Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 3 appraisals
Pituitary
The hook effect in macroprolactinomas: tumor size thresholds, prolactin patterns, and clinical consequences - a systematic review.
PURPOSE: The immunoassay "hook effect" may cause spuriously low prolactin (PRL) measurements in patients with macroprolactinomas, leading to misdiagnosis and inappropriate management. This systematic review aimed to determine the tumor size threshold and distribution at which the hook effect has been documented, characterize the pre-dilution PRL pattern, quantify the magnitude of PRL underestimation, and assess the clinical consequences of unrecognized hook effect. METHODS: PubMed, Embase, Scopus, Google Scholar, and Web of Science were searched for articles published between January 2000 and August 2025. Studies reporting individual patient data with confirmed hook effect (pre- and post-dilution PRL, tumor size, and confirmation by serial dilution) were included. Quality was assessed using the JBI Critical Appraisal Checklist for Case Reports. Data were synthesized using individual patient data (IPD) quantitative methods. The review was registered on PROSPERO (CRD420261375863) and reported per PRISMA 2020 guidelines. RESULTS: Twenty-three patients from 14 studies across 9 countries were included, with a median maximum tumor diameter of 48.0 mm (IQR 35.5-55.0; range 22-100 mm); the smallest confirmed hook-effect tumor diameter measured 22 mm, reported in two independent cases, and 9 of 23 cases (39.1%) occurred in tumors below the conventional giant adenoma threshold (≥ 40 mm). Median pre-dilution PRL was 100.0 ng/mL (IQR 62.0-164.5), while median post-dilution PRL was 6,460.0 ng/mL (IQR 3,608.5-16,657.5), yielding a median fold increase of 64.7× (IQR 46.8-141.5). Pre-dilution PRL ranged from 26 to 200 ng/mL in 82.6% of cases (95% CI: 62.9-93.0%), values often misattributed to stalk effect. Unrecognized hook effect led to unnecessary surgery in 55.6% of cases with documented clinical outcomes. The hook effect was documented across multiple immunoassay platforms. CONCLUSIONS: 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.
30 May 2026
Read appraisal →European radiology experimental
MRI radiomics-based approach to predict pituitary neuroendocrine tumor invasiveness
OBJECTIVES: To assess the diagnostic potential of magnetic resonance imaging (MRI) radiomics and machine learning models using T2-weighted and contrast-enhanced (CE)-T1-weighted images, individually and combined, to predict the invasiveness of pituitary neuroendocrine tumors (PitNETs). MATERIALS AND METHODS: Patients with macro-PitNETs were retrospectively enrolled from 2019 to 2022. Radiomic features were extracted from manually segmented lesions on preoperative T2-weighted and CE-T1-weighted images and, after a feature selection step, used to assess invasiveness, defined following Trouillas' classification. Five machine learning models (logistic regression, random forest, gradient boosting, AdaBoost, XGBoost) were trained using CE-T1-weighted, T2-weighted, and CE-T1-weighted plus T2-weighted features. Performance was evaluated on a test set using the area under the receiver operating characteristic curve (AUC). RESULTS: Two hundred patients were included in the study: 95 PitNETs were noninvasive (74 grade 1a; 21 grade 1b) and 105 invasive (70 grade 2a; 35 grade 2b). A total of 102 radiomic features were extracted per sequence. The best-performing model was the XGBoost, using five combined CE-T1-weighted and T2-weighted features, with an AUC of 0.85 (95% confidence interval: 0.75‒0.95). Lower AUC values were obtained for logistic regression using CE-T1-weighted images (0.80) and AdaBoost using T2-weighted images (0.78). CONCLUSION: The XGBoost model, incorporating tumor shape, texture, and first-order features extracted from both CE-T1-weighted and T2-weighted MRI, showed high performance in predicting PitNETs invasiveness. This radiomic model might help identify tumors with a higher risk of disease persistence, recurrence, or progression. RELEVANCE STATEMENT: The radiomic model based on contrast-enhanced T1-weighted and T2-weighted MRI demonstrated high discriminative ability in predicting invasiveness of pituitary neuroendocrine tumors and could aid in identifying tumors that may be at higher risk for recurrence or progression, ultimately improving patient outcomes through personalized treatment strategies. KEY POINTS: Pituitary neuroendocrine tumors (PitNETs) represent a significant challenge in clinical practice. Accurate preoperative prediction of PitNET invasiveness is crucial for surgery and prognosis. Contrast-enhanced T1-weighted and T2-weighted MRI-based radiomic model effectively predicts PitNET invasiveness. The developed radiomic model could help optimize individualized treatment decisions before surgery.
21 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis
CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly. OBJECTIVE: Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. METHODS: MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. RESULTS: Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. CONCLUSION: This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.
19 May 2026
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