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Premature atherosclerosis is a clinical feature in adult-onset GH deficiency. Evidence is accumulating that disturbances in triglyceride metabolism, reflected by abnormalities in circulating remnant lipoproteins, are associated with increased atherogenic potential. In a case-controlled intervention study, we investigated postprandial lipoprotein metabolism using a new remnant lipoprotein method based on immunoseparation principle [RLP-cholesterol (RLP-C)]. In addition, we analyzed retinyl ester (RE) analysis in plasma and in Sf , 1000 fraction. Endothelial function was assessed as flow-mediated dilatation (FMD). Eight patients diagnosed with acquired adult-onset GH deficiency and eight controls matched for gender, age, body mass index, and apolipoprotein (apo) E genotype were enrolled in the study. Oral vitamin A fat loading tests were performed at baseline in both groups and after 6 months of treatment with recombinant human GH (rh-GH) in the adult-onset GH-deficient patients. Adult-onset GHdeficient patients had significantly higher fasting RLP-C, postprandial RLP-C concentrations (plasma RLP-C, 0.29 6 0.14 mmol/L; and incremental area under the curve-RLP-C, 2.13 6 1.60 mmol*h/L, respectively) than controls (0.19 6 0.06 mmol/L and 1.05 6 0.72 mmol*h/L (P , 0.05), respectively). They also had significantly higher postprandial RE in plasma and Sf , 1000 fraction. Treatment with rh-GH significantly reduced postprandial RLP-C concentrations (incremental area under the curve-RPL-C 0.73 6 0.34 mmol*h/L; P , 0.05) but had no effects on the fasting RLP-C concentrations (0.317 6 0.09 mmol/L, P , 0.05), or on the postprandial RE in plasma and in Sf , 1000 fraction. Endothelial function measured as FMD was improved from 5.9 6 3.3% to 10.2 6 4.0% (P , 0.05) in patients treated with rh-GH. It is concluded that patients with adult-onset GH deficiency have increased levels of fasting and postprandial RLP-C and an impaired endothelial function as measured as FMD. Treatment with rh-GH resulted in a decrease of postprandial RLP-C concentration, thereby improving the postprandial atherogenic lipoprotein profile and improvement of endothelial function, however, the clearance of large chylomicron particles as reflected by RE remained disturbed. (J Clin Endocrinol Metab 85: 4683‐ 4689, 2000)

Nerve dysfunction in diabetes is associated with increased oxidative stress. Vitamin E depletion also leads to enhanced presence of reactive oxygen species (ROS). We compared systemic and endoneurial ROS activity and nerve conduction in vitamin E-depleted control and streptozotocin-diabetic rats (CE− and DE−), and in normally fed control and diabetic animals (CE+ and DE+). Nerve conduction was reduced in both diabetic groups. Vitamin E depletion caused a small further nerve conduction deficit in the diabetic, but not in the control animals. The combination of vitamin E deficiency and streptozotocin-diabetes (group DE−) appeared to be lethal. In the remaining groups, an important rise in sciatic nerve malondialdehyde (MDA) was observed in the vitamin E-depleted control rats. In contrast, plasma MDA levels were elevated in group DE+ only, whereas hydrogen peroxide levels were increased in group CE−. Endoneurial total and oxidized glutathione and catalase were predominantly elevated in group DE+. These data show that nerve lipid peroxidation induced by vitamin E depletion does not lead to reduced nerve conduction or changes in antioxidant concentrations as observed in STZ-diabetes. The marked systemic changes in MDA and antioxidants suggest that nerve dysfunction in experimental hyperglycemia is rather a consequence of systemic than direct nerve damage.

Selective iron deposition in the zona glomerulosa of the adrenal cortex is observed in hemochromatosis. Hypoaldosteronism should be excluded before starting venesection, to avoid long-term volume depletion. We evaluated the aldosterone status in patients with hemochromatosis. As other endocrine organs can be affected by the disease as well, we simultaneously evaluated anterior pituitary, gonadal, thyroid and pancreatic beta-cell activity. Nine patients with hereditary or acquired hemochromatosis and highly increased plasma ferritin levels were investigated. In patients, liver cirrhosis had been confirmed histologically. Five patients complained of sexual dysfunction, and one had impaired glucose tolerance. Plasma aldosterone (PA) and renin activity (PRA) were measured after a period of normal (100 mmol/day) and low (10 mmol/day) sodium intake. A combined anterior pituitary function test and a glucagon stimulation test were undertaken to evaluate other endocrine functions. Both PA and PRA levels were decreased in one patient with liver cirrhosis, who also presented attenuated cortisol, prolactin and gonadotrophin secretion. No patients had signs of primary hypoaldosteronism with hyperreninemia. Hypogonadotropic hypogonadism was observed in 3 males and 1 female. Pituitary ACTH reserve was impaired in 2, GH and prolactin response in 1, and thyroid function in none of the patients. Glucagon-stimulated plasma C-peptide was impaired in one patient. In conclusion, primary aldosterone deficiency was not observed in patients with severe iron overload. Hyporeninemic hypoaldosteronism was found in one patient who also presented other endocrinopathies. Hypogonadotropic hypogonadism is the most frequent endocrine abnormality in hemochromatosis.

As increased oxidative stress is probably a pathogenetic factor in the development of diabetic complications, we studied nerve function and endogenous antioxidants in plasma, erythrocytes and sciatic nerve of untreated and insulin-treated streptozotocin-diabetic rats. After 18 weeks, the diabetes-induced sciatic nerve conduction velocity deficits were approximately 65% improved by insulin (P < 0.001). Plasma superoxide dismutase was significantly reduced in diabetes (P < 0.01); smaller decreases in plasma catalase and glutathione levels were observed. These changes were corrected by insulin treatment. In erythrocytes, decreased superoxide dismutase (P < 0.05) and increased total glutathione levels (P < 0.05) were found. All effects of diabetes, including a rise in plasma malonyldialdehyde (P < 0.05), were partially reversed by insulin treatment. In nervous tissue, diabetes caused increased catalase activity, uninfluenced by insulin (P < 0.05). Nerve superoxide dismutase and glutathione did not change. The data suggest that in diabetes, changes in systemic rather than endoneurial oxidative stress lead to nerve dysfunction.