dironyl and Pituitary-Neoplasms

Hyperprolactinemia can successfully be treated by dopaminagonists such as bromocriptin or lisuride. About 10% of patients complain about side effects like orthostatic hypotension, nausea or vomiting, which may lead to discontinuation of treatment. We therefore conducted a study using terguride--a new dopaminagonist--in 5 patients with hyperprolactinemia and intolerable side effects under conventional treatment. Terguride is the transdihydroderivative of lisuride (Dopergin). We treated 5 patients, 2 men with macroprolactinoma and 3 women with microprolactinoma with terguride. The mean duration of treatment was 15.6 months (7-37 months). Patients were treated with up to 5 mg terguride daily. All 5 patients had a marked initial decrease of elevated prolactin levels 8 h after administration of 0.25 mg terguride orally. Three patients became normoprolactinemic after sufficient increase of the dose of terguride, 2 female patients with a microprolactinoma got eumenorrhoeic thereafter. The treatment with terguride was tolerated without side effects by all patients. There were no significant changes of the examined parameters of clinical chemistry nor the other pituitary hormones. Results of cranial computertomography did not change in 4 patients, one patient had tumor progression. Tergurid as a dopaminagonist is an effective inhibitor of prolactin with little side effects and thus a useful drug in the treatment of hyperprolactinemia.

Topics: Adult; Clinical Trials as Topic; Dose-Response Relationship, Drug; Ergolines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies

A 48-year-old female presented with a sudden onset of headache and visual impairment. Nineteen years before, she had undergone a transsphenoidal surgery for a prolactin producing pituitary adenoma at our hospital without intraoperative arterial bleeding. On arrival, she exhibited dilated pupils and loss of bilateral visual acuity, but improved immediately after all examinations. MRI revealed a pituitary tumor with intratumoral hemorrhage, intraventricular hemorrhage and subdural hemorrhage. Cerebral angiography revealed a left intracavernous carotid artery aneurysm. Her medical history and radiological findings suggested the rupture of a de novo aneurysm causing a hemorrhage into a pituitary adenoma mimicking pituitary apoplexy. Endovascular occlusion of the aneurysm was performed by use of platinum coils. Because of rapid improvement of visual acuity, administration of terguride was chosen for shrinking the pituitary adenoma. If a pituitary adenoma is present, the possibility of a coincidental aneurysm should always be considered. This association should be kept in mind when evaluating any case of pituitary apoplexy.

Topics: Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Hemorrhage; Diagnosis, Differential; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Lisuride; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Rupture, Spontaneous

A 23-year-old female with polycystic ovary syndrome (PCOS) and a growth-hormone (GH)-producing pituitary adenoma is described. A reduction in the elevated GH levels to normal levels following the administration of dopaminergic agents decreased plasma insulin-like growth factor (IGF)-1 and ovarian dysfunction. Menstrual cycles were therefore restored and the number of ovarian cysts reduced, suggesting that insulin and/or IGF-1, stimulators of theca cell proliferation, may be pathogenetic factors in PCOS.

Topics: Acanthosis Nigricans; Acromegaly; Adenoma; Adult; Bromocriptine; Dopamine Agents; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lisuride; Magnetic Resonance Imaging; Menstrual Cycle; Ovary; Pancreatic Function Tests; Pituitary Function Tests; Pituitary Neoplasms; Polycystic Ovary Syndrome; Theca Cells

We evaluated the results of medical treatment for male prolactinomas. We encountered eight patients with male prolactinomas. The age was 25 to 54 years old (mean 43 years) and the chief clinical symptoms were visual acuity/field defect in three patients, pituitary apoplexy in one patient, disturbance of ejection in one patient, generalized convulsion in one patient, headache in one patient and general fatigue in one patient. The serum prolactin level was 279 to 7,360 ng/ml (mean 2,832 ng/ml). The tumors in all patients were large with a mean diameter of 34.9 mm (range, 21 to 43 mm). In only one patient, the operation was performed due to pituitary apoplexy. All the patients were treated by medication, with bromocriptine being used in seven patients and terguride in one. The follow-up period was 0.8 to 13 years (mean 5.9 years) and, in all patients, the medical treatment was continued. The tumor decreased in size in all patients and the serum prolactin level at the last follow-up observation was 0.5 to 70.5 ng/ml (mean 26.9 ng/ml). All the neurological symptoms disappeared in the early stage of treatment. As for the complications of medical treatment; in one patient, orthostatic hypotension occurred during the initial administration of bromocriptine and one patient suffered CSF leakage two months after the administration of bromocriptine, so the repair of the sella floor by transsphenoidal surgery was necessary. The medical treatment for male prolactinomas is effective for a long term and should be the primary treatment for the male prolactinomas. In conclusion, patients can maintain a good quality of life for a long time by using dopamine agonists.

Topics: Adult; Bromocriptine; Dopamine Agonists; Humans; Lisuride; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prolactin; Prolactinoma

Prolactinomas found in male patients show distinct clinical features compared to those in female patients, which may warrant a different treatment strategy.. To clarify their clinical features and to evaluate the treatment results, specifically the results of surgical treatment and non-surgical treatment solely with oral bromocriptine, we retrospectively reviewed our experience in male prolactinoma cases.. From 1988 to 1998, we had 184 pituitary adenoma patients, and thirteen of those were male patients with a pure prolactinoma. Of the thirteen patients, eight underwent transsphenoidal surgery followed by oral bromocriptine (surgical group), and five were treated solely with bromocriptine or terguride (non-surgical group). In both groups, the visual symptoms and signs resolved after the treatment, and the serum prolactin levels were normalised with minimal maintenance dose of bromocriptine. Notably, improvement of the visual symptom in the three non-surgically treated patients was observed within a week following the bromocriptine administration.. Although surgery would continue to play an important part of treatment in some cases with a large tumour, our experience suggests that drug treatment without surgery can be a safe and effective option in the management of male prolactinoma patients.

Topics: Adult; Bromocriptine; Decompression, Surgical; Dopamine Agonists; Hormone Antagonists; Humans; Libido; Lisuride; Male; Middle Aged; Optic Chiasm; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome; Visual Fields

The effects of bromocriptine and terguride on the estrogen-stimulated anterior pituitary gland of the female Wistar rat were investigated. Pituitary weight and serum prolactin (PRL) levels were reduced by treatment with bromocriptine or terguride. Immunohistological staining for proliferating cell nuclear antigen (PCNA) revealed that the PCNA labeling index of PRL-producing cells was significantly decreased by treatment with bromocriptine or terguride compared with untreated cells. The number of apoptotic cells analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate-biotin nick end labeling method was significantly increased in rats treated with bromocriptine or terguride. Suppression of cell proliferation and induction of apoptosis are important effects of bromocriptine and terguride in the treatment of prolactinomas and other hyperprolactinemias.

Topics: Animals; Apoptosis; Bromocriptine; Cell Division; Cell Migration Inhibition; Dopamine Agonists; Estradiol; Female; Hormone Antagonists; Lisuride; Neoplastic Cells, Circulating; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar

Terguride, a derivative of the ergot alkaloid, was characterized as a new anti-hyperprolactinemic agent in rats and dogs in comparison with bromocriptine. Terguride was found to bind selectively to the pituitary dopamine D2-receptors with a high affinity (Kd = 0.39 nM). In reserpinized rats, terguride at 0.03 mg/kg, p.o. significantly reduced the serum prolactin (PRL) level. The PRL lowering effect and the effective dose were longer lasting and about 30 times lower than those of bromocriptine, respectively. In rats bearing estrogen-induced pituitary prolactinoma, chronic terguride induced shrinkage of the prolactinoma as well as reduction of the high serum PRL level. In lactating rats, terguride (1.0 mg/kg, s.c.) reduced milk production in the mammary gland, whereas bromocriptine showed no significant effect up to 10 mg/kg, s.c. Terguride (10 mg/kg, p.o.) did not induce any stereotypy and hypermotility in reserpinized rats, while bromocriptine induced both stereotypy and hypermotility significantly at 10 mg/kg, p.o. In dogs, terguride, like bromocriptine, reduced the serum PRL level, but did not affect the serum levels of growth hormone and luteinizing hormone. In dogs, bromocriptine induced both emesis and PRL-lowering at almost the same dose, whereas emesis-inducing doses of terguride were about 100 times higher than the PRL-lowering dose. These results suggest that terguride as a dopamine D2-agonist is a potent inhibitor of PRL secretion with less neurotropic side effects compared to bromocriptine, and thus a useful drug for the treatment of galactorrhea and hyperprolactinemia including prolactinoma.

Topics: Animals; Bromocriptine; Dogs; Dopamine Agents; Estradiol; Female; Glutathione; Hyperprolactinemia; Lactation; Lisuride; Luteinizing Hormone; Male; Motor Activity; Pituitary Neoplasms; Prolactinoma; Rats; Rats, Wistar; Receptors, Dopamine D2; Reserpine; Stereotyped Behavior; Vomiting

MMQ cells, a prolactin-secreting cell line possessing dopamine receptors, were exposed to the calcium channel activator maitotoxin and dopamine or adrenoceptor agonists or antagonists. Dopamine (500 nM) or the dopamine agonists lisuride (50 nM), terguride (50 nM), and N-0437 (50 nM) decreased maitotoxin-stimulated prolactin release from perifused MMQ cells. In this system, sulpiride (100 nM), a dopamine D2 antagonist, reversed the prolactin inhibition produced by lisuride (20 nM). In static incubations of MMQ cells, lisuride (10-500 nM) inhibited maitotoxin-stimulated prolactin release in a concentration-dependent manner; this inhibition was attenuated in a concentration-related manner by sulpiride (100-500 nM). In addition, sulpiride reversed dopamine (50-500 nM), lisuride (10-500 nM), and terguride (50-500 nM) inhibition of forskolin-stimulated cAMP generation. The alpha 2-adrenergic agonist clonidine inhibited maitotoxin-stimulated prolactin release from perifused MMQ cells; this inhibition was abolished by idazoxan, an alpha 2-adrenergic antagonist. In contrast, serotonin or the serotonin antagonist methysergide had no effect on prolactin release from MMQ cells. These data indicate that activation of dopamine D2 receptors and alpha 2-adrenoceptors by classically defined pharmacological agents inhibits prolactin release and cellular cAMP levels in MMQ cells. Therefore, MMQ cells may provide a valuable model for the development of pharmacological agents and assist in the identification of the mechanisms involved in the dopaminergic inhibition of prolactin release.

Topics: Adrenergic Agonists; Cyclic AMP; Depression, Chemical; Dopamine; Humans; Lisuride; Marine Toxins; Oxocins; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Tumor Cells, Cultured

Two patients with macroprolactinomas were treated with the partial dopamine agonist, terguride. The prolactin (Prl) levels were lowered very effectively and in both cases the clinical symptoms improved markedly during the first days of treatment. Computerized tomography (CT) and magnetic resonance imaging (MRI) follow-up studies showed distinct tumour shrinkages which were first documented by MRI within 2 weeks of treatment. Tumour residues were, however, still demonstrable by MRI after more than one year respectively 3 months of therapy. In principal, results from both imaging techniques were comparable with the exception of the one year follow-up study of patient 1. In CT no residual tumour mass was visible whereas MRI showed only little reduction when compared to the 30th week scan. Throughout the treatment terguride was well tolerated without any side effects up to a maximal daily dosage of 3 mg given orally. Presumably the partial agonistic features of terguride contributed to the good tolerance of the treatment as compared to that of full dopamine agonists like bromocriptine of lisuride. Thus, these preliminary results indicate that terguride may be a beneficial alternative in the treatment of prolactinomas and other hyperprolactinaemic states.

Topics: Adenoma; Adult; Ergolines; Female; Follow-Up Studies; Humans; Lisuride; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Thyrotropin-Releasing Hormone; Tomography, X-Ray Computed

The pharmacokinetics of oral terguride 1 mg was evaluated in a single-dose study in 8 patients with a prolactinoma and one with acromegaly. A radioreceptor assay was used to measure the plasma levels of terguride. The peak plasma concentration (2.3 +/- 0.7 ng/ml, mean +/- SEM) was attained within 1 h of drug administration. Moment analysis gave a mean residence time of 4.3 +/- 0.6 h. Plasma prolactin was also determined by radioimmunoassay. The plasma prolactin was reduced to 30 +/- 3% of its pretreatment value after 4 h.

Topics: Acromegaly; Adult; Ergolines; Female; Half-Life; Humans; Kinetics; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin

The long term effectiveness and tolerance of terguride, a new ergot derivative, as initial therapy were evaluated in 20 patients with pathological hyperprolactinemia (PHP; group A) and 7 patients with acromegaly. We also studied 10 patients with PHP whose treatment was changed from bromocriptine or lisuride to terguride (group B). Terguride, given for at least 6 months in divided doses ranging from 0.25-1.50 mg/day to group A patients, resulted in normal (11 patients) or markedly reduced plasma PRL levels. Gonadal function was restored in all but 2 patients in this group, and the tumors shrank in 3 of 5 patients with a macroprolactinoma and in 1 of 3 patients with a microprolactinoma. In group B patients, positive effects of the previous treatment on PRL levels, gonadal function, and tumor growth were maintained by terguride. Terguride suppressed plasma GH levels below 50% of baseline in 4 of the 7 acromegalic patients. Two of the 27 patients initially treated with terguride complained of mild nausea and postural hypotension only after the first dose (0.25 mg) of the drug. No patient in group B had any side-effects during terguride, with the exception of 1 patient who was also intolerant to bromocriptine. We conclude that terguride is an effective well tolerated dopaminergic agent in PHP.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Menstruation; Middle Aged; Pituitary Neoplasms