Tyrosine kinase inhibitors (TKIs) have been used in the treatment of multiple types of cancer. Pazopanib is one of the TKIs and is considered a first-line treatment for adult patients with metastatic renal cell carcinoma. Many endocrine-related adverse effects have been noted with the use of TKIs including hypothyroidism, vitamin D deficiency, altered bone density, secondary hyperparathyroidism, abnormal glucose metabolism, gynecomastia, and hypogonadism. Subclinical glucocorticoid deficiency and adrenal insufficiency have been reported with the use of TKIs in only a few cases so far; thus, its true prevalence and clinical significance have yet to be fully elucidated. The mechanism is still not fully understood; however, adrenal toxicity with hemorrhage and/or necrosis of the adrenal glands has been observed in studies. In this article, we describe the first reported case of pazopanib inducing primary adrenal insufficiency in a patient with metastatic renal cell carcinoma diagnosed after the exclusion of all other causes of primary adrenal insufficiency.