Acute and Subacute Thyroiditis

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Acute and Subacute Thyroiditis Powered By Docstoc
					                      Acute and Subacute Thyroiditis

                 Revised by John Lazarus ,M.D.1 February 2003


The diagnostic term thyroiditis includes a group of inflammatory or inflammatory-like conditions.
The terminology that has been employed is confusing, and no classification is ideal. We prefer
the following nomenclature, which takes into account the cause when known.
1. Infectious thyroiditis, also referred to as either acute or chronic, and which in fact may be
either, along with the qualifying term suppurative, nonsuppurative, or septic thyroiditis. It
includes all forms of infection, other than viral, and is caused by invasion of the thyroid by
bacteria, mycobacteria, fungi, protozoa, or flatworms. The disorder is rare.
2. DeQuervain's thyroiditis, commonly known as subacute thyroiditis but also termed
subacute nonsuppurative thyroiditis, granulomatous, pseudotuberculous, pseudo-giant cell or
giant cell thyroiditis, migratory or creeping thyroiditis, and struma granulomatosa. This
condition, most likely of viral origin, lasts for a week to a few months, with a tendency to recur.
The eponym was selected because of its uncertain cause.
3. Autoimmune thyroiditis, commonly referred to as chronic, Hashimoto's, or lymphocytic
thyroiditis and also known as lymphadenoid goiter and struma lymphomatosa. This indolent
disease usually persists for years and in the Western world is the principal cause of
non-iatrogenic primary hypothyroidism. Nonspecific focal thyroiditis, characterised by local
lymphoid cell infiltration without parenchymal changes, may be a variant of the autoimmune
disease. The condition is covered in detail in Chapter 8. Another form of thyroiditis, also
believed to be of autoimmune cause, has recently been described. It has been variably
referred to as painless, silent, occult, subacute, subacute nonsuppurative, and atypical (silent)
subacute thyroiditis, as well as hyperthyroiditis, transient thyrotoxicosis with low thyroidal RAIU
and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism. There is no
agreement on an inclusive name. The features of this disease entity overlap deQuervain's
thyroiditis and Hashimoto's thyroiditis. The clinical course, with the exception of a the high
erythrocyte sedimentation rate, is indistinguishable from deQuervain's thyroiditis. Yet,
histologically, the condition cannot be differentiated from a milder form of Hashimoto's disease.
This condition often occurs in the postpartum period and is also termed postpartum thyroiditis.
All forms of autoimmune thyroiditis are considered in Chapter 8.
4. Riedel's thyroiditis is another disorder of unknown etiology. Synonyms include Riedel's
struma, ligneous thyroiditis and invasive fibrous or chronic sclerosing thyroiditis. This condition
is characterised by overgrowth of connective tissue which often extends into neighboring
5. Miscellaneous varieties of thyroid inflammation or infiltration including local manifestations
of a generalized disease processes. Among these are sarcoid and amyloid involvement of the
thyroid. Radiation and direct trauma to the thyroid gland may also cause thyroiditis.

Infectious Thyroiditis.
The thyroid gland is remarkably resistant to infection. This has been attributed to its high
vascularity, the presence of large amounts of iodine in the tissue, the fact that hydrogen
peroxide is generated within the gland as a requirement for the synthesis of thyroid hormone
and its normal encapsulated position away from external structures. However, in certain
situations, particularly in children (1,2,2a), a persistent fistula from the pyriform sinus may
make the left lobe of the thyroid particularly susceptible to abscess formation (3-7). Recurrent
left-sided thyroid abcess has also been reported due to a fourth branchial arch sinus fistula8.
In the immuno-compromised host, fungal infection may occur 9-12. Occasionally, acute
bacterial supporative thyroiditis occurs in children receiving cancer chemotherapy13. Rarely,
infection will occur in a cystic or degenerated nodule. As will be discussed, the principal
differential diagnosis is generally between acute, meaning infectious, and subacute, meaning
post-viral (non-infectious) inflammation of the gland.


<SMALL>Virtually any bacterium can infect the thyroid. Streptococcus, staphylococcus,
pneumococcus, salmonella 14,15, 15a, bacteroides, t. pallidum, pasteurella spp 16 and m.
tuberculosis 17-19 have all been described. The subject has been extensively reviewed
10,20,21. In addition, certain fungi, including coccidioides immitis, aspergillus, actinomycosis,
and candida albicans (22), nocardia(23), acinobacter baumanii(24) and cryptococcus (24a)
have also been associated with thyroiditis. In the latter cases, the hosts have often been
immuno-compromised, either due to malignancy or to AIDS (25). Malignancy may also be
associated with thyroid abscess due to a fistulous connection (26).</SMALL>
Most commonly, however, especially in children, infection of the thyroid gland is a result of
direct extension from an internal fistula from the pyriform sinus (3-,5,21,27). This tract is
thought to represent the course of migration of the ultimo branchial body from the site of its
embryonic origin in the fifth pharyngeal pouch (5a). Careful histopathological studies of these
fistulae have demonstrated that they are lined by squamous columnar or ciliated epithelium
and occasionally form branches in the thyroid lobe (3,5). In addition, occasional cells positive
for calcitonin have been found in the fistulae and increased numbers of C-cells were noted in
the thyroid lobe at the point of termination of the tract. The predominance of acute thyroiditis in
the left lobe of the thyroid gland, particularly in infants and children, is explained by the fact
that the right ultimo branchial body is often atrophic and does not develop in the human (as
well as in other species such as reptiles). The reason for this phenomenon is not known. Acute
thyroiditis may involve a normal gland, or arise in a multinodular goiter. At times, no source of
infection can be demonstrated. The possibility of a persistent thyroglossal duct should be
considered for patients with midline infections (9).


Pathological examination reveals characteristic changes of acute inflammation. With bacterial
infections, heavy polymorphonuclear and lymphocytic cellular infiltrate is found in the initial
phase, often with necrosis and abscess formation. Fibrosis is prominent as healing occurs. In
material obtained by fine needle aspiration, the infectious agent may be seen on a gram, acid
fast or appropriate fungal stains. Fungal thyroiditis was clearly demonstrated in a patient with
candida albicans (4).

Clinical Manifestations

Acute thyroiditis is quite rare with no more than one to two patients per year observed in a
large tertiary care hospital. As the number of immunocompromised patients increase, cases of
suppurative thyroiditis are increasing. It may be somewhat more common in the pediatric age
group, although it is still quite unusual. The proper treatment of an acute thyroiditis in children
generally requires the surgical removal of the fistula. (3-5) This almost always leads to a
permanent cure of the condition.
The dominant clinical symptom is pain in the region of the thyroid gland which may
subsequently enlarge and become hot and tender. The patient is unable to extend the neck
and often sits with the neck flexed in order to avoid pressure on the thyroid gland. Swallowing
is painful. There are usually signs of infection in structures adjacent to the thyroid, local
lymphadenopathy as well as temperature elevation and, if bacteremia occurs, chills. Gas
formation has been noted with suppurative thyroiditis (25a). Symptoms are generally more
obvious in children than in adults. Adults may present with a vague slightly painful mass in the
thyroid region without fever, which may raise the possibility of a malignancy. It may occur more
commonly in the fall and winter following upper respiratory tract infections.
In general, there are no signs or symptoms of hyper- or hypothyroidism. However, exceptions
to both have been reported particularly if the thyroiditis is generalized, such as occurs with
fungal processes (24a) or mycobacterial infections. At times, even in patients with bacterial
thyroiditis, destruction of the thyroid gland is sufficient to release thyroid hormone in amounts
sufficient to cause symptomatic hyperthyroidism (17). The adult thyroid gland contains
approximately 600 ug of T4/g (28). Given a typical 15 to 20 g gland, sufficient hormone can be
released to cause transient thyrotoxicosis.


Pain in the anterior neck will usually lead to a consideration of the possibility of thyroiditis.
Since the major differential diagnosis will lie between acute suppurative thyroiditis and
subacute thyroiditis, it is critical to compare the history, physical, and particularly laboratory
data in these two conditions (see Table 19-1). In general, the patient with acute thyroiditis
appears septic, has greater and more localized pain in the thyroid gland, may have an
associated upper respiratory infection, has lymphadenopathy and may be
immuno-compromised. Localization of the tenderness to the left lobe should suggest the
possibility of an infection as should any erythema or apparent abscess formation. The
presence of an elevated white blood count with a shift to the left would argue for infection,
however, elevations in sedimentation rate are common in both acute and subacute thyroiditis.
As mentioned, patients with bacterial thyroiditis are not hyperthyroid, but exceptions do occur.
This is more common, but, by no means universal in patients with subacute thyroiditis.
Depending on the age and clinical circumstances, one may wish to proceed with invasive or
non-invasive studies. The most discriminating tests for recognizing a difference between the
two conditions are either an iodine uptake or scan showing a very low value in subacute
thyroiditis with a normal value found in the patient with localized bacterial thyroiditis (21). If a
thyroid ultrasound shows a localized process, a needle aspiration can be performed. This will
be definitive. A CT scan may be useful in identifying the location of the abscess, but this is
required only in unusual situations (29). Gallium scans are sometimes performed in the course
of an evaluation for a fever of unknown origin. Localization of gallium to the thyroid gland is a
very useful finding confirming thyroid inflammation as the source of the problem (22). If an
infectious process is identified, particularly of the left lobe of a younger individual, then a
barium swallow should be performed with attention to the possibility of a fistulous tract located
on the left side between the pyriform sinus and the thyroid gland. In general bacterial infections
tend to be localized whereas the post viral subacute thyroiditis is more often generalized,
although intermediate conditions can certainly exist.
Occasionally, pain from an infectious process elsewhere in the neck will present as anterior
neck tenderness. For example, a retropharyngeal abscess may present with typical symptoms
of acute thyroiditis. The thyroid gland, however, will have a normal uptake, be normal on scan,
and only on CT scan will the retropharyngeal abscess be recognized. The tendency for the
pain of thyroid inflammation to be referred to the throat or ears should be kept in mind,
although recognition of the anatomic source of the problem is usually not such a difficult issue
in patients with acute thyroiditis due to their localized symptoms.


The diagnosis and choice of antibiotic therapy are often aided by microscopic examination and
appropriate staining of a fine needle aspirate. The procedure is best done under ultrasound
guidance so that the source of the specimen is identified. It may also serve as a mechanism
for drainage of an abscess and can be repeated to facilitate healing. Some abscesses will
require surgical exploration and drainage. The choice of therapy will also depend on the
immune status of the patient. Systemic antibiotics are required for severe infections. Candida
albicans thyroiditis can be treated with amphotericin B and 5 fluconazol 100 mg daily. While
patients with tuberculosis or parasitic infections tend to have a more indolent course, these
infections can present with acute symptoms and this possibility should be considered if the
epidemiology is consistent. For example, thyroidal echinococcosis occurs in countries in which
this parasite is endemic (30). Trypanosomiasis of the thyroid has also been reported (21).


In some patients with thyroiditis, the destruction may be sufficiently severe that hypothyroidism
results. Thus, patients with a particularly diffuse thyroiditis should have follow-up thyroid
function studies performed to determine that this has not occurred. Surgical removal of a
fistula or branchial pouch sinus (30a) is required to prevent recurrence when this is present.

Subacute Thyroiditis

Subacute thyroiditis, sometimes referred to as granulomatous or De Quervain's thyroiditis, is a
spontaneously remitting inflammatory condition of the thyroid gland that may last for weeks to
several months (21,31). It has a tendency to recur. The gland is typically involved as a whole,
and thyroidal RAIU is much depressed. Transient hyperthyroxinemia, elevation of the serum
Tg concentration and the erythrocyte sedimentation rate and sometimes the WBC during the
early acute phase are characteristic if not pathognomic.


A cause can rarely be established. A tendency for the disease to follow upper respiratory tract
infections or sore throats has suggested a viral infection. Earlier suggestions that the disease
may represent a bacterial infection have been disproven. An autoimmune reaction is also
unlikely. The development during the illness of cell-mediated immunity against various thyroid
cell particulate fractions or crude antigens appears to be related to the release of these
materials during tissue destruction (32,33).

Although the search for a viral cause has usually been unrewarding, a few cases seem to be
due to the virus that causes mumps (31,34). The disease has occurred in epidemic form. High
titers of mumps antibodies have been found in some patients with subacute thyroiditis, and
occasionally parotitis or orchitis is associated with thyroiditis. The mumps virus has been
cultured directly from thyroid tissue involved by subacute thyroiditis. Although the mumps virus
seems to be one discrete etiologic factor, the disease has been reported in association with
other viral conditions including measles, influenza, adenovirus infection, infectious
mononucleosis, myocarditis, cat scratch fever, and coxsackie virus (Figure 19-1) (35). Two
comprehensive studies (36,37) failed to find evidence of enteroviruses in 27 patients and
Epstein-Barr virus or cytomegalo virus in 10 patients, respectively but a single case report has
implicated EB virus in a case of subacute thyroiditis with typical clinical features (38).
                    Figure 9-1. Viral antibody titers in subacute thyroiditis. The graph shows

                    serial viral antibody titers in 32 patients who had 4-fold changes in the

                    dilution of these antibodies. Only the single viral antibody showing the

                    greatest change in dilution during the period of observation is depicted for

                    each patient. The antibody titers are characteristically high at the onset of

                    the illness and gradually diminish. (From Volpe et al, 23 with permission.)

Numerous attempts to culture viruses from cases not associated with mumps have failed.
Virus-like particles have been demonstrated in the follicular epithelium of a single patient
suffering form subacute thyroiditis (35). However, viral antibody titers to common respiratory
tract viruses are often elevated in these patients. Since the titers fall promptly, and multiple
viral antibodies may appear in the same patient, the elevation probably is an anamnestic
response to the inflammatory condition. (Figure 19-1, above) Histo-compatibility studies show
that 72% of patients with subacute thyroiditis manifest HLA-Bw35 (31). Familial occurrence of
subacute thyroiditis associated with HLA-B35 has been reported (31a). Thus, the susceptibility
to subacute thyroiditis is genetically influenced and it has also been suggested that subacute
thyroiditis might occur by transmission of viral infection in genetically predisposed individuals
(38). A reported association between subacute thyroiditis and acute febrile neutrophilic
dermatosis (Sweet's syndrome) (40) may imply a common role for cytokines in both these
New treatments, particularly those in which there is manipulation of the immune system, have
led to the development of a subacute thyroiditis (42). Infusion of interleukin 2 caused
hyperthyroxinemia with a low radioiodine uptake in six patients who received this in
combination with TNF a or a interferon (43). The patients proceeded to pass through the
pattern of hyperthyroidism and transient hypothyroidism, with a re-establishment of normal
thyroid function typical of the patient with autoimmune painless thyroiditis. However, none of
the patients had detectable antithyroid antibodies. This condition is thus intermediate between
subacute lymphocytic (painless) thyroiditis (Chapter 13) and subacute thyroiditis which is
typically painful.In patients with chronic hepatitis C studies following interferon therapy (IFN)
showed that a minority (15%) developed a destructive thyroiditis while others had a mild
elevation of TSH. 43 IFN can exacerbate previous thyroid autoimmunity and cause destructive
thyroidal changes de novo. Subacute thyroiditis has recently been noted in patients treated
with combination therapy of IFN plus ribavirin for this disease (44,45), as well as during
treatment of hepatitis B with Interferon (45a). The condition has also been reported in
association with Takayasu's arteritis suggesting an immune abnormality (45b). On the other
hand, subacute thyroiditis has been reported in a patient receiving long term
immunosuppressive therapy and lithium, suggesting a minimal role for autoimmunity in the
condition (46). Other reports of subacute thyroiditis for example with renal cell carcinoma (46a)
or after gastric bypass (46b) do not contribute to its etiology.


The thyroid gland may be adherent to its capsule or to the strap muscles but it can usually be
dissected free, a feature distinguishing subacute thyroiditis from Riedel's thyroiditis. The
involved tissue appears yellowish or white and is more firm than normal.

The gland is enlarged, and the enlargement is usually bilateral and uniform, but it may be
asymmetrical, with predominant involvement of one lobe. Although the lesion may extend to
the capsular surface, it can also be confined to the thyroid parenchyma and merely be
palpable as a suspiciously hard area.

The macroscopic pathologic picture of subacute thyroiditis frequently bears a striking
resemblance to cancer. The lesion is firm to dense in consistency, pale white in color, and has
poorly defined margins that encroach irregularly on the adjacent normal thyroid.
Microscopically, one sees a mixture of subacute, chronic, and granulomatous inflammatory
changes associated with zones of parenchymal destruction and scar tissue. Early infiltration
with polymorphonuclear leukocytes is replaced by lymphocytes and macrophages. The normal
follicles may be largely replaced by an inflammatory reaction, but a few small follicles
containing colloid remain (Fig. 19-2, below). Three dimensional cytomorphological analysis of
fine needle aspiration biopsy samples from patients with subacute thyroiditis examined with
scanning and transmission electron microscopy has shown a loss of a uniform, honeycomb
cellular arrangement; variation in size and decrease or shortening of microvilli in follicular cells
together with the appearance of round or ovoid giant cells (46c). The most distinctive feature is
the granuloma, consisting of giant cells clustered about foci of degenerating thyroid follicles
(Fig. 19-2). The early literature contains accounts of tuberculous thyroiditis, a diagnosis largely
based on the granulomatous tissue reaction, from which the descriptive but unfortunate term
pseudotuberculous thyroiditis arose (47). Data on the mechanism of inflammation and the
pathogenesis of subacute thyroiditis at the cellular level are sparse. However a study of
apoptosis and expression of Bcl 1-2 family proteins in 11 patients with SAT has suggested that
apoptotic mechanisms may be involved in the development of SAT48. A detailed
immunohistochemical study of growth factors in SAT (49) has shown that growth factor rich
monocytes/macrophages (containing VEGF, beta FGF, PDGF and TGF beta 1) mediate the
granulomatous stage. EGF is important in the regenerative stage as it has mitogenic effects on
the thyrocyte. VEGF and betaFGF contribute to the angiogenesis at both these stages of the
disease. In a recent analysis of factors influencing the severity of the acute phase response
during the course of SAT, it was found that serum interleukin -1 receptor antagonist may have
a significant anti-inflammatory role in the condition (50).

Mast cells play an important part in the repair process of thyroid tissue affected by the disease
via production of growth factors and biomolecules which modulate thyroid folliculogenesis and
angiogenesis (51).

           Figure 9-2. Subacute thyroiditis. Note the discrete granulomas, with giant cells, and the diffuse

           fibrosis (85 X).


Subacute thyroiditis is encountered infrequently, but each year a handful of cases will be
identified in a busy thyroid clinic. Woolner et al (28b) collected 162 cases diagnosed on clinical
grounds at the Mayo Clinic over a 5-year period; during the same time, 1,250 patients with
Graves' disease were seen. Thus, the disease had approximately one-eighth the incidence of
Graves' disease in this clinic population. Although the disease has been described at all ages,
it is rare in children (27a). Female patients outnumbered male patients in a ratio of 3-6:1, and
there is a preponderance of cases in the third to fifth decades (20,31,47). A recent study of 160
patients during 37 years at the Mayo Clinic resulted in an age and sex adjusted incidence of
4.9 cases/100,000/yr (47a).

Clinical Manifestations

Characteristically, the patient has severe pain and extreme tenderness in the thyroid region. A
small minority of patients have been noted to present with painless or minimally painful
subacute thyroiditis following viral symptomatology (52). These may be regarded as atypical
subacute thyroiditis patients but their natural history of the disease is not known. When the
symptom is difficulty in swallowing, the disorder may be initially mistaken for pharyngitis. At
times, the pain begins in one pole and then spreads rapidly to involve the rest of the gland
("creeping thyroiditis"). It may radiate to the jaw or the ears. Malaise, fatigue, myalgia and
arthralgia are common. A mild to moderate fever is expected, and at times a high, swinging
fever causes temperatures to rise daily above 104oF (40.0oC). The disease may reach its peak
within 3 to 4 days and subside and disappear within a week, but more typically, a gradual
onset extends over 1 to 2 weeks and continues with a fluctuating intensity for 3 to 6 weeks.
Several recurrences of diminishing intensity extending over many months may be the unhappy
fate of the patient.

The thyroid gland is typically enlarged two or three times the normal size or larger and is
tender to palpation, sometimes exquisitely so. It is smooth and firm. Occasionally the condition
may be confined to one lobe (53,54).

Approximately one-half of the patients present during the first weeks of the illness, with
symptoms of thyrotoxicosis, including nervousness, heat intolerance, palpitations,
tremulousness, and increased sweating. These symptoms are caused by excessive release of
thyroid hormone from the thyroid gland during the acute phase of the inflammatory process. As
the disease process subsides, transient hypothyroidism occurs in about one-quarter of the
patients. Ultimately thyroid function returns to normal and permanent hypothyroidism occurs in
less than 10 percent of the cases (20,21,31). Occasionally the condition may be painless and
present as fever of unknown origin (55).


Table 19-1 provides a comparison between the clinical and laboratory findings of patients with
subacute and acute thyroiditis 21,56-67. Laboratory examination may disclose a moderate
leukocytosis. A curious and striking elevation of the erythrocyte sedimentation rate, at times
above 100 mm/hr, or serum C-reactive protein (67a) is a useful diagnostic clue. Short of tissue
diagnosis, most helpful is the characteristic combination of elevated erythrocyte sedimentation
rate, high serum T4, T3, and TG concentrations in the presence of low thyroidal RAIU, and an
absent or low titer of circulating TG antibodies. While the estimation of thyrotropin receptor
antibodies (TRAb) in a thyrotoxic patient may be clinically useful in Graves' disease there have
been reports of positive TRAb in patients with subacute thyroiditis although the frequency of
positivity is low (67b,c,d, 70). Mild anemia and hyperglobulinemia may be present. The value
of a 99m-Tc-pertechnetate scintigraphy as a marker of disease actviity and severity has been
noted (68). Further imaging studies have shown diffuse increased uptake of Tc-99m sestamibi
in the thyroid region of patients in the acute phase (thyrotoxic) of subacute thyroiditis
suggesting increased perfusion; at the same time Tc-99m pertechnetate uptake was markedly
reduced. It is possible that Tc-99m sestamibi uptake in the early phase may reflect the
inflammatory process associated with the disease (68a). In the same patients color Doppler
ultrasonography showed an absence of vascularization in the acute phase. Subacute
thyroiditis with thyrotoxicosis may also be distinguished from Graves' hyperthyroidism by using
T1- and T2- diffusion weighted magnetic resonance imaging (68b) although this investigation
may not be available or even desirable in all centres.

      Table 19-1 Features Useful in Differentiating Acute Suppurative Thyroiditis and Subacute
                                                       Characteristic                      Acute Thyroiditis
History                           Preceding upper respiratory infection                          88%               17%
                                  Fever                                                         100%               54%
                                  Symptoms of thyrotoxicosis                                  uncommon             47%
                                  Sore throat                                                    90%               36%
Physical   Examination   of   the Painful thyroid swelling                                      100%               77%
thyroid                           Left side affected                                             85%           not specific
                                  Migrating thyroid tenderness                                 possible            27%
                                  Erythema of overlying skin                                     83%            not usually
Laboratory                        Elevated white blood cell count                                57%             25-50%
                                  Elevated erythrocyte sedimentation rate (>30mm/hr)            100%               85%
                                  Abnormal thyroid hormone levels(elevated or depressed)        5-10%              60%
                                  Alkaline phosphatase, transaminases increased                  rare            common
Needle Aspiration                 Purulent, bacteria or fungi present                           ~100%               0
                                  Lymphocytes, macrophages, some polys, giant cells               0              ~100%
                                    I uptake low                                              uncommon           ~100%
Radiological                      Abnormal thyroid scan                                          92%                —
                                  Thyroid scan or ultrasound helpful in diagnosis                75%                —
                                  Gallium scan positive                                         ~100%            ~100%
                                  Barium swallow showing fistula                               common               0
                                  CT scan useful                                                rarely         not indicated
Clinical Course                   Clinical response to glucocorticoid treatment                transient          100%
                                  Incision and drainage required                                 85%                No
                                  Recurrence following operative drainage                        16%                No
                                     Pyriform sinus fistula discovered            96%          No
                                12, see also Shabb et al (41d)
Modified from Szabo and Allen

Subacute Thyroiditis

          A.S., a 46-year old woman, noted the onset of a tender, slowly enlarging
          swelling in the low anterior neck in December. There was no antecedent
          infection or virus-like syndrome. She was aware of associated increased
          nervousness, mild tremor, increased sweating, and anorexia, without
          alteration in weight. In January, increasing pain that radiated to the back of her
          head and orbits necessitated medical consultation. A family history of thyroid
          disease was not elicited.

          On physical examination she appeared to be in pain, BP was 155/80, and
          pulse 112/min and regular. Clinically, she appeared to be euthyroid. The
          thyroid gland was estimated to be 40 grams in weight and was tender, firm,
          and slightly irregular. The remainder of the examination was non-contributory.

          Laboratory data included an erythrocyte sedimentation rate of 58 mm/min,
          FT4I of 16.1 m g/dl (normal, 3.6 to 9.3 m g/dl), TT4 level of 14.9 m g/dl (normal
          4.2 to 9.4), and a Tg antibody titer of 1/40.

          Figure 19-3 (below) shows a sequence of 125I and 241Am scans obtained
          throughout the course of her illness. On presentation, there was no 125I
          uptake seen on thyroid scintiscan, with an RAIU of 1 percent. At the same
          time, the 241Am scan showed virtually no stable iodine in the thyroid. A
          241Am scan repeated in March showed continuing low 127I levels in the
          thyroid, at which time the serum TT4 level was 1.7 m g/dl and the FT4I was
          0.8 m g/dl. The 241Am scans on these two dates demonstrate mainly
          background radiation scatter. With the resolution of her clinical syndrome over
          the next few months, the results of the thyroid scans were seen to return to
          normal. The result of the 125I scintiscan in June was completely normal, with
          an RAIU of 20 percent, at which time her TT4 level and FT4I had returned to
          the normal range. The 241Am scan 3 months later showed some
          reaccumulation of 127I, but the stable iodine store was still reduced. The last
          241Am scan 14 months after onset demonstrated total repletion of her
          thyroidal 127I stores. At this time, the gland was normal in size (weight 20 g)
          and consistency.
                      125                   241
Figure 9- 3. Serial     I scintiscans and     Am fluorescent scans in a patient during the course of subacute thyroiditis. The first two fluorescent scans, done at a
                                                                                                                       127                                    63
high sensitivity setting without background subtraction, have much neck "background" but demonstrate virtually no        I in the thyroid. (From Rapoport et al, with


                 If subacute thyroiditis affects only one part of the thyroid gland, the serum T4 concentration
                 and thyroidal RAIU may be entirely normal. A thyroid scan will demonstrate failure of the
                 involved areas of the gland to concentrate iodide. When the thyroid is diffusely involved, which
                 is more typical, a dramatic disturbance in iodine metabolism is observed.

                 During the initial phase of the disease, the RAIU is depressed or entirely absent and the
                 concentrations of serum T4 and T3 are often elevated. Due to the concomitant release of
                 nonhydrolyzed iodoproteins from the inflamed tissue, the serum T3 level is also high. During
                 this phase the serum TSH level is low, and the TSH response to TRH is suppressed (60) due
                 to the high levels of circulating thyroid hormone. Iodide that is collected and metabolized by
                 the gland is rapidly secreted because of the decreased ability to store colloid (63). At this time,
                 the involved tissue shows decreased but not necessarily depleted stores of iodine, as
                 determined by x-ray fluorescence (57,63). Administration of TSH usually fails to produce a
                 normal increase in RAIU. Evidently, thyroid cell damage reduces the ability of the gland to
                 respond to TSH. As the process subsides, the serum T4, T3, and TG levels decline, but the
                 serum TSH level remains suppressed. The normal concentrations of SHBG in the hyperthyroid
                 phase probably reflect the short duration of exposure to increased thyroid hormone (69).

                 Later, during the recovery phase, the RAIU becomes elevated with the resumption of the
                 ability of the thyroid gland to concentrate iodide. The serum T4 concentration may fall below
                 normal; the TSH level may become elevated. Usually after several weeks or months, all the
                 parameters of thyroid function return to normal (Fig. 19-4). Restoration of iodine stores
                 appears to be much slower and may take more than a year after the complete clinical
                 remission (57,6). In about 2% of patients subacute thyroiditis may trigger auto-reactive B cells
to produce TSH receptor antibodies, resulting in TSH antibody associated thyroid dysfunction
in some patients (70).

   Figure 9-4. Thyroid function in a patient during the course of deQuervain’s (subacute) thyroiditis. During the

   thyrotoxic phase (days 10 to 20), the serum TG concentration was greatly elevated, the FTI was high, and TSH was

   suppressed; the erythrocyte sedimentation rate was 86 mm/hr, and the thyroidal RAIU was 2 percent. The TG level

   and FTI declined in parallel. During the phase of hypothyroidism (days 30 to 63), when the FTI was below normal, a

   modest transient increase in the serum TG level occurred in parallel with the increase in serum TSH. All parameters of

   thyroid function were normal by day 150, 5 months after the onset of symptoms.

Differential Diagnosis

Diagnosis is usually not difficult. With an acutely enlarged, tender thyroid, an RAIU near zero,
and elevated serum T4 and Tg concentrations and ESR, the diagnosis is almost certain.
Circulating thyroid autoantibodies are absent or the titer is low. Among the diagnostic
alternatives, infectious thyroiditis must be considered and the possibility of invading bacteria
excluded (see Table 19-1). The thyroid in Hashimoto's thyroiditis may be slightly tender and
painful, but this event is rare, and the typical disturbances in iodine metabolism and
erythrocyte sedimentation rate are not found. Hemorrhage into a cyst in a nodular thyroid
gland may be confused with subacute thyroiditis. Hemorrhage is usually more sudden and
transient, a fluctuant mass may be found in the involved region, and the erythrocyte
sedimentation rate is normal. Occasionally, subacute thyroiditis mimics hyperthyroidism in a
patient whose RAIU is suppressed by iodine. This event occurs particularly in transient
thyrotoxicosis induced by iodine (64). The sudden onset of subacute thyroiditis, the presence
of toxic symptoms without the typical signs of long-term hyperthyroidism, the tender gland, the
constitutional symptoms, and the high erythrocyte sedimentation rate are helpful in making the
differentiation. In some instances, measurement of antibodies and thyroid-stimulating
immunoglobulins, and observation of the course of the illness may be required to confirm the

The single disease entity that is probably most difficult to differentiate from subacute thyroiditis
is a variant of lymphocytic thyroiditis (66,67). This condition is unrelated to iodine ingestion and
most likely is a variant of autoimmune thyroiditis. The patient presents with goiter, mild
thyrotoxicosis, and a low RAIU. The course of the disease is indistinguishable from that of
subacute thyroiditis and proceeds from a thyrotoxic phase through a hypothyroid phase to
spontaneous remission with normalization of thyroid function. The goiter is typically painless,
and there are no associated systemic symptoms. This condition has been formerly confused
with subacute (deQuervain's) thyroiditis, whence come the misleading terms silent, painless,
or atypical subacute thyroiditis. The most helpful distinguishing features, short of histologic
examination of biopsy material, are the absence of pain and a normal erythrocyte
sedimentation rate. (See also Chapter 13.) Localized subacute thyroiditis, with induration, mild
tenderness, and depressed iodine binding visualized on scan, can be very suggestive of
thyroid cancer. Usually the degree of pain and tenderness, elevated erythrocyte sedimentation
rate and leukocytosis, and remission or spread to other parts of the gland make clinical
differentiation possible. Gray-scale and color Doppler sonography may be helpful in this
situation (71) but a fine needle aspiration is required for a definitive differentation between
these two processes (71).


In some patients, no treatment is required. However, for many, some form of analgesic therapy
is required to treat the symptoms of the disease until it resolves. At times, this relief of
symptoms can be achieved with non-steroidal anti-inflammatory agents or aspirin. However, if
this fails, as it often does when the symptoms are severe, prednisone administration should be
employed (20,31). Large doses promptly relieve the symptoms through non-specific
anti-inflammatory effects. Treatment is generally begun with a single daily dose of 40 mg
prednisone. After one week of this treatment, the dosage is tapered over a period of 6 weeks
or so. The relief of the tenderness in the neck is so dramatic as to be virtually diagnostic of the
problem as being due to subacute thyroiditis. As the dose is tapered, most patients have no
recrudescence of symptoms, but occasionally this does occur and the dose must be increased
again. Alternatively oral cholecystographic agents (such as sodium ipodate or sodium
iopanoate) may be used safely and effectively for the management of hyperthyroidism in these
patinents even when they have relapsed after corticosteroid therapy (72a). The recurrent rate
of subacute thyroiditis after cessation of prednisolone therapy is about 20% but no difference
has been found in routine laboratory data between recurrent and non-recurrent groups of
patients (73). Levothyroxine administration may be useful in situations where the patient is not
already hyperthyroid due to the release of thyroidal contents into the circulation. It is thought
that TSH suppression will reduce the thyroid stimulation which might otherwise prolong the
inflammatory process. It is also necessary to administer thyroid hormones, at least transiently,
if the patient enters a phase of hypothyroidism subsequent to the acute inflammation.
TSH-suppressive doses of levothyroxine should only be administered when there is evidence
that exacerbation of the condition occurs when TSH is present. Otherwise, the return of thyroid
function to normal, which presumably is facilitated by TSH, can be prevented or delayed.
During the recovery process, there may be a marked but transient increase in the 24 hour
radioactive iodine uptake which can reach levels typical of Graves' Disease. This occurs prior
to re-establishment of normal thyroid function and should not be confused with
hyperthyroidism due to Graves' Disease. Surgical intervention is not the primary treatment for
subacute thyroiditis. Experience from the Mayo clinic (74) has shown that if surgery is
performed for a clinically indeterminate thyroid nodule resection is safe and with low morbidity.


In 90% or more of patients, there is a complete and spontaneous recovery and a return to
normal thyroid function. However, the thyroid glands of patients with subacute thyroiditis may
exhibit irregular scarring between islands of residual functioning parenchyma, although the
patient has no symptoms. Up to 10% of the patients may become hypothyroid and require
permanent replacement with levothyroxine. It is of interest that elevated levels of serum Tg
may persist well over a year after the initial diagnosis, indicating that disordered follicular
architecture and/or low grade inflammation can persist for a relatively long period (59,75).


In 1896 Riedel described a chronic sclerosing thyroiditis, occurring especially in women, that
tends to progress inexorably to complete destruction of the thyroid gland and frequently
causes pressure symptoms in the neck (76-78). It is exceedingly rare. In the Mayo Clinic
series it occurred approximately on-fiftieth as frequently as Hashimoto's thyroiditis. It is
approximately twice as frequent in men as in women and is found most often in the 30- to 60-
year age group. The thyroid gland is normal in size or enlarged, usually symmetrically involved,
and extremely hard. Occasionally involvement may be unilateral. Diagnostic confustion with
sarcoma of the thyroid region has been reported (79). On pathologic examination the gland is
replaced by dense fibrosis in which are scattered solitary follicular cells and occasional acini
with small amounts of colloid. The fibrosis binds the thyroid firmly to the trachea and the strap
muscles, from which it can be separated only with the greatest difficulty (ligneous thyroiditis)
(80). The fibrosis may compress the trachea or esophagus. The disease may remain stable
over many years, or it may progress slowly and produce hypothyroidism. Dyspnea, dysphagia,
hoarseness, and aphonia are caused by the local pressure, and if there is enough pressure on
both recurrent laryngeal nerves, there may be stridor. Sometimes the disease is asymptomatic
and discovered only incidentally. The pathologic process may advance to complete
replacement of the gland, and then symptoms and signs of hypothyroidism appear.
Involvement of the parathyroid glands by the fibrotic process may result in hypoparathyroidism
(81-84, 84a). Rarely, Riedel's thyroiditis may be associated with similar fibrosclerotic
processes in other areas, including the lacrimal glands, orbits (84b), parotid glands,
mediastinum, lung, myocardium, retroperitoneal tissues, and bile ducts in varying
combinations in the syndrome of multifocal fibrosclerositis (85). Fluorine-18
fluorodeoxyglucose [FDG] positron emission tomographic images have shown metabolic
activity in an abdominal mass and increased glucose metabolism in the thyroid, probably
resulting from active inflammation involving lymphocytes, plasma cells and fibroblant
proliferation (86). FDG metabolic activity can also be used to assess a patient's response to
therapy (86a). This mixture of inflammatory cell infiltrate and fibrosis can also be visualised
using dynamic magnetic resonance imaging with gadpentate dimeglumine (87) and
appropriate T1- and T2- weighted images (88). Subcutaneous fibrosclerosis has also been
noted but it is very rare (89). The occurrence of cerebral sinus thrombosis suggests that
Riedel's thyroiditis may cause venous stasis, vascular damage, and possibly
hypercoaguability (90). The results of laboratory tests of thyroid function are usually normal,
but about one-third are hypothyroid. The erythrocyte sedimentation rate is not elevated, as in
subacute thyroiditis, and there is no leukocytosis. Antithyroid antibodies are present in 67% of
reported cases (78) and a mixed population of B- and T-cells is present in the thyroid,
suggesting an autoimmune etiology or association. The B cell proliferation has been shown to
be polyclonal (78a). The occurrence of marked tissue eosinophilia and the extracellular
deposition of eosinophil granule major basic protein suggests a role for eosinophils and their
products in the development of fibrosis in Riedel's thyroiditis (91). Fibrosis may also be related
to the action of TGF beta 1, as seen in murine thyroiditis (92). The manifestations of Riedel’s
thyroiditis can be confusing. A patient was recently reported who, over 18 months after biopsy
proven Riedel’s thyroiditis, developed hyperthyroidism, spontaneous primary
hypoparathyroidism, acute compressive neck symptoms requiring emergency isthmusectomy,
vocal cord paralysis, syncopal-like episodes, and Horner’s syndrome due to compression of
the right carotid sheath. This patient is under therapy with glucocorticoids and tamoxifen (98a

Management of Riedel's Thyroiditis

Although there is no specific therapy for Riedel's thyroiditis, several management strategies
are available dependent on the clinical features of the disease in the individual patient.
Corticosteroid therapy has been found to be effective in some cases (85,93-95 95a,95b),
probably those with active inflammation. Initial doses of up to 100mg per day of prednisolone
have been used but sustained improvement has been reported with lower doses of 15-60 mg
per day (85). There are no controlled trials of steroid therapy in Riedel's and although some
patients obtain long term benefit after steroid withdrawal (96) others may relapse (97). The
reasons for this variation are unclear but inflammatory activity and duration of disease may be
relevant factors. In those who fail to respond to steroid therapy or relapse after withdrawal,
Tamoxifen therapy should be tried. Three reports have described an encouraging response
with this agent, admittedly in only a small number of patients (98,99, 99a). It is possible that
Tamoxifen acts in Riedel's by inhibition of fibroblast proliferation through the stimulation of
TGF beta.

As hypothyroidism is rare in Riedel's, thyroxine therapy is usually not required and is not
thought to influence the course of the disease. Surgical intervention may be necessary to
release the trachea or perform tracheotomy in the case of severe stridor. Unilateral lobectomy
has been performed for unilateral disease 100 and larger resections should be considered in
some instances. It is recommended that surgical exploration and biopsy are usually required to
exclude malignancy which may be suspected at presentation.

In addition to the varieties of thyroiditis already mentioned, which are diseases specifically of
the thyroid gland, generalized or systemic diseases may also involve the thyroid gland (20).
The lesions of sarcoid may appear in the thyroid gland of patients with systemic sarcoidosis,
and huge deposits of amyloid occasionally causes goiter in amyloidosis. Painless thyroiditis
has been noted in a woman with rheumatoid arthritis and secondary amyloidosis infiltrating the
thyroid gland (101). Radiotherapy for tonsillFar carcinoma has been reported to result in
thyroiditis (102) and radiation during 131 I therapy produces thyroiditis, which is occasionally
symptomatic. This situation is discussed in Chapters 11 and 18. Irradiation to the thyroid
during therapy for breast cancer or lymphoma can also induce hypothyroidism. Therapy
should be directed toward the primary disease rather than the thyroid, but administration of
thyroid hormone may be necessary if destruction of thyroid tissue is sufficient to produce
hypothyroidism. Finally, surgery to the neck has been reported to cause throiditis but this is
rare (103,104).


The thyroid, like any other structure, may be the seat of an acute or chronic suppurative or
nonsuppurative inflammation. Various systemic infiltrative disorders may leave their mark on
the thyroid gland as well as elsewhere. Infectious thyroiditis is a rare condition, usually the
result of bacterial invasion of the gland. Its signs are the classic ones of inflammation: heat,
pain, redness, and swelling, and special ones conditioned by local relationships, such as
dysphagia and a desire to keep the head flexed on the chest in order to relax the peritracheal
muscles. The treatment is that for any febrile disease, including specific antibiotic drugs if the
invading organism has been identified and its sensitivity to the drug established. Otherwise, a
broad-spectrum antibiotic may be used. Surgical drainage may be necessary and a search for
a pyriform sinus fistula should be made, particularly in children with thyroiditis involving the left
lobe. Subacute (granulomatous) thyroiditis is a more common and protracted disease that
usually involves the thyroid symmetrically. The gland is swollen and tender, and the systemic
reaction may be severe, with fever and an elevated erythrocyte sedimentation rate. During the
acute phase of the disorder, tests of thyroid function disclose a diminished thyroidal RAIU and
increased serum concentrations of T4, T3, and Tg. The cause of this disease has been
established in only a few instances in which a viral infection has been the initiating factor.
There may be repeated recurrences of diminishing severity. Usually, but not always, the
function of the thyroid is normal after the disease has subsided. Subacute thyroiditis may be
treated with rest, non-steroidal anti-inflammatory drugs or aspirin, and thyroid hormone. If the
disease is severe and protracted, it is usually necessary to resort to administration of
glucocorticoids, but recurrence may follow their withdrawal. Riedel's thyroiditis is a chronic
sclerosing replacement of the gland that is exceedingly rare. The process involves the
immediately adjacent structures, making any surgical attack very difficult. The cause is
unknown, and no treatment is available beyond resecting the isthmus of the thyroid gland to
relieve the symptoms of tracheal or esophageal compression. Sarcoid may involve the thyroid,
and amyloid may be deposited in the gland in quantities sufficient to cause goiter. In all of
these diseases it may be necessary to give the patient levothyroxine replacement therapy if
the function of the gland has been impaired.
1. Chi H, Lee YJ, Chiu NC, Huang RY, Huang CY, Lee KS, Shih SL, Shih BF. 2002 Acute
suppurative thyroiditis in children. Pediatri Infect Dis J 21:384-7.

2. Chang P, Tsai WY, Lee PI, Hsiao PH, Huang LM, Lee JS, Peng SF, Li YW. 2002 Clinical
characteristics and management of acute suppurative thyroiditis in children. J Formos Med
Assoc 101:468-71.

2a. Brook I. 2003 Microbioplogy and management of acute suppurative thyroiditis in children.
Int J Pediatr Otorhinolaryngol 67:447-51.

3. Hatabu H, Kasagi K, Yamamoto K, Tida Y, Misaki T, Hidaka A, Endo K, Konishi J. 1990
Acute suppurative thyroiditis associated with piriform sinus fistula: sonographic findings.
American Journal of Medicine 155:845-847..

4. Lucaya J, Berdon WE, Enriquez G, Regas J, Carreno JC. 1990 Congenital pyriform sinus
fustula: a cause of acute left-sided suppurative thyroiditis and neck abscess in children.
Pediatr Radiol 21:27-29.

5. Miyauchi A, Yokozawa T, Matsuzuka F, Kuma K. 1998 Acute suppurative thyroiditis;
infection in thyroid nodules or infection through a piriform sinus fistula. Thyroidol. Clin Exp

5a. Miyauchi A, Matsuzuka F, Kuma K, Katayama S. 1992 Piriform sinus fistula and the
ultimobranchial body. Histopathology 20:221-227.

6. Shah SS, Baum SG. 2000 Diagnosis and management of infectious thyroiditis. Curr Infect
Dis Rep 2:147-153.

7. Fukata S, Miyauchi A, Kuma K, Sugawara M. 2002 Acute suppurative thyroiditis caused by
an infected piriform sinus fistula with thyrotoxicosis. Thyroid 12:175-8.

8. Minhas SS, Watkinson JC, Franklyn J. 2001 Fourth branchial arch fistula and suppurative
thyroiditis: a life-threatening infection. J Laryngol Otol 115:1029-31.

9. Gandhi RT, Tollin SR, Seely EW. 1994 Diagnosis of Candida thyroiditis by fine needle
aspiration. J Infect 28:77-81.

10. Berger SA, Zonszein J, Villamena P, Mittman N. 1983 Infectious diseases of the thyroid
gland. Rev Inf Dis 5:108-122.

11. Fernandez JF, Anaissie EJ, Vassilopoulou-Sellin R, Samaan NA. 1991 Acute fungal
thyroiditis in a patient with acute myelogenous leukemia. J Intern Med 230:539-541.
12. Vandjme A, Pageaux GP, Bismuth M, Fabre JM, Domergue J, Perez C, Makeieff M,
Mourad G, Larrey D. 2001 Nocardiosis revealed by thyroid abscess in a liver-kidney transplant
recipient. Transpl Int 14:202-204

13. Imai C, Kakihara T, Watanabe A, Ikarashi Y, Hotta H, Tanaka A, Uchiyama M. 2002 Acute
suppurative thyroiditis as a rare complication of aggressive chemotherapy in children with
acute myelogeneous leukemia. Pediatr Hematol Oncol 19:247-253

14. Chiovato L, Canale G, Maccherini D, Falcone V, Pacini F, Pinchera A. 1993 Salmonella
brandenburg: a novel cause of acute suppurative thyroiditis. Acta Endocrinol 128:439-442.

15. Su DH, Huang TS. 2002 Acute Suppurative Thyroiditis Caused by Salmonella typhimurium:
A Case Report and Review of the Literature. Thyroid 12:1023-1027.

15a. Dai MS, Chang H, Peng MY, Ho CL, Chao TY. 2003 Suppurative salmonella thyroiditis in
a patient with chronic lymphocytic leukemia. Ann Hematol 82:646-648.…

16. Fernandez Pena C, Morales Gorria MJ, Morano Amado LE, Lopez Miragalla MI, Pena
Gonzalez E. 1999 Pasteurella spp: a new micro-organism to the cause of acute suppurative
thyroiditis. An Med Interna 16:637-638.

17. Nieuwland Y, Tan KY, Elte JW. 1992 Miliary tuberculosis presenting with thyrotoxicosis.
Postgrad Med J 68:677-679.

18. Das DK, Pant CS, Chachra KL, Gupta AK. 1992 Fine needle aspiration cytology diagnosis
of tuberculous thyroiditis. A report of eight cases. Acta Cytol 36:517- 522.

19. Orlandi F, Fiorini S, Gonzatto I, Saggiorato E, Pivano G, Angeli A, Paso R. 1999
Tubercular involvement of the thyroid gland: A report of two cases. Horm Res 52:291-294.

20. Singer PA. 1991 Thyroiditis. Acute, subacute, and chronic. Med Clin North Am 75:61-77.

21. Szabo SM, Allen DB. 1989 Thyroiditis. Differentiation of acute suppurative and subacute.
Case report and review of the literature. Clin Pediatr 28:171-174.

22. Trites J, Evans M. 1998 Actinomycotic thyroiditis in a child. J Paed Surg 5:781- 782.

23. Carriere C, Marchandin H, Andrieu JM, Vendome A, Perez C. 1999 Nocardia thyroiditis:
unusual location of infection. J Clin Microbiol 37(7):2323-2325.

24. Yu EH, Ko WC, Chuang YC, Wu Tj. 1998 Supperative Acinetobacter baumanii thyroiditis
with bacteremic pneumonia. Case report and review. Clin Infect Dis 27(5):1286-1290.

24a. Avram AM, Sturm CA, Michael CW, Sisson JC, Jaffe CA. 2004 Cryptococcal thyroiditis
and hyperthyroidism. Thyroid 14:471-474.
25. Orkar KS, Dakuni KN, Kidmas AT, Awani KU. 2001 Pyogenic thyroiditis and HIV infection.
West Afr J Med 20:173-175.

25a. Reksoprawiro S. 2003 Suppurative thyroiditis with gas formation. Asian J Surg

26. Premawardhana LD, Vora JP, Scanlon MF. 1992 Suppurative thyroiditis with oesophageal
carcinoma. Postgrad Med J 68:592-593.

27. Hopwood NJ, Kelch RP. 1993 Thyroid masses: approach to diagnosis and management in
childhood and adolescence. Pediatr Rev 14:481-487.

27a. Ogawa E, Katsushima Y, Fujiwara I, Iinuma K. 2003 Subacute thyroiditis in children:
patient report and review of the literature. J Pediatr Endocrinol Metab 16:897-900.

28. Larsen PR. 1975 Thyroidal triiodothyronine and thyroxine in Graves' disease correlation
with presurgical treatment, thyroid status and iodine content. J Clin Endocrinol Metab

29. Bernard PJ, Som PM, Urken ML, Lawson W, Biller HF. 1988 The CT findings of acute
thyroiditis and acute suppurative thyroiditis. Otolaryngol Head Neck Surg 99:489-493.

30. Georgiades N, Papadimas B. 1962 Echinococcus cyst of the thyroid. Helliniki Chir 5:575.

30a. Pereira KD, Losh GG, Oliver D, Poole MD. 2004 Management of anomalies of the third
and fourth branchial pouches. Int J Pediatr Otorhinolaryngol 68:43-50.

31. Volpe R. 1993 The management of subacute (de Quervain's) thyroiditis. Thyroid 5:253-5.

32. Galluzzo A, Giordano C, Andronico F, Filardo C, Andronico G, Bompiani G. 1980
Leucocyte migration test in subacute thyroiditis: hypothetical role in cell-mediated immunity. J
Clin Endocrinol Metab 50:1038-1041.

33. Tamai H, Nozaki T, Mikuta T, Morita T, Matsubayashi S, Kuma K, Kumagai LF, Nagataki.
1991 The incidence of thyroid stimulation blocking antibodies during the hypothyroid phase in
patients with subacute thyroiditis. J Clin Endocrinol Metab 73:245-250.

34. Parmar RC, Bavdekar SB, Sahu DR, Warke S, Kamat JR. 2001 Thyroiditis as a presenting
feature of mumps. Pediatr Infect Dis J 20:637-638.

35. Satoh M. 1975 Virus-like particles in the follicular epithelium of the thyroid from a patient
with subacute thyroiditis (deQuervain's). Acta Pathol Jpn 25:499-501.

36. Luotola K, Hyoti H, Miettinen A, Helin A, Pasternak A. 1998 Evaluation of infectious
etiology in subacute thyroiditis - a lack of association with coxsackie virus infection. APMIS
37. Mori K, Yoshida K, Funato T, Ishii T, Nomura T, Hori S, Ito S, Sasaki T. 1998 Failure in
detection of Epstein-Barr virus and cytomegaly virus in specimen obtained by fine needle
aspiration biopsy in patients with subacute thyroiditis. Tokohu J Exp Med 186:13-17.

38. Espino Montoro A, Medina Perez M, Gonzalez Martin MC, Asencio Marchante R, Lopez
Chozas JM. 2000 Subacute thyroiditis associated with positive antibodies to the Epstein-Barr
viru. An Med Interna 17:546-548.

39. Kabalak T, Ozgen AG. 2002 Familial occurrence of subacute thyroiditis. Endocr J

40. Kalmus Y, Kovatz S, Shilo L, Ganem G, Shenkman L. 2000 Sweet's syndrome and
subacute thyroiditis. Postgrad Med J 76:229-230.

41. Bech K, Nerup J, Thomsen M et al. 1977 Subacute thyroiditis de-Quervain: a disease
associated with HLA-B antigen. Acta Endocrinol 86:504-509

42. Vassilopoulou-Sellin R, Sella A, Dexeus FH, Theriault RL, Pololoff DA. 1992 Acute thyroid
dysfunction (thyroiditis) after therapy with interleukin-2. Horm Metab Res 24:434-438.

43. Amenomori M, Mori T, Fukuda Y, Sugawa H, Nishida N, Furukawa M, Kita R, Sando T,
Komeda T, Nakao K. 1998 Incidence and characteristics of thyroid dysfunction following
interferon therapy in patients with chronic hepatitis C. Intern Med 37:246-252.

44. Parana R, Cruz M, Lyra L, Cruz T. 2000 Subacute thyroiditis during treatment with
combination therapy (interferon plus ribavirin) for hepatitis C virus. J Viral Hepat 7:393-395.

45. Kryczka W, Brojer E, Kowalska A, Zarebska-Michaluk D. 2001 Thyroid gland dysfunction
during antiviral therapy of chronic hepatitis C. Med Sci Monit 7 Suppl 1:221-225.

45a. Omur O, Daglyoz G, Akarca U, Ozean Z. 2003 Subacute thyroiditis during interferon
therapy for chronic hepatitis B infection. Clin Nucl Med 28:864-865.

45b. Ohta Y, Ohya Y, Fujii K, Tsuchihashi T, Sato K, Abe I, Iida M. 2003 Inflammatory
diseases associated with Takayasu's arteritis. Angiology 54:339-344.

SMALL>46. Obuobie K, Al-Sabah A, Lazarus JH. 2002 Subacute thyroiditis in an
immunosuppressed patient. J Endocrinol Invest 25:169-171.

46a. Algun E, Alici S, Topal C, Ugras S, Erkoe R, Sakarya ME, Ozbey N. 2003 Coexistence of
subacute thyroiditis and renal cell carcinoma: a paraneoplastic syndrome. CMAJ 168:985-986.

46b. Carneiro JR, Macedo RG, Da Silveira VG. 2004 Thyrotoxicosis after gastric bypass.
Obes Surg 14:699-701.
46c. Chang TC, Lai SM, Wen CY, Hsiao YL. 2004 Three-dimensional cytoorphology in fine
needle aspiration biopsy of subacute thyroiditis. Acta Cytol 48:155-160.

47. Woolner LB, McConahey WM, Beahrs OH. 1957 Granulomatous thyroiditis (de Quervain
thyroiditis). J Clin Endocrinol Metab 17:202.

47a. Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jaconbsen SJ. 2003 Clinical
features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County,
Minnesota, study. J Clin Endocrinol Metab 88:2100-2105.

48. Koga M, Hirumatsu Y, Jimi A, Toda S, Koike N, Nonaka K. 1999 Immunohistochemical
analysis of Bcl-2 Bax and Bak expression in thyroid glands of patients with subacute thyroiditis.
J Clin Endocrinol Metab 84:2221-2225.

49. Toda S, Nishimura T, Yamada S, Koike N, Yonemitsu N, Watanable K, Matsimura S,
Gartner R, Sugihara H. 1999 Immunohistochemical expression of growth factors in subacute
thyroiditis and their effects on follicogenesis and angiogenesis in collagen gel matric culture. J
Pathol 188:415-422.

50. Luotola K, Mantula P, Salmi J, Haapala AM, Laippala P, Hurme M. 2001 Allele 2 of
interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in
subacute thyroiditis. APMIS 109:454-460.

51. Toda S, Tokuda Y, Koike N, Yonemitsu N, Watanabe K, Koike K, Fujit N, Hiromatsu Y,
Sugihara H. 2000 Growth factor-expressing mast cells accumulate at the thyroid
tissue-regenerative site of subacute thyroiditis. Thyroid 10:381-386.

52. Daniels GH. 2001 Atypical subacute thyroiditis: preliminary observations. Thyroid

53. Nakamura S, Saio Y, Ishimori M. 1998 Recurrent hemi thyroiditis: a case report. Endocr J

54. Sari O, Erbas B, Erbas T. 2001 Subacute thyroiditis in a single lobe. Clin Nucl Med

55. Mizokami T, Okamura K, Sato K, Hirata T, Yamasaki F, Fujishima M. 1999 Localized
painful giant cell thyroiditis without inflammatory signs in a euthyroid patient followed by serial
sonography. J Clin Ultrasound 26:329-332.

56. Czernick P, Harrell-Steinberg A. 1957 The chronology of events in the development of
subacute thyroiditis, studied by radioactive iodine. J Clin Endocrinol Metab 17:1448-1453

57. Fragu P, Rougier P, Schlumberger M, Tubiana M. 1982 Evolution of thyroid 127I stores
measured by x-ray fluorescence in subacute thyroiditis. J Clin Endocrinol Metab 54:162-166.
58. Van Herle AJ, Uller RP, Matthews NL, Brown J. 1973 Radioimmunoassay for
measurement of thyroglobulin in human serum. J Clin Invest 52:1320-1327.

59. Glinoer D, Puttemans N, van Herle AJ, Camus M, Ermans AM. 1974 Sequential study of
the impairment of thyroid function in the early stage of subacute thyroiditis. Acta Endocrinol

60. Gordin A, Lamberg BA. 1973 Serum thyrotrophin response to thyrotrophin releasing
hormone and the concentration of free thyroxine in subacute thyroiditis. Acta Endocrinol

61. Intenzo CM, Park CH, Kim SM. 1993 Clinical, laboratory, and scintigraphic manifestations
of subacute and chronic thyroiditis. Clin Nucl Med 18:302-306.

62. Ingbar SH, Freinkel N. 1958 Thyroid function and the metabolism of iodine in patients with
subacute thyroiditis. Arch Intern Med 101:339-346

63. Rapoport B, Block MB, Hoffer PB, DeGroot LJ. 1973 Depletion of thyroid iodine during
subacute thyroiditis. J Clin Endocrinol Metab 36:610-611.

64. Savoie JC, Massin JP, Thomopoulos P, Leger F. 1975 Iodine-induced thyrotoxicosis in
apparenlty normal thyroid glands. J Clin Endocrinol Metab 11:685-691.

65. Larsen PR. 1974 Serum triiodothyronine, thyroxine, and thyrotropin during hyperthyroid,
hypothyroid, and recovery phases of subacute thyroiditis. Metabolism 23:467-471.

66. Gluck FB, Nusynowitz MI, Plymate S. 1975 Chronic lymphocytic thyroiditis, thyrotoxicosis
and low radioioactive iodine uptake: report of four cases. N Engl J Med 293:624-628.

67. Woolf PD. 1980 Transient painless thyroiditis with hyperthyroidism: a variant of
lymphocytic thyroiditis? Endocr Rev 1:411-420.

67a. Pearce EN, Bogazzi F, Martino E, Brogioni S, Pardini E, Pellegrini G, Parkes AB, Lazarus
JH, Pinchera A, Braverman LE. 2003 The prevalence of elevated serum C-reactive protein
levels in inflammatory and noninflammatory thyroid disease. Thyroid 13:643-648.

67b. Takasu N, Kamijo K, Sato Y, Yoshimura H, Nagata A, Ochi Y. 2004 Sensitive
thyroid-stimulating antibody assay with high concentrations of polyethylene glycol for the
diagnosis of Graves' disease. Clin Exp Pharmacol Physiol 31:314-319.

67c. Fujii S, Miwa U, Seta T, Ohoka T, Mizukami Y. 2003 Subacute thyroiditis with highly
positive thyrotropin receptor antibodies and high thyroidal radioactive iodine uptake. Intern
Med 42:704-709.

67d. Kamijo K. 2003 TSH-receptor antibody measurement in patients with various
thyrotoxicosis and Hashimoto's thyroiditis: a comparison of two two-step assays, coated plate
ELISA using porcine TSH-receptor and coated tube radioassay using human recombinant
TSH-receptor. Endocr J 50:113-116.

68. Hiromatsu Y, Ishibashi M, Miyake I, Nonaka K, 1998. Technetium-99 tetrofosmin imaging
in patients with subacute thyroiditis. Eur J Nucl Med 25(10):1448-1452.

68a. Hiromatsu Y, Ishibashi M, Nishida H, Kawamura S, Kaku H, Baba K, Kaida H, Miyake I.
2003 Technetium-99m sestamibi imaging in patients with subacute thyroiditis. Endocr J

68b. Tezuka M, Murata Y, Ishida R, Ohashi I, Hirata Y, Shibuya H. 2003 MR Imaging of the
thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy. J
Magn Reson Imaging 17:163-169.

69. Vierhapper H, Bieglmayer CH, Nowotny P, Waldhausl W. 1998 Normal serum
concentrations of sex hormone-binding globulin in patients with hyperthyroidism due to
subacute thyroiditis. Thyroid 8:1107-1111.

70. Itaka M, Momotani N, Hisaoka T, Noh Y, Ishikawa N, Ishii J, Katayama S, Ito K. 1998 TSH
receptor antibody-associated thyroid dysfunction following subacute thyroiditis. Clin Endocrinol

71. Zacharia TT, Perumpallichira JJ, Sindhwani V, Chavhan G. 2002 Gray-scale and color
Doppler sonographic findings in a case of subacute granulomatous thyroiditis mimicking
thyroid carcinoma. J Clin Ultrasound 30:442-444.

72. Shabb NS, Tawil A, Gergeos F, Saleh M, Azar S. 1999 Multinucleated giant cells in
fine-needle aspiration of thyroid nodules: Their diagnostic significance. Diagn Cytopathol

72a. Martinez DS, Chopra IJ. 2003 Use of oral cholecystography agents in the treatment of
hyperthyroidism of subacute thyroiditis. Panminerva Med 45:53-57.

73. Mizukoshi T, Noguchi S, Murakami T, Futata T, Yamashita H. 2001 Evaluation of
recurrence in 36 subacute thyroiditis patients managed with prednisolone. Intern Med

74. Duininck TM, van Heerden JA, Fatourechi V, Curlee KJ, Farley DR, Thompson DB, Grant
CS, Lloyd RV. 2002 de Quervain's thyroiditis: surgical experience. Endocr Pract 8:255-258.

75. Izumi M, Larsen PR. 1978 Correlation of sequential in serum thyroglobulin, triiodothyronine,
and thyroxine in patients with Graves' disease and subacute thyroiditis. Metabolism

76. Riedel BMCL. 1896 Die chronische, zur bildung eisenhaster tumoren fuhrende entzudung
der schilddrus. Verh Dtsch Ges Chir 25:101.
77. de Lange WF, Freling NJ, Molenaar WM, Doorenbos H. 1989 Invasive fibrous thyroiditis
(Reidel's struma): a manifestation of multifocal fibrosclerosis? A case report with review of the
literature. Quart J Med 72:709-717.

78. Zimmermann-Belsing T, Feldt-Rasmussen U. 1994 Reidel's thyroiditis: an autoimmune or
primary fibrotic disease? J Intern Med 235:271-274.

78a. Kojima M, Nakamura S, Yamane Y, Shimizu K, Sugiharal, S, Masawa N. 2003 Riedel's
thyroiditis containing cytologically atypically appearing B-cells: a case report. Pathol Res Pract

79. Torres-Montaner A, Beltran M, Romero de la Osa A, Oliva H. 2001 Sarcoma of the thyroid
region mimicking Riedel's thyroiditis. J Clin Pathol 54:570-572.

80. Schwaegerle SM, Bauer TW, Esselstyn CB Jr. 1988 Reidel's thyroiditis. Am J Clin Pathol

81. Chopra D, Wool MS, Crosson A, Sawin CT. 1978 Reidel's struma associated with
subacute associated with subacute thyroiditis, hypothyroidism, and hypo- parathyroidism. J
Clin Endocrinol Metab 46:869-871.

82. Marin F, Araujo R, Paramo C, Lucast Salto L. 1989 Reidel's thyroiditis associated with
hypo-thyroidism and hypoparathyroidism. Postgrad Med J 65:381-383.

83. Best TB, Munro RE, Burwell S, Volpe R. 1991 Riedel's thyroiditis associated with
Hashimoto's thyroiditis, hypoparathyroidism, and retroperitoneal fibrosis. J Endocrinol Invest

84. Yasmeen T, Khan S, Patel SG, Reeves WA, Gonsch FA, de Bustros A, Kaplan EL. 2002
Clinical case seminar: Riedel's thyroiditis: report of a case complicated by spontaneous
hypoparathyroidism, recurrent laryngeol nerve injury, and Horner's syndrome. J Clin
Endocrinol Metab 87:3543-3547.

84a. Nazal EM, Belmatoug N, de Roquancourt A, Lefort A, Fantin B. Hypoparathyroidism
preceding Riedel's thyroiditis. 2003 Eur J Intern Med 14:202-204.

84b. Egsgaard Nielsen V, Hecht P, Krogdahl AS, AndersenPB, Hegedus L. 2003 A rare case
of orbital involvement in Ridel's thyroiditis. J Endocrinol Invest 26:1032-1036.

85. Owen K, Lane H, Jones MK. 2001 Multifocal fibrosclerosis: a case of thyroiditis and
bilateral lacrimal gland involvement. Thyroid 1187-1190.

86. Drieskens O, Blockmans D, Van den Bruel A, Mortelmans L. 2002 Riedel's thyroiditis and
retroperitoneal fibrois in multifocal fibrosclerosis: positron emission tomographic findings. Clin
Nucl Med 27:413-415.
86a. Kotilainen P, Airas L, Kojo T, Kurki T, Kataja K, Minn H. Nuutila P. 2004 Positron
emission tomography as an aid in the diagnosis and follow-up of Riedel's thyroiditis. Eur J
Intern Med 15:186-189.

87. Takahashi N, Okamoto K, Sakai K, Kawana M, Shimada-Hiratsuka M. 2002 MR Findings
with dynamic evaluation in Riedel's thyroiditis. Clin Imaging 26:89-91.

88. Papi G, Corrado S, Cesinaro AM, Novelli L, Smerieri A, Carapezzi C. 2002 Riedel's
thyroiditis: clinical, pathological an imaging features. Int J Clin Pract 56:65-67.

89. Natt N, Heufelder AE, Hay ID, Grant CS, Goellner JR. 1997 Extracervical ibrosclerosis
causing obstruction of a ventriculo-peritoneal shunt in a patient with hydrocephalus and
invasive fibrous thyroiditis (Reidel's struma). Clin Endocrinol 47: 107-111.

90. Vaiydya B, Coulthard A, Goonetilleke A, Burn DJ, James RA, Kendall-Taylor P 1998.
Cerebral venous sinus thrombosis: a late sequel of invasive fibrous thyroiditis. Thyroid

91. Heufelder AE, Goellner JR, Bahn RS, Gleich GJ, Hay ID 1996 Tissue eosinophilia and
eosinophil degranulation in Riedel's invasive fibrous thyroiditis. J Clin Endocrinol Metab

92. Chen K, Wei Y, Sharp GC, Braley-Mullen H. 2000 Characterization of thyroid fibrosis in a
murine model of granulomatous experimental autoimmune thyroiditis. J Leukoc Biol

93. Vaidya B, Harris PE, Barret P, Kendall-Taylor P. 1997 Corticosteroid therapy in Riedel's
thyroiditis. Postgrad Med 73:817-819.

94. Lo JC, Loh KC, Rubin AL, Cha I, Greenspan FS. 1998 Riedel's thyroiditis presenting with
hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine
therapy. Clin Endocrinol 48:415-818.

95. Tutuncu NB, Erbas T, Bayraktar M, Gedik O. 2000 Multifocal idopathic fibrosclerosis
manifesting with Riedel's thyroiditis. Endocr Pract 6:447-449.

95a. Hostalet F, Hellin D, Ruiz JA. 2003 Tumefactive fibroinflammatory lesion of the head and
neck treated with steroids: a case report. Eur Arch Otorhinolaryngol 260:299-331.

95b. Moulik PK, Al-Jafari MS, Khaleeli AA. 2004 Steroid responsiveness in a case of Riedel's
thyroiditis and retroperitoneal fibrosis. Int J Clin Pract 58:312-315.

96. Thomson JA, Jackson IMJ, Duguid WP. 1968 The effect of steriod therapy on Riedel's
Thyroiditis. Scott Med J 13:13-16.

97. Katsikas D, Shorthouse AJ, Taylor S. 1976 Riedel's thyroiditis. Br J Surg 63:929-931.
98. Few J, Thompson NW, Angelos P, Simeone D, Giodano T, Reeve T. 1996 Riedel's
thyroiditis: treatment with Tamoxifen. Surgery 120:993-998.

99. De M, Jaap A, Dempster J. 2002 Tamoxifen therapy in steroid-resistant Riedels disease.
Scott Med J 47:12-13.

99a. Dabelic N, Jukie T, Labar Z, Novosel SA, Matesa N, Kusic Z. 2003 Riedel's thyroiditis
treated with Tamoxifen. Croat Med J 44:239-241.

100. LB Woolner, McConahey WM, Beahrs OH. 1957 Invasive fibrous thyroiditis (Riedel's
struma). J Clin Endocrinol Metab 17:201-220.

101. Bando Y, Ushiogi Y, Toya D, Tanaka N, Fujisawa M. 2001 Painless thyroiditis associated
with severe inflammatory reactions in amyloid goiter: a case report. Endocr J 48:323-329.

102. Bryer-Ash M, Lodhi W, Robbins KT, Morrison R. 2001 Early thyrotoxic thyroiditis after
radiotherapy for tonsillar carcinoma. Arch Otolaryngol Head Neck Surg 127:209-211.

103. McDermott A, Onyeaka CV, Macnamara M. 2002 Surgery-induced thyroiditis: fact or
fiction? Ear Nose Throat J 81:408-410

104. Blenke EJ, Vernham GA, Ellis G. 2004 Surgery-induced thyroiditis following laryngectomy.
J Laryngol Otol 118:313-314.

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