Congenital growth hormone (GH) deficiency and atherosclerosis: Effects of GH replacement in GH-naive adults

Joselina L.M. Oliveira, Manuel H. Aguiar-Oliveira, Argemiro D'Oliveira, Rossana M.C. Pereira, Carla R.P. Oliveira, Catarine T. Farias, José A. Barreto-Filho, Fernando D. Anjos-Andrade, Celi Marques-Santos, Adão C. Nascimento, Érica O. Alves, Francielle T. Oliveira, Viviane C. Campos, Roberto Ximenes, Amanda Blackford, Giovanni Parmigiani, Roberto Salvatori

Research output: Contribution to journalArticle

Abstract

Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. Methods: We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 ± 14.5 yr; 122 ± 7.7 cm; 36.7 ± 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout. Results: Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline. Conclusion: In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intimamedia thickness and in the number of atherosclerotic carotid plaques.

Original languageEnglish (US)
Pages (from-to)4664-4670
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number12
DOIs
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Oliveira, J. L. M., Aguiar-Oliveira, M. H., D'Oliveira, A., Pereira, R. M. C., Oliveira, C. R. P., Farias, C. T., Barreto-Filho, J. A., Anjos-Andrade, F. D., Marques-Santos, C., Nascimento, A. C., Alves, É. O., Oliveira, F. T., Campos, V. C., Ximenes, R., Blackford, A., Parmigiani, G., & Salvatori, R. (2007). Congenital growth hormone (GH) deficiency and atherosclerosis: Effects of GH replacement in GH-naive adults. Journal of Clinical Endocrinology and Metabolism, 92(12), 4664-4670. https://doi.org/10.1210/jc.2007-1636