Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung

Abstract

Thyroiditis is characterised by transient hyperthyroidism, followed sometimes by hypothyroidism, and then recovery. We report a case of painless drug-induced thyroiditis-in a patient with no history of any thyroid disorder-treated with Nivolumab (an IgG4 monoclonal antibody against Programmed Death Receptor 1). The purpose of this case report is to increase awareness among clinicians regarding this possible adverse effect from Nivolumab, and discuss the possible pathophysiology and management strategies in such patients.

Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies

“…Painless thyroiditis has also been reported in a 55-year-old woman who developed dyspnea, anxiety, diarrhea and palpitations 3 weeks after her second nivolumab treatment; levels of TSH were undetectable and levels of free T 4 (2.06 ng/dl) and T 3 (554.2 pg/dl) were high 120 . Thyroid autoantibody assays showed the patient had normal levels of TPO antibodies and normal thyroid-stimulation immunoglobulins with elevated thyroglobulin antibodies which indicated a level of thyroid autoimmunity; ultrasonography, which usually is not a diagnostic test for thyroiditis and can appear normal in mild cases, showed normal vasculature and density within the thyroid gland 120 .…”

“…Thyroid autoantibody assays showed the patient had normal levels of TPO antibodies and normal thyroid-stimulation immunoglobulins with elevated thyroglobulin antibodies which indicated a level of thyroid autoimmunity; ultrasonography, which usually is not a diagnostic test for thyroiditis and can appear normal in mild cases, showed normal vasculature and density within the thyroid gland 120 . This patient returned to a euthyroid state after therapy with β-blockers and withdrawal of immunotherapy, but it is important to note that thyrotoxicosis can still progress to a hypothyroid state as described above 118 .…”

“…Supportive therapy with β blockers can help to alleviate adrenergic symptoms and signs of hyperthyroidism, and immunotherapy could be held if severe symptoms are present 120 . Radioactive iodine uptake can be inaccurate given the frequency with which iodine contrast-enhanced imaging is used in cancer patients 40 .…”

“…We further recommend that TFTs are monitored in those undergoing anti-PD1 therapy. Given that primary thyroid dysfunction can present as early as 3 weeks and as late as 3 years after treatment 12032 , TFTs should be monitored monthly for the first 6 months of treatment. For the management with CTLA4 immunotherapy, we recommend that for those receiving PD1 antibodies, if thyroid function is normal and the patient is asymptomatic, testing could be done every 3 months for 6–12 months followed by every 6 months for years 2 and 3.…”

Urgent need to define Pretreatment predictors of immune check point inhibitors related endocrinopathies: A case report and review of literature

“…[33] This calls for frequent monitoring and cautious use of THRT or thionamides as the case might be. [34] Hypothyroidism is more common as was seen in our case, although the patient had an underlying subclinical hyperthyroidism. The highest grade of this side effect is usually classified as grade 2 in checkmate 057 trial, in which nivolumab was assessed in the treatment of nonsquamous cell non-small cell lung cancer (NSCLC).…”