S P E C I A L F E A T U R E

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
R results in destruction of the thyroid and infiltra-
tion into surrounding tissues (1–3). Recently, several
authors have proposed that this inflammatory condi-
tion of the thyroid is a local manifestation of a systemic
fibrotic process (1) or an autoimmune process (3). Syn-
onyms include Riedel’s struma, struma fibrosa, ligneous
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 jcem.endojournals.org 3031

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 3032 Hennessey Riedel’s Thyroiditis
itis, and chronic sclerosing or productive thyroiditis (4).
The condition is characterized by an overgrowth of pro-
gressively fibrosing connective tissue that may invade
surrounding structures (5, 6).
History and Incidence
Described initially by Semple in 1864 and Bolby in 1888
(7), the condition that Riedel reported to the Interna-
tional Congress of Surgery in 1894 and 1896 (8 –10)
was an inflammatory process resulting in “eisenharte”
(iron-hard), fixed, and usually painless enlargement of
the thyroid (3, 5, 8). Riedel’s thyroiditis is exceedingly
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
over a 64-yr period during which over 56,000 thyroidec-
tomies were performed at the Mayo Clinic (14). The 37
cases of invasive fibrous thyroiditis were identified among
the 3.5 million patients registered at Mayo during that
time. Estimated incidence in the population was noted to
be 1.06 cases per 100,000 population and 37 of 57,000
(0.06%) documented thyroidectomy outcomes (14). Es-
timates based on outcomes of thyroid surgery done for all
disorders indicate a variable incidence of up to 0.98% in
another relatively small surgical series (16). Women have
been noted to be affected 3-fold more frequently than men
(4, 8, 17, 18); a recent series noted 81% of those evaluated
at Mayo Clinic with a confirmed Riedel’s diagnosis from
1976 –2008 were women (19). Estimates indicate that pa-
tients between 30 and 50 yr of age are the most affected (4,
17, 19).
Pathology
Thyroid and perithyroidal involvement in this process
may be limited or extensive; a lobe or the entire thyroid
may be replaced by this inflammatory fibrotic process,
which may extend into adjacent structures. The resulting
invasion and replacement of structures involves parathy-
roid glands, skeletal muscle, nerves, blood vessels, as well
as the trachea. The inflammatory process forms a firm to
hard (woody) palpable mass that, upon gross examina-
tion, appears pale gray, similar in appearance to a malig-
nant lesion (20). There are typically no tissue planes discern-
able macroscopically, making precise surgical resection
impossible. The cut surface of the mass is typically stark
white in appearance because of specimen hypovascularity
(21). Histologically, the normal tissues are replaced by a mass
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J Clin Endocrinol Metab, October 2011, 96(10):3031–3041
consisting of inflammatory cells, predominantly a mixed
population of lymphocytes, plasma cells, eosinophils (4,
22), and small amounts of colloid (11, 13, 15) in a dense
matrix of hyalinized connective tissue. Characteristically,
an inflammatory reaction of the venous vascular struc-
tures has been described (20). An oft-stated criterion use-
ful in assuring the pathological diagnosis is to note the
absence of granulomatous tissue and malignancy (4, 20,
21). A potentially difficult differential diagnostic decision
may be encountered with rare sarcomas of the thyroid
region (23) or with the paucicellular variant of anaplastic
thyroid cancer, which although similar in gross appear-
ance will have distinctive histopathological immunohis-
tochemical findings (24).
Etiology
The true etiology of this disorder is as yet unclear. Poten-
tial characterizations have included Riedel’s thyroiditis as
a thyroid or cervical location for a systemic fibrosing dis-
order with identical histopathological features (25), a
variant of Hashimoto’s thyroiditis, a primary inflamma-
tory disorder of the thyroid, or even a manifestation of
end-stage subacute thyroiditis (1, 11, 12). The presence of
eosinophilic infiltration on histopathology has suggested
for years a unique autoimmune response stimulating fi-
brosis in affected tissue (4). Others have noted an associ-
ation of Riedel’s and autoimmunity (26, 27), which has
been supported by the finding of mononuclear cell infil-
tration, vasculitis, the ever-present fibrosis (11), and re-
inforced by reports of positive antithyroid antibodies (2).
Riedel’s has been reported in the presence of clinically
thyrotoxic Graves’ disease, and Hashimoto’s thyroiditis,
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-
specific antibodies, normal serum complement levels, and
the specific lymphocyte subpopulation profiles observed
(25) do not support a common etiology. This has led some
investigators to conclude that the positive thyroid anti-
bodies should be considered reactive (2) to thyroid tissue
destruction. Recently, a link between Hashimoto’s thy-
roiditis and IgG4-related systemic disease has been re-
ported (32, 33). Because Riedel’s has also now been as-
sociated with IgG4-related systemic disease (see below),
the potential link between Hashimoto’s and Riedel’s may
be clarified as this potential relationship is further inves-
tigated (34).
A consistent event in the pathological picture of Rie-
del’s is fibroblast proliferation induced by cytokine release
 J Clin Endocrinol Metab, October 2011, 96(10):3031–3041
from B and/or T lymphocytes (4). The tissue eosinophilia,
previously cited as an indication of autoimmune involve-
ment, also allows an alternative disease mechanism as sug-
gested by Heufelder et al. (22), who have alluded to the
potential presence of an as yet unidentified eosinophil de-
granulation product thought to induce aggressive fibrosis
seen in the Riedel’s patient.
The role of long-term follow-up observation to assess
etiology, emergence, progression, or outcomes of Rie-
del’s thyroiditis provides another perspective in under-
standing this disease process. A few reports of Riedel’s
developing in patients with recurrent painful episodes
where a clinical diagnosis of subacute thyroiditis was
reached have been published (18, 25, 31, 35, 36). It is
certainly possible that these cases designated as sub-
acute thyroiditis were early and unusual (painful) pre-
sentations of Riedel’s because the histological picture
may be somewhat similar (7, 20). When followed for
many years, patients with Hashimoto’s thyroiditis almost
never (37) develop the features of Riedel’s (4), but this
sequence of diagnoses has been reported (38).
Evidence has been accumulating that Riedel’s thy-
roiditis is an organ-specific manifestation of multifocal
idiopathic fibrosclerosis by virtue of its presentation in
association with other histologically related fibrosing
processes such as retroperitoneal fibrosis (1, 39 – 44),
fibrosing mediastinitis (39, 45– 49), sclerosing cholan-
gitis (44, 50), pancreatitis (19, 51), lacrimal fibrosis (1),
orbital fibrosis (pseudotumor) (1, 52–55), and tume-
factive fibroinflammatory lesions of the head and neck
(56 –58). The entity described as multifocal idiopathic
fibrosclerosis above has also been called multifocal fibroscle-
rosis (44, 46), which more recently seems to be synonymous
with the emerging multiple organ system condition ini-
tially described in patients with a pancreatic inflammatory
condition termed “autoimmune pancreatitis” (59, 60).
This multisystem fibrotic process is histologically defined
like Riedel’s by the presence of inflammation, described as
lymphoplasmacytic with eosinophilia (61). The latest de-
scriptive designations are based on the high proportion of
IgG4⫹ plasma cells demonstrable in the inflammatory in-
filtrates by immunohistochemistry (61). Additionally, this
IgG4-related systemic sclerosing disease is histologically
characterized by differing degrees of fibrosis that replace
affected tissue (61). Lastly, IgG4-related systemic disease
(IgG4-RSD) affects medium and small veins in the tissues
leading to an obliterative phlebitis demonstrable on his-
topathology (61). Individuals with IgG4-RSD frequently
demonstrate elevated serum IgG4 levels that have proven
a useful tool in the identification of the nature of the un-
derlying inflammatory disease (59, 61, 62). A thyroid link
to IgG4-RSD was noted by an increased incidence of (ap-
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parently autoimmune) hypothyroidism among those with
autoimmune pancreatitis (63). Most recently, investiga-
tors have directly linked Riedel’s to the IgG4-RSD by dem-
onstrating excessive numbers of IgG4⫹ plasma cells in
clinically diagnostic thyroid histology samples by immu-
nohistochemistry (38). Further research into this apparent
connection between Riedel’s and IgG4-RSD is required
because not all reported cases have documented the pres-
ence of IgG4⫹ plasma cells in the inflammatory tissues
analyzed (64), nor is there a reported case of Riedel’s with
elevated IgG4 serum levels (19).
Once diagnosed, most patients with Riedel’s do not
develop other manifestations of destructive fibroses (1). At
most, about one third eventually manifest other signs of
systemic fibrosis (14, 19, 30). Similarly, Riedel’s is very
uncommonly diagnosed in populations where the initial
diagnosis of retroperitoneal fibrosis has been established
(4); an estimated incidence of less than 1% has been doc-
umented (65). Increasing numbers of case reports seem to
indicate that extracervical fibrosis may occur in more than
one additional site when Riedel’s is present (64, 66).
Unlike other forms of systemic fibrosis, there does
not seem to be a reported association of medication use
preceding the onset of Riedel’s (1, 4). No clear-cut pat-
terns of genetic inheritance have been observed among
those with the Riedel’s (46). A role for Epstein-Barr
virus has been postulated in regard to the provocation
of Riedel’s (67), but further confirmation is lacking.
Finally, a recent report links smoking history to the
presence of Riedel’s and indicates that a history of cur-
rent or previous exposure was more frequently found
among those with confirmed Riedel’s than in a control
population with Hashimoto’s thyroiditis (19). The im-
pact of smoking cessation on the onset or clinical course
of Riedel’s has not been described.
Clinical Presentation
Riedel’s thyroiditis presents as a firm mass in the thyroid
commonly associated with compressive symptoms (1, 4, 5,
8, 14, 17, 19). The presence of dyspnea, dysphagia,
hoarseness, and aphonia, caused by local pressure or in-
filtration of the advancing fibrotic process, is classically
described (4, 14, 15) and may precede the recognition of
physical findings (19). Initial clinical concerns include the
potential of a thyroid malignancy (13) because the palpa-
ble mass is typically rock hard and may not be freely mov-
able upon swallowing. If observed by a surgeon at the time
of operation, the involved thyroid and surrounding struc-
tures including muscles, nerves, and trachea may appear to
be a mass of fibrosclerosing tissue (68, 69). Grossly, this is
 3034 Hennessey Riedel’s Thyroiditis J Clin Endocrinol Metab, October 2011, 96(10):3031–3041

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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 J Clin Endocrinol Metab, October 2011, 96(10):3031–3041
thyroid involvement (see Clinical course and prognosis)
should prompt the assessment of calcium status.
Routine imaging of the thyroid with ultrasonography
finds a diffuse, hypoechoic, hypovascular appearance due
to the extensive fibrosis (69, 71, 75, 80, 81). Unique to the
patient with Riedel’s would be finding carotid artery en-
casement that is not typically seen in usual forms of multi-
nodular goiter or Hashimoto’s goiter (19, 82). The ultra-
sound evidence of arterial encasement has also been
reported to resolve when effective antiinflammatory treat-
ment has been applied (82). Application of thyroid ultra-
sonographic elastography demonstrates significant stiff-
ness in the Riedel’s inflammatory tissue (82). If clinically
indicated by significant obstructive symptomatology,
computed tomography (CT) images of the neck reveal en-
largement of the affected area and hypodense tissue, which
does not enhance with the administration of iodinated
contrast dye (80). Most CT images have demonstrated
evidence of the extrathyroidal invasion (80, 83) and may
demonstrate vascular encasement with more than half of
carotid arteries and one third of internal jugular veins re-
ported affected (19). Magnetic resonance imaging (MRI)
reveals hypointense images on both T1- and T2-weighted
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-
parent hypointensity of CT and MRI images, positron
emission tomography (PET) using fluorine-18 fluorode-
oxyglucose demonstrates intense uptake in the areas of the
fibrotic inflammation seen in patients with Riedel’s (82,
86, 87). Positron emission tomography may also be useful
in identifying other areas of fibrosis and especially in the
follow-up of individuals. After successful medical inter-
vention, fluorine-18 fluorodeoxyglucose uptake is re-
duced significantly and correlated with the symptomatic
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-
nuclide imaging of the thyroid with Tc-99 or 123/131-I
demonstrates heterogeneous and typically low radioactive
iodine uptake as is commonly seen in other forms of
chronic thyroiditis (4, 11, 13). An exception to this pattern
is posed by the patient with Graves’ disease or toxic nod-
ular goiter with superimposed Riedel’s, where intense up-
take in the hyperfunctioning portion of uninvolved thy-
roid would be expected (75). Lastly, it has recently been
reported that the inflammatory process of Riedel’s may be
identified in the course of gallium scanning (88).
Diagnostic Criteria
Evaluation of a palpable thyroid lesion would typically
lead to the performance of a fine-needle aspiration study
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of the affected area. Results of fine-needle aspiration are
usually nondiagnostic (4, 17, 19, 21), but some may yield
findings of inflammation (19), fragments of fibrous tissue
with bland spindle-shaped cells and myofibroblasts (89),
or even cytopathology consistent with follicular neoplasm
(77). Definitive diagnosis is made only with histopathol-
ogy, from an open biopsy (17), or after decompressive
goiter surgery performed for clinical symptoms. Specific
histopathological criteria for a diagnosis of Riedel’s thy-
roiditis have been established and refined over the past
several years (90, 91). At this point the following are re-
quired to establish the diagnosis of Riedel’s thyroiditis in
an individual patient. 1) There should be an inflammatory
process in the thyroid with extension into surrounding
tissue. 2) The inflammatory infiltrate should contain no
giant cells, lymphoid follicles, oncocytes, or granulomas.
3) There should be evidence of occlusive phlebitis. 4) There
should be no evidence of thyroid malignancy (91). In light
of the recent work in defining Riedel’s as a potential man-
ifestation of the IgG4-related systemic sclerosing disease
(38, 61), the potential role of incorporating immunohis-
tochemical plasma cell assessment and circulating IgG4
levels into the diagnostic criteria remains to be defined.
Differential Diagnosis
Riedel’s thyroiditis must be differentiated clinically and
histologically from malignancies, especially anaplastic
thyroid cancer (24), thyroid lymphoma (70), and sarcoma
of the thyroid (23). Additional differentiation must be
made with the fibrosing variant of Hashimoto’s thyroid-
itis, which accounts for approximately 10% of Hashimo-
to’s cases and is said to be more frequently seen among the
elderly presenting with Hashimoto’s (3) (Table 1).
Clinical Course and Prognosis
The course of Riedel’s thyroiditis is quite variable, with
mild cases being found incidentally and more aggressive
presentations leading to dramatic and progressive clinical
symptoms (17, 21). In general, because of the slowly pro-
gressive course of most cases, the diagnosis is delayed for
variable periods of time after the onset of clinical symp-
toms. This delay has been estimated to range from more
than 10 months to 2 yr after the onset of observable signs
such as goiter (19). After initial presentation, it has been
observed that the process may stabilize or even regress (4,
21, 92). Progressive fibrosis leads to increasing local symp-
toms such as sensations of suffocation, stridor, and pain-
less neck pressure out of proportion to the size of the goiter
present (27, 93). Initial estimates of 30 to 40% of cases
 3036 Hennessey Riedel’s Thyroiditis J Clin Endocrinol Metab, October 2011, 96(10):3031–3041

eventually having developed hypothyroidism (3, 35, 71,
74) have been superseded by the finding that more than
80% are hypothyroid during the course of follow-up (19).
Involvement of the parathyroid glands in the progressive
fibrosis results in primary hypoparathyroidism (3, 18, 35,
71, 74) in up to 14% of those presenting with Riedel’s and
a positive effect of medical intervention on this deficiency
may be seen (19). Mortality in older reports has resulted
from tracheal compression, upper airway compromise,
and respiratory failure. Rates of disease-specific death
have ranged in frequency from 6 –10% (11, 13). A recent
series from the Mayo Clinic reported no mortality over a
mean follow-up of 9.5 yr and reported that 86% of the
subjects followed (frequently on medical therapy) were
stable or improved symptomatically (19). Contemporary
outcomes await further studies of cohorts followed after
current therapeutic interventions.
Local complications are encountered as the Riedel’s
thyroiditis runs its course and include impairment of the
recurrent laryngeal nerves (3, 74), Tolosa-Hunt syndrome
(94), and Horner’s syndrome (74). Involvement of the cer-
vical blood vessels (occlusive phlebitis) (42, 95, 96) may
also result in cerebral venous sinus thrombosis (97, 98).
Estimates as high as 38% or more associate Riedel’s
with the occurrence of other fibrotic processes. These
other forms of fibrosis may be present before or at the time
of Riedel’s diagnosis or may be observed during follow-up
(19). These fibrosing lesions include ocular involvement,
with exophthalmos or range of motion defects or optic
nerve abnormalities as seen in orbital pseudotumor (52,
53, 55), which may be similar to the clinical presentation
of Graves’ ophthalmopathy. The multifocal fibrosclerosis
process may result in suprasellar lesions (99); only one
such case of pituitary fibrosis has been reported, unfortu-
nately without endocrine data (100). A case of pituitary
failure (101) has been reported with Riedel’s (4, 101). The
multihormonal pituitary failure noted was reversible with
L-thyroxine while the patient was treated with prednisone
for the inflammatory process. The pituitary function was
stable after withdrawal of glucocorticoids. Because no le-
sion of the pituitary was present at postmortem examina-
tion (101), the role of the fibrotic process in these findings
is unclear.
Tumefactive fibroinflammatory lesions of the head or
neck (56 –58) and infiltration of the parotid glands (fi-
brous parotitis) (102) have been documented. Mediastinal
fibrosis (13, 14, 19, 20), resulting in superior vena cava
syndrome (103, 104), tracheoesophageal fistula (105),
pleuropericardial effusions (106), and fibrosis involving
the left anterior descending coronary artery resulting in
coronary obstruction (19) are seen. Additionally, an in-
flammatory sc chest mass has been noted to result in the
fibrosis of a ventriculoperitoneal shunt, resulting in dis-
ruption of shunt function (19, 107). Retroperitoneal fi-
brosis (1, 14, 39, 71, 76) reported in patients with Riedel’s
results in renal failure and hydroureteronephrosis (71).
Hepatic involvement with sclerosing cholangitis is well
documented (4, 21, 64). Pancreatic fibrosis presents with
abdominal pain, evidence of cholestasis, and abnormal
cholangiography (51, 64). An overview of clinical findings
associated with Riedel’s thyroiditis is outlined in Table 2.
Therapeutic Considerations
Riedel’s thyroiditis has no agreed upon standard treat-
ment. Patients commonly undergo surgery to relieve ob-
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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 J Clin Endocrinol Metab, October 2011, 96(10):3031–3041
After establishment of the diagnosis, most are then treated
medically with varying degrees of success. Appropriate
intervention for identified endocrine system deficiencies
should include the initiation of L- thyroxine replacement
therapy for those presenting with primary hypothyroid-
ism, and calcium as well as calcitriol therapy for control of
concomitant hypoparathyroidism. Finally, antiinflamma-
tory treatments aimed at diminishing the inflammatory
mass are applied.
Surgical therapy
Effective treatment of the Riedel’s goiter includes deb-
ulking surgery usually limited to isthmusectomy to relieve
constrictive pressure (4, 5, 72, 77) when total thyroidec-
tomy is not possible. Due to the obliteration of tissue
planes by the fibrotic process, the danger of hypoparathy-
roidism and recurrent nerve damage make aggressive sur-
gical intervention problematic. One recent series indicates
that although complete resection of the sclerotic neck mass
was not possible in any patient, open biopsy, isthmusec-
tomy, and excision of at least a portion of the thyroid were
carried out in the majority. Despite limited surgical inter-
vention, seven of the 18 (39%) subjects had complications
such as permanent vocal cord paralysis to surgical hypo-
parathyroidism when treated by expert surgical teams
(19). Previous and contemporary experience has therefore
led to the recommendation that extensive surgical proce-
dures be considered inappropriate in the management of
Riedel’s (17, 19, 21, 77).
Medical therapy
After establishment of the diagnosis of Riedel’s, initi-
ation of medical treatments to arrest the progression of
symptomatic disease should be pursued. The medical in-
terventions used are not thoroughly validated by con-
trolled clinical trials due to the rarity of the condition, but
they include empiric application of glucocorticoids (2, 28,
35, 108 –110) and tamoxifen (111). Although not consid-
ered a standard of care, glucocorticoids are usually the first
step in the medical management of the patient with the
established diagnosis of Riedel’s thyroiditis (112). Gluco-
corticoid therapy has been reported to result in dramatic
improvement in symptoms associated with the Riedel’s
inflammatory mass (98). Reduction in the size and con-
sistency of the mass and upper airway symptoms have in
some cases resolved (35, 98, 108). Symptoms of dysphonia
and recurrent laryngeal nerve involvement have also been
reported to clear (108).
Glucocorticoids have been considered more effective
when initiated early in the course of disease (109), and this
concept has recently been supported by the histopatho-
logical appearance of the thyroid in a patient undergoing
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jcem.endojournals.org 3037
thyroidectomy in two steps separated by 2 yr (38). The
initial histopathology demonstrated an active hypercellu-
lar inflammatory fibrotic process composed of lympho-
cytes, plasma cells (excessively IgG4⫹), and eosinophils
extending into the surrounding extrathyroidal tissue. Two
years later, the other lobe showed extensive intra- and ex-
trathyroidal fibrosis, which was largely acellular (IgG4⫹
plasma cells were not detected) and hyalinizing in nature
without the robust inflammatory infiltrate that characterized
the initial specimen (38).
The dosing of glucocorticoid therapy is empiric. A re-
cent textbook reference recommends 100 mg of predni-
sone daily initially (4). It is clear that various reports doc-
ument positive results with other glucocorticoids and
equivalent doses as low as 15 to 60 mg of prednisone per
day (28, 70, 74, 108, 110). Some patients reported seem to
have experienced enduring responses after the tapering
and withdrawal of the glucocorticoids (25, 113), but other
reports have noted either no response or recurrence of
symptoms associated with the fibrotic process after com-
pletion of sometimes lengthy courses of glucocorticoids.
Failure of glucocorticoids to control the inflammatory
process usually leads the reporting authors to turn to ad-
ditional or alternative treatments to suppress disease ac-
tivity (74, 111, 114). A recent observation indicates a po-
tential influence of smoking history on glucocorticoid
response in Riedel’s thyroiditis. Active smokers with more
aggressive fibrotic progression needed repeated courses
and longer duration of glucocorticoid therapy for symp-
tomatic disease when compared with nonsmokers (19).
Further study of the effects of smoking and smoking ces-
sation on the course of Riedel’s would be useful.
Tamoxifen has also been reported to be an effective
medical intervention in Riedel’s thyroiditis (74, 106, 111,
115–119) as well as other forms of the underlying multi-
focal fibrosis (116). Proposed mechanisms of positive ac-
tion of tamoxifen in this and associated inflammatory con-
ditions (116) involve the induction of autocrine secretion
of TGF-␤1 as observed in both estrogen receptor-positive
and -negative tumor samples in vitro (111, 120, 121) and
the potential for subsequent inhibition of fibroblastic
function, perhaps through its influence on the production
of TGF␤, a potent growth inhibitor (72, 121, 122). Doses
of 10 to 20 mg of tamoxifen either in conjunction with
continued prednisone or as monotherapy have been re-
ported in the literature to be successful (74, 111, 115,
117), significantly reducing mass size and clinical symp-
toms with apparent persistent effectiveness during contin-
ued therapy in most but not all cases reported (19, 114).
The durability of suppressing the fibrotic process with
tamoxifen therapy is not clear.
 3038 Hennessey Riedel’s Thyroiditis
A recent report demonstrates significant reduction of
goiter size using a combination of mycophenolate mofetil
(1 g twice daily) and 100 mg prednisone daily (114). This
report documents an individual unsuccessfully treated
with combined tamoxifen and prednisone. The addition
of mycophenolate mofetil resulted in symptomatic relief
and successful subtotal thyroidectomy after 90 d of
treatment (114). Mycophenolate mofetil, a recently
identified therapy for disorders associated with sys-
temic fibrosis (123), is activated to mycophenolic acid
and directly inhibits T- and B-lymphocytic proliferation
and antibody production (124). It is also considered to
possess antifibrotic properties in nonimmune experi-
mental models of chronic kidney disease and pulmonary
fibrosis (125–128). The potential usefulness of this in-
tervention awaits confirmation.
Low-dose irradiation has been attempted in patients
with Riedel’s thyroiditis (21). A recent search of the
PubMed database, however, does not contain any pro-
spective or outcomes data in regard to irradiation of the
Riedel’s lesion. Only a few reports of radiation treatment
in associated fibrotic processes such as orbital pseudotu-
mor (129) and tumefactive fibroinflammatory lesions of
the head and neck (49) have appeared in the literature.
Neither of these reports offers any information on clinical
outcomes, nor did any of these subjects have Riedel’s.
Summary and Conclusions
Riedel’s thyroiditis should be suspected in patients pre-
senting with a thyroid mass and certain unique clinical
features. Findings that increase the likelihood of finding
Riedel’s such as local restrictive or infiltrative symptoms,
which may be out of proportion to the size or extent of the
demonstrable mass lesion, or simultaneous biochemical
deficiencies especially of calcium should lead the clinician
to consider this diagnosis. Surgical intervention should be
limited to rule out the presence of malignancy and obtain
the histopathological confirmation of the presence of Rie-
del’s. Extensive surgery due the risk of complications
should be avoided. Once the diagnosis of Riedel’s thyroid-
itis is established, a search for related fibrotic conditions
and medical treatment should be considered. Replacement
of T4 and, when appropriate, calcium and vitamin D ther-
apy should be started along with antiinflammatory med-
ications in those with symptomatic fibroinflammatory
disease. The potential diagnostic role of serum IgG4 mea-
surement, which may influence both diagnostic and ther-
apeutic decisions, and the optimal duration of antiinflam-
matory treatment await further study.
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J Clin Endocrinol Metab, October 2011, 96(10):3031–3041
Acknowledgments
Thanks to Pamela Hartzband, M.D., and the JCEM reviewers
for helpful review of the manuscript.
Address all correspondence and requests for reprints to: Dr.
James V. Hennessey, Beth Israel Deaconess Medical Center, Di-
vision of Endocrinology, 330 Brookline Avenue, GZ-6, Boston,
Massachusetts 02215. E-mail: jhenness@bidmc.harvard.edu.
Disclosure Summary: The author has nothing to declare.
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