• Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease.

      Höybye, Charlotte; Ragnarsson, Oskar; Jönsson, Peter J; Koltowska-Häggström, Maria; Trainer, Peter J; Feldt-Rasmussen, Ulla; Biller, Beverly M K; Department of Endocrinology, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. charlotte.hoybye@karolinska.se (2010-04)
      OBJECTIVE: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. DESIGN AND METHODS: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. RESULTS: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). CONCLUSION: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.
    • The pituitary gland and age-dependent regulation of body composition.

      Van Beek, André P; Wolffenbuttel, Bruce H R; Runge, Evelien; Trainer, Peter J; Jönsson, Peter J; Koltowska-Häggström, Maria; Department of Endocrinology, University Medical Center Groningen, University of Groningen, De Brug 4.069, AA 31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. a.p.van.beek@int.umcg.nl (2010-08)
      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.