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Publications

Journal Article Multicenter Study Ppublish

PubMed: 42573676 DOI: 10.1007/s40618-026-03016-w

Determinant factors for headache at acromegaly diagnosis: findings from an Iberian multicenter study encompassing 726 patients.

J Endocrinol Invest 49(11):3335-3343

Authors: Marta Vaz Lopes, Mariana de Griné Severino, Ema Lacerda Nobre, Luís Miguel Cardoso, Carmen Fajardo-Montañana, Concepción Blanco, Edelmiro Menéndez Torre, Betina Biagetti, Rogelio García-Centeno, Laura González Fernandéz, María Dolores Ollero García, Ana Irigaray Echarri, Fernando Cordido, Claudia Lozano-Aida, Fernando Vidal-Ostos De Lara, Fernando Guerrero-Pérez, Cristina Novo-Rodríguez, Carmen Tenorio-Jiménez, María Dolores Moure Rodríguez, Miguel Paja Fano, Beatriz Rodríguez Jiménez, Rosario Oliva Rodríguez, Inmaculada González Molero, Pedro Iglesias, Mónica Marazuela, Manel Puig-Domingo, Pedro Marques, Marta Araujo-Castro

Affiliations

  • Endocrinology Department, Hospital de Santa Maria, ULS Santa Maria, Lisbon, Portugal.
  • Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
  • Endocrinology Department, ULS Coimbra, Coimbra, Portugal.
  • i3S - Institute for Research and Innovation in Health of the University of Porto, Porto, Portugal.
  • Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
  • Endocrinology and Nutrition Department, Hospital Universitario de la Ribera, Alzira, Valencia, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Príncipe de Asturias, Madrid, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Central de Asturias, Asturias, Spain.
  • Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Navarra, Pamplona, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario de A Coruña, Universidad de A Coruña, Coruña, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario de Bellvitge, Cataluña L'Hospitalet de Llobregat, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Virgen de las Nieves, Granada, Spain.
  • Granada Biosanitary Research Institute (ibs.GRANADA), Granada, Spain.
  • Department of Medicine, Faculty of Medicine, University of Granada, Granada, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario de Cruces, Bilbao, Spain.
  • Endocrinology and Nutrition Department, Biobizkaia Health Research Institute, Osakidetza, Basurto University Hospital, EHU, Basque Country University, Bilbao, Bizkaia, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Virgen de la Macarena, Sevilla, Spain.
  • Endocrinology and Nutrition Department, Hospital Regional Universitario de Málaga, Málaga, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
  • Endocrinology and Nutrition Department, Hospital La Princesa, Madrid, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Germans Trias i Pujol, Cataluña, Spain.
  • Pituitary Tumor Unit, Endocrinology Department, Hospital CUF Descobertas, Lisbon, Portugal.
  • Faculty of Medicine, Universidade Católica Portuguesa, Lisbon, Portugal.
  • Endocrinology and Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
  • Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain.

Abstract

PURPOSE

Headache is a debilitating symptom in acromegaly, often attributed to mass effect in patients with large tumors, however other factors beyond size may contribute. We aimed to identify determinant factors for headache at diagnosis in a large acromegaly cohort.

METHODS

We performed a registry-based multicentric retrospective study including patients diagnosed with acromegaly between 1970 and 2025 from 35 Iberian centers. Primary outcome was presence of headache at acromegaly diagnosis recorded as a binary variable (present/absent). Variables associated with headache in univariable regression and/or deemed clinically relevant were included in the multivariable regression.

RESULTS

Out of 726 patients, 321 (44.2%) had headaches at acromegaly diagnosis. Patients with headache at diagnosis were younger (45.8 ± 15.4 vs. 50.4 ± 14.2 years, p < 0.001), had higher prevalence of macroadenoma (86.1 vs. 72.4%, p < 0.001), larger volume (2650 vs. 1147 mm³, p < 0.001), and more invasive tumors (Knosp > 2: 34.2 vs. 20.2%, p < 0.001). Hyperprolactinemia (32.5 vs. 24.1%, p = 0.01) and hypopituitarism (26.8 vs. 16.3%, p < 0.001) were also more frequent in patients with headache. In the univariable analysis, younger age, larger volume, higher Knosp grade, higher growth hormone levels, hypopituitarism and hyperprolactinemia were associated with headache. In the multivariable analysis, macroadenomas, larger volume remained independent factors for headache.

CONCLUSION

Headache is common in acromegaly, particularly in young patients with larger and invasive pituitary tumors, and in cases presenting with hyperprolactinemia and hypopituitarism. Tumor size was the dominant and independent determinant contributing to headache at acromegaly diagnosis. Future studies should integrate detailed headache phenotyping and investigate other factors relevant to acromegaly-related headache.

MeSH

Headache, Endocrinology, Hyperprolactinemia, Neoplasms, Hypopituitarism, Acromegaly, Diagnosis