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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A serie of 12 cases of hypopituitarism (Sheehan's syndrome, pituitary adenoma, idiopathic) associated with hyperlipidemia (type IIb in general), is reported. It is suggested that: 1--Growth hormone deficiency seems to have a protective effect against atherosclerosis in hyperlipidemia because there are no cardiovascular signs in 10 cases with a history of growth hormone deficiency lasting from 5 to 57 years and a manifesting hyperlipidemia (lasting a mean of 23 years), and there is stabilisation or improvement of ischemic signs in 2 other cases. 2--Lipid abnormalities are frequently seen in hypopituitarism even after thyroid replacement therapy. 3--The hyperlipidemia can be familial or can result from growth hormone deficiency alone.
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PMID:[Hypopituitarism and hyperlipidemia. Protective effect of growth hormone deficiency against atherosclerosis (author's transl)]. 54 77

Twelve cases of hypopituitarism (Sheehan's syndrome, pituitary adenoma, idiopathic) associated with hyperlipidemia (type IIb in general) are reported. It is suggested that: 1 - Growth hormone deficiency seems to have a protective effect against atherosclerosis in hyperlipidemia because there are no cardiovascular signs in 10 cases with a history of growth hormone deficiency lasting from 5 to 57 years and a patent hyperlipidemia (lasting a mean of 23 years), and there is stabilisation or improvement of ischemic signs in 2 other cases. 2 - Lipid abnormalities are frequently seen in hypopituitarism even after thyroid replacement therapy. 3 - The hyperlipidemia can be familial or can result from growth hormone deficiency alone.
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PMID:[Hypopituitarism and hyperlipidemia. Protective effect of growth hormone deficiency against atherosclerosis (author's transl)]. 54 16

Non-arteriosclerotic, virgin and arteriosclerotic breeder rats were subjected to chronic treatment with prolactin or prolactin-releasing drugs such as perphenazine and reserpine for 12 weeks. Males and females responded to the prolactin as evidenced by increased milk secretion, adrenal hyperplasia and thymus gland involution. Although the prolactin- and reserpine-treated animals gained weight and manifested pituitary gland basophilia, the perphenazine-treated animals showed considerable loss of body weight as well as involution of the pituitary gland, ovaries and testes, suggesting a condition of induced hypopituitarism. Chronic treatment with prolactin, both directly and indirectly, caused uniform increases in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, lipids, e.g., triglycerides, free fatty acids and cholesterol, glucose and BUN. Corticosterone production was enhanced by prolactin, reduced by perphenazine and unaffected by reserpine. Prolactin did not induce any arterial disease in the arteriosclerosis-resistant, virgin rats but it did cause eracerbation of the usual severity of arteriosclerosis in the hilar renal arteries of the arteries sclerosis-prone, breeder rats as well as an increased incidence of "old" and "new" foci of myocardial necrosis, characteristically found in breeder rats. It is suggested that hypothalamic control of prolactin as well as ACTH release may play a role in the spontaneous arteriosclerosis which develops in repeatedly-bred, male and female rats.
Atherosclerosis
PMID:Comparative effects of prolactin, perphenazine and reserpine on non-arteriosclerotic (virgin) vs arteriosclerotic (breeder) rats. 94 17

Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p < 0.005). In multiple regression analysis, patients' age was the dominant factor determining carotid intima-media thickness. Symptom-free adults with hypopituitarism show an increased prevalence of atherosclerosis.
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PMID:Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. 809 46

Hyperlipidemia has been reported in adults with hypopituitarism, and human (h) GH therapy has been shown to lower plasma cholesterol in patients with hypercholesterolemia. Macrophage cholesterol accumulation is an early event in atherosclerosis, and these cells have been shown to respond to GH and insulin-like growth factor (IGF-I). The present study was aimed at investigating the activity of GH and IGF-I in macrophages, and used murine macrophages as a model system to investigate the effects of GH and IGF-I on cellular uptake and metabolism of low density lipoprotein (LDL). The J-774 murine macrophage cell line was shown to bind hGH, to respond to hGH by an increase in cell IGF-I content, and to have specific high affinity binding sites for IGF-I. Mouse peritoneal macrophages and the J-774 macrophage cell line respond to hGH with a dose-dependent stimulation of cellular association and degradation of LDL as well as an enhanced cholesterol esterification rate. A similar response was observed after in vitro treatment of the cells with IGF-I. Preliminary results in human monocyte-derived macrophages showed similar results. The dependency of the effect of hGH on locally produced IGF-I was shown by abrogation of the hGH effect after adding anti-IGF-I antibody to the culture medium. It is concluded that murine macrophages possess the machinery to bind GH, produce IGF-I, and bind IGF-I. This machinery is used by macrophages, and apparently by other cells, to execute GH-dependent IGF-I-mediated stimulation of cellular uptake and metabolism of LDL. This may provide the explanation for both the elevated plasma LDL concentration in patients with GH deficiency and the effect of GH therapy to reduce plasma LDL levels.
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PMID:Growth hormone and insulin-like growth factor-I increase macrophage uptake and degradation of low density lipoprotein. 161 24

We investigated the effects of long-term testosterone replacement in hypogonadal and elderly men on lipids and lipoproteins. Twenty-two men with initial serum testosterone concentrations below 3.5 ng/ml took part in the study: 11 with hypopituitarism (1st group) and 11 otherwise healthy elderly men with low testosterone levels (2nd group). Testosterone deficiency was replaced by intramuscular injections of testosterone enanthate 200 mg every second week. Plasma levels of sex hormones, gonadotropins, SHBG, lipids and lipoproteins were determined before the treatment and after 3, 6 and 12 months of treatment. During the treatment serum testosterone and estradiol increased significantly, reaching normal levels. This was associated with a decrease in total cholesterol (from 225 +/- 16.9 mg/dl to 202 +/- 13.6 mg/dl after 6 months and 198 +/- 12.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 255 +/- 12.1 mg/dl to 214 +/- 10.6 mg/dl after 6 months and 206 +/- 9 mg/dl after 1 year of treatment, P < 0.0001 in men with hypopituitarism) and LDL-cholesterol concentrations (from 139 +/- 12.5 mg/dl to 126 +/- 10.7 mg/dl after 6 months and 118 +/- 9.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 178 +/- 10.3 mg/dl to 149 +/- 10.2 mg/dl after 6 months and 140 +/- 7.3 mg/dl after 1 year of treatment, P < 0.001 in men with hypopituitarism). However, no significant decrease in HDL-cholesterol levels or HDL2- and HDL3-cholesterol subfractions was observed. The effects of testosterone replacement therapy on lipids and lipoproteins were similar in both groups with different aetiology of hypogonadism. No side effects on the prostate were observed. The results of this study indicate that testosterone replacement therapy in hypogonadal and elderly men may have a beneficial effect on lipid metabolism through decreasing total cholesterol and atherogenic fraction of LDL-cholesterol without significant alterations in HDL-cholesterol levels or its subfractions HDL2-C and HDL3-C.
Atherosclerosis 1996 Mar
PMID:Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. 867 22

The effect of growth hormone replacement therapy in near physiological doses on lipoprotein composition and serum lipoprotein(a) concentrations was investigated in growth hormone-deficient subjects. A randomised, double-blind, placebo-controlled trial of recombinant growth hormone was undertaken for 6 months followed by an open extension for a further 6 months (0.125 IU/kg per week for the first 4 weeks of each 6 month period and thereafter 0.25 IU/kg per week). A total of 18 patients with isolated growth hormone deficiency or hypopituitarism were studied. Lipid concentrations were estimated in lipoprotein fractions and protein concentrations were measured in low density lipoprotein (LDL). Glucose and glycated haemoglobin in blood and insulin, cholesterol, triglyceride, apolipoproteins A-I and B and lipoprotein(a) concentrations were measured in serum. In the placebo-controlled phase fasting blood glucose concentrations increased with growth hormone treatment from 5.0 +/- 0.2 to 5.8 +/- 0.2 mmol/l (P = 0.02) (mean +/- S.E.M.), although no significant changes were seen in lipids or lipoproteins. In the group receiving active treatment total serum cholesterol decreased from 6.0 +/- 0.4 to 5.2 +/- 0.3 mmol/l (P = 0.002) after 6 months, due to reduced LDL cholesterol concentrations. Low density lipoprotein protein concentrations fell (0.8 +/- 0.1 versus 0.7 +/- 0.1 g/l) (P = 0.005), and LDL phospholipid levels decreased from 0.9 +/- 0.1 to 0.7 +/- 0.1 mmol/l (P = 0.007). Serum cholesterol and LDL composition reverted to pre-treatment values by 12 months. Fasting blood glucose remained above pre-treatment values (P = 0.036) and fasting insulin was significantly increased (P = 0.044). There was no effect of growth hormone therapy on serum triglyceride, apolipoprotein or lipoprotein(a) concentrations. In conclusion, growth hormone therapy with near physiological doses has no long term effects on serum lipoprotein(a) concentrations or lipoprotein composition.
Atherosclerosis 1997 Aug
PMID:The effect of growth hormone replacement therapy for up to 12 months on lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults. 925 15

Adult hypopituitarism is known to be associated with reduced life expectancy related to excess vascular events, and endothelial dysfunction is present in patients with this condition. We studied the relationship between biophysical and biochemical markers of endothelial dysfunction, including E-selectin, intercellular cell adhesion molecule-1, von Willebrand factor, and thrombomodulin in 52 adult patients with hypopituitarism and severe GH deficiency (<2 ng/ml on provocative testing) compared with 54 age-, sex-, and smoking-matched normal controls. We also examined endothelium-dependent dilatation of the brachial artery to postischemic occlusion and carotid artery morphology (intima-media thickness) by high-resolution ultrasonography. The patients were stable on conventional hormone replacement therapy but not on GH therapy, and none of the subjects had a known risk factor for vascular disease. Levels of E-selectin [57 +/- 3 vs. 49 +/- 2 ng/ml (mean +/- SEM)] (P < 0.043), intercellular cell adhesion molecule-1 (308 +/- 11 vs. 266 +/- 10 ng/ml) (P < 0.001), thrombomodulin (49 +/- 3 vs. 35 +/- 2 ng/ml) (P < 0.001), and von Willebrand factor (132 +/- 7% vs. 105 +/- 5%) (P < 0.004) were significantly higher in patients than in controls. Brachial artery endothelium-dependent dilatation was significantly lower in patients than in controls [4.7% (0.00-9.77) vs. 10.5% (6.4-16.2) (median, interquartile range)] (P < 0.001). This difference in endothelium-dependent dilatation was more marked in female patients than in controls (P < 0.003), although it disappeared when estrogen-sufficient female patients were compared with controls (P = 0.31). However, the female patients who were not replaced with estrogen continued to show a striking difference compared with estrogen-deficient control females (P < 0.004). There was no difference in carotid intima-media thickness between patients of either sex and controls. On univariate analysis, brachial artery endothelium-dependent dilatation correlated inversely with intercellular cell adhesion molecule-1 (r = -0.225, P < 0.033). Intercellular cell adhesion molecule-1 correlated positively with E-selectin (r = 0.466, P < 0.0001) and negatively with IGF-I (r = -0.238, P < 0.016). E-selectin correlated with thrombomodulin (r = 0.215, P < 0.034) and von Willebrand factor (r = 0.218, P < 0.03) and negatively with IGF-I (r = -0.255, P < 009). Thrombomodulin correlated positively with von Willebrand factor (r = 0.422, P < 0.0001) and inversely with IGF-I (r = -0.266, P < 0.008). These correlations persisted after correction for age, sex, body mass index, and waist to hip ratio, with the exception of IGF-I, which now correlated with thrombomodulin only. These results confirm significant endothelial dysfunction in hypopituitarism and provide insight into the relationship of biochemical and biophysical markers of early atherosclerosis in hypopituitary GH-deficient adults. The negative correlation of IGF-I with some biochemical markers of endothelial dysfunction and the predictive nature of GH deficiency in stepwise regression analysis in this study supports the hypothesis that GH deficiency may play a role in these abnormalities. Future studies will determine whether GH treatment can reverse these abnormalities. Furthermore, the more significant endothelium-dependent dilatation abnormality in the female estrogen-deficient subjects compared with those who were estrogen replete suggests that estrogen replacement in these patients is a crucial element in protecting against vascular disease.
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PMID:Biochemical and biophysical markers of endothelial dysfunction in adults with hypopituitarism and severe GH deficiency. 1154 53

In the last decade, retrospective cohort data has provided evidence of premature atherosclerosis in patients with hypopituitarism which may account for the recently observed increased death rate from vascular events in these patients. The exact mechanism(s) for such propensity to atherosclerotic vascular disease is not yet completely clear. It is possible that hormonal factors may be the initiating mechanisms with subsequent secondary metabolic abnormalities acting as risk factors for development of atherosclerosis. This seems to be more evident in female hypopituitary patients compared with their male counterparts. Female patients have higher frequency and more pronounced abnormalities of various risk factors as well as surrogate markers of early vascular disease. This may explain why morbidity and mortality in women is in excess of men in retrospective epidemiological studies. Addressing abnormal hormonal factors, especially in females, is a primary objective in managing these patients both in the clinical arena as well as in trials designed to reduce the risk of atherosclerotic vascular disease in these patients. While short-term growth hormone treatment may ameliorate some of the vascular risk factors and improve endothelial function, it remains to be shown whether this translates into long-term reduction in morbidity and mortality from vascular, especially cerebrovascular, disease.
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PMID:Hypopituitarism and atherosclerosis. 1168 Jul 96

Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism and GH deficiency. However, little is known about inflammatory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and 111 healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BMI), and estrogen use. There was an interaction between the effect of BMI and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.
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PMID:Inflammatory cardiovascular risk markers in women with hypopituitarism. 1210 75


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