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Biomedical subjects

E Endert

Publications and source records attributed to E Endert.

At least 37 records · Page 2Linked to original sources
PubMed2001

Simultaneous gas chromatographic determination of concentration and isotopic enrichment of fatty acids in human plasma using flame ionization and mass spectrometric detection.

Free fatty acids (FFAs) are important not only because they provide substrate for oxidation but also because they have the potential to regulate several metabolic and hormonal processes. Using stable isotope tracers, these processes can be studied. Here we present a gas chromatographic method to measure FFA concentrations and enrichments after extraction from plasma and subsequent derivatization in one analytical run, using both flame ionization and mass-selective detection. For concentration determinations intra-assay variation ranged from 1.5 to 4.9%, inter-assay variation ranged from 3 to 11%. Intra- and inter-assay variations of the enrichment determination of palmitic acid were 1.4 and 0.9%, respectively.

Chromatography, Gas↗
PubMed2001

Isocaloric carbohydrate deprivation induces protein catabolism despite a low T3-syndrome in healthy men.

Dietary carbohydrate content is a major factor determining endocrine and metabolic regulation. The aim of this study was to evaluate the relation between thyroid hormone levels and metabolic parameters during eucaloric carbohydrate deprivation. We measured thyroid hormone levels, resting energy expenditure (by indirect calorimetry) and urinary nitrogen excretion in six healthy males after 11 days of three isocaloric diets containing 15% of energy equivalents as protein and 85%, 44% and 2% as carbohydrates. In contrast to the high and intermediate carbohydrate diets, carbohydrate deprivation decreased plasma T3 values (1.78 +/- 0.09 and 1.71 +/- 0.07 vs. 1.33 +/- 0.05 nmol/l, respectively, P < 0.01), whereas reverse T3, T3 uptake and free T4 levels increased simultaneously compared to the other two diets. TSH values were not different among the three diets. Although dietary carbohydrate content did not influence resting energy expenditure, carbohydrate deprivation increased urinary nitrogen excretion (10.91 +/- 0.67 and 12.79 +/- 1.14 vs. 15.89 +/- 1.10 g/24 h, respectively, P = 0.03). Eucaloric carbohydrate deprivation increases protein catabolism despite decreased plasma T3 levels. Because it has previously been shown that starvation decreases plasma T3 levels, resting energy expenditure and nitrogen excretion, these discordant endocrine and metabolic changes following carbohydrate deprivation indicate that the effects of starvation on endocrine and metabolic regulation are not merely the result of carbohydrate deprivation.

Adult↗
PubMed2001

Aminophylline stimulates insulin secretion in patients with type 2 diabetes mellitus.

In healthy subjects, paracrine factors partly regulate insulin secretion and basal endogenous glucose production. Administration of pentoxifylline, an adenosine receptor antagonist, inhibits transiently endogenous glucose production in healthy humans without any changes in glucoregulatory hormone concentrations. To evaluate the modulatory role of adenosine on endogenous glucose production and basal insulin secretion in type 2 diabetes, aminophylline, a potent adenosine receptor antagonist, was administered intravenously to 5 patients with type 2 diabetes mellitus in a saline-controlled study. Endogenous glucose production was measured before and during 6 hours after administration of aminophylline/saline by primed, continuous infusion of [6,6-(2)H(2)]glucose. During both experiments, the decrease in plasma glucose concentration was similar (16% v 18% from basal, not significant [NS]). After aminophylline administration, basal endogenous glucose production was transiently inhibited within 15 minutes to 70% from basal, whereas it did not change significantly in the control experiment (P =.02). The inhibition of glucose production coincided with stimulation of insulin secretion to 144% from basal 90 minutes after the administration of aminophylline (P =.008). In the control experiment insulin secretion decreased gradually by 29% during 6 hours. We conclude that aminophylline inhibits endogenous glucose production in type 2 diabetes by stimulation of insulin secretion. Paracrine factors, such as adenosine, may be involved in the regulation of basal insulin secretion in type 2 diabetes mellitus.

Aged↗
PubMed2001

Indomethacin does not affect endogenous glucose production in type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production is partly regulated by paracrine intrahepatic factors. It is currently unknown whether paracrine intrahepatic factors also influence the increased basal endogenous glucose production in patients with type 2 diabetes mellitus. Administration of indomethacin to patients with type 2 diabetes mellitus stimulates endogenous glucose production and inhibits insulin secretion. Our aim was to evaluate whether this stimulatory effect on glucose production is solely attributable to inhibition of insulin secretion. In order to do this, we administered indomethacin to 5 patients with type 2 diabetes during continuous infusion of somatostatin to block endogenous insulin and glucagon secretion and infusion of basal concentrations of insulin and glucagon in a placebo-controlled study. Endogenous glucose production was measured 3 hours after the start of the somatostatin, insulin and glucagon infusion, for 4 hours after administration of placebo/indomethacin, by primed, continuous infusion of [6,6-(2)H(2)] glucose. At the time of administration of placebo or indomethacin, there were no significant differences in plasma glucose concentrations and endogenous glucose production rates between the two experiments (16.4 +/- 2.09 mmol/l vs. 16.6 +/- 1.34 mmol/l and 17.7 +/- 1.05 micromol/kg/min and 17.0 +/- 1.06 micromol/kg/min), control vs. indomethacin). Plasma glucose concentration did not change significantly in the four hours after indomethacin or placebo administration. Endogenous glucose production in both experiments was similar after both placebo and indomethacin. Mean plasma C-peptide concentrations were all below the detection limit of the assay, reflecting adequate suppression of endogenous insulin secretion by somatostatin. There were no differences in plasma concentrations of insulin (76 +/- 5 vs. 74 +/- 4 pmol/l) and glucagon (69 +/- 8 vs. 71 +/- 6 ng/l) between the studies with levels remaining unchanged in both experiments. Plasma concentrations of cortisol, epinephrine, and norepinephrine were similar in the two studies and did not change significantly. We conclude that indomethacin stimulates endogenous glucose production in patients with type 2 diabetes mellitus by inhibition of insulin secretion.

Aged↗
PubMed2001

Dietary fat content alters insulin-mediated glucose metabolism in healthy men.

BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin resistance. OBJECTIVE: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.

Adult↗
PubMed2001

Glucose production and gluconeogenesis in adults with cerebral malaria.

Hypoglycaemia is an important complication in severe malaria, ascribed to an inhibition of gluconeogenesis. However, the only data available suggested that in severe malaria, total glucose production is increased. We measured glucose production and gluconeogenesis after an overnight fast in all seven patients with cerebral malaria (CM) consecutively admitted to Bao Loc General hospital over a 2-year period, and in six healthy sex- and age-matched controls. Glucose production was measured by infusion of [6,6-(2)H(2)]glucose and the contribution of gluconeogenesis by oral ingestion of (2)H(2)O. Compared to controls, plasma glucose concentration was 42% higher in CM patients (p=0.004), and glucose production was doubled (p=0.003). Gluconeogenesis contributed 100% of the total glucose in CM patients but only 58% in controls (p=0.003). The plasma concentrations of the substrates for gluconeogenesis and the glucoregulatory hormones were not different between patients and controls, except for an increase in lactate and cortisol in the patients. Cerebral malaria is associated with increases rather than decreases in plasma glucose, glucose production and gluconeogenesis, and there is no contribution of glycogenolysis to glucose production. Factors other than malaria per se are involved in the pathogenesis of hypoglycaemia associated with CM.

Adult↗
PubMed2001

Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs.

The purpose of the present in vivo study was to determine the role of nitric oxide (NO) in the regulation of glucose metabolism in response to endotoxin by blocking NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA). In five dogs, the appearance and disappearance rates of glucose (by infusion of [6,6-(2)H(2)]glucose), plasma glucose concentration, and plasma hormone concentrations were measured on five different occasions: saline infusion, endotoxin alone (E coli, 1.0 microg/kg i.v.), and endotoxin administration plus three different doses of primed, continuous infusion of L-NMMA. Endotoxin increased rate of appearance of glucose from 13.7 +/- 1.6 to 23.6 +/- 3.3 micromol x kg(-1) x min(-1) (P < 0.05), rate of disappearance of glucose from 13.9 +/- 1.1 to 24.8 +/- 3.1 micromol x kg(-1) x min(-1) (P < 0.001), plasma lactate from 0.5 +/- 0.1 to 1.7 +/- 0.1 mmol/l (P < 0.01), and counterregulatory hormone concentrations. L-NMMA did not affect the rise in rate of appearance and disappearance of glucose, plasma lactate, or the counterregulatory hormone response to endoxin. Plasma glucose levels were not affected by endotoxin with or without L-NMMA. In conclusion, in vivo inhibition of NO synthesis by high doses of L-NMMA does not affect glucose metabolism in response to endotoxin, indicating that NO is not a major mediator of glucose metabolism during endotoxemia in dogs.

Animals↗
PubMed2001

The suprachiasmatic nucleus generates the diurnal changes in plasma leptin levels.

At present it is not clear which factors are responsible for the diurnal pattern of plasma leptin levels, although the timing of food intake and circulating hormones such as glucocorticoids and insulin have both been proposed as independent determinants. In this study we show that ablation of the biological clock by thermal lesions of the hypothalamic suprachiasmatic nucleus (SCN) completely eliminates the diurnal pattern of plasma leptin levels. By contrast, removal of the diurnal corticosterone signal by adrenalectomy and corticosterone replacement did not affect diurnal plasma leptin levels. More importantly, removal of the nocturnal feeding signal by submitting the animals to a regular feeding schedule of six meals per day did not abolish the diurnal plasma leptin levels. However, both SCN lesions and the regular feeding schedule did cause an increase in the 24-h mean plasma leptin levels. As neither rhythmic feeding, insulin, or corticosterone signals can completely explain the diurnal plasma leptin rhythm, we conclude that biological clock control of the sympathetic input to the adipocyte is essential for regulation of the daily rhythm in leptin release.

Adipocytes↗
PubMed2001

The quantification of gluconeogenesis in healthy men by (2)H2O and [2-(13)C]glycerol yields different results: rates of gluconeogenesis in healthy men measured with (2)H2O are higher than those measured with [2-(13)C]glycerol.

The quantification of gluconeogenesis (GNG) by (2)H2O and [2-(13)C]glycerol and the mass isotopomer dilution analysis of glucose does not involve assumptions regarding the enrichment of the oxaloacetate precursor pool. To compare these two methods we measured GNG in six healthy postabsorptive males under identical, strictly standardized, eucaloric conditions, once after oral administration of (2)H2O and once during a primed continuous infusion of [2-(13)C]glycerol. Endogenous glucose production (EGP) was measured by infusion of [6,6-(2)H(2)]glucose. EGP was not different after (2)H2O administration or during [2-(13)C]glycerol infusion (12.2 +/- 0.7 vs. 11.7 +/- 0.3 micromol/kg.min). However, GNG measured after (2)H2O administration was significantly higher than that during [2-(13)C]glycerol infusion (7.4 +/- 0.7 vs. 4.9 +/- 0.6 micromol/kg.min; P = 0.03), representing approximately 60% and 41% of EGP, respectively. The (2)H2O study was repeated during primed continuous infusion of unlabeled glycerol, showing that infusion of glycerol at the rate used in the [2-(13)C]glycerol method does not affect the measurement of GNG with (2)H2O, viz. 7.4 +/- 0.7 without glycerol vs. 7.6 +/- 0.9 micromol/kg.min with glycerol, representing approximately 60% vs. 62% of EGP. In conclusion, GNG measured by (2)H(2)O yields higher results than those measured by [2-(13)C]glycerol. This discrepancy is not merely caused by infusion of glycerol per se. Rather, the discrepancy between both methods probably relates to conceptual problems in underlying assumptions in one or both methods.

Adult↗
PubMed2001

Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients.

OBJECTIVE: Total peripheral vascular resistance (TPR) decreases in thyrotoxicosis and increases in hypothyroidism. Several mechanisms may be involved, including adaptation to changes in heat production and direct non-genomic effects of tri-iodothyronine (T3) on vascular smooth muscle cells. The aim of this study was to see if changes in TPR are related to changes in plasma concentrations of the endothelial hormones adrenomedullin and endothelin-1 as well as other hormones affecting vasculature. DESIGN: A prospective study. SUBJECTS: Eleven hypothyroid patients (pretreatment: thyroid-stimulating hormone (TSH) 68 (38-201) mU/l, T3 0.7 (0.35-1.5) nmol/l, fT4 3.0 (2.0-5.9) pmol/l, median (range)) and 14 with hyperthyroidism (pretreatment: TSH 0.02 (<0.01-0.06) mU/l, T3 6.4 (2.3-13.0) nmol/l, fT4 56.1 (22.9-70.0) pmol/l) were studied before treatment and 3 months after reaching the euthyroid state. Blood collection was carried out simultaneously with the recording of finger arterial pressure (FINAP). Cardiac output and TPR were derived from stroke volume computations by modelling flow from the FINAP signal. RESULTS: Thyroid-function tests of hypothyroid and thyrotoxic patients did not differ after restoration of the euthyroid state. TPR, expressed in arbitrary units (AU), decreased after correction of hypothyroidism (from 1.32+/-0.65 to 0.96+/-0.36 AU, P=0.04) and increased after correction of hyperthyroidism (from 0.75+/-0.18 to 1.10+/-0.35 AU, P=0.007). Adrenomedullin concentrations did not change during the transition from the hypothyroid state 3.2(0.9-11.0) pmol/l to the euthyroid state 4.9(0.9-8.6) pmol/l, but decreased after treatment of hyperthyroidism, from 5.2(0.9-11.0) pmol/l to 2.2(0.9-5.4) pmol/l. Plasma endothelin-1 was undetectable in all samples. Changes in TPR upon treatment correlated with log DeltafT4 (r=-0.65, P=0.001), log DeltaT3, (r=-0.57, P=0.006), Delta noradrenaline (r=0.54, P=0.02) and Delta ANP (atrial natriuretic peptide) (r=-0.59, P=0.004). Multiple linear regression analysis indicated that only T3 was an independent determinant of TPR. Changes in T3 accounted for 46% of the variability in the changes in TPR. CONCLUSIONS: TPR is reduced in thyrotoxicosis and increased in hypothyroidism. Restoration of the euthyroid state normalizes TPR. Changes in TPR are not related to plasma adrenomedullin concentrations, but 46% could be explained by changes in T3. Altered ANP secretion and adrenergic tone may contribute to the T3-induced changes in TPR.

Adrenomedullin↗
PubMed2000

Indomethacin decreases insulin secretion in patients with type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production (EGP) is partly regulated by paracrine intrahepatic factors. Administration of indomethacin, an inhibitor of prostaglandin synthesis, resulted in a transient stimulation of EGP without changes in glucoregulatory hormone concentrations. It is unknown whether similar paracrine factors influence basal EGP in type 2 diabetes mellitus. The effects of 150 mg indomethacin, a nonendocrine stimulator of glucose production in healthy adults, and placebo on EGP were measured in a randomized placebo-controlled study in patients with type 2 diabetes mellitus (3 men and 3 women; mean age, 58.5 years; mean body mass index, 28.6 kg x m(-2)). EGP was measured before and for 6 hours after administration of placebo/indomethacin, by a primed, continuous infusion of [6,6-2H2]glucose. After indomethacin, plasma glucose and EGP increased in all subjects by 14% (P < .05) and 48% (P < .05), respectively. In the control experiment, plasma glucose and EGP declined gradually in all subjects by 22% (P < .001) and 17% (P = .004), respectively. The stimulation of glucose production coincided with the inhibition of insulin secretion by 52% within 1 hour after administration of indomethacin (P < .001). In the control experiment, insulin secretion decreased gradually by 18% after 6 hours (P < .001). Thus, indomethacin inhibits insulin secretion and stimulates EGP in type 2 diabetes.

Adult↗
PubMed2000

Continuous or intermittent vascular clamping during hemihepatectomy in pigs: hyaluronic acid kinetics in the assessment of early microvascular liver damage.

OBJECTIVE: To assess the uptake of hyaluronic acid (HA) as a marker of microvascular damage in a model of hemihepatectomy in pigs having continuous or intermittent vascular inflow occlusion. DESIGN: Prospective, animal study. SETTING: Laboratory for experimental surgery, University hospital, The Netherlands. INTERVENTIONS: Total liver ischaemia was achieved during 90 minutes by continuous (n = 5) or intermittent (n = 5) occlusion of the portal vein and hepatic artery followed by 120 minutes of reperfusion. In a second series of pigs (n = 8) a left hemihepatectomy was added to the protocol. MAIN OUTCOME MEASURES: Uptake of exogenous HA was assessed before ischaemia and after 120 minutes of reperfusion, together with the galactose elimination capacity. Plasma activities of aspartate aminotransferase (AST), alanine amino transferase, and lactate dehydrogenase were measured and specimens of liver were obtained for histopathological examination. RESULTS: HA uptake was slightly reduced after reperfusion in unresected livers compared with uptake before ischaemia. After hemihepatectomy HA uptake after reperfusion was significantly reduced after both continuous and intermittent occlusion, but more HA was taken up after continuous occlusion (p = 0.02). Release of AST after reperfusion was increased only after hemihepatectomy. CONCLUSIONS: Microvascular damage, as assessed by HA uptake capacity, significantly contributed to normothermic ischaemia and reperfusion injury in porcine liver. Vascular inflow occlusion during 90 minutes in combination with hemihepatectomy resulted in less liver damage when vascular occlusion was continuous rather than intermittent.

Animals↗
PubMed2000

Administration of interferon-gamma in healthy subjects does not modulate thyroid hormone metabolism.

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-2), IL-6, and interferon-alpha (IFN-alpha), alter human thyroid hormone metabolism and may be involved in the pathogenesis the euthyroid sick syndrome. Experimental data suggest that interferon-gamma (IFN-gamma) could be another cytokine that might influence thyroid hormone metabolism. To evaluate whether IFN-gamma can be involved in the pathogenesis of the alterations in thyroid hormone metabolism in humans with nonendocrine illness, we measured thyroid hormone concentrations in six healthy volunteers during 24 hours in a placebo controlled trial: once after subcutaneous administration of IFN-gamma (Immukine, [Boehringer Ingelheim GmbH, Ingelheim/Rheim, Germany] 100 microg/m2 subcutaneous) and once after the administration of saline (control). In addition, we measured cytokine concentrations in plasma (TNF-alpha and IL-6). IFN-gamma did not induce effects on any of the measured thyroid hormone and thyroid-stimulating hormone (TSH) plasma concentrations. Moreover, IFN-gamma did not affect TNF-alpha plasma levels. Only a modest but significant elevation of plasma IL-6 levels was detected after administration of IFN-gamma (p < 0.05 vs. control). It is concluded that IFN-gamma administration to healthy humans does not result in short term alterations of thyroid hormone metabolism. These data do therefore not support a role of IFN-gamma in the pathogenesis of the euthyroid sick syndrome in humans as might be deduced from in vitro and in vivo animal studies.

Body Temperature↗
PubMed2000

The effects of carbohydrate variation in isocaloric diets on glycogenolysis and gluconeogenesis in healthy men.

To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets were eucaloric and provided 15% of energy as protein. Postabsorptive glucose production was measured by infusion of [6,6-2H2]glucose, and fractional gluconeogenesis was measured by ingestion of 2H2O. Postabsorptive glucose production rates were 13.0 +/- 0.7, 11.4 +/- 0.4, and 9.7 +/- 0.4 micromol/kg x min after high carbohydrate, control, and very low carbohydrate diets, respectively (P < 0.001 among the three diets). Gluconeogenesis was about 14% higher after the very low carbohydrate diet (6.3 +/- 0.2 micromol/kg x min; P = 0.001) compared to the control diet, but was not different between the high carbohydrate and control diets (5.5 +/- 0.3 vs. 5.5 +/- 0.2 micromol/kg x min). The rates of glycogenolysis were 7.5 +/- 0.5, 5.9 +/- 0.3, and 3.4 +/- 0.3 micromol/kg x min, respectively (P < 0.001 among the three diets). We conclude that under eucaloric conditions in healthy subjects, dietary carbohydrate content affects the rate of postabsorptive glucose production mainly by modulation of glycogenolysis. In contrast, dietary carbohydrate content affects the postabsorptive rate of gluconeogenesis minimally, as evidenced by only a slight increase in gluconeogenesis during severe carbohydrate restriction.

Adult↗
PubMed2000

Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes.

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles caused by changes in expression of LDL receptors on liver cell surfaces. Changes in cholesterol ester transfer activity partly explain changes in HDL-C. It has been suggested that the magnitude of these changes is related to polymorphisms of involved genes. The aim of the present study is to investigate whether the polymorphic AvaII restriction site in exon 13 of the LDL receptor gene and the polymorphic TaqIB site in intron 1 of the cholesterol ester transfer protein are associated with the magnitude of the changes in plasma LDL-C and HDL-C, respectively, in the transition from the hypo- or hyperthyroid to the euthyroid state. From a consecutive group of 66 untreated hypothyroid and 60 hyperthyroid patients, 47 Caucasians in each group were analyzed. Fasting LDL-C and HDL-C were measured at baseline and 3 months after restoration of the euthyroid state. Genotype was determined by means of PCR techniques. The homozygous presence of a restriction site was designated as +/+, heterozygous as +/-, and absence as -/-. Trend analysis was done with ANOVA. Among hypo- or hyperthyroid patients, subgroups with different genotypes did not differ in thyroid function pre- or post treatment. The mean decrease in LDL-C (mmol/L +/- SD) in hypothyroid patients with different AvaII genotypes did not differ: - 1.07 +/- 1.44 (-/-, N = 15), -1.25 +/- 1.53 (+/-, N = 19), and -1.18 +/- 1.01 (+/+, N = 13) mmol/L [not significant (NS)]; neither did the mean increase in hyperthyroid patients: 1.07 +/- 0.90 (-/-, N = 18), 0.92 +/- 1.00 (+/-, N = 21), and 1.20 +/- 0.45 (+/+, N = 6) (NS). The mean decrease in HDL-C (mmol/L +/- SD) in hypothyroid patients with different TaqIB genotypes did not differ: -0.22 +/- 0.26 (-/-, N = 13), -0.15 +/- 0.23 (+/-, N = 21), and -0.12 +/- 0.22 (+/+, N = 9) (NS); neither did the mean increase in hyperthyroid patients: 0.29 +/- 0.39 (-/-, N = 7), 0.26 +/- 0.23 (+/-, N = 22), and 0.19 +/- 0.31 (+/+, N = 18) (NS). Changes in LDL-C and HDL-C correlated with the logarithm of the change in free T4 (fT4), expressed as the fT4 posttreatment/fT4 pretreatment ratio (r = -0.81, P < 0.001; and r = -0.62, P < 0.001, respectively). In conclusion, in the transition from hypo- or hyperthyroidism to euthyroidism, no association is found between AvaII genotype and changes in plasma LDL-C nor between TaqIB genotype and changes in HDL-C. Changes in LDL-C and HDL-C correlate with changes in fT4.

Adult↗
PubMed2000

Acute effects of interferon-alpha administration on testosterone concentrations in healthy men.

OBJECTIVE: Recombinant human interferon alpha (rhIFN-alpha) is used therapeutically in malignant disorders and chronic hepatitis. The present study was assessed to study the effects of rhIFN-alpha on the hypothalamic-pituitary-testicular (HPT) axis. DESIGN AND METHODS: We performed a saline-controlled cross-over study in six healthy men, sequentially measuring the serum concentrations of gonadotropins, testosterone, the free androgen index (FAI) and sex hormone-binding globulin (SHBG) after a bolus subcutaneous injection of rhIFN-alpha. RESULTS: rhIFN-alpha induced a sustained decrease of both testosterone (from 19.5+/-1.88 to a nadir of 5.49+/-0.51nmol/l at the end of the study) and FAI (from 98.7+/-14.7 to a nadir of 32. 1+/-5.3 at the end of the study), whereas concentrations of LH, FSH and SHBG were not different between the two studies. CONCLUSIONS: Our results suggest that rhIFN-alpha affects the HPT axis at the testicular level, either directly or indirectly, and changes feedback relationships between the pituitary and the testis.

Adult↗
PubMed1999

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients.

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

Aged↗