Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan

Gleeson, Helena; Souza, Anita H. O.; Gill, Matthew S.; Wieringa, Gilbert E; Barretto, Elenilde S. De A.; Barretto-Filho, J. A. S.; Shalet, Stephen M; Aguiar‐Oliveira, Manuel H.; Clayton, Peter E.

doi:10.1046/j.1365-2265.2002.01568.x

Cited by 38 publications

(22 citation statements)

References 27 publications

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“…These data seem to indicate that heterozygosity for the Itabaianinha GHRHR mutation causes a decline both in FM and FFM, albeit more marked for FFM. Reduction in FFM is commonly found in adults with acquired GHD (30), and we have found it in GH-naive GHD patients from Itabaianinha throughout life span (15)(16)(17). However, the reduction in FFM caused by GHD is usually associated with an increase in absolute and percentage FM (31).…”

Section: Discussionmentioning

confidence: 96%

Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition

Pereira

Aguiar‐Oliveira

Sagazio

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD).Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype. Methods:We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT). Results:We found no difference in adult height and SD score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups.Conclusions: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.

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Section: Discussionmentioning

confidence: 96%

Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition

Pereira

Aguiar‐Oliveira

Sagazio

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…As crianças e os adolescentes com DIGH de Itabaianinha apresentam níveis elevados de colesterol LDL e de colesterol total em comparação com os controles da mesma região (21,23), que continuam durante toda a vida (10,22), efeito eventualmente associado à redução da expressão dos receptores hepáticos para o colesterol LDL. Estudos em ratos e humanos mostraram efeito importante de GH no metabolismo hepáti-co do colesterol.…”

Section: Metabolismo Lipídicounclassified

“…Alia-se a isso complexo conjunto de alterações metabólicas e de composição corporal com fatores adversos ou protetores para a saúde em geral e sem piora da QV. O tratamento com GH subcutâneo diário em crianças, além de provocar o ganho estatural, melhora o perfil lipídico e a composição corporal (21,23). Resultados semelhantes sobre o perfil lipídico e a composição corporal foram obtidos em adultos, sem repercussões sobre a glicemia ou a hemoglobina glicada, com a administração do GH de depósito subcutâneo a cada 15 dias (34), acrescido de melhora da remodelação óssea, de padrão anabólico, com conseqüente aumento da resistência óssea (32).…”

Section: Considerações Finaisunclassified

Conseqüências em longo prazo da deficiência do hormônio de crescimento

Oliveira

Pereira

Barreto‐Filho

et al. 2008

Arq Bras Endocrinol Metab

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RESUMOeste artigo descreve as conseqüências puras, em longo prazo, da deficiência isolada e vitalícia do hormônio de crescimento (gH) porque usa um modelo único de resistência ao hormônio liberador do gH (gHrH), em virtude da mutação homozigótica no gene do receptor do gHrH, em uma centena de indivíduos acometidos. elas incluem baixa estatura grave com estatura final entre -9,6 a -5,2 desvios-padrão abaixo da média, com redução proporcional das dimensões ósseas, redução do volume da adenohipófise corrigido para o volume craniano e da tireóide, do útero, do baço e da massa ventricular esquerda, todos corrigidos para a superfície corporal, em contraste com o tamanho de pâncreas e fígado, maior que o de controles, quando igualmente corrigidos. As alterações características da composição corporal incluem redução acentuada da quantidade de massa magra (kg) e aumento do percentual de gordura com depósito predominante no abdome. nos aspectos metabólicos são encontrados aumento de colesterol total e ldl, redução de insulina e do índice de resistência à insulina homeostasis model assessment, acompanhados de aumento da proteína c reativa de alta sensibilidade e da elevação da pressão arterial sistólica nos adultos, embora sem evidências de aterosclerose precoce. outros achados incluem resistência óssea menor, embora acima do limiar de fraturas, puberdade atrasada, fertilidade normal, paridade diminuída, climatério antecipado e qualidade de vida normal. ABSTRAcTLong Time Consequences of the Growth Hormone Deficiency. this article describes the long time consequences of the isolated and lifetime growth hormone (gH) deficiency using a single model of gH releasing hormone resistance (gHrH) due to a homozygous mutation in the gHrH receptor gene, in a hundred of subjects. these consequences include severe short stature with final height between -9.6 and -5.2 standard deviations below of the mean, with proportional reductions of the bone dimensions; reduction of the anterior pituitary corrected to cranial volume and the thyroid, the uterus, the spleen and left ventricular mass volume, all corrected to body surface, in contrast of pancreas and liver size, bigger than in controls, when equally corrected. Body composition features included marked reduction in the amount of fat free mass (kg) and increase of fat mass percentage, with predominant abdominal deposit. in the metabolic aspects, we find increase in the total cholesterol and ldl cholesterol; reduction of the insulin and the insulin resistance assessed by Homeostasis model assessment; increase of ultra sensitive c reactive protein and systolic body pressure in adults, although without evidences of premature atherosclerosis. other findings include smaller bone resistance, although above of the threshold of fractures, delayed puberty, normal fertility, small parity, anticipated climacteric and normal quality of life.

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“…Due to logistic problems, plasma ghrelin measurements have not yet been done. These IGHD subjects exhibit high serum total and LDL cholesterol levels throughout life (45,47). There is also a mild increase in systolic blood pressure in adults, and arterial hypertension in the elderly, without evidence of cardiac hypertrophy.…”

Section: Metabolic and Cardiovascular Consequencesmentioning

confidence: 99%

“…These features have been published in 42 different publications (2,19,22,25,27,29,30,31,32,33,36,37,38,40,41,44,45,46,47,48,49,50,51,52,53,54,56,57,61,62,63,64,66,67,68,74,75,76,77,78,79,80). We have used this experiment of nature to discover 'usual laws of nature' as suggested by William Harvey, and to understand some aspects of more common conditions such as short stature, insulin resistance, diabetes, atherosclerosis, osteoporosis, cancer and ultimately longevity.…”

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: 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

Souza

Oliveira

et al. 2017

European Journal of Endocrinology

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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.

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Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan

Abstract: The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood.

Cited by 38 publications

References 27 publications

Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition

Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition

Conseqüências em longo prazo da deficiência do hormônio de crescimento

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

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