Rhabdomyolysis associated with hyponatremia and adrenal insufficiency

It is well known that severe hyponatremia can cause rhabdomyolysis [1]. However, rhabdomyolysis with hyponatremia associated with Addison’s disease is extremely rare. A 52-year-old man was brought to our hospital with coma and convulsion. On the day prior to admission he had reported general fatigue. He had taken betamethasone (0.5 mg/day) for 7 years because of chronic eczema. His temperature was 38.4 C, pulse was 110 beats/min, and blood pressure was 140/93 mmHg. Laboratory studies showed serum sodium 118 mEq/l, potassium 3.7 mEq/l, chloride 80 mEq/l, and creatine kinase 4735 IU/l (normal range 53–288). Creatine kinase concentrations rose over the next 48 h, peaking at 11 902 IU/l, though the convulsion was subsided. Urinary analysis showed myoglobulinuria and the sediment was loaded with leukocytes. An infusion of 0.9% sodium chloride in water and ceftazidime (2.0 g/day) resulted in increasing plasma sodium to 124 mEq/l and improved the comatose status 24 h later. The creatine kinase concentrations dropped to within its normal range the moment myoglobinuria disappeared. An endocrine examination showed a plasma arginine vasopressin level of 2.4 pg/ml (normal range 0.8–6.3) and serum cortisol and adrenocorticotrophic hormone concentrations (ACTH) at 7:00 AM of 2.6 lg/dl (normal range 3.8–18.4) and 23 pg/ml (normal range 7–56), respectively. The osmolalities of the plasma and urine were 249 mOsm/kg (normal range 276–292) and 642 mOsm/kg (normal range 50–1300), respectively. The cortisol response to an acute ACTH intravenous injection (250 lg) was blunted [Fig. 1a]. While the ACTH level slightly increased in response to an intravenous injection of human corticotrophin-releasing hormone (CRH) (100 lg), the cortisol level barely increased in response to CRH [Fig. 1b]. Thus, a diagnosis of hyponatremia induced by secondary adrenal insufficiency was confirmedby the endocrinological findings. After the patient was given orally a daily dose of 15 mg of hydrocortisone, plasma sodium level was maintained in the normal range and rhabdomyolysis did not recur. This report describes a patient of rhabdomyolysis complicated with hyponatremia induced by adrenal insufficiency. The adrenal insufficiency was likely to be caused by long-standing administration of betamethasone. To our knowledge, only one case of rhabdomyolysis with hyponatremia associated with Addison’s disease is reported [2]. The pathogenesis of rhabdomyolysis due to hyponatremia is thought to be a result of hypo-osmolality of the extracellular fluid, which leads to muscle cell swelling [1]. After the cellular swelling normalizes, as a result of extrusion of intracellular potassium, the potassium-depleted muscle cells then fail to release potassium, and blood flow becomes insufficient. Furthermore, in the potassium-deficient cells, the cellular transmembrane potential is decreased, leading to release of creatine kinase and myoglobin [3]. Recently, de Witte et al.[4] described a patient in which rhabdomyo(a)