Session: SUN 50-71-HPA Axis
Poster Board SUN-68
Objective:Our aim was to report 5 patients with abnormally high ACTH levels measured on Siemens Immulite 2000 which were not consistent with the clinical diagnosis and to describe several commonly available laboratory-based approaches to investigate these spurious results.
Methods and Results: Samples from 2 patients (Cases 1 and 2) with bilateral adrenal macronodular hyperplasia during the dexamethasone suppression test (1mg PO every 6 h), 1 patient with panhypopituitarism (Case 3), 1 patient with an incidental adrenal mass (Case 4) and 1 obese patient (Case 5) were considered inadequate for clinical data when first measured on Siemens Immulite 2000 (normal range, up to 46 pg/mL). Plasma ACTH levels were repeated in the duplicate on Roche Modular E170 (normal range, 7 to 63 pg/mL). The detected levels were: Case 1 – 77.0 vs < 1.0 pg/mL; Case 2 – 12.0 vs < 1.0 pg/mL, Case 3 – 64.0 vs 3.8 pg/mL, Case 4 – 80.0 vs 3.7 pg/mL and Case 5 – 125.0 vs 18.0 pg/mL . In contrast, no differences were found when plasma ACTH was compared in 73 random samples measured on Immulite and E170 (68 vs 69 pg/mL, p= 0.8, by paired t-test). In Case 5, plasma ACTH levels varied from 80 to 200 pg/mL. Serial dilution of this sample up to 1:10 using pooled plasma with low ACTH levels showed a non-linear increase in ACTH recovery (226 to 508%), confirming the presence of an interfering substance. Anti-peroxidase antibodies were positive. Polyethylene glycol precipitation showed reduced ACTH recovery (8% in patient sample vs 68-87% in control samples), suggesting the presence of a high molecular weight interfering substance. Finally, the sample was incubated with plasma collected from a patient with primary adrenal insufficiency (273 pg/mL on Immulite) at 1:1 ratio. ACTH recovery after incubation was 138% (expected concentration, 207 pg/mL; measured concentration, 285 pg/mL on Immulite).
Conclusions: Our findings suggest the presence of a high molecular weight interfering substance on Immulite ACTH assay. This may be caused by heterophile antibodies or perhaps an anti-ACTH IgG. Further studies are under way to evaluate these possibilities.
Nothing to Disclose: LPB, GAA, HPLV, MEFP, MCBVF, BBM, MCB
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