CLINICAL COMMUNICATION TO THE EDITOR
Symptomatic Graves’ Disease After Autoimmune Hypothyroidism To the Editor: In 2002, a healthy 26-year-old Chinese man developed fatigue. Examination revealed an enlarged, nontender thyroid without nodules. Thyroid-stimulating hormone was 313.28 mU/mL (normal, 0.4-6.0). Free T4 was 2.0 pmol/L (normal, 7.5-21). Thyroid peroxidase antibody was >70 IU/mL (normal, 0-2). Thyroglobulin antibody was 39.6 IU/mL (normal, 0-2). Hashimoto thyroiditis was diagnosed. Levothyroxine was initiated with normalization of thyroidstimulating hormone and free T4. The patient remained asymptomatic until April 2014, when he noted decreased energy. The heart rate was 94 beats/min; otherwise, the examination was unchanged. Thyroid-stimulating hormone was 0.07 mU/mL, and free T4 was 22.1 pmol/L. Levothyroxine was decreased. The patient was lost to follow-up until March 2015, when he presented with sweating and a 12-kg weight loss since April 2014. The heart rate was 120 beats/min. Proptosis was absent. Otherwise, the examination was unchanged. Levothyroxine was discontinued, but thyroid-stimulating hormone remained <0.03 mU/mL, free T4 was 68.2 pmol/L, and T3 was 489.4 ng/dL (normal 80-200). Thyroid peroxidase antibody was 742 IU/mL (normal <9), thyroglobulin antibody was 30 IU/mL (normal <2), thyrotropin-blocking antibody was 77% inhibition (normal <17), and thyroidstimulating antibody was 382% of baseline (normal, <140). Radioactive iodine uptake scan showed an enlarged thyroid with increased and diffuse uptake (Figure). Ultrasound demonstrated an enlarged, heterogeneous thyroid with increased vascularity. Graves’ disease was diagnosed. Methimazole was initiated, and the patient’s condition improved. The patient declined propranolol. This patient initially presented with autoimmune hypothyroidism and 12 years later developed symptomatic Graves’ disease. The diagnosis became clear when he remained hyperthyroid despite levothyroxine discontinuation.
Funding: None. Conflict of Interest: None. Authorship: Both authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Sam Brondfield, MD, University of California, San Francisco, Department of Medicine, 505 Parnassus Ave, Rm 987, San Francisco, CA 94143-0119. E-mail address: sam.brondfi
[email protected]
0002-9343/$ -see front matter Published by Elsevier Inc.
Hashimoto thyroiditis is the most common form of autoimmune hypothyroidism, whereas thyrotropin-blocking, antibody-induced hypothyroidism is more rare. Differentiating these causes of hypothyroidism is difficult when both subsets of antibodies are present. Each may present with or without goiter. A recent review describes rare switching between thyrotropin-blocking antibodies and thyroid-stimulating antibodies in patients receiving levothyroxine.1 An association between levothyroxine and an increase in thyroid-stimulating antibody level has been reported in patients with autoimmune hypothyroidism.2 Thyrotropinblocking antibodies may be a precursor of stimulating antibodies.3 Graves’ disease was reported in 4 middle-aged female patients after 2 to 7 years of painful Hashimoto thyroiditis.4 This patient developed symptomatic Graves’ disease after 12 years of painless autoimmune hypothyroidism, longer than any previously reported interval to our knowledge. In this patient, blocking antibodies may have progressed to stimulating antibodies leading to clinical Graves’ disease. Alternatively, examination demonstrating a soft, enlarged thyroid could be consistent with an initial simultaneous
Figure Radioactive iodine uptake scan in a patient with treated autoimmune hypothyroidism demonstrating an enlarged thyroid gland with increased and diffuse uptake consistent with Graves’ disease.
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diagnosis of Graves’ disease with hypothyroid antibodies predominating. Rare cases of concomitant Graves’ disease and autoimmune thyroiditis have been reported.5 If hyperthyroid symptoms prompt a decrease in levothyroxine dosing in patients with treated autoimmune hypothyroidism, close monitoring of thyroid function and vigilance for Graves’ disease are warranted. Clinicians should be alerted to this potentially life-threatening complication that may occur after many years of wellcontrolled autoimmune hypothyroidism. Sam Brondfield, MDa,b Kenneth R. Feingold, MDa,b a
Department of Medicine, University of California, San Francisco b Department of Medicine, San Francisco VA Medical Center San Francisco, Calif
http://dx.doi.org/10.1016/j.amjmed.2015.12.017
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2016
References 1. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23:14-24. 2. Takasu N, Matsushita M. Changes of TSH-stimulation blocking antibody (TSBAb) and thyroid stimulating antibody (TSAb) over 10 years in 34 TSBAb-positive patients with hypothyroidism and in 98 TSAbpositive Graves’ patients with hyperthyroidism: reevaluation of TSBAb and TSAb in TSH-receptor-antibody (TRAb)-positive patients. J Thyroid Res. 2012;2012:182176. 3. Ochi Y, Kajita Y, Hachiya T, Arata N, Hamaoki M. Conversion of TBAb response to TSAb response by anti-human IgG antibody. Endocr Metab Immune Discord Drug Targets. 2013;13:311-315. 4. Ohye H, Nishihara E, Sasaki I, et al. Four cases of Graves’ disease which developed after painful Hashimoto’s thyroiditis. Intern Med. 2006;45:385-389. 5. Majumder A, Sanyal D. A case of simultaneous occurrence of Graves’ disease and Hashimoto’s thyroiditis. Indian J Endocrinol Metab. 2012;16:S338-S339.