Thyroid
Janki Patel, MD, MBBS (she/her/hers)
Physician Fellow
University of Texas Health Science Center at Houston
Houston, Texas, United States
Over the recent years, the widespread adoption of immune checkpoint inhibitors (ICPis) has revolutionized cancer treatment. These agents, however, bring about distinctive immune-related adverse events (irAEs), adding a layer of complexity to their clinical management. Thyroid dysfunction induced by immune checkpoint inhibitors (ICPis) represents a common immune-related adverse event (irAE). Typically, ICPi-induced thyrotoxicosis marks the initial phase of a biphasic thyroiditis, often progressing to hypothyroidism. However, the emergence of ICPi-induced Graves’ disease (GD), characterized by the stimulating activity of TSH-receptor autoantibodies, remains exceptionally rare in clinical occurrences. We present a case of a Graves’ disease induced by anti-PD-1 therapy.
Case(s) Description :
nodes was initially being treated with carboplatin and pemetrexed. After completing 6 cycles of this treatment, pembrolizumab was added to her therapy. Carboplatin had to be discontinued at cycle 9 due to hypersensitivity, and pemetrexed was discontinued after an additional 8 cycles due to myelosuppression. She then transitioned to single agent pembrolizumab for maintenance and received a total of 30 cycles.
She had a preexisting history of hypothyroidism and was taking levothyroxine at a daily dose of 50 mcg when she was diagnosed with lung cancer. During her cancer therapy, levothyroxine dose was increased to 112 mcg daily. Her thyroid-stimulating hormone (TSH) and free T4 levels remained stable.
Prior to her 30th cycle of pembrolizumab, she reported new-onset fatigue and palpitations. Laboratory tests showed evidence of thyrotoxicosis, with a free T4 level of 2.69 (0.93-1.70) and a TSH level of 0.02 (0.27-4.20). Labs performed 3 weeks later showed a free T4 level of 2.83, a TSH level below 0.01, and a Total T3 level of 369 (80-200). Consequently, levothyroxine treatment was discontinued. At this juncture, it was suspected that her thyroiditis was induced by checkpoint inhibitors (CPI). Propranolol was prescribed.
Despite discontinuation of levothyroxine, her hyperthyroidism persisted and even worsened over the course of an additional 3 months. A thyrotropin receptor antibody test revealed elevated levels at 33.3 units/L (0.1-1.75), which was suggestive of Graves' disease. Methimazole was initiated, which had successfully controlled her thyroid hormone levels but she had developed a goiter, mild Graves’ ophthalmopathy without proptosis, and pretibial myxedema. Ultimately, she opted for a surgical total thyroidectomy. Remarkably, her cancer remained in remission for over three years following the completion of pembrolizumab.
Discussion :
Although thyroid disorders related to ICI therapy are frequently encountered, the occurrence of Graves' disease is relatively rare. However, it should be considered when dealing with patients who present with symptomatic thyrotoxicosis that doesn't resolve after 1-3 months or is linked to goiter, ophthalmopathy, or pretibial myxedema.