Limitations of Basal Cortisol in the Diagnosis of Cushing Syndrome

Abstract

Cushing syndrome (CS) is one of the most challenging diseases to diagnose due to the difficulties that may arise during laboratory test interpretations. A random serum cortisol level is often obtained by a general practitioner as a first step in the work-up of suspected CS patients. In this respect, it is rarely useful and has limitations. We report an extremely unusual case of a female patient who presented with adrenocorticotropic hormone-independent CS and corticosteroid-binding globulin (CBG) deficiency. The patient was initially misdiagnosed with and treated for adrenal insufficiency because of persistently low basal cortisol levels, in detriment of her exacerbated Cushing features and symptoms. We describe the limitations of using basal cortisol in the diagnosis of CS and review the differential diagnosis of patients with CS who have low basal cortisol. CBG variants may explain the findings of high urinary and salivary cortisol, in the absence of increased serum cortisol.