The hook effect in macroprolactinomas: tumor size thresholds, prolactin patterns, and clinical consequences - a systematic review
Authors' conclusion
Pre-dilution PRL values often overlap with the range attributed to stalk effect, and serial dilution testing should be considered for pituitary macroadenoma with PRL disproportionately low relative to tumor size, regardless of whether the tumor meets the giant adenoma threshold to prevent misdiagnosis, unnecessary surgical intervention and delayed initiation of dopamine agonist therapy.
Study context
- Population
- Patients with macroprolactinomas and confirmed hook effect (pre- and post-dilution prolactin (PRL), tumor size, confirmation by serial dilution), articles 2000–August 2025
- Participants
- 23 patients14 studies
- Outcome
- Tumor size threshold and distribution at which hook effect documented
Methodological detailsindividual patient data synthesis, PRISMA 2020, Quality assessed with JBI Critical Appraisal Checklist for Case Reports, Searched PubMed, Embase, Scopus, Google Scholar, Web of Science
- Individual patient data synthesis
- PRISMA 2020
- Quality assessed with JBI Critical Appraisal Checklist for Case Reports
- Searched PubMed, Embase, Scopus, Google Scholar, Web of Science
Pooled result
As reported in the abstract
Maximum tumor diameter, median (IQR; range)
48.0 mm
IQR 35.5–55.0; range 22–100 mm
Smallest confirmed hook-effect tumor diameter (2 independent cases)
22 mm
Cases in tumors below giant adenoma threshold (≥ 40 mm)
9 of 23
39.1%
Further pooled results
Pre- and post-dilution PRL
- Median pre-dilution PRL
- 100.0 ng/mL (IQR 62.0-164.5)
- Median post-dilution PRL
- 6,460.0 ng/mL (IQR 3,608.5-16,657.5)
- Median fold increase
- 64.7× (IQR 46.8-141.5)
- Pre-dilution PRL 26–200 ng/mL (often misattributed to stalk effect)
- 82.6% (95% CI: 62.9-93.0%)
Clinical consequences of unrecognized hook effect
- Unnecessary surgery among cases with documented clinical outcomes
- 55.6%
- Hook effect documented across multiple immunoassay platforms
Original publication
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