Lifetime Growth Hormone (GH) Deficiency: Impact on Growth, Metabolism, Body Composition, and Survival Capacity

  • Manuel Herminio Aguiar-Oliveira
  • Roberto Salvatori
Chapter

Abstract

A model of growth hormone (GH) deficiency (GHD) due to GH-releasing hormone (GHRH) resistance caused by a homozygous-inactivating mutation in the GHRH receptor gene was used to assess the impacts of lifetime GH deficiency on growth, metabolism, body composition, and survival capacity. Affected individuals go through life with very low activity of the GH–insulin-like growth factor-I (IGF-I) axis. As a result, they present severe short stature with adult height standard deviation score from – 9.6 to –5.1 and proportionate reduction of bone dimensions. The reduction of the cephalic perimeter is less accentuated than the reduction on the facial height, causing a disproportion between the calvarium and the face, resulting in a “doll” or cherubim angel facies, which together with the underdevelopment of larynx leads to high pitch voice. Even when corrected by body surface, they have reduced size of the pituitary, thyroid, heart, uterus, and spleen. They also exhibit an increase in total and LDL cholesterol that persists throughout adulthood together with high levels of C-reactive protein and higher blood pressure. Body composition is markedly changed since childhood with reduction in fat-free mass with a mirror increase in percent fat mass. Despite this, they have an increase in insulin sensitivity. Bone strength is somewhat reduced without apparent increase in fractures. Puberty is delayed, but reproductive life and quality of life are normal. Despite unfavorable metabolic, inflammatory, blood pressure, and body composition profile, they did not exhibit premature atherosclerosis, with longevity similar to their normal-stature relatives.

Keywords

Cholesterol Obesity Europe Osteoporosis Assure 

Abbreviations

ALS

Acid-labile subunit

AOGHD

Adult-onset GH deficiency

BMI

Body mass index

COGHD

Childhood-onset GH deficiency

CRP

C-reactive protein

FFM

Fat-free mass

FM

Fat mass

GH

Growth hormone

GHD

Growth hormone deficiency

GHRH

Growth hormone-releasing hormone

GHRHR

GHRH receptor

HtSDS

Height standard deviation score

IGFBP

IGF-binding protein

IGF-I

Insulin-like growth factor type I

IGF-II

Insulin-like growth factor type II

IGHD

Isolated growth hormone deficiency

IMT

Intima-media thickness

LDL cholesterol

Low-density lipoprotein cholesterol

QoL

Quality of life

Notes

Acknowledgments

Manuel H. Aguiar-Oliveira was supported by a grant BEX 4309/08-1 from Capes, “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior,” from the Brazilian government.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Manuel Herminio Aguiar-Oliveira
    • 1
    • 2
  • Roberto Salvatori
    • 3
  1. 1.Division of EndocrinologyFederal University of SergipeSergipeBrazil
  2. 2.Department of MedicineFederal University of SergipeSergipeBrazil
  3. 3.Division of EndocrinologyJohns Hopkins University School of MedicineBaltimoreUSA

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