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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 9  |  Issue : 5  |  Page : 144-146

Thyrotoxic graves' disease-induced by interferon-ribavirin therapy in a patient with amiodarone-induced hypothyroidism on thyroxine replacement


Diabetes and Endocrine Unit, Department of Medicine, Faculty of Medicine, Hawary Teaching Hospital, University of Benghazi, Benghazi, Libya

Date of Web Publication4-Sep-2017

Correspondence Address:
Adela Elamami Absat
Diabetes and Endocrine Unit, Department of Medicine, Faculty of Medicine, Hawary Teaching Hospital, University of Benghazi, Benghazi
Libya
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmbs.ijmbs_35_17

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  Abstract 


An unusual type of drug-induced thyroid dysfunction is described. Thyrotoxicosis was seen in association with the use of interferon therapy despite prior established amiodarone-induced hypothyroidism. A 63-year-old female patient with a history of hypertension, high-grade ventricular arrhythmia on sotalol 80 mg daily was diagnosed to have amiodarone-induced hypothyroidism previously. She has been receiving thyroxine replacement therapy for 4 years. During the second cycle of interferon for hepatitis C virus relapse. She developed autonomous thyrotoxicosis. Her anti-thyroid peroxidase antibody was persistently negative before, during, and after either amiodarone or interferon while anti-thyroid stimulating hormone receptor antibody titer. Thyroid Tc-99m scan showed a high uptake during interferon therapy. To the best of the author's knowledge, this is the first report of a case of long-term hypothyroidism-induced by amiodarone therapy evolving into thyrotoxic Graves' disease-induced by interferon/ribavirin combination therapy in Libya reflecting an interaction of drugs and the background autoimmune disease.

Keywords: Amiodarone, Graves' disease, Interferon, Libya, thyroid dysfunction


How to cite this article:
Absat AE. Thyrotoxic graves' disease-induced by interferon-ribavirin therapy in a patient with amiodarone-induced hypothyroidism on thyroxine replacement. Ibnosina J Med Biomed Sci 2017;9:144-6

How to cite this URL:
Absat AE. Thyrotoxic graves' disease-induced by interferon-ribavirin therapy in a patient with amiodarone-induced hypothyroidism on thyroxine replacement. Ibnosina J Med Biomed Sci [serial online] 2017 [cited 2020 Sep 18];9:144-6. Available from: http://www.ijmbs.org/text.asp?2017/9/5/144/213922




  Introduction Top


Amiodarone is an effective class III antiarrhythmic drug used in the treatment of ventricular and supraventricular arrhythmias. Pharmacologically, it is an Iodine-containing compound with some structural similarity to thyroxine.[1] Some adverse effects of amiodarone are relatively mild, others can require intervention, for example, thyroid dysfunction (hypothyroidism 1%–22%, hyperthyroidism 2%–10%), pneumonitis 2%–17%, and hepatitis <3%.[1] Amiodarone-induced thyrotoxicosis (AIT) is more prevalent in iodine-sufficient areas and predominantly occurs in men, and may develop anytime during amiodarone therapy or even after the drug is discontinued. AIT in a patient with preexisting thyroid abnormality such as diffuse or nodular goiter or latent Graves' disease is called AIT Type I, whereas AIT in a patient with apparently normal thyroid gland is called AIT Type II.[2] AIT Type II may be related to destructive inflammatory thyroiditis caused by the increased iodine load.[3] In fact, mixed forms often exist.[3] In Type I AIT, 24-h uptake of radioactive iodine by the thyroid gland is normal to high, conversely, in Type II, uptake is low.[2] Amiodarone-induced hypothyroidism is believed to result from the inability of the thyroid to escape from the Wolff–Chaikoff effect after an iodine load and to resume normal thyroid hormone synthesis. It mostly affects old females with anti-thyroid peroxidase (TPO) antibodies from iodine sufficient areas.[2] On the other hand, the interferons are a group of proteins with antiviral activity is used therapeutically in chronic hepatitis B and C and in certain malignancies. It can precipitate or exacerbate autoimmune endocrine diseases, especially of the thyroid gland.[3] The thyroid gland dysfunction affects 4%–14% of patients.[4],[5] Secondary appearance on interferon therapy of elevated thyroid auto antibodies (anti-microsomal, anti-thyroglobulin, and/or anti-thyroid stimulating hormone [TSH] receptor antibodies) was a risk factor.[6] The most common type is interferon-induced thyroiditis, others include Graves' such as thyrotoxicosis and diphasic thyroiditis.[7],[8] The addition of ribavirin to interferon α does not seem to increase the incidence of thyroid dysfunction.[9],[10] Hepatitis C infection itself is associated with autoimmune diseases.[11]


  Case Report Top


A 63-year-old female patient was referred to the endocrine clinic in May 2011 with a history of hypertension on perindropril 4 mg. She received the first cycle of interferon/ribavirin combination in 2008 for hepatitis C with no complications. Thyroid function and anti-TPO at baseline and after interferon were negative. Her past medical history revealed that in 2009, she had had high-grade ventricular arrhythmia for which she was treated with amiodarone therapy in Tunisia. After 6 months of amiodarone therapy, she developed primary hypothyroidism, and her anti-TPO antibodies remained negative. Amiodarone was stopped, and the patient was started on sotalol 80 mg daily. Since hypothyroidism persisted, she was started on levothyroxine 75 mcg. On this dose, she remained euthyroid for 4 years. During the present episode (2011), she was biochemically and clinically euthyroid on thyroxine 75 mcg daily. In October 2012, her hepatologist restarted her on interferon/ribavirin combination therapy. After 5 months on this treatment, she became clinically thyrotoxic. Therefore, thyroxine doses were gradually tapered and eventually discontinued. Anti-TPO antibodies remained negative. At this stage, she traveled elsewhere for second opinion and treatment where anti-TSH receptor antibodies which was found to be positive and a Tc-99m scan revealed a high diffuse uptake [Figure 1]. Interferon was stopped, and the patient received an ablation dose of radioiodine. After 8 weeks of arrival back home, thyroid function was revealed a high serum TSH at 100 mU/L and very low serum T4 and T3 diagnostic of post-radioiodine hypothyroidism. The patient started on levothyroxine 100 μg daily which was later adjusted to 125 mcg daily. She remained well till the time of this report.
Figure 1: Tc-99m scan of the patient to illustrate the high uptake

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  Discussion Top


This case presents an example for the interaction of side effects of medications with autoimmune disease. The patient is an elderly female, so her sex and age predispose her more to an autoimmune disorder induced by drugs such as amiodarone and interferon. She developed high-grade ventricular arrhythmia a few months after finishing the first cycle of interferon therapy. It is well known that interferon therapy may induce a different type of arrhythmias during therapy but whether it can induce arrhythmia even few months after treatment had stopped this is not clear.

The use of amiodarone for the control of arrhythmia in this patient having been treated with interferon recently may have predisposed her more to thyroid dysfunction and choosing beta blocker as the first choice for this patient may be was more prudent. The patient resided in Benghazi which is a coastal city presumed to be iodine-sufficient despite the lack of formal studies to confirm this. This at variance to many other cities in the south of Libya, far from the sea to be safely presumed to be iodine-deficient. Consequently, she would theoretically be more likely to develop hypothyroidism with amiodarone treatment because the inability of the thyroid to escape from the Wolff–Chaikoff effect and less likely due to autoimmune thyroiditis because her anti-TPO antibody was negative during and after treatment with amiodarone. The present patient developed thyroid disease after 6 months of therapy in line with the predicted course of events in amiodarone-induced thyroid dysfunction typically occurring between 6 and 12 months of treatment (2).

The development of thyrotoxicosis with evidence of high radioactive uptake and positive high titer of anti-TSH receptor antibodies may point to Graves' disease, probably being induced by interferon therapy. Most cases of Graves' disease develop in patient with preexisting anti bodies, especially anti-TPO. This patient is unique in that anti-TPO was negative before and after she developed autoimmune disease. However, there is a reported case of negative preexisting anti-TPO which turn to be positive after the development of Graves' disease.[12]

As the patient was a case of hepatitis C virus treating her with the anti-thyroid drug was not a choice so she underwent RAI therapy (with increasing dose of beta-blocker) which render here hypothyroid again. The persistently negative anti-TPO antibodies make the diagnoses of hashitoxicosis very unlikely. Furthermore, the high and diffuse radioactive Tc-99m uptake with positive high titer of the anti-TSH receptor antibodies makes thyroiditis unlikely. This case lends support to the notion that follow up of thyroid function in every patient treated with either amiodarone or interferon is important. In addition, when a patient develops thyroid dysfunction the careful evaluation and determination of the specific underlying pathology and the exact type should lead to a rational management.

Acknowledgment

The authors would like to thank the patient for consenting for this case report and providing the nuclear medicine scans.

Author's contribution

Single author.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Compliance with ethical principles

None required for non-identifiable single case reports. Patient consented for case report on anonymous basis.



 
  References Top

1.
Siddoway LA. Amiodarone: Guidelines for use and monitoring. Am Fam Physician 2003;68:2189-96.  Back to cited text no. 1
    
2.
Porsche R, Brenner ZR. Amiodarone-induced thyroid dysfunction. Crit Care Nurse 2006;26:34-41.  Back to cited text no. 2
    
3.
Chan WB, Chow CC, Cockram CS. Interferon alpha treatment and endocrine disease. J R Soc Med 2003;96:481-5.  Back to cited text no. 3
    
4.
Murakami M, Kakizaki S, Takayama H, Takagi H, Mori M. Autoimmune thyroid disease induced by interferon therapy. Nihon Rinsho 1999;57:1779-83.  Back to cited text no. 4
    
5.
Marazuela M, García-Buey L, González-Fernández B, García-Monzón C, Arranz A, Borque MJ, et al. Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy. Clin Endocrinol (Oxf) 1996;44:635-42.  Back to cited text no. 5
    
6.
Baudin E, Marcellin P, Pouteau M, Colas-Linhart N, Le Floch JP, Lemmonier C, et al. Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C. Clin Endocrinol (Oxf) 1993;39:657-61.  Back to cited text no. 6
    
7.
Prummel MF, Laurberg P. Interferon-alpha and autoimmune thyroid disease. Thyroid 2003;13:547-51.  Back to cited text no. 7
    
8.
Wong V, Fu AX, George J, Cheung NW. Thyrotoxicosis induced by alpha-interferon therapy in chronic viral hepatitis. Clin Endocrinol (Oxf) 2002;56:793-8.  Back to cited text no. 8
    
9.
Kee KM, Lee CM, Wang JH, Tung HD, Changchien CS, Lu SN, et al. Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis. J Gastroenterol Hepatol 2006;21:319-26.  Back to cited text no. 9
    
10.
Carella C, Mazziotti G, Morisco F, Rotondi M, Cioffi M, Tuccillo C, et al. The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism. Eur J Endocrinol 2002;146:743-9.  Back to cited text no. 10
    
11.
Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'etude et de recherche en medecine interne et maladies infectieuses sur le virus de l'hepatite C. Medicine (Baltimore) 2000;79:47-56.  Back to cited text no. 11
    
12.
El Shafie O, Hussein S, El Awady W, Woodhouse N. Graves' disease following interferon therapy for chronic hepatitis C infection. Sultan Qaboos Univ Med J 2008;8:75-7.  Back to cited text no. 12
    


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