Reincke M, Allolio B, Petzke F, Heppner C, Mbulamberi D, Vollmer D, Winkelmann W, Chrousos G P
Department of Medicine, University of Würzburg, FRG.
Clin Endocrinol (Oxf). 1993 Oct;39(4):455-61. doi: 10.1111/j.1365-2265.1993.tb02393.x.
Sleeping sickness (African trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. The treatments of choice are the antiparasitic agents suramin and/or melarsoprol. Experimental infection 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 trypanosomiasis before, during and after specific therapy.
Prospective, controlled, cross-sectional study.
Sixty-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-sectional study after giving informed consent. Fourteen patients were studied 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 micrograms 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 determined by RIA or ELISA.
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 fT3 (2.7 +/- 0.5 vs 5.8 +/- 0.3 pmol/l; P = 0.0002) and fT4 concentrations (10.3 +/- 1.2 vs 15.4 + 0.8 pmol/l; P = 0.007) were low. Stimulated TSH concentrations 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 and were indistinguishable from controls after cure. Plasma concentrations 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-1 beta (2.0 +/- 0.2 vs 0.9 +/- 0.2, ng/l P = NS), were elevated, when thyroid 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 fT3 concentrations (TNF-alpha: r = -0.34, P = 0.003; IL-6: r = -0.43, P = 0.0001).
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 due to the elevated plasma cytokine concentrations found in these patients or may be the result of parasitic thyroiditis.
昏睡病（非洲锥虫病）是一种由采采蝇传播的人畜共患病。首选治疗药物是抗寄生虫药苏拉明和/或美拉胂醇。用布氏锥虫对动物进行实验性感染会导致垂体和/或甲状腺出现炎性病变。从生化角度来看，这些动物存在甲状腺功能减退。我们评估了非洲锥虫病患者在特异性治疗前、治疗期间及治疗后的下丘脑 - 垂体 - 甲状腺轴功能完整性。
前瞻性、对照、横断面研究。
65例昏睡病患者（女性31例，男性34例；年龄18 - 66岁；32例患有血淋巴型昏睡病接受静脉注射苏拉明治疗，33例患有脑型昏睡病接受美拉胂醇治疗）和13名对照者（女性6例，男性7例；年龄21 - 60岁）在获得知情同意后纳入横断面研究。14例患者在因昏睡病入院后不久接受研究，19例在治疗过程中，18例在5周治疗期结束时，14例在治愈后。所有受试者于12:00接受静脉推注400微克促甲状腺激素释放激素（TRH）后的TRH刺激试验。在0分钟时采集血样测定游离三碘甲状腺原氨酸（fT3）、游离甲状腺素（fT4）、促甲状腺激素（TSH）、反三碘甲状腺原氨酸（rT3）、肿瘤坏死因子 -α（TNF -α）、白细胞介素 -1（IL -1）和白细胞介素 -6，在60分钟时测定TSH。所有激素和细胞因子均通过放射免疫分析（RIA）或酶联免疫吸附测定（ELISA）进行测定。
与正常受试者相比，未用药的昏睡病患者基线TSH浓度（均值±标准误）升高（2.6±0.4 vs 1.4±0.2 mU/l；P = 0.01），而fT3（2.7±0.5 vs 5.8±0.3 pmol/l；P = 0.0002）和fT4浓度（10.3±1.2 vs 15.4 + 0.8 pmol/l；P = 0.007）较低。刺激后的TSH浓度与正常对照组无显著差异。昏睡病患者的反T3浓度正常（2.2±0.3 vs 2.4±0.2 nmol/l；P = 无显著性差异）。在治疗过程中，基线TSH、fT3和fT4浓度缓慢恢复正常，治愈后与对照组无差异。当甲状腺功能损害和疾病活动处于最严重程度时，血浆TNF -α浓度（对照组为2.9±1.4 ng/l，患者组为16.0±4.1 ng/l；P = 0.003）和白细胞介素 -6浓度（对照组为1.3±0.2 ng/l，患者组为19.2±7.3 ng/l；P = 0.0001）升高，但白细胞介素 -1β浓度（2.0±0.2 vs 0.9±0.2 ng/l，P = 无显著性差异）未升高，且随着治疗逐渐降至正常范围。我们发现基线细胞因子浓度与fT3浓度之间存在负相关（TNF -α：r = -0.34，P = 0.003；IL -6：r = -0.43，P = 0.0001）。
我们得出结论，未用药的昏睡病与甲状腺功能显著受损有关，特异性治疗可使其逆转。TSH浓度升高以及fT3和fT4浓度降低提示昏睡病患者存在原发性甲状腺功能减退。然而，不能排除垂体和/或下丘脑的其他因素。这种损害可能是由于这些患者血浆细胞因子浓度升高所致，也可能是寄生虫性甲状腺炎的结果。
