What to do for elevated 17-hydroxyprogesterone (17-OHP) levels?

From the Guidelines

For elevated 17-hydroxyprogesterone (17-OHP) levels, screening for congenital adrenal hyperplasia (CAH) with 17-hydroxyprogesterone is recommended, especially in patients with bilateral adrenal incidentalomas. The management of elevated 17-OHP levels depends on the underlying cause, and CAH is a significant consideration. According to the study by 1, screening for CAH with 17-hydroxyprogesterone is essential in patients with bilateral adrenal incidentalomas.

Causes and Severity

The elevation of 17-OHP levels can be due to various causes, including CAH, adrenal incidentalomas, or other adrenal disorders. The severity of the elevation and the underlying cause will guide the management approach. For instance, if the elevation is due to CAH, glucocorticoid replacement therapy may be necessary, whereas if it's due to an adrenal incidentaloma, further imaging and potentially surgery may be required.

Treatment Approach

The treatment approach for elevated 17-OHP levels due to CAH typically involves glucocorticoid replacement therapy, with hydrocortisone being the first-line treatment. The dosing of hydrocortisone varies depending on the age and severity of the condition, with children usually requiring 10-15 mg/m²/day divided into three doses, and adults requiring 15-25 mg daily in divided doses. Mineralocorticoid replacement with fludrocortisone may also be necessary if aldosterone production is affected. Regular monitoring of 17-OHP levels, electrolytes, blood pressure, and growth is crucial to adjust medication dosing.

Importance of Monitoring and Stress Dosing

Regular monitoring and stress dosing during illness or surgery are vital to prevent adrenal crisis and other complications. The goal of treatment is to suppress excess androgen production while providing adequate hormone replacement. Untreated CAH can lead to severe consequences, including adrenal crisis, virilization in females, and early puberty in males.

Non-Classical Forms

For milder, non-classical forms of CAH, treatment may only be needed if symptoms are present. The study by 1 highlights the importance of considering the individual patient's needs and preferences when tailoring treatment decisions. However, this study does not provide direct guidance on the management of elevated 17-OHP levels, and therefore, the recommendations are based on the general principles of managing CAH and adrenal incidentalomas.

Key Considerations

• Screening for CAH with 17-hydroxyprogesterone is recommended in patients with bilateral adrenal incidentalomas.
• Glucocorticoid replacement therapy is typically recommended for CAH, with hydrocortisone being the first-line treatment.
• Regular monitoring and stress dosing are crucial to prevent adrenal crisis and other complications.
• The goal of treatment is to suppress excess androgen production while providing adequate hormone replacement.

From the Research

Elevated 17-OHP: Understanding and Management

Elevated 17-hydroxyprogesterone (17-OHP) levels can be an indicator of congenital adrenal hyperplasia (CAH), a condition characterized by impaired steroidogenesis in the adrenal glands. The management of elevated 17-OHP involves a comprehensive approach, including:

• Diagnosis: Elevated 17-OHP levels can be detected through newborn screening or clinical presentation of symptoms such as virilization, premature adrenarche, or irregular menses 2, 3.
• Treatment: Hydrocortisone is the standard replacement therapy for children with CAH, aiming to suppress adrenal androgen production and replace deficient glucocorticoids 4, 5, 3.
• Monitoring: Regular monitoring of 17-OHP levels, as well as other hormones such as androstenedione and cortisol, is essential to adjust treatment and prevent overtreatment or undertreatment 4, 5.
• Dose adjustment: The dose of hydrocortisone may need to be adjusted based on individual patient responses, with the goal of maintaining normal 17-OHP levels and preventing hyperandrogenism 4, 5.

Key Considerations

Some key considerations in the management of elevated 17-OHP include:

• Individual variability: Concentration profiles of cortisol, 17-OHP, and androstenedione can be highly variable in children with CAH, making personalized therapy essential 5.
• Hydrocortisone pharmacokinetics: The rapid half-life of hydrocortisone can make it challenging to closely approximate normal circadian profiles, highlighting the need for careful dose adjustment and monitoring 5.
• Long-term comorbidities: Classic CAH is associated with long-term comorbidities, including cardiometabolic risk factors, impaired cognitive function, adrenal rest tumors, and bone health effects, emphasizing the importance of early identification and treatment 3.

Additional Factors

Other factors that may influence the management of elevated 17-OHP include:

• Sex hormone-binding globulin (SHBG): SHBG levels can be used as an indicator of hyperandrogenemia in pubertal children 4.
• ACTH stimulation test: This test can be used to diagnose non-classical CAH, particularly in cases with normal or moderately raised 17-OHP levels 2.
• Autoimmune adrenalitis: This condition can lead to complete adrenal cortex failure, making it essential to consider in the differential diagnosis of elevated 17-OHP 6.