Cushing's Syndrome Due to Bilateral Cortisol-Secreting Adenomas with Unilateral DHEAS over-Secretion. a Case Report

Presentation Number: SUN-0782
Date of Presentation: June 22nd, 2014

Satoshi Monno*1, Takamitsu Tachikawa2, Takashi Maekawa3 and Hironobu Sasano3
1Chiba-Nishi General Hosp, Matsudo, Japan, 2Chiba-Nishi General Hospital, Matsudo, Japan, 3Tohoku University Graduate School of Medicine, Sendai, Japan


Background: Cushing’s syndrome due to bilateral cortisol-secreting adenomas with unilateral DHEAS over-secretion has not been reported.

Clinical case: 39yo female manifested typical clinical symptoms of Cushing’s syndrome (CS) including amenorrhea for 2 years and hirsutism.  Results of initial endocrine evaluation were consistent with ACTH independent-CS including elevated 24Hr urinary cortisol secretion (469 μg/d, n <50 μg/d), abnormal LDDST (cortisol after 1mg dex 30.2 μg/dL, n <5 μg/dL ), elevated mid-night serum cortisol (18.9 μg/dL , n<5.2 μg/dL), ACTH-concentration below the level of detection (<1 pg/ml).  Serum DHEAS concentration was also elevated (6901 ng/ml, n 230-2660 ng/ml).  An abdominal CT-scan demonstrated bilateral adrenal enlargement (diameter of adrenal glands, right 3.1cm,left 2.4cm).  131I-methylnorcholesterol incorporation into both glands with left higher uptake than right adrenal, suggesting bilateral oversecretion of cortisol. 

Laparoscopic adrenalectomy of both side were performed separately; left adrenalectomy first, then right adrenalectomy in 3 months later.   Following the left adrenalectomy, results of endocrine evaluations were consistent with ACTH-independent CS.  Serum DHEAS concentration, however, was below normal range (143 ng/ml, n 230-2660 ng/ml).  Unexpectedly, her menstruation resumed 2.5 months after left adrenalectomy (before right adrenalectomy).  Pathological examination of the resected adrenal glands showed bilateral adrenocortical adenomas, one in left 3cm in diameter, and two in right 0.7cm and 1.3cm in greatest dimension, with adjacent atrophied zona fasciculate and reticularis.  These three adenomas were all mainly composed of compact cell, with pronounced expression of SCC, 3βHSD, 17-OH-lase and CYP11B1 suggesting overproduction of cortisol.  In the left adenoma, DHEAST positive dysmorphic cells with abundant eosinophilic cytoplasm were pronounced but the two adenomas of right adrenal were associated with mainly compact cells with weak DHEAST immunoreactivity in one adenoma and compact cells intermingled with clear cells in another adenoma.  CYP11B2 was positive only in right adenomas, but negative in left adenoma, suggesting the presence of aldosterone production in right adenomas. Ki67 labeling index was higher in the left adenoma (2.5%) than the right adenomas (1.5%).  These results indicated more pronounced cell proliferation and DHEAS production in the left adenoma compared to the right adenomas, consistent with clinical endocrine findings.

Conclusion: This is the first case demonstrating bilateral cortisol-secreting adenomas with unilateral over-secretion of DHEAS , and with resumption of menstruation by removing DHEAS producing site. Immunohistochemical evaluation of steroidogenic enzymes could provide clinically relevant inert information as to the neoplastic steroidogenesis.


Nothing to Disclose: SM, TT, TM, HS