Journal of the Endocrine Society | 2021
Central Diabetes Insipidus Due to Acute Myeloid Leukemia
Abstract
\n Central diabetes insipidus (CDI) is a condition characterized by decreased secretion of antidiuretic hormone (ADH) and is commonly seen with pathology involving the hypothalamic/pituitary area. Common etiologies include congenital disorders, neurosurgery or trauma, infiltrative disorders, primary or secondary cancers, and idiopathic causes. CDI associated with acute myeloid leukemia (AML) is extremely rare, with about 100 published case reports, and typically occurs in patients with chromosome 3 or 7 abnormalities.\n A 49-year-old woman was admitted to the inpatient oncology service for chemotherapy with gemtuzumab with a goal of inducing remission of her AML prior to allogeneic hematopoietic cell transplantation. She had been diagnosed with AML 7 months prior to this admission and was considered high risk for poor clinical outcome due to cytogenetics demonstrating deletion of chromosome 7 and inversion of chromosome 3. She was noted to have increasing serum sodium and endocrine was consulted for evaluation of hypernatremia.\n Patient had a peak sodium of 154 meq/L which improved with free water replacement. She reported excessive thirst with associated polyuria and nocturia. Laboratory tests demonstrated inappropriately dilute urine for the degree of serum osmolality, consistent with a low ADH tone. A water deprivation test was performed which resulted in plasma and urine osmolalities of 311 mosm/kg and 103 mosm/kg, respectively. After the administration of desmopressin the Uosm increased to 345 mosm/kg at 2 hours and 484 mosm/kg at 5 hours, confirming a diagnosis of Central DI.\n Evaluation of other pituitary axes showed normal TSH and FT4 with a normal cortisol response on a cosyntropin stimulation test. She had low-normal LH and FSH plus a mildly elevated prolactin level (38.7 ng/mL) which were attributed to stress. An MRI of the brain done to rule out any hypothalamic/pituitary metastasis or hypophysitis was normal.\n AML associated with Central DI occurs rarely, is associated with a poor prognosis, and the pathogenesis is unclear. The most commonly reported cytogenetic aberrations in patients with AML and CDI are monosomy 7 and 3q alterations. Our patient had monosomy 7 and chromosome 3 inversion. Proposed pathogenic mechanisms include leukemic infiltration of the pituitary, overexpression of ectopic virus integration (EVI-1) site interfering with hypothalamic neuroendocrine secretion, and abnormal thrombopoiesis interfering with ADH levels in blood.\n This case illustrates a lesser-known cause for central diabetes insipidus. While other more common etiologies of CDI should still be considered first, recognition of this association can provide clarity to the origin of DI in select patients.