From the Guidelines
No, congenital adrenal hyperplasia (CAH) typically causes decreased cortisol levels, not increased cortisol. CAH is a group of genetic disorders characterized by enzyme deficiencies in the adrenal steroid synthesis pathway, most commonly 21-hydroxylase deficiency. This enzyme defect blocks the normal production of cortisol, leading to low cortisol levels in the bloodstream. The pituitary gland senses this cortisol deficiency and releases more adrenocorticotropic hormone (ACTH) to stimulate the adrenal glands. This excessive ACTH stimulation causes adrenal hyperplasia (enlargement) and overproduction of adrenal hormone precursors that get diverted into the androgen pathway, resulting in excess androgen production.
Key Points
- The normal production of cortisol is blocked due to enzyme deficiencies in CAH, leading to low cortisol levels 1.
- The pituitary gland releases more ACTH to stimulate the adrenal glands, causing adrenal hyperplasia and excess androgen production.
- Treatment typically involves glucocorticoid replacement therapy to replace the missing cortisol and suppress ACTH production, which in turn reduces excess androgen production 2.
- The goal of treatment is to provide adequate hormone replacement while minimizing side effects and preventing adrenal crises.
Treatment Considerations
- Glucocorticoid replacement therapy, such as hydrocortisone, prednisone, or dexamethasone, is used to replace the missing cortisol 2.
- Mineralocorticoid replacement with fludrocortisone is also necessary in salt-wasting forms of CAH.
- The treatment dose and regimen should be individualized to provide adequate hormone replacement while minimizing side effects.
From the Research
Congenital Adrenal Hyperplasia (CAH) and Cortisol Levels
- CAH is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens 3, 4, 5, 6.
- The impairment of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), adrenal hyperplasia, and excessive androgen synthesis 4.
- Patients with CAH require lifelong treatment with glucocorticoids to replace the endogenous cortisol deficiency and reduce excess adrenal androgens 3, 7, 4, 5, 6.
- The goal of treatment is to improve quality of life, ensure fertility, reduce the manifestations of hyperandrogenisation in females, and minimise the adverse effects of glucocorticosteroid treatment 4, 5, 6.
Effect of CAH on Cortisol Levels
- CAH is characterized by cortisol deficiency 3, 4, 5, 6.
- The use of glucocorticoids in CAH treatment can help replace the deficient cortisol levels 3, 7, 4, 5, 6.
- However, undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities 3.
Treatment and Management of CAH
- Treatment goals in CAH include replacing deficient hormones, controlling androgen excess, and avoiding the adverse effects of exogenous glucocorticoid 5.
- Novel therapies are being developed and studied to improve patient outcomes and reduce the drawbacks of currently available glucocorticoid therapy 5, 6.
- New management strategies, such as the use of modified-release hydrocortisone, have shown promise in improving biochemical disease control and reducing steroid dose over time 7.