Consequences of lifetime isolated Growth Hormone deficiency

终生孤立生长激素缺乏的后果

• 批准号: 7256898
• 负责人: Roberto Salvatori
• 金额: $ 27.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256898
• 关键词: Adult; Advocate; Affect; Age; Alleles; Area; Body Composition; Bone Density; Brazil; C-reactive protein; Cardiac; Cardiovascular Physiology; Cardiovascular system; Central obesity; Childhood; Communities; County; Cranial Irradiation; Data; Diagnosis; Fibrinogen; Frequencies; General Population; Genes; Genetic; Genotype; Gland; Goals; Heterozygote; Hormone Receptor; Hormone replacement therapy; Human; Hypothalamic structure; Individual; Inflammatory; Interleukin-6; LDL Cholesterol Lipoproteins; Life; Link; Metabolic; Metabolism; Modeling; Morbidity - disease rate; Muscle; Mutation; Numbers; Online Mendelian Inheritance In Man; Organ; Patients; Phenotype; Physiological; Pituitary Diseases; Pituitary Gland; Pituitary Hormones; Plasma; Population; Population Growth; Publishing; Radiation therapy; Rare Diseases; Receptor Gene; Replacement Therapy; Risk Factors; Serum; Somatotropin; Somatotropin-Releasing Hormone; Somatropin; Study Subject; Syndrome; Testing; Thyroid Gland; bone metabolism; cardiovascular disorder risk; cardiovascular risk factor; growth hormone deficiency; growth hormone-releasing hormone receptor; hormone therapy; member; muscle strength; null mutation; receptor; response; rural area; sex

DESCRIPTION (provided by applicant): 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.

描述（由申请方提供）：成人GH缺乏症（GHD）与身体组成、心血管功能、与心血管风险相关的代谢参数以及骨密度和代谢的变化相关。这些观察结果已被用于倡导GH治疗GHD成人。然而，迄今为止发表的研究大多是在经常患有慢性病、缺乏其他垂体激素的患者中进行的，这些患者的替代疗法可能不是最佳的，和/或接受过放射治疗（所有因素都能影响发病率）。关于GHD后果的可靠数据只能通过研究其他健康的患者来获得。巴西（Itabaianinha县）有大量GHRH受体（GHRHR）基因纯合突变导致的GHD成人GH初治人群。我们建议研究该突变的纯合子受试者，并将其与来自同一社区的正常受试者进行比较。我们的主要目标是确定终身GHD对身体组成，心血管功能和危险因素，骨密度和代谢以及甲状腺状态的影响，并测试这些参数中哪些可以通过6个月的hGH替代治疗逆转。第二个目标是检验突变的杂合性导致介于纯合正常和GHD个体之间的表型的假设。 具体目标1：研究20名GH初治GHD受试者的身体组成、心血管状况、心血管风险状况、代谢参数、甲状腺状况和骨矿物质密度，并将其与来自同一社区的20名年龄和性别匹配的对照组进行比较。 具体目的2：检查GHD个体对6个月GH治疗的反应。 具体目标3：对Itabaianinha群体的大量明显正常的成员进行基因分型，以将野生型等位基因纯合的受试者与GHRHR突变杂合的受试者分开，并将100个杂合子的表型与在100个纯合正常个体中观察到的表型进行比较。

项目成果

GH response to hypoglycemia and clonidine in the GH-releasing hormone resistance syndrome.

GH 释放激素抵抗综合征中 GH 对低血糖和可乐定的反应。

• DOI: 10.1007/bf03347374
• 发表时间: 2006
• 期刊: Journal of endocrinological investigation
• 影响因子: 5.4
• 作者: Salvatori,R;Serpa,MG;Parmigiani,G;Britto,AVO;Oliveira,JLM;Oliveira,CRP;Prado,CM;Farias,CT;Almeida,JC;Vicente,TAR;Aguiar-Oliveira,MH
• 通讯作者: Aguiar-Oliveira,MH

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.

由于 GHRH 受体基因纯合突变导致严重、未经治疗的先天性 GH 缺乏症，导致严重身材矮小的成年人的腹部器官大小。

• DOI: 10.1111/j.1365-2265.2007.03148.x
• 发表时间: 2008
• 期刊: Clinical endocrinology
• 影响因子: 3.2
• 作者: Oliveira,CarlaRP;Salvatori,Roberto;Nóbrega,LucianaMA;Carvalho,ErickOM;Menezes,Menilson;Farias,CatarineT;Britto,AllanVO;Pereira,RossanaMC;Aguiar-Oliveira,ManuelH
• 通讯作者: Aguiar-Oliveira,ManuelH

The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance.

• DOI: 10.1111/j.1365-2265.2011.04263.x
• 发表时间: 2012-09
• 期刊: Clinical endocrinology
• 影响因子: 3.2
• 作者: Gois MB Jr;Salvatori R;Aguiar-Oliveira MH;Pereira FA;Oliveira CR;Oliveira-Neto LA;Pereira RM;Souza AH;Melo EV;de Paula FJ
• 通讯作者: de Paula FJ

Climacteric in untreated isolated growth hormone deficiency.

未经治疗的孤立性生长激素缺乏症的更年期。

• DOI: 10.1097/gme.0b013e31815b97d4
• 发表时间: 2008
• 期刊: Menopause (New York, N.Y.)
• 作者: Menezes,Menilson;Salvatori,Roberto;Oliveira,CarlaRP;Pereira,RossanaMC;Souza,AnitaHO;Nobrega,LucianaMA;Cruz,EdlaAC;Menezes,Marcos;Alves,EricaO;Aguiar-Oliveira,ManuelH
• 通讯作者: Aguiar-Oliveira,ManuelH

Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency.

先天性孤立性 GH 缺乏症成人在中断 GH 替代后可阻止动脉粥样硬化进展。

• DOI: 10.1530/eje-12-0062
• 发表时间: 2012
• 期刊: European journal of endocrinology
• 影响因子: 5.8
• 作者: Araujo,VanessaP;Aguiar-Oliveira,ManuelH;Oliveira,JoselinaLM;Rocha,HertalineMN;Oliveira,CarlaRP;Rodrigues,TâniaMA;Nunes,MarcoA;Britto,IsabellaMPA;Ximenes,Roberto;Barreto-Filho,JoseAS;Meneguz-Moreno,RafaelA;Pereira,Ro
• 通讯作者: Pereira,Ro