Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study
Miguel Sampedro-Nuñez1, Aura Dulcinea Herrera-Martínez2,3, Alejandro Ibáñez-Costa3,4,5,6
1Department of Endocrinology and Nutrition Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain.
European Journal of Endocrinology
|May 3, 2024
Summary
Biomarkers for growth hormone-secreting pituitary tumors (GHomas) were identified, associating larger and invasive tumors with specific clinical and molecular features. Pre-treatment with medications did not significantly alter these key biomarkers, aiding personalized GHoma management.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Growth hormone (GH)-secreting pituitary tumors (GHomas) are the primary cause of acromegaly.
- Most GHomas are macroadenomas at diagnosis, often invading the cavernous sinus.
- Identifying biomarkers for GHoma growth and invasion is crucial for effective management.
Purpose of the Study:
- To identify clinical, hormonal, and molecular biomarkers linked to GHoma size and invasiveness.
- To assess the impact of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) on key molecular biomarker expression.
Main Methods:
- Evaluated clinical, analytical, and radiological data from 192 patients in the REMAH study.
- Assessed expression of somatostatin/ghrelin/dopamine system components and pituitary/proliferation markers in GHomas post-surgery.
- Utilized univariate/multivariate regression and penalized regression for variable association analysis.
Main Results:
- Larger, invasive GHomas correlated with younger age, visual issues, higher IGF1, and extrasellar/suprasellar growth.
- Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression were linked to invasiveness.
- Pre-operative DA/SSA therapy minimally affected biomarker expression, except for specific receptor/hormone genes.
Conclusions:
- A distinct set of clinical and molecular variables predicts GHoma invasiveness and growth.
- First-line acromegaly drug pre-treatment did not substantially alter crucial biomarker expression.
- Findings support improved risk stratification and personalized treatment strategies for GHomas.
