Pulsatility of glucocorticoid hormones in pregnancy: Changes with gestation and obesity

Abstract

SummaryObjectiveHypothalamic‐pituitary‐adrenal axis (HPA) activity is decreased in obese pregnancy and associates with increased foetal size. Pulsatile release of glucocorticoid hormones regulates their action in target tissues. Glucocorticoids are essential for normal foetal growth, but little is known about glucocorticoid pulsatility in pregnancy. We aimed to investigate the ultradian rhythm of glucocorticoid secretion during obese and lean pregnancy and nonpregnancy.DesignSerum cortisol, cortisone, corticosterone and 11‐dehydrocorticosterone were measured by LC‐MS/MS from samples obtained at 10‐minute intervals between 08.00‐11.00 hours and 16.00‐19.00 hours, from 8 lean (BMI <25 kg/m2) and 7 obese (BMI > 35 kg/m2) pregnant women between 16‐24 weeks gestation and again at 30‐36 weeks), and nonpregnant controls (lean n = 3, obese n = 4) during the luteal phase of their menstrual cycle. Interstitial fluid cortisol was measured by ELISA, from samples obtained using a portable microdialysis and automated collection device at 20‐minute intervals over 24 hours.ResultsSerum cortisol AUC, highest peak and lowest trough increased significantly with gestation in lean and obese pregnant compared with nonpregnant subjects. Pulsatility of cortisol was detected in interstitial fluid. In pregnant subjects, interstitial fluid pulse frequency was significantly lower with advancing gestation in obese, but not in lean.ConclusionsWe demonstrate cortisol pulsatility in interstitial fluid. Pulse frequency is altered with increased gestation and BMI. This may be a novel mechanism to explain decreased HPA activity in obese pregnancy.

European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity

“…The usual tests are not as easy to interpret during pregnancy. HPA axis activity is reduced in obese pregnancy that could contribute to foetal complications, including macrosomia (201). The systematic assessment of cortisol during pregnancy is not recommended, but obesity can further increase the difficulty to interpret usual tests during pregnancy.…”

Current strategies for quantification of estrogens in clinical research

“…Supported liquid extraction (SLE) opens doors to new approaches for extraction but as yet methods for estrogen analysis have been scarcely published, unlike with other steroids [91]. This strategy shows promise in company application notes [92] with successful application to androgen profiling for diseases such as congenital adrenal hyperplasia [93].…”

Sleep disordered breathing in pregnancy: A review of the pathophysiology of adverse pregnancy outcomes

“…Pregnancy is characterized by activation of the HPA axis, and a threefold increase in total serum levels of cortisol, the main glucocorticoid in humans, occurs between the first and third trimesters . Notably, obese women demonstrate a blunted activation of HPA axis activation during pregnancy compared to their lean counterparts …”