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

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.

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.

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.

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.