Introduction
Background
Subacute thyroiditis is a self-limited thyroid condition associated with a triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function. Subacute thyroiditis may be responsible for 15-20% of patients presenting with thyrotoxicosis and 10% of patients presenting with hypothyroidism. Recognizing this condition is important, because it is self-limiting, and no specific therapy, such as antithyroid or thyroid hormone replacement therapy, is necessary in most patients.
In general, the following 3 forms of subacute thyroiditis are recognized:
- Subacute granulomatous (see the image below), subacute painful, or de Quervain thyroiditis.
Three multinucleated, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.
- Lymphocytic thyroiditis (also known as subacute painless thyroiditis)
- Subacute postpartum thyroiditis
Although the etiology appears to be different for the 3 subtypes, the clinical courses are the same.
The high thyroid hormone levels are a result of destruction of the thyroid follicle and release of preformed thyroid hormone into the circulation. The high thyroid hormone levels are not a function of new thyroid hormone synthesis and secretion. Conditions of excess thyroid hormone synthesis and secretion (eg, Graves disease, toxic multinodular goiter, toxic adenoma) are discussed in the eMedicine article Hyperthyroidism.
Eventually, thyroid hormone is depleted and the patient may become hypothyroid. Often, the hypothyroidism is mild, and no thyroid hormone therapy is required unless the patient has signs or symptoms of hypothyroidism. The hypothyroid phase may last up to 2 months.
Ninety to 95% of patients return to normal thyroid function.
Pathophysiology
The hypermetabolic effect of thyrotoxicosis is the same, regardless of cause. Thyrotoxicosis affects every organ system, because thyroid hormones made in the thyroid travel via the circulation to reach every cell in the body. Thyroid hormone is necessary for normal growth and development, and it regulates cellular metabolism. Excess thyroid hormone causes an increase in metabolic rate that is associated with increased total body heat production, increased cardiovascular activity (eg, increased heart contractility, heart rate, vasodilation) to remove heat to the periphery and remove metabolic wastes, and perspiration to cool the body.
The major symptoms of thyrotoxicosis include palpitations, nervousness, sweating, hyperdefecation, and heat intolerance. Women often note a reduction in menstrual flow or oligomenorrhea. Common signs of thyrotoxicosis include weight loss despite increased appetite, lid lag and stare, sinus tachycardia, atrial fibrillation or high-output failure (in elderly persons), fine tremor, and muscle weakness. Synergism occurs between thyrotoxicosis and the adrenergic system, with increases in nervousness, stare, tremor, and tachycardia.
The manifestations of thyrotoxicosis vary among patients. Younger patients tend to exhibit more sympathetic activations (eg, anxiety, hyperactivity, tremor), while older patients have more cardiovascular symptoms (eg, dyspnea, atrial fibrillation) and unexplained weight loss. The clinical manifestation of thyrotoxicosis does not always correlate with the extent of the biochemical abnormality.
Subacute thyroiditis is a destructive thyroiditis resulting in the release of preformed thyroid hormone and not in the new synthesis of thyroid hormone. A characteristic finding in this thyrotoxic condition is a very low radioactive iodine uptake by the thyroid, as seen in the images below.
The 3 types of subacute thyroiditis are subacute granulomatous thyroiditis, also referred to as subacute painful thyroiditis; lymphocytic thyroiditis, which is silent and is also referred to as subacute painless thyroiditis; and postpartum thyroiditis. The etiology of each of these conditions is different, but all of them follow the same clinical course, including 6-8 weeks of thyrotoxicosis, 2-4 months of mild hypothyroidism, and finally, a return to the euthyroid state in 90-95% or more of the patients. A patient may experience 1 or more of these phases. The course is illustrated in the second image below.
Absence of iodine-123 (123I) radioactive iodine uptake in a patient with thyrotoxicosis and lymphocytic (subacute painless) thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T4), 21.2 mcg/dL (reference range, 4.5-11); total triiodothyronine (T3), 213 ng/dL (reference range, 90-180); T3-to-T4 ratio, 10; and erythrocyte sedimentation rate (ESR), 10 mm/h. The absence of thyroid uptake, the low T3-to-T4 ratio, and the low ESR confirm the diagnosis of lymphocytic thyroiditis.
Example of laboratory values during subacute granulomatous thyroiditis. The entire episode may evolve through all 3 phases over a period of as long as 6 months.
Thyroid biopsies in subacute granulomatous thyroiditis show characteristic multinucleated, giant cell granulomas and a mononuclear infiltration, as seen in the image below. Thyroid biopsy tissue from patients with postpartum and painless or lymphocytic thyroiditis shows a lymphocytic infiltration.
Three multinucleated, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.
A Japanese study derived from a medical records review of 852 patients with subacute thyroiditis found that most of the laboratory test–based indications for thyrotoxicosis and thyroiditis-associated inflammation peaked within a week after the onset of subacute thyroiditis.1
Frequency
United States
The thyrotoxicosis caused by lymphocytic, subacute painful, or postpartum thyroiditis is more frequently recognized as a cause of transient thyrotoxicosis. Estimates indicate that 20-25% of thyrotoxicosis is caused by these destruction-induced forms.
International
No difference in the worldwide prevalence of subacute thyroiditis is apparent.
Mortality/Morbidity
Thyrotoxicosis from subacute thyroiditis is brief, usually lasting no longer than 6-8 weeks. Patients can be extremely thyrotoxic during this period and can appear extremely ill, but concerns regarding left ventricular hypertrophy and osteoporosis are not as great as those associated with conditions of permanent hyperthyroidism. However, sudden-onset thyrotoxicosis and severe thyrotoxicosis can be associated with atrial arrhythmia and congestive heart failure (CHF).
Race
Subacute thyroiditis appears to affect all races and ethnic groups equally.
Sex
- Subacute granulomatous thyroiditis has a female-to-male prevalence ratio of 5:1.
- Lymphocytic thyroiditis and postpartum thyroiditis are associated with autoimmune thyroiditis. Lymphocytic thyroiditis occurs 2 times more often in women than it does in men.
- Postpartum thyroiditis occurs 1-6 months after giving birth. If a woman has postpartum thyroiditis with one baby, all other pregnancies are likely to be associated with this condition.
Age
- Lymphocytic thyroiditis can occur in any age group, while granulomatous thyroiditis usually occurs in adults (ie, aged 20-60 y).
- Postpartum thyroiditis occurs in women of childbearing age.
Clinical
History
Patient presentation depends on the etiology of the thyrotoxicosis. Subacute granulomatous thyroiditis is associated with an acute virallike illness with fevers and myalgias with a painful thyroid. A recent birth signals postpartum thyroiditis. Often, the thyrotoxicosis of lymphocytic thyroiditis, postpartum thyroiditis, or surreptitious use of thyroid hormone is symptomatic because of persistent tachycardia, nervousness, and weight loss. Symptoms of thyrotoxicosis that persist for longer than 2 months are probably not caused by subacute thyroiditis.
- Subacute granulomatous thyroiditis - These patients have the classic presentation of a viral illness. The onset is sudden, with high fever, myalgia, and neck pain.
- Lymphocytic thyroiditis - This form is associated with a painless, firm enlargement of the thyroid gland and high thyroid hormone levels. Only suspicion by the clinician and use of radioactive iodine uptake measurement can distinguish Graves hyperthyroidism from lymphocytic thyroiditis.
- Subacute postpartum thyroiditis - This form is associated with a painless, firm enlargement of the thyroid gland and high thyroid hormone levels. The identifying feature is its occurrence 1-6 months after childbirth. Autoimmune hyperthyroidism from Graves disease can also occur for the first time postpartum and must be distinguished from postpartum thyroiditis. Both conditions are associated with high antithyroid antibody titers.
Physical
All conditions described are associated with thyrotoxicosis and the signs and symptoms of hypermetabolism. None of the forms of subacute thyroiditis is associated with the thyroid eye disease observed primarily with Graves hyperthyroidism. The presence of bilateral proptosis and chemosis with high thyroid hormone levels and goiter is highly suggestive of Graves disease.
- Subacute granulomatous thyroiditis - Patients often present with an acute virallike illness characterized by high spiking fever, malaise, myalgia, fatigue, and prostration. Neck pain from the thyroiditis can be extremely painful, preventing swallowing of saliva, liquids, and food. The pain starts in the lower neck and can radiate to the jaw or ear on that side. Thyroid hormone levels are often extremely elevated, resulting in marked signs and symptoms of thyrotoxicosis. Cases of lesser severity also exist, and the etiology may be confusing.
- Lymphocytic thyroiditis - Patients present with a nonpainful thyroid enlargement and elevated thyroid hormone levels. This condition must be distinguished from Graves thyrotoxicosis because antithyroid medication is not indicated in this temporary condition.
- Subacute postpartum thyroiditis - Patients present 1-6 months postpartum with painless thyroid enlargement and elevated thyroid hormone levels. Patients may report lack of sleep, nervousness, fatigue, and easy weight loss. Sometimes, distinguishing between the usual postpartum changes in physiology and additional thyroid pathology is difficult.
Causes
The causes of subacute thyroiditis, other than those of subacute granulomatous thyroiditis, are not entirely clear.
- Subacute granulomatous thyroiditis - The most accepted etiology is a viral illness.2 Viral particles have never been identified within the thyroid, but episodes often follow upper respiratory infections and are associated with falling postconvalescent viral titers of various viruses, including influenza, adenovirus, mumps, and coxsackievirus. This condition is not associated with autoimmune thyroiditis but is associated with HLA (human leukocyte antigen)-B35. A genetic predisposition clearly exists; patients with HLA-Bw35 have a significantly increased risk of developing this condition. Whether the destructive thyroiditis is caused by direct viral infection of the gland or by the host's response to the viral infection is unclear. Granulomatous thyroiditis is not an autoimmune disease of the thyroid.
- Lymphocytic thyroiditis - This condition most likely is autoimmune in nature. Patients develop an autoimmune goiter and permanent hypothyroidism more often than they do with the painful form of subacute thyroiditis.
- An HLA association may be present, suggesting a genetic predisposition to painless thyroiditis.
- Certain drug exposures relating to excess iodine and cytokines may cause this form of silent thyroiditis. These drugs include amiodarone (iodine-rich), interferon-alpha, interleukin 2, and lithium. Lymphocytic thyroiditis resulting from these different medications is typically treated similarly (see Medication).
- Amiodarone has multiple established effects on thyroid function. One of the 2 types of amiodarone-induced thyrotoxicosis is a destructive lymphocytic thyroiditis. This form of thyroiditis is more common in men, likely due to the higher prevalence of amiodarone therapy in men. This form of silent thyroiditis typically occurs after more than 2 years of amiodarone therapy.
- Up to 5% of patients taking interferon-alpha may experience lymphocytic thyroiditis. This condition is detected biochemically more often than clinically after 3 months of therapy. Lymphocytic thyroiditis in patients taking interferon-alpha is associated with an increased antithyroid antibody concentration.
- Although case reports exist that interleukin 2 is associated with lymphocytic thyroiditis, its causative role is less established than is that of interferon-alpha.
- Lithium is a well-known cause of either subclinical or clinical hypothyroidism, as well as of goiter. Because of lithium’s ability to inhibit the release of thyroid hormone, it has been used as a treatment for thyrotoxicosis. However, reports exist of lithium-associated thyrotoxicosis due to a lymphocytic thyroiditis, with the classic picture of hyperthyroidism, absent neck tenderness, and low radioactive iodine uptake (see Medication). The lymphocytic thyroiditis can occur during lithium administration, as well as up to 5 months following discontinuation of lithium therapy. Increased thyroid antibodies in lithium users and a direct toxic effect of lithium have been proposed as possible mechanisms.
- Subacute postpartum thyroiditis - This condition is likely autoimmune in nature.3 Patients develop an autoimmune goiter and permanent hypothyroidism more often than with the painful form of subacute thyroiditis. In iodine-sufficient countries, such as the United States, postpartum thyroiditis occurs in approximately 5-8% of pregnant women. In Japan, nearly 20% of pregnancies are associated with this condition. Patients with positive test results for thyroid autoantibodies either before their pregnancy or during the third trimester are at much higher risk of developing postpartum thyroiditis.
- Cigarette smoking is also associated with an increased incidence of postpartum thyroiditis. Once patients have an episode of subacute postpartum thyroiditis, they are likely to have additional episodes following each pregnancy.
More on Subacute Thyroiditis |
 Overview: Subacute Thyroiditis |
| Differential Diagnoses & Workup: Subacute Thyroiditis |
| Treatment & Medication: Subacute Thyroiditis |
| Follow-up: Subacute Thyroiditis |
| Multimedia: Subacute Thyroiditis |
| References |
| Further Reading |
| Next Page » |
References
Nishihara E, Ohye H, Amino N, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med. 2008;47(8):725-9. [Medline]. [Full Text].
Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J. Jan 12 2009;6:5. [Medline]. [Full Text].
Filippi U, Brizzolara R, Venuti D, et al. Prevalence of post-partum thyroiditis in Liguria (Italy): an observational study. J Endocrinol Invest. Dec 2008;31(12):1063-8. [Medline].
Omori N, Omori K, Takano K. Association of the ultrasonographic findings of subacute thyroiditis with thyroid pain and laboratory findings. Endocr J. Jul 2008;55(3):583-8. [Medline]. [Full Text].
Nishimaki M, Isozaki O, Yoshihara A, Okubo Y, Takano K. Clinical characteristics of frequently recurring painless thyroiditis: contributions of higher thyroid hormone levels, younger onset, male gender, presence of thyroid autoantibody and absence of goiter to repeated recurrence. Endocr J. Feb 18 2009;[Medline]. [Full Text].
Bartalena L, Brogioni S, Grasso L, Bogazzi F, Burelli A, Martino E. Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J Clin Endocrinol Metab. Aug 1996;81(8):2930-3. [Medline]. [Full Text].
Bartalena L, Grasso L, Brogioni S, et al. Serum interleukin-6 in amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. Feb 1994;78(2):423-7. [Medline]. [Full Text].
Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. Jul 2005;118(7):706-14. [Medline].
Dang AH, Hershman JM. Lithium-associated thyroiditis. Endocr Pract. May-Jun 2002;8(3):232-6. [Medline].
Emerson CE, Farwell AP. Sporadic silent thyroiditis, postpartum thyroiditis, and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's The Thyroid. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:579-89.
Hamburger JI. The various presentations of thyroiditis. Diagnostic considerations. Ann Intern Med. Feb 1986;104(2):219-24. [Medline].
Hay ID. Thyroiditis: a clinical update. Mayo Clin Proc. Dec 1985;60(12):836-43. [Medline].
Lambert M, Unger J, De Nayer P, et al. Amiodarone-induced thyrotoxicosis suggestive of thyroid damage. J Endocrinol Invest. Jun 1990;13(6):527-30. [Medline].
Miller KK, Daniels GH. Association between lithium use and thyrotoxicosis caused by silent thyroiditis. Clin Endocrinol (Oxf). Oct 2001;55(4):501-8. [Medline].
Nikolai TF, Brosseau J, Kettrick MA, et al. Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (silent thyroiditis). Arch Intern Med. Apr 1980;140(4):478-82. [Medline].
Roti E, Minelli R, Giuberti T, et al. Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon-alpha. Am J Med. Nov 1996;101(5):482-7. [Medline].
Further Reading
Clinical guidelines:
Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.
Clinical trials:
Generic vs. Name-Brand Levothyroxine
Maternal Hypothyroidism in Pregnancy
Keywords
subacute thyroiditis, thyroid, hypothyroidism, thyroid disease, hyperthyroidism, hypothyroid, thyroid symptoms, thyroiditis, hyperthyroid, thyroid hormone, symptoms of thyroid, symptoms of thyroid problems, thyroid disorder, thyroxine, thyroid disorders, thyroid tests, thyroid hormones, T3 thyroid, T4 thyroid, thyrotoxicosis, postpartum thyroiditis, triiodothyronine, lymphocytic thyroiditis, de Quervain's, silent thyroiditis, de Quervain thyroiditis, subacute painless thyroiditis, subacute lymphocytic thyroiditis, subacute postpartum thyroiditis, subacute granulomatous thyroiditis, subacute painful thyroiditis, de Quervain's thyroiditis
