Renal transplant recipients are immunocompromised and predisposed to develop hyponatremia because they are exposed to immunological, infectious, pharmacological, and oncologic disorders. A 61-year-old female renal transplant recipient was admitted with diarrhea, anorexia, and headache for about a week during the tapering of oral methylprednisolone for chronic renal allograft rejection. She also presented hyponatremia and was suspected to have secondary adrenal insufficiency based on a low plasma cortisol level of 1.9 μg/dL and a low adrenocorticotropic hormone level of 2.6 pg/mL. Brain magnetic resonance imaging to assess the hypothalamic-pituitary-adrenal axis revealed an empty sella. She also developed septic shock and disseminated intravascular coagulation due to post-transplant pyelonephritis. She had reduced urine output and underwent hemodialysis. Both plasma cortisol and adrenocorticotropic hormone levels were relatively low (5.2 μg/dL and 13.5 pg/mL, respectively), which also suggested adrenal insufficiency. She was treated with hormone replacement therapy and antibiotics, successfully recovered from septic shock, and was withdrawn from dialysis. In empty sella syndrome, the somatotropic and gonadotropic axis are the most affected, followed by the thyrotropic and corticotropic axis. She did not present these abnormalities, which may suggest that empty sella syndrome is a separate pathology, and the axis suppression had occurred due to long-term steroid treatment. Diarrhea due to cytomegalovirus colitis might have induced steroid malabsorption and manifested adrenal insufficiency. Secondary adrenal insufficiency should be investigated as a cause of hyponatremia. It should always be borne in mind that diarrhea during oral steroid treatment may cause adrenal insufficiency associated with steroid malabsorption.