Morbidly obese subjects may present with abnormal thyroid function tests but the reported data are scarce. Therefore, we studied the thyroid parameters in 144 morbidly obese patients, 110 females and 34 males, to assess the prevalence of hypothyroidism. Eleven percent (11.8%) carried the diagnosis of hypothyroidism and were undergoing levothyroxine (LT4) replacement therapy, 7.7% had newly diagnosed subclinical hypothyroidism, 0.7% had subclinical hyperthyroidism and 7.7% were euthyroid with positive antibodies (anti-thyroid peroxidase antibodies [TPOAb]). From the 144 subjects, we selected a cohort of 78 euthyroid subjects with negative TPOAb, who did not receive LT4 replacement or suppression therapy (the experimental group) and compared them to 77 normal-weight euthyroid subjects, TPOA-negative, matched for age and gender who served as controls. The experimental group had higher serum levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and thyrotropin (TSH) compared to the control group. Serum TSH concentration was associated with fasting serum insulin levels and insulin resistance but not with serum leptin levels, body mass index (BMI), fat mass, and lean body mass. In conclusion, in morbidly obese individuals, the prevalence of overt and subclinical hypothyroidism was high (19.5%). The morbidly obese subjects have higher levels of T3, FT3, T4, and TSH, probably the result of the reset of their central thyrostat at higher level.
Stress hyperglycemia is frequent in critically ill patients. The aim of this study was to investigate the effect of blood glucose control with insulin on endocrine, metabolic, and immune function in an animal model of severe injury. Seventy-two hours after alloxan injection and exogenous insulin infusion combined with continuous iv parenteral nutrition, male New Zealand White rabbits received a burn injury and were allocated to a normoglycemic (n = 17) or hyperglycemic (n = 13) group. In the normoglycemic group, blood glucose levels were kept between 3.3 and 6.1 mmol/liter by insulin infusion, whereas in the hyperglycemic group blood glucose levels were maintained at 13.8-16.6 mmol/liter. Blood was drawn for biochemical analysis at regular time points. At 24 and 72 h after burn injury, immune function of monocytes was assessed in vitro. Maintenance of normoglycemia with exogenous insulin after severe trauma to a large extent prevented weight loss, lactic acidosis, and hyponatremia. Furthermore, within 3 d after injury, the intervention improved phagocytosis of monocytes investigated in fresh cells by more than a mean 150% (P = 0.006) and after 24-h incubation with or without lipopolysaccharide by more than a mean 4-fold (P = 0.001) and 2-fold (P = 0.05), respectively. Oxidative killing after 24-h incubation was also improved by 2-fold (P = 0.05), but no effect on chemotaxis was detected. Concomitantly, inflammation and stress-induced growth hormone hypersecretion were suppressed. Prevention of catabolism, acidosis, excessive inflammation, and impaired innate immune function may explain previously documented beneficial effects of intensive insulin therapy on outcome of critical illness.
Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1β and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1β levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis.
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