Subclinical Hypothyroidism in HIV-Infected Patients Is Not an Autoimmune Disease

Abstract

Aims and Methods: A study of 350 HIV+ patients in our region showed that 16% suffered from hypothyroidism. Twenty-two HIV+ hypothyroid patients (10 with subclinical hypothyroidism, 12 with low FT4 levels (LT4) (confirmed by a dialysis equilibrium assay) and 22 HIV+ euthyroid controls receiving highly active anti-retroviral therapy were included in an additional study. Results: No goiter or anti-thyroid antibodies were detected. Use of stavudine was more frequent in the LT4 subgroup (p < 0.01) and subclinical hypothyroidism group (p = 0.04). Use of didanosine (OR, 12.5, p < 0.01) and ritonavir (OR, 33.0, p < 0.01) was more frequent in the LT4 subgroup, with a greater didanosine cumulative dose (616.7 mg [180.0, 1,260.0] vs. 263.7 [63.0, 948.0], p = 0.01). Reverse T3, binding protein levels, the TSH response to thyrotropin-releasing hormone, urinary iodine, plasma selenium and thiocyanate levels did not differ. IFNγ levels were lower in the subclinical hypothyroidism group (pg/ml) (9.1 [0.0, 22.7] vs. 19.5 [0.0, 40.9], p = 0.03). Conclusion: None of the investigated mechanisms are able to explain the occurrence of hypothyroidism in HIV patients receiving highly active anti-retroviral therapy except the anti-retroviral treatment. In light of the absence of autoimmunity, the normal adenohypophysis and thyroid responses to thyrotropin-releasing hormone, central hypothyroidism is suspected and could explain LT4 and high TSH levels. Underlying mechanisms need further exploration.

Association between antiretrovirals and thyroid diseases: a cross-sectional study

“…In our study, only one of 23 patients was diagnosed with hypothyroidism or subclinical hypothyroidism and had positive anti-TPO values (4.34%). This value is below what is expected for the general population and gives consistency to the scientific evidence that HIV-infected patients with primary hypothyroidism have lower anti-TPO positivity (20,32). The absence of anti-TPO does not mean that the patients do not have thyroid autoimmune disease.…”

“…Subclinical hypothyroidism is characterized by slightly elevated TSH and normal FT 4 levels. In the present study, 12.82% of patients had these characteristics, which kept this result above the average prevalence among HIV-infected persons of 3.5% to 12.2% (20)(21)(22). This result was elevated with respect to the overall population, for which the prevalence is 4.3% (19).…”

“…The most common cause of primary hypothyroidism in the population is Hashimoto's thyroiditis, which has a prevalence of 0.3% (18,19). Among HIV-infected individuals, the prevalence of primary hypothyroidism is approximately 2.6% (20)(21)(22).…”

“…Another manifestation consistent with central dysfunction is the presence of isolated low levels of TSH with normal free T 4 (FT 4 ). This condition was found in 1.3 to 6.8% of HIV-infected individuals, especially those in advanced disease stages (20,(25)(26)(27)(28). However, administration of exogenous TSH releasing hormone (TRH) did not alter the response of TSH among individuals with low FT 4 , making hypothalamic or pituitary insufficiency the least likely scenario (29).…”

Autoimmune thyroid disease: What secrets we still need to unravel?

“…Most recently, new players has been added in the knowledge aiming to decipher the secrets of interaction risk factors. It has been hypothesized that non-infectious environmental stress could reactivate viral latent infections and triggering an autoimmune disease in genetically primed individuals (17). In addition, epigenetic modulation factors have been implicated as a plausible mechanism for interaction between susceptibility genes and environmental triggers.…”