Syndromes With Neonatal Salt Loss: Not Only Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency (21OH-ISC)

Neonatal salt loss can be caused not only by infections but also by rare endocrine disorders that resemble 21-hydroxylase deficiency but are not detected by neonatal screening. This study examines how often these conditions occur and describes their main clinical, genetic, and treatment features.

Study Overview

• Status: Recruiting
• Conditions: Congenital Adrenal Hyperplasia (CAH); Neonatal Salt Loss

Detailed Description

Salt loss (SL) is a major cause of neonatal hospitalization and can be life-threatening if not promptly treated. It typically presents with hyponatremia (<130 mEq/L), often accompanied by hyperkalemia, hypochloremia, and metabolic acidosis. Clinical signs are nonspecific-including vomiting, irritability, hypotonia, and, in severe cases, seizures. Newborns are particularly vulnerable to electrolyte disturbances due to reduced glomerular filtration rate, immature distal nephrons, and transient aldosterone resistance.

While infectious gastroenteritis is the most common cause of neonatal SL, several endocrine disorders may present with the same clinical picture. The leading endocrine cause is primary adrenal insufficiency due to 21-hydroxylase deficiency, but other rare genetic conditions must be considered. These include aldosterone synthase deficiency, X-linked adrenal hypoplasia congenita (DAX-1/NR0B1 mutations), and types of pseudohypoaldosteronism, each characterized by impaired aldosterone production or action and early-life salt wasting.

Despite their heterogeneity, treatment generally relies on salt replacement, with mineralocorticoid and/or glucocorticoid therapy required in selected conditions. Only limited epidemiologic data exist; an Italian study (2006-2015) showed that 21-hydroxylase deficiency accounted for 37% of endocrine SL cases, while other congenital adrenal disorders contributed to 25%.

Neonatal screening programs detect 21-hydroxylase deficiency early, but other endocrine causes of SL remain unscreened and must be considered in differential diagnosis. This study aims to quantify the frequency of non-21-hydroxylase endocrine causes of neonatal SL in patients diagnosed at our center, describe their clinical, genetic, and laboratory features, review treatment strategies and outcomes, and characterize each disorder individually.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Federico Baronio; Phone Number: 00390512144816; Email: federico.baronio@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Federico Baronio; Phone Number: 00390512144816; Email: federico.baronio@aosp.bo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients of both sexes born between January 1989 and December 2023 who presented with salt-loss syndrome within the first two months of life due to an endocrine cause other than 21-hydroxylase-deficient CAH, and who were evaluated at the Pediatric Unit, Pediatric Endocrinology and Metabolic Diseases Program of the IRCCS AOUBO.

Description

Inclusion Criteria:

• Patients with a diagnosis of endocrine-related salt loss, defined by laboratory findings of hyponatremia (serum sodium <130 mEq/L)
• Age at onset of salt loss between 0 and 60 days of life
• Patients born between January 1, 1989 and December 31, 2023 and managed at the Experimental Center
• Obtained Informed consent

Exclusion Criteria:

• Diagnosis of 21OH ISC

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the frequency of the different endocrine causes of salt loss not due to 21-hydroxylase-deficient CAH.	Percentage of different endocrine causes of salt loss (%)	at baseline

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gonadal Disorders; Congenital Abnormalities; Adrenal Gland Diseases; Disorders of Sex Development; Urogenital Abnormalities; Steroid Metabolism, Inborn Errors; Adrenogenital Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Adrenal Hyperplasia, Congenital
• Other Study ID Numbers: SW2024

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No