Acute myeloid leukaemia presenting with diabetes insipidus

Abstract

A 41‐year‐old man was diagnosed with hypogonadotropic hypogonadism managed with gonadotropins after routine fertility review. Eight months later he presented with new polydipsia and polyuria, lethargy and easy bruising. A full blood count showed 28% circulating blasts. A bone marrow biopsy confirmed a diagnosis of acute myeloid leukaemia with inv(3)(q21.3q26.2) with additional monosomy 7. Central diabetes insipidus (DI) was diagnosed following a water deprivation test. Pituitary magnetic resonance imaging showed a slightly thickened pituitary stalk, stable Rathke’s cyst, and new absence of the pituitary bright spot. The patient was commenced on desmopressin and induction chemotherapy, subsequently requiring a bone marrow transplant. Bone marrow examination at 100 days post‐transplant revealed cytogenetic remission. All symptoms of DI resolved and magnetic resonance imaging showed return of the posterior bright spot and a pituitary stalk of normal thickness. Biochemical hypogonadotropic hypogonadism persisted but was uninterpretable in the context of systemic illness and recent chemotherapy. DI is a rare complication of haematological malignancies, and the prevalence and pathophysiology of DI in this context are poorly understood. Pathogenic mechanisms proposed include leukaemic infiltration of the pituitary, interference with antidiuretic hormone synthesis, and abnormal thrombopoiesis influencing hormone levels. Particular cytogenetic abnormalities such as inv(3)(q21.3q26.2) and monosomy 7 appear to be more commonly associated with DI and also appear to confer worse outcomes. Aetiologies in the literature remain elusive but as DI is a recognised association of haematological malignancies it should be considered in a patient presenting with polydipsia and polyuria.

The sellar region as presenting theater for hematologic malignancies—A 17-year single-center experience

“…Acute and chronic leukemia may also present as a sellar mass lesion, thickened pituitary stalk or infiltration of a pituitary adenoma by leukemic cells [34][35][36][37][38][39][40]. An autopsy study of more than 1,200 patients who died due to acute or chronic leukemia showed that up to 20% of patients had infiltration of the pituitary gland [41].…”

“…In our series, one patient had AML and presented with diabetes insipidus, while another patient was in the leukemic phase of non-Hodgkin B-cell lymphoma. In the literature, there are 84 cases of AML with diabetes insipidus, associated with worse outcomes [38,[42][43][44]. The underlying mechanism of diabetes insipidus in these 84 patients is still unclear since some patients may present with normal sellar MRI finding.…”

Should the cardio‐protective properties of sodium‐glucose cotransporter 2 inhibitors dictate therapeutic decision‐making in patients with type 2 diabetes

“…In relation to the question whether baseline glycated haemoglobin (HbA1c) dictates cardiovascular response to SGLT2 inhibitors, this does not appear to be the case from secondary analyses of cardiovascular and renal outcome trials. 1,2 Furthermore, in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, patients with symptomatic heart failure with reduced ejection failure randomised to dapagliflozin had a significantly lower risk of worsening heart failure or cardiovascular death compared to placebo, irrespective of the presence of diabetes (55% of patients did not have diabetes). 3 In relation to whether the cardiovascular benefits of SGLT2 inhibitors are dependent on glycaemic improvement, data from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUT-COME) trial demonstrates that cardiovascular death or hospitalisation for heart failure was similarly reduced in those subjects who did and did not experience a reduction in HbA1c in the first 3 months of treatment.…”

“…3 In relation to whether the cardiovascular benefits of SGLT2 inhibitors are dependent on glycaemic improvement, data from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUT-COME) trial demonstrates that cardiovascular death or hospitalisation for heart failure was similarly reduced in those subjects who did and did not experience a reduction in HbA1c in the first 3 months of treatment. 1 In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CRE-DENCE) trial, there was a significant reduction in endstage kidney disease, a doubling of the serum creatinine level, or death from renal or cardiovascular causesin patients with type 2 diabetes and albuminuric chronic kidney disease (CKD) randomised to canagliflozin, despite an overall mean difference in HbA1c between the canagliflozin and placebo groups of only 0.25%. 4 Additionally, data from the three cardiovascular outcome trials (EMPA-REG OUTCOME, Canagliflozin Cardiovascular Assessment Study (CANVAS) and Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58)) demonstrates preserved cardiovascular benefits in people with CKD, 5 despite attenuated glycaemic effects in this population.…”

Central Diabetes Insipidus Induced by Acute Myeloid Leukemia with DNMT3A Mutation

“…When it occurs in patients with acute leukemia; it is often a poor prognostic indicator [ 2 ]. The gene for ADH is located at the cytogenetic location 20p13; however, most reports of patients with acute myeloid leukemia (AML) and diabetes insipidus (DI) describe cytogenetic aberrations of chromosomes 3 and 7 such as inv (3) (q21.3q26.2) and monosomy 7 [ 2 , 3 ]. Several mechanisms have been proposed to result in pituitary damage [ 4 ].…”