The Corticotrophin Releasing Hormone Test in Late Pregnancy: Lack of Adrenocorticotrophin and Cortisol Response*

Abstract

Biologically active corticotrophin-releasing-hormone (CRH) is produced by the placenta in large amounts and can be measured in the maternal circulation during third trimester of pregnancy. Its physiological significance is unknown. To further investigate the action of CRH in pregnancy, we performed a standard CRH-test (1 micrograms/kg synthetic human CRH) in seven pregnant women 1 week prior to their calculated delivery data and 4-5 weeks post-partum. No response of plasma ACTH to CRH administration could be measured in any of the third trimester pregnant women. Post-partum, basal ACTH levels were significantly lower (1.6 +/- 0.3 vs 5.3 +/- 0.2 pmol/l) and reacted promptly to CRH administration (1.6 +/- 0.3-4.2 +/- 0.5 pmol/l; P less than 0.05). Concentration of cortisol in plasma and salivary cortisol paralleled the ACTH response to administration of CRH. However, one pregnant woman experienced physical and emotional stress during the CRH-test and reacted with a sharp rise in cortisol secretion. The lack of the ACTH and cortisol response in this study to exogenously administered CRH in third trimester pregnancy may be due to high circulating glucocorticoid concentrations, desensitization of the pituitary corticotroph and/or in part due to circulating specific CRH-carrier protein.

The influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth

“…A significant difference was seen between T1 and T2 at awakening and 30 min and 12 h later and between T2 and T3 at 4 and 12 h after awakening. Pregnancy is characterized by a progressive and significant increase in plasma concentrations of corticotropin-releasing hormone (18), adrenocorticotropic hormone, and cortisol (19,20). Our result on cortisol awakening response and diurnal cortisol profile in pregnancy confirmed the results of other authors.…”

Corticotrophin-releasing hormone and ACTH levels in maternal and fetal blood during spontaneous and oxytocin-induced labour

“…A well-known hypothesis suggests that activity of the maternal HPA axis during pregnancy is under efficient inhibitory control before parturition. Schulte et al (5) found that injection of exogenous CRH in pregnant women does not induce an increase in circulating ACTH. This is probably because the high cortisol levels that occur during pregnancy may desensitize maternal pituitary corticotrophs, which is supported by data obtained by Thomson et al (13).…”

“…In contrast to the negative control on hypothalamic CRH, glucocorticoids stimulate the expression of human CRH mRNA in cultured cytotrophoblast, amnion, chorion and decidual cells (4). Experiments conducted by Schulte et al among others showed a disturbance of regulation of the maternal HPA axis during pregnancy, probably due to pituitary desensitization to CRH (5,6). Still there is discussion not only about the origin but also about the mechanism of action of CRH during labour.…”

Pregnancy and pituitary disorders

“…The HPA axis becomes resistant in the third trimester of pregnancy, and higher doses of CRH (2 mg/kg) are needed to evoke sufficient ACTH and cortisol response (28, 86,87). CRH stimulation by 100 mg causes an increase in ACTH and cortisol in pregnant patients with CD (88).…”

“…Pregnancy is a state of physiological hypercortisolism where CBG and cortisol levels increase. An insulin tolerance test and metyrapone tests are contraindicated during pregnancy, and the CRH test is useless due to its placental production (86). Standard ACTH stimulation test should be preferred during pregnancy, although cutoff values are not determined to diagnose adrenal insufficiency in pregnant women.…”