Semin Reprod Med 2002; 20(4): 375-380
DOI: 10.1055/s-2002-36710
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Corticosteroids and Pregnancy

Peter J. Trainer
  • Department of Endocrinology, Christie Hospital, Manchester, United Kingdom
Further Information

Publication History

Publication Date:
21 January 2003 (online)

ABSTRACT

Pregnancy results in major changes in the hypothalamo-pituitary-adrenal (HPA) axis, which in turn influence fetal growth and the timing of labor. From the beginning of the second trimester maternal cortisol secretion increases, and in late pregnancy the placenta, in large part mediated through corticotroph-releasing hormone, plays a crucial role in the regulation of the fetal HPA axis to ensure the synchronization of the various processes involved in parturition. Exposure of the fetus to excess glucocorticoid results in intrauterine growth failure and possibly "programs" the development of cardiovascular disease in adult life. Biochemical assessment of the HPA axis is complicated by the estrogen-induced elevation of circulating cortisol-binding globulin, resulting in misleadingly high circulating cortisol levels The hypercortisolemia of Cushing's syndrome causes infertility, but if pregnancy does occur it can result in increased morbidity and mortality in mother and fetus. However, the prospects of a successful pregnancy are greatly improved with control of hypercortisolemia by surgery and medical therapy with metyrapone. Hypoadrenalism can be difficult to diagnose during pregnancy but, once the diagnosis is made, with careful monitoring, dose adjustment as indicated, and parenteral cover for labor, a successful pregnancy should result.

REFERENCES

  • 1 Seckl J R, Cleasby M, Nyirenda M J. Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming.  Kidney Int . 2000;  57 1412-1417
  • 2 Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin.  Science . 1981;  213 1394-1397
  • 3 Petraglia F, Sawchenko P E, Rivier J, Vale W. Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta.  Nature . 1987;  328 717-719
  • 4 Barker D J, Osmond C, Golding J, Kuh D, Wadsworth M E. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease.  BMJ . 1989;  298 564-567
  • 5 Barker D J, Winter P D, Osmond C, Margetts B, Simmonds S J. Weight in infancy and death from ischaemic heart disease.  Lancet . 1989;  2 577-580
  • 6 Benediktsson R, Lindsay R S, Noble J, Seckl J R, Edwards C R. Glucocorticoid exposure in utero: new model for adult hypertension.  Lancet . 1993;  341 339-341
  • 7 Gitau R, Fisk N M, Teixeira J M, Cameron A, Glover V. Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses.  J Clin Endocrinol Metab . 2001;  86 104-109
  • 8 Stewart P M, Corrie J E, Shackleton C H, Edwards C R. Syndrome of apparent mineralocorticoid excess: a defect in the cortisol-cortisone shuttle.  J Clin Invest . 1988;  82 340-349
  • 9 Stewart P M, Rogerson F M, Mason J I. Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis.  J Clin Endocrinol Metab . 1995;  80 885-890
  • 10 Lindsay R S, Lindsay R M, Waddell B J, Seckl J R. Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone.  Diabetologia . 1996;  39 1299-1305
  • 11 Reinisch J M, Simon N G, Karow W G, Gandelman R. Prenatal exposure to prednisone in humans and animals retards intrauterine growth.  Science . 1978;  202 436-438
  • 12 Liggins G C, Howie R N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants.  Pediatrics . 1972;  50 515-525
  • 13 Howie R N. Pharmacological acceleration of lung maturation. In: Villee CA, Villee DB, Zuckerman J, eds. Respiratory Distress Syndrome London: Academic Press 1973: 385-396
  • 14 New M I, Carlson A, Obeid J. Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.  J Clin Endocrinol Metab . 2001;  86 5651-5457
  • 15 Lado-Abeal J, Rodriguez-Arnao J, Newell-Price J D. Menstrual abnormalities in women with Cushing's disease are correlated with hypercortisolemia rather than raised circulating androgen levels.  J Clin Endocrinol Metab . 1998;  83 3083-3088
  • 16 Aron D C, Schnall A M, Sheeler L R. Spontaneous resolution of Cushing's syndrome after pregnancy.  Am J Obstet Gynecol . 1990;  162 472-474
  • 17 Chico A, Manzanares J M, Halperin I, Martinez de Osaba J M, Adelantado J, Webb S M. Cushing's disease and pregnancy: report of six cases.  Eur J Obstet Gynecol Reprod Biol . 1996;  64 143-146
  • 18 Newell-Price J, Trainer P J, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states.  Endocr Rev . 1998;  19 647-672
  • 19 Ross R J, Chew S L, Perry L, Erskine K, Medbak S, Afshar F. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery.  Eur J Endocrinol . 1995;  132 722-726
  • 20 Trainer P J, Lawrie H S, Verhelst J. Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment.  Clin Endocrinol . 1993;  38 73-78
  • 21 Aron D C, Schnall A M, Sheeler L R. Cushing's syndrome and pregnancy.  Am J Obstet Gynecol . 1990;  162 244-252
  • 22 Gormley M J, Hadden D R, Kennedy T L, Montgomery D A, Murnaghan G A, Sheridan B. Cushing's syndrome in pregnancy: treatment with metyrapone.  Clin Endocrinol . 1982;  16 283-293
  • 23 Close C F, Mann M C, Watts J F, Taylor K G. ACTH-independent Cushing's syndrome in pregnancy with spontaneous resolution after delivery: control of the hypercortisolism with metyrapone.  Clin Endocrinol (Oxf) . 1993;  39 375-379
  • 24 Wallace C, Toth E L, Lewanczuk R Z, Siminoski K. Pregnancy-induced Cushing's syndrome in multiple pregnancies.  J Clin Endocrinol Metab . 1996;  81 15-21
  • 25 Hana V, Dokoupilova M, Marek J, Plavka R. Recurrent ACTH-independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone.  Clin Endocrinol (Oxf) . 2001;  54 277-281
  • 26 Naing S, Wieringa G, Perry L A. What value do cortisol measurements provide in monitoring metyrapone therapy?. British Endocrine Societies, Harrogate, April 2002
  • 27 Verhelst J A, Trainer P J, Howlett T A. Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome.  Clin Endocrinol . 1991;  35 169-178
  • 28 Sonino N, Boscaro M, Paoletta A, Mantero F, Ziliotto D. Ketoconazole treatment in Cushing's syndrome: experience in 34 patients.  Clin Endocrinol . 1991;  35 347-352
  • 29 Zollner E, Delport S, Bonnici F. Fatal liver failure due to ketoconazole treatment of a girl with Cushing's syndrome.  J Pediatr Endocrinol Metab . 2001;  14 335-338
  • 30 Berwaerts J, Verhelst J, Mahler C, Abs R. Cushing's syndrome in pregnancy treated by ketoconazole: case report and review of the literature.  Gynecol Endocrinol . 1999;  13 175-182
  • 31 George L D, Selvaraju R, Reddy K, Stout T V, Premawardhana L D. Vomiting and hyponatraemia in pregnancy.  Br J Obstet Gynaecol . 2000;  107 808-809
  • 32 McGill I G. Addison's disease presenting as a crisis in the puerperium.  Br Med J . 1971;  2 566
  • 33 Goldman M H, Sfedu E, Aboul-Hosn H, Nutt R. Addison's disease presenting in the postpartum state.  J Med Soc N J . 1983;  80 1030-1031
  • 34 McLean M, Smith R. Corticotropin-releasing hormone in human pregnancy and parturition.  Trends Endocrinol Metab . 1999;  10 174-178
    >