Endocrine Abstracts (2006) 11 P51

Isolated ACTH deficiency following long-term benzodiazepine treatment

K Müssig1, E Friess2, K Mörike3, H-U Häring1 & D Overkamp1


1Department of Endocrinology, Metabolism and Pathobiochemistry, University Hospital of Internal Medicine, University of Tübingen, Tübingen, Germany; 2Max Planck Institute of Psychiatry, Munich, Germany; 3Division of Clinical Pharmacology, University Hospital of Tübingen, Tübingen, Germany.


Objective: Benzodiazepines are among the most commonly used symptomatic treatment of insomnia and anxiety. Human and animal studies suggest that benzodiazepines suppress the hypothalamo-pituitary adrenal (HPA) axis. We report on a rare case of isolated ACTH deficiency due to long-term treatment with flunitrazepam.

Case report: A 66-year-old man presented to our outpatient department with persistent feelings of physical exhaustion, low vitality, reduced daily acitivities during the last 2 months. The patient’s past medical history revealed a continuous intake of 1 mg flunitrazepam daily over the past 35 years because of sleep disturbances following a severe car accident. According to a psychiatric interview with an experienced clinical psychiatrist there was no present or past history of other psychiatric disorders else than a low-dose dependency of hypnotics (DSM-IV 304.10). Decreased basal concentrations of plasma ACTH, serum cortisol, as well as mean 24-h urinary free cortisol excretion, a blunted response of ACTH and cortisol levels to intravenous application of 100 μg CRH, and concentrations of the other anterior pituitary hormones within the normal range were consistent with secondary adrenal insufficiency due to an isolated ACTH-deficiency. Magnetic resonance imaging of the pituitary gland revealed no abnormal findings. Immunological studies, including CNS specific and thyroid antibodies, were negative. After tapering from the benzodiazepine treatment we observed a stable increase to normal levels of the serum and urinary concentrations of cortisol and plasma levels of ACTH. The patient suffered from a mild benzodiazepine withdrawal syndrome. However, at the end of the tapering period he reported a clear improvement in vitality.

Conclusion: Clinicians should be alert of possible inhibiting effects of benzodiazepines on the HPA axis in patients with suspected dysfunctions of the corticotroph function.

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