Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is caused by steroid 21-hydroxylase deficiency (21-OHD), which results from mutations in the CYP21A1 gene.
The lack of negative feedback of cortisol to the hypothalamus and the pituitary gland prompts corticotropin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH) elevations. The increased ACTH concentrations lead to chronic stimulation of the adrenal cortex and overstimulate adrenal steroidogenesis, resulting in an accumulation of steroids above the enzymatic blockage. When sustained, ACTH elevation promotes adrenal gland enlargement.
The mainstay of treatment is glucocorticoid replacement, which fails to replicate the physiological cortisol circadian rhythm and supraphysiological doses of glucocorticoids are required to restore the negative feedback loop. This is associated with the risk of unfavourable effects similar to hypercortisolism, such as weight gain, cushingoid features, and metabolic syndrome. On the other hand, undertreatment entails the risk to develop a life-threatening Addisonian crisis and signs of hyperandrogenism.
Inadequate hormonal control and long-term adverse health outcomes, including gonadal dysfunction, infertility, and cardiovascular and metabolic co-morbidity with reduced quality of life, are very commonly observed in CAH patients with current treatment strategies despite efforts from patient and health professionals.
Furthermore, the use of traditional biomarkers such as serum 17OHP4 normally used to assess disease control and to guide treatment in patients with 21OHD are wrought with variabilities.
The current Research Topic aims to explore recent advances in the diagnosis and treatment of 21-OHD. We welcome Original Research, Methods, Review, and Mini-Review articles that cover, but are not limited to, the following topics:
- New approaches to monitor biochemically 21-OHD with traditional biomarkers;
- Novel biomarkers to diagnose and monitor 21-OHD;
- New therapeutic approaches to mimic physiological glucocorticoid levels;
- Current and new therapeutic approaches to treat neonates and children with 21-OHD;
- Current situation of neonatal mass screening of 21-OHD worldwide;
- Complementation of glucocorticoid treatment with novel non-glucocorticoid treatment approaches;
- Gene and cell-based therapy.
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is caused by steroid 21-hydroxylase deficiency (21-OHD), which results from mutations in the CYP21A1 gene.
The lack of negative feedback of cortisol to the hypothalamus and the pituitary gland prompts corticotropin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH) elevations. The increased ACTH concentrations lead to chronic stimulation of the adrenal cortex and overstimulate adrenal steroidogenesis, resulting in an accumulation of steroids above the enzymatic blockage. When sustained, ACTH elevation promotes adrenal gland enlargement.
The mainstay of treatment is glucocorticoid replacement, which fails to replicate the physiological cortisol circadian rhythm and supraphysiological doses of glucocorticoids are required to restore the negative feedback loop. This is associated with the risk of unfavourable effects similar to hypercortisolism, such as weight gain, cushingoid features, and metabolic syndrome. On the other hand, undertreatment entails the risk to develop a life-threatening Addisonian crisis and signs of hyperandrogenism.
Inadequate hormonal control and long-term adverse health outcomes, including gonadal dysfunction, infertility, and cardiovascular and metabolic co-morbidity with reduced quality of life, are very commonly observed in CAH patients with current treatment strategies despite efforts from patient and health professionals.
Furthermore, the use of traditional biomarkers such as serum 17OHP4 normally used to assess disease control and to guide treatment in patients with 21OHD are wrought with variabilities.
The current Research Topic aims to explore recent advances in the diagnosis and treatment of 21-OHD. We welcome Original Research, Methods, Review, and Mini-Review articles that cover, but are not limited to, the following topics:
- New approaches to monitor biochemically 21-OHD with traditional biomarkers;
- Novel biomarkers to diagnose and monitor 21-OHD;
- New therapeutic approaches to mimic physiological glucocorticoid levels;
- Current and new therapeutic approaches to treat neonates and children with 21-OHD;
- Current situation of neonatal mass screening of 21-OHD worldwide;
- Complementation of glucocorticoid treatment with novel non-glucocorticoid treatment approaches;
- Gene and cell-based therapy.