Endocrine Abstracts

Introduction: Levothyroxine monotherapy is the standard treatment for hypothyroidism; it is safe and inexpensive, restores thyroid function tests to within the reference range, and improves symptoms in most patients. However, some patients require Liothyronine (LT3) to improve symptoms, and there is less safety data available for this. Here we report a case of sudden death in a patient using Liothyronine and present a safety data review for Liothyronine and Levothyroxine using national mortality and adverse-drug event records.

Case Summary: A 42-year-old woman was found dead in her house unexpectedly, one morning. She did not have any recent illnesses or significant past medical history and no regular medication was recorded in her general practitioner’s record. However, she had previously seen a private practitioner and had been diagnosed with possible chronic fatigue syndrome and an ‘under active thyroid’. For these, she took sertraline, clonazepam and liothyronine, bought off the internet and dosed by herself. Post-mortem examination showed no cardiac abnormalities, but did show bilateral pulmonary oedema, focal hepatic necrosis without inflammation, and an atrophic thyroid gland. Serum toxicology was unremarkable. The medical examiner reported the cause of death as “Sudden Unexpected Death in the setting of (chronic) liothyronine use”. To set the coroner’s conclusion in context, we assessed national statistics for mortality data in Wales over the last 10 years (2013-2022), to determine the overall deaths attributed to ’unknown cause’ and to thyroid disease. We found that while deaths due to unknown causes are rare (n = 681, 0.185% of all deaths), deaths attributed to thyroid disease (excluding cancer) or thyroid medications, are even rarer (n = 101, 0.029% of all deaths). We found no death due to thyroid disease or thyroid medications in the patient’s age-bracket. Lastly, we reviewed the number of adverse safety events including deaths due to Liothyronine and Levothyroxine in reports published by the UK medicines regulator, MHRA, via their yellow card reporting scheme since the early 1970s. The MHRA reported 23 deaths associated with Levothyroxine with no reported deaths associated with Liothyronine. Both treatments had similar profiles for other related non-fatal adverse events.

Conclusion: While this case raised concern that LT3 may be associated with sudden death, our safety data review is reassuring, and does not support an association between Liothyronine and sudden death. Nonetheless, there is a pressing need for systematic studies on LT3 safety in larger populations.