High prevalence of metabolic syndrome features in patients previously treated for non-functioning pituitary macroadenoma

Introduction Patients treated for non-functioning pituitary macroadenoma (NFMA) have alterations in sleep characteristics and circadian rhythmicity. These symptoms may be related to dysfunction of the suprachiasmatic nucleus of the hypothalamus, since a vast majority experienced compression of the adjacent optic chiasm. In accordance, structural hypothalamic damage is associated with increased prevalence of the metabolic syndrome. However, metabolic sequelae in patients treated for NFMA are not well established, since these patients are usually studied in the setting of growth hormone deficiency (GHD) of heterogeneous origin. Aim To study the prevalence of (features) of the metabolic syndrome in patients with NFMA. Methods The metabolic syndrome (NCEP-ATP III criteria) was studied in an unselected cohort of patients in long-term remission after treatment for NFMA, receiving adequate substitution for any pituitary deficiencies. Population based normative data of 63,995 Dutch inhabitants were derived from the LifeLines cohort study. Standardized morbidity ratios (SMR) were calculated after indirect standardization of data stratified for age and gender. Results We included 145 patients (mean age 64 ± 12 yrs, 56% male) in remission at least 1 year postoperatively (mean 12 ± 9 yrs). Visual field defects before surgery were present in 86%, and 47% had received adjuvant radiotherapy. Any pituitary deficiency was present in 92%, and GHD in 75% (of which 75% used rhGH therapy). Patients had an increased risk for reduced HDL-cholesterol (SMR 1.59 (95% CI 1.13-2.11)), raised triglycerides (SMR 2.31 (95% CI 1.78-2.90)) and the metabolic syndrome (SMR 1.60 (95% CI 1.22-2.02)). Visual field defects at baseline were independently associated with increased blood pressure (OR 6.8 (95% CI 1.9-24.0)). Presence of GHD or rhGH therapy showed a BMI-dependent relation with the metabolic syndrome and reduced HDL-cholesterol, but not with increased triglycerides. Cortisol substitution and radiotherapy were of no influence. Conclusion Patients treated for NFMA have an increased prevalence of the metabolic syndrome, and visual field defects were associated with increased blood pressure. Hypothalamic dysfunction may explain these metabolic abnormalities, in addition to intrinsic imperfections of hormone replacement therapy or untreated GHD. Additional research is required to explore the relation between derangements in circadian rhythmicity and metabolic syndrome in this patients group.