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

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 10; pp. 3954 - 3961
• Main Authors: Filipsson, Helena, Monson, John P, Koltowska-Häggström, Maria, Mattsson, Anders, Johannsson, Gudmundur
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.10.2006
• Subjects: Adrenocorticotropic Hormone - deficiency; Adult; Aged; Biological and medical sciences; Body Mass Index; Comorbidity; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Glucocorticoids - administration & dosage; Growth Hormone - therapeutic use; Hormone Replacement Therapy; Humans; Hypopituitarism - drug therapy; Hypopituitarism - metabolism; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor I - analysis; Lipids - blood; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Risk Factors; Vertebrates: endocrinology; Endocrinopathy; Human; Concomitant disease; Replacement therapy; Prognosis; Hypophyseal insufficiency; Pituitary diseases; Metabolism; Therapeutic protocol; Endocrinology
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2006-0524

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.