Thyroiditis

Acute suppurative thyroiditis is rare in childhood because the thyroid is remarkably resistant to hematogenously spread infection. Most cases of acute thyroiditis involve the left lobe of the thyroid and are associated with a developmental abnormality of thyroid migration and the persistence of a pyriform sinus from the pharynx to the thyroid capsule. The usual organisms responsible include Staphylococcus aureus, Streptococcus hemolyticus, and pneumococcus. Other aerobic or anaerobic bacteria may also be involved.

Subacute thyroiditis is generally thought to be due to viral processes and usually follows a prodromal viral illness. Various viral illnesses may precede the disease, including mumps, measles, influenza, infectious mononucleosis, adenoviral or Coxsackievirus infections, myocarditis, or the common cold. Other illnesses or situations associated with subacute thyroiditis include catscratch fever, sarcoidosis, Q fever, malaria, emotional crisis, or dental work. The disease is more common in individuals with human leukocyte antigen (HLA)–Bw35.

Because chronic thyroiditis in children is usually due to an autoimmune process, it is HLA-associated, similar to other autoimmune endocrine diseases. The specific alleles in the atrophic and goitrous forms of the disease vary. The histologic disease picture varies, but lymphocytic thyroid infiltration is the hallmark of the disease and frequently obliterates much of the normal thyroid tissue. Follicular thyroid cells may be small or hyperplastic. The degree of fibrosis among patients also widely varies. Children usually have hyperplasia with minimal fibrosis. The blood contains autoantibodies to thyroid peroxidase and, frequently, autoantibodies to thyroglobulin. Autoimmune thyroiditis is also frequently part of the polyglandular autoimmune syndromes.

Covid-19

A case study by Brancatella et al suggested that in some patients, subacute thyroiditis may arise from coronavirus disease 2019 (COVID-19). The report involved a woman aged 18 years who was found to have no thyroid disease before then testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About three weeks later, she tested negative for the virus, but, a few days after that, presented with symptoms of subacute thyroiditis, which was subsequently diagnosed. The timing of the thyroiditis, the investigators believe, points to a COVID-19 origin, particularly in light of the fact that subacute thyroiditis is commonly thought to develop in response to viral infection or a postviral inflammatory reaction in persons with a genetic predisposition.[1, 2]  

Additional research has continued to point to the development of a condition resembling subacute thyroiditis in persons with COVID-19. This includes an Italian study that found that among 85 patients with COVID-19 admitted to high-intensity-care units (HICUs), up to 13 (15%) were thyrotoxic, compared with just 1% of HICU patients from pre-pandemic 2019 who were studied in the report.[3, 4]  However subacute thyroiditis following COVID-19 has not been reported in the pediatric age group, with the youngest reported case being age 18 years.[1, 5]

Further investigation indicates that subacute thyroiditis may persist months later in patients in whom the thyroid gland becomes inflamed during acute COVID-19 illness, even after normalization of thyroid function. In addition, the effects of SARS-CoV-2 on thyroid function appear to be multifactorial, with the thyroiditis being atypical in that no neck pain seems to be involved and more men than women appear to be affected. In addition, patients who were examined exhibited low TSH and free triiodothyronine (T3) levels, while free T4 levels were normal or elevated.[6]

There may also be an association between COVID-19 vaccination and the development of subacute thyroiditis, including with regard to mRNA and non-mRNA vaccines. However, a study by Ippolito et al indicates that the subacute thyroiditis cases are primarily of mild to moderate severity, with the investigators stating that most of these can be treated via symptomatic therapy or a short course of steroids. Therefore, according to the report, the vaccination/thyroiditis association “should not raise any concern regarding the need to be vaccinated, since the risks of COVID-19 undoubtedly outweigh the risks of the vaccination." The study did not report any instances of subacute thyroiditis following vaccination in patients younger than 18 years.[7]

Ippolito and colleagues also mention the possibility that in persons who receive an mRNA COVID-19 vaccine, the likelihood of developing subacute thyroiditis may be greater in those who have a previous history of thyroid disease. They found that out of the 51 patients in their study who developed subacute thyroiditis, approximately 12% (all of whom had been given an mRNA vaccine) had thyroid disease history; however, they indicate that further research is needed to support this contention.[7]

Frequency

United States

Studies in the United States and Western Europe report a prevalence of 1.2% in individuals aged 11-18 years. Approximately 25% of adults with type 1 diabetes have thyroiditis, about one half of whom have hypothyroidism. Approximately 10% of children with type 1 diabetes have antithyroid antibodies. Thirteen of 121 children with vitiligo were also found to have subsequent evidence of autoimmune thyroiditis.[8]  Similarly, a Korean study, by Bae et al, indicated that persons with vitiligo have an odds ratio for the autoimmune disease Hashimoto thyroiditis of 1.609.[9]

The disease is also more common in children with Down syndrome or Turner syndrome. However, a study by Vassilatou et al indicated that the risk of autoimmune thyroiditis is not increased in psoriatic patients with or without psoriatic arthritis, finding the prevalence of autoimmune thyroiditis to be 20.2% in psoriatic patients (n = 114) and 19.6% in controls (n = 286).[10]  This contrasts with a study by Kiguradze et al, which reported an odds ratio of 2.49 for Hashimoto thyroiditis in persons with psoriasis.[11]

Acute suppurative thyroiditis is rare in Western nations. Subacute thyroiditis is rare in childhood.

International

The prevalence of chronic autoimmune thyroiditis varies depending on screening procedures. A Greek study showed a prevalence of thyroid antibodies as high as 12.5% in some areas. Few data are available regarding the incidence of the various forms of thyroiditis in the non-Western world. Acute thyroiditis is more common in geographic areas where antibiotic use is less prevalent.

Mortality/Morbidity

Long-term morbidity or mortality from thyroiditis is uncommon. Patients with autoimmune thyroiditis frequently develop hypothyroidism and require lifelong treatment. Patients with subacute thyroiditis may briefly have hyperthyroidism but usually regain normal thyroid function. Patients with acute thyroiditis generally maintain normal thyroid function.

A retrospective study by Ieni et al found that one third of patients with papillary thyroid cancer had chronic lymphocytic thyroiditis and that the thyroiditis patients tended to have more favorable characteristics with regard to their cancer. The investigators reported that in the patients with thyroiditis, tumors were smaller on average than in the other patients (9.39 mm vs 12 mm, respectively), and the lymph node metastasis rate was lower (12.5% vs 21.96%, respectively), while the tumor-node-metastasis (TNM) stage was prognostically better. The thyroiditis patients also tended to be younger.[12]

Similarly, a retrospective study by Pilli et al found that at a mean follow-up of 6.28 years, subsequent to treatment of papillary thyroid cancer with thyroidectomy and radioiodine remnant ablation, patients whose cancer was concurrent with chronic lymphocytic thyroiditis had a higher cure rate (91.8%) than did nonthyroiditis patients (76.3%).[13]

A prospective study by Zhao et al indicated that in patients with subacute thyroiditis, the early maximum thyroid-stimulating hormone (TSH) value (cutoff 7.83 mIU/L within 3 months of onset of subacute thyroiditis) predicts the development of hypothyroidism 2 years after the disease’s onset.[14]

Sex

The pediatric male-to-female ratio for autoimmune thyroiditis ranges from 1:2 to 1:6. This is low when compared with the 90% female predominance in adults.[15, 16, 17]

Acute thyroiditis

Recovery is usually complete, and thyroid function returns to normal.

Subacute thyroiditis

This self-limiting disease may last 2-7 months.

Chronic autoimmune thyroiditis

Permanent hypothyroidism is the main complication. Approximately 20% of children with subclinical hypothyroidism enter remission and become euthyroidism.[17]

Acute thyroiditis

A history of acute illness, including fever, chills, neck pain, sore throat, hoarseness, and dysphagia, is common.

Neck pain is frequently unilateral and radiates to the mandible, ears, or occiput. Neck flexion reduces the severity of the pain. The pain worsens with neck hyperextension.

Subacute thyroiditis

Neck tenderness and swelling may occur.

Occasionally, the initial symptoms are those of hyperthyroidism.

Systemic symptoms such as weakness, fatigue, malaise, and fever are usually low grade.

Chronic autoimmune thyroiditis

Chronic autoimmune thyroiditis is observed in the following 3 patterns:

• Goiter that is usually diffuse and nontender: Systemic illness is not evident. The thyroid gland is frequently 2-3 times its normal size and may be larger. The patient, parent, or physician may discover the goiter.

• Symptoms of hypothyroidism: In children, this frequently includes poor growth or short stature. Adolescent girls may have primary or secondary amenorrhea. Boys may have delayed puberty. Because the disease develops slowly, the patient or parent may not notice other signs of hypothyroidism, including constipation, lethargy, and cold intolerance. The child with diabetes may have decreasing insulin requirement.

• Symptoms of hyperthyroidism: These may include poor attention span, hyperactivity, restlessness, heat intolerance, or loose stools.

Asymptomatic thyroiditis

Asymptomatic thyroiditis with or without thyroid function abnormalities may also be discovered upon routine screening of children at high risk; these include children with Down syndrome or Turner syndrome and children with other autoimmune endocrine disorders (eg, type 1 diabetes, Addison disease, vitiligo).

Celiac disease

The prevalence of celiac disease is increased in those with autoimmune thyroid disease and comorbidities such as type 1 diabetes and Down syndrome.[18]

Acute thyroiditis

The patient may have a fever of 38-40°C.

Acute illness may be evident.

Neck tenderness is present, and the swollen thyroid gland is tender. The swelling and tenderness may be unilateral. Erythemas develop over the gland, and regional lymphadenopathy may develop as the disease progresses. Abscess formation may occur.

Subacute thyroiditis

The patient may have signs of systemic illness, such as low-grade fever and weakness.

Signs of hyperthyroidism, including increased pulse rate, widened pulse pressure, fidgeting, tremor, nervousness, tongue fasciculations, brisk reflexes (possibly with clonus), weight loss, and warm, moist skin, may be present.

The thyroid gland may be enlarged and tender, with tenderness exacerbated by neck extension.

Chronic autoimmune thyroiditis

Initially, an enlarged, lumpy, bumpy, and nontender thyroid is often present. The gland may not be enlarged, particularly in children who have profound hypothyroidism. Signs of hypothyroidism include slow growth rate; weight gain; slow pulse; cold, dry skin; coarse hair and facial features; edema; and delayed relaxation of the deep tendon reflexes.

Signs of hyperthyroidism are occasionally present early in the disease.

Acute suppurative thyroiditis is more common in poorer geographic areas where antibiotic use is less prevalent. It usually occurs in children with embryologic abnormalities such as a persistent thyroglossal duct or brachial cleft cysts.

Chronic autoimmune thyroiditis is more common in developed countries with increased iodine intake.

Children with Down syndrome or Turner syndrome and those who have type 1 diabetes or another autoimmune endocrine disease are at particular risk of chronic thyroiditis.

Acute thyroiditis

Laboratory abnormalities in acute thyroiditis reflect the acute systemic illness. Findings include leukocytosis with a left shift and an increased sedimentation rate. Thyroid function test results are within the reference range.

Subacute thyroiditis

The primary laboratory abnormalities are consistent with abnormal thyroid function. Initially, the thyroid-stimulating hormone (TSH) level is suppressed, and the free thyroxine (T4) level is increased. As the disorder progresses, transient or sometimes permanent hypothyroidism may develop.

The WBC count is usually within the reference range but may be mildly elevated. High-sensitivity C-reactive protein levels are usually elevated in subacute thyroiditis.

Chronic thyroiditis

Laboratory abnormalities reflect thyroid function abnormality and evidence of autoimmunity.

TSH levels are increased in children with subclinical and overt hypothyroidism. Free T4 levels are within the reference range in the former and low in the latter. In children with hyperthyroidism, TSH levels are suppressed. Many children have normal thyroid function and normal TSH levels.

Antithyroid peroxidase (antithyrocellular, antimicrosomal) antibody levels elevated above the reference range are the most sensitive indicator of thyroid autoimmunity. Many children also have antithyroglobulin antibodies, although this is less sensitive and less specific.

Radioactive iodine thyroid scanning

Radioactive iodine thyroid scanning is not necessary for acute suppurative thyroiditis because the results are normal and do not aid in diagnosis. A scan may be helpful after diagnosis to identify a persistent thyroglossal duct as a route for infection.

This test is also unnecessary for chronic thyroiditis because the results can be misleading and may show increased uptake consistent with Graves disease, a multinodular goiter, or a hypofunctioning or hyperfunctioning nodule.

Radioactive iodine thyroid scanning is helpful in patients with hyperthyroidism who are thought to have subacute thyroiditis, because the extremely low uptake is consistent with the thyrocellular destruction in progress.

Thyroid ultrasonography

Thyroid ultrasonography is useful in revealing abscess formation in patients with acute thyroiditis.

The degree of hypoechogenicity on ultrasonography is related to the degree of thyroid dysfunction but its clinical use in chronic thyroiditis is questionable and does not alter management in children with chronic thyroiditis.[19]

A study by Lee and Kim on the ultrasonographic characteristics and interval changes of subacute thyroiditis found a high prevalence of nodular subacute lesions, as well variable interval changes. Out of 64 patients with subacute thyroiditis, 39 had nodular lesions, with 10 patients having both nodular and nonnodular lesions. Common interval changes were classified as “disappeared,” “decreased,” and “eventually smaller.”[20]

The overall of specificity of thyroid ultrasonography to identify specific concerns is questionable. A study in Germany found thyroid ultrasonography abnormalities in 40% of a random adult population, including nodules in 35.6%.[21]

A study by Nishihara et al reported that under ultrasonographic evaluation, hypoechoic inflammatory regions in subacute thyroiditis can severely obscure coexisting papillary carcinoma. Consequently, the investigators advised that ultrasonographic reexamination be performed after a sufficient interval in patients with subacute thyroiditis.[22]

Fine-needle thyroid aspiration

This procedure is advocated by some to document the presence of thyroid lymphocytic infiltration in autoimmune thyroiditis. Histologic results are predictive of thyroid function; however, the results can be misinterpreted and can lead to unnecessary thyroid surgery.

Reserve this test for patients in whom underlying malignancy is suggested by a discrete thyroid nodule.

In patients with acute thyroiditis, needle aspiration can be used to obtain material for culture, enabling appropriate antibiotic therapy.

Acute thyroiditis

• Acute thyroiditis requires immediate parenteral antibiotic therapy before abscess formation begins. For initial antibiotic therapy, administer penicillin or ampicillin to cover gram-positive cocci and the anaerobes that are the usual causes of the disease.

• In patients who are allergic to penicillin, cephalosporins are appropriate.

• Patients with acute thyroiditis may require inpatient care to complete 10-14 days of antibiotics.

Subacute thyroiditis

• Subacute thyroiditis is self-limiting; therefore, the goals of treatment are to relieve discomfort and to control the abnormal thyroid function. The discomfort can usually be relieved with low-dose aspirin (divided every 4-6 h). In the rare cases that aspirin does not relieve the discomfort, administer prednisone for 1 week and then taper.

• Propranolol can be used to reduce signs and symptoms of hyperthyroidism.

• Low-dose levothyroxine may be necessary in some patients who develop hypothyroidism.

Chronic autoimmune thyroiditis

• Treatment for chronic autoimmune thyroiditis depends on the results of the thyroid function tests. Patients with overt hypothyroidism who have high thyroid-stimulating hormone (TSH) and low free T4 levels require treatment with levothyroxine. The dose is age dependent. TSH levels should be monitored and the dose should be adjusted to maintain levels within the reference range.

• The treatment of subclinical hypothyroidism in patients with elevated TSH and normal free T4 levels is controversial. These children may enter a remission phase and may not have permanent hypothyroidism. This appears to be a minority of subjects. One study found that 4 of 14 subjects had normalization of TSH after a follow-up of 3-12 years. Most pediatric endocrinologists recommend treatment of subclinical hypothyroidism during childhood to ensure normal growth and development. If thyroxine administration may not be permanently required, treatment may be stopped once the patient has completed pubertal development, and thyroid function then can be reassessed. Guidelines for the diagnosis and management of subclinical thyroid disease have been established.

• The use of thyroxine treatment in patients with a goiter due to autoimmune thyroiditis who have normal TSH and free T4 levels is even more controversial. Some studies have suggested that treatment may decrease gland size,[23, 24] but other studies suggest that reduction in gland size is likely only in children with initially elevated TSH levels.[17]

In acute thyroiditis, surgery may be necessary to drain the abscess and to correct the developmental abnormality responsible for the condition.

The surgical service consulted depends on the institution and the physician who has the most experience with thyroid surgery. Options include the following:

• Pediatric surgery

• Otolaryngology

• A specialized endocrine surgery service

Acute thyroiditis: Consulting with a pediatric infectious disease specialist may be useful for selecting appropriate antibiotic therapy.

Subacute and chronic thyroiditis: Consulting with a pediatric endocrinologist should be considered in treating children with these disorders. This is particularly true if the child has experienced poor growth possibly due to hypothyroidism, has symptoms of overt hyperthyroidism, or has a discrete thyroid nodule.

No dietary limitations are necessary.

Children with overt hyperthyroidism or hypothyroidism have poor exercise tolerance. These children usually limit their own activity. As treatment progresses and thyroid function levels return to normal, their exercise tolerance should increase.

Subacute thyroiditis

• This is a self-limiting disease that may last 2-7 months.

• During this time, monitor thyroid function and adjust medications as needed.

Chronic autoimmune thyroiditis

• Outpatient care involves monitoring thyroid function tests. Patients with normal thyroid function test results should be examined every 6 months to ensure that they do not develop hypothyroidism. After a year, these visits may be annual.

• Children who require thyroxine therapy should undergo thyroid function tests every 3-12 months, depending on age. More frequent testing is required in younger children. Thyroid-stimulating hormone (TSH) and free T4 levels should be checked 1 month after any change in dosage.

Class Summary

These agents are used to treat acute suppurative thyroiditis. First-line antibiotic choices to treat acute thyroiditis include parenteral penicillin or ampicillin. These drugs cover most of the gram-positive cocci and anaerobes that cause the disease.

Penicillin G (Pfizerpen)

Antibiotic with activity against gram-positive, some gram-negative, and some anaerobic bacteria. Penicillin binds to PBPs, inhibiting bacterial cell wall growth.

Ampicillin (Principen)

Penicillin antibiotic with activity against gram-positive and some gram-negative bacteria. Binds to PBPs, inhibiting bacterial cell wall growth.

Class Summary

These drugs are used to decrease discomfort in patients with subacute thyroiditis.

Aspirin (Anacin, Bayer)

Most patients respond well to aspirin as a first-line therapy. Treats mild to moderate pain. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Prednisone (Sterapred)

Used when aspirin is ineffective in controlling discomfort in patients with subacute thyroiditis. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Class Summary

Many signs and symptoms of hyperthyroidism are due to increased beta-adrenergic sensitivity. In particular, these include the hemodynamic abnormalities of tachycardia and hypertension. Beta-adrenergic blockade can reduce many of these symptoms. These agents are the DOC in treating cardiac arrhythmias that result from hyperthyroidism. These agents control cardiac and psychomotor manifestations within minutes.

Propranolol (Inderal)

Can be immediately initiated in patients with hyperthyroidism due to either subacute thyroiditis or autoimmune thyroiditis. Because of the self-limiting nature of these situations, they may be the only drugs needed.

Class Summary

These agents are used to treat hypothyroidism due to autoimmune thyroiditis. Use thyroid-stimulating hormone (TSH) levels to monitor dose and keep them within the reference range.

Levothyroxine (Levothroid, Levoxyl, Synthroid)

Levothyroxine is a synthetic form of thyroxine involved in normal growth, metabolism, and development.