African sleeping sickness (SS) is a severe, potentially lethal parasitic disease. The treatments of choice are the antiparasitic agents suramin, which is adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis of patient with SS before, during, and after therapy with suramin and/or melarsoprol, in two sequential stages. First, we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test (250 µg i.v.) to assess the maximal adrenocortical responsiveness of 69 patients with SS and 38 normal controls. We demonstrated paradoxically subnormal Cortisol responses before suramin therapy [net Cortisol response 60 min after stimulation: 10.5 ± 2.9 (mean ± SE) vs. 17.5 ± 1.0 µg/dl for controls, p = 0.004], with 27% of the patients falling within the adrenal insufficiency range (stimulated cortisol concentration <20 µg/dl). These responses subsequently and unexpectedly improved with suramin and/or melarsoprol therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test (100 µg i.v.) in 68 additional patients with SS and 14 control subjects to examine whether the glucocorticoid deficiency observed was primary and/or secondary. Compared to controls, the ACTH and Cortisol responses to hCRH were blunted (ACTH after 60 min: 29 ± 7 vs. 58 ± 8 pg/ml in controls, p = 0.014; cortisol: 15.2 ± 1.5 vs. 19.6 ± 0.7 µg/dl, p = 0.018), suggesting the presence of secondary adrenal insufficiency. There was improvement of both ACTH and cortisol responsiveness to hCRH with therapy, with cortisol recovery occurring before ACTH, suggesting an additional primary component of adrenal dysfunction in these patients. Plasma concentrations of tumor necrosis factor (TNF)-Α (16.0 ± 4.1 vs. 2.9 ± 1.4 pg/ml in controls, p = 0.003) and interleukin (IL)-6 (19.2 ± 7.3 vs. 1.3 ± 0.2 pg/ml, p = 0.0001), but not IL-1Β (2.0 ± 0.2 vs. 0.9 ± 0.2, p = NS), were elevated when adrenocrotical function impairment and disease activity were at their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentrations and maximal Cortisol concentrations during hCRH testing (TNF-Α: r = –0.31, p = 0.003; IL-6: r = –0.34, p = 0.002). We conclude that unmedicated SS is associated with significant impairment of adrenocortical function which is reversed with suramin and/or melarsoprol therapy in the majority of patients. This impairment may be due to the elevated plasma cytokine concentrations, and may represent a natural adaptation of the HPA axis in inflammatory states. A controlled therapeutic trial is necessary to demonstrate whether supplemental glucocorticoids could be beneficial in SS.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.