dihydroergotoxine and Pituitary-Neoplasms

Topics: Adenoma; Adrenocorticotropic Hormone; Bromocriptine; Dihydroergotoxine; Dopamine; Drug Administration Schedule; Ergolines; Growth Hormone; Levodopa; Lisuride; Metergoline; Methysergide; Pergolide; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9 ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergoline. Serum OC levels significantly increased after 12 month therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p less than 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Density; Cabergoline; Dihydroergotoxine; Dopamine Agents; Ergolines; Estradiol; Female; Humans; Hyperprolactinemia; Osteocalcin; Pituitary Neoplasms; Prolactin; Prolactinoma

Although it is well known that bromocriptine (BC) is effective in the treatment of functioning pituitary adenoma, this agent sometimes causes severe gastrointestinal side effects. In this study, dihydroergotoxine mesylate (EX), which is composed of ergot alkaloids and is similar to BC, was administered to 11 patients with functioning pituitary adenomas who could not tolerate the adverse effects of BC. Three patients (27%) showed clinical improvement with EX treatment alone (1 to 6 mg/day). In another patient, computed tomography demonstrated tumor shrinkage. The remaining seven patients experienced adverse effects while taking EX. These results indicate that EX is a useful alternative to BC in the treatment of functioning pituitary adenoma, particularly in patients who cannot tolerate the side effects of BC. Moreover, pretreatment with EX appears to reduce the incidence of side effects of BC.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents; Dihydroergotoxine; Drug Evaluation; Drug Tolerance; Female; Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Bromocriptine; Dihydroergotoxine; Drug Administration Schedule; Female; Humans; Pituitary Neoplasms; Prolactin; Time Factors

One tenable hypothesis for the etiology of the development of prolactin-secreting adenomas is that a decrease in inhibitory dopaminergic regulation leads to increased lactotroph proliferation. Dopamine receptors have been repeatedly characterized on prolactin-secreting adenomas using labelled antagonists as ligands; however, no data are available on characterization of the receptor with a dopaminergic agonist. An agonist was utilized as the radioligand in the present study to permit the direct comparison of the pharmacological characteristics of the binding site with the biological response, the inhibition of prolactin secretion. This comparison has never been reported in tissues from the same species. Binding of the dopamine agonist and alpha-adrenergic antagonist [3H]-dihydroergocryptine ([3H]-DHE) to particulate fractions of surgically resected human prolactin-secreting adenomas was high affinity, monophasic, and saturable. Careful characterization of the [3H]-DHE binding by competitions with a large number of dopaminergic and alpha-adrenergic agents revealed the presence of both dopaminergic and alpha-adrenergic binding sites. The presence of a saturable, high affinity alpha-adrenergic binding site was confirmed with the specific alpha-adrenergic antagonist [3H]-WB4101 as a radioligand. Although the rank order of potency for dopaminergic compounds to compete for [3H]-DHE binding was consistent with an interaction with a dopamine receptor, the inhibitory constants (Ki) calculated from the competitions were higher than expected at an anterior pituitary dopamine receptor. This appeared to be due to the lower affinity of these agents at the alpha-adrenergic sites. The observed potency of dopaminergic compounds was inversely related to the number of alpha-adrenergic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adolescent; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adult; Binding, Competitive; Dihydroergotoxine; Dioxanes; Dopamine; Dopamine Antagonists; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Receptors, Adrenergic, alpha; Receptors, Dopamine

The endocrine effects of a relatively potent dopaminergic agent, dihydroergokryptine, have been studied in normal subjects, and in hyperprolactinaemic and acromegalic patients. A single 6 mg oral dose of the drug caused a marked, long lasting fall in prolactin (PRL) plasma levels in healthy subjects, in hyperprolactinaemic patients and in normoprolactinaemic acromegalics. Growth hormone (GH) levels decreased in 1-DOPA - responder, acromegalic patients, but dihydroergokryptine did not affect GH levels in normal volunteers or in 1-DOPA non-responder, acromegalic patients. The PRL- and GH- lowering activity of 6 mg dihydroergokryptine was significantly greater than that of 6 mg dihydroergocristine, and was similar to that of an oral dose of 500 mg 1-DOPA.

Topics: Acromegaly; Adenoma; Adult; Aged; Dihydroergotoxine; Female; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Time Factors

Topics: Acromegaly; Adenoma; Adolescent; Adult; Amenorrhea; Dihydroergotoxine; Dopamine; Female; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Nomifensine; Pituitary Gland; Pituitary Neoplasms; Prolactin

Topics: Adenoma; Adult; Apomorphine; Bromocriptine; Cells, Cultured; Dihydroergotoxine; Dopamine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin