Endocrine Abstracts

Context: Monoclonal antibodies to Immune Check Point inhibitors (ICPis) are powerful anti-cancer drugs. They trigger the immune system against cancer cells, blocking inhibitory signals of T-Cells. However, ICPi therapy can also stimulate autoimmune reactions, inducing the so-called immune-related adverse events (irAEs). Endocrinopathies are common iRAEs and thyroid disfunction is the most common endocrinopathy during ICP therapy. We report three cases of thyroid disfunction during Nivolumab (Anti-PD1) therapy.

Case 1: A 65 year old male that undergoing Nivolumab treatment for metastatic non-small cell lung cancer. At baseline, FT4, FT3 and TSH were in the normal range, while thyroid autoantibodies (TgAb and TPOAb) were slightly positive. Neck ultrasonography showed a hypoechoic normal size thyroid with no nodules. Eight weeks later, thyroid function test demonstrated an overt hyperthyroidism. TRAb were undetectable and thyroid scintigraphy showed low uptake. During follow-up, FT4, FT3 and TSH normalized spontaneously within 3 months and remained in the normal range during Nivolumab treatment.

Case 2: A 67 year old female came to our observation because of recent onset of fatigue and hair loss. She was administered the third infusion of Nivolumab because of a metastatic non-smal cell lung cancer. Thyroid function tests revealed an overt hypothyroidism (FT4: 0.5 ng/dl (normal range 0.7–1.7); TSH: 38 mcUI/ml (normal range 0.4–4)). At baseline, thyroid function test was in the normal range and thyroid autoantibodies were highly positive. Neck ultrasonography showed a markedly hypoechoic thyroid of small size. Levothyroixe treatment was started. Euthyroidism was restored in 2 months with improvement of symptoms.

Case 3: A 51 year old male came to observation because of palpitations, heat intolerance and insomnia. He was at the sixth infusion of Nivolumab for a metastatic melanoma. Before the immune therapy thyroid function tests were in the normal range; autoantibodies were undetectable. An increased heart rate and sweaty skin were found at physical examination. Thyroid function tests showed an overt hyperthyroidism (FT4: 2.28 ng/dl; FT3: 7.82 pg/ml (normal range 2.7–5.7) TSH: < 0.004 mcUI/ml). Thyroid autoantibodies remained undetectable. Neck ultrasonography showed an enlarged hypoechoic thyroid with a hypervascular pattern. Tc99 thyroid scintigraphy showed an increased uptake. Methymazole therapy was started and a normal thyroid function was restored within a few days.

Conclusions: Thyroid dysfunction during immunotherapy is a common irAE that may have variable presentation and impact negatively on patient’s general conditions. When thyroid dysfunction is managed properly, immunotherapy does not usually need to be discontinued.