FAMILIAL ADRENOCORTICOTROPIN-INDEPENDENT CUSHINGS-SYNDROME WITH BILATERAL MACRONODULAR ADRENAL-HYPERPLASIA

Familial Cushing's syndrome is rare, and when it occurs, it is usually associated with primary micronodular dysplasia. We report two cases, a mother and daughter, who each presented with clinical features of Cu shing's syndrome at age 38 yr and were found to have ACTH-independent macronodular adrenal hyperplasia. In each case, bilateral adrenalectom y revealed the massively thickened adrenal cortex with nodules up to 1 .3 cm in diameter and hyperplasia between nodules. Dynamic testing sho wed no suppression of free cortisol with high dose dexamethasone and n o stimulation of 17-hydroxycorticosteroids with metyrapone. Two sample s of serum obtained preoperatively from one patient that showed ACTH i mmunoreactivity of 4.6 and less than 2.2 pmol/L, respectively, each sh owed less than 2.2 pmol/L ACTH bioactivity. The lack of suppression wi th high dose dexamethasone, lack of stimulation with metyrapone, and l ow levels of ACTH immunoreactivity and bioactivity suggest that the bi lateral hyperplasia was not dependent upon ACTH. These patients repres ent the first cases of ACTH-independent macronodular adrenal hyperplas ia occurring in two generations of one family and illustrate the expan ding clinical spectrum of Cushing's syndrome.