Partially autonomous cortisol secretion by incidentally discovered adrenal adenomas

Recent studies of the function of adrenal "incidentalomas" have revealed that a proportion of those tumors secrete cortisol insufficiently to produce overt clinical Cushing s syndrome, but that their autonomous cortisol production can suppress the hypothalamo-pituitaryadrenal (HPA) axis to various degrees; this needs to be recognized to avoid acute adrenal insufficiency after adrenalectomy. Several diagnostic approaches have been utilized to identify the partially autonomous cortisol-secreting adenomas. It has been suggested that a lack of normal suppression of cortisol (> 140 nmol/L) on the morning after 1-mg oral dexamethasone at bedtime would identify most functional autonomous cortisol-secreting tumors. Based on this criterion, approximately 18% of published cases of incidentalomas would secrete cortisol autonomously. However, other tests indicating alterations of the HPA axis, such as abnormal adrenal iodocholesterol uptake or decreased plasma levels of dehydroepiandrosterone sulfate (DHAS), were found to be present in up to 79%-86% of incidentalomas. This is illustrated by the description of three patients with incidentalomas with plasma cortisol levels < 140 nmol/L in 2 of 3 patients after 1-mg dexamethasone overnight; however, various degrees of HPA axis suppression were demonstrated by an i.v. dexamethasone (4-mg) suppression test, decreased plasma DHAS levels and unilateral adrenal iodocholesterol uptake. After laparoscopic adrenalectomy, the response of plasma cortisol to 250 mug i.v. of ACTH (1-24) was subnormal in 2 of 3 patients and was restored to normal within 2 months. We conclude that the criterion of a plasma cortisol level > 140 nmol/L, after an overnight 1-mg dexamethasone suppression test, underestimates the incidence of partially autonomous cortisol-secreting adrenal adenomas. The literature on this subject is reviewed, and recommendations for evaluation and treatment are presented.