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Thyroid gland dysfunction in the patient with HIV

Thyroid gland dysfunction in the patient with HIV
Literature review current through: Jan 2024.
This topic last updated: Mar 09, 2022.

INTRODUCTION — Early in the acquired immunodeficiency syndrome (AIDS) epidemic, endocrine manifestations of human immunodeficiency virus (HIV) infection were often a consequence of opportunistic infections, neoplasms, or concomitant medical conditions. The widespread use of potent antiretroviral therapy in resource-rich settings has led to a decline in the incidence of glandular infiltration by opportunistic infections and neoplasms.

This topic addresses the evaluation of thyroid disorders in patients with HIV. Issues related to pituitary and adrenal disorders, insulin resistance, bone and calcium disorders, and hypogonadism are discussed elsewhere. (See "Pituitary and adrenal gland dysfunction in patients with HIV" and "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy" and "Treatment of HIV-associated lipodystrophy" and "Bone and calcium disorders in patients with HIV" and "Hypogonadism in males with HIV".)

OVERVIEW — In general, the approach to thyroid disorders in a patient with HIV is similar to that in an uninfected individual. However, HIV infection may also cause changes in thyroid function that are adaptive and do not require treatment. In addition, many of the symptoms and signs of thyroid dysfunction are nonspecific and can overlap with those of non-endocrine disorders that are common in patients with HIV. Lastly, some medications used to treat HIV infection and its complications can induce thyroid dysfunction. (See 'Effects of medications' below.)

GLANDULAR INFILTRATION — Infection by a diverse array of organisms, as well as HIV-associated malignancies (eg, Kaposi sarcoma, lymphoma), have been detected in the thyroid gland in patients with AIDS (table 1). Such occurrences were far more common prior to the widespread use of potent antiretroviral therapy (ART), although they may still be observed in patients not receiving ART or who have developed antiretroviral drug resistance.

The infrequency of infectious and neoplastic thyroid disease in patients with HIV was illustrated in a retrospective study of 102 autopsy cases in the United States from 1980 to 2007 [1]. Interstitial fibrosis and thyroid hyperplasia were the most common histologic findings (5 and 2 percent of cases, respectively), whereas infection was identified in fewer than 3 percent and Kaposi sarcoma was present in only one case.

Glandular infiltration may be suspected on clinical grounds or as the result of an imaging study (eg, ultrasound). Tissue is generally required for a definitive diagnosis. Fine-needle aspiration of the thyroid is safe, effective, and widely available. Functional testing with a thyroid-stimulating hormone level should also be performed since thyroid dysfunction may accompany glandular infection or infiltration.

ALTERATIONS IN THYROID FUNCTION — Disturbances in thyroid function can lead to hypo- or hyperthyroidism, which can be asymptomatic or clinically overt. The presentation and diagnosis of thyroid disorders is discussed in detail elsewhere (see "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Diagnosis of hyperthyroidism"). The effect of HIV infection on thyroid function is discussed below. (See 'Effects of medications' below.)

Asymptomatic patients with HIV with stable body weight generally maintain normal thyroid function [2,3]. By contrast, changes similar to those seen in non-thyroidal illness (NTI) in uninfected individuals are often present in patients with AIDS [4]. NTI is generally characterized by low to normal thyroid-stimulating hormone (TSH), low tri-iodothyronine (T3), high reverse T3 (rT3), and normal free thyroxine (T4) levels related to impaired peripheral T4 to T3 conversion and reduced rT3 clearance. Low T3 levels in NTI may be adaptive by lowering metabolic rate and decreasing protein catabolism in the setting of systemic illness or reduced caloric intake [5]. (See "Thyroid function in nonthyroidal illness".)

However, T3 levels are often higher and rT3 levels lower in AIDS patients than expected for NTI, raising concern that these protective effects may be compromised [6]. The difference in T3 levels is not explained by the increased levels of thyroid hormone-binding globulin (TBG) seen in individuals with HIV [7]. Reduction in T3 levels are sometimes observed in AIDS patients with opportunistic infections and anorexia [6,7].

Prevalence of thyroid dysfunction — Several cross-sectional studies of patients with HIV suggest that the prevalence of thyroid dysfunction is high [8-13]. However, in the modern combination antiretroviral therapy (ART) era, there may be no increased risk of thyroid dysfunction among those who have achieved full viral suppression. In a cohort of 826 people living with HIV (95 percent with undetectable viral loads), there was no difference in the prevalence of either hypo- or hyperthyroidism compared with 2503 matched uninfected controls [14].

Thyroid dysfunction appears to be more prevalent in those with more advanced HIV disease. One multicenter study of 350 patients with HIV reported a 16 percent prevalence of hypothyroidism, although there was no uninfected control group for comparison [8]. The risk of hypothyroidism was increased among patients with lower CD4 counts. Symptoms ranged from overt hypothyroidism (2.6 percent) to subclinical disease (6.6 percent) to an isolated low free T4 level (6.8 percent).

In another study of newly diagnosed patients with HIV with advanced immunodeficiency (71 percent had a CD4 count <200 cells/microL), the overall prevalence of thyroid dysfunction was 76 percent compared with 16 percent among a control group of healthy volunteers [10]. Subclinical hypothyroidism was again the most common abnormality, affecting almost 53 percent of patients. Thyroid dysfunction correlated with declining CD4 counts. In clinical practice, however, many of these patients probably do not require treatment. (See "Subclinical hypothyroidism in nonpregnant adults".)

Effects of medications — Thyroid dysfunction is more frequent in patients on ART compared with ART-naïve patients, usually manifesting as hypothyroidism [13,15]. One study of 410 patients with HIV reported that increased TSH was associated with ART duration and nucleoside reverse-transcriptase inhibitor (NRTI) use [12]. Another cross-sectional study of 117 patients with HIV reported a fourfold risk of subclinical hypothyroidism among those who had a history of stavudine (older NRTI) use [11].

By increasing clearance of thyroid hormone, some medications (eg, ritonavir, rifampin) may precipitate clinical hypothyroidism in patients with HIV and marginal thyroid reserve. These medications may increase the metabolism of levothyroxine through induction of glucuronidation. Cases of hypothyroidism have been reported when levothyroxine is coadministered with ritonavir, indinavir, or lopinavir/ritonavir [16,17]. Patients on thyroid replacement therapy should have thyroid hormone values monitored closely with dose adjustment of levothyroxine if necessary.

Effects of immune reconstitution inflammatory syndrome — When potent ART leads to immune reconstitution, autoimmune thyroid diseases can result from the production of new immune cells targeting thyroid antigens [18]. Such patients typically present with symptoms and signs of Graves' disease one to two years after beginning ART [19-23]. These patients generally have low or undetectable viral loads and no preexisting thyroid disease. Occasionally, they may develop associated thyroid eye disease [24]. Response to treatment is not different than other patients with Graves’ disease [25]. Immune reconstitution inflammatory syndrome can also lead to development of Hashimoto's thyroiditis [26], which may explain reports suggesting an increased prevalence of hypothyroidism among patients on ART [8,9,15]. (See "Immune reconstitution inflammatory syndrome".)

ASSESSMENT OF THYROID FUNCTION — The changes in thyroid function tests described above usually do not require treatment and should be interpreted in their appropriate clinical context. If a patient with HIV presents with typical symptoms and/or signs of hypo- or hyperthyroidism (see "Clinical manifestations of hypothyroidism" and "Overview of the clinical manifestations of hyperthyroidism in adults"), thyroid-stimulating hormone should be the initial laboratory test ordered. If there is reason to suspect secondary (pituitary) hypothyroidism, then a free T4 should also be checked. Even though some studies have reported increased prevalence of hypothyroidism in patients with HIV [8], we do not suggest routine screening in this population.

MANAGEMENT

Hypothyroidism — In patients with AIDS or wasting who are diagnosed with symptomatic hypothyroidism, we initially prescribe a low dose of thyroid replacement hormone (eg, levothyroxine 25 to 50 mcg daily) with gradual upward titration and monitoring of thyroid function tests. Other patients with HIV are treated similarly to the general population. (See "Treatment of primary hypothyroidism in adults".)

Hyperthyroidism — The management of the patient with HIV with hyperthyroidism is similar to that of the general population, with the notable exception that a tender thyroid gland in a patient with AIDS warrants fine-needle aspiration to exclude opportunistic infection or neoplasm. (See "Disorders that cause hypothyroidism".)

Thyroid nodules — Thyroid nodules that meet certain size or radiologic criteria also require fine-needle aspiration to rule out malignancy. (See "Diagnostic approach to and treatment of thyroid nodules".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary care of adults with HIV".)

SUMMARY AND RECOMMENDATIONS

Early in the AIDS epidemic, endocrine manifestations of HIV infection were often a consequence of opportunistic infections, neoplasms, or concomitant medical conditions. The widespread use of potent antiretroviral therapy (ART) in the developed world has led to a decline in the incidence of glandular infiltration by opportunistic infections and neoplasms. (See 'Introduction' above.)

In general, the approach to thyroid disorders in a patient with HIV is similar to that in an uninfected individual. However, HIV infection may also cause changes in thyroid function that are adaptive and do not require treatment. (See 'Overview' above.)

Infection by a diverse array of organisms, as well as HIV-associated malignancies (eg, Kaposi sarcoma, lymphoma), have been detected in the thyroid gland in patients with AIDS (table 1). Tissue is generally required for a definitive diagnosis. (See 'Glandular infiltration' above.)

Patients with AIDS may have laboratory evidence of non-thyroidal illness, and there is higher prevalence of subclinical hypothyroidism in this population. People living with HIV who are well-treated with combination ART may not have an increased risk for thyroid dysfunction. (See 'Alterations in thyroid function' above.)

Certain medications, such as rifampin and ritonavir, can precipitate clinical hypothyroidism in patients with HIV with marginal thyroid reserve. (See 'Effects of medications' above.)

Immune reconstitution after initiation of potent ART can sometimes lead to Graves' disease or Hashimoto's thyroiditis. (See 'Effects of immune reconstitution inflammatory syndrome' above.)

In most instances, the management of hypo- and hyperthyroidism in the patient with HIV is similar to that of the general population. However, in patients with AIDS or wasting diagnosed with symptomatic hypothyroidism, we initially prescribe a low dose of thyroid replacement hormone with gradual upward titration and monitoring of thyroid function tests. In patients with AIDS diagnosed with hyperthyroidism who have a tender thyroid gland, fine-needle aspiration is warranted to rule out opportunistic infection or neoplasm. Thyroid nodules that meet certain size or radiologic criteria also require fine-needle aspiration to rule out malignancy. (See 'Management' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.

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