The aetiology of
ACTH-independent macronodular adrenal hyperplasia (
AIMAH) is uncertain. We examined a 55 year old man with
Cushing's syndrome due to
AIMAH, whose
cortisol levels increased after stimulation with lysine-8-vasopressin (LVP) in vitro as well as in vivo. Abdominal MRI revealed nodular enlargement of both adrenal glands. No
adenoma was evident on pituitary MRI. 131I-adosterol scintigraphy exhibited marked uptake into both adrenal glands. Although baseline plasma
cortisol levels were within normal limits, urinary free
cortisol excretion was 3-fold higher than the upper limit of the normal range. Plasma
ACTH levels were undetectable. Oral
dexamethasone failed to suppress plasma
cortisol levels irrespective of dose, and administration of
corticotrophin releasing
hormone failed to increase plasma
ACTH and
cortisol levels. LVP injection failed to increase plasma
ACTH levels, but elicited an increase in plasma
cortisol levels. The direct stimulatory effect of LVP on
cortisol secretion was confirmed in vitro in cultured adrenocortical cells from macronodules obtained at surgery. Food intake,
gastric inhibitory polypeptide (GIP), or
octreotide administration, which were reported to regulate
cortisol release in patients with
AIMAH, failed to affect plasma
cortisol levels. In conclusion, plasma
cortisol responsiveness to LVP, GIP, and
octreotide is heterogeneous in patients with
AIMAH.