ESPE Abstracts (2018) 89 P-P3-405

Lessons from Wolfram Syndrome: Initiation of DDAVP Therapy Causes Renal Salt Wasting due to Elevated ANP Levels, Rescued by Fludrocortisone Treatment

Kleanthis Kleanthousa, Eirini Maratoub, Dora Spyropoulouc, Eleni Dermitzakid, Christina Bothoue, Anastasios Papadimitriouf, George Zoupanosg, Paraskevi Moutsatsoub, Fumihiko Uranoh & Dimitrios T. Papadimitrioud


aDepartment of Pediatrics, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari, Greece; bDepartment of Clinical Biochemistry, Medical School, National and Kapodistrian University of Athens, University General Hospital ‘ATTIKON’, Haidari, Greece; c3rd Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari, Greece; dDepartment of Pediatric-Adolescent Endocrinology & Diabetes, Athens Medical Center, Maroussi, Greece; eDivision of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany; fDivision of Pediatric Endocrinology, 3rd Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari, Greece; gDepartment of Pediatric Urology, Athens Medical Center, Maroussi, Greece; hWashington University School of Medicine, St. Louis, MO, USA


Background-Hypothesis: Sudden initiation of treatment for diabetes insipidus (DI) with DDAVP causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuteric Peptide (ANP) (1). ANP blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW) (2). Cases: Two sisters, a 19-year-old girl (A) and a 7-year-old girl (B) with Wolfram Syndrome presented to our pediatric endocrinology clinic with severe polyuria-polydipsia and neurogenic bladder due to never treated DI (3). Both hospitalized, initiated therapy with oral melt preparation of DDAVP at the dose of 120–240 mg × 3/day, under close clinical and biochemical surveillance. Plasma levels of ANP were quantitatively detected by a competitive enzyme immunoassay kit (RayBiotech, Norcross, USA, sensitivity 1.02 pg/ml). Results: Patient A presented RSW at day 2 after DDAVP initiation. Hyponatremia 123 mmol/L, hyperkalemia 5.7 mmol/L with high natriuresis 120–170 mmol/L occurred, with low plasma renin activity (PRA) 0.94 ng/ml/h (0.5–4.7) and aldosterone 2.26 ng/dl (4–31) and extremely elevated ANP 2359.5 pg/ml (normal < 42). Patient B presented RSW at day 11 after DDAVP initiation. ANP was elevated 1911.5 pg/ml with low PRA 0.78 ng/ml/h and aldosterone 3.46 ng/dl. Both had signs of volume depletion: negative water balance, tachycardia and increased cardiac rate with low blood pressure. Fludrocortisone 100–200×2 μg/day controlled natriuresis and restored electrolytes to normal within 48hrs in both patients. Fludrocortisone could be stopped at 1 month in patient B, but ANP levels remained too high 1200–1350 pg/ml, probably due to severe hydronephrosis secondary to grade III bilateral vesicoureteral reflux, in addition to the neurogenic bladder already installed. Patient A still requires - a year after - fludrocortisone at 50×2 μg/day with elevated but much lower ANP (250–500 pg/ml). Conclusions: Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP, caused by sudden volume expansion following DDAVP initiation.

References: 1. Mineralocorticoid deficiency in post-operative cerebral salt wasting. Papadimitriou DT et al. J Pediatr Endocrinol Metab. 2007 PMID: 18051934. 2. Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth Hormone Deficiency. Papadimitriou DT et al. Indian J Pediatr. 2018 PMID: 29455327. 3. A novel detrimental homozygous mutation of WFS1 gene in two sisters from non-consanguineous parents with untreated Diabetes Insipidus. Papadimitriou DT et al. ESPE 2018.