Isotretinoin Associated Reversible Hypothyroidism

Isotretinoin (13-cis retinoic acid) has been regarded as an effective drug for the treatment of acne. Its wide range of adverse effects limits its use, however (1). Isotretinoin has been reported to disturb thyroid function, causing both reversible hypoand hyperthyroidism (1–3), but this impression is not conclusive. The patient presented here supports an association between use of oral 13-cis retinoic acids and reversible hypothyroidism. A 25-year-old woman presented to the Endocrinology Clinic of Aga Khan University Hospital in February 2010 with complains of a weight gain of 3 kg, along with dull mood and mennorrhagia for the previous 3–4 months. There was no history of cold intolerance, constipation, excessive sleep, lethargy, or hair loss. There was no family history of hypothyroidism. Drug history revealed that for 6 months she had taken isotretinoin, 20 mg once daily, for the treatment of acne. This had been stopped about 6 weeks before her presentation. There was no history of alcohol consumption or any other drug intake during this period. On examination, her pulse was 86 beats per minute, blood pressure was 130/80 mm Hg, and weight was 50.5 kg. A small diffuse goiter was noted; the remainder of her physical examination was unremarkable. Thyroid function tests done 1 month before visit, approximately 2 weeks after stopping the isotretinoin, showed a serum thyroid-stimulating hormone (TSH) of 78.97 mIU/mL (normal range 0.4–4.2), triiodothyronine of 1.51 nM (normal range 1.3–3.1), and thyroxine of 4.42 mg/dL (normal range 5.0–12.0). As she reported progressive improvement in her symptoms over the previous month, thyroid hormone replacement therapy was not instituted and she was asked to repeat her serum TSH. Her TSH done on the day of visit, that is, 6 weeks after stopping isotretinoin, was 15.03 mIU/mL. There was no history of thyrotoxic phase during the preceding several months that could have suggested the hypothyroid phase of thyroiditis. She was advised to follow-up in 6 weeks. When she presented again in March for another visit, she was symptom free. Her lab work-up on that day, 12 weeks after stopping isotretinoin, showed a serum TSH of 3.33 mIU/mL and antithyroid peroxidase enzyme levels of 3.30 IU/mL (<12 IU/mL). She was advised to follow-up in case of recurrence of symptoms and have her serum TSH repeated after 6 months. The effects of vitamin A derivatives on thyroid function have been a topic of interest for a number of years. Bexarotene, a compound closely related to isotretinoin, causes hypothyroidism both by central mechanism and by increasing the peripheral degradation of thyroid hormones by a nondeiodinase mediated pathway (4). In the study conducted by Marsden et al. (2), seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 weeks. Their levels of serum triiodothyronine and thyroxine were significantly lower after treatment, but the response to thyrotropin releasing hormone (TRH) stimulation was retained. These findings were partially attributed to induction of hepatic microsomal enzymes by isotretinoin. Another study conducted by Lyons et al. (1) showed mild decrease in the indices of thyroid function after treatment with 0.8 mg/kg 13-cis retinoic acid for 3 months. It was noticed that these changes reverted to normal 1 month after discontinuation of therapy. Oral isotretinoin therapy is increasingly used as an effective antiacne medication. It needs to be kept in mind that this drug could have antithyroid effects in susceptible patients. Therefore, there should be a low threshold for checking thyroid function tests in patients taking isotretinoin even if they have subtle signs or symptoms of thyroid dysfunction.