Inflammatory diseases, taken together, are the most common thyroid disorder encountered in clinical practice.Though many of these patients are seen initially by internists or endocrinologists, some come to the office of the otolaryngologist with complaints of neck pain, odynophagia, sore throat, neck mass, or even dyspnea.
There are classified according to rapidity of onset, duration of symptoms, severity of symptoms, and histologic findings.
In 1969, Werner proposed a classification scheme which distinguishes between acute and chronic thyroiditis. Acute thyroiditis included suppurative and nonsuppurative varieties, and chronic thyroiditis included invasive, nonsuppurative, and lymphocytic varieties. Since that time, two varieties of subacute inflammation have been defined, and the term chronic nonsuppurative thyroiditis has fallen out of favor because it encompasses several uncommon infectious and infiltrative processes such as tuberculosis, syphilis, actinomycosis, sarcoidosis and amyloidosis.
Singer put forward a scheme which reflects the current understanding of this disorder. His scheme incorporates the broad categories of acute, subacute, and chronic thyroiditis. Subacute disease included granulomatous (or DeQuervains thyroiditis) and lymphocytic thyroiditis. The chronic group included lymphocytic (Hashimotos thyroiditis) and invasive fibrous (Riedels) thyroiditis.
Acute thyroiditis is also known as pyogenic or suppurative thyroiditis, or may be abbreviated with the acronym AST for acute suppurative thyroiditis. It presents with anterior neck pain which may be referred to the mandible or ear.
Pharyngitis, sore throat or dysphonia may also be present. The patient will often hold the head immobile and flex the neck. The gland is tender and warm. This process is usually unilateral.
The majority of cases are Gram-positive bacterial infections. AST affects young adult men and women. Often there is a history of prior or coexisting thyroid disease. The most common agents are Staph and Strep species followed by fungi and parasites. The thyroid is generally resistant to infection because of its rich vascular supply, protective capsule and high iodine content. Typically there is some predisposing condition such astrauma, sepsis, or local soft tissue infection which allows the organisms access to the gland.
laboratory findings include a leukocytosis with a left shift and in elevated ESR. These patient are usually euthyroid and have no thyroid autoantibodies. Therapy for acute thyroiditis involves local heat and intravenous antibiotics. If abscesses form, they are drained surgically and cultured.
The presence of a pyriform sinus fistula must considered in children with recurrent AST. Barium swallow two months after the acute phase can identify the tract, which was on the left, ipsilateral to the abscess, in 36 of 38 cases described by Szabo and Allen. This structural defect which leaves a residual passage from the pyriform sinus to the thyroid is thought to be a 4th pharyngeal pouch remnant. Treatment involves complete excision of the fistula.
Subacute Granulomatous Thyroiditis or SAGT, is also known as DeQuervains disease. This form of thyroiditis is seasonal, more common in middle-aged women, and associated with viral upper respiratory infections.
Adenovirus, Coxsackievirus, Influenzae, Epstein-Barr virus, mumps, echovirus and enteroviruses have been implicated. They represent both RNA and DNA viruses. Tomer and Davies reviewed a group of studies which showed that both thyroiditis and autoantibodies to thyroid antigens could be induced by viral infections in mice, rats and chickens. SAGT is preceded by a viral prodrome of myalgias, fever, lassitude, sore throat and dysphagia after which the patients develop a painful, tender gland. Over half the patient will have symptomatic hyperthyroidism secondary to release of colloid from the diseased gland. SAGT is the most common cause of a painful anterior neck mass according to Singer.
Laboratory tests reveal normal white cell count or mild leukocytosis with mild anemia. The estimated erythrocyte sedimentation rate is greatly elevated. The thyroid function tests are elevated with T4 greater than T3, reflecting the intrathyroidal concentrations. Fifty percent of patient will have transient antibodies to thyroglobulin and thyroid peroxidase, probably due to T-call sensitization to antigen released during inflammation.
The FNA or other biopsy will reveal a mixed inflammatory infiltrate with foreign body giant cells and follicular disruption. One may seen granulomas with central liquefactive necrosis surrounded by histiocytes and macrophages and giant cells with multiple nuclei. Lower power light microscopy shows follicular disruption with an inflammatory infiltrate.
Patients with SAGT classically pass through four states: a 3 to 6 week hyperthyroid phase with increased circulating T4 due to release of colloid, and decreased TSH due to feedback inhibition; then a week or two of euthyroidism as they pass into a hypothyroid state before returning to a euthyroid state. The hypothyroid state results from depleted glandular stores as the circulating T4 is cleared. This phase lasts from 2 to 7 weeks with return to a euthyroid state as the patient recovers. Mild cases may never become hypothyroid, while 5% of cases will remain permanently hypothyroid.
Treatment includes patient reassurance and symptomatic case. A typical dose of propranolol would be 40 mg tid to qid. The recommended course of prednisone is 20 to 40 mg per day tapered over 2 to 4 weeks.
The third form of inflammatory thyroid disease is Subacute lymphocytic thyroiditis which is also known as silent or painless thyroiditis and occurs in sporadic and postpartum forms. This form generally occurs in middle aged women. It accounts for up to half of the thyroiditis and a quarter of the hyperthyroidism in North America. SALT presents with symptoms of thyrotoxicosis and a near normal neck exam. Patients with SALT complain of weight loss, anorexia, heat intolerance and sweating; on examination they exhibit tachycardia and tremor.
Graves disease is an autoimmune stimulation of the thyroid gland via the TSH receptor. It also presents with thyrotoxicosis and must be distinguished from SALT. Patients with Graves disease report a gradual onset of symptoms and may have proptosis. They have an increased uptake of radioactive iodine by scintiscan. One can also demonstrate circulating antibodies to the TSH receptor in these patients.
The postpartum variety of SALT troubles 4% to 6% of new mothers. A predilection to this disorder is inherited with the HLA-DR4 antigen. Eighty percent of these patients have antibodies to thyroid peroxidase, formerly called the antimicrosomal antibody.
Laboratory and imaging tests reveal a low RAIU. This is the fraction of ingested I-131 or I-123 concentrated in the thyroid at 4 and 24 hours postinfusion. This shows that although the circulating T$ may be high, the gland cannot trap organic iodine. In the absence of ophthalmopathy, this is the most reliable way to distinguish SALT from Graves disease.
Therapy for SALT is mostly symptomatic care. These are mixed reports about the efficacy of steroids in this disease. Six percent of these patient will suffer permanent hypothyroidism according to Hamburgers 1981 article.
The fourth form of thyroiditis is Chronic Lymphocytic Thyroiditis, first described by Dr. Hashimoto of the University of Kiushiu in 1912. It is also known as autoimmune or chronic lymphadenoid thyroiditis or struma lymphomatosa. The inflammation is thought to spring from a T-cell attack on the thyroid with secondary production of antibodies to thyroid antigens producing gradual destruction and hypothyroidism.
CLT is the most common inflammatory thyroid disease afflicting up to 2% of women. There is a strong hereditary component associated with 2 HLA antigens. CLT is associated with a family of autoimmune diseases. Volpe et al demonstrated the autoimmune nature of CLT by xenografting thyroid tissue from patients with CLT into athymic "nude" mice and SCID mice. The athymic mice accepted the grafted tissue but lysed the passenger lymphocytes - this halted the destruction of the gland, whereas the severe combined immune deficiency mice accepted the graft and its lymphocytes, and this allowed the continued destruction of the gland.
Patients with Hashimotos thyroiditis complain of fatigue or mild pressure in the neck. Palpating the neck reveals smooth enlargement of the entire gland which may be bosselated. At presentation, most patients with CLT are euthyroid. Twenty percent are hypothyroid and 5% are hyperthyroid, which has been termed "Hashitoxicosis." Gross thyroid specimens from patient with CLT are firm and holden or flesh-colored like a lymph node. Light microscopy demonstrated a lymphocytic infiltrate and atrophic acini lined by endothelium which exhibits Hürthle cell changes such as abundant eosinophilic cytoplasm. FNA smears may reveal clusters of Hürthle cells within the lymphocytic infiltrate.
The association of CLT with thyroid carcinoma has been widely reported, but there is little agreement about its incidence, with estimates ranging from 1% to 23%. Because of the risk of carcinoma in patients with CLT, Walker and Palyoyan list the following indications for thyroidectomy. Patients with CLT who have a solitary cold nodule, suspicious FNA findings or a history of neck irradiation may require removal of the gland, as well as those whose nodules do not regress on TSH therapy. Excluding these indications, the therapy for CLT is observation and hormone supplementation as needed.
The fifth form of thyroiditis is Invasive fibrous thyroiditis. Described by Bernhard Riedel in 1883, it is the rarest form of thyroiditis. Other names for this disease are chronic fibrous thyroiditis and ligneous thyroiditis, which denotes the woody hardness of the gland. Patients are usually under age 50 and there is a female predominance. Thirty to 40% of cases are associated with other sclerosing syndromes.
Patients with Invasive Fibrous Thyroiditis report weeks to years of painless anterior neck enlargement with gradually increasing pressure leading to hoarseness, dysphagia and even dyspnea. There is a firm, fixed gland on neck examination. Because of the density of fibrosis, FNA biopsy is nearly impossible and excisional biopsy is often needed to rule out carcinoma All but the most advanced cases are euthyroid. Mild elevations of the sedimentation rate and white count are seen, and half of the patients have autoantibodies to TPO. Microscopic exam of tissue in IFT shows extensive fibrosis and replacement of acini with connective tissue. Massons trichrome stain renders the collagenous areas blue-green contrasting them with the atrophic acini. Therapy for IFT includes a trial of high dose steroids which may slow the fibrosis, followed by surgery for patients with obstructive symptoms or for biopsy. Singer recommends a wide resection of the isthmus in patients with compressive symptoms. complete resection may be ill-advised due to the obliteration of surgical landmarks by fibrosis. Girod recommends low dose radiation therapy for recurrent disease or unresectable cases such as those with extension into the mediastinum.
In summary, AST and SAGT have infectious etiologies; SALT and CLT are autoimmune disorders, and IFT is thought to be a connective tissue disorder. AST and SAGT may present with neck pain, while the other forms are generally painless. An abrupt onset of symptoms suggests AST or SAGT, or occasionally SALT. Radioactive iodine uptake is less than 5% in SAGT and SALT and variable in the other forms. FNA may be useful in subacute and chronic thyroiditis.