Thyroid storm is a rare, life-threatening endocrine emergency with a high mortality rate of up to 30%. We present a unique management challenge of a critically ill patient who developed thyroid storm in the setting of a duodenal perforation from amphetamine-associated non-occlusive mesenteric ischaemia. The diagnosis of 'thyroid storm' was made based on clinical criteria and a Burch-Wartofsky score of 100. During emergent exploratory laparotomy, a 1 cm duodenal perforation with surrounding friable tissue was found and repaired. Intraoperatively, a nasogastric tube was guided distal to the area of perforation to allow for enteric administration of medications, which was critical in the setting of thyroid storm. Therapeutic plasma exchange achieved biochemical control of our patient's thyroid storm but ultimately did not prevent in-hospital mortality.