Partial Growth Hormone Deficiency Is Associated With Adverse CV Risk
Partial Growth Hormone Deficiency Is Associated With Adverse CV Risk
Objective To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI).
Context Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults has yet to be comprehensively studied.
Design A cross-sectional case controlled study.
Patients Thirty GHD adults, 24 GHI, and 30 age- and sex-matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3–7 μg/l).
Measurements Serum lipids and apolipoproteins, plasminogen activator inhibitor type-I (PAI-I), C-reactive protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid intima-medial thickness (IMT).
Results IGF-I levels of GHI adults were lower than controls (373 ± 123 vs 295 ± 104 μg/l; P < 0·001). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI-I levels [80 (13–98) vs 50·5 (3–98) ng/ml; P = 0·01], although no there were differences in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic blood pressure were shown between study groups. In parallel with the increased vascular risk profile of GH-insufficient adults, carotid IMT was significantly increased (0·503 ± 0·08 vs 0·578 ± 0·130 mm; P = 0·02). TC, LDL-C, Waist-Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF-I levels and GH status. TG, KITT, and PAI-I additionally correlated with GH status, but not with IGF-I levels.
Conclusion GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.
Hypopituitary patients on conventional anterior hormone replacement, but not GH, have a twofold increased relative risk of mortality and show clustering of surrogate markers of cardiovascular risk including an elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), fibrinogen, and plasminogen activator inhibitor type-I (PAI-I); high-density lipoprotein cholesterol (HDL-C) is reduced, and insulin sensitivity impaired. Additionally, GH deficiency (GHD) patients have increased truncal fat mass (tFM), and evidence of impaired endothelial function and cardiac performance. It is not surprising, therefore, that the observed excess mortality of hypopituitary patients has been attributed, at least in part, to GHD.
GHD is defined by a peak GH response of <3 μg/l to the insulin tolerance test (ITT). Data from healthy adults confirm that a normal GH response to the ITT is significantly higher than this arbitrarily defined cut-off. In patients with putative hypopituitarism as a result of primary hypothalamo-pituitary pathology, a cohort with intermediate GH responses (peak GH 3·1–7·0 μg/l) can be defined. The clinical impact of this partial GHD (GH insufficiency, GHI) in adults has been partially characterized. GHI adults have increased total FM and tFM, insulin resistance, an adverse lipid profile, and impaired cardiac performance, but are not osteopenic. The current study is the first to comprehensively quantify surrogates of cardiovascular risk in hypopituitary adults with GHI.
Abstract and Introduction
Abstract
Objective To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI).
Context Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults has yet to be comprehensively studied.
Design A cross-sectional case controlled study.
Patients Thirty GHD adults, 24 GHI, and 30 age- and sex-matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3–7 μg/l).
Measurements Serum lipids and apolipoproteins, plasminogen activator inhibitor type-I (PAI-I), C-reactive protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid intima-medial thickness (IMT).
Results IGF-I levels of GHI adults were lower than controls (373 ± 123 vs 295 ± 104 μg/l; P < 0·001). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI-I levels [80 (13–98) vs 50·5 (3–98) ng/ml; P = 0·01], although no there were differences in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic blood pressure were shown between study groups. In parallel with the increased vascular risk profile of GH-insufficient adults, carotid IMT was significantly increased (0·503 ± 0·08 vs 0·578 ± 0·130 mm; P = 0·02). TC, LDL-C, Waist-Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF-I levels and GH status. TG, KITT, and PAI-I additionally correlated with GH status, but not with IGF-I levels.
Conclusion GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.
Introduction
Hypopituitary patients on conventional anterior hormone replacement, but not GH, have a twofold increased relative risk of mortality and show clustering of surrogate markers of cardiovascular risk including an elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), fibrinogen, and plasminogen activator inhibitor type-I (PAI-I); high-density lipoprotein cholesterol (HDL-C) is reduced, and insulin sensitivity impaired. Additionally, GH deficiency (GHD) patients have increased truncal fat mass (tFM), and evidence of impaired endothelial function and cardiac performance. It is not surprising, therefore, that the observed excess mortality of hypopituitary patients has been attributed, at least in part, to GHD.
GHD is defined by a peak GH response of <3 μg/l to the insulin tolerance test (ITT). Data from healthy adults confirm that a normal GH response to the ITT is significantly higher than this arbitrarily defined cut-off. In patients with putative hypopituitarism as a result of primary hypothalamo-pituitary pathology, a cohort with intermediate GH responses (peak GH 3·1–7·0 μg/l) can be defined. The clinical impact of this partial GHD (GH insufficiency, GHI) in adults has been partially characterized. GHI adults have increased total FM and tFM, insulin resistance, an adverse lipid profile, and impaired cardiac performance, but are not osteopenic. The current study is the first to comprehensively quantify surrogates of cardiovascular risk in hypopituitary adults with GHI.
Source...