Endocrine Abstracts

Introduction: Pazopanib is a tyrosine kinase inhibitor (TKI), approved for the treatment of metastatic renal cell carcinoma and could improve progression-free survival and overall survival. The frequency of Pazopanib-induced hypothyroidism was reported to be 10–29%. We aim through this case to highlight the importance of thyroid function monitoring during treatment with TKI.

Case report: Female patiente of 41 years old, followed in oncology departement for clear cell renal carcinoma with hepatic metastasis, treated with pazopanib 1 mg per day for 8 months. During the follow-up the patient was refereed to our department for an elevated TSHus 1 ui/l. She presented an intermittent constipation and frilosity. Clinical examination noted no goiter. Neck-ultrasoud showed a normal thyroid gland volume with heterogenous stucture of thyroiditis aspect. Anti-TPO and anti-TG antibodies were negative. The patient started L-thyroxine 75 mg per day with good evolution and normalisation of TSHus levels. After 5 months the patient stopped Pazopanib for 2 months (availability issu), and presented signs of thyrotoxicosis with suppressed TSHus level 0.1 UI/l, L-thyroxine therapy was discontinued 6 weeks later TSHus remained normal 2.1 UI/l. One month later Pazopanib has been restarted, then the patient, represented once again an elevated TSHus: 8.1 UI/l requiring resumption of L-thyroxine therapy. The clinical evolution was favorable, appropriate follow up is planned.

Conclusions: In patients treated with TKI, the thyroid toxicity is common and pauci-symptomatic at the beginning of their evolution but can lead to prolonged hypothyroidism. Pathophysiological mechanisms linked to hypothyroidism in patients receiving TKI are unclear. Some researchers have hypothesized that the hypothyroidism may be due to the direct toxicity of TKI on the thyroid. Other hypotheses have been suggested; VEGF/R-TKI block thyroid hormone biosynthesis through thyroid peroxidase inhibition, increasing type 3 deiodination\.. The classic presentation of dysthyroidism associated with TKI is silent thyroiditis, beginning with a phase of thyrotoxicosis secondary to thyroid vesicles destruction releasing the stock of thyroid hormones, it can be treated with non-cardioselective β-blockers or even with cholestyramine. Then the patient may develop hypothyroidism, which is reversible in half of the cases. Thyroid function monitoring is important, it’s recommended by the French Society of Endocrinology, to measure the TSH/free T4 levels before starting treatment, and every 3 to 4 weeks during the first 6 months as changes in free T4 levels precede the changes in TSH by 3 to 6 weeks. After this period, TSH measurement alone may be conducted every 2-3 months.