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Urinary free cortisone, but not cortisol, is associated with urine volume in severe obesity
Authors:Karsten Müssig  Andreas Fritsche  Christiane Maser-Gluth
Institution:a Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital of Tübingen, Germany
b Department of Nutrition and Health, Research Institute of Child Nutrition, Dortmund, Germany
c Nutritional and Preventive Medicine, Department of Internal Medicine, University Hospital of Tübingen, Germany
d Steroid Laboratory, Department of Pharmacology, University of Heidelberg, Germany
Abstract:

Background

High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.

Experimental

In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m2) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m2), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.

Results

In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).

Conclusions

In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.
Keywords:BP  blood pressure  BMI  body mass index  E  cortisone  F  cortisol  GC  glucocorticoid  GFR  glomerular filtration rate  11β-HSD1  11β-hydroxysteroid dehydrogenase type 1  11β-HSD2  11β-hydroxysteroid dehydrogenase 2  IFG  impaired fasting glucose  IGT  impaired glucose tolerance  ISI  insulin sensitivity index  MDRD  Modification of Diet in Renal Disease  OGTT  oral glucose tolerance test  RIA  radioimmunoassays  THE  tetrahydrocortisone  THF  tetrahydrocortisol  5α-THF  5α-tetrahydrocortisol  TSH  thyroid-stimulating hormone  UFE  urinary free cortisone  UFF  urinary free cortisol
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