Continuing Education Activity
In general, thyroiditis is defined as an inflammation of the thyroid gland. There are several kinds of thyroiditis, and they can be associated with either increased, decreased, or normal thyroid function. Furthermore, they can be classified as painful or painless, depending on the etiology. Typically, painful thyroiditis is caused by radiation, trauma, or infection, while painless thyroiditis is caused by autoimmune diseases or medications. Painful thyroiditis can be further divided into subacute granulomatous (de Quervain) thyroiditis, suppurative thyroiditis, and thyroiditis caused by radiation/trauma. This activity reviews the presentation of De Quervain thyroiditis and highlights the role of the interprofessional team in its treatment.
- Describe the presentation of De Quervain thyroiditis.
- Review the evaluation of a patient suspected of De Quervain thyroiditis.
- Summarize the treatment for De Quervain thyroiditis.
- Outline the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by De Quervain thyroiditis.
In general, thyroiditis is defined as an inflammation of the thyroid gland. There are several kinds of thyroiditis, and they can be associated with either increased, decreased, or normal thyroid function. Furthermore, they can be classified as painful or painless, depending on the etiology. Differentiating between the different kinds is dependent on the clinical setting, medical and family history, how fast the symptoms progressed, and most importantly, the presence or absence of neck pain.
Typically, painful thyroiditis is caused by radiation, trauma, or infection, while painless thyroiditis is caused by autoimmune diseases or medications. Painful thyroiditis can be further divided into subacute granulomatous (de Quervain) thyroiditis, suppurative thyroiditis, and thyroiditis caused by radiation/trauma.
Painless thyroiditis can be subdivided into Hashimoto thyroiditis, postpartum thyroiditis, subacute lymphocytic thyroiditis, drug-induced (amiodarone, interferon-alpha, interleukin 2, lithium) thyroiditis, and Riedel (fibrosis) thyroiditis.
This article will focus on subacute granulomatous thyroiditis, also known as subacute thyroiditis, painful thyroiditis, subacute nonsuppurative thyroiditis, giant cell thyroiditis, or de Quervain thyroiditis. It is an infrequent cause of hyperthyroidism. The common symptoms are neck pain or discomfort, tenderness to palpation, and a predictable course of hyperthyroidism followed by euthyroidism, hypothyroidism, and back to euthyroidism.
Viral infections are presumed as a cause of subacute thyroiditis. Many patients may have a history of viral upper respiratory infection 2 to 8 weeks before developing thyroiditis. De Quervain thyroiditis is the most common cause of thyroid/neck pain. Some studies have suggested that the seasonal distribution of thyroiditis coincides with the peak incidences of coxsackievirus (groups A & B) and echovirus infections. It is also associated with mumps, measles, influenza, SARS-CoV-2, and other viruses.
Autoimmunity is not significant in subacute thyroiditis, unlike other thyroiditis, but it is commonly associated with human leukocyte antigen (HLA)- B35. The follicular thyroid cells share some structural similarities with viral antigens. Viral antigens or viral-host tissue damage particles bind to HLA - B 35; these complexes activate cytotoxic T cells, thus also damaging thyroid follicular cells.
The best available epidemiologic data on the incidence of subacute thyroiditis is from a study conducted by Fatourechi V et al. in Olmstead County, Minnesota, USA, during the period from 1960 to 1997. The overall age and sex-adjusted incidence of subacute thyroiditis during this period were 4.9 cases per 100,000/year. The most common symptom was pain (96%); even though most patients achieved complete resolution and a euthyroid state, about 15% of patients required continuous thyroid replacement therapy during long-term follow-up, and 1.6 to 4% of patients developed recurrence subacute thyroiditis after the initial episode.
This disease affects women almost 4 to 5 times as often as men and typically occurs between 25 to 35 years. With increasing age, the incidence of subacute thyroiditis decreases. The prevalence of subacute thyroiditis appears to be seasonal, as most cases occur in the summer and fall.
Thyroiditis causes damage to thyroid follicular cells, resulting in no new thyroid hormone production and excessive release of large amounts of triiodothyronine(T3) and thyroxine(T4). These excess hormones contribute to clinical and biochemical hyperthyroidism and inhibition of TSH (negative feedback). With the release of the stored thyroid hormone and the absence of new thyroid hormone production, the phase of hyperthyroidism can last only for 2 to 8 weeks. During this early inflammatory state, the thyroid gland is mildly enlarged and is tender to palpate.
After the inflammation is subsided, new thyroid follicular cells are generated and resume thyroid hormone synthesis. This whole process may take 2 to 8 weeks, during which time the patient goes through a short phase of euthyroidism and hypothyroidism before returning to normal thyroid function.
Hyperthyroidism in subacute thyroiditis is usually mild and transient, but it can rarely cause ventricular tachycardia and even thyroid storm.
In subacute thyroiditis, the predominant inflammatory cells are lymphocytes with a unique type of follicular disruption with predominant histiocytes surrounding colloid masses, producing giant cells. Interestingly, even though the entire thyroid gland is tender on gross examination, histologic examinations show patchy changes with varying stages of the disease. In the early phase, follicular cells are disrupted and are replaced with microabscesses and neutrophils. The classic granulomatous changes appear a little later in the disease with a large aggregation of lymphocytes, plasma cells, and large histiocytes in the damaged thyroid follicles. Multinucleated giant cells surround the fragments of colloid, and sometimes colloid can also be seen in the giant cells. In the late stages, there are many lymphocytic infiltrates and fibrosis. Rarely different histologic stages can be found in the same gland suggesting the confluence nature of destruction.
Subacute thyroiditis has both granulomatous and non-granulomatous patchy lesions under electron microscope examination. The predominant finding seen in granulomatous lesions is loss of honeycomb cellular architecture of follicular cells with decreased or shortened size of follicular cell microvilli with predominant giant cells. In the non-granulomatous lesions, the follicular basement membrane is disrupted and is replaced with T lymphocytes, monocytes, and histiocytes.
History and Physical
It is essential to elicit from the patient the timing and duration of any symptoms, any sick contacts, any family or medical history pertinent to the patient's chief complaint, and any recent upper respiratory illness the patient has experienced. Family members may be a good source of information to help narrow down a differential if the patient's mental status is altered or confused for some other reason. Pain is the most common complaint, and it can radiate to the jaw, upper chest, neck, and throat. It can be exacerbated by turning the head, coughing, and swallowing. Fever, malaise, body pains, fatigue, and anorexia are frequently associated with subacute thyroiditis. Patients can also have symptoms of hyperthyroidism like tachycardia, sweating, restlessness, and weight loss, but neck pain is the chief complaint.
A thorough physical exam should include a full HEENT (head, eyes, ears, nose, and throat) exam to rule out any other causes of neck pain. On examination, the thyroid gland is slightly enlarged and always tender to palpate. In most cases, both the thyroid lobes are involved initially; rarely, it can be unilateral, start on one side, and migrate to the side, called "creeping thyroiditis."
The diagnosis is based on history, clinical context, physical findings, and laboratory testing. Standard tests in the emergency department are thyroid studies (including free thyroxine (T4), T3 and thyroid-stimulating hormone levels (TSH), erythrocyte sedimentation rate (ESR), and C-reactive protein along with other tests as needed based on patient presentation. All patients have laboratory evidence of hyperthyroidism-mildly elevated serum free T4 and T3 and low TSH concentrations during the early stages of illness. This hyperthyroidism is transient and lasts for 2 to 8 weeks, followed by a period of transient, asymptomatic, or sometimes subclinical hypothyroidism. The interpretation of labs should be based on detailed history and examination findings.
Patients with de Quervain thyroiditis will often have elevated ESR (50-100) and CRP levels, along with elevated thyroglobulin concentrations, anemia, and mild leukocytosis. Liver function tests can be abnormal during the initial hyperthyroid phase and return to normal after 2 to 3 months. Levels of antithyroid peroxidase and antithyroglobulin antibodies are generally undetectable or low normal. Because patients often present with a fever, a septic workup is usually done. EKG should be performed in the presence of tachycardia. Patients with this disease go through different phases over weeks to months. Initially, they will be hyperthyroid and then transition to a brief euthyroid phase, followed by a hypothyroid phase, before eventually returning to being euthyroid. Hyperthyroidism, in this case, is caused by the follicular cells being attacked by cytotoxic T lymphocytes, which causes the release of large amounts of T4 and T3 into the circulation. Patients will remain hyperthyroid for weeks until their thyroid stores are diminished. Laboratory values during this period will likely reflect accordingly, with low TSH levels and elevated free T4.
The hyperthyroidism found in de Quervain can be differentiated from Graves disease by the lack of exophthalmos and pretibial myxedema. It also has a mild elevation of serum T3 and normal thyroid vascularity on ultrasonography. In the hypothyroid phase, TSH levels are elevated, and free T4 is low. During the transition period from hyper to hypothyroidism, low TSH and T4 levels can be found; this finding can lead to the mistaken diagnosis of central hypothyroidism.
The thyroid gland might be slightly enlarged or normal with a diffuse or focal hypoechogenic appearance on ultrasonography. The presence of ill-defined hypoechoic thyroid lesions without a round or oval shape is diagnostic for subacute thyroiditis in the proper clinical setting. Color Doppler sonography shows decreased flow during the hyperthyroid phase in subacute thyroiditis, compared with Graves' disease's increased flow. Radioiodine or technetium imaging during the initial hyperthyroid state may show decreased uptake.
Subacute thyroiditis is a clinical diagnosis. Neck pain with tender thyroid gland on the exam is sufficient enough to establish the diagnosis. Signs and symptoms of hyperthyroidism may be present or not. The diagnosis is confirmed with low TSH, elevated free T4, T3, ESR, C-reactive protein, and low radioiodine uptake. Radioiodine imaging can be deferred in a mild hyperthyroid state from subacute thyroiditis. Thyroid ultrasonography can help identify cysts, abscesses, or mass lesions in patients with less apparent clinical presentation and examination findings. Doppler sonography can help distinguish from Graves' disease; rarely, needle aspiration is required to distinguish from lymphoma, thyroid cancer, and hemorrhage.
Treatment / Management
The goals of subacute thyroiditis treatment are pain relief and symptom control. Treatment recommendations are based on observational data and expert opinion. Unfortunately, no clinical trials assessed optimal treatment for subacute thyroiditis.
Treatment for de Quervain thyroiditis is pretty straightforward, with anti-inflammatory treatment being the key. Patients with mild to moderate pain are generally treated with rest and salicylic acid 600 mg orally every 6 hours, naproxen 500 to 1000 mg twice a day, or ibuprofen 400 to 800 mg orally every 8 hours. For more severe neck pain, oral corticosteroids (Prednisone) can be started with 40 mg daily. Usually, symptoms improve in 2 to 3 days with NSAIDS; prednisone should be initiated if no improvement is noted. Steroids should provide pain relief in 1 to 2 days. The typical steroid course can be two months, occasionally longer. The persistence of pain beyond two days should need a further workup for other causes of neck pain. Once pain is improved, an attempt should be made to use the lowest possible dose, and dosing can be titrated by decreasing 5 to 10 mg every week. Recurrent pain should require up-titration of prednisone dose. Unfortunately, prednisone has no role in preventing thyroid dysfunction.
Mild and transient symptoms of hyperthyroidism do not require any treatment. Palpitations, anxiety, and tremors need to be treated with propranolol or atenolol with close follow-up. Thionamides should not be used to treat hyperthyroidism of subacute thyroiditis, such as radioiodine therapy, because the disorder is caused by the release of preformed thyroid hormone from destroyed follicles instead of the synthesis of new T3 and T4.
Subacute thyroiditis usually resolves, and patients return to a normal euthyroid state in 3 or 4 months. Rarely do patients have hypothyroidism which can be transient or permanent. Patients with hypothyroidism with TSH greater than 10 microU/L or having symptoms of hypothyroidism need levothyroxine treatment for 1 to 2 months. Levothyroxine should be discontinued, and thyroid function tests should be done in 1 month to ensure hypothyroidism is transient. Some patients may need treatment with levothyroxine for a long time.
After sub-acute thyroiditis is diagnosed, serial thyroid function tests should be done every 2 to 8 weeks to confirm the improvement of hyperthyroidism and follow the natural course of disease till they are normalized.
The principal differential diagnosis for de Quervain thyroiditis is acute infectious thyroiditis and hemorrhagic thyroid nodule. Thyroid function tests are usually normal. Infectious thyroiditis is associated with leukocytosis, and a thyroid ultrasonogram might show an abscess—needle aspiration show neutrophil predominant fluid in infectious thyroiditis and blood in a hemorrhagic thyroid nodule.
The other differential diagnosis for subacute thyroiditis is painless thyroiditis, postpartum thyroiditis, amiodarone (Iodine) induced thyroiditis, checkpoint inhibitor-induced thyroiditis, radiation thyroiditis, and palpation thyroiditis. Urine iodine levels are < 500 mcg/L in subacute thyroiditis compared to amiodarone-induced thyroiditis. Thyroid cancer, lymphoma, and painful Hashimoto thyroiditis are other differential diagnoses to consider in less classic presentations of subacute thyroiditis.
There have been cases where patients present with a fever of unknown origin, and the workup only reveals subacute thyroiditis.
De Quervain thyroiditis is generally self-limited, with patients returning to a euthyroid state within a few months. Recurrence is uncommon but can occur in up to 2% of patients. Hypothyroidism may also become permanent in 5% of cases.
Most of the time, subacute thyroiditis resolves completely, and rarely it can cause permanent hypothyroidism. Some patients may have severe symptoms from hypothyroidism, but usually, it is transient. Rarely subacute thyroiditis has been known to cause thyroid storm, ventricular tachycardia, and fever of unknown origin.
In moderate to severe cases, inpatient admission should be considered, depending on clinical and patient presentation, and may even require endocrinologist evaluation.
Deterrence and Patient Education
Patients can be advised that their condition will likely last a few weeks, barring any complications, and to follow up with their primary care provider as soon as possible for continued monitoring of TSH levels and radioactive iodine uptake (RAIU) testing.
Enhancing Healthcare Team Outcomes
The majority of patients with De Quervain thyroiditis will present to the primary care provider and nurse practitioner. Unfortunately, the diagnosis is not always straightforward, and a consult from an endocrinologist is recommended. If the patient is pregnant, then a consult from an obstetrician is recommended. Most patients can be treated with NSAIDs, and recovery occurs within 2 to 12 weeks. Serial thyroid levels are necessary because some patients may be rendered hypothyroid. Recurrence is known to occur in about 2% of patients. The condition is benign and does not reduce life expectancy.