Autoimmune Diseases Common in Turner Syndrome | Turner Syndrome Foundation

Autoimmune Diseases Common in Turner Syndrome

autoimmune diseases common in turner syndrome

In this post, we will discuss some of the autoimmune diseases commonly associated with Turner Syndrome (TS), including Hashimoto’s thyroiditis, diabetes, and celiac disease. Learn more about the causes, symptoms, diagnosis, and treatment of these conditions below.

Note: The information in this post is educational and should not replace medical advice from your physician(s). Always consult with a medical professional regarding any health concerns.

Hashimoto’s Thyroiditis & Hypothyroidism

Hashimoto’s thyroiditis (HT) is the most common thyroid disease in the U.S., affecting over 10 million people. This autoimmune disease is very commonly associated with Turner Syndrome, affecting 10-30% of individuals with TS. HT Is characterized by the destruction of healthy thyroid cells by the body’s own immune system. This response can lead to insufficient amounts of thyroid hormone, or hypothyroidism. Thyroid hormone is important for many physiological processes related to growth, nervous system development, cardiovascular function, and metabolism.

Causes

With HT, this immune response compromises the thyroid cells’ ability to generate thyroid hormone. Several studies suggest that environment and gene interactions may lead to HT. Individuals with TS generally have a higher risk of developing hypothyroidism. Those with structural abnormalities of the X chromosome—in particular, the isochromosome Xq—are at higher risk of autoimmunity, overall. Risk is even higher if the individual’s family has a history of the condition. 

Symptoms

The aforementioned destruction of thyroid cells can result in hypothyroidism. HT may not cause symptoms for many years and could remain undiagnosed until detection of an enlarged thyroid gland or an abnormal blood test during a routine exam. Initial symptoms often begin with neck pressure due to goiter—enlargement of the thyroid gland in the neck region—or low levels of thyroid hormone. In addition to goiter, patients who develop HT might experience the following symptoms:

  • fatigue,
  • drowsiness,
  • forgetfulness,
  • learning difficulties,
  • dry, brittle hair and nails,
  • dry, itchy skin,
  • puffy face,
  • constipation,
  • sore muscles,
  • weight gain,
  • heavy menstrual flow,
  • increased frequency of miscarriages, and
  • increased sensitivity to certain medications.

Consider seeking medical attention to address potential hypothyroidism/HT if you have any combination of these symptoms.

Diagnosis

Goiter is a hallmark sign of HT during a physician’s physical examination. Hypothyroidism can be identified by characteristic symptoms, certain physical signs, and appropriate lab tests. Elevated levels of thyroid-stimulating hormone (TSH) is a typical lab finding—and the most accurate indicator of hypothyroidism. TSH is a hormone produced by the pituitary gland, which is located behind the nose at the base of the brain. This hormone functions by alerting the thyroid gland that it needs to make more thyroid hormone. Thus, when the pituitary gland underproduces thyroid hormone levels, TSH levels rise to try to alert the thyroid gland.

Treatment

For patients with thyroid enlargement (goiter) or hypothyroidism, thyroid hormone therapy is typically prescribed to correct thyroid hormone levels. Treatment generally consists of taking a single, daily tablet of levothyroxine. Older patients with underlying heart disease generally start on a low dose that gradually increases, while younger, healthy patients can be started on full-replacement doses.

Improvement may occur within in a week of starting thyroid hormone replacement therapy but could take longer (e.g., skin changes may take up to three to six months to resolve). Additionally, due to the often-permanent nature of HT, patients require treatment throughout their lifetime, and thyroid hormone dosages may need to be adjusted throughout treatment.

Appropriate adjustment of thyroid hormone dosage, guided by laboratory tests rather than symptoms alone, is critical, because the body is very sensitive to small changes in thyroid hormone. The consistent, daily dosage of levothyroxine tablets is essential to prevent the progression of symptoms. Be sure to consult your physician if any symptoms increase or any inconsistencies occur during your treatment.

Diabetes & Glucose Intolerance

Another autoimmune disease commonly associated with Turner Syndrome is diabetes, or the dysregulation of glucose metabolism. Glucose-related abnormalities are present in >70% of adults with TS. These include impaired glucose tolerance, excess insulin in the blood, and reduced sensitivity to insulin. Impaired glucose tolerance means the body has a weakened response once glucose is absorbed into the bloodstream through nutrients. Excess insulin in the blood can have metabolic consequences. Reduced sensitivity to insulin is a hallmark of type 2 diabetes (T2D). There are several different forms of diabetes, but for this post, we will focus on autoimmune-related diabetes.

Causes

The prevalence of autoimmune-related diabetes in patients with TS is greater than for the general population (two-fold compared to females, four-fold compared to males). Research suggests that patients with TS have a greater likelihood of containing erroneous antibodies directed toward the cells that produce insulin. Damage to these cells can lead to mismanagement of glucose metabolism. The exact mechanism, however, is still unclear.

Symptoms

Diabetes symptoms may present differently per person. If any of these symptoms present, consider blood glucose testing:

  • excessive urination,
  • increased thirst,
  • increased hunger,
  • unexplained weight loss,
  • blurry vision,
  • numb or tingling hands/feet,
  • fatigue,
  • excessively dry skin,
  • slow-healing sores, and
  • increased infections.

Diagnosis

Since most patients with TS who demonstrate glucose dysfunction-related symptoms have an autoimmune condition related to inappropriate antibody production, physicians will test for the antibody in question. A yearly Hgb A1c IS recommended. GAD-65 antibody testing is recommended for those who have been given an initial diagnosis of diabetes. Patients suspected of having diabetes should also receive an HbA1c test, which measures blood glucose levels over a three-month period.

Treatment

Patients can manage diabetes, in part, by closely monitoring blood glucose levels. Sometimes physicians will prescribe insulin supplements to maintain appropriate levels of glucose and insulin in the blood. Be sure to consult a physician to clarify specific needs relating to monitoring these levels. Lifestyle management practices, like diet and exercise, can also help to reduce the risk of developing T2D.

Growth hormone (GH), a common therapy for patients with TS, may disrupt normal insulin functions and potentially alter glucose metabolism. Because the risks of GH therapy in patients with TS is not fully clear, their glucose tolerance should be monitored closely.

Celiac Disease

Celiac disease (CD) is another autoimmune disease commonly associated with TS. The risk of CD is up to 8% greater patients with TS than the general population. CD is an autoimmune reaction to the ingestion of gluten, a protein found in wheat, rye, and barely. This reaction causes damage to the absorption structures in the small intestine and can cause malnutrition or damage to other organ systems.

Causes

As an autoimmune disease, the cause of CD is an immune reaction enlisted by the body on its own cells. CD involves the immune system inappropriately identifying gluten as a pathogen and initiating a response against it. Gluten acts as an environmental trigger that causes the body to react to its own cells, specifically in the intestine. Research suggests that the genetic causes and increased prevalence of CD in patients with TS are linked to the full-to-partial loss of the X chromosome in patients with TS.

Symptoms

CD has several symptoms that are commonly associated and natural consequences of destruction to areas in the small intestines. These areas lose their ability to properly absorb nutrients resulting in some of the following symptoms.

  • anorexia,
  • diarrhea,
  • bloating/gas,
  • vomiting,
  • constipation,
  • lactose intolerance,
  • abdominal pain
  • pale or foul-smelling stool,
  • weight loss, and
  • muscle wasting.

Some non-classic symptoms can also occur and may be indicative of more severe CD.

  • failure to thrive in infants,
  • anemia resistant to oral iron therapy,
  • autoimmune thyroid disease,
  • unexplained short stature or delayed puberty,
  • seizures,
  • neuropathy/ataxia,
  • recurrent fetal loss (intrauterine growth retardation),
  • delayed or missed periods/infertility,
  • osteoporosis (bone loss) or osteopenia (bone in the blood),
  • oral sores,
  • loss of tooth enamel, and
  • vitamin deficiencies.

Diagnosis

Screening of blood has shown to be an effective way to detect the presence of CD in patients with TS. Lab examinations will look for the presence of anti-endomysial antibodies, which are antibodies that target the parts of the digestive tract. These antibodies drive the autoimmune reactions that occur in people with TS affected by CD.

Other blood and serum tests (e.g., total antibodies) may be run to confirm CD, but the aforementioned is typically considered strongly suggestive. Physicians may also seek biopsies or visualization through endoscopy from the digestive tract as well.

Treatment

Currently, the primary form of treatment for CD is a commitment to a gluten-free diet. Besides wheat foods, foods that contain barley, bulgur, durum, farina, Graham flour, malt, rye, semolina, spelt, and triticale should be avoided to prevent the autoimmune reactions that can damage the small intestines.

It is advised that patients affected by CD consider certain vitamin and mineral supplements for any nutritional deficiencies or anemia associated with their condition. Be sure to consult a physician or dietitian about nutritional guidance for CD.

Written by Reyn Kenyon, TSF volunteer blog post writer and editor. Edited by Susan Herman, TSF volunteer blog post editor and translator.


To view the recording of a recent webinar about autoimmune diseases commonly associated with Turner Syndrome, please click below:
Sources
  1. Pyzik, A. et al. Immune Disorders in Hashimoto’s Thyroiditis: What Do We Know So Far. Journal of Immunology Research 2015, (2015). [PubMed]
  2. TSF Thyroid Resource
  3. Sun, L. et al. Glucose Metabolism in Turner Syndrome. Frontiers in Endocrinology 10, 49 (2019). [PubMed]
  4. TSF Diabetes Resource
  5. CDC Diabetes
  6. Khater, D. Autoimmune diseases in Turner Syndrome: an overview. Acta Biomedica 90(3), 341-344 (2019). [PubMed]
  7. TSF Celiac Disease Resource
  8. Mayo Clinic Celiac Disease
  9. Caio, G. et al. Celiac disease: a comprehensive current review. BMC Medicine 17, 142 (2019). [PubMed]

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