Primary adrenal insufficiency with X-linked inheritance in children

Abstract

Primary adrenal insufficiency (PAI) is a rare pathology with a prevalence of 100 to 140 cases per one million. X-linked adrenoleukodystrophy (X-ALD) and X-linked congenital adrenal hypoplasia (X-CAH) are the leading pathologies among boys (after congenital cortical dysfunction adrenal glands) and account for 3.1% and 2.0% of all PAI, respectively. Establishing the PAI etiology is necessary to predict the course of the disease and adhere to special protocols for examining patients. The purpose of this research was to compare the PAI course in diseases with an X-linked type of inheritance. Materials and methods used: a single-center, one-stage observational comparative retrospective study was conducted in 25 male patients with genetically confirmed diagnoses of X-ALD, X-CAH and who had PAI as a component of the disease. The study was conducted at the Pediatric Endocrinology Institute with the Endocrinology Research Centre of the Ministry of Healthcare of Russia (Moscow, Russia) in 2019-2022 as well as based on the patients’ medical records that have been forwarded for a genetic search for the causes of adrenal insufficiency under the “Alfa-Endo” Charity Program for children with endocrine diseases in the same period of time. Results: X-ALD was detected in 11/25 (44%) patients, median age of manifestation was 6.2 [4.5; 7.2] y/o and 2 y/o was the earliest. A single patient with X-ALD was found to have TARTs (testicular adrenal rest tumors). X-CAH was diagnosed in the remaining 14/25 (56%) patients, median age of manifestation was 1.9 [0.04; 3.9] y/o, p=0.015. The oldest age of manifestation was 14 y/o. A single patient was found to have hypogonadotropic hypogonadism (HH) and another one had bilateral cryptorchidism. There were no statistically significant differences in symptoms, adrenocorticotropic hormone (ACTH), cortisol levels during the manifestation of PAI and doses of replacement therapy (p=0.756 for ACTH, p=0.591 for cortisol, p=0.825 for hydrocortisone and p=0.148 for fludrocortisone). Conclusion: it is necessary to exclude X-ALD and X-CAH when diagnosing PAI in boys regardless of the age of the disease manifestation. It is highly recommended to conduct a genetic study of a panel of genes responsible for the development of PAI in order to establish the PAI etiology, and regardless of the established PAI etiology it is necessary to perform an ultrasonic study of the testicles with the purpose of excluding the space-occupying formations. It is necessary to evaluate ACTH levels in patients with testicular masses for timely diagnosis of PAI and optimal treatment.