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PubMed1989

In vitro short-term effects of SMS 201-995, bromocriptine and TRH on growth hormone cell morphology from human pituitary adenomas.

This study reports, by immunocytochemistry, ultrastructure and morphometry, the in vitro effects of SMS 201-995 (10 nM), bromocriptine (1 microM) and TRH (10 microM) on the morphology of cells from two acromegalic patient adenomas containing immunoreactive growth hormone (GH). By electron microscopy, one tumor presented numerous large secretory granules (densely granulated growth hormone cell adenoma) while they were scarce and small in the other (sparsely granulated growth hormone cell adenoma); fibrous bodies could be seen in the specimen and in vitro. In the sparsely granulated growth hormone cell adenoma, TRH produced an increase in endoplasmic reticulum surface density compared to the other cultures. Bromocriptine increased the number and decreased the secretory granule diameters, while SMS 201-995 produced no significant changes in the same time. In the densely granulated growth hormone cell adenoma, the three substances increased the number of granules. TRH increased the mitochondrial volume density and endoplasmic reticulum surface density (with respect to the other cultures). SMS 201-995 decreased the mitochondrial and lysosome volume densities and endoplasmic reticulum surface density. We conclude that 1) TRH produces in cultured cells of both adenoma types an increase in cellular activity. 2) In cultured sparsely granulated growth hormone adenoma cells, bromocriptine has a stronger inhibitory effect than SMS 201-995. In cultured densely granulated growth hormone cells adenoma, bromocriptine has smaller inhibitory effect than SMS 201-995.

Adenoma↗
PubMedDate not supplied

Bromocriptine-induced hypothermia: D-2 receptor involvement.

Bromocriptine (2-16 mg/kg, i.p.) caused a dose-dependent fall in core body temperature of mice. The hypothermic effect of bromocriptine was decreased by pretreatment of the animals with sulpiride, but SCH 23390, methergoline, phenoxybenzamine, propranolol and atropine did not decrease the response. Administration of reserpine plus alpha-methyl-p-tyrosine prior to bromocriptine injection abolished hypothermia in mice. It is concluded that D-2 dopamine receptors may be involved in bromocriptine-induced hypothermia.

Adrenergic alpha-Antagonists↗
PubMed1989

[A case of bromocriptine-induced interstitial pneumonitis in an iron factory worker exposed to sand dust].

A 62-year-old male, was admitted on Oct. 7, 1987 because of productive cough and dyspnea. He worked for an iron factory, where pneumoconiosis was regarded as an occupational disease, for 40 years. No abnormal finding had been noted on his mass screening chest roentgenograms. He was well until three years ago when hypertension and Parkinsonism were noted. Since then he was treated with beta blockers, L-DOPA, amantadine and bromocriptine. Two weeks before admission, he suddenly complained of dyspnea and productive cough. His chest roentgenograms showed diffuse reticulonodular infiltration in both lung fields. The partial pressure of oxygen of the arterial blood was 65.9 Torr. The first transbronchial lung biopsy obtained from right B8 on Sept. 29, 1987 (before the admission) revealed some epithelioid granulomas and the second biopsy obtained from right B10 on Oct. 14, 1987 demonstrated bronchiolar edema and infiltration of inflammatory cells. Fibrotic changes associated with carbon dust between airways and vessels were also noted. Lymphocyte stimulation index by bromocriptine was 362%, and that by amantadine, 139%, L-DOPA, 150%, respectively. After ceasing the administration of bromocriptine, productive cough, dyspnea and the reticulonodular shadows diminished gradually. These findings strongly suggest that the interstitial pulmonary lesions are bromocriptine-induced interstitial pneumonitis. His occupational exposure to inorganic dust may be a predisposing factor.

Bromocriptine↗
PubMedDate not supplied

[Macroprolactinoma resistant to bromocriptine].

A 24 year old female with amenorrhea-galactorrhea due to a pituitary macroprolactinoma that eventually responded to bromocriptine with improvement of visual fields and intracranial hypertension syndrome is presented. After 2 years of treatment with bromocriptine her symptoms relapsed and she underwent transphenoidal hypophysectomy. The high serum prolactin levels detected initially decreased under bromocriptine to ward normal levels and was not modified after surgery, while gonadotropin production remain scarce. Growth hormone (GH) serum levels despite its normal concentration decreased significantly (p = less than 0.5) after pituitary ablation. We assume that the lack of response to bromocriptine in this case could have been due to a mixed hormonal nature of the tumor without overproduction or clinical expression of GH activity.

Adult↗
PubMed1987

Prolactin secretion after surgery or bromocriptine treatment of prolactinoma.

In prolactinoma patients, the unresponsiveness of prolactin (PRL) to dynamic tests with thyrotropin-releasing hormone (TRH) or dopamine agonist or antagonist drugs suggests that the disease is caused by the failure of central dopaminergic inhibition. The absence of PRL secretory response to dopamine or TRH in prolactinoma patients also may be an effect of the disease. Twenty-six women diagnosed by dynamic tests and radiologic examination as having PRL-secreting adenoma were treated surgically (15) or with bromocriptine (11) and their condition was evaluated one to three years later by TRH, nomifensine, and domperidone tests. Basal PRL levels decreased after surgery and bromocriptine treatment. At the time of the follow-up study, PRL levels were elevated in six of the 15 surgically treated patients and in six of the 11 treated with bromocriptine. Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients. These results indicate that the alteration of TRH or dopaminergic receptors in the regulation of PRL secretion in prolactinoma is related to the disease and disappears when the tumor is removed or treated successfully with bromocriptine.

Adenoma↗
PubMed1977

Gonadotropic responsiveness to clomiphene, LRH, estradiol, and bromocriptine in galactorrheic women.

Twenty hyperprolactinemic patients with galactorrhea were studied to determine their gonadotropic responses to various stimuli. Five women lacked response to gonadotropin following the administration of clomiphene citrate. Ten patients who had luteinizing hormone releasing hormone (LRH) tests before and during bromocriptine administration exhibited varied FSH and LH responses that apparently were unaffected by bromocriptine therapy. A loss of the normal positive feedback of estrogens at the level of the hypothalamus was demonstrated in most patients before and during bromocriptine therapy. Long-term treatment with bromocriptine in 11 women resulted in a decrease of serum prolactin, cessation of lactation in all, and pregnancy in 8. These results suggest that the failure of normal secretion of gonadotropins in hyperprolactinemic women may result from 1) inadequate release of endogenous LRH, and 2) loss of the positive feedback of estrogens, as a result of the same hypothalamic disturbance that provokes the hyperprolactinemia. In turn, the elevated prolactin levels may exert a short-loop negative feedback at the hypothalamic level, inhibiting cyclic gonadotropin release.

Bromocriptine↗
PubMed1988

A nation-wide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease. First interim report in Japan.

Two prospective projects were started in May 1985 to evaluate the long-term effects of bromocriptine in patients with Parkinson's disease. One of the projects is to see if combination therapy with levodopa and bromocriptine is superior to levodopa alone with regard to the prevention of late side effects of levodopa therapy. The other is to see the long-term effects of bromocriptine monotherapy. Patients with Parkinson's disease were allocated randomly to either combination or levodopa group in the first project. Parkinsonian symptoms, disabilities of daily life and severity of late side effects of long-term levodopa therapy were evaluated by a semiquantitative rating scale. This communication represents the first interim report. Methods of the studies and synopsis of the results at the end of the 12th month are described. A total of 702 patients was enrolled in the study (combination therapy, n = 216; levodopa therapy, n = 200, bromocriptine monotherapy, n = 286). At the end of the 12th month, the numbers of patients who dropped out from the study were 19, 16 and 55 in the three groups, respectively. It appears to be too early to make any definite conclusion with regard to which mode of treatment is superior, however, some evidence suggesting a superiority of the combination therapy over levodopa alone was noted in managing wearing-off phenomenon and dyskinesia. As many patients are sticking to the originally intended mode of treatment, it appears to be possible to obtain more meaningful data in several years.

Adult↗
PubMed1987

Double-blind comparison of amantadine and bromocriptine for ambulatory withdrawal from cocaine dependence.

Amantadine hydrochloride and bromocriptine mesylate were compared on a double-blind basis for withdrawal from cocaine dependence. Both amantadine and bromocriptine appear effective in alleviating the symptoms of cocaine withdrawal. In doses higher than previously reported, however, bromocriptine caused enough side effects to produce treatment dropouts; neither drug produced euphoria. Amantadine appears to primarily exert its therapeutic influence by releasing dopamine and norepinephrine from neuronal storage sites that are depleted by chronic cocaine dependence, and bromocriptine acts as a dopamine agonist and stimulates dopamine receptors.

Adolescent↗
PubMed1987

Bromocriptine in an injectable retard form for puerperal lactation suppression: comparison with Estandron prolongatum.

Intramuscular injection of a single 50-mg dose of long-acting bromocriptine microspheres was compared with a single intramuscular dose of an estradiol/testosterone ester combination in a single-blind, randomized study of 54 subjects. Bromocriptine was significantly more effective than the steroid drug in preventing milk flow, and rebound lactation was not observed in any bromocriptine-treated patients. Neither group showed deleterious side effects or significant biologic changes in coagulation parameters. There were no blood pressure or electrocardiographic alterations. Postpartum prolactin suppression was more intense after bromocriptine administration than after steroid therapy.

Adult↗
PubMed1979

Prolactin levels and bromocriptine treatment of short luteal phase.

Moderate hyperprolactinemia was found in 14 of 30 infertile patients with short luteal phase indicating a possible hypothalamic disorder in these patients. While the cycle length was normal, 28 days, late ovulation around day 18 of the cycle was characteristic of these patients. During bromocriptine treatment, 2.5 mg twice daily, ovulation took place earlier and luteal phase became longer irrespective of the basal serum prolactin level. The mean (+/- SEM) duration of luteal phase was 9.9 +/- 0.2 days in control cycles, and 11.7 +/- 0.5 and 12.2 +/- 0.3 days in two successive bromocriptine cycles (P less than 0.001). In patients taking bromocriptine, luteal phase became longer than 11 days in 37 of 60 treatment cycles, but no significant difference was recorded in the circulating progesterone and LH levels during mid- and late luteal phase. Three patients became pregnant and they all had normal baseline serum prolactin concentrations. Our results show that bromocriptine may be effective even when no apparent indication for prolactin suppression can be demonstrated.

Bromocriptine↗
PubMed1986

Bromocriptine reduces growth hormone in acromegaly.

We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT). Serum GH levels were measured after five weeks of bromocriptine mesylate therapy, 20 mg daily (P1), after five weeks without bromocriptine mesylate therapy (P2), and again five weeks following restarting treatment with bromocriptine, 20 mg daily (P3). During the 24-hour profile, the following occurred: (1) mean serum GH level of the group was lower during P1 (20.5 mU/L) and P3 (20.8 mU/L) than P2 (49.6 mU/L); (2) in six individual patients during P1 and P3, there was a significant reduction in the mean serum GH value; and (3) a marked circadian variation in the serum GH value was present both with and without the drug therapy in five patients. During the GTT, the mean serum GH value was lower during P1 (18.4 mU/L) and P3 (16.7 mU/L) than P2 (43.3 mU/L), and in seven individual patients during P1 and P3, there was a significant reduction in the mean serum GH value. Overall, a clear reduction in serum GH values due to bromocriptine was demonstrated. In individual patients, serum GH values during a 24-hour profile and GTT gave similar indications of response.

Acromegaly↗
PubMed1986

Bromocriptine therapy in normoprolactinemic women with unexplained infertility and galactorrhea.

Forty-three women with unexplained infertility and 16 women who ovulated with clomiphene citrate therapy, yet failed to conceive, were evaluated because of the presence of expressible galactorrhea and normal random prolactin levels. The overall mean duration of infertility for these women was 5.68 +/- 0.33 years (mean +/- standard error) and their mean age was 30.20 +/- 0.46 years. Fifty-two of these women had primary infertility. Three treatment protocols were evaluated. Twenty-five women with unexplained infertility (Group A) received low-dose bromocriptine (1.25 to 2.5 mg) at bedtime for the first 18 days of the cycle; 18 women with unexplained infertility (group B) received 100 mg of pyridoxine continuously; and 16 women receiving clomiphene citrate (group C) also received bromocriptine in a manner similar to that for group A. All subjects were followed for six treatment cycles or until pregnancy occurred. The estimated cumulative pregnancy rate after six treatment cycles was 65% for groups A and C, which is significantly higher than the 22% rate for group B (Lee-Desu statistic = 4.66, P = 0.03). Women treated with bromocriptine were 2.3 times more likely to conceive than women treated with pyridoxine. Furthermore, those infertile galactorrheic women whose random prolactin level was greater than or equal to 15 ng/ml were most likely to conceive. Expressible galactorrhea in women with unexplained infertility and high normal prolactin concentrations may serve as a clinical sign indicating those women who may benefit from low-dose bromocriptine treatment administered at bedtime.

Adult↗
PubMed1987

Bromocriptine treatment of neuroleptic malignant syndrome.

Five patients with neuroleptic malignant syndrome were treated with bromocriptine mesylate 7.5-45 mg/day in three divided doses for at least 10 days. Response to therapy was assessed by monitoring vital signs and serum creatine kinase (CK) levels. In addition, a disability score was determined using a scale based on variables assessed on neurologic examinations. In all five patients, significant improvement was noted 24-72 hours after initiation of bromocriptine treatment and was accompanied in four patients by a rapid drop in serum CK levels. Resolution of confusion and mutism was noted within 24-48 hours after treatment. Normalization of vital signs occurred within 48 hours to 4 days, and resolution of extrapyramidal rigidity occurred within 1 week. In two patients, early discontinuation of bromocriptine resulted in relapse of neuroleptic malignant syndrome, which responded to reinstitution of the drug. The results suggest a therapeutic role for bromocriptine in the treatment of neuroleptic malignant syndrome.

Adolescent↗
PubMed1987

[Effect of tamoxifen on the treatment of pituitary adenomas with bromocriptine].

Administration of 2-Br- alpha-ergocryptine (bromocriptine = CB-154) in combination with an estrogen-receptor blocking agent tamoxifen were performed in two patients with prolactinoma and non-functioning adenoma, respectively. Case 1 was a 50-year-old male with hyperprolactinemia, impaired pituitary function and visual disorders, in whom a large invasive sellar mass lesion was disclosed by CT scans, which extended supra- and parasellarly and extracranially into paranasal sinuses and pterygopalatine fossa on the left side. As the effect of bromocriptine therapy was partial in tumor size reduction and decrease of serum PRL level and it could not be gained further improvement except for the well recovered visual acuity, tamoxifen was used together with bromocriptine resulting further reduction of tumor size and normalization of serum PRL level. Unexpectedly the medication was ceased during and after a couple of bypass surgery for angina pectoris, and it was followed by elevation of serum PRL level and regrowth of the sellar tumor as well as impairment of vision. By tamoxifen therapy the visual acuity showed some improvement, but the serum PRL level and the tumor size remained as before. Then the combination therapy with bromocriptine and tamoxifen was started again. Case 2 was a 38-year-old female with three children, who had secondary amenorrhea, galactorrhea, borderline level of serum PRL with impaired pituitary function and visual disorders. Under the diagnosis of a non-functioning pituitary adenoma with supra-sellar extension, a craniotomy was done and intracapsular partial removal of the tumor was made, revealing a chromophobe adenoma in light microscopy and undifferentiated cell adenoma in electron-micrographs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1985

Influence of bromocriptine on plasma prolactin, human placental lactogen, beta-HCG and steroid hormones in early human pregnancy.

To study the role of prolactin in the regulation of the production of 17 beta-oestradiol, HPL, beta-HCG, progesterone, testosterone, delta 4-androstenedione and 5 alpha-dihydrotestosterone, 20 healthy women were given 5 mg of bromocriptine daily for two weeks between 7-9 weeks of normal pregnancy. Plasma HPRL, HPL, HCG, oestradiol, progesterone, testosterone, delta 4-androstenedione and 5 alpha-dihydrotestosterone levels were measured before and one and two weeks after the start of bromocriptine-application, and they were compared with those examined in control groups (18 women). Bromocriptine induced a significant HPRL depression at one week and two weeks. Other hormones, except progesterone, showed no significant differences between two groups. These data suggest that neither maternal hypoprolactinemia nor bromocriptine during normal early human pregnancy interfere with the normal synthesis of sex steroids.

Adolescent↗
PubMed1985

[Bromocriptine treatment of hyperprolactinemia].

In 36 female patients with microprolactinoma was carried out a primary therapy and in 19 patients (10 males, 9 females) with a postoperatively persisting hyperprolactinaemia a secondary therapy with bromocriptine. In close correlation between the PRL-levels and the bromocriptine dose we achieved a normalisation of the hormone levels in the microprolactinomas. A normalisation of the cycle was observed in 80%, a persisting of the galactorrhoea in about 90% and a conception in nearly two thirds of the women. Also in those patients who underwent a secondary therapy in nearly 80% a decrease of the PRL-levels into the normal region developed. In a longterm therapy with bromocriptine a reduction of the dose may become possible, so that controls of the hormone levels are necessary in larger intervals. Most side effects of a bromocriptine treatment are transitory.

Adenoma↗
PubMed1979

[Comparative action of L-dopa and bromocriptine on thyreostimulating hormone (T.S.H.) in primary hypothyroïdism (author's transl)].

The comparative action of fixed I-dopa (500 mg orally) and bromocriptine (2,5 mg orally) doses on T.S.H. of 20 patients (8 men and 12 women) with primary hypothyroïdism was studied. T.S.H. was significantly decreased from first hour with I-dopa (p less than 0.005) and the greater decrease was reached at the second hour. T.S.H. was the thereafter progressively increased and was like basal value at the fifth or the sixth hour of the test. T.S.H. was likewise significantly decreased from first hour with bromocriptine (p less than 0,01), but the decrease was progressive during the six hours and the greater decrease was reached at the sixth hour (p less than 0,005). The decreased T.S.H. was greater for woman than for man as much with I-dopa (p less than 0,005), as with bromocriptine (p less than 0,002). The greater decrease was the same with I-dopa or bromocriptine. These results were comparatively discussed with others. They favoured an inibiting action of dopaminergic axis on T.S.H. secretion in primary hypothyroïdism.

Adult↗
PubMedDate not supplied

Bromocriptine treatment of pituitary adenomas. Evaluation of withdrawal effect.

Forty patients wtih pituitary adenomas, i.e. 22 prolactinomas, 13 acromegalies, 5 non-secreting adenomas, were submitted to bromocriptine therapy 19.3 +/- 1.7 mg/day (mean +/- SEM) (range 7.5-40.0 mg/day) for 5 to 41 months (10.1 +/- 1.31). Remission of the tumoral mass was documented by air tomograms (PETG) or computerized tomograms (CT) in all but one prolactinomas and in 2 mixed HGH and PRL-secreting adenomas. Six empty sella syndromes (ESS) were produced, 4 of them during primary chemotherapy. Serum PRL decreased to normal in all but 3 prolactinomas, and serum HGH levels in 5 out of 13 acromegalies. Bromocriptine withdrawal was followed by a rapid increase of serum PRL into the pathological range, without a rapid reexpansion of the tumoral remnants: GT or surgical exploration of 4 cases, remitted until ESS showed a minimal evolution along 8 months after bromocriptine withdrawal. It is suggested that the antitumoral effect of bromocriptine is specific to lactotrophic cells and at least partially irreversible.

Acromegaly↗