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Top 10 Series: Top 10 Points Lupus Patients Should Know About Autoimmune Thyroid Diseases

Zeynep Belce Erton
Medical Student, Academic Visitor, Hospital for Special Surgery

Image - Photo of Emily Margaret Stein, MD, MS
Emily Margaret Stein, MD, MS

Associate Attending Physician, Hospital for Special Surgery
Associate Research Scientist, Hospital for Special Surgery

Image - Photo of Doruk Erkan, MD, MPH
Doruk Erkan, MD, MPH
Associate Attending Rheumatologist, Hospital for Special Surgery
Associate Physician-Scientist, Barbara Volcker Center for Women and Rheumatic Disease

1. What is an autoimmune thyroid disease?

Autoimmune thyroid diseases, including Graves’ disease, Hashimoto’s thyroiditis (also known as chronic lymphocytic thyroiditis and Hashimoto’s disease), postpartum thyroiditis and atrophic autoimmune hypothyroidism, are complex organ specific autoimmune diseases that arise due to an interaction between environmental and genetic factors.

In patients with autoimmune thyroid diseases, autoantibodies bind to the thyroid gland, resulting in inflammation, thyroid dysfunction and other clinical manifestations.

  • Graves’ disease – results in uncontrolled production of thyroid hormone and hyperthyroidism (increased thyroid function).
  • Hashimoto’s thyroiditis – characterized by loss of thyroid gland cells, which are responsible for the production and secretion of thyroid hormones, leading eventually to hypothyroidism (decreased thyroid function).
  • Postpartum thyroiditis – occurs soon after a woman gives birth and may reoccur after subsequent pregnancies; it usually presents with hyperthyroidism followed by hypothyroidism.
  • Atrophic autoimmune hypothyroidism – a rare condition characterized by autoantibodies and functional hypothyroidism (also known as subclinical hypothyroidism).

 

2. What are the symptoms of autoimmune thyroid diseases?

The symptoms of hyperthyroidism include weight loss despite having a normal appetite, abnormal menstrual cycles, heat intolerance (feeling hot when other people in the same room do not), increased sweating, palpitations, tremors, restlessness, increased bowel movements and nervousness.

The symptoms of hypothyroidism include weight gain, weakness, dry skin, impaired memory, cold intolerance (feeling cold when other people in the same room do not), abnormal menstrual cycles, hair loss, constipation and depression.

Patients with both hyperthyroidism and hypothyroidism can experience severe fatigue. Some patients with thyroid disease may have no clinical symptoms, or the symptoms can be so mild that they may be unnoticed. It is also important to realize that many of the symptoms of thyroid disease are not specific, meaning they could be caused by a variety of conditions.

 

3. Which tests help us diagnose autoimmune thyroid diseases?

The most commonly used tests to diagnose autoimmune thyroid diseases are:

  • Thyroid-stimulating hormone (TSH) – used to screen for thyroid dysfunctions
  • Thyroid hormone levels – total thyroxine (T4), total triiodothyronine (T3), free T4 and free T3
  • Thyroid autoantibodies – anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and anti-TSH receptor antibodies

In Graves’ disease, the TSH level is usually lower than normal, whereas thyroid hormones are elevated. Anti-thyroperoxidase and anti-Tg antibodies are usually positive. Thyroid stimulating hormone receptor antibody (TSH-R) is also generally positive.

In Hashimoto’s thyroiditis, the TSH level is elevated, whereas thyroid hormones are decreased. Anti-thyroperoxidase and anti-Tg antibodies are usually positive.

 

4. What types of autoimmune thyroid diseases are seen in patients with systemic lupus erythematosus (SLE)?

The first reported case of coexistence of autoimmune thyroid disease with SLE was published in 1961, followed by large-scale controlled studies that demonstrated an increased incidence of Hashimoto’s thyroiditis and Graves’ disease in lupus patients compared to that of the general population.

In addition, both anti-Tg and anti-TPO antibodies are found with higher frequency in people with SLE (15% to 50%) than in the general population – even in lupus patients who do not have clinical thyroid disease.

 

5. Do all thyroid-autoantibody-positive lupus patients develop clinical thyroid disease?

Many patients have thyroid autoantibodies but normal thyroid blood tests and no signs or symptoms of thyroid disease. Patients with antibodies may develop clinical thyroid disease in time, but many will not. This is similar to what is observed in the general population, the majority of the anti-TPO and anti-Tg antibody-positive patients do not have symptoms and do not develop autoimmune thyroid disease.

Also it is important to note that antinuclear antibodies (ANA) are sometimes found in patients with autoimmune thyroid diseases. A positive ANA test does not always indicate a systemic autoimmune disease such as lupus; it may be due to a number of conditions, including Hashimoto’s thyroiditis or Graves’ disease.

 

6. What is the frequency of autoimmune thyroid diseases in systemic lupus erythematosus?

The frequencies of hyperthyroidism and hypothyroidism in the general population range between 1% to 2% and 4% to 5%, respectively. In comparison, 0% to 11% and 4% to 24% of lupus patients have hyperthyroidism and hypothyroidism, respectively. These widely varying frequencies of hyperthyroidism and hypothyroidism in lupus patients is probably due to differences in clinical study designs, sample sizes and follow-up periods.

Based on recent studies, approximately 0.03% and 0.015% of the general population have Hashimoto’s thyroiditis and Graves’ disease, respectively. In comparison, 2% to 3% and 1% to 3% of the lupus patients have Hashimoto’s thyroiditis and Graves’ disease, respectively.

 

7. Why are autoimmune thyroid diseases more common in patients with systemic lupus erythematosus?

Different mechanisms have been proposed to explain the association between autoimmune thyroid diseases and lupus:

  • Shared demographic features – Young to middle-aged women are more likely to have an autoimmune disease than are men, including autoimmune thyroid diseases and lupus. However, it is still a subject of discussion as to whether SLE is an independent risk factor for autoimmune thyroid diseases or whether this is a coincidental finding because the group most at risk for SLE is precisely the same group at risk for autoimmune thyroid diseases.
  • Polyautoimmunity – This refers to a single patient having more than one autoimmune disease. Patients with one autoimmune disease are at higher risk for other autoimmune conditions. Given that the thyroid gland can be a target for some lupus autoantibodies, it has been suggested that there may be cross-reactions between lupus antibodies and thyroid antigens.
  • Genetics – Similar mechanisms within autoimmune diseases have stimulated searches for common genetic roots. There are some genetic factors that occur more commonly both in patients with lupus and autoimmune thyroid disease than in general population.
  • Treatment of Graves’ disease – Treatment of Graves’ hyperthyroidism with drugs such as methamizole or propylthiouracil (PTU) can induce a lupus-like disease, i.e., rash or joint pain.

 

8. Should we follow systemic lupus erythematosus patients for the development an autoimmune thyroid disease?

Given that lupus patients are predisposed to the development of autoimmune thyroid diseases, screening of lupus patients for autoimmune thyroid diseases can be considered. Furthermore, some of the nonspecific complaints of autoimmune thyroid diseases such as fatigue, hair loss and joint pain can be attributed to SLE. For this reason, a periodic thyroid disease screening can be justified to rule out subclinical and clinical autoimmune thyroid disease.

A 2004 panel, sponsored by American Association of Clinical Endocrinologist (AACE), American Thyroid Associations (ATA) and the Endocrine Society, advocated thyroid disease screening in patients with autoimmune diseases, including lupus. However, this was not a strong recommendation as the number and quality of studies addressing the question were limited.

Pregnant women with lupus and also thyroid disease may have a greater risk of pregnancy complications, so women should be screened who are considering pregnancy.

 

9. Is there any risk of developing thyroid cancer in patients with systemic lupus erythematosus?

The lifetime risk of thyroid cancer in general population is approximately 1%. The frequency of thyroid cancer is higher in patients with autoimmune thyroid diseases, including patients with lupus, compared to that of the general population. Based on a meta-analysis (combined analysis) of recent studies, the risk of thyroid cancer in lupus patients is doubled compared to that of the general population.

The proposed mechanism of this association is possibly due to the basic defects in the immune system function of lupus patients, resulting in immune dysregulation. These defects could be created or increased by immunosuppressive therapies increasing the risk of cancer.

Similar to the general population, lupus patients with autoimmune thyroid diseases should be checked for thyroid cancer if they develop thyroid nodules. Patients with autoimmune thyroid disease are also at increased risk for development of lymphoma.

 

10. What are the commonly used medications for the treatment of autoimmune thyroid disease?

Treatment for Hashimoto's disease may include observation or medications. If the thyroid gland is functioning normally, observation is recommended. However, if Hashimoto's disease causes thyroid hormone deficiency, patients will need thyroid hormone replacement therapy. This usually involves the use of synthetic form of thyroxine (T4), which is levothyroxine. Treatment with levothyroxine is usually lifelong, causes no side effects when used in the appropriate dose and is also safe during pregnancy.

The treatment goal for Graves' disease is to inhibit the production of thyroid hormones. Some treatments include:

  • Radioactive iodine therapy
  • Anti-thyroid medications such as propylthiouracil (PTU) and methimazole
  • Beta blockers (of note, these medications may cause cold hands and feet, which can be especially problematic for lupus patients experiencing Raynaud’s phenomenon)
  • Thyroid surgery

References

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  2. Bloch DB. Patient education: Antinuclear antibodies (ANA) (Beyond the Basics). 2018. https://www.uptodate.com/contents/antinuclear-antibodies-ana-beyond-the-basics. Accessed on May 7, 2018.
  3. Boey ML, Fong P, Lee JSC, et al. Autoimmune Thyroid Disorders in SLE in Singapore. Lupus 1993;2:51-54.
  4. Brenta G, Vaisman M, Sgarbi JA,et al. Task Force on Hypothyroidism of the Latin American Thyroid Society (LATS). Arq Bras Endocrinol Metabol 2013;57:265-291.
  5. Buyon JP, Wallace DJ. The Use of Exogenous Estrogens, Endocrine System, and Urogenital Tract. In: Dubois’ Lupus Erythematosus. Eds: Wallace DJ, Hahn BH. Philadelphia: Lippincott Williams & Wilkins, 2002, p: 821-841.
  6. Byron MA, Mowat AG. Thyroid Disorders in Systemic Lupus Erythematosus. Ann Rheum Dis 1987;4:174-175.
  7. Cortes S, Jeronimo A, Isenberg D. Systemic Lupus Erythematosus and Endocrine Disorders.    In: Handbook of Systemic Autoimmune Diseases: Endocrine Manifestations of Systemic Autoimmune Diseases. Eds: Walker SE, Jara LJ. Oxford: Elsevier, 2008, p:173-184.
  8. Ferrari SM, Elia G, Virili C, et al. Systemic Lupus Erythematosus and Thyroid Autoimmunity. Front Endocrinol 2017;8:138.
  9. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988-1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-499.
  10. Noone AM, Howlader N, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2015.National Cancer Institute. 2018. https://seer.cancer.gov/statfacts/html/thyro.html. Accessed on May 9, 2018.
  11.  Pyne D, Isenberg DA. Autoimmune Thyroid Disease in Systemic Lupus Erythematosus. Ann Rheum Dis 2002;61:70-72.
  12. Swain M, Swain T, Mohanty BK. Autoimmune Thyroid Disorders-An Update. Indian J Clinic Biochem 2017;20:9-17.
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  14. Yun JS, Bae JM, Kim KJ, et al. Increased Risk of Thyroid Diseases in Patients with Systemic Lupus Erythematosus: A nationwide population-based Study in Korea. PLoS ONE 2017; 12:e0179088.
  15. Zhang M, Li XM, Wang GS, et al. Thyroid Cancer in Systemic Lupus Erythematosus: A Meta Analysis. Int J Clin Exp Pathol 2014;7:6270-6273.
 

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