Subclinical Cushing's Syndrome Due to ACTH-Independent Macronodular Adrenal Hyperplasia Associated with Possible Mccune-Albright Syndrome

Presentation Number: SUN-0786
Date of Presentation: June 22nd, 2014

Saba Wasim Aziz*1, Deepika Nallala2 and Carmel Maria Fratianni1
1Southern Illinois University School of Medicine, Springfield, IL, 2Springfield Diabetes and Endocrine Center, Springfield, IL

Abstract

Background: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an uncommon cause of glucocorticoid excess, responsible for <1% of cases of Cushing’s Syndrome (CS). AIMAH with cortisol excess associated with McCune-Albright syndrome (MAS) is a rarely reported constellation, although they are allied phenotypes mapping to 20q13.32 with somatic mutations of GNAS1. We present a case of subclinical CS due to AIMAH arising in association with possible MAS.

Clinical Case: A 66 y/o male with h/o early onset puberty, Graves’ disease with postablative hypothyroidism & colonic adenomas was evaluated for incidentally noted bilateral adrenal nodules: 4.6cm on Right and 3.4cm on Left with radiographic features consistent with benign adenomas. Interval radiographic stability had been noted over 3 years time. There was no family h/o adrenal nodules or endocrine hyperfunction. The patient had no clinical features of Cushing’s aside from osteopenia documented by DEXA scan. He gave a clear h/o early puberty, and was “shaving a real beard” by 11 years. No café au lait spots or other lentingines were evident on physical examination which was otherwise unremarkable. Biochemical Evaluation: ACTH levels are repeatedly subnormal: ACTH 5.3, 7.5 pg/mL (10 – 60) with normal range am cortisol 13.0 mcg/dL (8-27.0). AM cortisol levels following 1 mg Overnight Dexamethasone Suppression Testing (ONDST) are reproducibly elevated:  cortisol 4.3, 3.2 and 3.4 mcg/dL (normal<1.8), with simultaneous Dexamethasone level documenting absorption:  Level  230 ng/dL (Expected 8am post 1 mg ONDST: 140 -195). Abnormal cortisol dynamics are documented with salivary cortisol done 12 hours apart, 12Noon & Midnight: Salivary Cortisol 134 ng/dL and 165 ng/dL (normal 7-9am 100-750, Midnight <100). Assessments of 24 hour Urine Free Cortisol have been in the normal or high normal range however: 45 , 43 and 17 mcg/24h [Normal 3.5 to 45]. While 24 hour urine cortisol is not frankly elevated, the inappropriate cortisols following ONDST and abnormal midnight salivary cortisol suggests subclinical CS. In retrospect he gives a history of sexual precocity and atraumatic fracture of left lower leg in childhood with persistent knee, back and hip pains. Radiologies are pending. Endocrine hyperfunction with past hyperthyroidism is also notable and could suggest MAS.

Conclusion: Patient with subclinical CS due to AIMAH should be monitored periodically for development of overt CS. Identification of aberrant receptors could direct a tailored pharmacological approach to control abnormal steroidogenesis; alternatively, unilateral or bilateral adrenalectomy could be considered. CS associated with MAS is a rare variant of AIMAH and should be suspected in patients with sexual precocity, skeletal manifestations and other endocrine hyperfunction.

 

Nothing to Disclose: SWA, DN, CMF