Interferon-Alpha Induced Severe Hypothyroidism Followed by Graves' Disease in a Patient Infected with Hepatitis C Virus

Kyoung Jin Kim; Kang Won Lee; Ju Hee Choi; Jee Hyun An

doi:10.11106/ijt.2015.8.2.230

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Kim, Lee, Choi, and An: Interferon-Alpha Induced Severe Hypothyroidism Followed by Graves' Disease in a Patient Infected with Hepatitis C Virus

Case Report

Int J Thyroidol 2015;8(2):230-234.

Published online: 20 November 2015

DOI: https://doi.org/10.11106/ijt.2015.8.2.230

Interferon-Alpha Induced Severe Hypothyroidism Followed by Graves' Disease in a Patient Infected with Hepatitis C Virus

Kyoung Jin Kim, Kang Won Lee, Ju Hee Choi, Jee Hyun An

Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

Correspondence: Jee Hyun An, MD, PhD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea Tel: 82-2-920-6272, Fax: 82-2-953-9355, E-mail: jeehyunan@gmail.com

Received 7 July 2015 Revised 19 September 2015 Accepted 2 October 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Interferon-alpha (IFN-α) is an important therapeutic agent for hepatitis C virus (HCV) infection, but has various side effects including thyroiditis. We report a case of interferon-induced non-autoimmune hypothyroidism followed by autoimmune-medicated Graves' disease. A 59-year-old woman was diagnosed with chronic active hepatitis C; she had been treated with IFN-α and ribavirin for 24 weeks. Before starting the IFN-α, her thyroid function was normal and she was negative for autoantibodies. Severe hypothyroidism developed 5 weeks after halting the IFN-α, with the Graves' disease phase arising at 32 weeks. For accurate diagnosis and appropriate treatment of thyroid dysfunction during treatment with IFN-α, we need to understand and consider rare cases of multiphasic disorder involving both non-autoimmune and autoimmune thyroiditis induced by IFN-α.

Keywords: Interferons, Non-autoimmune hypothyroidism, Graves', disease

References

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Fig. 1.

Tc-99m scintigraphy in the thyrotoxic period. (A) After taking levothyroxine for hypothyroidism for 7 weeks. (B) Eight weeks after disconti-nuing levothyroxine with con-firmed TSH receptor antibody positivity.

Fig. 2.

The clinical course of thyroid function in the HCV- infected patient on IFN-α therapy: the biphasic pattern of thyroid function after initiation of IFN-α therapy.

Table 1.

Summaries of multi-phasic thyroiditis in five cases

	Case 1	Case 2	Case 3	Case 4	Case 5
Reference	Bohbot et al.¹⁰⁾	Bohbot et al.¹⁰⁾	Bohbot et al.¹⁰⁾	Kim et al.⁹⁾	Tran³⁾
Sex/Age	M/41	M/39	M/47	F/31	M/53
History of thyroid disease	None	None	None	None	None
Duration of IFN-α	12 months	13 months	7 months	12 months	12 months
Phase	Tri-phasic	Tri-phasic	Tri-phasic	Bi-phasic	Tri-phasic
Course	Silent thyroiditis	Silent thyroiditis	Silent thyroiditis	Destructive	Two peaks of
(as mentioned in the case)	followed by Graves' disease	followed by Graves' disease	followed by Graves' disease	e thyroiditis followed by Graves' disease	thyrotoxicosis bisected by hypothyroidism
1st phase	Thyrotoxicosis	Thyrotoxicosis	Thyrotoxicosis	Thyrotoxicosis	Thyrotoxicosis
– Month to 1st	4 month	4 month	6 month	7 month	7 month
– Antibody: TPOAb/TgAb/TSHRAb	(−/+/-)	(+/ND/-)	(+/ND/-)	(−/-/-)	(+/-/-)
– Scintiscan	No uptake	No uptake	No uptake	No uptake	No uptake
2nd phase	Hypothyroidism	Hypothyroidism	Hypothyroidism	Thyrotoxicosis	Hypothyroidism
– Month to 2nd	5 month	6 month	8 month	14 month	9 month
3rd phase	Thyrotoxicosis	Thyrotoxicosis	Thyrotoxicosis	–	T3-Thyrotoxicosis
– Month to 3rd	9 month	8 month	11 month	–	14 month
Last finding
– Antibody: TPOAb/TgAb/TSHRAb	(+/+/+)	(ND/ND/+)	(ND/ND/+)	(ND/+/+ → −)	(+/+/+)
– Scintiscan	Intense uptake	Intense uptake	Intense uptake	Intense uptake	Intense uptake
Treatment for thyroid +	ATD, B-blocker and LT4	ATD and LT4	ATD	B-blocker and ATD	B-blocker and ATD
IFN-α treatment	Continued	Discontinued	Discontinued	Continued	Continued

ATD: anti-thyroid drug, IIT: interferon induced thyroiditis, LT4: levothyroxine, ND: not done.

Normal range: Case 1–3 TSH (0.27–4.2 mIU/l), FT4 (9.3–17 ng/l), T3 (2.57–4.43 ng/l); Case 4 TSH (0.35–5.5 mIU/l), FT4 (9–26 pM/l), T3 (1.1–2.9 nM/l), Total T4 (64–154 Nm/l); Case 5 TSH (0.4–4.0 mIU/l), FT4 (10.1–24.5 pM/l), T3 (3.3–5.9 pmol/l).

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