Biomedical subjects

E Endert

Publications and source records attributed to E Endert.

At least 19 recordsLinked to original sources

PubMed2006

Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during coronary artery surgery.

BACKGROUND: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG. METHODS: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1)) normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD). RESULTS: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group. CONCLUSION: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.

Adrenocorticotropic Hormone↗

PubMed2006

Endocrine intervention during irradiation does not prevent damage to the thyroid gland.

Radiation to the head-neck region may damage the thyroid gland, leading to hypothyroidism or thyroid carcinoma. Outcomes of radiation protection by lowering plasma thyroid-stimulating hormone (TSH) have thus far been ambiguous. Our aim was to evaluate the radioprotective effect of inhibiting the thyroid gland's activity during x-radiation. For this purpose, of 80 5-week old Wistar rats, 64 received cervical irradiation with 15 Gy (single dose). During irradiation, endocrine intervention was done, using thyroxine (T(4)), T(4) plus iodine, or iodine alone compared to placebo. During the endocrine interventions and follow-up, TSH and T(4) concentrations were measured periodically. Histologic examination of thyroid, pituitary gland, or the hypothalamus and any suspect lymph nodes, lungs, and liver was performed after 6 and 54 weeks. It was found that during the endocrine intervention, plasma levels of TSH were lower in rats given T(4) and higher in rats given iodine. After 6 and 54 weeks, no significant reduction in hypothyroidism or thyroid carcinoma was found between the different groups of rats given any endocrine intervention or no intervention. In conclusion, the administration of T(4), iodine or the combination during x-irradiation does not protect against radiation-induced thyroid damage.

Animals↗

PubMed2005

Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism.

BACKGROUND: During T(4) supplementation of patients with thyroidal (primary) congenital hypothyroidism (CH) TSH concentrations are frequently elevated despite free T(4) (FT(4)) concentrations being well within the reference range. To examine the thyroid's regulatory system, we analyzed thyroid function determinants in children with congenital and acquired thyroid disorders and in controls. METHODS: Retrospectively, plasma FT(4), TSH, and T(3) concentrations were analyzed in T(4)-supplemented children aged 0.5-20.0 yr with thyroidal CH, central (secondary or tertiary) CH, or autoimmune thyroid disease and in control children with type 1 diabetes mellitus. RESULTS: When TSH was within the reference range (0.4-4.0 mU/liter), mean FT(4) in thyroidal CH [1.65 ng/dl; 95% confidence interval (CI), 1.62-1.67] was significantly higher than in autoimmune thyroid disease (1.15 ng/dl; 95% CI, 1.11-1.19) and diabetes (1.08 ng/dl; 95% CI, 1.06-1.10). In central CH, when TSH was less than or equal to 0.02 mU/liter, mean FT(4) was 1.27 ng/dl (95% CI, 1.24-1.29). When FT(4) was within the reference range (0.78-1.79 ng/dl), 43% of the TSH measurements in thyroidal CH were more than 4.0 mU/liter, compared with 18% in autoimmune thyroid disease and 0% in type 1 diabetes mellitus; in central CH, 95% of TSH measurements were less than 0.4 mU/liter. CONCLUSIONS: In T(4)-supplemented patients with thyroidal CH, when TSH concentrations are established within the reference range, FT(4) concentrations tend to be elevated, and vice versa. Because this phenomenon could not be observed in acquired thyroidal hypothyroidism, we hypothesize that a pre- and/or perinatal hypothyroid state shifts the setpoint of the thyroid's regulatory system. In central CH, when FT(4) concentrations are established within the reference range, the pituitary secretes only minute amounts of TSH. For monitoring T(4) supplementation, reference ranges for FT(4) and TSH should be adapted to the etiology of hypothyroidism.

Adolescent↗

PubMed2005

The effect of cervical X-irradiation on activity index of thyrocytes and plasma TSH: a pre-clinical model for radiation-induced thyroid damage.

Because radiotherapy in the head and neck region is necessary in the treatment of childhood cancer, possibilities to prevent damage to the thyroid gland must be explored. We developed a model in which radiation-induced effects can be investigated in a way that these effects can be quantified, using thyroid dysmorphology and plasma TSH. Thirty-five Wistar rats, 5 weeks old, were X-irradiated on the cervical region, with a single dose varying from 0 to 20 Gy. After 6 weeks, TSH, T4 and T3 were determined, and thyroid glands were processed for histological examination by two independent pathologists. A histological classification scale was developed, using follicular size, colloid density and cell height of thyrocytes to measure hyperplasia and hypertrophy. By the sum of these scores, a cell-activity index was calculated, which was related to plasma TSH concentration. Numbers of PAS-positive droplets and epithelial desquamation were also counted. Inter-observer reliability was assessed. Good to very good reliability was found for scores of follicular size, colloid density and cell height. Significant increase of cell-activity index was found after 10, 15 and 20 Gy. The plasma TSH concentration was positively correlated to the cell-activity index, increasing with radiation-doses up to 15 Gy. The number of desquamated cells was significantly increased after radiation doses >10 Gy, with moderate reliability. In conclusion, this model using cell-activity index of thyrocytes together with plasma thyrotropin concentrations and desquamation of cells can be used for interpretation and future (pre-clinical) studies of prevention of radiation-induced thyroid damage.

Animals↗

PubMed2005

Evaluation of endocrine tests. B: screening for hypercortisolism.

BACKGROUND: While reference values for 24-hour free urinary cortisol excretion and the overnight 1 mg dexa-methasone-suppression test in the healthy population are available, cut-off values in patients clinically suspected of Cushing's syndrome have to be established. METHODS: This was a prospective follow-up study in one academic centre of 144 patients with clinical suspicion of Cushing's syndrome (group A) and 50 patients with adrenal incidentaloma (group B) who were referred for putative hypercortisolism between 1 January 1993 and 1 January 2003. The 24-hour urinary free cortisol and post-dexamethasone plasma cortisol were measured. Accurate diagnosis of (absence of) Cushing's syndrome was confirmed by histopathological data and long-term follow-up. Based on the data obtained in group A, sensitivity, specificity and receiver operating characteristic (ROC) curves were calculated. RESULTS: Complete follow-up was obtained in 86%, and partial follow-up was obtained in 8% of patients. Median follow-up was 36 (1 to 122) months. In group A, 17 patients were found to have Cushing's syndrome. In this group median 24-hour urinary free cortisol was 77 (<5 to 51458) mmol/24 hours and median post-dexamethasone plasma cortisol was <50 (<50 to 4900) nmol/l. Area under the ROC curve was 0.958 for 24-hour urinary free cortisol and 0.985 for post-dexamethasone plasma cortisol. Optimal cut-off values were 180 nmol/24 hours (sensitivity 94%, specificity 94%) and 95 nmol/l (sensitivity 100%, specificity 94%) respectively. CONCLUSION: We established cut-off values for 24-hour free urinary cortisol excretion (180 nmol/24 hours) and for post-dexamethasone plasma cortisol (95 nmol/l) in the evaluation of patients referred for hypercortisolism.

Adrenal Cortex Function Tests↗

PubMed2005

Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency.

BACKGROUND: The short Synacthen test, the overnight metyrapone test and the insulin tolerance test are frequently used in the evaluation of patients suspected of adrenal insufficiency. in the present study, we established reference values for these diagnostic tests, as well as for baseline morning plasma cortisol and adrenocorticotrophic hormone (ACTH). METHODS: We studied 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. A short ACTH stimulation test (250 microg Synacthen iv), an overnight metyrapone test (2.0, 2.5, or 3.0 g given orally depending on body weight at 23.30 hours) and an insulin tolerance test (0.15 U/kg actrapid iv) were performed. Reference intervals are given as the means +/- 2SD of observed hormone concentrations after logarithmic transformation. RESULTS: The following reference values were established: 09.00 hr plasma cortisol 150 to 802 nmol/l, 09.00 hr plasma ACTH 8 to 93 ng/l, peak plasma cortisol after Synacthen 591 to 1,113 nmol/l, peak plasma cortisol after insulin-induced hypoglycaemia 557 to 1,015 nmol/l, and plasma 11-deoxycortisol after metyrapone 197 to 759 nmol/l. CONCLUSION: We established reference values for diagnostic tests that are useful in the evaluation of patients suspected of primary or secondary/tertiary adrenal insufficiency.

Adrenal Cortex Function Tests↗

PubMed2004

FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in adults with uncomplicated P. falciparum malaria.

In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased. To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated falciparum malaria, we investigated the effect of inhibition of lipolysis by acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were given acipimox, and six served as controls. Also as controls, six matched healthy subjects were studied on two occasions with and without acipimox. After 16 h of fasting, glucose production and GNG were significantly higher in the malaria patients compared with the healthy controls (P = 0.003 and < 0.0001, respectively), whereas GLY was significantly lower (P < 0.001), together with elevated plasma concentrations of cortisol and glucagon. During the study, glucose production in patients declined over time (P < 0.0001), without a statistically significant difference between the acipimox-treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared with nontreated controls (P = 0.005). GNG was unchanged over time in patients as well as in healthy controls, and no influence of acipimox was found. In patients, GLY declined over time (P < 0.001), without a difference between acipimox-treated and untreated patients. In contrast, in controls treated with acipimox, no change over time was found, which was statistically different from the decline in untreated controls (P = 0.002). In conclusion, in falciparum malaria, FFAs are not involved in regulation of glucose production, nor of GNG or GLY.

Adult↗

PubMed2004

Glycogenolysis during short-term fasting in malaria and healthy subjects--the potential regulatory role of glycogen content on glycogen breakdown: a hypothesis.

BACKGROUND & AIMS: During short-term starvation (< 24 h), glucose production decreases 10-20% due to a decrease in glycogenolysis. In the fed state glycogen regulates its rate of breakdown, in order to limit glycogen accumulation. Whether in the fasted state a similar mechanism exists to preserve glycogen content is not known. In malaria, the rate of glycogen breakdown after an overnight fast is considerably lower than in healthy subjects. If glycogen content regulates its rate of breakdown during fasting, we postulate that the rate of glycogenolysis should decrease faster in patients with malaria than in healthy subjects. METHODS: In six non-severe falciparum malaria patients and 6 healthy controls glucose production with [6,6-2H2]-glucose, and glycogenolysis was calculated after measuring gluconeogenesis with the 2H2O-method between 16 and 22 h of fasting. RESULTS: Glucose production after 16 h of fasting was 15% higher in the malaria patients than in controls. Glycogenolysis in the malaria patients was 2.3 +/- 0.37 and 8.4 +/- 0.93 micromol/kg/min in the controls. The absolute decrease in glycogenolysis was slower in malaria patients than in controls (P = 0.001), whereas the relative decrease in glycogenolysis from baseline was not different. CONCLUSION: During fasting the relative decrease in glycogenolysis is independent of the absolute rate of glycogenolysis. The regulation of glycogenolysis during fasting seems not preferentially dictated by glycogen content but, at least in subjects with a low (presumed) glycogen content, driven by the necessity to guarantee glucose output and maintain euglycemia.

Adult↗

PubMed2004

Free fatty acids increase hepatic glycogen content in obese males.

Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose pathways in lean and obese subjects. Six lean and 6 obese males were studied twice during a 16- to 22-hour fast, once with and once without acipimox, an inhibitor of lipolysis. Intrahepatic glucose fluxes were measured by infusion of [2-(13C1)]glycerol, [1-(2H1)]galactose, and [U-(13C6)]glucose. Acetaminophen was administered as a glucuronate probe. In both lean and obese control studies, plasma FFA levels increased progressively, whereas acipimox completely suppressed plasma FFA levels for the whole study period. In lean males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). In lean males, neither glycogen synthesis, glycogen synthesis retained as glycogen, nor glycogen balance differed between control and acipimox studies. In obese males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). Glycogen synthesis did not change in either study. Glycogen synthesis retained as glycogen did not change in acipimox study, but increased in the control study (P = .03). Glycogen balance did not change in the acipimox study, but increased in the control study (P < .01). This study demonstrates that in obese males physiological levels of FFA contribute to the retention of hepatic glycogen during short-term fasting by inhibiting breakdown of glycogen and increasing glycogen synthesis retained as glycogen, whereas in lean males this effect was absent due to unaltered glycogen synthesis retained as glycogen.

Adult↗

PubMed2004

Influence of prolonged starvation on glucose kinetics in pregnant patients infected with Plasmodium falciparum.

Hypoglycaemia is a recognised complication of malaria in pregnancy, but its pathophysiology is not well understood. We studied the influence of fasting on glucose production and gluconeogenesis by infusion of [6,6-(2)H(2)]glucose and ingestion of (2)H(2)O in 20 female subjects, eight pregnant patients with uncomplicated falciparum malaria, six pregnant controls matched for age and trimester and six non-pregnant controls matched for age. Infection with Plasmodium falciparum induced a significant increase in glucose production (16.7+/-0.3 vs. 12.4+/-0.8 micromol/kg/min; P=0.002) and gluconeogenesis (12.5+/-0.6 vs. 8.2+/-0.7 micromol/kg/min; P=0.001) without a change in the glucoregulatory hormone milieu, compared to the healthy pregnant controls. Extension of the fast from 20.30 to 24.30 h resulted in a rate of decline of glucose production that was similar in patients with malaria and healthy pregnant subjects, a decline that was steeper compared to the non-pregnant subjects (-0.283 and -0.426 vs. -0.065 micromol/kg/min/h; P=0.037). The plasma glucose concentration measured at 20.30 h of fasting in the malaria patients was intermediate between the value found in the pregnant and the non-pregnant controls (4.01+/-0.2 mmol/l) while it was significantly lower in the non-infected pregnant women compared to non-pregnant controls (3.59+/-0.14 vs. 4.70+/-0.29 mmol/l; P=0.009). Plasma glucose concentration declined at a similar rate in patients with malaria and pregnant controls but faster compared to the non-pregnant controls (-0.078 and -0.093 vs. -0.044 mmol/l/h; P < 0.05). We conclude that fasting is a major risk factor for hypoglycaemia in pregnancy. Non-severe Plasmodium falciparum infection in pregnant women results in higher glucose production and higher glucose levels, thereby, compared to healthy pregnant patients, delaying of the occurrence of hypoglycaemia due to fasting. The exact mechanism of hypoglycaemia in fasting pregnant women remains to be elucidated.

Animals↗

PubMed2004

Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood.

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

Adolescent↗

PubMed2004

Gluconeogenesis and fasting in cerebral malaria.

BACKGROUND: In healthy subjects after an overnight fast, glucose production is for approximately 50% derived from glycogenolysis. If the fast is prolonged, glucose production decreases due to a decline in glycogenolysis, while gluconeogenesis remains stable. In cerebral malaria, glucose production is completely derived from gluconeogenesis after an overnight fast. It is not known if glucose production also decreases during fasting when its only source is gluconeogenesis. DESIGN: Glucose production was measured by infusion of [6,6-2H2]glucose in seven patients with cerebral malaria after prolonging a fast from 20.30 to 00.30 hours. RESULTS: Glucose production decreased by approximately 10% (27.4 +/- 2.1 to 24.7 +/- 1.6 micromol/kg/min, p = 0.05), without changes in the plasma concentrations of glucoregulatory hormones, FFA or precursors. CONCLUSIONS: In the patients with cerebral malaria, glucose production decreases during fasting due to a decrease in the rate of gluconeogenesis. These data suggest that the decrease in the rate of glucose production during short-term fasting is actively regulated and not simply due to shrinkage of glycogen content, as in the absence of glycogenolysis, glucose production decreases at the same rate as normally seen in healthy subjects whose glucose production is for approximately 50% derived from glycogen and in whom gluconeogenesis is stable.

Adult↗

PubMed2003

Establishment of reference values for endocrine tests. III: Primary aldosteronism.

BACKGROUND: In our laboratory well-defined reference values for the screening test and confirmation test used in the diagnosis of primary aldosteronism were lacking. In this study we established the reference-values of the plasma aldosterone concentration (PA), plasma renin activity (PRA) and PA/PRA ratio after a two-hour upright period, and of the urinary aldosterone excretion after oral sodium loading. METHODS: Fifty healthy volunteers, equally distributed according to sex and aged between 20 and 70 years, went through the screening and confirmation test of primary aldosteronism. PA, PRA and the PA/PRA ratios were measured after a two-hour upright period (screening test). Urinary aldosterone excretion was determined in two 24-hour urine samples after an oral suppletion of 6 g NaCl a day for five days (confirmation test). RESULTS: The following reference values were established: PA (after two-hour upright position) <0.03-1.05 nmol/l (mean: 0.47), PA/PRA ratio 0.05-0.47 (mean: 0.15) and urinary aldosterone excretion after sodium loading <3.0-47.0 nmol/24h (mean: 10.5). PRA showed a significant decrease with advancing age: median values in the 3rd to 7th decade are 3.9, 3.5, 2.5, 1.6 and 2.1 ng A1/ml/h respectively (p=0.04). PA was lower in subjects > or = 50 years old. Age did not affect the PA/PRA ratio or the urinary aldosterone excretion. There were no significant differences between the sexes in any of the above-mentioned parameters. CONCLUSION: In this study we established reference values for the screening and confirmation test used in the diagnosis of primary aldosteronism.

Adult↗

PubMed2003

Evaluation of endocrine tests. A: the TRH test in patients with hyperprolactinaemia.

BACKGROUND: In a previous study, we determined reference values for basal and thyrotropin-releasing hormone (TRH)-stimulated plasma concentrations of prolactin (PRL). The aim of the present study was to determine the clinical usefulness of the PRL response to TRH in the work-up of patients with hyperprolactinaemia. METHODS: We studied 92 consecutive patients referred for evaluation of hyperprolactinaemia. Patients with confirmed hyperprolactinaemia were divided into three groups: group A (pharmacological hyperprolactinaemia; n=2), group B (pathological hyperprolactinaemia; n=6) and group C (all other patients). Patients in group C underwent MRI of the pituitary and were subdivided into C1 (normal pituitary on MRI; n=6), C2 (slightly abnormal MRI; n=21), and C3 (evident microadenoma or macroadenoma on MRI; n=25 and 12, respectively). The MRI was technically insufficient in four patients. Basal PRL as determined by fluoroimmunometric assay and the PRL response to 400 microg TRH were determined in all patients. RESULTS: Hyperprolactinaemia was confirmed in 83% of the referred patients. Non-response, defined as a <2.5-fold PRL increase after TRH, occurred in one patient (50%) in group A, in 66% of patients in group B and in 99% of patients in group C. Within group C, basal PRL was not different between group C1 and C2, but higher (p=0.06) in group C3. The absolute PRL increase after TRH did not differ between the three subgroups. The relative PRL increase was smaller (p=0.03) in group C3 but overlapped considerably with groups C1 and C2. All patients except one in group C were so-called non-responders. Basal PRL and absolute PRL increases after TRH correlated with the adenoma diameter on MRI (r=0.66, p=0.0002 and r=0.49, p=0.008, respectively). CONCLUSION: In patients referred for elevated serum PRL, hyperprolactinaemia should be confirmed under standardised conditions. The absolute or relative PRL increase after 400 microg TRH does not help to differentiate between patients with prolactinoma or idiopathic hyperprolactinaemia. Therefore, the TRH stimulation test is not useful in the work-up of hyperprolactinaemia.

Adult↗

PubMed2002

Interferon-gamma administration does not affect human thyroid hormone metabolism in the post-surgical euthyroid sick syndrome.

Cytokines are thought to be involved in the pathogenesis the euthyroid sick syndrome. Experimental data from in vitro and animal in vivo studies suggest that interferon-gamma (IFN-gamma) could be another cytokine that might influence thyroid hormone metabolism, although in a previous study in healthy subjects we could not demonstrate an effect of IFN-gamma on thyroid hormone indices. Possibly, however, a non-stressed system is not a representative environment to study the effects of a mediator, which might exert its role during pathological circumstances in which it may interact synergistically with other inflammatory mediators. Therefore, we studied the effects of a single dose of recombinant human IFN-gamma (Immukine, 100 microg/m2, sc) on thyroid hormone concentrations in a placebo-controlled trial in 13 major surgery patients. Basal IFN-gamma levels did not increase. IFN-gamma induced a significant increase in monocyte HLA-DR expression (post-operative 50%; 24 h after IFN-gamma 90%), but did not affect thyroid hormone and thyroid stimulating hormone concentrations. We therefore conclude that IFN-gamma does not appear to be involved in the major changes in thyroid hormone metabolism in patients with non-thyroidal illness.

Aged↗

PubMed2002

Cortisol is increased in postmortem cerebrospinal fluid of multiple sclerosis patients: relationship with cytokines and sepsis.

Hypothalmo-pituitary-adrenal (HPA) axis activity is altered in patients with multiple sclerosis (MS), resulting in elevated basal levels and enhanced response of cortisol in stimulation tests. HPA axis hyperactivation in MS is thought to be the result of complex interactions of genetic, immunologic, and neuroendocrinological mechanisms. In order to investigate whether cytokine levels in the central nervous system are associated with the activation of the HPA axis in MS, we measured cortisol, interleukin (IL)-6, IL-10 and TNF-alpha levels in postmortem cerebrospinal fluid (CSF) of 18 patients with severe MS and 50 controls. We also investigated the cortisol and cytokine levels in the CSF of a group of MS patients and controls who died with sepsis, in order to see whether acute infectious situations affect the association between cortisol and cytokines. The cortisol levels in MS patients were increased by 80% in comparison to controls (p=0.008). There was no difference in IL-6 levels between the groups, while IL-10 and TNF-alpha levels of the majority of subjects were below detection limits. There was a positive correlation between cortisol and IL-6 only in control patients with sepsis (r=0.89, p=0.019), but not within the MS patents with sepsis or MS and control groups without sepsis. Cortisol levels in postmortem serum and CSF were highly correlated (r>0.78, p<0.001). We concluded that the basal level of cortisol is significantly increased in the CSF of MS patients and that IL-6 is not responsible for this rise. The relationship between cortisol and IL-6 in sepsis is discussed.

Aged↗

PubMed2001

Adrenocorticotropic hormone and cortisol levels in relation to inflammatory response and disease severity in children with meningococcal disease.

This prospective observational study investigated the relationship of the hypothalamic-pituitary-adrenal axis to inflammatory markers and to disease severity in children with meningococcal disease. In total, 32 children were studied: 10 with distinct meningococcal meningitis (MM), 10 with MM and septic shock, and 12 with fulminant meningococcal septicemia (FMS). Levels of adrenocorticotropic hormone (ACTH) and interleukin (IL)-6, IL-8, and IL-10 were lowest in the MM group and dramatically elevated in the FMS group. Cortisol and C-reactive protein levels were highest in the MM group and relatively low in the FMS group. Levels of ACTH and inflammatory markers decreased within the first 24 h of admission, but cortisol levels did not fluctuate. Cortisol was significantly inversely correlated with IL-6, IL-8, and IL-10 (P < or =.04). These results suggest that the adrenal reserve in children is insufficient to handle the extreme conditions and stress associated with severe meningococcal disease.

Adrenocorticotropic Hormone↗

PubMed2001

Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways.

BACKGROUND: Treatment for HIV-1 infection is complicated by fat redistribution (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more comprehensively in HIV-1-infected patients with lipodystrophy. We assessed glucose disposal and its pathways, glucose production, plasma free fatty acid (FFA) levels, and the degree to which these parameters could be suppressed by insulin. METHODS: Six HIV-1-infected men on protease inhibitor-based HAART with lipodystrophy (HIV+LD) were studied. The results were compared with those in six matched healthy male volunteers. Insulin sensitivity was quantified by hyperinsulinemic euglycaemic clamp. Glucose production and uptake were assessed by tracer dilution employing 6,6D(2)-glucose. RESULTS: At post-absorptive insulin concentrations, glucose production was 47% higher in HIV+LD than controls (P = 0.025). During clamp, glucose production was suppressed by 53% in HIV+LD, but by 85% in controls (P = 0.004). Glucose disposal increased in both groups, but by only 27% in HIV+LD versus 201% in controls (P = 0.004). Consequently, insulin-stimulated total glucose disposal was lower in HIV+LD patients (P = 0.006). Non-oxidative glucose disposal as percentage of total disposal did not differ significantly between groups (63% in HIV+LD and 62% in controls). Baseline plasma FFA concentrations were higher (0.60 versus 0.35 mmol/l; P = 0.024), whereas FFA decline during hyperinsulinemia was less (65 versus 85%; P = 0.01) in HIV+LD versus controls. CONCLUSIONS: Post-absorptive glucose production is increased in HIV-1-infected patients with lipodystrophy. Moreover, both the ability of insulin to suppress endogenous glucose production and lipolysis, and to stimulate peripheral glucose uptake and its metabolic pathways is reduced, indicating severe resistance concerning multiple effects of insulin.

Adult↗