SUN-400 Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure: A Case Series

The reliable measurement of plasma ACTH is essential for the accurate diagnosis and differential diagnosis of Cushing’s syndrome (CS). We report 5 women with the misdiagnosis or incorrect differential diagnosis of CS due to spurious results from an ACTH assay (method I). Plasma ACTH (pg/mL), measured by other methods (C and A), provided accurate results. Case 1: 22-year-old (yo): Basal (203) and post oDST (83) ACTH(I) were elevated; however, AM serum cortisol, late-night salivary cortisol (LNSC), and post 1 mg overnight dexamethasone suppression test (oDST) cortisol were all normal. ACTH-dependent CS was suspected. MRI suggested a pituitary microadenoma; IPSS ACTH(I) showed a significant pituitary ACTH gradient. Pituitary surgery found a possible microadenoma (ACTH-negative). 3 months post-op, ACTH(I) was 57; heterophile Abs were negative. Repeat testing with ACTH(C) was 28. Final diagnosis: CS was ruled out; symptoms attributed to Lyme disease.Case 2: 31 yo: ACTH(I) (62), UFC, LNSC, and oDST cortisol were elevated. MRI found a pituitary microadenoma; IPSS found no gradient. Systemic imaging was negative other than a unilateral adrenal neoplasm. Occult ectopic ACTH-dependent CS was suspected. On metyrapone, ACTH(I) was 45; ACTH(C) was 2.4. A benign adrenal adenoma was removed followed by secondary adrenal insufficiency (AI). Final diagnosis: ACTH-independent (adrenal) CS, in remission.Case 3: 58 yo: CT found a 2 cm R adrenal nodule. ACTH(I) (41-143), serum cortisol, UFC, and oDST cortisol were elevated. MRI showed a possible 3 mm pituitary lesion. IPSS by ACTH(I) found no gradient. Occult ectopic ACTH-dependent CS was suspected. ACTH(C) was 3.3; serum cortisol and LNSC were normal. A benign adrenal adenoma was removed followed by secondary AI. Final diagnosis: ACTH-independent (adrenal) CS, in remission.Case 4: 59 yo: ACTH(I) was 367-1031. Referred for IPSS. Ectopic ACTH was suspected. However, ACTH(C) was 7.3; serum cortisol and DHEA were normal. LNSC was elevated. Patient had a history of alcohol abuse. After alcohol was stopped, LNSC normalized. Final diagnosis: alcohol-induced ACTH-dependent hypercortisolism. Case 5: 23 yo referred for IPSS with elevations of UFC, LNSC, and post-oDST cortisol. ACTH(I) was 22. ACTH-dependent CS was suspected. Basal ACTH(C) was 1.0 without an increase after CRH. CT showed a 3 cm R adrenal nodule. Adenoma removed followed by secondary AI. Final diagnosis: ACTH-independent (adrenal) CS, in remission.College of American Pathologists Proficiency Testing sample TMB-05-2016 found a very high ACTH(I)(103) whereas ACTH(C) and ACTH(A) were 2.4. Conclusion: ACTH(I) may provide misleading elevations of ACTH and cause an incorrect diagnosis or etiology of CS. When confronted with incongruously increased plasma ACTH results, clinicians should inquire as to the method used and request reanalysis of the sample using an alternate method.