Endocrine Abstracts

Introduction: It is known that hypothyroidism has multiple etiologies including tyrosinkinase inhibitors (TKI) agents which can cause thyroid disfunction through different mecanisms, not fully defined yet- Vascular endothelial growth factor receptor (VEGFR) blockade, thyroiditis, iodine uptake blockade, increased activity of deiodinase 3, increased hormone clearance. Some recent trials suggest that there is a correlation between the incidence of hypothyroidism and the outcome of patients treated with TKI, therefore the occurrence of hypothyroidism during Sunitinib treatment is a predictive marker of a progression-free survival.

Case report: We report the case of a 62-year-old female, with a family history of hypothyroidism (daughter- Hashimoto’s disease). The patient was diagnosed in 2007 with metastatic retroperitoneal tumor GIST and since 2010 she has been treated with Sunitinib. She was first referred to our Institute in June 2017, after being diagnosed with pericarditis (medium pericardial effusion, without cardiac tamponade). The patient complained about gaining weight (7 kg in the past few months), extreme fatigue, palpebral edema, dry skin and cold intolerance. The hormonal profile found a TSH level=69 μUI/ml (normal range=0.5–4.5) with FT₄=3.84 pmol/l (normal range=10.3–24.4) and a negative ATPO. Biochemical tests revealed hypercholesterolemia (cholesterol=227 mg/dl), hypertrigliceridemia (trygliceride=258 mg/dl), increased serum creatinine level (creatinine=1.63 mg/dl), moderate anemia (hemoglobin =10.1 g/dl), neutropenia (1.6×1000/ul) and high inflammatory markers (VSH=65 mm/h). Thyroid ultrasound revealed a typical pattern for atrophic thyroiditis and a group of macrocalcifications in the left lobe. We initiated the treatment with 37.5 μg levothyroxine for the first 10 days, then progressively raised at 50 μg/day for the next 14 days; then to 62.5 μg/day, 75 μg/day, 87.5 μg/day until the dosage of 100 μg/day, with a decline in TSH from 69–1.55 μUI/ml and an improvement in renal function from a 1.63 mg/dl creatinine level to 0.85 mg/dl. Also, the pacient has a good response to Sunitinib, based on the long progression free survival (2010–2018).

Conclusion: Hypothyroidism induced by Sunitinib is a common side effect of the molecule. It is important to recognize it in a patient who is being treated with TKI in order to prevent possible complications. In addition, this case report comes to strengthen some recent opinions regarding a longer progression free survival in patients who develop hypothyroidism during treatment with Sunitinib.