Acute Myeloid Leukemia Leading to Central Diabetes Insipidus

Background: Central diabetes insipidus (CDI) as a complication of acute myeloid leukemia (AML) is rare, occurring in less than 0.6% of AML cases. The mechanism is thought to involve leukemic infiltration in or around the pituitary gland, not always seen on imaging. In one study, as many as 61.4% of patients with CDI due to AML had no abnormalities on MRI, and at autopsy 46% of AML patients had perihypohyseal leukemic infiltration in the absence of overt CDI. CDI is also associated with AML in cases that involve monosomy 7 and inversion 3q21q26, both of which result in ectopic viral integration site 1 (EVI-1) overexpression. It is postulated that EVI-1 overexpression interferes with hypothalamic secretion of antidiuretic hormone (ADH) or may lead to its inactivation. We present a case of adipsic CDI due to AML in a patient with monosomy 7. Case: A 70-year-old female presented for routine follow-up and was found to have a white blood cell count of 2.6 K/µL with 29% blasts, anemia (Hgb 10.3 g/dL) and normal platelets (300 K/µL). She was diagnosed with AML and molecular evaluation showed del (3)(q21),-7,add(17(p13) consistent with monosomy 7. She was admitted for induction chemotherapy with cytarabine, daunorubicin and intrathecal methotrexate. She denied thirst. On physical exam she was euvolemic and visual fields were full on confrontation. Her admission sodium was 146 mmol/L, urine osmolality was 149 mOsm/kg H(2)O, urine sodium 14 mmol/L. Urine output was 5.1 L over the first 24 hours. She underwent a 6 hour water deprivation test, during which her urine output averaged 250 cc/hr. Her sodium increased to 158 mmol/L, serum osmolality 331 mOsm/kg H(2)O, urine osmolality 146 mOsm/kg H(2)O. She was then administered 100 µg of DDAVP PO and her serum sodium and osmolality decreased to 155 mmol/L and 326 mOsm/kg H(2)O, respectively, while her urine osmolality nearly doubled to 292 mOsm/kg H(2)O. Urine output decreased to 50-100 cc/hr. At no point during her testing did she report thirst. The patient’s pituitary laboratory profile did not show any other abnormalities. Her pituitary MRI revealed subtle thickening of the proximal infundibulum and hypothalamus but no definitive intra-sellar pathology. She was discharged on twice daily DDAVP with a sodium of 142. Unfortunately, her AML was refractory to treatment. She was transitioned to comfort care and died peacefully. Conclusion: CDI as a complication of AML is very rare and is a poor prognostic marker. Based on her MRI findings, the most likely mechanism in this case was infundibular/hypothalamic infiltration. Her adypsia is interesting and may point to more generalized hypothalamic involvement including thirst center. Her monosomy 7 mutation may have also played a role. We present this case to bring awareness to this etiology of DI and its proposed mechanisms.