A case of primary glucocorticoid resistance

A 79-year-old woman developed hypokalemia and metabolic alkalosis after breast cancer surgery. She was suspected of having primary glucocorticoid resistance on the basis of high plasma ACTH and serum cortisol levels without the features of Cushing's syndrome. To clarify the end-organ resistance to cortisol, we characterized the glucocorticoid receptors (GR) in cultured skin fibroblasts from the patient. The GRs in whole cell assays decreased binding affinity (Kd = 11.1 +/- 0.6 nM) and the number of binding sites for [3H]dexamethasone (binding capacity was 15,600 +/- 1,255 sites per cell). These results strongly suggest that our patient had primary glucocorticoid resistance caused both by a decreased number of GRs and a reduction in the affinity of GRs to cortisol.