SUBACUTE THYROIDITIS

SUBACUTE THYROIDITIS
Synonyms: granulomatous thyroiditis, pseudotuberculous thyroiditis, giant cell thyroiditis
Subacute de Quervain’s thyroiditis is a self-limiting disease accounting for 0.5–3% of all thyroid pathologies and lasts a few weeks to 2 months. Women are 3–6 times more affected than men. The peak incidence is between the second and fifth decade of life.
ETIOLOGY

• The etiology of subacute de Quervain’s thyroiditis remains uncertain, but evidence implicates viral infection.
• Subacute thyroiditis is an inflammatory disorder of the thyroid gland.
• Previously, this condition was termed granulomatous thyroiditis, De Quervain thyroiditis, struma granulomatosa, and pseudotuberculous thyroiditis.
• The pathologic hallmarks are granulomas and pseudo giant cells.

Evidence that suggests a viral infection includes the following:

1. A postviral cytokine-mediated inflammation of
   the thyroid is suspected because a seasonal frequency
   and an association with upper respiratory tract infection
   is noted.
2. There is no associated polymorphonuclear leukocytosis.
3. In half of the patients antibodies against mumps, measles, influenza, adenovirus, coxsackievirus, or echovirus are found.
4. The mumps virus has been cultured from thyroid tissue of patients with subacute thyroiditis.
5. The process is self-limited.
6. Furthermore, a genetic predisposition exists with the haplotype HLA-Bw35. Hashimoto disease, have a higher frequency of a certain human leukocyte antigen (HLA) haplotype (HLA-B35)7; it is possible that this HLA association may reflect a genetic susceptibility to subacute thyroiditis after various viral infections

All current evidence suggests that subacute thyroiditis is not an autoimmune disease.

• Although low levels of antithyroid antibodies may appear transiently during the course of the disorder, the levels are not of the same magnitude seen in patients with other autoimmune thyroid disorders. Subjects with subacute thyroiditis, but not those with.

CLINICAL FEATURES

• These patients characteristically present with a painful, tender goiter that is firm, with pain radiating to the ears, mandible, or occiput.
• In some patients, however, these features may be minimal or even absent.
• Cervical lymphadenopathy usually is not present, but many patients have prodromal symptoms of an upper respiratory tract infection, fever, myalgia, or arthralgia.
• Additionally, patients with subacute thyroiditis often experience a series of changes in thyroid function related to the inflammatory effects in the gland.

Early in the course, symptomatic thyrotoxicosis may arise from the leakage of thyroid hormones from damaged follicular cells.

Subsequently, patients may develop transient hypothyroidism after passing through a euthyroid phase.

The hypothyroidism results from a depletion of thyroxine (T4) and triiodothyronine (T3) from the thyroid gland after the destructive, inflammatory process.

• However, patients usually experience a spontaneous recovery of normal thyroid function.

Not all patients with subacute thyroiditis experience all phases of these alterations in thyroid function.

• The duration of the illness often is 6 weeks but may be 3 to 6 months.
• The inflammatory process may migrate from one area of the thyroid to another and often crosses between the two lobes (“creeping thyroiditis”).

The differential diagnosis encompasses acute suppurative thyroiditis. In contrast to acute suppurative thyroiditis, the gland sonographically reveals irregular hypoperfused areas instead of hyperperfused tissue. On fine-needle biopsy, the differential diagnosis further includes palpation thyroiditis, as well as other granulomatous diseases such as sarcoidosis, tuberculosis,
and rheumatoid diseases.

LABORATORY EVALUATION
Laboratory evaluation usually reveals the following:

• elevated erythrocyte sedimentation rate (often >55 mm per hour);
• normal or near-normal leukocyte count;
• transient elevations of antithyroid antibodies in low titers;
• and serum T4 and T3 values that may be high, normal, or low, depending on the phase of the disease.
• In the thyrotoxic phase, the serum thyroid-stimulating hormone (TSH) value is suppressed but may be detectable in third-generation assays in nearly 80% of those evaluated.

TSH is normal during the euthyroid phase and elevated during the hypothyroid phase. A thyroid scan during an episode of subacute thyroiditis shows a cold region in the involved section of the thyroid.

Additionally, during the thyrotoxic and euthyroid phases, the radioactive iodine (RAI) uptake is often <1%.>

• This finding is of diagnostic importance in the evaluation of patients with suspected thyrotoxicosis, as a low uptake reflects the underlying etiology of destructive thyroiditis—not increased thyroid hormone production and secretion, as in Graves disease or toxic nodular goiter (in which the uptake is normal or high).
• Further, the serum thyroglobulin is frequently markedly elevated, a finding that is of value in the differential diagnosis of thyrotoxicosis that is due to surreptitious ingestion of thyroid hormone (thyrotoxicosis factitia).
• In the latter disorder, the RAI uptake and the serum thyroglobulin are low.

Although the diagnosis of subacute thyroiditis usually is apparent in patients with typical clinical features, occasionally there is difficulty in establishing the diagnosis—such as with sudden enlargement of the thyroid gland—raising the possibility of anaplastic carcinoma.

• In this situation, a thyroid biopsy may be helpful.

The usual microscopic features include degeneration of the follicular epithelium; infiltration of the tissue with leukocytes, lymphocytes, and histiocytes; and formation of granulomas composed of giant cells surrounding colloid. In approximately one-half of patients, microabscesses may be found. In most patients with subacute thyroiditis, the diagnosis can be made clinically.

TREATMENT
The management of patients with subacute thyroiditis is based on relief of symptoms, because no specific therapy is available.

Two aspects of this therapy must be addressed in each patient:

1. the local symptoms
2. and the effects of thyroid dysfunction.

Frequently, pain and tenderness in the neck respond to treatment with salicylates, 0.65 g every 4 hours. If no benefit ensues within 48 hours, nonsteroidal antiinflammatory agents may be administered, although it is unclear whether these agents are superior to the salicylates.

• Approximately 5% of patients require cortico-steroids for the relief of symptoms.
• Prednisone in doses of 30 to 40 mg per day usually results in prompt improvement; however, it may be difficult to reduce the dose without return of pain, so that treatment for 4 to 8 weeks may be necessary before a successful tapering is accomplished.
• If the patient does not respond to prednisone within 24 to 48 hours, the diagnosis of subacute thyroiditis should be reevaluated.
• Thyroidectomy occasionally is used in patients with severe or recurrent pain that is unresponsive to other therapy, but this approach is required infrequently.
• If thyrotoxic symptoms are foremost, the patient should be managed with b-blockade (e.g., propranolol).
• The thyrotoxic phase in these patients is transient, and definitive therapy with RAI is neither indicated nor of value because the thyroid uptake is low.
• Likewise, the antithyroid drugs propyl-thiouracil or methimazole (Tapazole) should not be given because these medications are also ineffective.
• These drugs impair thyroid hormone synthesis, but the excess serum thyroid hormone levels in subacute thyroiditis result from leakage of T3 and T4 from the damaged follicles and not from enhanced synthesis and secretion.
• The hypothyroid phase of subacute thyroiditis is usually transient and is often asymptomatic; therefore, thyroid hormone replacement frequently is not necessary.
• Additionally, the increased TSH secretion at this time may be important in the recovery of thyroid gland function; consequently, there may be a relative contraindication to thyroid hormone treatment unless the patient is clearly symptomatic.
  
• The long-term prognosis for patients with subacute thyroiditis is excellent.
• Recurrent episodes, although uncommon, do occur, in as many as 2% of affected patients yearly, but eventual normal thyroid function is the rule.
• Discomfort in the thyroid area can, however, continue for many months.
• Rarely, patients with subacute thyroiditis may develop permanent hypothyroidism.
• Patients who have had prior thyroid surgery or who have coexistent autoimmune thyroiditis may be especially prone to such an outcome.