The high dose hook effect in prolactinomas; Following the guidelines?

Background: Prolactinomas are the most common type of secretory pituitary adenoma. The measurement of prolactin is one of the diagnostic tools in the assessment of patients suspect of a prolactinoma. The Endocrine Society's Clinical Guideline "Diagnosis and Treatment of Hyperprolactinemia" (2011) recommends that in case of discrepancy between a very large pituitary tumor and a mildly elevated prolactin level, dilution of samples need to be performed to eliminate a possible high dose hook (HDH) effect. Methods: In the current study, implementation of this guideline by clinical pathologists in Dutch clinical laboratories was investigated. In addition, the manufacturers of prolactin assays in the Netherlands were questioned whether they had anticipated in the design of their assays for the possibility of a HDH effect since the report of this effect in 1992. Results: The majority of the academic hospitals follows the Guideline recommendation. However, unexpectedly in case of regional hospitals, the majority performs dilutions to increase the linear range. From the manufacturer's point of view, besides relying on a large linear range and a low cut-off level above which an (automatic) dilution is performed, four out of five did not introduce additional modifications in the prolactin assays to prevent the HDH effect. Conclusions: The current study shows that not all laboratories follow the prolactin guideline. The difference in characteristics of the specific prolactin assays as well as sample handling emphasizes the importance of good communication between the clinical pathologist and physician for a correct (laboratory) diagnosis of prolactinoma.