Cortisol (serum / plasma)
During pregnancy, total cortisol increases 2–3× due to estrogen-driven increases in cortisol-binding globulin (CBG) and up-regulation of the maternal hypothalamic–pituitary–adrenal (HPA) axis.
| Units | Nonpregnant Adult | 1st Trimester | 2nd Trimester | 3rd Trimester |
|---|---|---|---|---|
| µg/dL | 0 – 25 | 7 – 19 | 10 – 42 | 12 – 50 |
| nmol/L | 0 – 690 | 193 – 524 | 276 – 1159 | 331 – 1380 |
Pregnancy physiology
- Estrogen increases cortisol-binding globulin → higher total cortisol.
- Free cortisol also rises due to HPA axis up-regulation.
- Loss of normal diurnal variation late in pregnancy.
- Third-trimester cortisol approximates levels of Cushing syndrome in nonpregnant adults.
- Interpretation of adrenal disorders requires trimester-adjusted reference values.
Causes of elevated cortisol
- Normal pregnancy (physiologic and expected)
- Cushing syndrome
- Severe stress (trauma, infection, surgery)
- Preeclampsia
- Seizures, hypoglycemia
- Psycho-emotional stress, depression
- Medications: corticosteroids, oral estrogens
Interpretation: In pregnancy, total cortisol is always high; late-night salivary cortisol and urinary free cortisol (UFC) require trimester-specific cutoffs.
Causes of decreased cortisol
- Primary adrenal insufficiency (Addison disease)
- Secondary adrenal insufficiency (pituitary ACTH deficiency)
- Chronic glucocorticoid therapy / suppression
- Congenital adrenal hyperplasia with adrenal failure
- Severe liver disease (low CBG → low total cortisol)
- Hereditary CBG deficiency (total cortisol falsely low)
Low cortisol in pregnancy is abnormal and should prompt evaluation for adrenal insufficiency, especially with hyponatremia, hypotension, or unexplained fatigue.
References
- Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114:1326–31.