Familial Isolated Growth Hormone Deficiency Is Associated with Increased Systolic Blood Pressure, Central Obesity, and Dyslipidemia

Abstract

To assess the metabolic and cardiovascular consequences of GH deficiency (GHD) on cardiovascular risk factors, we studied a homogeneous population with GHD due to a homozygous defect in the GHRH receptor gene. Anthropometric, metabolic, and cardiovascular measurements (at rest, during treadmill exercise, and during orthostatic stress) and echocardiographic data were obtained from 16 GH-naive, GH-deficient (GHD) adults and 31 age-, sex-, and body mass index-matched control (CO) subjects. The percentage of fat mass, waist to hip ratio, and total and low density lipoprotein cholesterol were higher in the GHD group. However, high density lipoprotein cholesterol, triglyceride, and fasting glucose levels were similar between groups, and fasting insulin and homeostasis model assessment of insulin resistance (HOMA(IR)) were lower in the GHD group. Systolic blood pressure (SBP) was higher in the GHD group, but no difference in diastolic blood pressure or heart rate (HR) existed. Blood pressure and HR responses to exercise did not differ between groups. During passive orthostatic stress the decrease in SBP was higher in the GHD than in the CO group, whereas an increase in diastolic blood pressure was not observed in the GHD group. Moreover, the increase in HR was blunted in the GHD compared with the CO group. Left ventricular mass and mass index were lower in the GHD group. In conclusion, this genetically homogeneous isolated GHD population presents a syndrome characterized by central obesity, dyslipidemia, and elevated SBP but reduced cardiac dimensions compared with controls.

Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice

“…It is possible that the discrepant data could be due to other effects of GHR deficiency in females and males. GH-deficient humans and hypophysectomized rats have higher LDL cholesterol and apoB levels than normal controls (4,17,40,41). However, GH-deficient humans (44), hypophysectomized rats (40), and GHR Ϫ/Ϫ mice have in common lower levels of HDL cholesterol than controls.…”

Conseqüências em longo prazo da deficiência do hormônio de crescimento

“…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.…”

“…Embora a DIGH moderada de início na idade adulta seja associada à insulino-resistência (27,28), os indiví-duos com DIGH de Itabaianinha apresentam níveis insulínicos reduzidos e dos valores de índice de resistência à insulina homeostasis model assessment, HOMA-IR (glicemia (mMol) × insulina (uU/mL) ÷ 22,5) menores que dos controles da mesma região (10,22), até em idade avançada. Estudos de sensibilidade à insulina utilizando teste endovenoso de tolerância à glicose, com a aplicação da análise do modelo mínimo das variações das concentrações de glicose e de insulina após a administração da glicose (29), deverão ser realizados nestes indivíduos para melhor avaliar a secreção insulínica.…”

Growth hormone-induced blood pressure decrease is associated with increased mRNA levels of the vascular smooth muscle KATP channel

“…Besides affecting cardiac structure and contractility (Fazio et al 1997, Longobardi et al 2000, Barreto-Filho et al 2002, both experimental and clinical GH deficiency has been associated with increased systemic vascular resistance (Fazio et al 1997, Longobardi et al 2000 and abnormal vascular reactivity (Rossoni et al 1999, Evans et al 2000, Capaldo et al 2001. Accordingly, an increased prevalence of hypertension (Barreto-Filho et al 2002) and atherosclerotic disease (Pfeifer et al 1999) has been reported among patients with GH deficiency, and hypopituitary patients show increased cardiovascular morbidity and mortality (Rosen & Bengtsson 1990).…”

“…Besides affecting cardiac structure and contractility (Fazio et al 1997, Longobardi et al 2000, Barreto-Filho et al 2002, both experimental and clinical GH deficiency has been associated with increased systemic vascular resistance (Fazio et al 1997, Longobardi et al 2000 and abnormal vascular reactivity (Rossoni et al 1999, Evans et al 2000, Capaldo et al 2001. Accordingly, an increased prevalence of hypertension (Barreto-Filho et al 2002) and atherosclerotic disease (Pfeifer et al 1999) has been reported among patients with GH deficiency, and hypopituitary patients show increased cardiovascular morbidity and mortality (Rosen & Bengtsson 1990). GH treatment in GH deficient states has been shown to normalize systemic vascular resistance (Boger et al 1996, Longobardi et al 2000, arterial stiffness (Smith et al 2002), endothelial and/or endothelium-independent vasodilation (Rossoni et al 1999, Evans et al 2000, Capaldo et al 2001, and may reverse markers of early atherosclerosis (Pfeifer et al 1999).…”