Increased cortisol - Cortisone ratio in acute pulmonary tuberculosis

To evaluate a possible role for altered cortisol metabolism in mediating th e immunoparesis associated with progressive tuberculosis (TB), we have stud ied the hypothalamic-pituitary-adrenal axis, and the activities of the 11 b eta -hydroxysteroid dehydrogenases (11-HSDs) that interconvert active corti sol and inactive cortisone. In active pulmonary tuberculosis (PTB), the rat io of cortisol/cortisone metabolites in 24-h urine showed a shift towards a ctive cortisol (ratio, 1.19 +/- 0.1, n = 16 versus 0.89 +/- 0.05 in cured p ulmonary tuberculosis (CTB), n = 13, p < 0.01; and 0.78 +/- 0.04 healthy vo lunteers (HV), n = 11, p < 0.005). Conversion of cortisone (administered as 25 mg orally) to cortisol in peripheral plasma was higher in PTB (peak 1,1 57 +/- 55 nM, n = 14 versus 862 +/- 50 nM in CTB, n = 10, p < 0.005, and 88 2 +/- 73 nM in HV, n = 10; p < 0.005). Cortisol/cortisone ratio was increas ed in bronchoalveolar lavage fluid in PTB (7.73 +/- 1.48, mean +/- SE, n = 13) compared with HV (4.05 +/- 0.38, n = 11, p < 0.05) but was not differen t in plasma (PTB, 3.25 +/- 0.68; HV, 4.01 +/- 0.92). Responses of plasma co rtisol to dexamethasone, CRH stimulation, and multidose ACTH stimulation we re not different. These data suggest that in pulmonary tuberculosis, centra l control of glucocorticoid production is normal but that peripheral metabo lism, in particular in the lung, is deviated in favor of the active metabol ite cortisol. This offers a possible mechanism to explain the immunoparesis observed in progressive pulmonary tuberculosis.