Abstract
Introduction - The combination of sodium glucose cotransporter-2 inhibitor (SGLT-2i) use and glucocorticoid excess can trigger ketone production by reducing insulin secretion/sensitivity and stimulating glucosuria, glucagon production, and lipolysis. In addition, metabolic alkalosis caused by glucocorticoid excess (via mineralocorticoid receptor activation) may combine with diabetic ketoacidosis (DKA) to create a mixed acid-base disorder, which can potentially obscure SGLT-2i-associated DKA. Case Description - A 45 year-old man with well-controlled type 2 diabetes on an SGLT-2i presented to the Emergency Room with edema, weakness, palpitations, polyuria/polydipsia, hypertension, and hyperglycemia. Exam was significant for a blood pressure of 195/111mmHg, moon facies, supraclavicular fat pad fullness, obese abdomen with violaceous striae, and reduced bilateral hip flexor weakness. He was found to have potassium 2.5mmol/L, glucose 296mg/dL, bicarbonate 28mmol/L, and anion gap 20mmol/L. Venous pH was 7.51, with pCO2 38mmHg. Beta-hydroxybutyrate was >8.0mmol/L (<0.40). Random cortisol was 59.1ug/dL (5-25ug/dL) and ACTH 313pg/mL (15-66pg/mL). 24hr Urine Cortisol was 1567mcg/24hrs (3.5-45mcg/24hrs). Pituitary MRI showed diffuse pituitary enlargement and a 7mm pituitary adenoma. The patient’s DKA was managed with IV fluids and insulin, and potassium was aggressively replaced. He underwent successful trans-sphenoidal pituitary adenoma resection, with positive ACTH staining on pathology. ACTH and cortisol 12 hours postoperatively were 78pg/mL and 15.1ug/dL, respectively, and continued to downtrend. On the second postoperative day, the patient developed severe anxiety, which improved with increased glucocorticoid supplementation. Conclusion - DKA is a rare side effect of SGLT-2i use, and even rarer in the setting of Cushing’s Disease. In this case, the patient’s underlying Cushing’s Disease likely contributed to the development of SGLT-2i-associated DKA and severe hypokalemia, while also obscuring the diagnosis by causing a concurrent metabolic alkalosis that normalized the pH and bicarbonate. The competing physiologic mechanisms at play led to this unusual presentation of SGLT-2i-associated DKA with an alkalotic pH and normal bicarbonate.