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Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy

¹ Department of Internal Medicine, Centralsjukhuset, Kristianstad, Lund, Sweden² Department of Endocrinology and Diabetes, Lund University Hospital, SE-221 85 Lund, Sweden³ Endocrine Unit, Division of Internal Medicine, Department of Medical and Health Sciences, University Hospital, Linköping, Sweden⁴ Competence Centre for Clinical Research, Lund University Hospital, Lund, Sweden⁵ Department of Neurosurgery, University Hospital, Lund, Sweden⁶ Neuroendocrine Unit, Institute of Endocrinology, University Clinical Center, Belgrade, Serbia

(Correspondence should be addressed to E-M Erfurth; Email: eva_marie.erfurth{at}med.lu.se)

Context: Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified.

Objective: To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk.

Design and participants: In a cross-sectional study of operated CO craniopharyngiomas (1958–2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17–57) and assessed CVD risk of 20 (4–40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10–12 years in women and men.

Results: In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55–60% of female patients had a medium–high CVD risk, compared with 10–20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients.

Conclusions: Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.