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Coexistent presentation of Graves’ disease and a Riedel’s thyroiditis -

Diagnostic dilemma

Gvianishvili T.1 Gogiashvili L.

1

Abstract Background: The coexistence of Riedel's thyroiditis and Graves' disease is quite rare, presents a diagnostic dilemma and requires a particular clinical approach. Case report: We describe a 69-year-old man who had two autoimmune processes - Riedel's thyroiditis and Graves' disease, which develop at the same time in different lobes of the thyroid with contradictory manifestations. The diagnosis was confirmed by histological examination. Conclusions: Present case is unique by development and management, especially, it should be noted that iodine deficient thyroid diseases are endemic to the Caucasus region (Georgia), although the present case is the only one in our observation period (2016-2019). (TCM-GMJ April 2020; 5(1):P27-P30) Keywords: Riedel's thyroiditis; Graves' disease; Autoimmune thyroiditis

Introduction

iedel's thyroiditis (RT) is a rare, chronic in-flammatory disease of the thyroid gland char-acterized by a dense fibrosis that replaces thy-roid parenchyma (1-3). The fibrotic process

invades adjacent structures of the neck and extends be-yond the thyroid capsule. This feature differentiates RT from other inflammatory or fibrotic disorders of the thy-roid. Extension beyond the thyroid also differentiates this from the fibrosing variant of Hashimoto thyroiditis (HT) (3-5). In contrast, unit cases of coexistence of Riedel's thy-roiditis and Graves' disease are described (6, 7). It should be noted, that the case described relates to a patient who, after surgical treatment of hyperthyroidism, developed Riedel's thyroiditis in the remaining tissue of the thyroid gland. (6). According to Bryan Mclver et al. case report (2010), Graves' disease developed of the background of unilateral Riedel’s thyroiditis (7). All named authors have recommended surgical treatment of Riedel's thyroiditis, which the differential diagnosis from anaplastic carcino-ma was not possible, based on extensive radiological find-ings (6-8). We present a case of thyroid pathology, where simulta-neously developed Riedel's thyroiditis in right lobe and

R Greaves disease in the left lobe - two different clinical-morphological forms of autoimmune thyroiditis that have not been compared in the literature as coexisting process.

Case presentation

Patient: Male, 69 years old. Chief complaint: Increase in thyroid gland size, com-pression on the trachea, and shortness of breath 2 months before hospitalization. Present medical condition: A 69-year-old man referred to the clinic for a dense formation in the anterior neck, anxiety, difficulty breathing, swallowing and discomfort in the neck area, which had been observed for about two months. Previously, the patient had not undergone any examination or treatment. Family medical history: No medical problems. Physical examination: The patient was medically stable with a blood pressure of 140/90 mm Hg, pulse of 92 beats per minute, respiration rate of 18 breaths per mi-nute, and a temperature of 36.3ºC. Hard globe protrusion in the anterior neck region and middle exophthalmia were observed; scleral icterus and conjunctival anemia not pre-sent. On auscultation: systolic murmur, breath sounds in norm. Electrocardiography: 92 beats per minute at rest, nor-mal sinus rhythm. Laboratory results: Complete blood and urine test are done in table (tab.1). This condition was interpreted by consilium as subclinical hyperthyroidism. Thyroid ultrasound: In the thyroid left lobe were ob-served a well-defined irregular and hypoechoic nodules measuring at 1- 6X3X0,5 cm in size, 2 - 6X4X0.7 cm in

From the ¹Iv. Javakhishvili Tbilisi State University, Al. Natishvili Insti-tute of Morphology,Department of Clinical and Experimental Pathology Received 29.03.2020; accepted 20.04.2020 Address requests to: Gvianishvili Tamuna MD, PhD Student E-mail: tamuna_gv@yahoo.com Copyright © 2020 Translational and Clinical Medicine-Georgian Medical Journal. Published online www.tcm.tsu.ge

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size, 3 - 4,5X3X5X1,5 cm in diameter, along with large scattered dense calcifications. Right lobe – dense mass, homogeneously hypoechoic with the poor demarcation of the gland borders. Enlarged cervical lymph nodes and in-vasion into the parathyroid glands were not present. Thyroid fine needle aspiration (FNA) cytology: Cyto-pathological results (Bethesda) have shown glandular and stromal cells and few liquid substances. Computed tomography (CT) scan of the neck: In the thyroid left lobe were: 1- 6X3,5X0,5 cm in size, 2 - 6X4X0.7 cm in size, 3 - 4,5X3X5X1,5 cm nodular lesion occupying most of the left lobe of the thyroid. A peripher-al calcified lesion was also identified. Right lobe demon-strates compression of local structures by an enlarged thy-roid with low attenuation change within areas of the in-volved thyroid gland. Surgery: Total thyroidectomy was taken. Complex mass with hard consistency and a thick capsule that compressed and deformed the trachea were seen. Macroscopy: The test material contains two lobes of the thyroid gland: Left lobe is divided into 3 parts: 1 - 6X3,5X0,5 cm in size, 2 - 6X4X0.7 cm in size, 3 - 4,5X3X5X1,5 cm in size. Adjacent to the left lobe of the gland - 3,5X1,7X0,5 cm. Right lobe - 5X4X1cm in size, separately presented as well 1 - 4X1,5X0.6 cm in size, 2 - 3,5X0,7X0,7 cm in size. H&E microscopy: Left lobe - micro- macrofollicular goiter with follicular cells hyperplastic buds and tall epithe-lial cells. Cystic degeneration and necrotic areas also are evident. Chronic lymphocytic thyroiditis with large fused germinal centers was seen (Fig. 1. A, B). Adjacent to the left lobe of the thyroid, composed by fibrotic cords with hemorrhage foci. Right lobe – the multifocal fibrosclerosis with thyroid architectural distortion due to the marked proliferation of fibrous tissue, severe atrophy of the follicles and evident infiltration by mononuclear inflammatory cells confirm the diagnosis of Riedel's thyroiditis (Fig. 1. C, D). Using electronmicroscopic investigation method (osmium tetraoxide fixation, epon-araldyte embedding, Tesla BS500 microscope) the following results were ob-tained: electron micrographs of thyroid gland samples from left lobe were shown multilayered follicles with large euchromatic nuclei, heterogenous colloid in lumen, under-ling basal lamina and blood capillary with erythrostasis (Fig. 2. A, B, C, D). Outcome: Not since of complication after surgery and during postsurgical replacement therapy with levothyrox-ine.

Discussion

It is known, that Riedel's thyroiditis is a thyroid gland rare, chronic inflammatory disease (1-3), but etiology not well known. Recent concept defines RT as autoimmune disease with systemic extrathyroidal fibrosis mainly associ-ated with IgG4-related systemic disease (IgG4-RSD) (9-12). However, IgG4-RSD may unify two well known path-

ogenesis postulate: One theory of pathogenesis postulates that RT results from an autoimmune process. A second theory holds RT to be a primary fibrotic disorder (13). The presented study demonstrate unusual case, because two different functionally opposite autoimmune diseases progress within one organ, into right and left thyroid lobe. Based on laboratory and FNA data, we cannot determine which are the lieder, primary developed - Riedel's thyroidi-tis or Graves' disease, as the characteristic changes of both processes are pronounced. Histologic and ultrastructural images of a surgically re-moved thyroid gland confirm in left lobe the process char-acteristic of Graves’ disease: follicular cell hyperplasia, ex-tensive lymphoplasmocytic infiltration with the develop-ment of fuse active germinal centers, and secondary de-generative changes. In the right side there was hard avas-cular tissue with atrophy of the glandular parenchyma so-called stone-like, dense fibrosis, which confirm characteris-tic of Riedel's thyroiditis. But, elevated TSH level, abnormal cardiac signs and middle exophthalmia contribute to trend of parenchyma hyperplasia and subclinical hyperthyroidism. Due to the low incidence of Riedel’s thyroiditis, there are no guidelines or large clinical studies that refer to the optimal management of the condition as extensive com-prehensive reviews present (6-8, 14), moreover, with Graves’ disease combination. This creates a diagnostic difficulty as laboratory data show subclinical hyperthyroid-ism, on one hand, and high levels of thyroid peroxidase (TPO) and thyrotropin receptor antibodies (TRAb), on the other hand, which is strongly conflicting. Marine-Lenhart-Syndrom was excluded, because our patient has two types of autoimmune thyroiditis by differ-ent pathophysiologic mechanisms, moreover, RT and Graves’s disease are postulated from CT and FNA results. We can share with Wu, Leung et al. (15) that mechanisms underlying Marine-Lenhart-Syndrom include somatic con-stitutively active mutations of the TSH receptor, but the absence of TSH receptor autoantibodies and over expres-sion of Thyrotropin receptor antibodies (TRAb), Thyroid peroxidase (TPO) antibodies and Thyroglobulin antibody confirm that reported case is unusual and baseline symp-toms of hyperthyroidism coexist with other type of auto-immunity, such as RT. Overall, we believe that the case to be of special interest as a diagnostic dilemma, which may have a similar pattern of Riedel’s thyroiditis and Graves’ disease. It is empha-sized that iodine deficient thyroid diseases are endemic to the Caucasus region (Georgia), although the present case is the only one in the period from 2016 to 2019 (our obser-vation period).

Conclusion

The reported case is to focused on two different histo-pathologically and pathophysiologically opposite autoim-mune processes that present clinical risk and required dif-ferent management.

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Acknowledgement

The case report was supported by Iv. Javakhishvili Tbilisi State University, Al. Natishvili Institute of Mor-phology.

Conflict of interest disclosure

Authors declare no potential conflicting interests relat-

ed to this paper.

References

1. Riedel B.M. Die chronische, zur Bildung eisenharter Tumoren führende Entzündung der Schilddrüse. Verh. Dtsch. Ges. Chir. 1896; 25: 101–105.

2. Schwaegerle SM, Bauer TW, Esselstyn CB Jr. Riedel's thyroiditis. Am J Clin Pathol. 1988; 90(6):715-22.

3. Guerin CK. Riedel Thyroiditis. Medscape. 2017. 4. Gvianishvili T, Gogiashvili L, Chkhobadze M. Molec-

ular-biological thyroid profile during autoimmune dis-ease - Hashimoto and Riedel’s Thyroiditis. Georgian Medical News №5 (290), 2019,

5. Rurua N, Gogiashvili L, Tsagareli Z. Immunohisto-chemical Investigation of Angiogenesis Activity in Thyroid Gland under Hashimotos Thyroiditis versus Diffuse Toxic Goiter. Journal of Basic & Clinical Medicine 2015, 4(1):32-36

6. Lee DY, Moon JS, Kim GE, Kim HK, Kang HC. Riedel Thyroiditis in a Patient with Graves Disease. Endocrinol Metab. 2013; 28(2): 138–143. doi: 10.3803/EnM.2013.28.2.138.

7. McIver B, Fatourechi MM, Hay ID, Fatourechi V. Graves disease after unilateral Riedel’s thyroiditis. J Clin Endocrinol Metab 2010;95:2525-6.

8. Pi GY, Lee YS, Hong SW, Chang HS, Park CS. A case of Riedel’s thyroiditis. J Korean Surg Soc 2012;82:317-20.

9. Katabathina VS, Khalil S, Shin S, Lath N, Menias CO, Prasad SR. Immunoglobulin G4-Related Disease: Re-cent Advances in Pathogenesis and Imaging Findings. Radiol Clin North Am. 2016; 54 (3):535-51.

10. Li Y, Zhou G, Ozaki T, Nishihara E, Matsuzuka F, Bai Y, et al. Distinct histopathological features of Hashimoto’s thyroiditis with respect to IgG4-related disease. Mod Pathol. 2012; 25:1086-97.

11. Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel's thyroiditis and multifocal fibro-sclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res (Hoboken). 2010; 62(9):1312-8.

12. Takeshima K, Inaba H, Ariyasu H, Furukawa Y, Doi A, Nishi M, et al. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related dis-ease in Japan. Endocrine Journal. 2015; 62(8):725-31. doi: 10.1507/endocrj.EJ15-0175.

13. Pusztaszeri M, Triponez F, Pache JC, Bongiovanni M. Riedel's thyroiditis with increased IgG4 plasma cells: evidence for an underlying IgG4-related sclerosing disease? Thyroid. 2012; 22(9):964-8.

14. Blanco VM, Páez CA, Victoria AM, Arango LG, Ar-runategui AM, Escobar J, et al. Riedel’s Thyroiditis: Report of Two Cases and Literature Review. Case Re-ports in Endocrinology 2019:5130106.

15. Wu SY, Leung AM, Chambers MD, Chen CL, Khan MU, Brent GA, et al. Coexistent presentation of Graves' disease and an autonomous thyroid nodule following administration of an iodinated contrast load. Journal of Clinical and Translational Endocrinology: Case Reports 2018.

Test Result Reference range Blood Urea Nitrogen (BUN)/Creatinine 23/0.5 mg/dL 7-20/ 0.6-1.2 mg/dL

Total protein/albumin 7.2/4.3 g/dL 6-8.3/ 3.5-5.5 g/dL

AST/ ALT 21/20 IU/L 8-20/5-40 IU/L Na 140 mEq/L 135-145 mEq/L K 5.0 mEq/L 3.5 to 5.5 mEq/L Cl 110 mEq/L 96-106 mEq/L

Ca 4.8 mEq/L 4.5-5.2 mEq/L

Erythrocyte sedimentation rate (ESR) 16 mm/hr 0-22 mm/hr C-reactive protein <1 mg/L <10 mg/L

IgG4/IgG ratio >30% 5-6%

TSH 0,15 mU/L 0.3-4 mU/L FT4 4.25 ng/dL 0.7-2 ng/dL

FT3 890 pg/dL 230-619 pg/dL

Thyrotropin receptor antibodies (TRAb) 8 IU/mL 0-1.75 IU/mL

Thyroid peroxidase (TPO) antibodies 17 IU/mL 0-9 IU/mL

Thyroglobulin antibody 15 IU/mL 0-4 IU/mL

Table 1. Blood and urine test

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Figure 1. H&E. A. Graves disease, proliferative thyroid epithelial cells and cystic degeneration (1), X100; B. Graves disease, large fused lymphoid nodule with germinal center (arrow), X200. C. Riedel thyroiditis, fibrous tissue replaced thyroid follicles, follicles atrophy and inflammatory mononuclear cells infiltration, X200; D. Riedel thyroiditis, extensive fibrosis replaced thyroid parenchyma, X200.

Figure 2. Electron micrographs. A. B. Graves dis-

ease, X2000. Multilayered follicles with large eu-

chromatic nuclei (1), underling basal lamina and

blood capillary with erythrostasis, heterogenous col-

loid in lumen (2). C. Riedel’s thyroiditis, fibrosclero-

sis area with active fibroblast (arrows) and dense

collagen fibers replaced follicles, X4000; D. Riedel’s

thyroiditis, extensive fibrosis and atrophy of folli-

cles, pyknosis of nuclei (arrows), X2000.