Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
neoplasia syndrome characterized by the occurrence of
tumors in the parathyroid glands, pancreas, and anterior pituitary. Approximately 30-40% of MEN1 patients also have adrenal lesions, such as
hyperplasia, benign
adenoma, and
adrenocortical carcinoma. Most of the cases are hormonally silent. We describe the case of a 60-year-old man with bilateral macronodular adrenal lesions, in addition to parathyroid
tumors, multiple
insulinomas, and non-functioning pituitary microadenoma. Endocrinological tests revealed subclinical
hypercortisolism; midnight
cortisol level rose slightly (8.0 µg/dL), although basal plasma
ACTH and
cortisol levels were within the normal range (19.5 pg/mL and 12.0 µg/dL, respectively). One and 8 mg
dexamethasone suppression tests showed
cortisol levels of 2.3 and 9.8 µg/dL, respectively. (131)I-adosterol scintigraphy under
dexamethasone suppression revealed bilateral adrenal uptake with right-sided predominance. The histological features of the removed right adrenal gland were consistent with
ACTH-independent macronodular adrenal hyperplasia (
AIMAH): immunoreactivity of 17α-hydroxylase was predominantly observed in the small compact cells, while that of 3β-hydroxysteroid
dehydrogenase was exclusively expressed in the large clear cells. The
glucose-dependent insulinotropic
polypeptide (
GIP) receptor was expressed at high levels in compact cells, suggesting that GIP is responsible for the development of
AIMAH. Unilateral small adrenal lesions were detected in the patient's 2 children, who also presented with MEN1 symptoms. Genetic abnormalities in the MEN1, p27, and p18 genes were not found, however, the present case may provide a clue to the understanding of the etiology of MEN1 and
AIMAH.