Thyroid Disease as a Side Effect of Nivolumab

A 52-year-old female patient, previously treated only for arterial hypertension and type 2 diabetes mellitus, was diagnosed with a left kidney tumor in 2007. The patient underwent a left-sided nephrectomy in November. Histologically, the diagnosis of clear cell renal carcinoma, stage pT2N0M0, was confirmed.

In 2012, due to the presence of a solitary lesion, resection of the 9th pulmonary segment on the right side was performed. Histologically, metastasis of clear cell renal carcinoma was confirmed. In August 2015, another surgery followed, this time extirpation of a paravertebral lesion ranging from L3 to S2 on the left side. Again, it was metastasis of clear cell renal carcinoma. Postoperatively, a restaging CT of the trunk described recurrence at the sacrum and new bilateral metastatic lung involvement. The patient was referred to an oncology clinic based on this finding.

Oncological treatment began in November 2015. Pazopanib was chosen for the first line of treatment and continued until 2018. The first interruption of therapy occurred in September 2016, when, based on a suspicious finding on imaging, encapsulation of the tumor in the right kidney was performed. Subsequently, a duplicate clear cell renal carcinoma on the right was diagnosed. The therapy with pazopanib had to be interrupted again in April 2018, this time for surgery for abscessing cholecystitis. Perioperatively, a splenectomy and partial pancreatectomy were also performed, finding three more metastatic lesions in the pancreas. The post-operative restaging CT described a new lesion at the resection site on the right, a metastatic lesion in the retrocaval lymph node, and progression of lung tumor involvement (Figures 1 and 2).

In July 2018, the second line of treatment began. This time cabozantinib was chosen. However, this therapy had to be soon interrupted due to significant skin toxicity, especially on the soles of the feet. An attempt to continue treatment at a reduced dose followed, but resulted in skin toxicity nearly preventing walking. Despite good radiological response, this therapy had to be discontinued.

Nivolumab was selected as the next therapy, starting in October 2018. Thyroid function was checked before immunotherapy initiation. Levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were normal. However, before the 3rd cycle, these hormone levels were pathological. TSH was elevated (8.64 mU/l), and free hormone levels were low. An endocrinologist was consulted with this finding, but substitution therapy was not recommended at this time. By early January 2019, before the 4th cycle, thyroid function was checked again. TSH levels were very high (88 mU/l), and free hormone levels were almost zero. The patient did not experience any subjective difficulties. Antithyroid antibodies (anti-TPO, ATG, TRAK) were also measured and found to be negative. Another consultation with an endocrinologist followed, and this time hormone substitution therapy (Euthyrox 100 μg daily) was recommended.

At the next thyroid function check in late January 2019, TSH levels had already decreased (5.16 mU/l). Before the 6th cycle, about a month after starting hormone substitution therapy, results were completely normalized. The restaging CT described slight progression at the right kidney lesion, but other lesions appeared to be regressing. The finding was evaluated as pseudoprogression according to iRECIST criteria. The patient herself is in very good clinical condition, without any limiting difficulties. The plan is to continue the current therapy with nivolumab.

MUDr. Aneta Kyllarová