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The Impact of Glucocorticoid Replacement Regimens on Metabolic Outcome and Comorbidity in Hypopituitary Patients

Department of Endocrinology (H.F., G.J.), Sahlgrenska Academy at Gothenburg’s University, SE-413 45 Gothenburg, Sweden; St. Bartholomew’s Hospital (J.P.M.), Queen Mary University of London, London EC1A 7BE, United Kingdom; KIGS/KIMS/ACROSTUDY Medical Outcomes (M.K.-H., A.M.), Endocrine Care, Pfizer, SE-191 90 Sollentuna, Sweden; and Department of Pharmacy (M.K.-H.), Uppsala University, Uppsala, Sweden

Address all correspondence and requests for reprints to: Helena Filipsson, Department of Endocrinology, Gröna Stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: helena.filipsson{at}telia.com.

Background: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features.

Objective: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy.

Method: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age.

Results: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects.

Conclusion: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.

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