Wednesday, March 23, 2011

Adult Growth Hormone Deficiency: Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency

Nicholas A. Tritos, Susan L. Greenspan, Donna King, Amir Hamrahian, David M. Cook, Peter J. Jönsson, Michael P. Wajnrajch, Maria Koltowska-Häggstrom and Beverly M. K. Biller

Neuroendocrine Unit (N.A.T., B.M.K.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Medicine (S.L.G.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260; Department of Endocrinology, Diabetes, and Metabolism (A.H.), Cleveland Clinic, Cleveland, Ohio 44195; Department of Endocrinology (D.M.C.), Oregon Health & Science University, Portland, Oregon 97239; KIMS Medical Outcomes (P.J.J., M.K.-H.), Pfizer Endocrine Care, 191 90 Sollentuna, Sweden; and Pfizer Inc. (D.K., M.P.W.), New York City, New York 10017

Address all correspondence and requests for reprints to: Nicholas A. Tritos, M.D., D.Sc., Neuroendocrine Unit, Massachusetts General Hospital, Zero Emerson Place, Suite 112, Boston, Massachusetts 02114. E-mail:

Context: GH deficiency (GHD) is associated with low bone mineral density (BMD). Risk factors for lower BMD in this GHD population have not been fully elucidated. In particular, there are limited published data in GH-naïve subjects.

Objective: The objective of the study was to identify endocrine correlates of low BMD in treatment-naïve adult GHD subjects.

Design: This was a retrospective analysis of data extracted from the (Pfizer International Metabolic Study) KIMS database.

Setting: The study was an international epidemiological survey of more than 15,000 adult GHD patients from 31 countries.

Patients: A total of 1218 subjects with stringently defined GHD of adult onset (641 women and 577 men) who were GH naïve and had BMD measured in the posterior anterior lumbar spine and femoral neck by dual-energy X-ray absorptiometry.

Main Outcome Measures: Variables associated with standardized BMD (sBMD) in adult-onset GHD were examined.

Results: In the LS, body mass index (r = 0.13, P < 0.01), unreplaced sex steroid deficiency (r = –0.17, P < 0.0001), and corticotropin deficiency (r = –0.11, P < 0.01) were independently associated with sBMD. In the FN, age (r = –0.19, P < 0.0001), female gender (r = –0.18, P < 0.0001), body mass index (r = 0.21, P < 0.0001), and decreased IGF-I SD scores (r = 0.10, P < 0.001) were independently associated with sBMD.

Conclusions: Hormone variables associated with lower sBMD in patients with adult-onset GHD include unreplaced sex steroid deficiency and corticotropin deficiency in the LS and lower IGF-I SDS in the FN.