Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

Abstract

Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.

Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis

“…Congenital adrenal hyperplasia (CAH) is a group of rare autosomal recessive diseases, which are characterized by largely decreased or absent cortisol biosynthesis. In 90–95% of cases, a deficiency of the 21-hydroxylase enzyme is the cause for CAH ( Podgórski et al, 2018 ; Balsamo et al, 2020 ). A major complication in patients is an adrenal crisis which may even lead to death.…”

A Novel Heterozygous Mutation of the CYP17A1 Gene in a Child with a Micropenis and Isolated 17,20-Lyase Deficiency

“…Importantly, 17,20-lyase deficiency is reported to be less frequent than 17-hydroxylase deficiency [ 15 ], and it is usually difficult to distinguish between these forms in terms of the clinical and biochemical outcomes [ 16 ]. The two enzyme’s activities are responsible for the synthesis of 17OH-pregnenolone from pregnenolone and of 17OH-progesterone from progesterone and the production of DHEA from 17OH-pregnenolone [ 17 ]. Therefore, CYP17A1 is the exclusive gateway to sex steroid production.…”

Pediatric Adrenal Insufficiency: Challenges and Solutions

“…The salt-wasting form is the most severe and affects 75% of patients with classic 21OHD. 1,10,12,14 Nonclassic CAH (NCCAH) is more prevalent than the classic form, in which there is 20-50% of residual enzymatic activity. Two-thirds of NCCAH individuals are compound heterozygotes with different CYP21A2 mutations in two different alleles (classic severe mutation plus mild mutation in two different alleles or homozygous with two mild mutations).…”

“…Females show atypical genitalia with signs of virilization (clitoral enlargement, labial fusion, urogenital sinus), whereas males have normal-appearing genitalia, except for subtle signs as scrotal hyperpigmentation and enlarged phallus. 1,10,12,14 Neonates with CMPD may display nonspecific symptoms including hypoglycemia, lethargy, apnea, poor feeding, jaundice, seizures, hyponatremia without hyperkalemia, temperature and hemodynamic instability, recurrent sepsis, and poor weight gain.…”

“…Acquired causesTemporary isolated ACTH deficiency due to suppression ofCRH releaseCessation of prolonged glucocorticoid therapyInfants born to glucocorticoid-treated mothersBrain injuryCranialirradiation, brain tumor, brain haemorrhage, brain surgery Infiltrative conditions Hypophysitis, Langerhans cell histiocytosis, sarcoidosis, Abbreviations: ACTH, adrenocorticotropin hormone; POMC, pro-opio-melanocortin. Therapeutics and Clinical Risk Management 2022:18 https://doi.org/10.2147/TCRM.S294065 DovePress 51 males, diagnosis typically occurs between 3 and 4 years of age with pubarche, accelerated growth velocity, and advanced bone age at presentation 1,10,12,14. …”