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J R Soc Med. 2002 October; 95(10): 506.
PMCID: PMC1279180

Discrepant thyroid function tests in a patient treated with interferon-alpha

Interferon-alpha treatment is associated with autoimmune thyroid dysfunction1,2. Antibody to thyroxine (T4) can confuse the interpretation of thyroid function tests3.


A woman of 24 was referred with suspected hypothyroidism. For twenty months she had been receiving interferon-alpha for chronic myelogenous leukaemia. A check on thyroid function four months into treatment had shown thyroid-stimulating hormone (TSH) 7.12 mIU/L (normal range 0.3-4.0) and free T4 15.4 pmol/L (10.2-19.6). At sixteen months she noted facial puffiness and weight gain, at which time TSH was > 150 mIU/L. Her symptoms partly subsided on treatment with L-thyroxine 50 μg daily. At the time of referral, TSH was > 150 mIU/L but she also had raised free T4 at 20.4 pmol/L. Antimicrosomal antibody titre was 6400; antithyroglobin was negative. In view of the improvement of symptoms and the inconsistent thyroid function test results, L-thyroxine was temporarily stopped and the tests were repeated. TSH remained > 150 mIU/L with a free T4 of 20.8 pmol/L. The simultaneous free T3 concentration was 2.3 pmol/L (normal range 3.5-6.5 pmol/L) and the erythrocyte zinc concentration was 334 μmol/L (155-237). Thus all biochemical results were consistent with primary hypothyroidism except for the high free T4. A two-step free T4 assay was arranged and she was given L-thyroxine 100 μg daily. On this dose the TSH fell to 52.5 mIU/L while the free T3 rose to 3.2 mIU/L. The free T4 result obtained with the two-step assay was later reported as 7.67 pmol/L, suggesting that T4 antibody had interfered with the one-step analogue assay. L-thyroxine was then gradually titrated down to 50 μg daily, on which dose TSH was 2.7 mIU/L while the free T4 result with the one-step assay was 19.5 pmol/L. Her thyroid function tests remained stable thereafter.


Interferon-alpha has been widely used in chronic myelogenous leukaemia2, and various endocrine diseases have been reported in association with this treatment4. In a series of 581 patients with chronic myelogenous leukaemia treated with interferon-alpha, 2% became hypothyroid2. Development of autoantibodies alone is much more common, reaching 20% in some series5. Thyroid dysfunction may be more prevalent in those who are antibody-positive before treatment. On withdrawal of interferon, the antibodies sometimes disappear and sometimes persist1.

Anti-T4 antibodies are well-known to account for a spuriously high free T4 result in the one-step analogue assay. The underlying mechanism is binding of the T4 analogue by antibody3. Antibodies are present in less than 1% of normal individuals6. Our patient had a normal free T4 three months after starting interferon, so she is unlikely to have had pre-existing T4 antibody. A causal relation is further indicated by the disappearance of T4 antibody when interferon treatment was stopped.


1. Carella C, Mazziotti G, Morisco F, et al. Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment. J Clin Endocrinol Metab 2001;86: 1925-9 [PubMed]
2. Sacchi S, Kantarjian H, O'Brien S, Cohen PR, Pierce S, Talpaz M. Immune-mediated and unusual complications during interferon alpha therapy in chronic myelogenous leukaemia. J Clin Oncol 1995;13: 2401-7 [PubMed]
3. Sapin R, Gasser F, Schlienger JL. Familial dysalbuminemic hyperthyroxinemia and thyroid hormone autoantibodies: interference in current free thyroid hormone assays. Horm Res 1996;45: 139-41 [PubMed]
4. Wesche B, Jaeckel E, Trautwein C, et al. Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C. Gut 2001;48: 378-83 [PMC free article] [PubMed]
5. Gisslinger H, Gilly B, Woloszczuk W, et al. Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha. Clin Exp Immunol 1992;90: 363-7 [PubMed]
6. Sakata S, Matsuda M, Ogawa T, et al. Prevalence of thyroid hormone autoantibodies in healthy subjects. Clin Endocrinol (Oxf) 1994;41: 365-70 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press