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      Desmopressin Lyophilisate for the Treatment of Central Diabetes Insipidus: First Experience in Very Young Infants

      case-report

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          Abstract

          Introduction:

          In neonates and small infants, early diagnosis of central diabetes insipidus (CDI) and treatment with desmopressin in low doses (avoiding severe hypo- or hypernatremia) are important to prevent associated high morbidity and mortality in this particular age group.

          Case Presentation:

          We described pharmacokinetic and pharmacodynamic results of the use of recently launched oral desmopressin lyophilisate (Minirin Melt®) in two infants with CDI, diagnosed at the age of 12 and 62 days, respectively. We observed that a starting dose of 60 μg of Minirin Melt® in the first case resulted in a pharmacokinetic profile largely exceeding the reference frame observed in children with nocturnal enuresis, while a dose of 15 μg in the second case resulted in acceptable concentrations. After initial dose adjustments, administration of sublingual lyophilisate resulted in rather stable serum sodium concentrations.

          Conclusions:

          Using Minirin Melt® in infants with CDI appears to be effective, easy to use and well tolerated.

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          Most cited references11

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          Central diabetes insipidus in children and young adults.

          M Aricò, Samuel Cohen, B Boscherini … (2000)
          Central diabetes insipidus is rare in children and young adults, and up to 50 percent of cases are idiopathic. The clinical presentation and the long-term course of this disorder are largely undefined. We studied all 79 patients with central diabetes insipidus who were seen at four pediatric endocrinology units between 1970 and 1996. There were 37 male and 42 female patients whose median age at diagnosis was 7.0 years (range, 0.1 to 24.8). All patients underwent magnetic resonance imaging (MRI) and periodic studies of anterior pituitary function. The median duration of follow-up was 7.6 years (range, 1.6 to 26.2). The causes of the central diabetes insipidus were Langerhans-cell histiocytosis in 12 patients, an intracranial tumor in 18 patients, a skull fracture in 2 patients, and autoimmune polyendocrinopathy in 1 patient; 5 patients had familial disease. The cause was considered to be idiopathic in 41 patients (52 percent). In 74 patients (94 percent) the posterior pituitary was not hyperintense on the first MRI scan obtained, and 29 patients (37 percent) had thickening of the pituitary stalk. Eighteen patients had changes in the thickness of the pituitary stalk over time, ranging from normalization (six patients) or a decrease in thickness (one patient) to further thickening (seven patients) or thickening of a previously normal stalk (four patients). Anterior pituitary hormone deficiencies, primarily growth hormone deficiency, were documented in 48 patients (61 percent) a median of 0.6 year (range, 0.1 to 18.0) after the onset of central diabetes insipidus. Most children and young adults with acquired central diabetes insipidus have abnormal findings on MRI scans of the head, which may change over time, and at least half have anterior pituitary hormone deficiencies during follow-up.
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            Desmopressin 30 years in clinical use: a safety review.

            Ann Raes, P Nørgaard, Johan Vande Walle … (2007)
            Desmopressin acetate is the synthetic analogue of the antidiuretic hormone arginine vasopressin. It has been employed clinically for >30 years in a range of formulations: intranasal solution (since 1972), injectable solution (since 1981), tablets (since 1987), and most recently, an oral lyophilisate (since 2005). The antidiuretic properties of desmopressin have led to its use in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. While a large body of clinical data is available for desmopressin, and despite its widespread use, comprehensive reviews of the safety of desmopressin are lacking (although some case series have attempted to correlate patient and/or dosing characteristics with the occurrence of adverse reactions). The purpose of this paper is to review the safety of desmopressin, based on analyses of both published data (MedLine) and of adverse reactions reported to Ferring Pharmaceuticals, the major manufacturer of desmopressin. Based on the findings, suggested strategies to reduce the risk of adverse reactions are proposed. Treatment with intranasal and oral formulations of desmopressin is generally well tolerated, and side effects are usually minor. The risk of hyponatraemia, although small, can be reduced by adhering to the indications, dosing recommendations and precautions when prescribing desmopressin.
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              The management of central diabetes insipidus in infancy: desmopressin, low renal solute load formula, thiazide diuretics.

              N Dunbar, Greame Wilson, S A Rivkees (2007)
              Infants consume most of their calories as formula. Because of this large fluid intake, infants normally produce dilute urine, not far off from that seen in individuals with diabetes insipidus (DI). Infants with DI are therefore prone to water intoxication if fixed antidiuresis is achieved using the long-acting vasopressin analog desmopressin (DDAVP), which induces a state of high urine concentration. DI treatment approaches applied to older children and adults, who consume the their calories as solids, are difficult to apply to infants with DI. When used in infants, oral and intranasal DDAVP can be associated with wide swings in serum sodium concentration (SNA). In comparison, precisely administered subcutaneous doses of DDAVP can be successfully used in infants with DI, and appear to be superior to oral or intranasal DDAVP therapy. Alternatively, consistent eunatremia can be simply achieved in infantile DI using low renal solute load (RSL) formula and thiazide diuretics. Low RSL formula reduces obligatory urinary water losses, and thiazide diuretics concentrate the urine to levels seen in normal formula-fed infants. This report addresses treatment options of DI in infancy and the delicate management issues involved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Endocrinol Metab
                Journal ID (iso-abbrev): Int J Endocrinol Metab
                Journal ID (doi): 10.5812/ijem
                Journal ID (publisher-id): Kowsar
                Title: International Journal of Endocrinology and Metabolism
                Publisher: Kowsar
                ISSN (Print): 1726-913X
                ISSN (Electronic): 1726-9148
                Publication date (Electronic): 01 October 2014
                Publication date Collection: October 2014
                Volume: 12
                Issue: 4
                Electronic Location Identifier: e16120
                Affiliations
                [1 ]Department of Paediatric Endocrinology, University Hospital Ghent, Ghent, Belgium
                [2 ]Department of Pediatric Nephrology , University Hospital Ghent, Ghent, Belgium
                [3 ]Department of Neonatology, University Hospital Ghent, Ghent, Belgium
                [4 ]Department of Paediatric Endocrinology, University Hospital Brussels, Brussels, Belgium
                Author notes
                [* ]Corresponding author: Jean De Schepper, Department of Pediatrics, Division of Paediatric Endocrinology, University Hospital Ghent, Ghent, Belgium. Tel: +32-93322760, Fax: +32-93323875, E-mail: jean.deschepper@ 123456uzgent
                Article
                DOI: 10.5812/ijem.16120
                PMC ID: 4338649
                SO-VID: 19e26d9b-064e-44bf-b1d5-3235f4c122c3
                Copyright © Copyright © 2014, Research Institute For Endocrine Sciences and Iran Endocrine Society; Published by Kowsar Corp.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 January 2014
                Date revision received : 26 April 2014
                Date accepted : 23 May 2014
                Categories
                Subject: Case Report

                Keywords: desmopressin,diabetes insipidus,infant,hypernatremia
                Data availability:
                Keywords: desmopressin, diabetes insipidus, infant, hypernatremia

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