UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Cushing's syndrome in pregnancy

Author
Lynnette K Nieman, MD
Section Editors
André Lacroix, MD
Charles J Lockwood, MD, MHCM
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Cushing's syndrome (CS) is rarely associated with pregnancy as hypercortisolism typically results in anovulatory infertility. However, there are over 200 reported cases of CS in pregnancy.

This topic will review issues related to CS in pregnancy. The clinical manifestations, diagnosis, and treatment of CS in nonpregnant patients are discussed separately. (See "Epidemiology and clinical manifestations of Cushing's syndrome" and "Establishing the diagnosis of Cushing's syndrome" and "Overview of the treatment of Cushing's syndrome".)

OVERVIEW

Frequency — Cushing's syndrome (CS) is associated with a high prevalence (up to 75 percent) of ovulatory disturbances induced by cortisol excess [1-3]. As a result, women with untreated CS rarely become pregnant [2]. However, there are over 220 reported cases of CS in pregnancy, most of which were associated with important maternal and fetal complications [4].

Normal HPA axis changes — Normal pregnancy is associated with changes in the maternal hypothalamic-pituitary-adrenal (HPA) axis, including increased production of cortisol-binding globulin (CBG); increased concentrations of serum, salivary, and urinary free cortisol (UFC); and lack of suppression of serum cortisol after dexamethasone. In addition, the placenta produces corticotropin (ACTH) and corticotropin-releasing hormone (CRH). Thus, the biochemical diagnosis of CS during pregnancy is more challenging than in the nonpregnant state.

Serum total and free cortisol concentrations and urinary cortisol excretion are increased in pregnant women, but the bedtime nadir of serum cortisol is maintained and urinary 17-hydroxycorticosteroid excretion is normal [5]. One study in normal women reported that plasma cortisol values in pregnancy increased from 14.9±3.4 mcg/dL at 12 weeks (411±94 nmol/L) to 35.2±9.0 mcg/dL (971±248 nmol/L) at 26 weeks gestation and changed minimally thereafter [6]. This same study found a two to threefold increase in UFC in the second and third trimesters.

               
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Oct 27, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Aron DC, Schnall AM, Sheeler LR. Cushing's syndrome and pregnancy. Am J Obstet Gynecol 1990; 162:244.
  2. Buescher MA, McClamrock HD, Adashi EY. Cushing syndrome in pregnancy. Obstet Gynecol 1992; 79:130.
  3. Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, et al. 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.
  4. Caimari F, Valassi E, Garbayo P, et al. Cushing's syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 2017; 55:555.
  5. Buescher, MA. Cushing's syndrome in pregnancy. Endocrinologist 1996; 6:357.
  6. Carr BR, Parker CR Jr, Madden JD, et al. Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am J Obstet Gynecol 1981; 139:416.
  7. Manetti L, Rossi G, Grasso L, et al. Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol. Eur J Endocrinol 2013; 168:315.
  8. Odagiri E, Ishiwatari N, Abe Y, et al. Hypercortisolism and the resistance to dexamethasone suppression during gestation. Endocrinol Jpn 1988; 35:685.
  9. Lindsay JR, Jonklaas J, Oldfield EH, Nieman LK. Cushing's syndrome during pregnancy: personal experience and review of the literature. J Clin Endocrinol Metab 2005; 90:3077.
  10. Caticha O, Odell WD, Wilson DE, et al. Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia. J Clin Endocrinol Metab 1993; 77:494.
  11. Spaniol A, Mulla BM, Daily JG, Ennen CS. Carney complex: a rare cause of Cushing syndrome in pregnancy. Obstet Gynecol 2014; 124:426.
  12. Guilhaume B, Sanson ML, Billaud L, et al. Cushing's syndrome and pregnancy: aetiologies and prognosis in twenty-two patients. Eur J Med 1992; 1:83.
  13. Hadden DR. Adrenal disorders of pregnancy. Endocrinol Metab Clin North Am 1995; 24:139.
  14. Cohade C, Broussaud S, Louiset E, et al. Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature. Gynecol Endocrinol 2009; 25:624.
  15. Close CF, Mann MC, Watts JF, Taylor KG. ACTH-independent Cushing's syndrome in pregnancy with spontaneous resolution after delivery: control of the hypercortisolism with metyrapone. Clin Endocrinol (Oxf) 1993; 39:375.
  16. Hána V, Dokoupilová 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.
  17. Jones SA, Brooks AN, Challis JR. Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta. J Clin Endocrinol Metab 1989; 68:825.
  18. Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. Endocr Rev 2001; 22:75.
  19. Wy LA, Carlson HE, Kane P, et al. Pregnancy-associated Cushing's syndrome secondary to a luteinizing hormone/human chorionic gonadotropin receptor-positive adrenal carcinoma. Gynecol Endocrinol 2002; 16:413.
  20. Lindsay JR, Nieman LK. The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment. Endocr Rev 2005; 26:775.
  21. Jung C, Ho JT, Torpy DJ, et al. A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. J Clin Endocrinol Metab 2011; 96:1533.
  22. Lopes LM, Francisco RP, Galletta MA, Bronstein MD. Determination of nighttime salivary cortisol during pregnancy: comparison with values in non-pregnancy and Cushing's disease. Pituitary 2016; 19:30.
  23. Barasch E, Sztern M, Spinrad S, et al. Pregnancy and Cushing's syndrome: example of endocrine interaction. Isr J Med Sci 1988; 24:101.
  24. Abrahamson MJ, Miller JL, Alperstein AL, Barron JL. Cushing's syndrome in pregnancy. A case report. S Afr Med J 1986; 69:834.
  25. Da Motta LA, Motta LD, Barbosa AM, et al. Two pregnancies in a Cushing's syndrome. Case report. Panminerva Med 1991; 33:44.
  26. Casson IF, Davis JC, Jeffreys RV, et al. Successful management of Cushing's disease during pregnancy by transsphenoidal adenectomy. Clin Endocrinol (Oxf) 1987; 27:423.
  27. Ross RJ, Chew SL, Perry L, et al. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. Eur J Endocrinol 1995; 132:722.
  28. Blanco C, Maqueda E, Rubio JA, Rodriguez A. Cushing's syndrome during pregnancy secondary to adrenal adenoma: metyrapone treatment and laparoscopic adrenalectomy. J Endocrinol Invest 2006; 29:164.
  29. Orth DN, Liddle GW. Results of treatment in 108 patients with Cushing's syndrome. N Engl J Med 1971; 285:243.
  30. Amado JA, Pesquera C, Gonzalez EM, et al. Successful treatment with ketoconazole of Cushing's syndrome in pregnancy. Postgrad Med J 1990; 66:221.
  31. 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.
  32. Leiba S, Weinstein R, Shindel B, et al. The protracted effect of o,p'-DDD in Cushing's disease and its impact on adrenal morphogenesis of young human embryo. Ann Endocrinol (Paris) 1989; 50:49.
  33. Knappe G, Gerl H, Ventz M, Rohde W. [The long-term therapy of hypothalamic-hypophyseal Cushing's syndrome with mitotane (o,p'-DDD)]. Dtsch Med Wochenschr 1997; 122:882.
  34. Kriplani A, Buckshee K, Ammini AC. Cushing syndrome complicating pregnancy. Aust N Z J Obstet Gynaecol 1993; 33:428.