关键词: 结核,抗多种药物性, 药物疗法,联合, 丙硫异烟胺, 对氨水杨酸, 甲状腺功能减退症, 临床方案, 对比研究

Abstract:

Objective To analyze the occurrence and characteristics of hypothyroidism in patients with multidrug-resistant tuberculosis (MDR-TB) after anti-tuberculosis treatment with prothionamide (Pto) and/or para-aminosalicylic acid (PAS). Methods According to the selection criteria, 336 MDR-TB patients both from outpatient and hospitalized in Department of Tuberculosis, the Public and Health Clinic Centre of Chengdu between October 1, 2017 and June 30, 2019 were selected. They were divided into Pto group (n=91, treated only with Pto) and Pto+PAS group (n=245, treated with Pto and PAS). Their thyroid function were tested before anti-tuberculosis treatment and 1, 3, 6, 9, 12, 18, 24 months after anti-tuberculosis treatment. The occurrence rate and time of hypothyroidism, and when treat with Levothyroxine Sodium Tablets, the rate of treantment, treatment effect and the dosage were compared. Results Of the 336 MDR-TB patients, incidence of drug-induced hypothyroidism was 28.87% (97/336); among the 97 patients, myxedema was found in 4, fatigue with hair loss was found in 2, and the other 91 were without any obvious symptoms. The occurrence rate of hypothyroidism was 19.78% (18/91) in Pto group, which was statistically different from that in Pto+PAS group (32.24% (79/245), χ ²=5.020, P=0.025). Hypothyroidism incidence in male group was significantly lower than that in female group (24.07% (52/216) vs. 37.50% (45/120), χ ²=6.772, P=0.009). Occurrence rate of drug-induced hypothyroidism decreased with the treatment duration, rates were 40.20% (39/97), 24.74% (24/97), 17.53% (17/97) and 17.53% (17/97), respectively, 1.5 months, 3 months, 3-6 months, and 6 months after treatment. Occurrence rate of drug-induced hypothyroidism in Pto+PAS group within 1.5 months after treatment was significantly higher than that in Pto group (46.83% (37/79) vs. 11.11% (2/18), Fisher, P=0.018). A total of 78 drug-induced hypothyroidism patients needed to be treat with Levothyroxine Sodium Tablets, and the number of cases from Pto+PAS group was significantly more than that from Pto group (84.81% (67/79) vs. 61.11% (11/18), χ ²=5.227,P=0.022). The dosage of Levothyroxine Sodium Tablets were ≤50 μg/d for 49 patients (62.82%), 51-75 μg/d for 20 patients (25.64%), >75 μg/d for 9 patients (11.54%). Four patients in Pto+PAS group were treated with the dosage of over 125 μg/d, but the effect was little, therefore, the Pto and PAS were discontinued; however, the other 74 patients had better prognosis. Conclusion Hypothyroidism are more likely to occur in MDR-TB patients treated with Pto+PAS than those treated with Pto alone. The incidence of hypothyroidism is high within 3 months after anti-tuberculosis treatment, and thyroid function needs to be closely monitored. If patients with drug-induced hypothyroidism have better prognosis when treated with Levothyroxine Sodium at different dosages, the Pto and PAS could be continued.

Key words: Tuberculosis,multidrug-resistant, Drug therapy,combination, Prothionamide, Aminosalicylic acid, Hypothyroidism, Clinical protocols, Comparative study