THYROID-DYSFUNCTION IN AFRICAN TRYPANOSOMIASIS - A POSSIBLE ROLE FOR INFLAMMATORY CYTOKINES

OBJECTIVE Sleeping sickness (African trypanosomiasis) is an anthropozo onosis transmitted by the tsetse fly. The treatments of choice are the antiparasitic agents suramin and/or melarsoprol. Experimental infecti on of animals with Trypanosoma brucei results in inflammatory lesions in the pituitary and/or the thyroid gland. In biochemical terms, these animals have hypothyroidism. We evaluated the functional integrity of the hypothalamic-pituitary-thyroid axis in patients with African tryp anosomiasis before, during and after specific therapy. DESIGN Prospect ive, controlled, cross-sectional study. PATIENTS AND MEASUREMENTS Sixt y-five patients with sleeping sickness (31 female, 34 male; aged 18-66 ; 32 with haemolymphatic sleeping sickness receiving suramin i.v., 33 with cerebral sleeping sickness receiving melarsoprol) and 13 control subjects (6 female, 7 male; aged 21-60) were enrolled in a cross-secti onal study after giving informed consent. Fourteen patients were studi ed shortly, after admission for sleeping sickness, 19 in the middle of the course of treatment, 18 at the end of the 5-week treatment period , and 14 patients after cure. All subjects underwent a TRH stimulation test at 1200 with bolus injection of 400,ug TRH i.v. Blood was drawn for determination of fT3, fT4, TSH, rT3, TNF-alpha, IL-1 and IL-6 at 0 minutes and TSH at 60 minutes. All hormones and cytokines were determ ined by RIA or ELISA. RESULTS Baseline TSH concentrations (mean+/-SEM) were elevated in unmedicated patients with sleeping sickness compared to normal subjects (2.6+/-0.4 vs 1.4+/-0.2 mU/l; P = 0.01), whereas f T3 (2.7+/-0.5 vs 5.8+/-0.3 pmol/l; P 0.0002) and fT4 concentrations (1 0.3+/-1.2 vs 15.4+0.8 pmol/l; P = 0.007) were low. Stimulated TSH conc entrations did not significantly differ from normal controls. Reverse T3 concentration in patients with sleeping sickness were normal (2.2 /- 0.3 vs 2.4 +/- 0.2 nmol/l; P = NS). During the course of treatment, baseline TSH, fT3 and fT4 concentrations slowly returned to normal an d were indistinguishable from controls after cure. Plasma concentratio ns of TNF-alpha (16.0+/-4.1 vs 2.9+/-1.4 ng/l in controls; P = 0.003) and interleukin-6 (19.2+/-7.3 vs 1.3+/-0.2 ng/l; P = 0.0001), but not interleukin-1beta (2.0+/-0.2 vs 0.9+/-0.2, ng/l P = NS), were elevated , when thyroid function impairment arid disease activity were al their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentratio ns and fT3 concentrations (TNF-alpha: r = -0.34, P = 0.003; IL-6: r = -0.43, P = 0.0001). CONCLUSIONS We conclude that unmedicated sleeping sickness is associated with significant impairment of thyroid function , which is reversed with specific therapy. Elevated TSH concentrations and low fT3 and fT4 concentrations suggest primary hypothyroidism in patients with sleeping sickness. However, an additional pituitary and/ or hypothalamic component cannot be excluded. This impairment may be d ue to the elevated plasma cytokine concentrations found in these patie nts or may be the result of parasitic thyroiditis.