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Increased prevalence of subclinical hypothyroidism in HIV patients treated with highly active antiretroviral therapy

2000; Lippincott Williams & Wilkins; Volume: 14; Issue: 8 Linguagem: Inglês

10.1097/00002030-200005260-00026

1473-5571

Michèle Grappin, Lionel Piroth, Bruno Vergès, Catherine Sgro, Gérard Mack, Marielle Buisson, Michel Duong, P. Chavanet, H. Portier,

Vitamin D Research Studies

Highly active antiretroviral therapy (HAART) has changed the clinical evolution of HIV infection. However, its adverse effects are increasingly being recognized, particularly those concerning protease inhibitors, and some of the secondary effects are probably not known yet. The observation of four cases of clinical hypothyroidism in patients treated with HAART for several months prompted us to look for thyroid dysfunction in HIV patients. We therefore conducted an epidemiological cross-sectionnal study to evaluate the prevalence of thyroid dysfunction in patients treated with HAART. The second aim of the study was to investigate the relationship between the different treatments associated with protease inhibitors and hypothyroidism. From February to June 1999, all patients infected by HIV and treated with antiretroviral therapy, including protease inhibitors, who consulted at the Infectious Diseases Department of Dijon University Hospital (France) were included in the study. They were clinically examined, with special attention paid to the signs of thyroidism. Serum-free thyroxine (T4), free triiodothyronine (T3) concentrations, thyrotropin levels, and anti-thyroperoxydase antibodies were performed in addition to routine biological tests. In addition, familial, personal history of thyroid diseases and data regarding HIV history were recorded. Comparison between quantitative variables was performed using the Mann–Whitney test. For qualitatives variables, the chi-squared test was used. Multivariate analysis was performed by using a backward logistic regression test. A P value of less than 0.05 was considered significant. A total of 212 patients were included in the study. The mean age was 40.8 years (SD = 9.54). The sex ratio of men : women was 2.6. Eighty-five patients were in stage A of the Centers for Disease Control and Prevention classification, 67 in stage B and 60 in stage C. Twenty-six patients (12.3%) presented at least one abnormal test of thyroid function. On these, no clinical dysthyroidism was noted. Four patients had a previous history of thyroid disorder, requiring the adjustment of levothyroxin doses after starting HAART. Therefore, after excluding the four patients with previous thyroid disease, biological thyroid dysfunction was assessed in 22 (10.4%) patients: 18 (8.5%) with subclinical hypothyroidism (defined by the existence of a significant elevation of thyrotropin levels with normal T3 and T4 levels) and four patients with elevated anti-thyroperoxydase antibody serum levels. No hyperthyroidism was found. In univariate analysis, excluding patients with a history of thyroid dysfunction (four patients in the group with biological thyroid abnormalities and one patient in the group without abnormalities), the cumulative daily dose of stavudine and lamivudine were found to be significantly (P = 0.01 and 0.04, respectively) greater in patients with hypothyroidism than in those without (Table 1). With regard to the daily cumulative doses of the different protease inhibitors, no differences were found between the two groups. In multivariate analysis, the cumulative daily dose of stavudine remainded associated with subclinical hypothyroidism (annual odds ratio 1.96; confidence interval 1.15–3.33;P = 0.01) whereas age, sex, hepatitis C virus status and cumulative daily doses of other treatments were not.Table 1: Comparison of patients with and without thyroid dysfunction after excluding patients with a medical history of thyroid abnormality. These results suggest an increased prevalence of subclinical hypothyroidism in the HIV treated population. Several studies have described abnormalities of thyroid function in HIV infection [1,2], but none in a population of treated patients. In the natural history of HIV, abnormalities of thyroid function tests can be observed, particularly in patients with AIDS [3,4], but a few cases of subclinical hypothyroidism have been described in the literature. A previous study in our centre, among 63 HIV patients who were not treated with HAART [5], did not find any abnormalities nor any differences in thyroid function tests in asymptomatic and AIDS patients. Because it was cross-sectional, this study presents some limitations and the results need to be confirmed. Despite this limitation, stavudine seems to be associated with biological hypothyroidism but the mechanism involved remains unknown. Because the T4 : T3 ratio showed no difference between the two groups of patients, a possible modification of T4 deiodation is unlikely. We suggest a direct effect of antiretroviral therapy, and particularly of stavudine, on the production or catabolism of thyroid hormones. In conclusion, thyroid function tests should be performed in patients treated with HAART, in particular those regimens including stavudine. Further prospective studies, especially with control groups are necessary to confirm this finding and to determine the relationship between antiretroviral therapy and hypothyroidism. Michèle Grappin Lionel Piroth Bruno Verges Catherine Sgro Gérard Mack Marielle Buisson Michel Duong Pascal Chavanet Henri Portier