What is the required hydrocortisone (cortisol) dose for women with Congenital Adrenal Hyperplasia (CAH) during pregnancy?

From the Guidelines

Pregnant women with Congenital Adrenal Hyperplasia (CAH) should be treated with hydrocortisone at a dose of 15-25 mg per day divided into 2-3 doses, with potential increases of 20-40% in the second and third trimesters due to increased cortisol-binding globulin levels and physiological stress of pregnancy, as recommended by recent guidelines 1. The management of CAH in pregnancy requires careful consideration of the balance between under-replacement and over-replacement of glucocorticoids.

• Under-replacement can lead to adrenal crisis or excessive androgen production affecting the female fetus,
• while over-replacement can cause maternal hypertension, glucose intolerance, and excessive weight gain. Monitoring should include regular clinical assessment for symptoms of under or over-replacement, blood pressure measurements, and periodic laboratory testing of 17-hydroxyprogesterone levels, aiming to keep them in the upper normal range or slightly elevated (but below 2000 ng/dL) 1. Dose adjustments should be made gradually, typically in 2.5-5 mg increments. Patients should be instructed to double or triple their hydrocortisone dose during times of illness, surgery, or labor, with a bolus parenteral dose of 100 mg of hydrocortisone given during delivery, and repeated if necessary every 6 h 1. Close collaboration between endocrinologists and obstetricians is essential for optimal management throughout pregnancy. The most recent guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK recommend maternal glucocorticoid supplementation in obstetric patients with adrenal insufficiency, with a higher maintenance dose during the later stages of pregnancy (20th week onwards), and stress dose supplementation using hydrocortisone 100 mg at the onset of labor 1.

From the Research

Hydrocortisol Dose for Congenital Adrenal Hyperplasia Women in Pregnancy

• The management of congenital adrenal hyperplasia (CAH) during pregnancy is crucial to prevent complications and ensure the health of both the mother and the fetus 2.
• Pregnant women with classic CAH need glucocorticoids to be adjusted during pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis 2.
• The choice of glucocorticoid and the dosage may vary, but hydrocortisone is commonly used 3.
• The dosage of hydrocortisone may need to be increased during pregnancy, with an average increase of 8.6 ± 5.4 mg per day in the third trimester 3.
• The goal of glucocorticoid replacement therapy is to mimic the normal physiological cortisol level, but current treatment regimens may not always achieve this, and over-treatment or under-treatment is often reported 4.

Glucocorticoid Replacement Regimens

• Different glucocorticoid replacement regimens have been compared in clinical trials, including hydrocortisone, prednisolone, and dexamethasone 4.
• The trials have shown varying results, with some indicating that different dose schedules of hydrocortisone may have little or no difference in terms of androgen normalization and 17-hydroxyprogesterone levels 4.
• However, the quality of the evidence is often low, and more research is needed to determine the most effective form of glucocorticoid replacement therapy in CAH for children and adults 4.

Pregnancy Outcomes

• Women with CAH can have successful pregnancies, but they are at risk of complications such as adrenal crisis, maternal hypertension, gestational diabetes, and cesarean section 2, 5.
• Fetal complications can also occur, including small for gestational age infants 2.
• Careful endocrine follow-up and repeated patient education are essential to reduce the risk of adrenal crisis and ensure positive outcomes 3.