LAUSR

To the Editor: Tacrolimus is an immunosuppressant used in organ transplant recipients to decrease the risk of rejection. It is known to cause hyperglycemia through multiple mechanisms. Studies have shown that it induces insulin resistance and strengthens intestinal glucose absorption by increasing the activity and expression of the sodium-glucose co-transporter 1.1,2 Interestingly, phenytoin has been used for tacrolimus toxicity because short-term administration of this enzyme inducer facilitates the reversal of elevated tacrolimus concentrations.3 A 40-year-old woman presented with 1-day history of altered mentation, particularly confusion, and one episode of vomiting. She also had polyuria. Her medical history was remarkable for acute myeloid leukemia, for which she underwent allogeneic stem cell transplant 12 years before admission, along with extensive chronic graft-versus-host disease. She was on tacrolimus as part of her home regimen. The patient had a normal mental status at baseline and was in her usual state of health till the night before admission when she started mumbling words and was not acting like herself. There was no weakness, numbness, dysarthria, headache, or any seizure-like activity. On examination, the patient looked dehydrated. She was oriented to place and person but was not oriented to time. Neurologic examination otherwise revealed intact cranial nerves, 5/5 strength in all extremities, normal sensation, and 2+ deep tendon reflexes. Initial workup showed blood glucose of 780 mg/dL, PH of 7.46, HCO3 29.5 mMol/L, and beta hydroxybutyrate was normal. Her calculated serum osmolality was 332 mOsm/kg. In addition, her tacrolimus level was significantly elevated at .120 ng/mL. Other laboratory findings included blood urea nitrogen 81 mg/dL and sodium 130 mMol/L, which was consistent with hyperosmolar hyperglycemic nonketotic syndrome. The patient was not known to have diabetes mellitus (DM) before admission, but hemoglobin A1C on admission was 9% consistent with new-onset DM. She was managed with intravenous (IV) fluids and an insulin drip initially for the hyperosmolar hyperglycemic nonketotic syndrome. Her blood sugar trended down and eventually normalized, and also her volume status was replenished. Regarding her acute tacrolimus toxicity, this was managed by primarily holding the medication during her stay. The levels were trended daily, and she was given a short course of phenytoin for tacrolimus toxicity. Figure 1 below demonstrates the trend of tacrolimus level throughout the hospitalization (Figure 1). Phenytoin 200 mg twice a day was started and was given for 3 days to help reduce the tacrolimus level. Four days into hospitalization, her tacrolimus levels normalized, and her mental status returned to baseline. Tacrolimus is a common immunosuppression agent used in organ transplantation. It primarily works through calcineurin inhibition and thus impairs the transcription of interleukin (IL)–2 and other cytokines in T lymphocytes.4 Despite its mainstay use, there