Endocrine Abstracts

Background: Alpelisib is a novel phosphotidylinositol 3-kinase (PI3K) inhibitor which, in combination with fulvestrant, has been shown to increase progression-free survival in patients with HR+/HER2-/PI3KCA mutated advanced breast cancer[1]. Hyperglycaemia, including alpelisib-induced diabetic ketoacidosis is a known adverse effect, along with rash, diarrhoea and stomatitis. No other associated endocrinopathy has been reported to date. Case presentation: We present the case of a 50-year-old woman with metastatic breast cancer was referred from the Oncology service with a two-week history of fatigue, tremors, palpitations, sweats and myalgia, associated with raised free T4 and free T3, and suppressed TSH. Two months prior, she had been commenced on the novel Phosphotidylinositol 3-kinase (PI3K) inhibitor, alpelisib, combined with fulvestrant, due to progression of her disease on first and second-line therapies. Alpelisib was held once abnormal thyroid function was noted. On examination the patient was tachycardic and tremulous. The thyroid was tender to palpation without a discernible goitre. TSH <0.02 mIU/l(0.27-4.20), FT4 62.4 pmol/l (12.0-22.0), FT3 25.1 pmol/l (3.1-6.8). Anti-TSH receptor and anti-thyroid peroxidase antibodies were undetectable. She was commenced on propanolol for symptom relief. Ultrasound thyroid showed a diffusely heterogenous gland without increased vascularity. Technetium 99 m radionuclide uptake scan showed diffusely reduced radiotracer uptake, consistent with thyroiditis. Although her hyperthyroidism initially improved with cessation of alpelisib, it deteriorated again with recommencement. The patient was commenced on prednisolone 30 mg once daily. This was weaned as her thyroid function improved, allowing for recommencement of alpelisib treatment. She currently remains euthyroid. Summary: This is the first reported case of alpelisib-induced thyroiditis in a patient treated for metastatic breast carcinoma. We have demonstrated efficacy in treatment with steroid therapy, allowing for continued treatment with this agent. Activation of the PI3K pathway has been shown to inhibit sodium-iodide symporter expression and function within thyroid follicular cells[2]. However, the pathophysiology of alpelisib-induced thyroiditis remains to be elucidated.

Bibliography

1. Andre, F., et al., Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med, 2019. 380(20): p. 1929-1940.

2. Garcia, B. and P. Santisteban, PI3K is involved in the IGF-I inhibition of TSH-induced sodium/iodide symporter gene expression. Mol Endocrinol, 2002. 16(2): p. 342-52.