Related Experiment Video
Updated: May 18, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Rare Causes of Pediatric Primary Adrenal Insufficiency: An Observational Cohort Study
Mathilde Schermesser-Sicard1, Dinane Samara-Boustani2, Florence Roucher-Boulez3
1Pediatric Endocrinology, Diabetology and Gynecology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
Insights
Rare causes of pediatric primary adrenal insufficiency (PAI) present diagnostic challenges, with monogenic diseases and autoimmune disorders being common. Understanding these diverse etiologies is key for effective management and improved patient outcomes.
Area of Science:
- Pediatric Endocrinology
- Rare Diseases
- Genetics
Background:
- Primary adrenal insufficiency (PAI) is a rare, chronic condition with potentially life-threatening complications, most commonly caused by 21-hydroxylase deficiency (21 OHD).
- Identifying less common etiologies of PAI is critical for optimizing patient management and improving long-term outcomes.
Purpose of the Study:
- To describe the spectrum of rare causes of pediatric PAI.
- To analyze the clinical characteristics, outcomes, and phenotypic variations associated with these rare conditions.
Main Methods:
- Retrospective, observational, single-center cohort study.
- Analysis of 172 pediatric patients diagnosed with PAI between 1980 and 2023.
- Categorization of PAI causes into 21 OHD, monogenic diseases, autoimmune disorders, and other rare conditions.
Main Results:
- Of 172 patients, 59 (34%) had rare causes of PAI, including monogenic diseases (64%), autoimmune disorders (25%), and bilateral adrenal hemorrhage (3%).
- MIRAGE syndrome was the most frequent rare cause. Mortality was 10% in the rare PAI group, with acute adrenal crisis occurring in 45% of patients, often linked to poor treatment adherence.
- Growth and pubertal development varied by genotype, with satisfactory growth outcomes reported, though some patients experienced early or delayed puberty.
Conclusions:
- A diverse range of rare causes for pediatric PAI exists, posing diagnostic challenges.
- Determining the underlying cause is achievable in most cases, enabling tailored and optimal therapeutic strategies.
- Phenotypic features like age of onset, growth, puberty, and BMI are genotype-dependent, necessitating targeted monitoring for conditions such as MIRAGE syndrome, Triple A syndrome, and NNT deficiency.
Objective:
Primary adrenal insufficiency (PAI) is a rare, chronic condition responsible for life-threatening complications and is usually due to 21-hydroxylase deficiency. Identifying other rare causes is crucial to ensure optimal management. The objective of this study was to describe rare causes of pediatric PAI.
Methods:
An observational, retrospective, single-center, cohort study.
Results:
Of 172 patients under 18 years diagnosed with PAI in 1980-2023: 113 with 21-hydroxylase deficiency and 59 (34%) with rare causes of PAI including monogenic diseases (n = 38, 64%), auto-immune disorders (n = 15, 25%), and bilateral adrenal hemorrhage (n = 3). Median follow-up was 7.6 years. The mortality was 6 of 59 (10%), with myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy syndrome as the most common cause. Acute adrenal crisis occurred in 26 (45%) patients, usually due to poor treatment adherence. Excess weight was common (16/59, 27%). Among 37 available data, puberty was normal in 26 (72%), early in 6 (17%), and delayed in 5 (14%). Growth outcomes were satisfactory of 28 (48%) patients who attained their adult height, median final height was -1.1 standard deviation score (SDS) in males and -0.4 SDS in females and median height in the 27 patients still growing was -0.4 SDS.
Conclusion:
The wide range of rare causes of PAI raises diagnostic challenges. In most cases, however, the cause can be determined, allowing optimal therapy. Phenotypic characteristics-including age at PAI onset, growth patterns, pubertal development, and body mass index-vary according to the underlying genotype (i.e., myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy syndrome Triple A syndrome, and NNT deficiency). Targeted monitoring of these features is therefore essential.
Related Concept Videos
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:26Cushing Syndrome I: Introduction
01:19Cushing Syndrome II: Pathophysiology
01:21Smooth Endoplasmic Reticulum
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:17Anatomy of the Adrenal Glands
These glands possess a distinctive yellow tinge due to the stored cholesterol and fatty acids required for hormone synthesis. They are encased in a fibrous capsule and cushioned by fat.
The adrenal gland comprises two distinct regions...