Introduction: Hyperostosis frontalis interna (HFI) is a cranial bone disorder associated with hormonal and metabolic factors; however, its relationship with Cushing syndrome has not been systematically evaluated. This study aimed to assess the prevalence of HFI and its association with cranial bone thickness in patients with endogenous Cushing syndrome. 

Material and methods: This retrospective cross-sectional study was conducted to evaluate adult patients with endogenous Cushing syndrome followed at a tertiary endocrinology center between January 2010 and December 2025 who had available cranial magnetic resonance imaging (MRI). Patients were categorized according to the presence or absence of HFI on cranial MRI. Frontal, parietal, and occipital bone thicknesses were measured on T1-weighted axial images. Clinical characteristics and biochemical parameters were compared between groups. 

Results: Among 26 patients with Cushing syndrome, HFI was identified in 9 patients, corresponding to a prevalence of 34.6%. No significant differences were observed between HFI-positive and HFI-negative patients with respect to age, disease duration, cortisol, IGF-1, prolactin, fasting plasma glucose, or HbA1c levels. Frontal bone thickness was significantly greater in HFI-positive patients; parietal and occipital bone thicknesses were also significantly greater. There were no significant differences between groups regarding sex, diabetes mellitus, hypothyroidism, Cushing etiology, or menopause or Cushing-related hypogonadism. 

Conclusions: Despite the well-established catabolic effects of chronic hypercortisolism on bone, patients with Cushing syndrome may exhibit selective cranial bone remodeling. The hormonal and metabolic alterations accompanying Cushing syndrome may contribute to the development of HFI. These observations indicate that cranial skeletal changes should be considered among the diverse osseous manifestations of Cushing syndrome.