopituitarism. A prospective trial was undertaken to assess the frequency with which changes in pituitary function and size of large tumours occurs. Nineteen patients were studied before and during treatment with bromocriptine (7.5 to 60 ml/day) for three to 22 months, using contrast radiology and a detailed assessment of pituitary function. Eighteen patients had hyperprolactinaemia and two of these also had raised concentrations of growth hormones; one patient had an apparently non-functioning tumour. In 12 patients (63%) tumour size decreased with bromocriptine and no tumour enlarged. Nine patients had visual-field defects, which improved in seven, becoming normal in five. Pituitary function improved in nine patients (47%) becoming entirely normal in three. Bromocriptine should be the treatment of choice in patients with large pituitary tumours with extrasellar extensions, provided close supervision is maintained.     

Abnormal dopamine sensitivity in some human prolactinomas

In most of human prolactin (PRL)-secreting adenomas, dopamine and dopamine agonists normally suppress the excessive PRL secretion. Nevertheless, a subpopulation of such patients presents a relative insensitivity to the ergot derivative bromocriptine. Six patients with a macroadenoma (n = 5) or microadenoma (n = 1) were considered resistant to bromocriptine which, at a daily dose of 15-60 mg, did not normalize high plasma PRL levels. Culture studies of these adenoma cells showed that: (1) 10(-8) M bromocriptine produced a 32 +/- 16% inhibition of PRL release versus 65 +/- 12% obtained in the same conditions with normal human pituitary cells; (2) sulpiride (10(-6) M) reversed the inhibitory effects of bromocriptine, and (3) the bacterial endotoxins, cholera toxin (10(-11) M) and pertussis toxin (250 ng/ml), respectively, produced a 45-500% increase and a total abolition of bromocriptine-induced PRL inhibition. These observations and recent data of the literature allow to discuss the possibility of receptor or postreceptor defects in such tumors.