The multiple facets of GHRH/GH/IGF-I axis: Lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation

Manuel H. Aguiar-Oliveira, Anita H.O. Souza, Carla R.P. Oliveira, Viviane C. Campos, Luíz A. Oliveira-Neto, Roberto Salvatori

Research output: Contribution to journalReview article

Abstract

Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of -7.2, total maxillary length of -6.5, total facial height of -4.3 and cephalic perimeter of -2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.

Original languageEnglish (US)
Pages (from-to)R85-R97
JournalEuropean Journal of Endocrinology
Volume177
Issue number2
DOIs
StatePublished - Aug 1 2017

Fingerprint

Pituitary Dwarfism
Insulin-Like Growth Factor I
Genu Valgum
Delayed Puberty
Blood Pressure
Insulin-Like Growth Factor Binding Protein 3
Mutation
Insulin-Like Growth Factor II
Abdominal Obesity
Sensorineural Hearing Loss
Optic Disk
Dizziness
Menopause
Hypoglycemia
C-Reactive Protein
LDL Cholesterol
HDL Cholesterol
Genes
Uterus
Brazil

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

The multiple facets of GHRH/GH/IGF-I axis : Lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation. / Aguiar-Oliveira, Manuel H.; Souza, Anita H.O.; Oliveira, Carla R.P.; Campos, Viviane C.; Oliveira-Neto, Luíz A.; Salvatori, Roberto.

In: European Journal of Endocrinology, Vol. 177, No. 2, 01.08.2017, p. R85-R97.

Research output: Contribution to journalReview article

Aguiar-Oliveira, Manuel H. ; Souza, Anita H.O. ; Oliveira, Carla R.P. ; Campos, Viviane C. ; Oliveira-Neto, Luíz A. ; Salvatori, Roberto. / The multiple facets of GHRH/GH/IGF-I axis : Lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation. In: European Journal of Endocrinology. 2017 ; Vol. 177, No. 2. pp. R85-R97.
@article{9cec7b14fd874d2c85ecd78af48f047d,
title = "The multiple facets of GHRH/GH/IGF-I axis: Lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation",
abstract = "Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of -7.2, total maxillary length of -6.5, total facial height of -4.3 and cephalic perimeter of -2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.",
author = "Aguiar-Oliveira, {Manuel H.} and Souza, {Anita H.O.} and Oliveira, {Carla R.P.} and Campos, {Viviane C.} and Oliveira-Neto, {Lu{\'i}z A.} and Roberto Salvatori",
year = "2017",
month = "8",
day = "1",
doi = "10.1530/EJE-16-1047",
language = "English (US)",
volume = "177",
pages = "R85--R97",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "2",

}

TY - JOUR

T1 - The multiple facets of GHRH/GH/IGF-I axis

T2 - Lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation

AU - Aguiar-Oliveira, Manuel H.

AU - Souza, Anita H.O.

AU - Oliveira, Carla R.P.

AU - Campos, Viviane C.

AU - Oliveira-Neto, Luíz A.

AU - Salvatori, Roberto

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of -7.2, total maxillary length of -6.5, total facial height of -4.3 and cephalic perimeter of -2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.

AB - Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of -7.2, total maxillary length of -6.5, total facial height of -4.3 and cephalic perimeter of -2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.

UR - http://www.scopus.com/inward/record.url?scp=85023197465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023197465&partnerID=8YFLogxK

U2 - 10.1530/EJE-16-1047

DO - 10.1530/EJE-16-1047

M3 - Review article

C2 - 28428227

AN - SCOPUS:85023197465

VL - 177

SP - R85-R97

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 2

ER -