Hashimoto Thyroiditis: Difference between revisions

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== Introduction ==
== Introduction ==
Hashimoto thyroiditis is an autoimmune disease. In this condition the thyroid cells are destroyed via cell and antibody-mediated immune action. In developed countries it is the most common cause of hypothyroidism, whereas  worldwide the most common cause is a deficient dietary intake of iodine. <ref>Mincer DL, Jialal I. [https://www.ncbi.nlm.nih.gov/books/NBK459262/ Hashimoto thyroiditis]. Available:https://www.ncbi.nlm.nih.gov/books/NBK459262/ (accessed 13.1.2023)</ref><br>{{#ev:youtube|oINxr8_nR_Y}}<ref>Graves' Disease and Hashimoto's Thyroiditis. Available from: https://www.youtube.com/watch?v=oINxr8_nR_[last accessed 03/20/2017]</ref>
Hashimoto thyroiditis is an autoimmune disease. In this condition the thyroid cells are destroyed via cell and antibody-mediated immune action. In developed countries it is the most common cause of hypothyroidism, whereas  worldwide the most common cause is a deficient dietary intake of iodine. <ref name=":0">Mincer DL, Jialal I. [https://www.ncbi.nlm.nih.gov/books/NBK459262/ Hashimoto thyroiditis]. Available:https://www.ncbi.nlm.nih.gov/books/NBK459262/ (accessed 13.1.2023)</ref><br>{{#ev:youtube|oINxr8_nR_Y}}<ref>Graves' Disease and Hashimoto's Thyroiditis. Available from: https://www.youtube.com/watch?v=oINxr8_nR_[last accessed 03/20/2017]</ref>


== Prevalence  ==
== Epidemiology ==
After age six, Hashimoto is the most common cause of hypothyroidism in those areas of the world where iodine intake is adequate.


Hashimoto's (chronic) Thyroiditis "is the is the most common cause of [[hypothyroidism]] in the United States.<ref name="Pathology">Goodman CC, Fuller KS. Pathology: implications for the physical therapist. St. Louis, MO: Elsevier Saunders; 2015.</ref> It is primarily found in "middle-aged women” and leads to a genetic disposition. Affecting approximately women more than men at a 10:1 ratio.<ref name="Pathology" /> However, Hashimoto’s thyroiditis can be diagnosed at any age , and may affect men and children.<ref name="Thyroid.org">http://www.thyroid.org/wp-content/uploads/patients/brochures/Hashimoto_Thyroiditis.pdf</ref>&nbsp;The causative factor regarding the prevalence of antibodies is unknown, however there seems to be a familial correlation.<ref name="ATA" />
* The incidence is estimated to be 0.8 per 1000 per year in men and 3.5 per 1000 per year in women.
* Studies suggests genetic genetic factors play a role and to a lesser degree environmental and sex hormone influences.  
* The prevalence of thyroid disease, in general, increases with age.<ref name=":0" />


== Etiology ==
== Etiology ==
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* Pernicious Anemia, a type of anemia caused by not having enough vitamin B12 in the body. In anemia, the number of red blood cells is less than normal, resulting in less oxygen carried to the body’s cells and extreme fatigue.  
* Pernicious Anemia, a type of anemia caused by not having enough vitamin B12 in the body. In anemia, the number of red blood cells is less than normal, resulting in less oxygen carried to the body’s cells and extreme fatigue.  
* Celiac Disease, a form of gastrointestinal gluten sensitivity, an autoimmune disorder in which people cannot tolerate gluten because it will damage the lining of the small intestine and prevent adsorption of nutrients. Gluten is a protein found in wheat, rye, and barley and in some products.  
* Celiac Disease, a form of gastrointestinal gluten sensitivity, an autoimmune disorder in which people cannot tolerate gluten because it will damage the lining of the small intestine and prevent adsorption of nutrients. Gluten is a protein found in wheat, rye, and barley and in some products.  
* Autoimmune Hepatitis, or nonviral liver inflammation, a disease in which the immune system attacks liver cells.<ref name="ATA" />  
* Autoimmune Hepatitis, or nonviral liver inflammation, a disease in which the immune system attacks liver cells.<ref name="ATA">Homepage [Internet]. American Thyroid Association. [cited 2017Mar21]. Available from: http://www.thyroid.org/</ref>


== Characteristics/Clinical Presentation  ==
== Characteristics/Clinical Presentation  ==


Hashimoto Thyroiditis does not present with any unique signs and symptoms.<ref name="Pathology" /> “The condition progresses very slowly over many years, people with Hashimoto’s thyroiditis may not have any symptoms early on. Many of the signs and symptoms mimic general hypothyroid conditions.&nbsp;<ref name="Differential">Goodman CC, Snyder TEK. Differential diagnosis for physical therapists screening for referral. St. Louis, MO: Saunders Elsevier; 2013.</ref>  
Hashimoto Thyroiditis does not present with any unique signs and symptoms.<ref name="Pathology">Goodman CC, Fuller KS. Pathology: implications for the physical therapist. St. Louis, MO: Elsevier Saunders; 2015.</ref> “The condition progresses very slowly over many years, people with Hashimoto’s thyroiditis may not have any symptoms early on. Many of the signs and symptoms mimic general hypothyroid conditions.&nbsp;<ref name="Differential">Goodman CC, Snyder TEK. Differential diagnosis for physical therapists screening for referral. St. Louis, MO: Saunders Elsevier; 2013.</ref>  


Signs and Symptoms:  
Signs and Symptoms:  
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* Forgetfulness  
* Forgetfulness  
== Medications  ==
== Medications  ==
The central component of treatment for hypothyroidism is thyroid hormone replacement. The drug used commonly is titrated levothyroxine sodium administered orally. Note the formation of thyroxine varies worldwide and there can be problems with absorption in patients with disorders of the gastric mucosa.<ref name=":0" />


Levothyroxine: "man-made form of T4 hormone." This medication "almost always"<ref name="Medline">MedlinePlus - Health Information from the National Library of Medicine [Internet]. MedlinePlus Trusted Health Information for You. [cited 2017Mar21]. Available from: https://medlineplus.gov/</ref>&nbsp;needs to be taken for the rest of a person's life and in the same manner each day.<ref name="ATA">Homepage [Internet]. American Thyroid Association. [cited 2017Mar21]. Available from: http://www.thyroid.org/</ref>&nbsp;"Most people see a decrease in the size of the goiter and remain stable for years with treatment."<ref name="Medline" /> The generic name of the drug is Levothyroxine, but it also goes by the brand names of Levothroid, Levoxyl, Synthroid, Tirosint, and Unithroid&nbsp;and it can also be administered orally or by injection.
== Diagnosis ==
== Populations  ==
Hashimoto’s thyroiditis is usuallt diagnosed when patients present with symptoms of hypothyroidism, often along with a goiter on physical examination. Laboratory testing of hypothyroidism shows elevated thyroid stimulating hormone (TSH) with or without a low thyroid hormone (Free thyroxine [Free T4]) levels.<ref>American Thyroid Association [https://www.thyroid.org/hashimotos-thyroiditis/ Hashimoto’s Thyroiditis (Lymphocytic Thyroiditis)] Available:https://www.thyroid.org/hashimotos-thyroiditis/ (accessed 13.1.2023)</ref>
 
Appropriate studies have not assessed pediatric or geriatric specific medication problems warranting a decreased use of Levothyroxine. This drug is classified as a pregnancy category A; stating that studies have shown no increased risk of fetal abnormalities.
 
== Drug Interactions  ==
 
It is advised that individuals on Levothyroxine consult with their physician before taking the following medications due the potential for adverse effects:
* Amineptine
* Amitriptyline
* Amitriptylinoxide
* Amoxapine
* Clomipramine
* Desipramine
* Dibenzepin
* Doxepin
* Imipramine
* Ketamine
* Lofepramine
* Maprotiline
* Melitracen
* Mirtazapine
* Nortriptyline
* Opipramol
* Protriptyline
* Tianeptine
* Trimipramine<br>
Side Effects include:<ref name="Medline" />
* Chest pain or discomfort
* Decreased urine output
* Difficult or labored breathing
* Difficulty with swallowing
* Dilated neck veins
* Extreme fatigue
* Fainting
* Fast, slow, irregular, pounding, or racing heartbeat or pulse
* Fever
* Heat intolerance
* Hives or welts
* Increased blood pressure
* Increased pulse
* Irregular breathing
* Irritability
* Menstrual changes
* Nausea
* Pain or discomfort in the arms, jaw, back, or neck
* Shortness of breath
* Skin itching, rash, or redness
* Sweating
* Swelling of the eyes, face, lips, throat, or tongue
* Tightness in the chest
* Tremors
 
== Diagnostic Tests/Lab Tests/Lab Values  ==
 
Diagnosis of Hashimoto’s is based on a physical exam and medical history, the person’s signs and symptoms, and the results of blood tests. The blood tests are used to measure levels of thyroxine (T4) the main hormone emitted by the thyroid, and thyroid stimulating hormone (TSH) which is emitted by the pituitary gland.<ref name="NIDDK">Hashimoto's Disease | NIDDK [Internet]. National Institutes of Health. U.S. Department of Health and Human Services; [cited 2017Mar21]. Available from: https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease</ref>&nbsp;T4 test Measures the actual amount of thyroid hormone circulating in the blood. In cases of hypothyroidism, T4 levels are lower than normal.<ref name="NIDDK" />&nbsp; TSH test The ultrasensitive TSH test is usually the first test performed. This test detects even tiny amounts of TSH in the blood and is the most accurate measure of thyroid activity available. Generally, a TSH reading above normal means a person has hypothyroidism.<ref name="NIDDK" />
 
Antithyroid Antibody test
 
This test focuses attention on thyroid autoantibodies, or molecules produced by a person’s body that mistakenly attack the body’s own tissues. Two principal types of anti-thyroid antibodies are:
* Anti-TG antibodies, which attack a protein in the thyroid called thyroglobulin
 
* Anti-thyroperoxidase (TPO) antibodies, which attack an enzyme called thyroperoxidase in thyroid cells that helps convert T4 to T3. Presence of TPO autoantibodies in the blood indicates the body’s immune system has attacked tyroid tissue in the past.. Most people with Hashimoto’s disease have these antibodies, although people whose hypothyroidism is caused by other conditions do not.
Other diagnostic tests may include an ultrasound or a computerized tomography (CT) scan.<ref name="NIDDK" />


== Medical Management  ==
== Medical Management  ==


According to the NIH,” Treatment generally depends on whether the thyroid is damaged enough to cause hypothyroidism. Health care providers may choose to treat Hashimoto’s disease to reduce the size of the goiter, or choose not to treat and simply monitor their patients for disease progression.<br>Hashimoto’s disease, is treated with synthetic thyroxine. Health care providers prefer to use synthetic T4, such as Synthroid, rather than synthetic T3, because T4 stays in the body longer, ensuring a steady supply of thyroid hormone throughout the day<br>Health care providers routinely test the blood of patients taking synthetic thyroid hormone and adjust the dose as necessary, typically based on the result of the TSH test. Hypothyroidism can almost always be completely controlled with synthetic thyroxine, as long as the recommended dose is taken every day as instructed”<ref name="NIDDK" /><br><br>Differential Diagnosis
According to the NIH,” Treatment generally depends on whether the thyroid is damaged enough to cause hypothyroidism. Health care providers may choose to treat Hashimoto’s disease to reduce the size of the goiter, or choose not to treat and simply monitor their patients for disease progression.<br>Hashimoto’s disease, is treated with synthetic thyroxine. Health care providers prefer to use synthetic T4, such as Synthroid, rather than synthetic T3, because T4 stays in the body longer, ensuring a steady supply of thyroid hormone throughout the day<br>Health care providers routinely test the blood of patients taking synthetic thyroid hormone and adjust the dose as necessary, typically based on the result of the TSH test. Hypothyroidism can almost always be completely controlled with synthetic thyroxine, as long as the recommended dose is taken every day as instructed”<ref name="NIDDK">Hashimoto's Disease | NIDDK [Internet]. National Institutes of Health. U.S. Department of Health and Human Services; [cited 2017Mar21]. Available from: https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease</ref>
 
Possible differential diagnoses:<ref name="McGraw">Hashimoto's thyroiditis [Internet]. Hashimoto's thyroiditis | Quick Answers: Physiotherapy | AccessPhysiotherapy | McGraw-Hill Medical. [cited 2017Mar21]. Available from: http://accessphysiotherapy.mhmedical.com/content.aspx?bookid=855§ionid=49734591</ref>
 
*Euthyroid Sick Syndrome
 
*Hypopituitarism (Panhypopituitarism)
 
*Goiter
 
*Polyglandular Autoimmune Syndrome, Type I
 
*Goiter, Diffuse Toxic
 
*Polyglandular Autoimmune Syndrome, Type II
 
*Goiter, Lithium-Induced
 
*Thyroid Lymphoma
 
*Goiter, Nontoxic
 
*Goiter, Toxic Nodular
 
Other possible issues include:<ref name="ATA" />  
 
*Addison disease
 
*Alopecia areata, totalis, and universalis
 
*Autoimmune gastritis (pernicious anemia)
 
*Chronic active hepatitis
 
*Idiopathic hypoparathyroidism * Polymyalgia rheumatica and giant cell arteritis
 
*Primary biliary cirrhosis
 
*Primary ovarian or testicular failure * Rheumatoid arthritis * Sjögren syndrome * Systemic lupus erythematosus
 
*Systemic sclerosis (scleroderma)
 
*Type 1 diabetes mellitus
 
*Vitiligo
 
== Systemic Involvement  ==
 
The patient may present with the symptoms listed above that mimic musculoskeletal pain.


== Physical Therapy Management  ==
== Physical Therapy Management  ==
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*B vitamins: Are important for maintaining energy and metabolic function.<ref name="Natural">Hashimoto's thyroiditis [Internet]. Hashimoto's thyroiditis | Quick Answers: Physiotherapy | AccessPhysiotherapy | McGraw-Hill Medical. [cited 2017Mar21]. Available from: http://accessphysiotherapy.mhmedical.com/content.aspx?bookid=855§ionid=49734591</ref>
*B vitamins: Are important for maintaining energy and metabolic function.<ref name="Natural">Hashimoto's thyroiditis [Internet]. Hashimoto's thyroiditis | Quick Answers: Physiotherapy | AccessPhysiotherapy | McGraw-Hill Medical. [cited 2017Mar21]. Available from: http://accessphysiotherapy.mhmedical.com/content.aspx?bookid=855§ionid=49734591</ref>


== Case Reports/ Case Studies  ==
== References ==
 
[http://www.physio-pedia.com/Hashimoto%27s_Thyroiditis_Case_Study Hashimoto's Thyroiditis Case Study]
 
<br>
 
A. M. McGregor, D. F. Roberts, and R. Hall. A study of triplets with Hashimoto's thyroiditis. Postgrad Med J. 1979 December; 55(650): 894–896. Click here for article.
 
<br>A Shuper, T Leathem, A Pertzelan, B Eisenstein, and M Mimouni. Familial Hashimoto's thyroiditis with kidney impairment. Arch Dis Child. 1987 August; 62(8): 811–814. Click here for article.
 
<br>Jan van Schaik,1 Olaf M. Dekkers,2 Eleonora P. M. van der Kleij-Corssmit,2 Johannes A. Romijn,2 Hans Morreau,3 and Cornelis J. H. van de Velde1*. Surgical Treatment for Unexplained Severe Pain of the Thyroid Gland: Report of Three Cases and Concise Review of the Literature. Case Report Med. 2011; 2011: 349756. Click here for article.
 
<br>G. T. Ko, C. C. Chow, V. T. Yeung, H. Chan, and C. S. Cockram. Hashimoto's thyroiditis, Sjogren's syndrome and orbital lymphoma. Postgrad Med J. 1994 June; 70(824): 448–451. Click here for article.
 
<br>P L Vold and P J Weiss. Rhabdomyolysis from tourniquet trauma in a patient with hypothyroidism. West J Med. 1995 March; 162(3): 270–271. Click here for article.
 
== Resources  ==
 
[http://www.thyroid.org/ American Thyroid Association]. &nbsp;
 
== References ==


<references />
<references />
[[Category:Autoimmune Disorders]]
[[Category:Autoimmune Disorders]]

Revision as of 09:28, 13 January 2023

Introduction[edit | edit source]

Hashimoto thyroiditis is an autoimmune disease. In this condition the thyroid cells are destroyed via cell and antibody-mediated immune action. In developed countries it is the most common cause of hypothyroidism, whereas worldwide the most common cause is a deficient dietary intake of iodine. [1]

[2]

Epidemiology[edit | edit source]

After age six, Hashimoto is the most common cause of hypothyroidism in those areas of the world where iodine intake is adequate.

  • The incidence is estimated to be 0.8 per 1000 per year in men and 3.5 per 1000 per year in women.
  • Studies suggests genetic genetic factors play a role and to a lesser degree environmental and sex hormone influences.
  • The prevalence of thyroid disease, in general, increases with age.[1]

Etiology[edit | edit source]

There are many factors that may play a role in acquiring Hashimoto’s disease, these factors include;

  • Genes - Some people are more apt to Hashimoto's disease due to their genes. Researchers are continuing to work on finding the gene or genes that are involved
  • Gender - Sex hormones are thought to take part in the cause. This may assist in explaining why Hashimoto's disease affects more women than men.
  • Pregnancy - Pregnancy affects the thyroid. Some women have thyroid problems after having a baby, which usually go away. But about 20 percent of these women develop Hashimoto's disease in later years. This suggests that pregnancy might trigger thyroid disease in some women.
  • Too much iodine and some drugs may bring about the onset of thyroid disease in people susceptible to acquiring it.
  • Radiation exposure has been shown to trigger autoimmune thyroid disease. This includes radiation from the atomic bomb in Japan, the nuclear accident at Chernobyl, and radiation treatment of Hodgkin's disease.[3]

BupaHealth UK. How a thyroid gland can become underactive.

[4]

Other Autoimmune Disease Associations[edit | edit source]

People with other autoimmune diseases are more likely to develop Hashimoto’s disease. The opposite is also true—people with Hashimoto’s disease are more likely to develop other autoimmune diseases. These diseases include

  • Vitiligo, a condition in which some areas of the skin lose their natural color.
  • Rheumatoid arthritis, a disease that causes pain, swelling, stiffness, and loss of function in the joints when the immune system attacks the membrane lining the joints.
  • Addison’s Disease, in which the adrenal glands are damaged and cannot produce enough of certain critical hormones.
  • Diabetes Mellitus type I, in which the pancreas is damaged and can no longer produce insulin, causing high blood glucose, also called blood sugar.
  • Pernicious Anemia, a type of anemia caused by not having enough vitamin B12 in the body. In anemia, the number of red blood cells is less than normal, resulting in less oxygen carried to the body’s cells and extreme fatigue.
  • Celiac Disease, a form of gastrointestinal gluten sensitivity, an autoimmune disorder in which people cannot tolerate gluten because it will damage the lining of the small intestine and prevent adsorption of nutrients. Gluten is a protein found in wheat, rye, and barley and in some products.
  • Autoimmune Hepatitis, or nonviral liver inflammation, a disease in which the immune system attacks liver cells.[5]

Characteristics/Clinical Presentation[edit | edit source]

Hashimoto Thyroiditis does not present with any unique signs and symptoms.[6] “The condition progresses very slowly over many years, people with Hashimoto’s thyroiditis may not have any symptoms early on. Many of the signs and symptoms mimic general hypothyroid conditions. [7]

Signs and Symptoms:

  • Painless thyroid enlargement
  • Gland is sometimes easily palpable
  • Fatigue and lethargy
  • Cold intolerance
  • Pale, dry skin
  • Constipation
  • Hoarseness
  • Dysphagia
  • Weight gain
  • Myalgia and stiffness
  • Proximal muscle weakness
  • Excess or prolonged menstrual bleeding
  • Increased PMS symptoms
  • Depression

Without treatment the signs and symptoms increase in severity and include:

  • Goiter: If the goiter is allowed to increase in size it can lead to "dysphagia and respiratory distress."
  • Constipation
  • Myxedema

As the disease progresses neurological involvement including:

  • Difficulty learning
  • Forgetfulness

Medications[edit | edit source]

The central component of treatment for hypothyroidism is thyroid hormone replacement. The drug used commonly is titrated levothyroxine sodium administered orally. Note the formation of thyroxine varies worldwide and there can be problems with absorption in patients with disorders of the gastric mucosa.[1]

Diagnosis[edit | edit source]

Hashimoto’s thyroiditis is usuallt diagnosed when patients present with symptoms of hypothyroidism, often along with a goiter on physical examination. Laboratory testing of hypothyroidism shows elevated thyroid stimulating hormone (TSH) with or without a low thyroid hormone (Free thyroxine [Free T4]) levels.[8]

Medical Management[edit | edit source]

According to the NIH,” Treatment generally depends on whether the thyroid is damaged enough to cause hypothyroidism. Health care providers may choose to treat Hashimoto’s disease to reduce the size of the goiter, or choose not to treat and simply monitor their patients for disease progression.
Hashimoto’s disease, is treated with synthetic thyroxine. Health care providers prefer to use synthetic T4, such as Synthroid, rather than synthetic T3, because T4 stays in the body longer, ensuring a steady supply of thyroid hormone throughout the day
Health care providers routinely test the blood of patients taking synthetic thyroid hormone and adjust the dose as necessary, typically based on the result of the TSH test. Hypothyroidism can almost always be completely controlled with synthetic thyroxine, as long as the recommended dose is taken every day as instructed”[9]

Physical Therapy Management[edit | edit source]

Physical therapy is not standard treatment for patients with this disorder. Physical therapists should know to screen for it.  Physical therapists also need to be aware of the disease because they may have a patient that has Hashimoto Thyroiditis as a co-morbidity.

A physical therapy screening for Hashimoto Thyroiditis should include:[10]

  • Subjective questioning
  • Upper and/or lower quarter clearing exam - depending on the patient's complaints
  • MMT - for the specific muscle(s)/area
  • ROM - for the specific muscle(s)/area
  • Special tests - for the specific joint/area
  • Palpation - thyroid and any other areas that are suspected as the cause of the symptoms
  • Any other measure that the physical therapist deems necessary for the patient's specific complaints

If the above screening does not indicate a musculoskeletal issue, the physical therapist should refer the patient to the appropriate health care provider.

Alternative/Holistic Management[edit | edit source]

Supplements:

  • Selenium: Research has found that it aids in the regulation of T3 and T4 hormones.
  • Probiotics: Aid in the support of gastrointestinal health
  • Vitamin D
  • B vitamins: Are important for maintaining energy and metabolic function.[11]

References[edit | edit source]

  1. 1.0 1.1 1.2 Mincer DL, Jialal I. Hashimoto thyroiditis. Available:https://www.ncbi.nlm.nih.gov/books/NBK459262/ (accessed 13.1.2023)
  2. Graves' Disease and Hashimoto's Thyroiditis. Available from: https://www.youtube.com/watch?v=oINxr8_nR_[last accessed 03/20/2017]
  3. ePublications [Internet]. Hashimoto's disease fact sheet. [cited 2017Mar21]. Available from: https://www.womenshealth.gov/publications/our-publications/fact-sheet/hashimoto-disease.html#d
  4. BH. How a Thyroid gland can become unactive [Internet]. How a Thyroid gland can become unactive. YouTube; 2013. Available from: http://www.youtube.com/watch?v=qIn8AHHB1_o[last acessed 3/21/17]
  5. Homepage [Internet]. American Thyroid Association. [cited 2017Mar21]. Available from: http://www.thyroid.org/
  6. Goodman CC, Fuller KS. Pathology: implications for the physical therapist. St. Louis, MO: Elsevier Saunders; 2015.
  7. Goodman CC, Snyder TEK. Differential diagnosis for physical therapists screening for referral. St. Louis, MO: Saunders Elsevier; 2013.
  8. American Thyroid Association Hashimoto’s Thyroiditis (Lymphocytic Thyroiditis) Available:https://www.thyroid.org/hashimotos-thyroiditis/ (accessed 13.1.2023)
  9. Hashimoto's Disease | NIDDK [Internet]. National Institutes of Health. U.S. Department of Health and Human Services; [cited 2017Mar21]. Available from: https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease
  10. Goodman C, Snyder T. Differential Diagnosis for Physical Therapists: Screening for Referral. St. Louis, Missouri: Saunders Elsevier; 2007.
  11. Hashimoto's thyroiditis [Internet]. Hashimoto's thyroiditis | Quick Answers: Physiotherapy | AccessPhysiotherapy | McGraw-Hill Medical. [cited 2017Mar21]. Available from: http://accessphysiotherapy.mhmedical.com/content.aspx?bookid=855§ionid=49734591