CLINICAL REVIEW Silent Thyroiditis Roland Sakiyama, MD Los Angeles, California Silent thyroiditis is an increasingly recognized cause of transient thyrotoxicosis. Inflammatory destruction of thyroid follicles results in release of preformed thyroxine and triiodothyronine. Patients present with symptoms of thyrotoxicosis, but unlike subacute thyroiditis, lack thyroid pain or ten­ derness. The thyrotoxic state spontaneously resolves in 2 to 12 weeks at which time the patient either returns to a euthyroid state or passes through a transient hypothyroid phase. Diagnostic laboratory findings include eleva­ tions of thyroxine and triiodothyronine and a markedly depressed radioactive iodine uptake. It is imperative for the primary care physician to distinguish silent thyroiditis from chronic causes of hyperthyroidism, eg, Graves' dis­ ease, since treatment must be palliative rather than definitive. Long-term prognosis is usually excellent. ver the past decade a newly recognized subacute majority of cases of hyperthyroidism. Silent thyroiditis O thyroid disorder has emerged as an important now accounts for upwards of 20 to 30 percent of newly cause of thyrotoxicosis. First described in 1975 by diagnosed cases of thyrotoxicosis.2'6 While growing Gluck et al,1 this disease, like classical subacute physician awareness may account for part of the in­ thyroiditis, is characterized by inflammation and dis­ creased incidence, this silent form of subacute thy­ ruption of normal thyroid architecture resulting in the roiditis appears to be occurring with increased fre­ release of preformed stores of thyroid hormone. Un­ quency.2 like subacute thyroiditis, however, patients lack Silent thyroiditis afflicts women more commonly thyroid pain or tenderness. This subacute form of than men in an approximately 2:1 to 3:1 ratio. The thyroid disease has been referred to by a variety of majority of patients are between 20 and 40 years of terms. Although lymphocytic thyroiditis with spontane­ age, although the range is from the first to the ninth ously resolving hyperthyroidism remains the most decade.2 The clinician needs to be aware of the fre­ accurate descriptive term, “silent” and “painless” quent occurrence of silent thyroiditis during the thyroiditis reflect the absence of thyroid pain and sub­ postpartum period. Thyroid dysfunction has been sequently have gained popularity. Recognition and found in 5.5 percent of postpartum women.6 Of those proper management of this newly described disorder are affected, transient thyrotoxicosis alone was found in critical, since its transient nature renders traditional 50 percent. The remaining patients were equally di­ means of treatment ineffective and potentially harm­ vided into having transient thyrotoxicosis followed by ful. transient hypothyroidism and transient hypothyroid­ ism alone. Of those patients found to have silent thyroiditis, 10 percent are postpartum women.7 INCIDENCE Until a decade ago chronic thyroid disease, such as PATHOGENESIS Graves’ disease (toxic diffuse goiter), toxic multinodu­ lar goiter, and toxic adenoma, accounted for the vast Fundamental to the pathogenesis of the thyrotoxic state in both silent and subacute thyroiditis is destruc­ tion of follicular epithelium and loss of integrity of the storage follicle. In this first phase of silent thyroiditis, Submitted, revised, June 27, 1986. free triiodothyronine (T3) and free thyroxine (T4) are From the Department of Medicine, School of Medicine, University of Cali­ released, producing the clinical manifestations of fornia, Los Angeles, Los Angeles, California. Requests for reprints should thyrotoxicosis (Figure 1). Suppressed thyroid-stimu­ f>o addressed to Dr. Roland Sakiyama, Department of Medicine, Division of Family Medicine, UCLA School of Medicine, CHS, BH-134, Los lating hormone (TSH) secretion from high levels of cir­ Angeles, CA 90024. culating T4 and T:i and destruction of follicular epithe- ® 1986 Appleton-Century-Crofts THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 4: 367-369, 1986 367 SILENT THYROIDITIS I n in m TABLE 1. DIFFERENTIAL DIAGNOSIS OF i i THYROTOXICOSIS ACCORDING TO RADIOACTIVE I IODINE UPTAKE (RAIU) \ 1 1 H yperthyroid \ I \ j fO 1 ' 1 - N 1 1 Low RAIU "D i i l ! / 1 1. Silent thyroiditis sr N 1 I 2. Subacute thyroiditis I ___ / | 3. Graves’ disease with iodine excess I l i H y p o t h y r o i d 4. Iodine-induced hyperthyroidism I 1 1 __|_ 1 1 (Jod-Basedow) T i m e — > 5. Factitious hyperthyroidism 6. Struma ovarii PHASE I II I I I IV 7. Metastatic thyroid cancer T4 a n d T 3 H ig h N o rm a l Low N o rm a l High RAIU R A IU Low Low Normal-high Normal-high 1. Graves' disease TSH Low Low Normal-high Normal-high 2. Toxic multinodular goiter 3. Toxic adenoma Figure 1. Four phases of silent thyroiditis 4. Pituitary tumor secreting thyroid-stimulating hormone 5. Trophoblastic tumor lium lead to suppression of iodine uptake, that is, low radioactive iodine uptake. As follicular stores of pre­ formed hormone are depleted, serum levels of T4 and symptoms typically seen in chronic thyroid diseases T3 normalize (phase 2), although 25 to 40 percent of such as Graves’ disease, onset of symptoms in silent patients transiently fall into a hypothyroid range thyroiditis is often sudden and can be pinpointed in (phase 3).8 During this stage, suppression of TSH secre­ time by the patient. The hallmark finding of pain or tion is released, with serum TSH rising often to ele­ tenderness of the thyroid seen in subacute thyroiditis vated levels. Radioactive iodine uptake returns to is absent in silent thyroiditis. Furthermore, patients normal or supranormal values. Thyroid hormone syn­ with silent thyroiditis lack associated symptoms of thesis is now stimulated by TSH and the increased malaise, myalgia, fatigue, and fever commonly seen in iodine uptake, returning the patient to a euthyroid subacute thyroiditis. Patients may present with the state (phase 4). typical eye stare and lid lag indicative of increased While both silent and subacute thyroiditis are man­ sympathetic tone from any cause of hyperthyroidism; ifest by similar alterations in thyroid hormone concen­ however, signs of infiltrative opthalmopathy (limita­ tration, they differ in a number of important ways. tion of extraocular movements and proptosis) and pre- Subacute thyroiditis is thought to have a viral origin tibial myxedema characteristic of Graves’ disease are and is associated with prodromal symptoms of myal­ rarely seen in silent thyroiditis. Examination may re­ gia, malaise, and fatigue. Histologically, subacute thy­ veal signs of thyrotoxicosis including a resting roiditis is found to have acute inflammatory changes tachycardia, warm, moist skin, fine tremor, and a with polymorphonuclear leukocytes, giant cells, and quickened Achilles-tendon relaxation time. In approx­ granulomas. The thyroid gland of patients with silent imately one half the patients, the thyroid is enlarged thyroiditis demonstrates distinctly different histologic and often firm, while the remainder lack a goiter.2’8'10 features characterized by diffuse or focal lymphocytic There are no historical or physical findings that are infiltration, scant fibrosis, and absence of giant cells diagnostic of silent thyroiditis. In the absence of infil­ and granulomas.2'7-9 Histologically, this state is remin­ trative opthalmopathy, it is virtually impossible to dis­ iscent of chronic lymphocytic (Hashimoto’s) thyroid­ tinguish between thyrotoxicosis caused by silent itis, an autoimmune disease of the thyroid. Whether thyroiditis and Graves’ disease. Proper diagnosis re­ silent thyroiditis is a variant of subacute thyroiditis quires appropriate use of laboratory aids. based on a parallel clinical presentation, a variant of Hashimoto’s thyroiditis based on its histologic find­ ings, or a newly recognized disease is still debated. LABORATORY EVALUATION The clinical suspicion of hyperthyroidism can be CLINICAL PRESENTATION readily confirmed by measurements of serum concen­ trations of T4 and T;,. A T /F, ratio of less than 20:1 Patients typically present during the initial stage of suggests the diagnosis of silent thyroiditis rather than thyroiditis with overt symptoms of thyrotoxicosis— uncomplicated Graves’ disease.11 The critical diag­ nervousness, palpitations, tremor, heat intolerance, nostic study is measurement of radioactive iodine up­ and weight loss. Contrary to the insidious onset of take (RAIU). During the initial thyrotoxic stage of si- 368 THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 4, 1986 SILENT THYROIDITIS lent thyroiditis, the RAIU is suppressed to values of PROGNOSIS less than 3 percent. The causes of thyrotoxicosis can be separated into two groups based on either a low or As previously stated, recurrent episodes of silent high RAIU reading (Table 1). Other causes of thyro­ thyroiditis occur in approximately 10 percent of pa­ toxicosis associated with suppressed RAIU can usu­ tients. In contrast, recurrent episodes of subacute thy­ ally be distinguished from silent thyroiditis based on roiditis are rare. Additionally, patients with silent thy­ historical or physical findings. Patients with thyrotoxi­ roiditis often have a persistent goiter and a positive cosis factitia often present a difficult diagnostic chal­ titer of antithyroid antibodies.15 Permanent hypothy­ lenge. Presence of a low level of serum thyroglobulin is roidism is a definite although uncommon sequela of an important diagnostic clue.12 silent thyroiditis. Subclinical hypothyroidism, how­ Additional laboratory studies