Pitfalls of Using ACTH Alone in the Localization of Cushing's Syndrome

Presentation Number: SUN-0773
Date of Presentation: June 22nd, 2014

Gillian M Goddard*1, Nikolina Babic2, Alice C Levine3, Kalmon D. Post1 and Eliza B. Geer4
1Icahn School of Medicine at Mount Sinai, New York, NY, 2Mount Sinai School of Medicine, 3Mt Sinai Med Ctr, New York, NY, 4Mount Sinai School of Medicine, New York, NY


Background: ACTH levels are often utilized to localize the source of Cushing’s Syndrome (CS), with suppressed ACTH levels suggesting adrenal etiology and detectable or elevated levels suggesting pituitary or ectopic ACTH production. The protocol for determining the etiology of CS when the ACTH value is between 10–20 pg/ml has not been established.

Hypothesis: Single determinations of ACTH in the 10-20 pg/ml range do not distinguish between adrenal and pituitary CS.

Case 1: 36 yo F presented with a 9 month history of irregular menses, acne, hypertension, easy bruising, increasing facial fullness and hair growth.  Physical Exam showed obesity, moon facies, and hirsutism.  Labs revealed an elevated urinary free cortisol (UFC) of 220 mcg/24 hrs (<45 mcg/24 hrs), serum cortisol 21 mcg/dl, ACTH 11 pg/ml, DHEA-S 84 mcg/dl (35-430 mcg/dl) and HbA1c of 5.9%.   After 1 mg dexamethasone, her serum cortisol was 18.8mcg/dl (<1.8 mcg/dl) and ACTH <5 pg/ml.  Adrenal MRI revealed a 3.7 x 2.6 cm right adrenal mass consistent with an adrenal adenoma. She underwent right adrenalectomy.  Post-operative cortisol was 0.8 mcg/dl.

Case 2: 52 yo F presented with new T2DM, weight gain, fatigue, easy bruising, hirsutism, and a recent pelvic and shoulder fracture.  Physical exam showed a round, ruddy face and facial hirsutism. Her UFC was elevated at 220 mcg/24 hrs, serum cortisol was 33.5 mcg/dl and ACTH 15 pg/ml.  Low dose dexamethasone suppression test showed a cortisol of 22.6 mcg/dl and an ACTH of 12 pg/ml.  Imagining revealed an 8mm pituitary adenoma. Transsphenoidal adenomectomy was performed.  POD 5 cortisol was 1.8 mcg/dl and pathology was consistent with corticotroph adenoma.

Discussion: These cases demonstrate that ACTH alone is not sufficient to determine the etiology of CS, especially in the range of 10-20 pg/ml.  New ACTH assays have improved precision at low concentrations, calling into question historical cutoffs.  A Low DHEA-S, particularly in a younger patient, suggests adrenal CS, whereas normal or elevated DHEA-S suggests a pituitary (or ectopic) etiology.  High dose dexamethasone suppression testing (8mg) resulting in a suppressed cortisol is suggestive of pituitary disease.  CRH stimulation testing may also be helpful.  Recent reports suggest that some forms of adrenal CS, notably macronodular hyperplasia, may be driven by adrenal production of ACTH, further emphasizing the pitfalls in utilizing ACTH levels to localize the source of CS.


Nothing to Disclose: GMG, NB, ACL, KDP, EBG