GH deficiency (GHD) in adults has been associated with changes in body composition, cardiovascular function, metabolic parameters associated with cardiovascular risk, and bone density and metabolism. These observations have been used to advocate GH therapy in GHD adults. However, the studies published to date were mostly done in patients who are often chronically sick, lack other pituitary hormones whose replacement therapies may not be optimal, and/or have had radiation therapy (all factors able to influence morbidity). Reliable data on the consequences of GHD can only be obtained by studying patients that are otherwise healthy. A large population of GH-naive adults with GHD due to a homozygous mutation of the GHRH receptor (GHRHR) gene resides in Brazil (Itabaianinha county). We propose to study the subjects homozygous for this mutation and compare them with normal subjects from the same community. Our primary goal is to determine the consequences of life-long GHD on body composition, cardiovascular function and risk factors, bone density and metabolism, and thyroid status, and to test which of these parameters are reversed by 6 months of hGH replacement therapy. The secondary goal is to test the hypothesis that heterozygosity for the mutation causes a phenotype that is intermediate between homozygous normal and GHD individuals. ? SPECIFIC AIM 1: to study body composition, cardiovascular status, cardiovascular risk profile, metabolic parameters, thyroid status, and bone mineral density in twenty GH-naive GHD subjects and compare them with twenty age- and sex-matched controls from the same community. ? SPECIFIC AIM 2: to examine the response of GHD individuals to 6 months therapy with GH. ? SPECIFIC AIM 3: to genotype a large number of apparently normal members of the ltabaianinha community to separate subjects homozygous for the wild-type allele from subjects heterozygous for the GHRHR mutation, and to compare the phenotype of one hundred heterozygotes with the one observed in one hundred homozygous normal individuals. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Endocrinology Study Section (END)
Program Officer
Malozowski, Saul N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Gois Jr, Miburge B; Salvatori, Roberto; Aguiar-Oliveira, Manuel H et al. (2012) The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance. Clin Endocrinol (Oxf) 77:379-84
Leite, N T F; Salvatori, R; Alcântara, M R S et al. (2012) Effects of depot growth hormone replacement on thyroid function and volume in adults with congenital isolated growth hormone deficiency. J Endocrinol Invest 35:265-8
Araujo, Vanessa P; Aguiar-Oliveira, Manuel H; Oliveira, Joselina L M et al. (2012) Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency. Eur J Endocrinol 166:977-82
Aguiar-Oliveira, Manuel H; Oliveira, Francielle T; Pereira, Rossana M C et al. (2010) Longevity in untreated congenital growth hormone deficiency due to a homozygous mutation in the GHRH receptor gene. J Clin Endocrinol Metab 95:714-21
Oliveira, Carla R P; Salvatori, Roberto; Meneguz-Moreno, Rafael A et al. (2010) Adipokine profile and urinary albumin excretion in isolated growth hormone deficiency. J Clin Endocrinol Metab 95:693-8
Barreto, Valeria M P; D'Avila, Jeferson S; Sales, Neuza J et al. (2009) Laryngeal and vocal evaluation in untreated growth hormone deficient adults. Otolaryngol Head Neck Surg 140:37-42
de Paula, Francisco J A; Góis-Júnior, Miburge B; Aguiar-Oliveira, Manuel H et al. (2009) Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short-term GH treatment on bone in adults with a mutation in the GHRH-receptor gene. Clin Endocrinol (Oxf) 70:35-40
Barbosa, Jorge A R; Salvatori, Roberto; Oliveira, Carla R P et al. (2009) Quality of life in congenital, untreated, lifetime isolated growth hormone deficiency. Psychoneuroendocrinology 34:894-900
Oliveira, Carla R P; Salvatori, Roberto; Nobrega, Luciana M A et al. (2008) Sizes of abdominal organs in adults with severe short stature due to severe, untreated, congenital GH deficiency caused by a homozygous mutation in the GHRH receptor gene. Clin Endocrinol (Oxf) 69:153-8
Menezes, Menilson; Salvatori, Roberto; Oliveira, Carla R P et al. (2008) Climacteric in untreated isolated growth hormone deficiency. Menopause 15:743-7

Showing the most recent 10 out of 15 publications