The Hypothalamic-Pituitary-Adrenal Axis in Pregnancy: Challenges in Disease Detection and Treatment

• Published in: Endocrine reviews 2005-10, Vol.26 (6), p.775-799
• Main Authors: Lindsay, John R, Nieman, Lynnette K
• Format: Article
• Language: English
• Subjects: Adrenal Gland Diseases - complications; Adrenal Gland Diseases - diagnosis; Adrenal Gland Diseases - therapy; Adrenal Glands - physiopathology; Adrenal Insufficiency - complications; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - epidemiology; Adrenal Insufficiency - therapy; Adrenocorticotropic hormone; Biological activity; Biological and medical sciences; Cortisol; Cushing Syndrome - complications; Cushing Syndrome - diagnosis; Cushing Syndrome - epidemiology; Cushing Syndrome - therapy; Desensitization; Diagnosis; Disease detection; Female; Fetal Death; Fetuses; Fundamental and applied biological sciences. Psychology; Gestation; Health services; Hormones; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - physiopathology; Hypothalamus; Maternal Mortality; Medical treatment; Morbidity; Nervous system diseases; Patients; Pituitary; Placenta; Pregnancy; Pregnancy Complications; Puerperium; Vertebrates: endocrinology
• ISSN: 0163-769X; 1945-7189
• DOI: 10.1210/er.2004-0025

Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing’s syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed.CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing’s disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used.Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed.