Congenital Adrenal Hyperplasia (CAH) owing to impairment of the 21-hydroxylase enzyme activity is characterized by defective cortisol synthesis with secondary rise in ACTH and shunting of steroid synthesis to the androgen pathway. The resultant hyperandrogenemia and cortisol deficiency (with or without mineralocorticoid deficiency) constitute the hallmark of the disease pathogenesis.
Standard CAH treatment with glucocorticoids aims to suppress the ACTH driven hyperandrogenemia, which inevitably subjects patients to lifelong supra-physiologic glucocorticoid doses that do not mimic the physiological circadian rhythm of cortisol secretion. The ultimate balance of “enough” glucocorticoids to suppress excess androgens and “not too much” to avoid unwanted side effects is seldom achieved.
Achievement of a physiological circadian rhythm with a subsequent enhancement in quality of life represents an important unmet need in the management of CAH. To this end, investigators proposed therapies, such as continuous subcutaneous administration of hydrocortisone via pump therapy or hydrocortisone formulations with a delayed and sustained absorption profile, to replicate physiological glucocorticoid replacement. Additionally, novel therapeutic molecules such as selective corticotropin releasing factor type 1-receptor inhibitors and ACAT-1 inhibitors are demonstrating attractive proofs of principle with promising outcomes in the research setting.
Optimal mental health care is another area with significant unmet needs in the care of people affected with CAH. Psychological morbidity and substance abuse, possibly related to prenatal androgen exposure, appear to be more frequent with CAH relative to the general population. Better understanding of the increased masculine related behavior traits, higher rates of gender dysphoria and other cognitive deficits is vital to provide optimal care for CAH individuals. The verbal memory and cognitive deficits associated with fetal prenatal dexamethasone exposure will also be highlighted in this Research Topic.
With hundreds of disease-causing mutations in the CYP21A2 gene, the understanding of the genetics of CAH continues to be vital in the correlation of genotype to clinical phenotype. This aids pre-conception and prenatal genetic testing.
Finally, we shed light on experiences with newborn screening programs including false positive results and interpretation of results based on gestational age and weight.
This Research Topic aims to elucidate novel therapies that target more physiological glucocorticoid replacement in CAH, provide in depth understanding of mental health morbidity and gender dysphoria encountered in CAH individuals. We also highlight the importance of genetics as the primary tool for pre-conceptional and prenatal diagnosis of CAH.
Congenital Adrenal Hyperplasia (CAH) owing to impairment of the 21-hydroxylase enzyme activity is characterized by defective cortisol synthesis with secondary rise in ACTH and shunting of steroid synthesis to the androgen pathway. The resultant hyperandrogenemia and cortisol deficiency (with or without mineralocorticoid deficiency) constitute the hallmark of the disease pathogenesis.
Standard CAH treatment with glucocorticoids aims to suppress the ACTH driven hyperandrogenemia, which inevitably subjects patients to lifelong supra-physiologic glucocorticoid doses that do not mimic the physiological circadian rhythm of cortisol secretion. The ultimate balance of “enough” glucocorticoids to suppress excess androgens and “not too much” to avoid unwanted side effects is seldom achieved.
Achievement of a physiological circadian rhythm with a subsequent enhancement in quality of life represents an important unmet need in the management of CAH. To this end, investigators proposed therapies, such as continuous subcutaneous administration of hydrocortisone via pump therapy or hydrocortisone formulations with a delayed and sustained absorption profile, to replicate physiological glucocorticoid replacement. Additionally, novel therapeutic molecules such as selective corticotropin releasing factor type 1-receptor inhibitors and ACAT-1 inhibitors are demonstrating attractive proofs of principle with promising outcomes in the research setting.
Optimal mental health care is another area with significant unmet needs in the care of people affected with CAH. Psychological morbidity and substance abuse, possibly related to prenatal androgen exposure, appear to be more frequent with CAH relative to the general population. Better understanding of the increased masculine related behavior traits, higher rates of gender dysphoria and other cognitive deficits is vital to provide optimal care for CAH individuals. The verbal memory and cognitive deficits associated with fetal prenatal dexamethasone exposure will also be highlighted in this Research Topic.
With hundreds of disease-causing mutations in the CYP21A2 gene, the understanding of the genetics of CAH continues to be vital in the correlation of genotype to clinical phenotype. This aids pre-conception and prenatal genetic testing.
Finally, we shed light on experiences with newborn screening programs including false positive results and interpretation of results based on gestational age and weight.
This Research Topic aims to elucidate novel therapies that target more physiological glucocorticoid replacement in CAH, provide in depth understanding of mental health morbidity and gender dysphoria encountered in CAH individuals. We also highlight the importance of genetics as the primary tool for pre-conceptional and prenatal diagnosis of CAH.