title: The hypothalamic-pituitary-adrenocortical axis in severe falciparum malaria: effects of cytokines.
abstract: Patients with malaria can have features of adrenal insufficiency. Because of the pathophysiological and clinical implications of an Addisonian state, the hypothalamic-pituitary-adrenocortical axis was assessed in nine Vietnamese adults with complicated malaria. A CRH test was performed on admission (in convalescence in five cases) and in six healthy controls. Basal plasma ACTH concentrations in the patients and controls were similar [median (range): 2.9 (0.2-9.7) vs. 3.5 (1.9-13.4) pmol/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 three (33%) had values within the control range. Basal serum corticosteroid-binding globulin concentrations were similar in patients and controls (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 interleukin-6 in this group (rs > or = 0.60; P < or = 0.04). Serum cortisol responses to CRH were depressed in acute illness [peak 990 (394-1, 805) nmol/L or 10 (0-50%) above baseline vs. 500 (429-703) nmol/L or 160 (10-380%) in controls; P < 0.05]. The median estimated serum cortisol t1/2 was 4.6 h in the patients and 1.6 h in the controls. These data suggest that, relative to a normal stress response, primary and secondary adrenal insufficiency can occur in severe malaria but may be attenuated by increased circulating interleukin-6 concentrations and impaired cortisol metabolism. The benefits of stress-dose corticosteroid replacement are unknown but could be considered in hypoglycemic patients or those with a serum cortisol within or below the reference range.
authors.affiliation: University of Western Australia, Department of Medicine, Fremantle Hospital, Australia. tdavis@cyllene.uwa.edu.au
authors.forename: T M
authors.initials: TM
authors.lastname: Davis
authors.forename: T A
authors.initials: TA
authors.lastname: Li
authors.forename: Q B
authors.initials: QB
authors.lastname: Tran
authors.forename: K
authors.initials: K
authors.lastname: Robertson
authors.forename: J R
authors.initials: JR
authors.lastname: Dyer
authors.forename: T D
authors.initials: TD
authors.lastname: Phan
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: M H
authors.initials: MH
authors.lastname: Beaman
authors.forename: K A
authors.initials: KA
authors.lastname: Trinh
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D016207:Cytokines; D009566:Nitrates; D013963:Thyroid Hormones; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone