We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5–30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23000±13 600 mU/1 (range 1500–141000 mU/1; 20 mU/l=1 μg/1) by 37 ± 11 % after 1 week, by 49±9% after 4 weeks, and by 65±11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20–25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.

SummaryOBJECTIVE We investigated the effect of intramuscular injections of long‐acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS Thirty patients with PRL‐secreting pituitary macroadenomas were treated with repeated 4‐weekly intramuscular injections of 50 or 100 mg of a long‐acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n= 7), oral bromocriptine (7), and pituitary Irradiation (2). MEASUREMENTS A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection therafter. RESULTS In all patients PRL was suppressed from a mean ± SEM pretreatment level of 32 620 ± 8680 to 4480 ± 1140 mU/l on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/l) with the first to fourth injection, in three additional patients PRL levels normalized after 8–15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean SEM) decreased to 66 ± 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side‐effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0 6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site.CONCLUSION We conclude that long‐acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long‐term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.

We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50–100 mg depot-bromocriptine at 4-week intervals for 3–24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 ±12.3 μg/l (mean ± SEM) to 19.4 ± 4.7 μg/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.

It is well recognized that starvation and malnutrition are associated with a low-T3 syndrome in man. A similar condition has been observed after intake of a low carbohydrate hypocaloric diet. However, little is known about the influence of iodine on these conditions. Therefore, we evaluated the effect of iodine supplementation on thyroid function before and after a short-term intake of a low carbohydrate diet in normal subjects residing in an iodine-deficient area. The study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5 females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4 days. Eight subjects received 500 micrograms iodine (oral) daily beginning 4 weeks before diet. The control group (n = 8) received no iodine. After iodine supplementation, iodine excretion increased from 52 to 405 micrograms iodine/g of creatinine. Total T4 showed a slight but significant increase (104.2 nmol/l vs. 115.8 micrograms/dl; p < 0.001); fT4 was unchanged. The intake of the hypocaloric low carbohydrate diet resulted in a striking decrease in both total and free T3 and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were not affected in either group. During diet, iodine administration resulted in a decrease of basal TSH from 2.3 to 1.2 mU/l (p < 0.05), delta TSH from 10.3 to 4.5 mU/l (p < 0.01) and delta T3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Summary. objective The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro.measurements After Incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0–2000 μM), radioactive metabolites were separated by thin‐layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium‐labelled precursors to products.results In vitro, ketoconazole showed a significant Inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20‐desmolase (IC50 2 μM), 16α‐hydroxylase (IC50 9 μM), 17α‐hydroxylase (IC50 18 μM), 18‐hydroxylase (IC50 28 μM), and 11 β‐hydroxylase (IC50 35 μM). In the tested concentrations ketoconazole had no Inhibitory effect on the 21‐hydroxylase, the 3β‐hydroxysteroid dehydrogenase and the 20‐hydroxysteroid dehydrogenase component of the C17,20‐desmolase enzyme system.conclusionsThe data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17,20‐desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states.

Prolactin is a 21,500 Dalton single-chain polypeptide hormone but may occur in 50 kDa and 150 kDa molecular variants.

Journal Article Effect of a long-acting injectable dopamine agonist on serum growth hormone levels in acromegaly Get access H Pfingsten, H Pfingsten Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar R Haase, R Haase Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar R Windeck, R Windeck Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar W Reinhardt, W Reinhardt Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar C Jaspers, C Jaspers Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar I Lancranjan, I Lancranjan Sandoz, Basel Search for other works by this author on: Oxford Academic Google Scholar G Benker, G Benker Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar D Reinwein D Reinwein Medizinische Klinik und Poliklinik, Universität Essen Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 120, Issue 3_Supplement, Jun 1989, Page S79, https://doi.org/10.1530/acta.0.120S079 Published: 01 June 1989

We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 17α-hydroxyprogesterone, 11-deoxycortisol and 11-deoxycorticosterone as well as plasma levels of ACTH before and during the oral administration of ketoconazole in five patients with Cushing's syndrome (3 with bilateral adrenal hyperplasia, 1 with adrenal adenoma and 1 with adrenal carcinoma) and in three controls. The influence of ketoconazole on the transformation of3H-17α-hydroxyprogesterone to3H-11-deoxycortisol and3H-cortisol and of3H-11-deoxycortisol to3H-cortisol as well as of3H-11-deoxycorticosterone to3H-corticosterone was also examined in slices or homogenates of normal and hyperplastic adrenal tissue from four patients. Ketoconazole induced a rise of 11-deoxycortisol and 11-deoxycorticosterone, but not of cortisol and inconsistantly of corticosterone which were increased by ACTH. Thus the ratio 11-deoxycortisol/cortisol rose more after ketoconazole than after ACTH and the ratio 11-deoxycorticosterone/corticosterone rose after ketoconazole but fell after ACTH. Plasma ACTH levels were stimulated 2–50 fold by ketoconazole. Incubation studies of adrenal tissue slices with3H-17α-hydroxyprogesterone showed that ketoconazole inhibited the transformation of3H-17α-hydroxyprogesterone to3H-cortisol but not to3H-11-deoxycortisol so that the ratio3H-11-deoxycortisol/3H-cortisol increased 15–80 fold. After incubation of adrenal slices with3H-11-deoxycortisol or3H-11-deoxycorticosterone and ketoconazole, a 2–260 fold increase of the ratios3H-11-deoxycortisol/3H-cortisol and3H-11-deoxycorticosterone/3H-corticosterone were also found.

We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 170~-hydroxyprogesterone, 11-deoxycortisol and 11-deoxycorticosterone as well as plasma levels of ACTH before and during the oral administration of ketoconazole in five patients with Cushing's syndrome (3 with bilateral adrenal hyperplasia, I with adrenal adenoma and I with adrenal carcinoma) and in three controls. The influence of ketoconazole on the transformation of 3H-17~-hydroxyprogesterone to 3H-11-deoxycortisol and 3H-cortisol and of 3H-11-deoxycortisol to 3H-cortisol as well as of 3H-1 l-deoxycorticosterone to 3H-corticosterone was also examined in slices or homogenates of normal and hyperptastic adrenal tissue from four patients. Ketoconazole induced a rise of l l-deoxycortisol and 11-deoxycorticosterone, but not of cortisol and inconsistantly of corticosterone which were increased by ACTH. Thus the ratio 1 l-deoxycortisol/cortisol rose more after ketoconazole than after ACTH and the ratio t 1-deoxycorticosterone/ corticosterone rose after ketoconazole but fell after ACTH. Plasma ACTH levels were stimulated 2-50 fold by ketoconazole. Incubation studies of adrenal tissue slices with 3H-17c~-hydroxyprogesterone showed that ketoconazole inhibited the transformation of 3H-17c~-hydroxyprogesterone to 3H-cortisol but not to 3H-1 l-deoxycortisol so that the ratio 3H-11-deoxycortisol/3H-cortisol increased 15-80 fold. After incubation of adrenal slices with 3H-11-deoxycortisol or 3H-ll-deoxycorticosterone and ketoconazole, a 2-260 fold increase of the ratios 3H-11-deoxycortisol/3H-cortisol and 3H-ll-deoxycorticosterone/3H-corticosterone were also found.