Just under 100 cases of Cushing syndrome in pregnancy have been reported.104,105,106,107,108,109 and 110 The distribution of causes in pregnant women differs from that in the nonpregnant population. Less than 50% of the patients described had pituitary adenomas, a similar number had adrenal adenomas, and 10% had adrenal carcinomas.104,105,106,107,108,109 and 110 Only one report described a pregnancy associated with the ectopic ACTH syndrome.106 In many cases, the hypercortisolism first became apparent during pregnancy, with improvement after parturition; this leads to the speculation that unregulated placental CRH was instrumental in causing this pregnancy-induced exacerbation.105,106

Diagnosing Cushing syndrome during pregnancy may be difficult. Both conditions may be associated with
weight gain in a central distribution, fatigue, edema, emotional upset, glucose intolerance, and hypertension. The striae associated with the weight gain and increased abdominal girth are usually white in normal pregnancy and red or purple in Cushing syndrome. Hirsutism and acne may point to excessive androgen production.

The laboratory evaluation of Cushing syndrome during pregnancy is not straightforward. Elevated total and free serum cortisol and ACTH levels, and urinary free cortisol excretion are compatible with that of normal pregnancy. The overnight dexa-methasone test usually demonstrates inadequate suppression during normal pregnancy.107 At least in the latter part of the third trimester, the elevated cortisol levels are not suppressed during the low-dose dexamethasone test but are suppressed during the high-dose test, as in patients with Cushing disease.108 ACTH levels are normal to elevated in pregnant patients with all forms of Cushing syndrome.104,105,106,107,108,109 and 110 These “normal” rather than suppressed levels of ACTH in patients with adrenal adenomas may result from the production of ACTH by the placenta or from the nonsuppressible stimulation of pituitary ACTH by placental CRH.

A persistent circadian variation in the elevated levels of total and free serum cortisol during normal pregnancy may be most helpful in distinguishing Cushing syndrome from the hyper-cortisolism of pregnancy, because this finding is characteristically absent in all forms of Cushing syndrome.101 In many cases, radiologic imaging is necessary. An adrenal mass often is visible with ultrasonography; however, CT or MRI scanning of the pituitary or adrenal may be required. Most adrenal lesions are unilateral, so that localization is important. Little experience has been reported with newer techniques such as CRH stimulation testing or petrosal venous sinus sampling during pregnancy (see Chap. 75). However, in a case study, a woman with Cushing disease who had the typical exaggerated ACTH response to CRH experienced no ill effects from such testing.108 CRH testing during petrosal sinus sampling was performed without ill effects in a woman at 14 weeks’ gestation, but catheterization was performed via the direct internal jugular vein approach rather than the femoral vein approach to minimize fetal irradiation.111