| Abstract|| |
Background: The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities, including abnormalities of thyroid gland. Materials and Methods: This study was designed to understand the spectrum of pathology of thyroid in Indian patients with AIDS. The present study describes the findings of retrospective autopsy findings of 158 patients with AIDS which revealed infectious diseases from a time period before the use of highly active antiretroviral regimen. Results: A wide range of bacterial, fungal, and viral infections were observed. Tuberculosis was recorded in 14 (09%) patients, Cryptococcus neoformans in 11 (7%) patients and cytomegalovirus in 3 (2%) patients. Hashimoto's thyroiditis and lymphocytic thyroiditis were seen in 02 (01%) patients each. One patient had dual infection comprising of tuberculosis and cytomegalovirus infection. The other microscopic findings observed were goiter (2 patients), interstitial fibrosis in thyroid (7 patients), and calcification in thyroid (8 patients). Conclusions: Abnormalities of thyroid are uncommon findings in patients with HIV infection however several case reports of thyroid involvement by infectious agents and neoplasm are described in these patients; hence patients with HIV infection should be closely followed up for development of goiter or abnormalities of thyroid functions.
Keywords: Acquired immunodeficiency syndrome, human immunodeficiency virus, infections, neoplasm, thyroid
|How to cite this article:|
Lanjewar DN, Ramraje SN, Lanjewar SD. Pathology of thyroid in acquired immunodeficiency syndrome
. Indian J Pathol Microbiol 2016;59:279-83
| Introduction|| |
According to National AIDS Control Organization, Ministry of Health and Family Welfare, New Delhi, the prevalence of AIDS in India in 2011 has reduced from 0.41 to 0.27 in 2001. While the National AIDS Control Organization estimated that 2.4 million people live with human immunodeficiency virus (HIV) in India in 2008–2009. A more recent investigation by the Million Death Study Collaborators in the British Medical Journal (2010) estimates the HIV-infected population in India to be between 1.4 and 1.6 million people. The spread of HIV in India has been uneven, with much of India having a low rate of infection; certain places have been more affected than others. The highest HIV prevalence rates are found in Maharashtra in the West, Andhra Pradesh, Tamil Nadu, and Karnataka in the South, and Manipur and Nagaland in the North East. In Maharashtra and Southern states, HIV is primarily spread through heterosexual contact. Infections in the North East are mainly found amongst injecting drug users and sex workers. The largest autopsy report on HIV-infected patients from Mumbai, Maharashtra described relative prevalence of opportunistic infections, tumors, and other HIV-associated pathologies in 236 patients. The purpose of this study is to describe the spectrum of thyroid diseases in patients with AIDS.
HIV infection and AIDS can lead to multiple organ involvement including the endocrine system. Endocrine manifestations include both pathological changes and disturbances in function. In these patients, endocrine functions may be altered because of the possible relationship between the immune and endocrine systems, direct involvement of the glands by HIV itself or by opportunistic infections or neoplasm., Among individuals with HIV infection, 1–2% manifest overt thyroid disease while others show subtle abnormalities in thyroid functions. Side effects of highly active antiretroviral therapy (HAART) can also alter endocrine functions., Autopsy series generally supports the notion that the involvement of thyroid parenchyma by the pathological process is an uncommon event during HIV infection. Despite the presence of a large number of HIV-infected population, there is no literature regarding the pathology of thyroid in patients with HIV/AIDS from India. Hence, this retrospective study is designed to describe pathological findings in the thyroid of patients with HIV/AIDS in a tertiary care hospital in Mumbai, India.
| Materials and Methods|| |
Sir J. J. Hospital in Mumbai is a tertiary care public hospital attached to Grant Government Medical College and is run by the state government that provides free services to patients and also treats all patients with HIV/AIDS. The patients in this study were admitted in medical wards of a 1352-bed hospital. A total of 236 autopsies were carried out in the Department of Pathology, Grant Government Medical College, Mumbai in a span of 20 years from 1988 to 2007. Thyroid specimens of 158/236 patients were available for study. None of these patients had clinical signs of thyroid dysfunction and no thyroid function tests were performed during their hospitalization. Thyroid specimens were examined macroscopically and microscopically. After external examination, each thyroid gland was bisected longitudinally, and their cut surfaces were examined meticulously. Irrespective of presence or absence of grossly visible lesions, a minimum of five sections were obtained from each thyroid gland (2 sections from each lobe and one from isthmus) for paraffin embedding and 4 µ thick tissue sections obtained for histopathological assessment. The slides were stained with hematoxylin and eosin, periodic acid-Schiff, Mucicarmine, Ziehl-Neelsen, gram-stain, and Gomori's methenamine silver nitrate stain.
The facilities for CD4 and CD8 testing were not available in our hospital until June 2007 and patients were unable to afford the cost of the CD4 and CD8 testing from private laboratories. In July 2007, CD4 and CD8 testing facilities were made available to our patients; however, none of our patients were investigated for CD4/CD8 counts. In April 2004, the Government of India launched a program of providing free HAART at the eight government hospitals (including Sir J. J. Hospital, Mumbai). None of the patients in this study had received HAART therapy through this program.
| Results|| |
Thyroid specimens obtained from autopsies of 158 HIV/AIDS patients were reviewed in this study. The demographic data of 158 patients with HIV infection shows that a total of 125 (79%) men and 33 (21%) women were included in the study. The majority of the patients 135 (85%) were aged 21–40 years. The main risk factor for HIV transmission was heterosexual contact in 151 (96%), patients while other risk factors were blood transfusion in 2 (1%) patients, men having sex with men in 2 (1%) patients, and unknown risk factor in 3 (2%) patients [Table 1].
|Table 1: Demographic data in patients with acquired immunodeficiency syndrome (n=158)|
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The thyroid gland weighed between 5 and 50 g. The gross examination of thyroid was unremarkable in 145 patients whereas in remaining 13 patients, thyroid showed grossly visible abnormality which comprised of slimy feel of thyroid due to cryptococcal infection in 6 patients, tuberculous abscess in 2 patients, miliary tuberculosis in 2 patients and goiter in 3 patients [Figure 1]a and [Figure 1]b. Histopathology of the thyroid demonstrated a variety of infectious disorders involving the gland parenchyma. A total of 50 pathologic lesions were identified which comprised a wide range of bacterial, fungal, and viral infections [Table 2]. Mycobacterium tuberculosis was recorded in 14 (09%) patients. In two patients thyroid showed characteristic tuberculous granuloma [Figure 1]c. In 12 patients, the histological pattern of tuberculosis was nonreactive, showing abundant granular necrosis, ill-formed or absent granuloma, scanty or no giant cells, scanty or no epithelioid cells and numerous acid-fast Bacilli on a Ziehl-Neelsen stain [Figure 1]d. All the patients with tuberculosis of thyroid had generalized tuberculosis in lungs, lymph nodes, spleen, liver, kidneys, gastrointestinal tract, adrenals and brain indicating that tuberculosis of thyroid in our patients was due to dissemination from other organs. Cryptococcus neoformans was identified in the thyroid of 11 (7%) patients, and all these patients had disseminated cryptococcal infection in the central nervous system, lungs, liver, spleen, kidneys, adrenals, and lymph nodes. Cryptococcus was identified in thyroid follicles and interstitial tissue, and there was no inflammatory response to cryptococcal infection [Figure 2]a. Cytomegalovirus (CMV) infection of thyroid was present in 3 (2%) patients. On histopathological examination, intranuclear and intracytoplasmic inclusions of CMV were observed in the follicular lining of thyroid and there was no inflammatory response to CMV infection [Figure 2]b. All three patients had disseminated CMV infection involving lungs, kidneys, adrenals, and CNS. In one patient, dual infection comprising tuberculosis with CMV was identified. Two cases each showed Hashimoto's thyroiditis and lymphocytic thyroiditis, respectively. In 3 (2%) patients, thyroid showed goiter, interstitial fibrosis of thyroid was noted in 7 (4%) patients and calcification of thyroid in 8 (5%) patients.
|Figure 1: (a) Cut section of thyroid gland shows tuberculous abscess (b) and miliary tubercles (c) microphotograph of thyroid shows tuberculous granuloma (H and E, ×400) and (d) histology of tuberculosis abscess shows necrosis, neutrophilic and histiocytic infiltration (H and E, ×400)|
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|Table 2: Pathologic lesions in thyroid of patients with acquired immunodeficiency syndrome|
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|Figure 2: (a) Microphotograph of thyroid shows round and yeast forms of cryptococci (GMS, ×400) and (b) shows enlarged thyroid follicular cells containing intracytoplasmic cytomegalovirus inclusions (H and E, ×400)|
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| Discussion|| |
This retrospective autopsy study of thyroid in patients who died of AIDS at a tertiary care hospital in Mumbai, India demonstrated that opportunistic infections of the gland parenchyma were not uncommon. Particularly, striking was the incidence of tuberculous thyroiditis among the studied patients. Although endocrine dysfunction has not been prominent in the course of most patients with AIDS, it does occur and may involve thyroid gland. Most of the literature on the involvement of thyroid in AIDS consists of case reports or small case series, therefore, it is difficult to determine the prevalence of thyroid dysfunction in HIV-infected patients.
Earlier it was believed that significant thyroid dysfunction is a relatively uncommon complication of HIV infection. However, published reports confirm that HIV-infected patients clinically presents with hypothyroidism, hyperthyroidism, diffuse or nodular enlargement of the thyroid, palpable thyroid masses and thyroid abscess.,,, To the best of our knowledge, only five papers describing autopsy findings of thyroid in patients with AIDS are reported in the literature of which three are from the United States of America and two are from South America, Brazil.,,,, The findings of these autopsy series are tabulated in [Table 3]. The first report of autopsy findings in the thyroid of 35 patients with AIDS from the United States of America demonstrated CMV infection of thyroid in 5 (14%) patients and Kaposi's sarcoma in 1 patient (6%) and all the 5 patients had CMV inclusions in lungs. Another study from the USA described pathological findings of 7 cases of thyroid of which CMV inclusions were seen in thyroid epithelial cells in 5 (71%) patients. None of their patients had clinical evidence of thyroid dysfunction, in two patients thyroid function tests were not performed while in remaining three patients thyroid function tests were within normal limit. Another larger autopsy study from the USA described findings of thyroid in 102 patients. This study showed CMV infection in 1 (1%) patient, M. tuberculosis in 1 (1%) patient, Cryptococcus neoformans in 1 (1%) patient, goiter in 3 (3%) patients and interstitial fibrosis in 5 (5%) patients. In addition to thyroid pathology, this study also described histopathological findings in parathyroid glands. The first report describing pathology of thyroid in AIDS from Brazil described findings of thyroid in 47 cases which comprised of Mycobacterium avium intracellulare (MAI) in 5 (10%) patients, Cryptococcus neoformans in 4 (8%), patients, Histoplasma capsulatum in 4 (8%) patients and paracoccidiomycosis in 1 (2%) patient. The second report from Brazil described findings of thyroid in 100 patients, this study was conducted before the advent of the HAART. The study showed M. tuberculosis in 23 (23%) patients, CMV infection in 17 (17%) patients, MAI in 5 (5%) patients, Pneumocystis carinii (Jerovecii) in 4 (4%) patients, H. capsulatum in 2 (2%) patients, Candida albicans in 2 (2%) patients, pyogenic bacterial infection of thyroid in 3 (3%) patients, Kaposi's sarcoma in 2 (2%) patients, and occult papillary carcinoma of thyroid in 4 (4%) patients. In four of their patients coexistent infections were observed which comprised CMV with H. capsulatum in one patient, CMV with C. albicans in the second patient, CMV with M. tuberculosis in third patient and pyogenic bacteria and C. albicans in the fourth patient.
|Table 3: Comparison of autopsy findings in thyroid of patients with acquired immunodeficiency syndrome|
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This study is the largest autopsy series describing findings of thyroid in 158 patients with AIDS. The findings of this study showed CMV infection in 3 (2%) patients, M. tuberculosis in 14 (9%) patients, cryptococcosis in 11 (7%) patients, Hashimoto's thyroiditis in 2 (1%) patients, lymphocytic thyroiditis in 2 (1%) patients, goiter in 3 (2%) patients, interstitial fibrosis in 7 (4%) patients, and calcification in 8 (5%) patients. The prevalence of tuberculosis and cryptococcosis of thyroid identified in our study is similar to Brazilian study., On the other hand, our findings are different from studies from the United States of America.,, We did not find any case of MAI infection in the present study. Pneumocystis pneumonia (PCP) (Jerovecii) was identified in 4% patients in Brazilian study while no case of PCP of thyroid was identified in this study. The prevalence of PCP described in Indian patients with AIDS is 5%. Extrapulmonary PCP has been increasingly reported in patients with AIDS, particularly in association with increasing use of aerosolized pentamidine.
Reports of cryptococcosis of thyroid presenting with the enlarged gland, or features of thyroiditis and hyperthyroidism are described as case reports., Similarly, several reports of P. carinii infection of the thyroid are described in patients with AIDS.,,,,,,,,, Clinically, these patients present with sub-acute thyroiditis, hypothyroidism or hyperthyroidism, diffuse or nodular enlargement of thyroid in one of the lobes and calcification of thyroid. In few cases, calcification was proven to be due to PCP infection. Fine-needle aspiration cytology or open lung biopsy is helpful in establishing the diagnosis of PCP. Occasional reports of thyroid involvement due to Rhodococcus equi and Aspergillus fumigatus are described in patients infected with the HIV.,
Simultaneous or multiple co-existing infections and/or neoplasm are commonly observed in patients with AIDS., In a study from USA multiple co-existing opportunistic infections were observed in 45% of patients in HIV group with thyroid pathology. These patients had more than two opportunistic infections and in one patient six (MAI, CMV, Cryptococcus, Candida, PCP and herpes) opportunistic infections were identified. Reports of concomitant tuberculosis and cryptococcosis and simultaneous CMV infection and Kaposi's sarcoma are also described in the thyroid of HIV-infected patients., In this study, only one case showed dual infection comprising tuberculosis and CMV infection.
To the best of our knowledge, no increase in neoplastic disorders of the thyroid has been described in the HIV-positive patients. Kaposi's sarcoma is described in 6% cases from the USA and 2% cases from Brazil., Kaposi's sarcoma and lymphoma can present as a palpable thyroid mass and hypo or hyperthyroidism.,,, Occult papillary carcinoma of the thyroid is described in 4% cases in Brazilian autopsy study. Recent reports described papillary thyroid carcinoma and medullary thyroid carcinoma in advanced HIV positive patients., We did not find any case of Kaposi's sarcoma, lymphoma, papillary or medullary carcinoma of the thyroid in this study.
| Conclusions|| |
The clinical presentation of thyroid dysfunction in HIV-infected patients has not been systematically studied. We conclude that thyroid abnormalities are not uncommon findings in the HIV-infected population; hence, clinicians should consider hyperthyroidism or hypothyroidism in the evaluation of HIV-infected individuals. Because of the possibility of involvement by opportunistic infections or neoplasm, the evaluation of a thyroid nodule or a goiter in HIV-infected individual first should include the biochemical workup checking thyroid stimulating hormone, T3, FT4 index. Fine-needle aspiration should be performed with cytology and cultures for bacteria, Mycobacterium, and fungi. Optimal treatment of patients with AIDS will require not only the awareness, judicious screening, recognition, and prompt treatment of these infections but also the maintenance of one's clinical suspicion for unusual problems. It is hoped that the incidence of thyroid disorders will decrease with the advent of antiretroviral combinations. On the other hand, longer survival with HAART may increase the chances of thyroid disorders in HIV-infected patients.
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Dr. Dhaneshwar Namdeorao Lanjewar
Department of Pathology, Grant Government Medical College and Sir J. J. Hospital, Byculla, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]