THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS IN SEVERE FALCIPARUM-MALARIA - EFFECTS OF CYTOKINES

Patients with malaria can have features of adrenal insufficiency. Beca use of the pathophysiological and clinical implications of an Addisoni an state, the hypothalamic-pituitary-adrenocortical axis was assessed in nine Vietnamese adults with complicated malaria. A CRH test was per formed on admission (in convalescence in five cases) and in six health y controls. Basal plasma ACTH concentrations in the patients and contr ols were similar [median (range): 2.9 (0.2-9.7) vs. 3.5 (1.9-13.4) pmo l/L, respectively; P > 0.1]. Serum cortisol levels were greater in the patients [882 (294-1682) vs. 190 (110-676) nmol/L; P < 0.01], but thr ee (33%) had values within the control range. Basal serum corticostero id-binding globulin concentrations were similar in patients and contro ls (P = 0.23). The post-CRH rise in plasma ACTH was attenuated in the patients [peak: 6.1 (0.9-23.2) vs. 14.5 (6.2-21.5) pmol/L in controls; P < 0.05]; basal and peak plasma ACTH correlated with plasma interleu kin-6 in this group (r(s) greater than or equal to 0.60; P less than o r equal to 0.04). Serum cortisol responses to CRH were depressed in ac ute illness [peak 990 (394-1, 805) nmol/L or 10 (0-50%) above baseline us. 500 (429-703) nmol/L or 160 (10-380%) in controls; P < 0.05]. The median estimated serum cortisol t(1/2) was 4.6 h in the patients and 1.6 h in the controls. These data suggest that, relative to a normal s tress response, primary and secondary adrenal insufficiency can occur in severe malaria but may be attenuated by increased circulating inter leukin-6 concentrations and impaired cortisol metabolism. The benefits of stress-dose corticosteroid replacement are unknown but could be co nsidered in hypoglycemic patients or those with a serum cortisol withi n or below the reference range.