Correspondence

Rifampin-Induced Hypothyroidism in Patients with Hashimoto's Thyroiditis

N Engl J Med 2005; 352:518-519February 3, 2005

Article

To the Editor:

Rifampin is often used to treat tuberculosis.1 Isley2 reported on a patient with treated hypothyroidism (euthyroid while taking stable doses of thyroxine) but who again became hypothyroid after receiving rifampin. We now report on three euthyroid patients with Hashimoto's thyroiditis who became frankly hypothyroid after the administration of rifampin.

A 62-year-old man with recurrent non-Hodgkin's lymphoma was admitted one month before the onset of a productive cough. He had been euthyroid (thyrotropin level, 2.0 to 2.4 mU per liter) but had positive tests for antithyroid antibodies (thyroid peroxidase antibody level, 28 U per milliliter [normal value, <6.7]; thyroglobulin antibody level, 42 U per milliliter [normal value, <2.6]). A positive chest radiograph and a sputum culture containing acid-fast bacilli led to a diagnosis of tuberculosis, for which the patient received rifampin. Within two weeks, the levels of thyrotropin increased to 170 mU per liter and the serum thyroxine (T₄) and triiodothyronine (T₃) levels decreased to 2.4 μg per deciliter and 18.0 ng per deciliter, respectively. Treatment with thyroxine was initiated. After the course of rifampin therapy had been completed, thyroxine was discontinued. The patient has remained euthyroid for four years.

A peritoneal-biopsy specimen containing Langhans' giant cells led to a diagnosis of tuberculous peritonitis in a 66-year-old woman with ascites; she received treatment with rifampin. She also had euthyroid goiter and positive tests for thyroid peroxidase antibody (10 U per milliliter) and thyroglobulin antibody (54 U per milliliter) and had not received thyroxine. However, hypothyroidism developed after the administration of rifampin (thyrotropin level, 12.5 mU per liter; T₄ level, 4.8 μg per deciliter; and T₃ level, 0.87 ng per milliliter). Thyroxine therapy was administered for three months and then discontinued. Hypothyroidism developed again, and thyroxine treatment was resumed for the duration of the course of rifampin therapy, after which thyroxine was discontinued. The patient has remained euthyroid for 42 months.

A 56-year-old woman with a liver abscess and lymphadenopathy underwent lymph-node biopsy that showed Mycobacterium tuberculosis with caseating granulomas. She had had euthyroid goiter and positive tests for antithyroid antibodies (thyroid peroxidase antibody level, 5.6 U per milliliter; thyroglobulin antibody level, 19 U per milliliter). Levels of thyrotropin were 3.2 to 3.9 mU per liter before rifampin therapy but rose to 21.3 mU per milliliter within two weeks after the initiation of treatment with rifampin, for which thyroxine was administered (Figure 1Figure 1Hypothyroidism Induced by Rifampin in a 56-Year-Old Woman with Tuberculous Lymphadenitis and a History of Euthyroid Hashimoto's Thyroiditis.). When rifampin was discontinued, the hypothyroidism resolved. Three weeks later, the patient again required rifampin, and hypothyroidism developed again, within four weeks, and again was managed with thyroxine. After the final course of rifampin, thyroxine was discontinued, and the patient has remained euthyroid for 12 months.

Hypothyroidism developed within two weeks after the administration of rifampin in these patients but resolved in each, once rifampin was discontinued. Rifampin increases T₄ clearance, possibly because of enhanced hepatic T₄ metabolism and biliary excretion of iodothyronine conjugates.3,4 Studies in normal volunteers indicate that rifampin decreases circulating thyroid hormone levels without affecting thyrotropin,5 suggesting that rifampin has a direct downward effect on thyroid hormone levels. Physicians should be aware that at-risk patients who receive rifampin may become hypothyroid.

Nobuyuki Takasu, M.D., Ph.D.
Masaki Takara, M.D., Ph.D.
Ichiro Komiya, M.D., Ph.D.
University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan
takasun@med.u-ryukyu.ac.jp

5 References

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   Isley WL. Effect of rifampin therapy on thyroid function tests in a hypothyroid patient on replacement L-thyroxine. Ann Intern Med 1987;107:517-518
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Citing Articles (6)

Citing Articles

1. 1

   Zachariah Thomas, Farooq Bandali, Karen McCowen, Atul Malhotra. (2010) Drug-induced endocrine disorders in the intensive care unit. Critical Care Medicine 38, S219-S230
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2. 2

   Francesco Torino, Salvatore Maria Corsello, Raffaele Longo, Agnese Barnabei, Giampietro Gasparini. (2009) Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nature Reviews Clinical Oncology 6:4, 219-228
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3. 3

   Nobuyuki Takasu, Jaeduk Yoshimura Noh. (2008) Hashimoto’s thyroiditis: TGAb, TPOAb, TRAb and recovery from hypothyroidism. Expert Review of Clinical Immunology 4:2, 221-237
   CrossRef

4. 4

   Dong-Lim Kim, Kee-Ho Song, Jung Hyun Lee, Kye Young Lee, Suk Kyeong Kim. (2007) Rifampin-Induced Hypothyroidism without Underlying Thyroid Disease. Thyroid 17:8, 793-795
   CrossRef

5. 5

   Eric J Forget, Dick Menzies. (2006) Adverse reactions to first-line antituberculosis drugs. Expert Opinion on Drug Safety 5:2, 231-249
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6. 6

   (2005) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 14:7, i-xii
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