Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping

Abstract

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic diseases characterized by cytopenia, dysplasia and increased risk of development to acute myeloid leukemia (AML). Unfavorable cytogenetic changes such as complex karyotypes or chromosome 7 anomalies are predictive of the progression to AML and poor prognosis. Central diabetes insipidus (CDI) is the result of a deficiency of arginine vasopressin, and its major causes are idiopathic, primary or secondary tumors, neurosurgery and trauma. Importantly, CDI is a rare complication of MDS. To date, only 5 cases of MDS co-occurring with CDI have been reported; 3 of 5 had cytogenetic abnormalities uncovered by metaphase cytogenetics and 3 of 5 evolved to AML. Here, we describe a 74-year-old woman who presented with CDI as her initial symptom of MDS and eventually progressed to AML. The metaphase cytogenetics, combined with the single-nucleotide polymorphism array (SNP-A)-based karyotyping, with superiority in resolution and detecting copy number variation, revealed a complex karyotype that included monosomy of chromosome 7, deletion of 20q, and absence of heterogeneity (AOH) in more than one chromosome. To the best of our knowledge, this is the first case report of MDS co-occurring with CDI with numerous cytogenetic abnormalities revealed by the SNP-A-based karyotyping. Our case supports that the cytogenetic abnormalities may be associated with the clinical features and the prognosis of MDS co-occurring with CDI. The SNP-A-based karyotyping is helpful in revealing more subtle cytogenetic abnormalities and unveiling their roles in the pathogenesis of MDS.

Myelodysplastic syndrome presenting with central diabetes insipidus is associated with monosomy 7, visible or hidden: report of two cases and literature review

“…The chromosomal anomalies we identi ed were closely related to AML/MDS with DI. Partial or complete monosomy of chromosome 7, which is the most commonly reported chromosome abnormality in DI-AML, was detected in both cases by MC analysis or SNP-based microarray; this abnormality was also found in 3 out of 5 reported cases of MDS with DI [4,6,10]. One possible explanation for this correlation is that monosomy 7 may affect expression of the neutrophil migration gene located on the 7q22 gene region.…”

“…MDS associated with DI has rarely been reported. To our knowledge, only ve MDS cases with CDI have been reported till now [4,6,7,9,10]. The information of reported DI-MDS cases was summarized in Table 2.…”

“…The mechanism of CDI occurs in AML and MDS is largely unknown. While AML and MDS with DI (DI-AML and DI-MDS) have been reported to be closely related with cytogenetic abnormalities, including partial or complete deletion of chromosome 7 and structural abnormalities of chromosome 3 [4][5][6][7][8]. In this report, we describe two patients with MDS and CDI.…”

“…Diabetes insipidus (DI) can be caused by either de ciency of antidiuretic hormone (ADH), which is known as central DI (CDI), or inadequate sensitivity of the kidney to ADH, which is known as nephrogenic DI. CDI is rare in cases of hematological malignancy but can be the initial manifestation of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [1][2][3][4]. The mechanism of CDI occurs in AML and MDS is largely unknown.…”

Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia

“…The patient subsequently experienced numerous complications, including the need for numerous platelet and PRBC transfusions, fevers in light of broad spectrum antibiotic therapy, reactions to azacitidine and platelet transfusions and purpuric rash. Although unusual presentations of MDS have been reported, such as pulmonary leukocytoclastic vasculitis [ 4 ], diabetes insipidus [ 5 ], tumor lysis syndrome [ 6 ], bilateral sensorineural hearing loss [ 7 ], and bilateral acute angle closure glaucoma [ 8 ], it is extremely unusual to present as a rapidly progressive acute leukemia, leading to the fear of delaying an APL diagnosis and the rapid initiation of treatment with ATRA. Clinicians should be aware that MDS may present in this acute manner in which, case therapy should be promptly initiated and de-escalated as is clinically indicated.…”