PSAT055 ACTH-Dependent or ACTH-Independent: The Importance of a Reliable ACTH Assay in Solving a Case of Cushing Syndrome

BACKGROUND: Reliable laboratory assays are of paramount importance in the field of endocrinology, as our ability to make diagnoses and recommend the appropriate treatment, rely heavily on them. CLINICAL CASE: A 36-year-old woman presented to our clinic with a history of a 30-pound weight gain over the course of a year and hypertension that was sub-optimally controlled on two antihypertensive medications. On physical exam she exhibited facial plethora, moon facies, central obesity, dorsocervical fat pad, and reddish abdominal striae. Laboratory data revealed a 24 hr urine free cortisol 277 mcg/24 h (n ≤ 45 mcg/24 h), 8 am cortisol after 1 mg dexamethasone suppression test 19.2 mcg/dL (cut-off <1.8 mcg/dL) with a dexamethasone level 179 ng/dL (n 140-295 ng/dL). Serum DHEAS <15 mcg/dL (n 35-430 mcg/dL) which was suggestive of an adrenal source of cortisol. CT scan of the adrenals revealed a 3.0×2.3 cm right adrenal nodule, 14 HU, relative washout of 58%, absolute washout of 68%, consistent with an adenoma. However, plasma ACTH was 20 pg/mL (n 0-46 pg/mL) which was suggestive of an ACTH-dependent etiology. Repeat ACTH levels through our local lab ranged between 17-27 pg/mL. An MRI of the brain was obtained which showed a normal pituitary gland without evidence of an adenoma. Due to the discrepancy between the clinical picture and the ACTH levels, the patient's case was discussed with the medical director of our local lab. It was decided to obtain another sample for ACTH which was tested for heterophile antibodies but did not yield any meaningful results. The patient denied being on any supplements that could interfere with the ACTH assay. The sample was then sent out to an outside lab with a plasma ACTH level <1 pg/mL (n 7.2-63 pg/mL), which was consistent with the patient's clinical presentation of an adrenal source of cortisol excess. Further investigation revealed that our local lab used a Siemens Immulite assay which was likely detecting interference, whereas the outside lab used the Roche Elecsys assay. In previous studies, the Roche assay has highly correlated with intact ACTH that has been measured by HPLC-MS/MS. The patient was started on ketoconazole and has been referred for right adrenalectomy. CLINICAL LESSONS: Heterophile antibodies and ACTH fragments are common culprits of ACTH immunoassay interference, but they can be difficult to detect if there is not a high index of suspicion. Erroneous laboratory results can lead clinicians to perform unnecessary procedures and delay patient care. This case highlights the importance of a reliable plasma ACTH assay to inform clinical judgment. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.