Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases

Abstract

Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

“…Moreover, the diagnosis of CS is rarely made during pregnancy and altered fertility is also frequent in patients with active hypercortisolism. Altogether, this explains why, to date, fewer than 200 cases of CS during pregnancy have been reported in the literature (6,7,11). The main atypical characteristic is the fact that the predominant etiology is adrenal adenoma, reported in 40-60% cases, in contrast to non-pregnant women for whom the most frequent cause is Cushing's disease, and adrenal adenomas only account for 10-15% of cases.…”

“…The management of CS during pregnancy is indeed highly challenging both for diagnosis, due to technical caveats or to the possibility of pregnancyinduced CS (5) and for therapy due to limited information on drug safety. This topic has previously been reviewed in recent years by Bronstein and colleagues (6) and by others (7,8,9,10). We will thus, in this present review, summarize in the form of a number of open questions, the main challenges clinicians face when managing a woman with CS who is pregnant or seeking to become pregnant.…”

Cushing’s syndrome during pregnancy with different clinical courses: Two case reports

“…In particular, hypertension and preeclampsia are the most common complications of CS in pregnancy and can result in foetal growth restriction (FGR). 2) Here we report two cases of CS during pregnancy that had different clinical courses and discuss the importance of blood pressure management in the early stage of pregnancy based on their placental pathological features.…”

A case of subclinical Cushing's syndrome in pregnancy with superimposed preeclampsia

“…However, it is unclear whether such complications occur in pregnancies with SCS. The diagnosis of SCS during pregnancy is challenging, as in the case of CS, due to the similarities of some of its features with that of a normal pregnancy, accompanied by physiological hypercortisolism . Estrogen increase can promote cortisol binding coupled with increases in placental ACTH and corticotrophin‐releasing hormone can lead to increases in free cortisol levels in plasma and the uterus .…”