Thyroid Dysfunction & Bone Disease in HIV & HCV

Thyroid Dysfunction & Bone Disease in HIV & HCV; Thyroid Testing Recommended by UK Group

NOF Osteoporosis Prevention - Risk Factors for Osteoporosis

There are many factors that determine who will develop osteoporosis. The first step in prevention is to determine whether you are at risk, ...

www.nof.org/prevention/risk.htm

"Hyperparathyroidism. This is a condition in which the parathyroid glands (two pairs of small glands located near the thyroid in the neck) produce too much parathyroid hormone (PTH). Having too much PTH causes bone loss. This condition is more common in women after menopause. A simple blood test can tell your healthcare provider if this is a problem.....Hyperthyroidism. In people with this condition, the thyroid gland produces too much thyroid hormone. This can lead to weak muscles and fragile bones. The same thing can happen if a person has an underactive thyroid and take too much thyroid hormone medication."
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"HIV infects many cell types in the body leading to diverse immunologic and metabolic effects. Much attention has been paid to emerging complications of HIV infection in patients receiving potent antiretroviral therapy. The main focus has been on metabolic problems associated with cardiovascular disease such as insulin resistance, hyperlipidemia, and fat redistribution. However, with the increasing life expectancy conferred by the new therapies, there is also an emerging increase in the risk of bone pathologies. The main issues areapparent increased rate of osteonecrosis and increased risk of developing osteopenia and osteoporosis. Decreased physical activity, prolonged bed rest associated with chronic illness, severe weight loss, malnutrition, disruption of the parathyroid hormone axis, and hypogonadism, which are all recognized risk factors for osteoporosis in men, are all common features in advanced HIV infection."

"up to 50% of HIV-1 infected men receiving highly active antiretroviral therapy (HAART) have osteopenia or osteoporosis and 21% of these patients have severe osteoporosis" .... "Prospective longitudinal studies of BMD before and after ART are needed to dissect the effects of HIV infection and drugs."....."several osteoporosis risk factors are relevant for HIV-positive subjects. These include prolonged bed rest associated with chronic illness, smoking, severe weight loss, hyperthyroidism, hypogonadism, malabsorption, and medications including corticosteroids, phenobarbital, pentamidine, and ketoconazole."......"Fractures result in morbidity, mortality, and an increased expenditure of health-care resources. After a hip fracture only 50% of patients regain the independence they enjoyed 12 months before the hip fracture occurred; 40% of patients are still unable to walk independently and 60% of patients have difficulty with activities of daily living 6 months after a hip fracture (10). The direct and indirect costs of caring for these patients are high, resulting in a total cost of $21,000 per patient for the first year after the fracture (11). Since the life span of HIV-positive patients on therapy is increasing, the risk of fracture and subsequent expenditure promises to outweigh the cost of osteoporosis treatment."....."antithyroid antibodies are present in 5 to 17 percent of patients with HCV infection"...."A separate issue is the development of thyroid disease in patients with HCV infection who are treated with interferon alfa. Approximately 1 to 5 percent of such patients develop painless thyroiditis"
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Thyroid Dysfunction and Relationship to Antiretroviral Therapy in HIV-Positive Individuals in the HAART Era
[Letters to the Editor]

JAIDS Journal of Acquired Immune Deficiency Syndromes:Volume 50(1)1 January 2009pp 113-114

Nelson, Mark; Powles, Tom; Zeitlin, Abigail; Sen, Priya; Scourfield, Andrew; Bower, Mark; Gazzard, Brian; Stebbing, Justin The Department of HIV Medicine The Chelsea and Westminster Hospital Imperial College School of Medicine London, United Kingdom

To the Editor:

The effects of highly active antiretroviral therapy (HAART) on thyroid function are unclear at present. Although it is noted that the majority of patients with HIV disease display normal thyroid function,1,2 there is an increasing awareness of a growing number of patients receiving HAART presenting with symptoms of thyroid disease requiring treatment.3 Conflicting results concerning the necessity of routine thyroid screening in HIV patients receiving HAART have been observed.4-6 A recent study from the Royal Free Hospital, London, United Kingdom, suggested that screening is not warranted due to an observed low frequency of thyroid abnormalities in their cohort,4 whereas the longitudinal study performed by the University of Sassari, Italy, indicates that screening was recommended.3

The Chelsea and Westminster Hospital HIV cohort in London is the largest single center HIV cohort in Europe, and information is prospectively collected on the individuals who attend. All patients in this study attended between April 1995 and June 2006 and had at least 1 blood test for thyroid function in the absence of a defined clinical protocol. Hyperthyroidism was defined as thyroid-stimulating hormone (TSH) level below normal (TSH normal range 0.3-4.4 mU/L) and free thyroxine (T4) or free triiodothyronine above that of the normal range (free T4 normal range 9.0-26.0 mU/L). Hypothyroidism was defined as TSH level above normal range and free thyroxine (T4) or free triiodothyronine below that of the normal range (normal range 2.23-5.3 pM). To establish incidence, person-days of follow-up were converted to person-years at risk. To keep the coefficient of the person-years at risk constant, this was log transformed and used as the offset in the Poisson regression before analysis using the Genmod procedure in SAS version 9.1 with loge link and Poisson error distributions.

A total of 2437 individuals had routine thyroid function tests performed. The incidence of hyperthyroidism was 3.4 (95% confidence interval: 1.5 to 6.8) per 10,000 patient-years and of hypothyroidism it measured 10.7 (95% confidence interval: 6.9 to 15.8) per 10,000 patient-years. Of these 2437 individuals, 54 (2.2%) were identified with abnormal thyroid function, of whom, 26 were diagnosed with hyperthyroidism and 28 with hypothyroidism. Twenty-one (80.8%) of 26 hyperthyroid patients were male and 5 (19.2%) were female. Twenty-two (78.6%) of 28 hypothyroid patients were male and 6 (21.4%) were female. The clinical prevalence of hyperthyroidism in our HIV cohort was calculated to be 1.01% and that of hypothyroidism was 1.2%. Of the patients tested, thyroid antibodies were present in 40% of those with hypothyroidism and 66.7% of patients with hyperthyroidism, a finding that may suggest an association with immune restoration after HAART.

Table 1 represents treatments that 54 patients demonstrating abnormal thyroid function were receiving in comparison with the entire clinical cohort. Of the patients receiving nonnucleoside reverse transcriptase inhibitors, 13 (81%) of the hypothyroid patients and 7 (81%) of the hyperthyroid patients were receiving efavirenz, which was statistically significant when compared with the total population (P = 0.025). Twelve of the patients who developed hyperthyroidism were prescribed protease inhibitors, which was also significant when compared with the entire population (P = 0.002). No significant associations were observed with simple confounding and residual factors of age, gender, race, nadir CD4 cell count, and time on antiretroviral therapy with thyroid function.

We have revealed a higher than expected incidence of hypothyroidism in a large cohort of HIV-infected individuals although the retrospective nature of our cohort with an absence of a defined clinical protocol for thyroid function testing results in selection bias. From these data, we found that hypothyroidism was most commonly associated with protease inhibitors and hyperthyroidism with nonnucleoside reverse transcriptase inhibitors, efavirenz in particular. As patients with HIV infection are now typically treated with HAART for decades, the metabolic complications of treatment require further exploration.

Based on the previous extensive work in this area, and these data, we recommend routine screening of thyroid function in HIV-infected patients receiving HAART. The association of thyroid disease including subclinical thyroid test abnormalities with different treatments requires further investigation.

Mark Nelson
Tom Powles
Abigail Zeitlin
Priya Sen
Andrew Scourfield
Mark Bower
Brian Gazzard
Justin Stebbing

The Department of HIV Medicine
The Chelsea and Westminster Hospital
Imperial College School of Medicine

London, United Kingdom

Funding source: none declared.

Conflict of interest: none. All authors had full access to the data.

REFERENCES

1. Lima MK, Freitas LL, Montandon C, et al. The thyroid in acquired immunodeficiency syndrome. Endocr Pathol. 1998;9:217-223.
2. Danoff A. HIV and the thyroid-what every practicing endocrinologist needs to know. Nat Clin Pract Endocrinol Metab. 2006;2:602-603.
3. Madeddu G, Spanu A, Chessa F, et al. Thyroid function in human immunodeficiency virus patients treated with highly active antiretroviral therapy (HAART): a longitudinal study. Clin Endocrinol (Oxf). 2006;64:375-383.
4. Madge S, Smith CJ, Lampe FC, et al. No association between HIV disease and its treatment and thyroid function. HIV Med. 2007;8:22-27.
5. Calza L, Manfredi R, Chiodo F. Subclinical hypothyroidism in HIV-infected patients receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;31:361-363.
6. Bongiovanni M, Adorni F, Casana M, et al. Subclinical hypothyroidism in HIV-infected subjects. J Antimicrob Chemother. 2006;58:1086-1089.