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Cushing's syndrome in pregnancy

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


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".)


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.

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Literature review current through: Nov 2017. | This topic last updated: Oct 27, 2017.
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