Endocrine Abstracts

Background: Many drugs are known to cause thyroid dysfunction. We describe a patient with hypothyroidism due to isotretinoin.

Case: A 28 year-old Chinese gentleman presented with 2-year history of fatigue and cold intolerance. He has acne vulgaris and has been taking isotretinoin for the last 3 years (20 mg daily for 1 year then 10 mg daily). He has a positive family history of thyroid disorders. He did not report any history of thyroiditis or known autoimmune disorders and is not on any other medications. Non-thyroidal illness was unlikely as he was otherwise well. Examination did not reveal any goiter or suggestion of autoimmune diseases. Laboratory investigations: free thyroxine (fT4) 11.4 pmol/l (RI: 8–20) and thyroid stimulating hormone (TSH) 6.17 mIU/l (RI: 0.45–4.5). Repeated thyroid function in a different laboratory: fT4 11.1 pmol/l (RI: 8–20) and TSH 8.08 mIU/l (RI: 0.45–4.5). Thyroid peroxidase antibody was negative. He reported increasing fatigue. As there were no other potential etiologies, the thyroid abnormality was attributed to isotretinoin. The patient was not willing to stop isotretinoin therapy and was started on replacement thyroxine 50mcg daily, which relieved his symptoms of hypothyroidism. At the last visit, thyroid function was normal: fT4 12 pmol/l (RI: 8–16) and TSH 2.72 mIU/l (RI: 0.45–4.5).

Discussion: Isotretinoin is known to be associated with lipid abnormalities and liver dysfunction but few are aware of its association with thyroid abnormalities. Proposed mechanisms include central gene-related inhibition and increased peripheral degradation of thyroid hormones via a non-deiodinase-mediated pathway. Even at a reduced dose of isotretinoin, our patient continued to exhibit symptoms of hypothyroidism, with abnormal thyroid function test results. Studies have shown significant decrease in levels of fT4 and TSH at both high and low doses. However, isotretinoin might not have an influence in them with intermittent treatment. It is likely that effects on thyroid metabolism may be dose-dependent but this requires further studies. Hypothyroidism is reported to show improvement with stopping isotretinoin. Given the anti-thyroid effects of isotretinoin, there has been a lower threshold for checking thyroid function tests.

Conclusions: We encourage routine thyroid function tests to be done at baseline and regular intervals thereafter, even in patients taking low doses of isotretinoin, given the effects it has on thyroid function. However, more studies are required to fully understand related dose-dependent changes. If the patient is not keen to stop medication, supplemental thyroxine will be beneficial in the treatment of isotretinoin-associated hypothyroidism.