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Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy

Departments of Public Health and Clinical Medicine (Å.J., T.O.) and Medical Biosciences (Å.J., K.C.), Umeå University Hospital, SE-901 85 Umeå, Sweden; Department of Internal Medicine (H.F.), Boden Hospital, SE-961 85 Boden, Sweden; and Department of Medical Sciences (R.A., B.R.W.), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Address all correspondence and requests for reprints to: Tommy Olsson, M.D., Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, SE-901 85 Umeå, Sweden. Tommy. Olsson{at}medicin.umu.se

Abstract

Dysfunction of the hypothalamic-pituitary-adrenal axis might contribute to metabolic disturbances frequently encountered in myotonic dystrophy. We hypothesized that abnormal adrenocortical sensitivity to ACTH and/or glucocorticoid metabolism could be important in myotonic dystrophy.

We assessed diurnal rhythmicity of saliva cortisol, adrenocortical reactivity by a low-dose (1 µg) Synacthen test, and glucocorticoid metabolism in blood and urine in 42 myotonic dystrophy patients (22 males) and 50 controls (27 males). CTG triplet repeat expansions were quantified by Southern blot.

Diurnal rhythmicity of saliva cortisol was flattened in both men and women with myotonic dystrophy, with significantly increased afternoon/evening levels (P < 0.013). The cortisol response to ACTH was associated with increased (CTG)_n expansions in myotonic dystrophy men and women (P < 0.01). Male myotonic dystrophy patients also had increased activation of cortisol from cortisone by 11ß-hydroxysteroid dehydrogenase type 1. Both men and women with myotonic dystrophy had an increased 5/5ß-reductase ratio (P < 0.05 and P < 0.01, respectively). Cortisol metabolites were related to the genetic defect in myotonic dystrophy men (P < 0.05), whereas ratios reflecting 11ß-hydroxysteroid dehydrogenase type 1 activity in myotonic dystrophy women were positively associated with obesity (P < 0.05).

Increased 11ß-hydroxysteroid dehydrogenase type 1 activity and adrenocortical reactivity to ACTH are related to the genetic defect in myotonic dystrophy men, whereas abnormal glucocorticoid metabolism is associated with alterations in body composition in female myotonic dystrophy patients. These disturbances may explain altered circulating cortisol levels and contribute to features of the metabolic syndrome in myotonic dystrophy.

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