MYELODYSPLASTIC SYNDROME PRESENTING AS CENTRAL DIABETES INSIPIDUS

Abstract

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Central diabetes insipidus (CDI) is characterized by a decreased release of antidiuretic hormone (ADH) and often caused by disorders that act at sites involved in either ADH secretion or delivery. Common causes of CDI include primary/secondary brain tumors, infiltrative diseases, trauma, and idiopathic CDI. Non-traumatic causes of CDI are less studied. Myelodysplastic syndrome (MDS), which describes a group of hematopoietic stem cell disorders that is characterized by dysplasia and cytopenia, is a rare but reported non-traumatic cause of CDI. We present a patient with a history of MDS that was found to have CDI during his hospital course. CASE PRESENTATION: A man in his 60s, with history of relapsed acute myeloid leukemia with induction chemotherapy one month prior to admission (PTA), presented with one week history of fevers and melena. Stated he had been urinating several times a day, with at least two episodes of nocturia, and severe thirst. Patient denied headache, nausea, vomiting, or trauma. On presentation, he was mentating well with dry mucous membranes. His initial sodium (Na) levels of 141 mEq/L increased to 160 mEq/L after two liters (L) of normal saline (NS) resuscitation, peaking at 164 mEq/L. Urinalysis revealed specific gravity of 1.006 when Na was 148 mEq/L. His urine osmolality became more concentrated with desmopressin (DDAVP) administration, increasing from 192 mOsm/kg to 381 mOsm/kg, suggestive of central diabetes insipidus (DI) over nephrogenic. Daily urine output progressed from 5.7L to 2.6L to 0.65L. MRI brain was negative for sella or pituitary findings. His Na levels improved to normal limits with DDAVP and 1/2 NS. Patient received a bone marrow cancer karyotype one year PTA, which revealed a t(6;16), (p21;q24) chromosome abnormality. DISCUSSION: There are three leading mechanisms for CDI as a complication of MDS: DNA methylation, chromosomal abnormality, and micro-infiltration of cancer cells. In a study of 184 patients with MDS and AML, DNA methylation microarray was used to assess the relative contributions of aberrant DNA methylation during disease progression and was notably seen in every case. With alterations of the mRNA-expression and promoter-related DNA methylation of vasopressin, particularly ANP precursor genes, as a pathophysiologic mechanism for CDI, DNA methylation is noted to be involved in both processes. Regarding chromosomal anomalies, the most common associated with MDS and CDI are 2,3,7,12, and 20. Our patient had a balanced translocation between the short arm of chromosome 6 and the long arm of chromosome 16. To our knowledge, this is a novel finding that warrants further research. Lastly, reported micro-infiltration of cancer cells to the hypothalamus leading a presentation of CDI have been documented. CONCLUSIONS: CDI should be considered in all AML/MDS patients presenting with polyuria and polydipsia with an unremarkable MRI of the brain. Reference #1: Jiang, Y., Dunbar, A., Gondek, L. P., Mohan, S., Rataul, M., Okeefe, C., … Maciejewski, J. P. (2009). Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood, 113(6), 1315–1325. doi: 10.1182/blood-2008-06-163246 Reference #2: Sun, R., Wang, C., Zhong, X., & Wu, Y. (2016). Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping. The Tohoku Journal of Experimental Medicine, 238(4), 305–310. doi: 10.1620/tjem.238.305 DISCLOSURES: No relevant relationships by Narjes Akhlaghi, source=Web Response No relevant relationships by Rohit Aloor, source=Web Response No relevant relationships by sai phani sree cherukuri, source=Web Response