Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyce ridemia, increased fat mass, and dysregulation of the hypothalamic-pituitar y-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alp ha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and deh ydroepiandrosterone in 18 men with adult onset RID and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insul in were also determined. Genetic analyses were performed, including calcula tion of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), A CTH (P < 0.05), and cortisol (P < 0.05)were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The d iurnal rhythms of these cytokines/hormones were disturbed in patients. Morn ing testosterone levels were decreased and insulin levels increased (P < 0. 01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testoste rone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulati on is disturbed in MD. Adiposity may contribute to these disturbances, whic h may be of importance for decreased adrenal androgen hormone production an d metabolic, muscular, and neuropsychiatric dysfunction in MD.