title: Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.
abstract: BACKGROUND
  Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine.
  
  
  METHODS
  A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission.
  
  
  RESULTS
  Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3β-Hydroxysteroid dehydrogenase (3βHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified.
  
  
  CONCLUSIONS
  Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants presenting with salt-wasting are immediately started on steroid therapy to avoid life-threatening complications, before the correct diagnosis is reached. Physicians involved in the management of infants with salt-wasting of suspected hormonal origin should remember that, whenever practicable, a blood sample for the essential hormonal investigations should be collected before starting steroid therapy, to guide the subsequent diagnostic procedures and in particular to address the analysis of candidate genes.
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy. carla.bizzarri@opbg.net.
authors.forename: Carla
authors.identifier: http://orcid.org/0000-0002-5616-9185
authors.initials: C
authors.lastname: Bizzarri
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Nicole
authors.initials: N
authors.lastname: Olivini
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pedicelli
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Marini
authors.affiliation: Department of Chemistry, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Giannone
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cambiaso
authors.affiliation: Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
mesh_terms: D000309:Adrenal Insufficiency / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D000450:Aldosterone / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007010:Hyponatremia / Q000175:diagnosis* / Q000235:genetics; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D007558:Italy; D008297:Male; D012189:Retrospective Studies; D014883:Water-Electrolyte Imbalance
chemical_list: D000450:Aldosterone
keywords: Adrenal insufficiency; Aldosterone; Infant; Newborn; Pseudohypoaldosteronism; Salt-wasting; Sodium