Current Problems in Cancer: Case Reports (Mar 2023)
Alpelisib-induced thyroiditis in a patient with metastatic breast cancer: Is routine monitoring of thyroid function required?
Abstract
Introduction: PIK3CA mutations occur in approximately 40% of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers, and confer a worse prognosis and inferior response to endocrine therapy. Alpelisib is an α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor that, when combined with fulvestrant, has demonstrated efficacy in HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer following progression on first-line endocrine therapy. Endocrine toxicity is known to occur commonly with alpelisib, with hyperglycaemia being the most commonly reported adverse event, however no other endocrine toxicity has previously been reported. Case Report: A 50-year-old woman was commenced on alpelisib, combined with fulvestrant, for the management of metastatic HR-positive, HER2-negative, PIK3CA-mutated breast cancer following progression on previous therapy. During week eight of alpelisib treatment, the patient reported fatigue, tremors, pruritus, myalgia, muscle weakness and insomnia. Thyroid function tests revealed profound hyperthyroidism – thyroid-stimulating hormone (TSH) <0.02mIU/L (reference range: 0.27–4.2mIU/L), free thyroxine (FT4) 62.4 pmol/L (12–22 pmol/L), free triiodothyronine (FT3) 25.1 pmol/L (3.1–6.8 pmol/L). TSH receptor antibodies and thyroid peroxidase antibodies were undetectable. An ultrasound of the thyroid showed a diffusely heterogenous thyroid gland without increased vascularity, consistent with thyroiditis. Alpelisib was held and thyroid function improved rapidly over the course of three weeks. However, on recommencement of alpelisib, thyroid function deteriorated again. The patient was commenced on prednisolone 30 mg once daily with rapid improvement in thyroid function tests, allowing for continuation of alpelisib. She subsequently developed biochemical hypothyroidism 16 weeks following the initial diagnosis of hyperthyroidism (TSH 21.16mIU/L, FT4 9.6 pmol/L, FT3 3.2 pmol/L). She was commenced on levothyroxine 50mcg once daily and thyroid function again improved. Conclusion: We report the first case of thyroiditis in a patient receiving alpelisib for the management of metastatic breast cancer. More real-world data is required to assess the frequency of this adverse event. Monitoring of thyroid function tests may need to be considered in all patients treated with alpelisib to allow early detection of thyroid dysfunction.
