Urinary adrenal steroid metabolites in tuberculosis--a new clue to pathogenesis?

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Abstract
Changes in adrenal function could explain several metabolic and immunological abnormalities in tuberculosis, and adrenal changes have been documented in a murine model of the disease. We used gas chromatography and mass spectrometry to measure 24 h urinary outputs of steroid metabolites, before (n = 10), and at intervals during (n = 9) treatment in tuberculosis patients, and in controls (n = 19). Before treatment, output of cortisol derivatives and of adrenal androgens was reduced (48%, p = 0.007; and 47%, p = 0.007, respectively). However, there was a striking increase in the ratio of cortisol to cortisone metabolites, so tetrahydrocortisol levels were normal. This agrees with the normal to raised plasma cortisol levels commonly seen in tuberculosis, and suggests reduced activity of 11β-hydroxysteroid dehydrogenase, or increased activity of the reductase. There was also an increase in the ratio of 16α-hydroxylated to reduced metabolites of dehydroepiandrosterone (DHEA). The changes in the ratios of cortisol to cortisone, and of DHEA to tetrahydrocortisol tended to correct themselves during treatment, but the abnormal pattern of metabolism of DHEA showed no resolution by 40 days. This may be due to further enzyme induction by rifampicin. These changes are not all disease-specific, but recent information on the functions of 11β-hydroxysteroid dehydrogenase and DHEA metabolites in the regulation of Th1/Th2 cytokine balance suggest a role in pathogenesis.

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