High-Dose Hook Effect in Patients with Macroprolactinoma

Background: Large amounts of antigen may produce false low values on immunoradiometric assays due to the so-called high-dose hook effect. The physicians' awareness of the possibility of the “high-dose hook effect” will prevent preoperative misdiagnosis. The study was designed to identify the frequency and clinical features of patients with pituitary macroadenomas in whom a high-dose PRL hook effect was documented. Methods: Our retrospective study involved 42 patients with non-functioning pituitary adenomas (tumor diameter > 30 mm) who underwent transsphenoidal microsurgery from between Jan 1999 to Aug 2004, and 6 patients with non-functioning pituitary adenoma (tumor diameter > 30 mm) were selected for prospective study from Sep 2003 to Feb 2004. Our retrospective study also involved 13 patients with macroprolactinoma for the comparison of the clinical features. Results: 1) The presence of a high-dose hook effect was retrospectively suggested when the PRL levels increased in 4 out of the 42 patients with non- functioning adenomas (tumor diameter > 30 mm) after surgery. Post-operative immunohistochemical staining of their pituitary specimens revealed the tumors to be prolactinoma. 2) Prospectively, dilution testing of the specimens obtained before surgery was done in the 6 patients, and one patient presented with a case of the hook effect. The patient's prolactin level was measured at 53.1 ng/mL before dilution and this was increased up to 22,600 ng/mL upon the 1:1000 dilution. 3) Conclusively, the hook effect was seen in 5 of the 48 patients (10.4%) with non-functioning pituitary adenoma (tumor diameter > 30 mm) 4) Compared with other 2 patient groups (the macroprolactinoma (N=13) group, and the non-functioning pituitary tumor (N=43) group), the high-dose PRL hook effect is more likely to be observed in male patients with large pituitary tumors. Conclusion: In order to avoid the high-dose hook effect, PRL should be assayed at 1:100~1:200 or even higher dilutions of serum from all patients (and especially the male patients) with large pituitary tumors (J Kor Soc Endocrinol 20:148～153, 2005).

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