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B. Allolio, W. Winkelmann and F. X. Hipp

Abstract.

In order to evaluate the possible role of endogenous histamine in ACTH secretion we investigated the effect of the H1 antagonist meclastine on plasma ACTH in patients with ACTH hypersecretion. Seven patients with primary adrenal insufficiency (group 1) and 5 patients with ACTH dependent Cushing's syndrome (group 2) were given an iv infusion of meclastine (4.8 mg/90 min). In patients of group 2 plasma ACTH was unaffected by meclastine infusion. However, in patients of group 1 with intact steroid feedback meclastine was followed by a significant drop in plasma ACTH as compared with ACTH levels after saline infusion (46.0 ± 4.6% vs 85.0 ± 7.0%, P < 0.01). These results suggest that histamine is involved in the control of ACTH secretion, possibly by stimulation of CRF release.

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B. ALLOLIO, R. STUTTMANN, W. WINKELMANN, H. FISCHER and U. LEONHARDT

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W. WINKELMANN, B. ALLOLIO, U. LEONHARDT and O. WILCKE

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U. DEUSS, B. ALLOLIO, G. FELTES and D. KAULEN

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F Callies, W Arlt, HJ Scholz, M Reincke and B Allolio

There is no established therapeutic regimen for treatment of hypoparathyroidism during pregnancy. This is due particularly to uncertainty about the use of vitamin D or its analogues, as in animal experiments teratogenic side-effects have been reported. Nevertheless, vitamin D or its analogues are required to control tetany predisposing to abortion and preterm labour. We herein report the course of two pregnancies in a hypoparathyroid woman treated with calcitriol (1,25(OH)2D3). Additionally, we describe the outcome of pregnancy in ten women receiving calcitriol, reported to the Drug Safety Department (DSD), Hoffmann-La Roche AG. A 29-year-old hypoparathyroid woman receiving chronic treatment with calcitriol (0.25 microg/day) and calcium (1.5 g/day) was referred in the 6th week of her first pregnancy. Calcitriol was initially discontinued, but during the 20th week of pregnancy recurrent tetany occurred (serum calcium 1.74 mmol/l). Calcitriol (0.25 microg/day) was added, stabilizing serum calcium around 2.15 mmol/l with 1,25(OH)2D3 concentrations around 60 ng/l (normal range 35-80 ng/l). To maintain normocalcaemia the calcitriol dose was increased to 0.5 microg/day during the 33rd week and to 0.75 microg/day shortly before delivery of a healthy girl in the 3 7th week. During her second pregnancy calcitriol was given initially at a dose of 0.25 microg/day with further adaptation to 0.5 microg/day during the 20th and to 1.00 microg/day in the 31st week. Serum calcium and 1,25(OH)2D3 were continually within the lower normal range. She gave birth to another healthy girl during the 39th week. In eight of the ten pregnancies reported to the DSD no adverse effects of calcitriol (0.25-3.25 microg/day) were seen and healthy babies were delivered. In two retrospectively reported cases, serious adverse events were described: premature closure of the frontal fontanelle, and stillbirth in the 20th week due to complex fetal malformation respectively. However, in both cases the causative role of calcitriol administration remains highly questionable. We conclude that, during pregnancy, management of maternal hypoparathyroidism with calcitriol and calcium is feasible, if the 1,25(OH)2D3 concentrations are adapted to the physiological needs during pregnancy and serum calcium levels are kept in the lower normal range.

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W. WINKELMANN, B. ALLOLIO, R. STUTTMANN, U. DEUSS and M. DOEHN

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W. WINKELMANN, B. ALLOLIO, U. DEUSS and H. M. SCHULTE

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C. JAURSCH-HANCKE, B. ALLOLIO, M. REINCKE and W. WINKELMANN