Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Home Print this page Email this page
Users Online: 411

 Table of Contents  
Year : 2014  |  Volume : 11  |  Issue : 3  |  Page : 121-123

ANCA positive vasculitis in a patient with nodular Graves' disease caused by carbimazole

Barbara Davis Center for Diabetes, University of Colorado, Denver, CO, USA

Date of Web Publication13-Aug-2014

Correspondence Address:
Viral N Shah
Barbara Davis Center for Diabetes, 1775 Aurora Ct, Aurora, Co 80045
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-0354.138560

Rights and Permissions

Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis is an uncommon and infrequently recognized adverse event with thionamide drugs. It is most commonly reported with propylthiouracil (PTU) and rarely with carbimazole (CBZ). We report a male patient who presented with arthralgias, fever, and other symptoms of hyperthyroidism who was on CBZ treatment on and off for the past 14 years. His laboratory evaluation revealed a diagnosis of ANCA positive vasculitis. CBZ was stopped and prednisolone was started in tapering doses while he underwent radioiodine ablation for control of hyperthyroidism. This treatment leads to clinical improvement in the patient. This is the second case report from India.

Keywords: ANCA vasculitis, carbimazole, Graves′ disease, thionamides

How to cite this article:
Shah VN. ANCA positive vasculitis in a patient with nodular Graves' disease caused by carbimazole. Thyroid Res Pract 2014;11:121-3

How to cite this URL:
Shah VN. ANCA positive vasculitis in a patient with nodular Graves' disease caused by carbimazole. Thyroid Res Pract [serial online] 2014 [cited 2022 Nov 29];11:121-3. Available from: https://www.thetrp.net/text.asp?2014/11/3/121/138560

  Introduction Top

About 1-2% of the patients with thyroid disorders have Graves' disease (GD). Palpable nodules in patients with GD are not uncommon and are seen in nearly 30% of Indian patients. [1] The mainstay of controlling hyperthyroidism initially in patients with GD is thionamides, namely propylthiouracil (PTU), carbimazole (CBZ), and methimazole (MMI).

These medications have a number of well-known adverse effects including allergic skin reactions, neutropenia, anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis, and rarely, agranulocytosis. ANCA positivity is seen more commonly in patients with GD than healthy individuals; however, those who are on thionamides have higher chances of being ANCA positive. [2] The most commonly implicated agent among thionamides in various studies is PTU. [2],[3] Nevertheless, ANCA positive vasculitis has been reported with CBZ and MI but uncommonly. [2],[3],[4],[5]

Sometimes, presentation of vasculitis such as fever, fatigue, and proximal muscle weakness is confused with uncontrolled hyperthyroidism; and hence, the recognition of this entity is of prime importance. Here, we report a diagnosed case of nodular GD disease on CBZ with the development of ANCA positive vasculitis.

  Case report Top

A 45-year-old man presented to clinic with complaints of weight loss, fever, tremors, joint pains and difficulty in getting up from a sitting position for 1 year and gradually getting worse. He was previously diagnosed with nodular GD disease for 14 years and was on medication initially. However, due to his large thyroid size and inability to get control with drugs, he was subjected to thyroidectomy 7 years ago. However, due to a surgical complication, a near total successful thyroidectomy could not be performed. There was no improvement in symptoms after surgery and he was started on CBZ. The doses ranged from 10 to 30 mg/day for 5 years. However, patient was not taking medications in between as he did not feel subjective improvement in his condition. In between, he was also prescribed MMI, but for shorter period of time (~1 month). On average, he is on CBZ for approximately 10 years. Because, his symptoms were getting worse despite an optimal dose of CBZ, he was referred for endocrine evaluation.

On examination, he was a thin male, weighing 50.15 kg and appeared diaphoretic. There was a noticeable tremor of his outstretched hands bilaterally. There was the presence of ophthamopathy (clinical activity score - 2/7 and severity score was moderate; inactive, moderate, thyroid-associated ophthalmopathy), but no dermopathy or acropachy. He had a grade 3 large goiter, nodular without retrosternal extension. There was a bruit over the thyroid. He had complaints of bilateral joint pain over his shoulders, elbows, knees, and sometimes over the finger joints. There was neither joint effusion nor swelling or tenderness nor restricted range of movement. There was no skin rash or lymphadenopathy. He had mild difficulty in getting up from a sitting position. Otherwise, the neurologic examination was unremarkable except for exaggerated knee reflexes. He had tachycardia (pulse - 120/min, regular), but no murmur on cardiovascular examination. Respiratory system examination was normal. His hemogram revealed a mild hypochromic microcytic anemia (Hemoglobin - 11.3 gm/dl, mean corpuscular volume - 68) with elevated erythrocyte sedimentation rate (ESR) (70 mm at 1 h). His serum electrolytes and renal and liver function tests were normal. His total thyroxine (T4) was 35 μg/dl (normal 4.5-12.5) and thyroid stimulating hormone was 0.01 (by third generation chemilumiscence assay; normal 0.4-4.5 mIU/ml). Thyroid ultrasound revealed enlarged lobes of thyroid bilaterally (right more than left) with multiple nodules ranging from 2 to 3 cm in size without any features suggestive of malignancy. Fine needle cytology from the largest left side nodule did not reveal malignancy.

Considering the above features, it was thought that these symptoms were due to uncontrolled hyperthyroidism, so the dose of CBZwas increased to 40 mg/day. After 3 weeks, the patient reported an increase in joint, muscular symptoms, and fever despite modest reduction in total T4; and hence, he was reevaluated. Further laboratory reports revealed elevated C-reactive protein and ESR, but normal differential counts (total counts - 8,500/mm 3 ), negative rheumatoid arthritis (RA) factor, positive antinuclear antibodies, positive ANCA (++ positivity with 1:10 dilutions by indirect immunofluroscence). Human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) were nonreactive. There was no hematuria and urine microscopic examination was normal for albumin excretion and sediments. After reviewing these laboratory results, diagnosis was revised to ANCA positive vasculitis and CBZ was discontinued. He was started on prednisolone 1 mg/kg in tapering doses, propranolol 40 mg twice a day, and given 10 mCi of 131 I (radioiodine ablation (RAI)) for control of hyperthyroidism. Two weeks after RAI, the patient reported improvement in symptoms. At 6 weeks, there was a remarkable improvement in joint symptoms, he was able to get up from sitting position without any difficulty, his pulse rate was reduced to 100 beats/min, his tremor has reduced remarkably, he gained 3 kg weight and his total T4 was 9.7 μg/ml (normal 3.4-9.3).

  Discussion Top

Though ANCA positive vasculitis due to thionamide particularly with PTU is not uncommon in patients with GD, it is rarely reported with CBZ. A literature search revealed that this is only the second case report of ANCA positive vasculitis from CBZ from India.

ANCA associated vasculitis is an inflammatory systemic disorder characterized by the involvement of multiple organs and histologically by the infiltration of inflammatory cells in smaller arteries. [6] ANCA is found in two forms, cytoplasmic ANCA (C-ANCA) and perinuclear ANCA (P-ANCA). P-ANCA is directed against a variety of antigens. ANCA are highly sensitive and specific markers for primary systemic vasculitis. [6] In a large study, the prevalence of ANCA was higher in patients with GD (19.9%) compared to euthyroid controls (4.6%), and ANCA vasculitis was two times higher in those who were treated with PTU. [2] There are a few case reports and a series of ANCA vasculitis with CBZ as well as with MMI. [2],[3],[4],[5],[6],[7],[8],[9]

The presentation of ANCA vasculitis depends on organ involvement. Any organ can be affected, but the most common is renal involvement followed by arthralgias and fever. [3],[9] Our case did not have renal involvement but he had arthralgias and fever. Thionamide-induced vasculitis has been reported in those who are receiving thionamides for more than 18 months or with recent commencement of treatment. [3] Nearly 75% of cases have been reported in females and it is more common in Asian patients. [2],[3] Our patient was on CBZ therapy for almost 10 years, but regularly on therapy for the past 1 year. It has been postulated that PTU accumulates within the neutrophil, binds with myeloperoxidase which alters the configuration resulting into antibody formation, and this may be the reason that ANCA vasculitis is more common with this drug. [2],[3],[4] However, the mechanism of ANCA positive vasculitis with CBZ and MMI is not clear.

Symptoms of hyperthyroidism due to increase in metabolism including fever, muscle weakness, and fatigue mimics the symptoms of vasculitis; and hence, sometimes it is difficult to differentiate between these two entities clinically. Clinical suspicion and deterioration of symptoms with thionamides may be clues to diagnose vasculitis. This is exactly what happened in our case. We initially presumed such symptoms may be due to uncontrolled toxicosis, but when our patient deteriorated with higher doses of CBZ, we reevaluated the case and revised our diagnosis. Furthermore, it is important to recognize this entity because the treatment is the discontinuation of the offending drugs and patients should be offered other treatments for hyperthyroidism like RAI or thyroidectomy.

Treatment of thionamide drug-induced ANCA vasculitis is the same as other vasculitis. [10] The mostly commonly used drug in the literature is prednisolone in tapering doses and the discontinuation of offending drugs. However, the duration of treatment and prognosis is not known because of the rarity of this entity and the lack of studies which have have looked into this aspect to date.

In conclusion, this case highlights the importance of recognizing this less known adverse effect of antithyroid medications. Early diagnosis and prompt withdrawal of the offending medication is the first important step in treating this entity.

  Acknowledgment Top

I am thankful to both, Parth Ganatra, internist, Bhavnagar and Emily Moser, BA, University of Colorado for the review of this manuscript.

  References Top

1.Mishra A, Mishra S. Thyroid nodules in Graves' disease: Implications in an endemically iodine deficient area. J Postgrad Med 2001;47:244-7.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.Harper L, Chin L, Daykin J, Allahabadia A, Heward J, Gough SC, et al. Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' disease. Clin Endocrinol (Oxf) 2004;60:671-5.  Back to cited text no. 2
3.Gunton JE, Stiel J, Clifton-Bligh P, Wilmshurst E, McElduff A. Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication. Eur J Endocrinol 2000;142:587.  Back to cited text no. 3
4.D'Cruz D, Chesser AM, Lightowler C, Comer M, Hurst MJ, Baker LR, et al. Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with anti-thyroid drug treatment. Br J Rheumatol 1995;34:1090-1.  Back to cited text no. 4
5.Yasude T, Kishida D, Tazawa KI, Matsuda M, Ishii W, Yazaki M, et al. ANCA- associated vasculitis with central retinal artery occlusion developing during treatment with methimazole. Intern Med 2012;51:3177-80.  Back to cited text no. 5
6.Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337:1512-23.  Back to cited text no. 6
7.Day C, Bridger J, Rylance P, Jackson M, Nicholas J, Odum J. Leukocytoclastic vasculitis and interstitial nephritis with carbimazole treatment. Nephrol Dial Transplant 2003;18:429-31.  Back to cited text no. 7
8.Calañas-Continente A, Espinosa M, Manzano-García G, Santamaría R, Lopez-Rubio F, Aljama P. Necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy. Thyroid 2005;15:286-8.  Back to cited text no. 8
9.Pandey S, Kushwaha RS, Mehndiratta P, Mehndiratta MM. Carbimazole induced ANCA positive vasculitis. J Assoc Physicians India 2008;56:801-3.  Back to cited text no. 9
10.Bonaci-Nikolic B, Nikolic MM, Andrejevic S, Zoric S, Bukilica M. Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: Comparison with idiopathic ANCA vasculitides. Arthritis Res Ther 2005;7:R1072-81.  Back to cited text no. 10


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case report

 Article Access Statistics
    PDF Downloaded279    
    Comments [Add]    

Recommend this journal