Endocrine Abstracts

Background: The development of thyroid dysfunction is a frequent side effect associated to sunitinib therapy but scanty data are available on thyroid function on long-term sunitinib-treated patients.

Objective: Prospective evaluation of 28 patients suffering from mRCC treated with sunitinib, enrolled between September 2013 and October 2015. 28 patients (24 men and 3 women (median age 57.7, range 51–77)) with comparable tumor staging, normal thyroid function and no evidence of thyroid autoimmunity (TA), were studied before and every 4 weeks after beginning Sunitinib (Sutent). In all patients, serum levels of TSH, FT3, FT4, thyroid antibodies (TgAb and TPOAb) and morphological evaluation were measured up to 24 months (median 17.6 months). We analyzed cumulative thyroid dysfunction and TA in surviving patients.

Results: 6 (21%) patients died with no evidence of thyroid dysfunction (after 2–5 months of treatment) and TA. 22 (78%) developed primary hypothyroidism and 11 (39%) developed detectable TPOAb (TPOAb+). TPOAb+ patient had higher degree of hypothyroidism (median TSH 14.1 mIU/l vs 8.8 mIU/l in TPOAb-negative hypothyroid patients). Cumulative prevalence of hypothyroidism and TPOAb-positivity was 33% after 6 months, 46% after 12 months, 57% after 18 months to 78% at 24 months. Cumulative prevalence of TPOAb was 21% at 4 months, 32% at 9 months and 39% at 24 months. A remarkable decrease of thyroid volume (12.5±11.6 ml to 2.2±0.5 ml (P<0.0001)) was observed in almost all patients, during the first 9 months of treatment, associated with the complete disappearance of thyroid nodules in four patients with thyroid nodular disease before sunitinib therapy. Presently, the survival of patients developing more severe hypothyroidism (TSH >15 mUI/l) was significantly longer (17.8±6.2 months) when compared to the other patients (13.5±5.3 months P<0.05).

Conclusions: Prolonged sunitinib treatment is associated with progressive increase of hypothyroidism and TA, affecting almost all patients after 24 month of therapy. Severity of thyroid dysfunction is associated with longer survival and may represent a biomarker of response in sunitinib treated mRCC patients.