What are the management and treatment options for elevated Dehydroepiandrosterone (DHEA) and cortisol levels during pregnancy?

Management of Elevated DHEA and Cortisol in Pregnancy

Critical First Step: Determine if Elevation is Physiologic or Pathologic

Elevated cortisol and DHEA during pregnancy are typically physiologic adaptations and should NOT be treated unless there is evidence of underlying pathology such as Cushing's syndrome or virilizing adrenal tumor. 1, 2

Understanding Normal Pregnancy Physiology

• Cortisol naturally increases throughout pregnancy, remaining stable until 36 weeks gestation and then rising significantly toward term, with further elevation during active labor 3
• DHEA-S increases at term gestation (>36 weeks) as the fetal adrenal produces prodigious quantities to serve as precursor for placental estrogen formation 1, 2
• The cortisol/DHEA-S ratio (stress index) physiologically increases with advancing gestation and active labor 3
• Only 10% of maternal corticosteroid dose reaches the developing fetus 4

When Elevated Levels Require Investigation

Red Flags Suggesting Pathologic Elevation

• Clinical signs of Cushing's syndrome: rapid weight gain, moon facies, purple striae, proximal muscle weakness, hypertension
• Virilization symptoms: hirsutism, voice deepening, clitoral enlargement (suggesting androgen-secreting tumor)
• Imaging findings: adrenal mass >4-5 cm, irregular margins, or heterogeneous appearance on ultrasound/MRI
• Severe anxiety with disproportionately elevated cortisol/DHEA-S ratio beyond expected pregnancy changes 5

Specific Pathologic Associations to Monitor

• Extremely elevated DHEA-S with low cortisol/DHEA-S ratio is associated with increased risk of stillbirth and adverse birth outcomes 6
• Pregnant women with highest circulatory DHEA-S levels (top quartile) have 2.79-fold increased odds of adverse birth outcomes and 8.47-fold increased odds of stillbirth 6

Management Algorithm

For Physiologic Elevation (Most Common Scenario)

No treatment is indicated for physiologic elevation of cortisol and DHEA during pregnancy. 1, 2, 3

• Screen for gestational diabetes mellitus if patient has any glucocorticoid exposure, as elevated cortisol increases GDM risk 4
• Monitor blood pressure throughout pregnancy, as elevated cortisol may contribute to hypertension 4
• Reassure patient that these hormonal changes are normal pregnancy adaptations 1, 2

For Pathologic Elevation from Adrenal Neoplasm

Surgical intervention with adrenalectomy is first-line treatment for confirmed adrenal neoplasms causing pathologic DHEA elevation. 7

• Laparoscopic adrenalectomy is recommended for benign tumors when feasible 7
• Open adrenalectomy is preferred for suspected malignant tumors (size >4-5 cm, irregular margins, heterogeneous appearance) 7
• Timing of surgery during pregnancy requires multidisciplinary consultation with maternal-fetal medicine and endocrine surgery

For Cushing's Syndrome During Pregnancy

Medical management with metyrapone may be considered if surgery is not feasible, but use with extreme caution. 8

• Metyrapone crosses the placenta and can decrease fetal cortisol production and impair biosynthesis of fetal and placental steroids 8
• Published reports document low cortisol levels at birth in infants exposed in utero following chronic metyrapone use 8
• Ketoconazole (400-1200 mg/day) can inhibit adrenal steroidogenesis but requires regular liver function monitoring 7
• Monitor closely for signs of adrenal insufficiency with any adrenostatic agent 7, 8

Critical Monitoring Parameters

Throughout Pregnancy

• Serial DHEA-S and cortisol measurements if pathologic elevation suspected, to assess for progressive increase beyond physiologic norms 6
• Glucose screening for gestational diabetes, particularly if cortisol markedly elevated 4
• Blood pressure monitoring at each prenatal visit for hypertension/preeclampsia 4
• Fetal surveillance with serial ultrasounds if DHEA-S in highest quartile due to stillbirth risk 6

At Delivery

• No glucocorticoid supplementation needed for physiologic cortisol elevation 4
• Consider stress-dose steroids only if patient has been on exogenous glucocorticoids >5 mg prednisolone daily for >3 weeks 4

Common Pitfalls to Avoid

• Do not treat physiologic pregnancy-related cortisol and DHEA elevation as this represents normal adaptation 1, 2, 3
• Do not confuse anxiety-related cortisol elevation with Cushing's syndrome—pregnant women with severe anxiety show elevated cortisol but this is reactive, not autonomous 5
• Do not ignore extremely elevated DHEA-S levels (top quartile) as these correlate with adverse outcomes including stillbirth 6
• Do not use metyrapone without understanding fetal risks—it impairs fetal steroid biosynthesis and causes low neonatal cortisol 8