India has the third highest burden of HIV in the world with an estimated 2.3 million people living with HIV (PLHIV) in 2021.^[1] Human immunodeficiency virus infection can lead to involvement of various organs and systems including endocrine glands. Alteration in endocrine functions may be due to the possible relationship between the immune and endocrine systems, direct involvement of the glands by the HIV itself, opportunistic infections or malignancies, highly active anti-retroviral therapy (HAART) and drugs used to treat the opportunistic infections. ^[2,3]

Thyroid hormones play a fundamental role in metabolism, and regulate immune system, modulating humoral and cell mediated immunity. ^[4,5] Although thyroid function tests are often abnormal in HIV patients, the prevalence of overt thyroid disorder is not significantly different from that of the general population. Most asymptomatic patients with HIV infection have normal thyroid function. Some, however, exhibit increased serum T4 and T3 concentrations. These increases are as a result of increases in serum thyroxine binding globulin, the cause of which is unknown. However, with progression of HIV infection and as the patients become more ill, serum T4 and T3 concentrations decline, as is obtained in most if not all chronically ill patients; serum thyrotropin concentrations however remain normal or slightly depressed. These changes are as a result of reduction in serum binding proteins, decreased extra thyroidal conversion of T4 to T3, and decreased secretion of thyrotropin.^[6]

Cytokines may be involved in some of these; especially the reduction in the peripheral conversion of T4 to T3. An increasing number of patients taking anti-HIV drugs are presenting with thyroid disorders as a result of improved immune function (immune reconstitution syndrome). Graves’ disease is the commonest among immune reconstitution syndromes; others include Hashimoto’s thyroiditis and hypothyroidism. Autoimmune Thyroid disease (AITD) occurs in 3% of women and 0.2% of men. ^[7]

A high prevalence of abnormalities in thyroid function tests among HIV infected adults has been noted in previous cross-sectional studies worldwide; however, there is paucity of Indian studies that are needed to evaluate the thyroid dysfunction in HIV infected Indian patients.^[3]

Hence the present study was undertaken with an aim to study the thyroid dysfunction in seropositive HIV patients attending at tertiary care center.

OBJECTIVES

• To study the thyroid dysfunction in seropositive HIV patients.

To correlate the Thyroid function changes in these patients with their   CD4 cell count and staging of HIV

The present cross sectional observational study was conducted at the Department of Medicine of tertiary care centre. The study was conducted from August 2022 to December 2023. The study population was confirmed cases of seropositive HIV coming to General medicine department and ART centre. Patients known case of thyroid disorder, on drugs altering thyroid hormone metabolism like stavudine, diabetes mellitus and abnormal liver function tests were excluded. Hundred individuals were selected after an informed consent. Study was started only after approval of the ethics committee. A detailed case history was recorded and routine blood investigations like CBC, BSL, RFT, urine routine microscopy, HIV profile with WHO staging ^[8] and thyroid profile was done for the selected individuals. Data were double entered using Microsoft excel 2007 and analysed using SPSS version 24.

A total of 100 cases of seropositive HIV were included during the study period.

Table 1: Distribution of patients according to demographic profile:

In the above table, most patients were in age group 41-50 years (33%) with mean age of the patients was 48.22 ±12.22 years. It was observed that majority of patients were male (63%) and females were 37%.

Table 2: Distribution of patients according to clinical profile:

According to WHO staging of HIV, most of patients belongs to Stage III (36%) followed by Stage II (30%). It was observed that, 56% patients on TLE regimen and 44% patients on ZLN regimen

Table 3: Distribution of patients according to Thyroid profile:

It was observed that, out of 100 patients, 23% patients were with thyroid dysfunction. Among 23 patients with thyroid dysfunction, 13 (56.52%) patients were with Subclinical hypothyroidism, 7 (30.43%) patients were with hypothyroidism, 2 (8.7%) patients of hyperthyroidism and one (4.35%) patient with low T3 levels.

Table no 4: Association of HARRT treatment and Thyroid dysfunction:

(*P<0.05 statistically significant)

The above table shows association of HARRT treatment and thyroid dysfunction. It was observed that patients on HARRT TLE regimen showed more thyroid dysfunction (78.26%) compared to ZLN regimen (21.74%) with statistically significant difference. (P<0.05)

Table no 5: Correlation of CD4 count and thyroid hormones:

(*P<0.001 statistically highly significant)

It was observed that a direct correlation between CD4 count and free T3 and free T4 values and an inverse correlation of CD4 counts with serum thyroid stimulating hormone (TSH) levels was seen with statistical significance. (P<0.001)

The present cross-sectional study was undertaken to study thyroid function among HIV infected patients on HAART and to correlate with absolute CD4 count in tertiary care hospital.

In the present study, it was observed that most patients were in age group 41-50 years (33%) with mean age of the patients was 48.22 ±12.22 years. It was observed that majority of patients were male (63%) and females were 37%. (Table 1)

Giordano Madeddu et al ^[9] in a study observed mean age of the patients 39·2 ± 6·6 years and among 202 adult patients, 134 (66.34%) were men and 68 (33.66%) were women. This finding was in accordance to present study. Similarly, in Savitha A. Sebastian et al ^[10] study the mean (SD) age of patients was 38.8 (10.8) years of whom 94 (59.11%) were males.

The distribution of patients according to WHO staging of patients showed that, most of patients belongs to Stage III (36%) followed by Stage II (30%). (Table 2) Sunita Kumawat et al ^[11] study the socio-demographic and clinical profile of HIV/AIDS patients observed 46.33% of patients were in WHO stage I of HIV/AIDS disease.

In present study, it was observed that, 56% patients on TLE regimen and 44% patients on ZLN regimen. (Table 2) Similarly, in Verma RK et al. ^[4] study out of 100, 58% patients were on ZLN (Zidovudine, Lamivudine, Nevirapine) and 42% patients were on TLE (Tenofovir, Lamivudine, Efavirenz).

In the present study, out of 100 patients, 23% patients were with thyroid dysfunction. Among 23 patients with thyroid dysfunction, 13 (56.52%) patients were with Subclinical hypothyroidism, 7 (30.43%) patients were with hypothyroidism, 2 (8.7%) patients of hyperthyroidism and one (4.35%) patient with low T3 levels. (Table 3)

Similarly, Verma RK et al. ^[4] in a study observed thyroid dysfunction among 20% patients while 80% patients were euthyroid with majority 12% patients had subclinical hypothyroidism, while 6% subjects had overt hypothyroidism (TSH values of >10). Only 2% of subjects had TSH values of <0.5. Giordano Madeddu et al ^[9] observed thyroid function parameter abnormalities were found in 12·6% HAART patients. Nine of 23 patients had subclinical hypothyroidism with high TSH and normal FT3 and FT4 levels. In Savitha A. Sebastian et al ^[10] study thyroid dysfunction was observed in 47 (29.55%) patients. The most commonly observed thyroid function abnormality was subclinical hypothyroidism in 29 (61.7%) patients. These wide variations in prevalence across studies may be explained by the heterogeneity of the cohort with regard to the duration and stage of illness, receipt of HAART, nature of HAART, associated infections and severity of immunodeficiency.

In the present study, it was observed that patients on HARRT TLE regimen showed more thyroid dysfunction compared to ZLN regimen with statistically significant difference. (P<0.05) (Table 4) Similarly, in Verma RK et al. ^[4] study thyroid dysfunction was associated with treatment of TLE regimen and this result was found to be statistically significant (p<0.05). Silva et al. ^[12] and Beltran et al. ^[13] suggested a link between the use of stavudine and thyroid dysfunction. In the study by Beltran et al., ^[13] the odds ratio (OR) for hypothyroidism in patients receiving HAART was 2.7.

The Correlation of CD4 count and thyroid hormones showed that a direct correlation between CD4 count and free T3 and free T4 values and an inverse correlation of CD4 counts with serum thyroid stimulating hormone (TSH) levels was seen. (P<0.001) (Table 5) Verma RK et al. ^[4] in a study observed as the CD4 counts decreases mean values of T3 and T4 also decreases while S.TSH level increases. Giordano Madeddu et al ^[9] study HAART patients CD4 count was negatively correlated with TSH levels with statistical significance. The association may be due to the increased risk of infections or infiltration of the thyroid gland in patients with lower CD4 counts.

The present study concludes that, subclinical hypothyroidism and overt hypothyroidism are the commonest thyroid abnormality seen, more commonly in females. CD4 counts have direct association with free T3 and free T4 and inverse association with Serum TSH level indicating trend for hypothyroidism as HIV disease progresses.

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