CONTEXT: The prevalence of obesity is increased in hypopituitarism. In the general population, body mass index (BMI) and waist circumference increase with advancing age. It remains uncertain whether age-related changes in pituitary function contribute to the changes in body composition associated with advancing years. OBJECTIVE: Our objective was to study the relationship between pituitary function, body composition, and age in a large cohort of patients with hypopituitarism and a matched reference population. DESIGN, SETTING, AND PARTICIPANTS: A total of 3632 GH-deficient adults with hypopituitarism, adequately replaced with all pituitary hormones except for GH, from the prospective KIMS database (Pfizer International Metabolic Database) were included in present analysis. A random sample of the general population (3427 subjects) was used as reference. Patients and controls were grouped by gender in five age cohorts of 10 yr from 28 yr onward. MAIN OUTCOME MEASURES: Differences in BMI and waist circumference were evaluated. RESULTS: Patients had a significantly higher BMI and waist circumference than controls, with larger differences at younger age. With advancing age, an increase in BMI and waist circumference was seen in controls but was virtually absent in the patients with adult-onset GH deficiency and hypopituitarism. CONCLUSION: Patients with hypopituitarism have more excess body fat than age-matched controls, especially in the youngest age groups. The normal increase in fat mass with advancing age is not seen in adult-onset GH-deficient hypopituitarism, suggesting a potential role for the normal pituitary gland as an age-dependent regulator of body composition in adult life.