J. Endocrinol. Invest. 17: 733-737,1994

CASE REPORT

Riedel's thyroiditis associated with high titers of anti microsomal and antithyroglobulin antibodies and hypothyroidism F. Zelmanovitz, T. Zelmanovitz, M. Beck, C.T. Cerski, H. Schmid, and M.A. Czepielewski Division of Endocrinology and Division of Pathology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sui, Porto Alegre, Brazil

ABSTRACT. Riedel's thyroiditis is a rare, chronic inflammatory disease of the thyroid gland. The ag­gressive fibrosis with extension beyond the thyroid into adjacent tissues contrasts with the diffuse, but intracapsular fibrosis of Hashimoto's thyroiditis. Most current studies refute the possibility of progression from a highly fibrosing form of Hashimoto's thy­roiditis to a Riedel's thyroiditis based on the distinct clinical and laboratory data, although an unknown immunological basis is suggested for both diseases. The authors describe a patient with Riedel's thy-

INTRODUCTION

Riedel's thyroiditis (invasive fibrous thyroiditis, lig­neous Eisenharte struma or Riedel's struma) is a rare and chronic inflammatory disease of the thyroid gland described by Riedel in 1896 (1). Its agressive fibrosis tends to progress inexorably to complete destruction of the thyroid gland but also, characteristically, spreads beyond the thyroid capsule into adjacent tis­sues such as nerves, blood vessels, and muscles (2, 3). Thyroid fibrosis can occur also in cases of thy­roiditis (subacute or chronic), radiation thyroiditis, nodular goiter, desmoplasia, scleroderma, trauma and amyloid disease, either focally or diffusely throughout the gland (4). The distinction between Riedel's thyroiditis and Hashimoto's thyroiditis (chron­ic Iymphocitic thyroiditis) is controversial since Dr. Hashimoto first described the disorder associated with his eponym (4, 5). It has been suggested that Riedel's thyroiditis may represent a late form of Hashimoto's thyroiditis, but since the microscopic cri-

Key-words: Riedel's thyroiditis, anti microsomal antibodies, antithy­roglabulin antibodies, hypothyroidism.

Correspondence: Dr. Flavio Zelmanovitz, Rua Fernandes Vieira 181/202, Porto Alegre, RS, CEP 90035, Brazil.

Received August 30, 1993; accepted April 5, 1994.

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roiditis, probably associated with Hashimoto's thy­roiditis, sent to surgery because her cytological ex­amination suggested thyroid malignancy. This pa­tient had clinical and laboratory features of hy­pothyroidism and very high titers of antimicrosomal and antithyroglobulin antibodies, which decreased after surgery. Pathology studies disclosed Riedel's thyroiditis with intense lymphocytic infiltration sug­gestive of Hashimoto's thyroiditis. Quantitative im­munohistochemical studies were not able to distin­guish between both diseases.

teria for the diagnosis of Riedel's thyroiditis were es­tablished by Woolner and associates in 1957 (6), and the redefinition of the fibrosing variant of Hashimoto's thyroiditis in 1974 by Katz and Vickery (7), most au­thors now agree that they are distinct diseases (2-4, 8-10). We describe a patient with Riedel's thyroiditis, probably associated with Hashimoto's thyroiditis, sub­jected to surgery because thyroid malignancy was suspected at cytological examination.

CASE REPORT

A 43-year-old woman presented with a six-month progressive goiter. She complained of gaining 10 kg in this period, tired easily, had constipation, men­strual irregularity and increased sensitivity to cold. On physical examination her height was 1.54 m, the weight was 65.0 kg. There was facial oedema in­cluding the periorbital area, with no signs of con­junctival inflamation or eye muscle involvement. The thyroid was enlarged (about 80 g) and stony hard at palpation. There was a palpable 1 cm submandibu­lar node. The laboratory evaluation showed T4-RIA 2,1ug/dL (N: 4-12); T3-RIA 40ug/dL (N: 70-190); TSH-IRMA 112m1U/L (N: 0,4-4,0); antithyroglobulin antibodies (detected by gelatin agglutination-Sera Tek-Ames) 1/102.400 (N: less than 1/100); antimi-

F. Zelmanovitz, T. Zelmanovitz, M Beck, et al.

Fig. 1 - Fine needle aspiration: numerous follicular cells, some with enlarged and pleomorphic nuclei suggestive of follicular neoplasia. Giemsa stain, X 1000.

crossomal antibodies (detected by gelatin agglu­tination - Sera Tek - Ames) 1/1.638.400 (N: less than 1/100); calcium 9,5 mg/dL: phosphorus 4,0 mg/dL; and albumin 3,9 g/dL. The X-Ray examination of the cervical region defined a goiter with extensive cal­cifications which did not penetrate the mediastinum, but reduced the tracheal lumen. Fine needle aspi­ration of the thyroid was performed and revealed nu­merous follicular celis, some of which had atypies (enlarged and pleomorphic nuclei) suggestive of fol­licular neoplasia (Fig. 1). The patient was treated with thyroxine and underwent subtotal thyroidectomy. The procedure was not completed due to undefined tis­sue planes found just beneath the skin and between the goiter and the trachea. Tracheostomy was per­formed due to stenosis of the tracheal lumens and

Fig. 2 - Residual follicle, extensive fibrosis and chronic inflam­atory cells. HE, X 100.

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Fig . 3 - Riedel'S thyroiditis with extensive fibrosis and chronic in­flamatory cells. HE, X 400.

the patient developed permanent postoperative hy­poparathyroidism. Pathological studies disclosed Riedel's thyroiditis. There was diffuse fibrosis with intense lymphocyt­ic infiltration and germinal centers in the thyroid (Fig. 2). The same histologic pattern was observed in the adjacent muscle and fat tissues (Fig. 3-4). No Hurthle cell was observed, although there was little residual thyroid tissue to be used for study. Quantitative immunohistochemical studies for Kappa and lambda chain detection with im­munoperoxidase techniques was carried out on step sections taken in pairs at regular intervals throughout the block. One of each pair was used to locate Kappa chains and the other to locate Lambda chains individually. Each section was ran-

Fig. 4 - Riedel's thyroiditis with extensive fibrosis and chronic in­flammatory cells infiltrating soft tissues in the immediate thyroid gland. HE, X 400.

Fig. 5 - Plasma cells containing Kappa chains. Immunoperoxi­dase technique, X 400.

domly examined at twenty affected fields, at a mag­nification of X 400, and numbers of Kappa and Lambda positive cells were expressed as a per­centage of the total. The average percentage ob­tained was 45.6% for plasmocytes containing Kappa chains (Fig. 5) and 54.4% for plasmocytes containing Lambda chains (Fig. 6). Extracervical fi­brosis was excluded by X-Rays and by computer­ized tomography of the abdomen and thorax. After 7 months, the patient was euthyroid and eucal­cemic with thyroxine 150 I-1g q.d., calcium carbon­ate 2g b.i.d. and 1,25 dihydroxyvitamin 0 3 0.251-1g b.i.d.; and both the titers of antithyroglobulin anti­bodies and antimicrossomal antibodies decreased, respectively to 1/1600 and 1/25600, and further to 1/1600 and 1/640. Facial oedema desappeared.

Fig. 6 - Plasma cells containing Lambda chains. Immunopero­xidase technique, X 400.

Riedel's thyroiditis and hypothyroidism

DISCUSSION

Riedel's thyroiditis is a very rare disorder, with on­ly 185 cases reported in the english language un­til 1988 (11), with a reported incidence between 0.03 and 0.98 of thyroidectomies in several surgical series (2). It was 0.06% in the Mayo Clinic series where only 37 cases were diagnosed between 1920 and 1984 (12). The etiology remains unknown and, although an im­munological basis is suggested for it , as for Hashimoto's thyroiditis, only two cases of progres­sion from the latter to Riedel's thyroiditis have been described (10,13). Harach and Williams suggest­ed that immunochemical distinctions were possi­ble by quantitative studies of the immunoglobulin­containing cells. These studies showed that, in fi­brous Hashimoto's thyroiditis, cells containing kap­pa light chains outnumbered lambda-containing cells (64% vs 36%) and IgG-containing cells pre­dominated over the IgA cells (85 vs 15%), but the opposite occurred in all Riedel's thyroiditis cases studied (29 vs 71 % and 53 vs 47%) (14). The same high proportion of IgA- and lambda-containing cells were found in the inflammatory cells infiltrating retroperitonial fibrosis, strengthening its common immunological basis with Riedel's thyroiditis (15). The patient described here had an inconclusive quantitative immunohistochemical study with re­sults just between those found in Riedel's and Hashimoto's thyroiditis. Other clinical and patho­logic features allow differentiation between Riedel's and Hashimoto's thyroiditis (Table 1), but some sim­ilar findings may exist and cause problems for the definitive diagnosis. Hay et al. found appreciable titers of thyroid autoantibodies in 45% of the pa­tients with Riedel's thyroiditis tested in the Mayo Clinic series (12). Schwaegerle and associates, re­viewing the 185 reported cases, found similar pro­portions of C04- and CD8-positive lymphocytes in Riedel's and Hashimoto's thyroiditis, and positive titers for thyroid antibodies in 67% of the 25 patients tested (11). Our patient showed very high titers of thyroid autoantibodies which declined after surgery. This is highly suggestive of the coexistence of Hashimoto's thyroiditis, but may also reflect an epiphenomenon, a reaction to antigens released from destroyed thyroid tissue as proposed by Schwaegerle (11). Livolsi describes the fibrosis of Hashimoto's thy­roiditis as not destroying the gland lobulation that is noted at low power. Broad fibrous bands separate residual zones of degenerating thyroid. The latter shows changes reminiscent of classic chronic lym­phocytic thyroiditis, including follicular atrophy, oxyphil metaplasia and lymphoid infiltration with ger-

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F. Zelmanovitz, T Zelmanovitz, M Beck, et al.

Table 1 - Clinical and pathologic features of thyroiditis.

Riedel

30-70

2-4/1

Hashimoto

20-50 Age (years)

Sex (F/M)

Symptoms

Thyroid antibodies

Following

Pressure goiter

Negative/very low

Rare hypothyroidism

4-10/1

Goiter/hypothyroid

Positive/high

Common progression to hypothyroidism

No Lobulation

Consistency

Extrathyroid invasion

Hurtle cells

Lymphocitis

Stony hard

yes

no

Gland architecture

Vascular changes

sparse

Effaced

Vasculitis

minal centers. This findings may be used to distin­guish Hashimoto's from Riedel's thyroiditis (4). The specimen obtained from our patient did not have enough thyroid tissue to show thyroid areas of inte­grallobulation and oxyphil metaplasia, but it had in­tense lymphoid infiltration and germinal centers. It is not unusual for a case of Riedel's thyroiditis to present as suspected neoplasia (16) . The differen­tial diagnosis with an anaplastic carcinoma due to the iron-hard consistency and major involvement of cervical structures should be considered less likely in young patients. The anaplastic carcinoma hypothesis was considered more probable in our middle-aged patient because she had a positive citopathology study and because we have an un­usually high incidence of anaplastic carcinoma (17% of cancers) , but just one case of Riedel 's thy­roiditis in more than 480 thyroidectomies reviewed. Kini (17) describes the fine-needle byopsy speci­men in Riedel's thyroiditis as acellular due to fibro­sis , although the thyroid may be totally or partially involved (4) . The specimen obtained in our case revealed numerous follicular cells, some of which had atypies suggestive of follicular neoplasia. The same occured in a case described by Marin et al. (16) , and their patient also showed Hurthle cells and had antimicrosomal antibody titers of 1/25.000 and hypothyroidism. The possibility of Hashimoto's thyroiditis involving the areas not destroyed by Riedel's thyroiditis should be suspected in both cases, as Hashimoto's thyroiditis is a classic pitfall in cytopathology, simulating cancer of the thyroid (18) and since hypothyroidism is not very common in Riedel's thyroiditis.

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yes

Firm

no

yes

Markedly diffuse

Preserved

Absent

The association of Riedel's thyroiditis with other ex­tracervical fiblosclerosis was first reported by Bowlby in 1885 (19). It was increasingly recognized since 1962, in 34% of the published cases (11), and may occur as an orbital pseudotumor (20), lacrimal gland fibrosis (21), retroperitoneal fibrosis (22) , mediastinal fibrosis (23), sclerosing cholangi­tis (24) or fibrous parotitis (25) . The patient de­scribed here showed no evidence of mediastinal or retroperitonial fibrosis at X-Ray, and no symp­toms related to fibrosis at other sites, but it is ac­knowledged that it may occur at some point after diagnosis, requiring strict follow-up (2) . Surgery is indicated in Riedel's thyroiditis for two main reasons: to exclude carcinoma, when it should be kept in mind to limit the extent of surgery if no malignancy is found; and to relieve tracheal com­pression, when the operation is limited to excising a wedge of thyroid isthmus if the process is diffuse (2) . A trial for more extensive surgical intervention, as performed in our case, may encounter major dif­ficulties , for instance undefined tissue planes with an increased risk of injury to adjacent structures such as the carotid arteries, the trachea, the recur­rent laringeal nerves or the parathyroids. The asso­ciation with hypoparathyroidism is unusual , but its occurrence is not rare after thyroidectomy. This can be explained by the previous destruction of some of the parathyroid glands secondary to the invasive nature of Riedel's disease (16). In conclusion, Riedel's thyroiditis, although not nec­essarilya late stage of Hashimoto's thyroiditis , may be associated with it, further complicating the clin­ical and pathological diagnosis. It should always

be considered in the diferential diagnosis of large or stony-hard cervical lesions, especially in young patients, in order to prevent extensive and risky surgery.

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sociated extracervical fibrosclerosis: Bowlby's dis­ease revisited. Ann. Endocrinol. (Abstract) 43: 29A, 1982.

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24. Bartholomew L.G., Cain J.C., Woolner L.B., Utz D.C., Ferris D.O. Sclerosing cholangitis: its possible association with Riedel's struma and fibrous retroperitonitis: report of two cases. N. Engl. J. Med. 269: 8,1963.

25. Hines R.C., Scheuermann H.A., Royster H.P., Rose E. Invasive fibrous (Riedel's thyroiditis) with bilateral fi­brous parotitis. JAMA 213: 869,1970.