Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation

Background: GH deficiency (GHD) acquired at adult age as a result of pathological processes of the pituitary gland or the hypothalamus causes changes that are associated with worsening cardiovascular risk. They include increase in abdominal obesity, total and low-density lipoprotein cholesterol, and C-reactive protein. GHD adults also have thickening of the carotid arteries. It has been postulated that GHD is the link between hypopituitarism and the increase in cardiovascular and cerebrovascular mortality observed in hypopituitarism. However, several confounding factors exist, such as associated pituitary deficits and replacement of other hormones or surgical or radiological therapies used to treat the underlying pituitary of hypothalamic pathologies. Objective: The aim of this study was to determine the consequences of lifetime isolated GHD (IGHD) on the metabolic and cardiovascular status of adult members of a large Brazilian cohort with severe IGHD due to a homozygous mutation in the GHRH receptor gene. Design: Twenty-two GH naive adult dwarfs ( 10 men and 12 women; aged 44 +/- 12 yr) were compared with 22 healthy volunteers ( 10 men and 12 women; aged 45 +/- 12 yr) living in the same area. Results: GHD subjects had increased abdominal obesity, higher total and low-density lipoprotein cholesterol, and higher C-reactive protein than controls. They did not have an increase in carotid wall thickness, and there was no evidence of premature atherosclerosis as evaluated by exercise echocardiography. Conclusions: In this homogeneous cohort residing in a rural area of Brazil, lifetime, untreated severe IGHD is not associated with evidence of premature atherosclerosis despite unfavorable cardiovascular risk profile.