A Case for Avoiding Unwarranted Surgery: A Patient with Primary Macronodular Adrenal Hyperplasia (PMAH) Initially Presenting As a Unilateral Adrenal Incidentaloma

Presentation Number: MON 403
Date of Presentation: April 3rd, 2017

Pejman Cohan1, Precious J. Lim*2 and Anne L Peters3
1Specialized Endocrine Care Center, Beverly Hills, CA, 2Corcept Therapeutics, Menlo Park, CA, 3Keck School of Medicine of the University of Southern California, Los Angeles, CA


Background: “Subclinical” Cushing Syndrome (SCS), controversial in name, definition and management, is often described as autonomous cortisol secretion associated with an adrenal adenoma without overt signs of cortisol excess. This can lead to unrecognized long-term exposure to cortisol excess with potentially deleterious metabolic, cardiovascular and skeletal consequences. Historically, there have been few reports of medical treatment for this condition.

We describe a patient with Primary Macronodular Adrenal Hyperplasia (PMAH) who likely had longstanding undiagnosed cortisol excess and ultimately underwent unnecessary surgery. She was then effectively treated with mifepristone (MIFE), a glucocorticoid receptor (GR) competitive antagonist.

Case: A 71 yo woman with a hx of nephrolithiasis, T2DM (BMI 18.8 kg/m2 at diagnosis; no family history; A1C 6% on metformin), easy bruising, and osteoporosis underwent an abdominal CT scan for hematuria, disclosing a 1.7 cm left adrenal nodule.

Physical examination was notable only for lower extremities bruising.

Hormonal labs: UFCs (116, 32, 69, 74, 57, 77 µg/day, ULN <50 µg/day), salivary cortisol (14, 6.7 nmol/L, ULN <4.3 nmol/L), 1-mg DST (18 μg/dL, ULN <1.8 μg/dL, dexamethasone 321 ng/dL nml:180-550 ng/dL), AM serum cortisol (19.1 μg/dL), AM ACTH (13 pg/mL), and DHEA-S (82 μg/dL ULN<111 μg/dL). A1C worsened to 7.9% at presentation.

Patient opted for a second opinion at a tertiary center where serial HPA axis tests were equivocal.

MIFE (300 mg/day) was started but stopped after 1 wk due to fatigue, dizziness, low K+ 3.4 mEq/L [3.5-5.0 mEq/L], hypertension, and bilateral pedal edema.

Patient subsequently elected to undergo left laparoscopic adrenalectomy, which was performed w/o complications. Pathology revealed macronodular adrenal hyperplasia with a predominant nodule.

Postoperatively, she developed fatigue and dizziness, and hydrocortisone replacement was initiated.

After 4 wks, no improvement in AM cortisol levels was observed and hydrocortisone was halted.

After 6 mos, A1C worsened to 8.1% with no improvement in excessive bruising.

MIFE was restarted at 300 mg/week and gradually increased to 300 mg three times a week (TIW). She developed fatigue (resolved w/o intervention) and TSH elevation (normalized on levothyroxine). After 8 mos, A1C decreased to 6.7% w/o dieting and she remains on MIFE 300 mg TIW.

Conclusions: Clinically relevant autonomous cortisol secretion can occur even without global symptoms of cortisol excess. In this patient, GR antagonism with low dose MIFE was well tolerated and elicited metabolic benefits. Medically modulating the underlying cortisol excess may be an option for patients w/ SCS in whom surgical benefit is uncertain, particularly those who potentially have bilateral adrenal disease.


Disclosure: PC: Consultant, Corcept, Speaker Bureau Member, Corcept, Speaker Bureau Member, Pfizer, Inc.. PJL: Employee, Corcept. ALP: Ad Hoc Consultant, Abbott Laboratories, Ad Hoc Consultant, Eli Lilly & Company, Speaker Bureau Member, Eli Lilly & Company, Investigator, Dexcom, Ad Hoc Consultant, Jansen Pharmaceuticals, Advisory Group Member, Lexicon Pharmaceuticals, Inc., Ad Hoc Consultant, Merck & Co., Ad Hoc Consultant, Novo Nordisk, Speaker Bureau Member, Novo Nordisk, Ad Hoc Consultant, Sanofi, Speaker, Roche Diagnostics, Ad Hoc Consultant, Medtronic Minimed, Ad Hoc Consultant, Boehringer-Ingelheim, Ad Hoc Consultant, Omada Health.