Assessment of adrenal reserve in pregnancy: defining the normal response to the adrenocorticotropin stimulation test

J Clin Endocrinol Metab. 2006 Oct;91(10):3866-72. doi: 10.1210/jc.2006-1049. Epub 2006 Aug 8.


Context: Normal pregnancy is a state of hypercortisolism, making adrenal insufficiency difficult to diagnose.

Objective: We sought to identify a normative, minimum-response threshold for the ACTH stimulation test in pregnancy. We hypothesized that salivary free cortisol (SaFC) would prove a more physiological and less variable measure of adrenal reserve in pregnancy than serum cortisol (SC).

Design: This is a prospective study of normal controls.

Setting: The study was conducted in an obstetrical clinic in a tertiary care hospital.

Patients: Patients included 36 healthy ambulatory pregnant women (aged 18-37 yr) with singleton pregnancies.

Intervention: The 250-microg ACTH stimulation test was performed in the healthy pregnant volunteers. Based on their gestational age at the time of recruitment, women were studied in one of the trimesters and were restudied at 11-14 wk postpartum.

Main outcome measures: Total SC, aldosterone, and SaFC concentrations were measured before and after ACTH. The response in pregnancy was compared with postpartum values.

Results: Basal SC (P = 0.01), aldosterone (P = 0.001), and SaFC (P = 0.01) values progressively increased during the trimesters of pregnancy and decreased postpartum, confirming that pregnant women have increased basal glucocorticoid and mineralocorticoid production. There was enhanced responsiveness of the maternal adrenal glands to ACTH stimulation as pregnancy progressed, as measured by peak stimulated SaFC (P = 0.009) and aldosterone (P = 0.01). In the milieu of altered binding globulins, SaFC is a more consistent, binding-globulin-independent measure of stimulated adrenal function than total SC. Minimum criteria for the normal SaFC response to ACTH stimulation in the second and third trimesters of pregnancy and postpartum have been generated based on a predominantly African-American group of subjects.

Conclusions: Reliable data are available for the evaluation of the adrenal axis in pregnancy with a noninvasive, outpatient measure of SaFC. Glucocorticoid therapy in pregnancy should take into account that adrenal reserve increases as pregnancy progresses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / physiology*
  • Adrenocorticotropic Hormone*
  • Adult
  • Aldosterone / blood*
  • Carrier Proteins / analysis
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Hydrocortisone / blood*
  • Pregnancy / physiology*
  • Prospective Studies
  • Saliva / chemistry*


  • Carrier Proteins
  • cortisol binding globulin
  • Aldosterone
  • Adrenocorticotropic Hormone
  • Hydrocortisone