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CASE REPORT
Year : 2015  |  Volume : 12  |  Issue : 2  |  Page : 74-76

Savior turning into destroyer: An interesting case of destructive thyroiditis


1 Department of Neurology, Command Hospital, Chandimandir, Panchkula, Haryana, India
2 Department of Endocrinology, Command Hospital, Chandimandir, Panchkula, Haryana, India

Date of Web Publication8-May-2015

Correspondence Address:
K V S Hari Kumar
Department of Endocrinology, Command Hospital, Chandimandir, Panchkula 134 107, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.153348

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  Abstract 

Rituximab is a monoclonal antibody directed specifically against the CD20 resulting in depletion of B lymphocytes. Rituximab is used in multiple autoimmune disorders across the medical specialties including multiple sclerosis, myesthenia grevis, rheumatoid arthritis and inflammatory bowel disease. In the field of endocrinology, rituximab is indicated specifically in resistant cases of Graves' opthalmopathy. We recently encountered a patient of multiple sclerosis, developing features of destructive thyroiditis after a course of rituximab and report the same here.

Keywords: Destructive thyroiditis, hypothyroidism, multiple sclerosis, rituximab


How to cite this article:
Ahmad FM, Kumar S, Kumar KH. Savior turning into destroyer: An interesting case of destructive thyroiditis . Thyroid Res Pract 2015;12:74-6

How to cite this URL:
Ahmad FM, Kumar S, Kumar KH. Savior turning into destroyer: An interesting case of destructive thyroiditis . Thyroid Res Pract [serial online] 2015 [cited 2019 Dec 15];12:74-6. Available from: http://www.thetrp.net/text.asp?2015/12/2/74/153348


  Introduction Top


Rituximab is a monoclonal B cell antibody targeting the CD20 antigen on the B cells. CD20 protein is located specifically on the pre B cells and the B cells. The binding by rituximab results in blocking of the B cell activation and differentiation leading to depletion of B cells. [1] The drug is specifically developed for the use in B cell lymphoma, but has been found to be useful subsequently in many autoimmune disorders. [2] Rituximab has been found useful in the field of thyroid, especially in resistant cases of thyroid ophthalmopathy. [3] Rituximab therapy has also been found useful in the treatment of thyroid MALT (mucosal associated lymphoid tissue) lymphoma. [4] The use of Rituximab resulted in reduction of the thyroid autoimmunity and possibly amelioration of Hashimoto's disease. [5] The adverse effects reported with the use of rituximab include injection reaction, reactivation of the infection and immune toxicity with depletion of the B cells.

Drug-induced thyroiditis has been reported with a variety of drugs. The commonly implicated drugs are the interferon, tetracyclines and amiodarone. [6] Destructive thyroiditis follow a triphasic course and the patients initially have thyrotoxic phase followed by euthyroid and subsequent hypothyroid stage. The literature suggests beneficial effects of rituximab in thyroidology without any adverse effects on the thyroid gland. Rituximab use has never been reported till date to result in destructive thyroiditis. In this report, we present a young lady with multiple sclerosis who developed destructive thyroiditis after receiving two cycles of rituximab.


  Case report Top


In Jun 2014, a 34-year-old women was referred to our department with a history of weight loss and palpitations of one week duration. The patient is a known case of multiple sclerosis (relapsing remitting type) for past eight years and has been treated with multiple drugs including interferon, natalizumab and glucocorticoids. In view of the progressive disease and frequent relapses, she was given a course of rituximab in April 2014. She was given two doses of 1000 mg of rituximab separated by two weeks of duration. She received the 2 nd injection in the last week of April 2014 and had no injection related side effects. Two weeks after receiving the rituximab, she noticed palpitations and involuntary weight loss of about 2-3 kg. She denied history of visual complaints and none of her family members have a thyroid ailment. Clinical examination revealed normal vital parameters except for tachycardia (116 beats per minute). There was no evidence of goiter, tremors, exophthalmos, skin and nail changes suggestive of Grave's disease. The rest of the systemic examination was normal.

Her hematological and biochemical parameters were all normal. Thyroid profile revealed total triiodothyronine - 219.6 ng/dL (normal 60-175), total thyroxine - 17.4 μg/dL (normal 4-11.5), thyroid stimulating hormone - 0.01 mIU/L (normal 0.3-4.5), thyroglobulin antibody - 11.4 IU/mL (normal 0-20) and thyroid peroxidase antibody - 10 IU/mL (normal 0-30). Ultrasonography showed normal vascularity of the thyroid and pertechnate scan showed normal uptake by the thyroid gland [Figure 1]. The patient was treated with propranolol 80 mg/day and the thyroid hormones returned to normal after 1 month with persisting low thyroid stimulating hormone ((TSH) 0.2 mIU/L). A repeat thyroid profile after 3 months revealed low T3 (32), low T4 (2.1) and elevated TSH (105.4) suggestive of primary hypothyroidism. She was started on 100 μg of levothyroxine and is under regular follow-up for further dose adjustments.
Figure 1: Ultrasonography thyroid showing normal vascularity (a) and tracer uptake on the pertechnate scan (b)

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  Discussion Top


Our patient is the seminal case of rituximab induced destructive thyroiditis leading to permanent hypothyroidism. Extensive literature search did not reveal any report of thyroid related adverse effects of rituximab. Our patient had the temporal relation of the destructive thyroiditis with the exposure to rituximab. Drug induced hypothyroidism has been described with the use of interferon, amiodarone, iodine, sunitinib and sorafenib. [7] The underlying mechanism differs with each drug and the resulting hypothyroidism may be transient or permanent. Previous reports suggest the change in immune response after pulse of monoclonal antibody therapy resulting in increased incidence of autoimmune thyroid disease. [8] However, thyroperoxidase (TPO) antibody titer in our patient does not suggest autoimmune etiology of hypothyroidism.

Rituximab has been used in many disorders of thyroid with beneficial effects. The drug is used widely in resistant or recurrent cases of thyroid opththalmopathy. Other thyroidal disorders where rituximab has been tried with partial benefit include MALToma, Reidel's thyroiditis, primary thyroid lymphoma and autoimmune thyroiditis. Previous reports suggest destructive thyroiditis with the use of other immunomodulating drugs like etanercept. [9] The depletion of B cells coupled with release of cytokines may explain the induction of the destructive thyroiditis in our patient. The clinical and hormonal profile of our patient suggests the cause and effect relation between the use of rituximab and thyroiditis, but cannot establish it definitely.

The side effects reported with the use of rituximab are divided into early and late stages after the exposure. Early effects include hypotension, tachycardia, febrile illness and flu- like syndrome. The late effects of the drug include urinary tract infection, ulcerative colitis and polyarthritis. The main cause of concern with the use of rituximab is the enhanced susceptibility to the infections. Few reports suggest an increased prevalence of Pneumocystis Jirovecii infection leading to mortality with the drug. [10] Hence, rituximab is used only in patients with failure to first- and second-line therapies of the autoimmune condition. Our patient had frequent relapses of multiple sclerosis, despite using multiple options, prompting the therapy with rituximab.

In conclusion, we report the first case of rituximab induced destructive thyroiditis leading to permanent hypothyroidism. Our report highlights the need of increased vigil on the part of all clinicians to identify thyroid related adverse effects with the use of other monoclonal antibodies.

 
  References Top

1.
Castillo-Trivino T, Braithwaite D, Bacchetti P, Waubant E. Rituximab in relapsing and progressive forms of multiple sclerosis: A systematic review. PLoS One 2013;8:e66308.  Back to cited text no. 1
    
2.
Silverman GJ, Weisman S. Rituximab therapy and autoimmune disorders: Prospects for anti-B cell therapy. Arthritis Rheum 2003;48:1484-92.  Back to cited text no. 2
    
3.
Chong KL, Khanna D, Afifiyan NF, Hwang CJ, Lee DK, Garneau HC, et al. Rituximab treatment of patients with severe, corticosteroid resistant thyroid associated ophthalmopathy. Ophthalmology 2010;117:133-9.  Back to cited text no. 3
    
4.
Kahara T, Iwaki N, Kaya H, Kurokawa T, Yoshida T, Ishikura K, et al. Transition of thyroid autoantibodies by rituximab treatment for thyroid MALT lymphoma. Endocr J 2011;58:7-12.  Back to cited text no. 4
    
5.
Oh HJ, Yun MJ, Lee ST, Lee SJ, Oh SY, Sohn I. Evans syndrome following long-standing Hashimoto's thyroiditis and successful treatment with rituximab. Korean J Hematol 2011;46:279-82.  Back to cited text no. 5
    
6.
Tacon L, Tan CT, Alvarado R, Gill AJ, Sywak M, Fulcher G. Drug-induced thyroiditis and papillary carcinoma in a minocycline-pigmented black thyroid gland. Thyroid 2008;18:795-7.  Back to cited text no. 6
    
7.
Faris JF, Moore AF, Daniels GH. Sunitinib (Sutent)-induced thyrotoxicosis due to destructive thyroiditis: A case report. Thyroid 2007;17:1147-9.  Back to cited text no. 7
    
8.
Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 1999;354:1691-5.  Back to cited text no. 8
    
9.
Andrés E, Limbach FX, Goichot B, Sibilia J. Silent thyroiditis associated with etanercept in rheumatoid arthritis. Ann Rheum Dis 2002;61:565.  Back to cited text no. 9
    
10.
Teichmann LL, Woenckhaus M, Vogel C, Salzberger B, Scholmerich J, Fleck M. Fatal pneumocystis pneumonia following rituximab administration for rheumatoid arthritis. Rheumatology 2008;47:1256-7.  Back to cited text no. 10
    


    Figures

  [Figure 1]


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