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C l i n i c a l R e v i e w

Riedel’s Thyroiditis: A Clinical Review

James V. Hennessey
Harvard Medical School and Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston,
Massachusetts 02215

Context: Riedel’s thyroiditis is a rare inflammatory process involving the thyroid and surrounding
cervical tissues and is associated with various forms of systemic fibrosis. Riedel’s presentation is
complex, including a thyroid mass associated with local symptoms, characteristic biochemical ab-
normalities such as hypocalcemia and hypothyroidism, as well as the involvement of a wide range
of other organ systems. Diagnosis of Riedel’s thyroiditis requires histopathological confirmation,
but due to high complication rates, the role of surgical intervention is limited to airway decom-
pression and diagnostic tissue retrieval. Unique among processes of the thyroid, Riedel’s is com-
monly treated with long-term antiinflammatory medications to arrest progression and maintain
a symptom-free course. Due to its rarity, Riedel’s may not be immediately diagnosed, so clinicians
benefit from recognizing the constellation of findings that should make prompt diagnosis possible.

Evidence Acquisition: A review of print and electronic reviews was conducted. Source references
were identified, and available literature was reviewed. A search of the PubMed database using the
search term “Riedel’s thyroiditis” was cross-referenced with associated clinical findings, systemic
fibrosis diagnoses, and therapeutic search terms. Because most of the literature consisted of case
reports and very small series, inclusion of identified articles was based on clinical descriptions of the
subjects included and the criteria for diagnosis reported. More weight was attributed to series,
using contemporary criteria for diagnosis. Case reports were included if the diagnosis was clear and
clinical presentation was unique to illustrate the spectrum of disease.

Evidence Synthesis: Because the majority of therapeutic intervention data were based upon case
reports and very small series, an evidence-based approach was problematic, but information is
presented as objectively and with as much balance as the limited quality of the data allows.

Conclusions: Clinical awareness of the characteristic presentations of Riedel’s thyroiditis should en-
hance our ability to make this diagnosis in a timely and focused manner. Recognition of certain clinical
finding patterns will increase the likelihood of recognizing Riedel’s thyroiditis promptly. Local restric-
tive or infiltrative symptoms out of proportion to a demonstrable mass or simultaneous biochemical
deficiencies especially of calcium should lead the clinician to consider this diagnosis. Likewise in this
setting, the surgeon alert to this possibility may minimize overly aggressive surgical intervention, thus
avoiding complications. Once Riedel’s thyroiditis is diagnosed, the application of antiinflammatory
therapies may greatly enhance the clinical outcome. Understanding the pathophysiological relation-
ship of this entity with other forms of systemic fibrosis and the role that IgG4 may play in this process
should result in enhanced diagnostic and therapeutic tools in the future. (J Clin Endocrinol Metab 96:
3031–3041, 2011)

iedel’s thyroiditis is a rare fibrotic condition that tion of the thyroid is a local manifestation of a systemic
R results in destruction of the thyroid and infiltra-
tion into surrounding tissues (1–3). Recently, several
fibrotic process (1) or an autoimmune process (3). Syn-
onyms include Riedel’s struma, struma fibrosa, ligneous
authors have proposed that this inflammatory condi- struma or thyroiditis, chronic invasive fibrous thyroid-

ISSN Print 0021-972X ISSN Online 1945-7197 Abbreviations: CT, Computed tomography; IgG4-RSD, IgG4-related systemic disease; MRI,
Printed in U.S.A. magnetic resonance imaging.
Copyright © 2011 by The Endocrine Society
doi: 10.1210/jc.2011-0617 Received March 9, 2011. Accepted July 14, 2011.
First Published Online August 11, 2011

J Clin Endocrinol Metab, October 2011, 96(10):3031–3041 3031

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itis, and chronic sclerosing or productive thyroiditis (4). consisting of inflammatory cells, predominantly a mixed
The condition is characterized by an overgrowth of pro- population of lymphocytes, plasma cells, eosinophils (4,
gressively fibrosing connective tissue that may invade 22), and small amounts of colloid (11, 13, 15) in a dense
surrounding structures (5, 6). matrix of hyalinized connective tissue. Characteristically,
an inflammatory reaction of the venous vascular struc-
tures has been described (20). An oft-stated criterion use-
History and Incidence ful in assuring the pathological diagnosis is to note the
absence of granulomatous tissue and malignancy (4, 20,
Described initially by Semple in 1864 and Bolby in 1888 21). A potentially difficult differential diagnostic decision
(7), the condition that Riedel reported to the Interna-
may be encountered with rare sarcomas of the thyroid
tional Congress of Surgery in 1894 and 1896 (8 –10)
region (23) or with the paucicellular variant of anaplastic
was an inflammatory process resulting in “eisenharte”
thyroid cancer, which although similar in gross appear-
(iron-hard), fixed, and usually painless enlargement of
ance will have distinctive histopathological immunohis-
the thyroid (3, 5, 8). Riedel’s thyroiditis is exceedingly
tochemical findings (24).
rare, occurring in some series one 50th as frequently as
Hashimoto’s thyroiditis (11–15). There is a paucity of
robust epidemiological data because the world’s liter-
ature consists primarily of case reports and small case
series. A group of 37 patients reported in 1985 were seen The true etiology of this disorder is as yet unclear. Poten-
over a 64-yr period during which over 56,000 thyroidec- tial characterizations have included Riedel’s thyroiditis as
tomies were performed at the Mayo Clinic (14). The 37 a thyroid or cervical location for a systemic fibrosing dis-
cases of invasive fibrous thyroiditis were identified among order with identical histopathological features (25), a
the 3.5 million patients registered at Mayo during that variant of Hashimoto’s thyroiditis, a primary inflamma-
time. Estimated incidence in the population was noted to tory disorder of the thyroid, or even a manifestation of
be 1.06 cases per 100,000 population and 37 of 57,000 end-stage subacute thyroiditis (1, 11, 12). The presence of
(0.06%) documented thyroidectomy outcomes (14). Es- eosinophilic infiltration on histopathology has suggested
timates based on outcomes of thyroid surgery done for all for years a unique autoimmune response stimulating fi-
disorders indicate a variable incidence of up to 0.98% in brosis in affected tissue (4). Others have noted an associ-
another relatively small surgical series (16). Women have
ation of Riedel’s and autoimmunity (26, 27), which has
been noted to be affected 3-fold more frequently than men
been supported by the finding of mononuclear cell infil-
(4, 8, 17, 18); a recent series noted 81% of those evaluated
tration, vasculitis, the ever-present fibrosis (11), and re-
at Mayo Clinic with a confirmed Riedel’s diagnosis from
inforced by reports of positive antithyroid antibodies (2).
1976 –2008 were women (19). Estimates indicate that pa-
Riedel’s has been reported in the presence of clinically
tients between 30 and 50 yr of age are the most affected (4,
thyrotoxic Graves’ disease, and Hashimoto’s thyroiditis,
17, 19).
and has significant responsiveness to glucocorticoid inter-
vention (28). Further autoimmune associations have been
observed with Addison’s disease, pernicious anemia, and
type 1 diabetes (2, 29 –31); the absence of other organ-
Thyroid and perithyroidal involvement in this process specific antibodies, normal serum complement levels, and
may be limited or extensive; a lobe or the entire thyroid the specific lymphocyte subpopulation profiles observed
may be replaced by this inflammatory fibrotic process, (25) do not support a common etiology. This has led some
which may extend into adjacent structures. The resulting investigators to conclude that the positive thyroid anti-
invasion and replacement of structures involves parathy- bodies should be considered reactive (2) to thyroid tissue
roid glands, skeletal muscle, nerves, blood vessels, as well destruction. Recently, a link between Hashimoto’s thy-
as the trachea. The inflammatory process forms a firm to roiditis and IgG4-related systemic disease has been re-
hard (woody) palpable mass that, upon gross examina- ported (32, 33). Because Riedel’s has also now been as-
tion, appears pale gray, similar in appearance to a malig- sociated with IgG4-related systemic disease (see below),
nant lesion (20). There are typically no tissue planes discern- the potential link between Hashimoto’s and Riedel’s may
able macroscopically, making precise surgical resection be clarified as this potential relationship is further inves-
impossible. The cut surface of the mass is typically stark tigated (34).
white in appearance because of specimen hypovascularity A consistent event in the pathological picture of Rie-
(21). Histologically, the normal tissues are replaced by a mass del’s is fibroblast proliferation induced by cytokine release
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from B and/or T lymphocytes (4). The tissue eosinophilia, parently autoimmune) hypothyroidism among those with
previously cited as an indication of autoimmune involve- autoimmune pancreatitis (63). Most recently, investiga-
ment, also allows an alternative disease mechanism as sug- tors have directly linked Riedel’s to the IgG4-RSD by dem-
gested by Heufelder et al. (22), who have alluded to the onstrating excessive numbers of IgG4⫹ plasma cells in
potential presence of an as yet unidentified eosinophil de- clinically diagnostic thyroid histology samples by immu-
granulation product thought to induce aggressive fibrosis nohistochemistry (38). Further research into this apparent
seen in the Riedel’s patient. connection between Riedel’s and IgG4-RSD is required
The role of long-term follow-up observation to assess because not all reported cases have documented the pres-
etiology, emergence, progression, or outcomes of Rie- ence of IgG4⫹ plasma cells in the inflammatory tissues
del’s thyroiditis provides another perspective in under- analyzed (64), nor is there a reported case of Riedel’s with
standing this disease process. A few reports of Riedel’s elevated IgG4 serum levels (19).
developing in patients with recurrent painful episodes Once diagnosed, most patients with Riedel’s do not
where a clinical diagnosis of subacute thyroiditis was develop other manifestations of destructive fibroses (1). At
reached have been published (18, 25, 31, 35, 36). It is most, about one third eventually manifest other signs of
certainly possible that these cases designated as sub- systemic fibrosis (14, 19, 30). Similarly, Riedel’s is very
acute thyroiditis were early and unusual (painful) pre- uncommonly diagnosed in populations where the initial
sentations of Riedel’s because the histological picture diagnosis of retroperitoneal fibrosis has been established
may be somewhat similar (7, 20). When followed for (4); an estimated incidence of less than 1% has been doc-
many years, patients with Hashimoto’s thyroiditis almost umented (65). Increasing numbers of case reports seem to
never (37) develop the features of Riedel’s (4), but this indicate that extracervical fibrosis may occur in more than
sequence of diagnoses has been reported (38). one additional site when Riedel’s is present (64, 66).
Evidence has been accumulating that Riedel’s thy- Unlike other forms of systemic fibrosis, there does
roiditis is an organ-specific manifestation of multifocal not seem to be a reported association of medication use
idiopathic fibrosclerosis by virtue of its presentation in preceding the onset of Riedel’s (1, 4). No clear-cut pat-
association with other histologically related fibrosing terns of genetic inheritance have been observed among
processes such as retroperitoneal fibrosis (1, 39 – 44), those with the Riedel’s (46). A role for Epstein-Barr
fibrosing mediastinitis (39, 45– 49), sclerosing cholan- virus has been postulated in regard to the provocation
gitis (44, 50), pancreatitis (19, 51), lacrimal fibrosis (1), of Riedel’s (67), but further confirmation is lacking.
orbital fibrosis (pseudotumor) (1, 52–55), and tume- Finally, a recent report links smoking history to the
factive fibroinflammatory lesions of the head and neck presence of Riedel’s and indicates that a history of cur-
(56 –58). The entity described as multifocal idiopathic rent or previous exposure was more frequently found
fibrosclerosis above has also been called multifocal fibroscle- among those with confirmed Riedel’s than in a control
rosis (44, 46), which more recently seems to be synonymous population with Hashimoto’s thyroiditis (19). The im-
with the emerging multiple organ system condition ini- pact of smoking cessation on the onset or clinical course
tially described in patients with a pancreatic inflammatory of Riedel’s has not been described.
condition termed “autoimmune pancreatitis” (59, 60).
This multisystem fibrotic process is histologically defined
like Riedel’s by the presence of inflammation, described as Clinical Presentation
lymphoplasmacytic with eosinophilia (61). The latest de-
scriptive designations are based on the high proportion of Riedel’s thyroiditis presents as a firm mass in the thyroid
IgG4⫹ plasma cells demonstrable in the inflammatory in- commonly associated with compressive symptoms (1, 4, 5,
filtrates by immunohistochemistry (61). Additionally, this 8, 14, 17, 19). The presence of dyspnea, dysphagia,
IgG4-related systemic sclerosing disease is histologically hoarseness, and aphonia, caused by local pressure or in-
characterized by differing degrees of fibrosis that replace filtration of the advancing fibrotic process, is classically
affected tissue (61). Lastly, IgG4-related systemic disease described (4, 14, 15) and may precede the recognition of
(IgG4-RSD) affects medium and small veins in the tissues physical findings (19). Initial clinical concerns include the
leading to an obliterative phlebitis demonstrable on his- potential of a thyroid malignancy (13) because the palpa-
topathology (61). Individuals with IgG4-RSD frequently ble mass is typically rock hard and may not be freely mov-
demonstrate elevated serum IgG4 levels that have proven able upon swallowing. If observed by a surgeon at the time
a useful tool in the identification of the nature of the un- of operation, the involved thyroid and surrounding struc-
derlying inflammatory disease (59, 61, 62). A thyroid link tures including muscles, nerves, and trachea may appear to
to IgG4-RSD was noted by an increased incidence of (ap- be a mass of fibrosclerosing tissue (68, 69). Grossly, this is
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especially suspicious for anaplastic thyroid cancer (24), TABLE 1. Differentiation of fibrosing Hashimoto’s and
thyroid sarcoma (23), or lymphoma (70). Riedel’s thyroiditis
As the extent of the fibrosis increases before diagnosis,
Riedel’s Fibrosing
not only will local symptoms become more prominent, but
Finding thyroiditis Hashimoto’s
function of the involved glands and surrounding struc-
Thyroid antibodies Yes, moderate titer Yes, high titer
tures complicate the clinical picture. Initial reports of Rie- Normal thyroid tissue Yes, sharp No, diffuse
del’s indicated that hypothyroidism was present only oc- demarcation involvement
casionally (71), but subsequent series have observed Venulitis Yes No
Extrathyroidal invasion Yes No
primary hypothyroidism at some point in the course of Hurthle cells No Yes
disease in 25 to 80% or more (1, 13, 15, 19). The fre- Lymphocyte light chains ␭ dominant (71%) ␬ dominant
quency with which hypothyroidism is present may be re- Plasma cell production IgA increased IgG dominant,
(47%) IgA (⬍15%)
lated to the extent of thyroid involvement in the infiltrative Associated autoimmune Yes Yes
process, with low incidence when less than total involve- disease
ment of the thyroid is reported (1, 15, 17, 71, 72), or to the Associated de Yes No
frequency with which concomitant Hashimoto’s thyroid- Quervain’s
Ultrasound appearance Hypoechoic Hypoechoic
itis is present. A recent series from the Mayo Clinic indi- Doppler flow Diminished Enhanced
cates that of 19 subjects with Riedel’s and available thy- Compiled and modified from Refs. 21, 34, 69, 71, 75, 77, 80, 81, 90,
roid function results at presentation, 14 (74%) were and 130.
hypothyroid and nine of the 10 evaluated had positive
antithyroid antibodies (19). Other thyroid function ab- Extension of the underlying fibrotic process can im-
normalities reported at or before presentation include thy- pact parathyroid function. Until the late 1990s, there
rotoxicosis followed by hypothyroidism, which have been had been only nine cases of Riedel’s associated with
attributed to subacute (de Quervain’s) thyroiditis (35, 36, hypoparathyroidism (1, 35, 71, 77–79). Review of this
73) or possibly lymphocytic subacute thyroiditis (74). literature demonstrates a spectrum of clinical presen-
Consistent with the potential autoimmune associations with tation from asymptomatic hypocalcemia with well-doc-
Riedel’s, a minority of patients have presented with hyper- umented PTH deficiency (77) to clear-cut symptomatic
thyroidism attributed to Graves’ disease (1, 13, 26, 75). tetany necessitating immediate intervention (71). Aside
The sequential or simultaneous appearance of true from the obvious potential for postoperative parathy-
Hashimoto’s thyroiditis and the fibrotic process of Rie- roid dysfunction, most cases of hypoparathyroidism
del’s struma has been observed (20, 37, 71, 76, 77). The documented in the literature have been spontaneous, as-
fibrotic form of Hashimoto’s is histologically character- sociated with the duration of the process, and usually ap-
ized by destruction of the thyroid architecture with follic- pearing after the establishment of primary hypothyroid-
ular atrophy, epithelial metaplasia, and keloid-like fibro- ism (71). Most recently, the presence of nonsurgical
sis, which is limited to the thyroid (3). Recent observations hypoparathyroidism observed at presentation was 14% of
using IgG4 as a marker indicate that the fibrosing form of those seen at the Mayo Clinic (19).
Hashimoto’s demonstrates significant involvement of Taken in isolation, the combination of primary hypo-
IgG4-positive plasma cells in the infiltrates, apparently thyroidism, positive antithyroid antibodies, and a goiter
resulting in the higher degree of stromal fibrosis (32). This therefore may be confused with the much more common
finding would seem to blur the differences between Hashimoto’s thyroiditis. The addition of sometimes dra-
matic local symptoms and findings of hypoparathyroid-
Hashimoto’s and Riedel’s, emphasizing the importance of
ism or other forms of fibrosis should lead the observant
this differential diagnosis (34). As recently reviewed (21),
clinician to recognize the unique picture suggestive of Rie-
consideration of clinical factors may be useful to differ-
del’s thyroiditis.
entiate the two entities, especially when fibrotic presen-
tations of Hashimoto’s are encountered (Table 1). Initial
reports of Riedel’s indicated that thyroid antibodies, when
Clinical Evaluation
evaluated, were seldom positive; when detected, titers
tended to be low (71, 77). As time has gone on, the pres- In addition to the assessment of thyroid function and an-
ence of thyroid autoantibodies documented in conjunc- tibodies, the general laboratory evaluation of the patient
tion with Riedel’s seems to be more common (5, 13, 14, with Riedel’s reveals white blood cell counts to be normal
36), most recently noted to be in 90% of those followed at or elevated, and the erythrocyte sedimentation rate is usu-
the Mayo Clinic (19). ally moderately elevated (11, 13). The potential of para-
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thyroid involvement (see Clinical course and prognosis) of the affected area. Results of fine-needle aspiration are
should prompt the assessment of calcium status. usually nondiagnostic (4, 17, 19, 21), but some may yield
Routine imaging of the thyroid with ultrasonography findings of inflammation (19), fragments of fibrous tissue
finds a diffuse, hypoechoic, hypovascular appearance due with bland spindle-shaped cells and myofibroblasts (89),
to the extensive fibrosis (69, 71, 75, 80, 81). Unique to the or even cytopathology consistent with follicular neoplasm
patient with Riedel’s would be finding carotid artery en- (77). Definitive diagnosis is made only with histopathol-
casement that is not typically seen in usual forms of multi- ogy, from an open biopsy (17), or after decompressive
nodular goiter or Hashimoto’s goiter (19, 82). The ultra- goiter surgery performed for clinical symptoms. Specific
sound evidence of arterial encasement has also been histopathological criteria for a diagnosis of Riedel’s thy-
reported to resolve when effective antiinflammatory treat- roiditis have been established and refined over the past
ment has been applied (82). Application of thyroid ultra- several years (90, 91). At this point the following are re-
sonographic elastography demonstrates significant stiff- quired to establish the diagnosis of Riedel’s thyroiditis in
ness in the Riedel’s inflammatory tissue (82). If clinically an individual patient. 1) There should be an inflammatory
indicated by significant obstructive symptomatology, process in the thyroid with extension into surrounding
computed tomography (CT) images of the neck reveal en- tissue. 2) The inflammatory infiltrate should contain no
largement of the affected area and hypodense tissue, which giant cells, lymphoid follicles, oncocytes, or granulomas.
does not enhance with the administration of iodinated 3) There should be evidence of occlusive phlebitis. 4) There
contrast dye (80). Most CT images have demonstrated should be no evidence of thyroid malignancy (91). In light
evidence of the extrathyroidal invasion (80, 83) and may of the recent work in defining Riedel’s as a potential man-
demonstrate vascular encasement with more than half of ifestation of the IgG4-related systemic sclerosing disease
carotid arteries and one third of internal jugular veins re- (38, 61), the potential role of incorporating immunohis-
ported affected (19). Magnetic resonance imaging (MRI) tochemical plasma cell assessment and circulating IgG4
reveals hypointense images on both T1- and T2-weighted levels into the diagnostic criteria remains to be defined.
protocols (80); after gadolinium administration, a spec-
trum from little to marked homogeneous enhancement
has been observed (80, 81, 83– 85). In contrast to the ap-
Differential Diagnosis
parent hypointensity of CT and MRI images, positron
emission tomography (PET) using fluorine-18 fluorode- Riedel’s thyroiditis must be differentiated clinically and
oxyglucose demonstrates intense uptake in the areas of the histologically from malignancies, especially anaplastic
fibrotic inflammation seen in patients with Riedel’s (82, thyroid cancer (24), thyroid lymphoma (70), and sarcoma
86, 87). Positron emission tomography may also be useful of the thyroid (23). Additional differentiation must be
in identifying other areas of fibrosis and especially in the made with the fibrosing variant of Hashimoto’s thyroid-
follow-up of individuals. After successful medical inter- itis, which accounts for approximately 10% of Hashimo-
vention, fluorine-18 fluorodeoxyglucose uptake is re- to’s cases and is said to be more frequently seen among the
duced significantly and correlated with the symptomatic elderly presenting with Hashimoto’s (3) (Table 1).
response (86, 87) in some but not all reports (82).
Although not usually indicated in the evaluation of eu-
thyroid individuals with a palpable thyroid mass, radio- Clinical Course and Prognosis
nuclide imaging of the thyroid with Tc-99 or 123/131-I
demonstrates heterogeneous and typically low radioactive The course of Riedel’s thyroiditis is quite variable, with
iodine uptake as is commonly seen in other forms of mild cases being found incidentally and more aggressive
chronic thyroiditis (4, 11, 13). An exception to this pattern presentations leading to dramatic and progressive clinical
is posed by the patient with Graves’ disease or toxic nod- symptoms (17, 21). In general, because of the slowly pro-
ular goiter with superimposed Riedel’s, where intense up- gressive course of most cases, the diagnosis is delayed for
take in the hyperfunctioning portion of uninvolved thy- variable periods of time after the onset of clinical symp-
roid would be expected (75). Lastly, it has recently been toms. This delay has been estimated to range from more
reported that the inflammatory process of Riedel’s may be than 10 months to 2 yr after the onset of observable signs
identified in the course of gallium scanning (88). such as goiter (19). After initial presentation, it has been
observed that the process may stabilize or even regress (4,
Diagnostic Criteria 21, 92). Progressive fibrosis leads to increasing local symp-
toms such as sensations of suffocation, stridor, and pain-
Evaluation of a palpable thyroid lesion would typically less neck pressure out of proportion to the size of the goiter
lead to the performance of a fine-needle aspiration study present (27, 93). Initial estimates of 30 to 40% of cases
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eventually having developed hypothyroidism (3, 35, 71, nately without endocrine data (100). A case of pituitary
74) have been superseded by the finding that more than failure (101) has been reported with Riedel’s (4, 101). The
80% are hypothyroid during the course of follow-up (19). multihormonal pituitary failure noted was reversible with
Involvement of the parathyroid glands in the progressive L-thyroxine while the patient was treated with prednisone
fibrosis results in primary hypoparathyroidism (3, 18, 35, for the inflammatory process. The pituitary function was
71, 74) in up to 14% of those presenting with Riedel’s and stable after withdrawal of glucocorticoids. Because no le-
a positive effect of medical intervention on this deficiency sion of the pituitary was present at postmortem examina-
may be seen (19). Mortality in older reports has resulted tion (101), the role of the fibrotic process in these findings
from tracheal compression, upper airway compromise, is unclear.
and respiratory failure. Rates of disease-specific death Tumefactive fibroinflammatory lesions of the head or
have ranged in frequency from 6 –10% (11, 13). A recent neck (56 –58) and infiltration of the parotid glands (fi-
series from the Mayo Clinic reported no mortality over a brous parotitis) (102) have been documented. Mediastinal
mean follow-up of 9.5 yr and reported that 86% of the fibrosis (13, 14, 19, 20), resulting in superior vena cava
subjects followed (frequently on medical therapy) were syndrome (103, 104), tracheoesophageal fistula (105),
stable or improved symptomatically (19). Contemporary pleuropericardial effusions (106), and fibrosis involving
outcomes await further studies of cohorts followed after the left anterior descending coronary artery resulting in
current therapeutic interventions. coronary obstruction (19) are seen. Additionally, an in-
Local complications are encountered as the Riedel’s flammatory sc chest mass has been noted to result in the
thyroiditis runs its course and include impairment of the fibrosis of a ventriculoperitoneal shunt, resulting in dis-
recurrent laryngeal nerves (3, 74), Tolosa-Hunt syndrome ruption of shunt function (19, 107). Retroperitoneal fi-
(94), and Horner’s syndrome (74). Involvement of the cer- brosis (1, 14, 39, 71, 76) reported in patients with Riedel’s
vical blood vessels (occlusive phlebitis) (42, 95, 96) may results in renal failure and hydroureteronephrosis (71).
also result in cerebral venous sinus thrombosis (97, 98). Hepatic involvement with sclerosing cholangitis is well
Estimates as high as 38% or more associate Riedel’s documented (4, 21, 64). Pancreatic fibrosis presents with
with the occurrence of other fibrotic processes. These abdominal pain, evidence of cholestasis, and abnormal
other forms of fibrosis may be present before or at the time cholangiography (51, 64). An overview of clinical findings
of Riedel’s diagnosis or may be observed during follow-up associated with Riedel’s thyroiditis is outlined in Table 2.
(19). These fibrosing lesions include ocular involvement,
with exophthalmos or range of motion defects or optic
nerve abnormalities as seen in orbital pseudotumor (52, Therapeutic Considerations
53, 55), which may be similar to the clinical presentation
of Graves’ ophthalmopathy. The multifocal fibrosclerosis Riedel’s thyroiditis has no agreed upon standard treat-
process may result in suprasellar lesions (99); only one ment. Patients commonly undergo surgery to relieve ob-
such case of pituitary fibrosis has been reported, unfortu- structive symptoms and establish a definitive diagnosis.

TABLE 2. Clinical presentation of Riedel’s thyroiditis and associated fibrotic conditions

Finding Clinical symptoms Pathology Diagnostic evaluation
Goiter Pressure Encasement Thyroid ultrasound
Dysphagia Esophageal CT neck/UGI
Vocal cord paralysis Recurrent nerve Laryngoscopy
Dyspnea/stridor Upper airway CT neck
CNS Carotid encasement Angiography
Hypothyroidism Fatigue Thyroid infiltration TSH, FT4, ATAbs
Hypoparathyroidism Tetany, cramping Parathyroid infiltration CaPO4/Alb/PTH
Systemic fibrosis
Retroperitoneal Low back/flank pain Hydroureteronephrosis U/A, BUN/Cr, U/S, pyelogram
Mediastinal SVC syndrome SVC restriction SVC venogram
Pulmonary restriction Pulmonary arteries or veins Pulmonary angiogram
Cholangitis Abdominal pain Irregular hepatic ducts Bili, AlkPhos, ALT, AST, ERCP
Pancreatitis Abdominal pain Irregular pancreatic ducts Bili, AlkPhos, ALT, AST, ERCP
Orbital pseudotumor Exophthalmos Intraorbital mass Orbital CT
Tumefactive fibroinflammatory Head/neck mass Soft tissue fibrosis Head/neck CT, biopsy
UGI, Upper gastrointestinal; CNS, central nervous system; FT4, free T4; SVC, superior vena cava; ATAbs, antithyroid antibodies; Alb, albumin; AST,
aspartate aminotransferase; ERCP, endoscopic retrograde choleangiopancreatography; Bili, bilirubin; AlkPhos, alkaline phosphatase; U/A, urinalysis;
U/S, ultrasound; BUN/Cr, blood urea nitrogen and creatinine.

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After establishment of the diagnosis, most are then treated thyroidectomy in two steps separated by 2 yr (38). The
medically with varying degrees of success. Appropriate initial histopathology demonstrated an active hypercellu-
intervention for identified endocrine system deficiencies lar inflammatory fibrotic process composed of lympho-
should include the initiation of L- thyroxine replacement cytes, plasma cells (excessively IgG4⫹), and eosinophils
therapy for those presenting with primary hypothyroid- extending into the surrounding extrathyroidal tissue. Two
ism, and calcium as well as calcitriol therapy for control of years later, the other lobe showed extensive intra- and ex-
concomitant hypoparathyroidism. Finally, antiinflamma- trathyroidal fibrosis, which was largely acellular (IgG4⫹
tory treatments aimed at diminishing the inflammatory plasma cells were not detected) and hyalinizing in nature
mass are applied. without the robust inflammatory infiltrate that characterized
the initial specimen (38).
Surgical therapy The dosing of glucocorticoid therapy is empiric. A re-
Effective treatment of the Riedel’s goiter includes deb- cent textbook reference recommends 100 mg of predni-
ulking surgery usually limited to isthmusectomy to relieve sone daily initially (4). It is clear that various reports doc-
constrictive pressure (4, 5, 72, 77) when total thyroidec- ument positive results with other glucocorticoids and
tomy is not possible. Due to the obliteration of tissue equivalent doses as low as 15 to 60 mg of prednisone per
planes by the fibrotic process, the danger of hypoparathy- day (28, 70, 74, 108, 110). Some patients reported seem to
roidism and recurrent nerve damage make aggressive sur- have experienced enduring responses after the tapering
gical intervention problematic. One recent series indicates and withdrawal of the glucocorticoids (25, 113), but other
that although complete resection of the sclerotic neck mass
reports have noted either no response or recurrence of
was not possible in any patient, open biopsy, isthmusec-
symptoms associated with the fibrotic process after com-
tomy, and excision of at least a portion of the thyroid were
pletion of sometimes lengthy courses of glucocorticoids.
carried out in the majority. Despite limited surgical inter-
Failure of glucocorticoids to control the inflammatory
vention, seven of the 18 (39%) subjects had complications
process usually leads the reporting authors to turn to ad-
such as permanent vocal cord paralysis to surgical hypo-
ditional or alternative treatments to suppress disease ac-
parathyroidism when treated by expert surgical teams
tivity (74, 111, 114). A recent observation indicates a po-
(19). Previous and contemporary experience has therefore
tential influence of smoking history on glucocorticoid
led to the recommendation that extensive surgical proce-
response in Riedel’s thyroiditis. Active smokers with more
dures be considered inappropriate in the management of
aggressive fibrotic progression needed repeated courses
Riedel’s (17, 19, 21, 77).
and longer duration of glucocorticoid therapy for symp-
Medical therapy tomatic disease when compared with nonsmokers (19).
After establishment of the diagnosis of Riedel’s, initi- Further study of the effects of smoking and smoking ces-
ation of medical treatments to arrest the progression of sation on the course of Riedel’s would be useful.
symptomatic disease should be pursued. The medical in- Tamoxifen has also been reported to be an effective
terventions used are not thoroughly validated by con- medical intervention in Riedel’s thyroiditis (74, 106, 111,
trolled clinical trials due to the rarity of the condition, but 115–119) as well as other forms of the underlying multi-
they include empiric application of glucocorticoids (2, 28, focal fibrosis (116). Proposed mechanisms of positive ac-
35, 108 –110) and tamoxifen (111). Although not consid- tion of tamoxifen in this and associated inflammatory con-
ered a standard of care, glucocorticoids are usually the first ditions (116) involve the induction of autocrine secretion
step in the medical management of the patient with the of TGF-␤1 as observed in both estrogen receptor-positive
established diagnosis of Riedel’s thyroiditis (112). Gluco- and -negative tumor samples in vitro (111, 120, 121) and
corticoid therapy has been reported to result in dramatic the potential for subsequent inhibition of fibroblastic
improvement in symptoms associated with the Riedel’s function, perhaps through its influence on the production
inflammatory mass (98). Reduction in the size and con- of TGF␤, a potent growth inhibitor (72, 121, 122). Doses
sistency of the mass and upper airway symptoms have in of 10 to 20 mg of tamoxifen either in conjunction with
some cases resolved (35, 98, 108). Symptoms of dysphonia continued prednisone or as monotherapy have been re-
and recurrent laryngeal nerve involvement have also been ported in the literature to be successful (74, 111, 115,
reported to clear (108). 117), significantly reducing mass size and clinical symp-
Glucocorticoids have been considered more effective toms with apparent persistent effectiveness during contin-
when initiated early in the course of disease (109), and this ued therapy in most but not all cases reported (19, 114).
concept has recently been supported by the histopatho- The durability of suppressing the fibrotic process with
logical appearance of the thyroid in a patient undergoing tamoxifen therapy is not clear.
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3038 Hennessey Riedel’s Thyroiditis J Clin Endocrinol Metab, October 2011, 96(10):3031–3041

A recent report demonstrates significant reduction of Acknowledgments

goiter size using a combination of mycophenolate mofetil
Thanks to Pamela Hartzband, M.D., and the JCEM reviewers
(1 g twice daily) and 100 mg prednisone daily (114). This
for helpful review of the manuscript.
report documents an individual unsuccessfully treated
with combined tamoxifen and prednisone. The addition Address all correspondence and requests for reprints to: Dr.
of mycophenolate mofetil resulted in symptomatic relief James V. Hennessey, Beth Israel Deaconess Medical Center, Di-
and successful subtotal thyroidectomy after 90 d of vision of Endocrinology, 330 Brookline Avenue, GZ-6, Boston,
Massachusetts 02215. E-mail:
treatment (114). Mycophenolate mofetil, a recently Disclosure Summary: The author has nothing to declare.
identified therapy for disorders associated with sys-
temic fibrosis (123), is activated to mycophenolic acid
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