The Hypothalamic-Pituitary-Adrenocortical Axis in Severe Falciparum Malaria: Effects of Cytokines1

• Published in: The journal of clinical endocrinology and metabolism Vol. 82; no. 9; pp. 3029 - 3033
• Main Authors: Davis, Timothy M. E, Thu, Li Thi Anh, Binh, Tran Quang, Robertson, Ken, Dyer, John R, Danh, Phan Thi, Meyer, Desiree, Beaman, Miles H, Anh, Trinh Kim
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01.09.1997
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.82.9.4196

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 ≥ 0.60; P ≤ 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.