Clinical Features and Hormonal Profile of Macroprolactinomas Presenting With the Hook Effect: A Systematic Review

Objective: An assay artifact known as the "hook effect" causes spuriously low serum prolactin levels. This systematic review aimed to examine clinical reports on the "hook effect" in patients with macroprolactinomas to describe associated clinical features.

Methods: We systematically searched multiple databases from database inception to April 16, 2024 for case reports, case series, or observational studies of macroprolactinomas presenting with the hook effect. Original data for hook effect cases from our institution were also included. Data pertaining to patient and tumor characteristics were extracted for data analysis.

Results: A total of 61 macroprolactinoma patients demonstrating the hook effect were analyzed. The mean (standard deviation) age was 40.0 years (15.7 years) with no statistically significant difference between genders. Seventy percent of the patients were male. The smallest reported macroprolactinoma volume demonstrating the hook effect was 3.4 cm³ with its largest dimension measuring 2.9 cm. Mean pre- and postdilution serum prolactin levels were 108.1 ng/mL and 38 526.9 ng/mL, respectively. Ophthalmologic symptoms were the most commonly reported manifestations, (80.9%), followed by headaches (66.0%). Galactorrhea was reported in 4 out of 15 females and in none of the males. Central hypogonadism (63.6%) and central hypothyroidism (44.1%) were the most common associated pituitary hormonal deficiencies. No significant gender differences were noted in tumor size or serum prolactin levels.

Conclusion: Clinical characteristics of macroprolactinomas that demonstrate the hook effect greatly resemble those that do not, underscoring the need to perform dilution studies of prolactin in all patients with pituitary macroadenomas with normal or mildly elevated serum prolactin.