IMPE Abstracts

Contemporary ACTH assays have variable susceptibility to interference by endogenous antibodies, particularly heterophile antibodies, leading potentially to unnecessary investigations^1-6. Often, determining the cause of the spurious ACTH results is impossible beyond identifying the presence of interference of heterophile antibodies⁶. Here we describe two cases of Cushing Syndrome due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD) whose evaluations were confounded by heterophile antibody interference with the Siemens Immulite ACTH assay. A 15-year-old girl with Carney Complex presented with multiple distinct episodes of hypercortisolism. Evaluation revealed an elevated 24-hour Urinary Free Cortisol (UFC): 1330.6 mg/24h (ref: 4.4-56.0 mg/24h) and a positive high-dose Dexamethasone Suppression Test (DST) with non-suppressed cortisol: 10.0 mg/dL (ref: <1.8). ACTH was detectable: 8.0 pg/mL (ref: 5-46 pg/mL). Since pituitary and adrenal imaging were normal, a Liddle Test was conducted to diagnose PPNAD given her known Carney Complex diagnosis. The test showed a classic paradoxical increase in UFC (pre-dexamethasone: 5 mg/24h; post-dexamethasone: 56 mg/24h). ACTH measured with a the Siemens Immulite assay, did not suppress after dexamethasone (pre: 7.0 pg/mL, post: 10.0 pg/mL). After pre-treating this sample with immunoglobulin purifying columns (Nab Spin Columns, Thermo Scientific), ACTH was re-measured and produced an undetectable ACTH (<5.0 pg/mL). PPNAD was thus diagnosed. A 12-year-old girl presented with symptoms of hypercortisolism. Evaluation at an outside institution revealed elevated midnight salivary cortisol concentrations (0.759 mg/dL, 0.856 mg/dL, ref: <0.112), suppressed ACTH (1.4 pg/mL ref: 5-46) and a non-suppressed high-dose DST: 21.4 mg/dL (ref: <1.8 mg/dL). While pituitary and adrenal imaging were unremarkable, the right ovary was enlarged. She was referred for ovarian and adrenal venous sampling. On admission, a midnight ACTH (Immulite) was 37.9 pg/mL. Ovarian and adrenal venous sampling revealed elevated cortisol secretion by both adrenal glands. Her ACTH was re-measured using the Immulite assay after pre-treatment with immunoglobulin purifying columns (Nab Spin Columns, Thermo Scientific), and the amended result was 8.0 pg/mL. When measured with the Roche Elecsys assay, ACTH was <5 pg/mL. The patient underwent bilateral adrenalectomy; surgical pathology showed PPNAD. In these cases of PPNAD, heterophile antibody interference on a Siemens Immulite platform affected ACTH determination. It is important to exclude heterophile antibodies when laboratory results do not fit the clinical picture. These cases reiterate the issues with the Siemens Immulite ACTH assay.

PMID References

1. 23873871 2. 31093000 3. 35699218 4. 30963134 5. 30423322