Endocrine Abstracts

Introduction: The tyrosine kinase inhibitor (TKI) lenvatinib, used in radioiodine-refractory differentiated thyroid cancer, is usually well-tolerated. However, severe side effects can occur. We describe a life-threatening complication under lenvatinib, followed by a challenging treatment with levothyroxine (LT4).

Case Report: A 62-year-old man was diagnosed with a bone-metastasized Hurthle cell thyroid carcinoma (pT3N0M1). He underwent a total thyroidectomy, external neck radiation and radioiodine after LT4 withdrawal (555 MBq; stimulated TSH 104.7 mU/l, stimulated thyroglobulin 2.7 µg/l, thyroglobulin antibodies <10 U/l). A I131 scintigraphy showed radioiodine-refractory disease. His medical history included a sleeve gastrectomy with conversion to gastric bypass and repeat surgical interventions for small bowel obstruction, eventrations and complicated abdominoplasty. He required LT4 250µg/day (weight 85 kg) to obtain a low normal TSH (table). Ten months after starting lenvatinib resulting in stable disease, he presented with an ischemic stomach pouch with perforation and fistulisation. An urgent laparotomy was performed and lenvatinib was stopped. Afterwards, he developed diarrhoea, for which cholestyramine 8g/day was started. Two months later, overt hypothyroidism was diagnosed (table, time 0) and the LT4 dose was doubled. An oral challenge with 1000µg LT4 showed an adequate increase of FT4, excluding deterioration of mucosal gastrointestinal malabsorption. After stopping cholestyramine, his thyroid hormone levels returned to baseline under LT4 250µg/day.

Conclusions: Treatment with lenvatinib can result in gastro-intestinal perforation and fistulisation, which is attributed to the anti-angiogenic effect. Caution is needed, especially in patients with a history of complex abdominal surgery. The need for high doses of LT4 should be reminiscent of either reduced gastrointestinal absorption or availability, such as interaction with cholestyramine. Cholestyramine, an anionic exchange resin used in the treatment of bile acid diarrhoea, binds LT4 in the intestine thereby reducing its absorption. The passage of LT4 through the enterohepatic circulation further contributes to this interaction. This interference can be minimized by providing at least four hours between ingestion of the two agents. m=months, d=days, hr=hours, reference range TSH (0.27-4.20 mU/L), FT4 (11.6-21.9 pmol/L)