Spurious elevations in PTH may be secondary to Heterophile Antibodies

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 199-237-Disorders of Parathyroid Hormone & Calcium Homeostasis
Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-206
Rajaa Nahra*, Steven Bogen and Ronald M Lechan
Tufts Medical Center, Boston, MA
Background: PTH assay like other immunoassays is vulnerable to interference leading to a falsely elevated PTH level.

Clinical case: A 54 yo female presented to her primary case physician with 6 days of anterior neck pain.  She did not have difficulty swallowing, fever, chills or symptoms of upper respiratory tract infection.  As part of the work up ordered by her PCP, iPTH was elevated to 679.4 pg/ml, but iCa was 1.25 (1.15-1.35 mmol/l), Cr 0.8 mg/dl, and 25 OH vit D 56.3 ng/ml.  Repeat iPTH was 486.6 pg/ml.  The patient did not have a history of hypertension, peptic ulcer disease, kidney stones, fractures or significant constipation and was 2 years postmenopausal.  Mild osteopenia was noted on DEXA. Medications included Calcium+vit D 600 mg/200 IU daily and Zolpidem 5 mg daily.  At the time of her evaluation in the Endocrinology clinic, her neck pain had subsided spontaneously.  On examination, she appeared well and had no palpable neck masses.  Repeat biochemical profile at our institution using the Siemens Centaur XP instrument revealed a iPTH of 776 (11-80 pg/ml), calcium 9.5 (8.5-10.5 mg/dl), albumin 4.5 (3.4-4.8 gm/dl), phosphorus 3.7 (2.7-4.5 mg/dl), alkaline phosphatase 73 (40-130 IU/L) and creatinine 0.78 (0.4-1.3 mg/dl).  Given that the patient did not have a clinical picture of hyperparathyroidism, the sample was sent to Quest Laboratory and iPTH was found to be 25 pg/ml using the Siemens Immulite instrument.  The possibility of a high dose "hook" effect artifact was excluded in dilutions of the sample.

Clinical lesson: The PTH assay uses a “sandwich” technique.  Therefore, a substance capable of binding to the capture and signal antibodies can cause false elevation of PTH.  This artifact can occur in the presence of natural antibodies such as heterophile antibodies (HAMA) or rarely in the presence of rheumatoid factor (1,2).  At least ten percent of the general population has been observed to carry HAMA.  HAMA interference is likely to occur when a 2-site assay involving 2 murine-derived antibodies is used.  Antibody interference can be removed by column chromatography or using heterophile antibody blocking tubes.  Unusual biochemical features that do not fit with the clinical presentation should always prompt confirmation of the validity of the assay. Misleading laboratory results may lead to unnecessary interventions.

1-Levin et al. Endocr Pract. 2011 Mar-Apr;17(2):e8-11 2-Cavalier et al. Clin Chim Acta. 2008 Jan;387(1-2):150-2

Nothing to Disclose: RN, SB, RML

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