Thyroiditis

Hashimoto's thyroiditis. Johns Hopkins

Author: Dr Paul W. Ladenson Johns Hopkins University 2008-06-10

1.Introduction

Thyroiditis means inflammation of the thyroid gland, which is a butterfly shaped organ located in the lower front of the neck.  Thyroiditis can have many causes, including infections, drugs, radiation, and most commonly, a person’s own immune system.  Some forms of thyroid inflammation are common, such as autoimmune thyroiditis, while others, such Reidel thyroiditis, are very rare.
  The symptoms (i.e., complaints) and signs (i.e., objective exam findings) of thyroiditis depend on the specific underlying cause. These may include thyroid gland enlargement (called a goiter), sometimes with compression of nearby structures, like the windpipe (trachea) or swallowing tube (esophagus); gland pain and tenderness; and problems related to excessive and inadequate thyroid hormone from the gland, which then affects other parts of the body.  Some kinds of thyroiditis are temporary, resolve completely, and never happen again, such as subacute thyroiditis; some tend to recur, such as postpartum thyroiditis; and others are typically permanent and irreversible, such as autoimmune thyroiditis.  The best treatment for thyroiditis depends on its cause and can include anti-inflammatory medications, thyroid hormone medication, and drugs to control symptoms of thyroid hormone excess.

Because the causes of thyroiditis, the problems that they cause, the way to diagnose them, and their treatments differ with each specific condition, they are presented individually below. A summary is presented in Table 1.
Autoimmune Thyroiditis (chronic lymphocytic or Hashimoto thyroiditis)
Autoimmune thyroiditis occurs when a person’s immune system turns against their own thyroid gland, inflaming it, usually causing the gland to swell, and often making it permanently underactive.  The condition is also called Hashimoto thyroiditis, named for the Japanese pathologist who first described it in 1912.  Like other autoimmune diseases, autoimmune thyroiditis is more common in women, but it also affects men.  Autoimmune thyroiditis can first appear in children and young adults, but its incidence increases sharply in middle aged and elderly people. (Figure 1) Among those over age 70 years, one in six women and one in seven men has blood test evidence of autoimmune thyroiditis.  The condition tends to run in families and is more common in whites and Hispanics than blacks. 

The immune system’s role in causing autoimmune thyroiditis is clear from the presence of antibodies directed against thyroid-specific proteins, such as thyroid peroxidase and thyroglobulin, both of which are essential for thyroid hormone to be made by the gland.  Detecting these antibodies can be important in diagnosing autoimmune thyroiditis.  However, it is direct infiltration of the thyroid by cytotoxic lymphocytes, key effectors of the body’s immune response, that accounts for most of the damage to thyroid cells.  This injury can then make the thyroid incapable of carrying out its normal function of making thyroid hormones and cause hypothyroidism, an underactive gland.

There is a strong genetic predisposition to autoimmune thyroiditis, with a 50-50 chance that someone with the condition will have an affected immediate family member.  However, the condition’s inheritance pattern is complex and incompletely understood, so there is currently no test to determine if relatives of an affected person are destined to develop autoimmune thyroiditis.  Higher dietary iodine intake is associated with a greater incidence of autoimmune thyroiditis in a population; but there is, as yet, no clear evidence that limiting iodine intake would help an individual prevent the condition.
  The main problems caused by autoimmune thyroiditis are goiter and hypothyroidism.  Most affected people have some degree of generalized gland enlargement from 1½- to 3-times normal size, but one in ten people have a small thyroid gland.  Although the gland enlargement can often be seen and sometimes causes a mild sensation of neck tightness with swallowing, it is only rarely painful.  The goiter itself almost never requires any specific treatment, and over time, the gland shrivels up in most individuals with the condition.  Sometimes the gland can be asymmetrically enlarged and appear to be a possible thyroid tumor.  In these cases, a thyroid sonogram often shows the generalized unevenness of the gland and absence of a discrete thyroid nodule.  (See “Thyroid Nodules and Goiter” Knol.)  If the gland must be biopsied to make the distinction, the aspirated material typically contains lymphocytes, the immune system’s inflammatory cells. 
Autoimmune thyroiditis is the most common cause of hypothyroidism.  In fact, when a person with an underactive thyroid gland has no history of previous thyroid history or radiation, it can usually be assumed to be the reason.  Typical symptoms of thyroid hormone deficiency include fatigue, intolerance of cold temperature, weight gain, constipation, dry skin, muscle cramps, slowed thinking, and depressed mood. (See “Hypothyroidism” Knol)  Since these symptoms are nonspecific, i.e., also common in people without a thyroid problem, blood testing is essential to confirm the diagnosis. 
Fortunately, many patients with autoimmune thyroiditis maintain normal thyroid gland function (euthyroidism) for years or forever, but they are at risk of progressing to thyroid failure.  Sometimes thyroid underactivity can be provoked by pregnancy or by medications, such as lithium carbonate (prescribed for bipolar disorder), amiodarone (for abnormal heart rhythm), or anti-seizure medications, such as phenytoin (Dilantin^®) or carbamazepine (Tegretol^®).  A very high intake of iodine, such as occurs with taking naturopathic kelp (seaweed) can also precipitate hypothyroidism in people with autoimmune thyroiditis.  Rarely, people with autoimmune thyroiditis can develop a period of short-lived thyroid hormone excess (thyrotoxicosis) before becoming permanently hypothyroidism, so called ‘Hashitoxicosis.’  Even more rarely, individuals with established hypothyroidism due to autoimmune thyroiditis may convert to having Graves disease, in which antibodies over-stimulate the thyroid gland.  (See “Hyperthyroidism” Knol.)      

To understand the blood tests for hypothyroidism, it is important to appreciate how the gland’s production of thyroid hormones is normally regulated.  The thyroid normally makes precisely the right amount of its hormones under the exacting control of the pituitary gland, which is an extension of the brain.  Specialized pituitary cells make thyroid stimulating hormone (TSH), which travels in blood to the thyroid gland, where TSH binds to its own receptors on thyroid cells, prompting them to grow and produce more of the thyroid hormones.  Normally, this system is kept in balance by the negative feedback of the thyroid hormones on TSH-secreting pituitary cells (as well as the part of the brain that controls them).  Consequently, when the thyroid is injured by autoimmune thyroiditis and no longer capable of making sufficient thyroid hormone, the pituitary senses this deficit and makes more TSH, in a futile attempt to restore the thyroid hormone production to normal.  This rise in the blood TSH level is a highly reliable way to determine if a person with thyroiditis has hypothyroidism.  With full blown thyroid hormone deficiency, the level of thyroxine (T4), the main thyroid hormone, is low.  However, in people with mild hypothyroidism (sometimes called subclinical hypothyroidism) the TSH level rises above normal even before the T4 level falls below its normal range. 

The diagnosis of autoimmune thyroiditis itself can be established by blood testing for antibodies directed against the thyroid gland.  The most sensitive of these tests, the anti-thyroid peroxidase antibody (anti-TPO) assay is positive in more than 90% of affected individuals.  Anti-thyroglobulin antibodies are detectable in 60% of patients.  These thyroid antibody tests can be useful to establish the cause of a goiter and to identify people at future risk of hypothyroidism, but their measurement is not needed to diagnose autoimmune thyroiditis in people with typical symptoms and signs.
  People with autoimmune thyroiditis are also susceptible to other autoimmune conditions although, fortunately, these related conditions occur in only a minority of individuals with thyroiditis.  These related disorders include vitiligo (causing white patches of skin), prematurely gray hair (before age 30 years)
,
atrophic gastritis (with little stomach acid production and poor absorption of iron and calcium), pernicious anemia (poor absorption and deficiency of vitamin B12), systemic sclerosis (also called scleroderma), and Sjögren’s syndrome (causing dry mouth and eyes).  Rarely, autoimmune thyroiditis is also accompanied by immune-mediated inflammation of other endocrine glands resulting in various combinations of hypothyroidism with, adrenal insufficiency, type 1 diabetes mellitus, hypoparathyroidism, hypopituitarism, and ovarian failure.  In addition, several studies have shown that women with autoimmune thyroiditis are more likely to suffer miscarriages.
  Painless Thyroiditis(postpartum, silent, or acute lymphocytic thyroiditis)
Painless thyroiditis is a self-limited painless (or silent) inflammation of the thyroid with short-lived thyroid hormone excess and/or deficiency (thyrotoxicosis and/or hypothyroidism) and little, if any, gland enlargement.  Because painless thyroiditis occurs in at least 5% of women from 2 to 12 months after the end of a pregnancy, it is also called postpartum thyroiditis.  The condition rarely occurs in women at other times, and it very rarely affects men.  Like Hashimoto thyroiditis, painless thyroiditis is an autoimmune disorder, as evidenced by infiltration of the thyroid gland by the immune system’s lymphocytes, a higher incidence in people with antithyroid antibodies in blood, and in some patients, by progression to conventional autoimmune thyroiditis with permanent hypothyroidism. 

Painless thyroiditis causes problems by interfering with the normal regulation of thyroid hormone production.  During the initial phase of gland inflammation, stored thyroid hormone is released in excess by the leaky gland.  Once the hormone supply is exhausted, this phase of the illness resolves, which typically takes 2 to 8 weeks.  In one-half of affected people, the thyroid gland is then unable to produce a normal amount of its hormones, causing hypothyroidism, which usually lasts for another 2 to 12 weeks.  In most people, the thyroid gland then returns to normal.  Although thyrotoxicosis followed by hypothyroidism is a common pattern for people suffering painless thyroiditis, some people suffer the thyrotoxic and hypothyroid phases alone. 

Individuals with painless thyroiditis have symptoms and signs caused by excess or deficient thyroid hormone.  Thyrotoxicosis typically causes weight loss, insomnia, anxiety, irritability, heat intolerance, trembling hands, and a hard or irregular heart beat (palpitations).  On the other hand, hypothyroidism (as described above) causes fatigue, cold intolerance, difficulty losing weight, constipation, dry skin, slowed thinking, and depressed mood.  It is easy to appreciate how both sets of complaints might be overlooked by both patients and doctors, particularly in a woman with a young child.
In the face of such nonspecific complaints, blood testing to evaluate thyroid function is key to making the diagnosis of painless thyroiditis.  The TSH blood level can reveal both thyroid hormone excess and deficiency, by low or elevated TSH values, respectively. 

Particularly when affected people are detected during the thyrotoxic phase, additional testing may include a nuclear medicine scan, which will show a very low uptake of the radioisotope by the gland due to its impaired function.  

Treatment of thyroid hormone excess or deficiency is possible when the diagnosis is made in a timely manner.  During the thyrotoxic phase, beta-adrenergic blocking agents, such as propranolol and metoprolol, can control some symptoms of thyrotoxicosis until this aspect of the illness resolves spontaneously.  During the hypothyroid phase, L-thyroxine can be given to provide thyroid hormone replacement.  In three-fourths of affected people, the condition resolves with no permanent impairment of the thyroid gland’s function; in one quarter, the condition progresses to permanent hypothyroidism, requiring lifelong thyroid hormone replacement medication.
  Women who suffer one episode of postpartum thyroiditis are very likely to have it again after subsequent pregnancies.  Women with type 1 diabetes and those with antithyroid antibodies in the blood are also considerably more likely to develop painless thyroiditis.  This has led to the recommendation by some that all pregnant women—or even those planning pregnancy—be screened for thyroid problems after delivery.
  Subacute Thyroiditis(painful or de Quervain thyroiditis) 
Subacute thyroiditis leads to three elements of illness: painful inflammation of the thyroid gland, a systemic illness like the flu, and a typical pattern of thyroid hormone excess followed by deficiency.  This form of thyroiditis is believed to be caused by a viral infection, but the responsible virus has not been identified with certainty, and there is no vaccine to prevent the condition nor an anti-viral drug to treat it.  Subacute thyroiditis is unusual, but a busy primary care doctor will usually have a handful of patients with the condition each year.  Fortunately, the majority of affected people enjoy a return to completenormalcy and never suffer a recurrence of thyroid illness.
  The thyroid pain caused by subacute thyroiditis can be located over the thyroid gland in the lower front of the neck, or it can ‘radiate,’ i.e., seem to be coming from somewhere else, such as the throat, ears, or jaw.  Sometimes patients and doctors mistakenly think this pain is due to throat or ear infection, temporomandibular joint (TMJ) arthritis, or other conditions.  The pain is typically accompanied by extreme tenderness to the touch of the thyroid gland itself.  Systemic symptoms can include a generalized feeling of sickness (malaise) such as one gets with the flu, fever, chills, and night sweats.  Sometimes these systemic inflammatory symptoms can dominate the picture, giving rise to concern about other serious infections or cancer.  

The reason that subacute thyroiditis causes problems is by interfering with the normal regulation of thyroid hormone production for the needs of the body.  During the initial phase of gland inflammation, thyroid hormone stored in the gland is released in excess by the leaky gland. (Figure 2)  Once the hormone supply is exhausted, this phase of the illness resolves, which typically takes 2 to 12 weeks.  In one-half of affected people, the thyroid gland then is unable to produce a normal amount of its hormones, causing hypothyroidism, which usually lasts for another few weeks.  In most people, the thyroid gland then returns to normal.  Although thyrotoxicosis followed by hypothyroidism is a common pattern for people suffering subacute thyroiditis, some people suffer the thyrotoxic and hypothyroid phases alone.  The third category of typical symptoms and signs are due to thyroid hormone excess and deficiency (as have been described above for painless thyroiditis).

Blood testing is again the key to making the diagnosis of subacute thyroiditis.  The erythrocyte sedimentation rate, a nonspecific indication of systemic inflammation, is usually markedly elevated in individuals with the early phase of this illness.  The TSH blood level can reveal both thyroid hormone excess and deficiency, by low or elevated TSH values, respectively.  When affected people are evaluated with nuclear medicine thyroid scan, there is typically a very low uptake of the radioisotope by the gland
,
   due to its impaired function.

Treatment of subacute thyroiditis begins with prescription anti-inflammatory medications and, sometimes includes additional drugs to control symptoms of thyroid hormone excess and deficiency.  For most people afflicted with subacute thyroiditis, aspirin or ibuprofen in relatively high doses, like those used to treat arthritis, will control the gland discomfort and symptoms of whole body inflammation.  For those whose complaints are not controlled with these agents, glucocorticoid (steroid) drugs like prednisone can be used.  Although glucocorticoids are highly effects—often providing relief in less than one day—their use may prolong the overall course of the illness, which can flare up as the steroid medication is tapered.  The uses of beta-adrenergic blocking agents to control thyrotoxic symptoms, and L-thyroxine to treat transient hypothyroidism have been described above in the treatment of painless thyroiditis.
Infectious Thyroiditis (suppurative or acute thyroiditis)
Bacterial infections beginning in the throat or beneath the skin of the neck can on rare occasion involve the thyroid gland.  Affected individuals have a very painful and exquisitely tender thyroid gland with swelling, redness, and warmth.  These patients are typically quite sick, with high fever, chills, and sweats.   
In patients who are immunocompromised, such as those with HIV infection or who are taking immunosuppressive drugs, the thyroid can be infected with opportunistic organisms that would not ordinarily affect it.  These can include pneumocystis carinii, tuberculosis, and fungi.   These individuals may have a more subtle presentation, with only mild fever and mild gland swelling and tenderness.
Patients with suppurative thyroiditis are usually very sick, requiring hospitalization and intravenous antibiotic drugs appropriate against the infectious organism.  It may be necessary to biopsy the gland to examine the aspirate under the microscope, and culture for the offending organism.  In cases where pus has collected in the thyroid gland, surgery to drain this may also be required. Drug-induced Thyroiditis Several medications are known to cause thyroiditis.  The anti-arrhythmic drug amiodarone can provoke thyrotoxicosis by inflaming the thyroid gland, a process that is painless and usually has its onset after months or years of amiodarone therapy.  This can occur in as many as one in five amiodarone-treated patients, and occurs more commonly in regions of the world with a relatively high dietary iodine intake.  Thyroiditis is only one of two mechanisms by which amiodarone provokes thyrotoxicosis; the other is so-called iodine-induced hyperthyroidism due to the iodine contained within the amiodarone molecule.  Amiodarone-related thyrotoxicosis often presents with only subtle symptoms, such as fatigue, weight loss, heat intolerance, and worsening of the patient’s heart condition.  Treatments for the two distinct causes of related thyrotoxicosis are quite different: beta-adrenergic blocking agents for amiodarone-induced thyroiditis and antithyroid medication for iodine-induced hyperthyroidism.  Unfortunately, differentiating between the two conditions is often impossible, as both lead to the same changes in blood thyroid hormone concentrations and the same low uptake of radioiodine on nuclear medical scanning.  Consequently, many patients are treated with both drugs, often for several months.  Some patients even require surgical thyroidectomy for cure.  The iodine in amiodarone can also cause hypothyroidism, especially in people who have underlying autoimmune thyroiditis.
Two drugs that affect functions of the immune system, interferon alfa and interleukin-2 cause thyroiditis in more than one in seven patients to whom they are given.  This form of thyroiditis is painless and causes no significant gland swelling, but it can provoke several kinds of thyroid gland dysfunction.  Some patients develop hypothyroidism, which typically resolves when the drug is stopped.  Others develop thyrotoxicosis, which can either be self-limited, like painless thyroiditis, or sustained, as in Graves disease.  These thyroid conditions can be diagnosed by measuring the blood TSH concentration, and the two forms of thyrotoxicosis can be distinguished by thyroid scanning with radioiodine. 
Sunitinib (Sutent^®), a chemotherapy drug for treatment of kidney and gastrointestinal cancers, can also cause painless thyroiditis with transient thyrotoxicosis followed by hypothyroidism, which can be permanent.
Reidel Thyroiditis
Riedel's thyroiditis is a very rare form of thyroiditis characterized by progressive gland fibrosis, which can involve nearby tissues.  Two-thirds of affected people have antithyroid antibodies in their blood, but whether the immune system causes this condition is unclear.  Patients with Riedel thyroiditis have a rock-hard, nontender goiter that does not move with swallowing due to its attachment to adjacent tissues in the neck.  Affected individuals may have cough or shortness of breath due to involvement of the trachea, or difficulty swallowing due to compression of the esophagus.  Ultimately, enough thyroid tissue can be destroyed that patients develop an underactive thyroid gland.  The condition is diagnosed by surgical biopsy of the thyroid gland.  Surgery to remove a portion of obstructing thyroid tissue may be helpful, and several drugs, including glucocorticoids, methotrexate, and tamoxifen have been used with reports of limited success.
Other Types of Thyroiditis
The thyroid gland can also be inflamed by radiation.  This can occur after radioiodine treatment of hyperthyroidism or remnant thyroid tissue after thyroid cancer surgery.  External beam radiotherapy, such as is used to treat lymphoma, can cause thyroiditis, which is usually painless, but causes hypothyroidism in up to one-half of exposed individuals. 
Physical injury to the thyroid gland can cause thyroiditis.  Even repeated vigorous palpation of the thyroid can lead to subtle symptoms, such as neck swelling and tenderness.

 Table 1.  Causes, Features, and Treatments for the Types of Thyroiditis 

Type of Thyroiditis	Cause	Typical Symptoms and Signs	Tests for Diagnosis	Treatment
Autoimmune thyroiditis (Hashimoto, chronic lymphocytic)	Persistent immune system inflammation of  person’s own thyroid	Thyroid gland enlargement (goiter) Underactive thyroid (hypothyroidism)	Anti-thyroid peroxidase (anti-TPO)antibody Anti-thyroglobulin antibody TSH to detect hypothyroidism	Thyroid hormone (L-thyroxine) for hypothyroidism
Painless thyroiditis (Postpartum, silent, acute lymphocytic)	Short-lived immune system inflammation of  person’s own thyroid	Painless modest gland enlargement Thyrotoxicosis, often followed by hypothyroidism (as well as other patterns of abnormal gland function)	Low thyroid uptake of radio iodine & 99mTc-pertechnetate TSH and T4 levels to detect thyrotoxicosis and hypothyroidism	Short-term beta-adrenergic blockers for thyrotoxic symptoms L-thyroxine for hypothyroidism
Subacute thyroiditis (painful, de Quervain)	Viral infection	Painful, tender and swollen gland Systemic symptoms of malaise, fever, chills, and night sweats Thyrotoxicosis, often followed by hypothyroidism (as well as other patterns of abnormal gland function)	Erythrocyte sedimentation rate elevation Low thyroid uptake of radio iodine & 99mTc-pertechnetate TSH and T4 levels to detect thyrotoxicosis and hypothyroidism	Aspirin, other anti-inflammatory drugs; Glucocorticoids (steroids such as prednisone)
Infectious thyroiditis (acute, suppurative)	Bacterial, fungal, and protozoan infections	Painful, tender and swollen gland with redness and warmth Fever in bacterial infections	White blood cell count elevated in bacterial infections	Antibiotic medication appropriate for responsible infecting organism
Reidel thyroiditis (fibrosing)	Unknown	Enlarged hard thyroid gland with fibrotic reaction extending into adjacent structures	Imagining studies showing enlarged thyroid gland encompassing adjacent structures	No clearly effective therapy.  Danazol, methotrexate, and glucocorticoids used

MORE INFORMATION ABOUT THYROIDITIS 

Web Resources

American Thyroid Association:  http://www.thyroid.org/patients/patient_brochures/thyroiditis.html  http://www.thyroid.org/patients/patient_brochures/postpartum.html  

UptoDate Patient Information: http://patients.uptodate.com/topic.asp?file=thyroid/12274   

Mayo Clinic:  http://www.mayoclinic.com/health/ (Then search for “Thyroiditis”) 

Medline Plus:  http://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=medlineplus&query=thyroiditis 

Web MD:  http://www.webmd.com/search/search_results/default.aspx?query=thyroiditis&sourceType=undefined

Books
Wood LC, Cooper DS, Ridgway EC. Your Thyroid: A Home Reference., Ballantine Books, New York, 1995
Surks MI.  The Thyroid Book. Consumer Reports Books, Yonkers, New York, 1993
Garber J, White SS. Harvard Medical School Guide to Overcoming Thyroid Problems. McGraw-Hill, 2005
 
Patient Support Organizations Thyroid Foundation of America, Inc.
One Longfellow Place Suite 1518
Boston, MA 02114
phone (toll-free) 800 832-8321
phone 617 534-1500
fax 617 534-1515
e-mail info@allthyroid.org

www.allthyroid.org 

Cutting Edge Thyroiditis Research

Clinical trials in progress: http://www.clinicaltrials.gov/ct2/results?term=Thyroiditis

Recently published clinical research: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(nodular%20goitre[Text%20Word]%20OR%20"goiter,%20nodular"[MeSH%20Terms]%20OR%20nodular%20goiter[Text%20Word])%20OR%20("thyroid%20nodule"[MeSH%20Terms]%20OR%20thyroid%20nodule[Text%20Word])%20AND%20("2007/02/19"[PDat]%20:%20"2008/02/18"[PDat]%20AND%20"humans"[MeSH%20Terms]%20AND%20English[lang]%20AND%20(Clinical%20Trial[ptyp]%20OR%20Meta-Analysis[ptyp]%20OR%20Practice%20Guideline[ptyp]%20OR%20Randomized%20Controlled%20Trial[ptyp]%20OR%20Review[ptyp]))

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