Avaliação da vasorreatividade cerebral, um marcador substituto da doença cerebrovascular, na deficiência congênita e isolada de GH

Abstract

Introduction: Cerebrovascular disease is a major cause of death and disability. Overweight, diabetes mellitus, arterial hypertension, dyslipidemia, sedentary lifestyle and smoking are risk factors for cardiovascular and cerebrovascular disease. The role of the GH/IGF-I axis in the risk of cerebrovascular disease is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit cerebrovascular disease predisposing factors, as low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness (IMT), an alternative marker of atherosclerosis. However, several confounders such as the primary hypothalamic-pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Objective: to evaluate cerebral vasoreactivity, a surrogate marker of cerebrovascular disease, in adult subjects with untreated isolated growth hormone deficiency (IGHD) due to c.57 + 1G> A mutation in the GH releasing hormone (GHRH) receptor gene. Methods: This is a cross-sectional study with 25 IGHD adult subjects and 25 age- and gendermatched controls. Interview, physical examination, laboratory exams with metabolic profile, calculus of the Framingham risk score, IMT measurement and transcranial Doppler were performed. The intracranial hemodynamics was evaluated by mean flow velocity (MFV), pulsatility (PI) and resistance indexes (RI), and the breath holding index, this one after vasodilatory stimulus of hypercapnia. Results: IGHD and control groups were similar with regard to cardiovascular risk factors, including the Framingham risk score. Carotid intima-media thickness, mean flow velocity, pulsatility, resistance and apnea indices were also similar between groups. There was a positive correlation between age with IMT, age with PI and age with RI, as well as 2-hour glucose in oral glucose tolerance test with IMT and with RI and between IMT with PI and IMT with RI. Conclusion: Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity.