Five Patients with Biochemical and/or Clinical Generalized Glucocorticoid Resistance without Alterations in the Glucocorticoid Receptor Gene

Cortisol resistance (CR) is a rare disease characterized by a generalized reduced sensitivity of end-organs to the actions of glucocorticoids (GCs).GC effects are mediated by the GC receptor (GR).The molecular alterations in CR described thus far were located in the hormone-binding domain of the GR gene.Recent reports of a considerable prevalence of abnormalities in the GR in patients attending the endocrine clinic prompted us to carry out further investigations with respect to GR protein and GR gene in patients attending the endocrine clinic for a broad spectrum of complaints and biochemical evidence suggesting a CR.In the present study, we describe five patients with biochemical and clinical CR.All patients showed a diurnal rhythm of serum cortisol concentrations (albeit at a high level), an insufficient suppression of serum cortisol concentration in reaction to 1 mg dexamethasone (DEX), and variable degrees of androgen overproduction, in the absence of clinical signs and symptoms of Cushing's syndrome.Three of the four female patients presented with complaints of androgen overproduction, two of them in combination with fatigue.The other female patient had severe steroid-resistant asthma.The only male patient and his son were asymptomatic.