Pregnancy-induced Cushing's Syndrome Research Articles

P-03 A report of recurring pregnancy-induced Cushing's Syndrome

Abstract Introduction The incidence of pregnancy-induced Cushing's syndrome (CS) is very low. However, the diagnosis of CS in pregnant patients is very difficult because of an overlapping signs and symptoms. Clinical Case A 20-year-old woman with polycystic ovarian syndrome (PCOS) was successfully treated with clomiphene for infertility and pregnant in September of 2016 for the first time. She experienced out of proportion abdominal obesity, excessive striosis, exacerbation of hirsutism and myasthenia during the first trimester of her pregnancy. Initial diagnosis of ovarian hyperstimulation syndrome (OHSS) was made and due to concomitant intrauterine growth retardation (IUGR), the pregnancy was electively terminated at the 8th week. All associated symptoms spontaneously regressed within 2-3 months after the abortion. The second pregnancy was induced with a pulse treatment of letrozole 5 mg, followed by 3 every other day injections of 100 units recombinant follicle-stimulating hormone. Within the first 4 weeks into the second pregnancy, the patient developed recurrence of OHSS symptoms. In addition to the prior symptoms and progressive proximal myasthenia, the patient developed hypertension, round moon-like face, back hump, and suprasternal fat pad consistent with the typical features of CS. In week 14 of pregnancy, the patient complained from acute-onset bilateral blindness and hypertension (blood pressure of 180/120 mmHg), which soon progressed into loss of consciousness and grand-mal seizure. She was admitted to the intensive care unit (ICU). Admission laboratory testing included those to assess the function of the pituitary-adrenal axis (HPA) due to the presence of symptoms related to CS. Based on available clinical information a diagnosis of hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome was made and emergency termination of pregnancy was carried out at the gestational age of 14 weeks. The patient`s clinical signs such as hypertension and acute blindness were totally subsided soon after the therapeutic abortion. Diagnosis of ACTH independent CS was made based on elevated 8 a.m. serum cortisol level unresponsive to low-dose dexamethasone (45-41 µg/ dL). Conclusion Diagnosis of CS in pregnancy is challenging as the physiological changes during pregnancy may mimic those of CS. Long-term treatment of gestational CS has not been as successful. However, in the case of adrenal hyperplasia, bilateral adrenalectomy offers a certain cure. Our patient had a therapeutic abortion due to severe maternal complications and development of CS during the early gestational age. The patient was reeducated on the subject of contraception and the possibility of adrenalectomy for future pregnancies. Due to the temporal relation between the occurrence of CS after each pregnancy the diagnosis of gestational hypercortisolism was made, and for further pregnancies bilateral adrenalectomy was recommended.

Endogenous Cushing's syndrome during pregnancy.

Endogenous Cushing's syndrome (CS) is rare during pregnancy, probably because hypercortisolism induces anovulation and infertility. To date, slightly above 200 cases have been reported in the literature. The most frequent etiology of CS diagnosed during gestation is from primary adrenal causes, namely adrenal adenomas and an entity called pregnancy-induced CS. The latter can be secondary to the aberrant adrenal expression of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) in the adrenal lesions. Diagnosis of CS during pregnancy is extremely challenging, as a consequence of the physiologic hypercortisolism normally present during pregnancy. Assessment of excess cortisol production tests should be interpreted cautiously using adapted upper limits of normal criteria for pregnant patients and a high index of suspicion is required for diagnosis. Imaging is also limited due to high risk of radiation exposure with computed tomography and teratogenicity with contrast agents. The optimal treatment strategy is surgical resection of adrenal adenoma or pituitary adenoma, ideally before 24 weeks of gestation to reduce the risk of maternal and fetal complications. In mild cases, surgery can be postponed until after delivery and treatment should focus on controlling metabolic complications of hypercortisolism, such as hypertension and dysglycemia. Maternal and fetal outcomes of excess cortisol exposure, except fetal loss, are not readily improved by successful treatment of hypercortisolism.

A report of recurring pregnancy-induced Cushing's syndrome

Introduction: The incidence of pregnancy-induced Cushing's syndrome (CS) is very low. However, the diagnosis of CS in pregnant patients is very difficult because of an overlapping signs and symptoms. Case report: Herein, a 20-year-old pregnant patient was reported that was afflicted by gestational CS during two pregnancies; termination of pregnancy was carried out in both cases. Bilateral adrenal hypertrophy was reported in magnetic resonance imaging. Following therapeutic abortion, signs of chemical evidence of CS was thoroughly regressed within a few months after each abortion without any treatment. Conclusion: Due to the temporal relation between the occurrence of CS after each pregnancy the diagnosis of gestational hypercortisolism was made, and for further pregnancies bilateral adrenalectomy was recommended.

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

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.

Transient pregnancy-induced Cushing's Syndrome with Aberrant Adrenal hCG receptor

Introduction: ACTH-independent Cushing's syndrome (CS) can be associated to the expression of ectopic- or overexpression of eutopic adrenal receptors. These receptors activate adenylate cyclase and subsequently stimulate steroid synthesis, resulting in ACTH-independent CS and growth promotion with hyperplasia or macronodular adrenal changes. Excess cortisol (Co)-secretion better correlates with variations of ligands for the aberrant receptors than the suppressed circulating ACTH.

Recurrent ACTH-independent cushing's syndrome in multiple pregnancies

A 27-year-old woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of each pregnancy. The latest three pregnancies all ended with natural abortion at about three months. It was the fourth time that she was pregnant. By week 18 of gestation, plasma cortisol diurnal rhythm was absent, basal urinary free cortisol was 1650 μg/24 h and ACTH levels were suppressed. The diagnosis of ACTH-independent Cushing's syndrome was established. Cushing's syndrome in the patient resolved within four weeks of abortion. But signs and symptoms of hypercortisolism recurred in the fifth pregnancy and resolved soon after abortion during the follow-up. The mechanisms by which pregnancy-induced Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical cells to a non-ACTH and non-CRH substance produced in excess in pregnancy should be considered.

The medical management of Cushing's syndrome during pregnancy

Cushing's syndrome during pregnancy is a rare metabolic condition that is associated with high maternal and foetal morbidity. Clinical symptoms may mimic those of normal pregnancy. A diagnosis is best made based on clinical presentation, laboratory and imaging findings as well as a high index of suspicion. Medical management with anti-steroidogenic agents such as metyrapone has been shown to be effective, but surgery is usually the recommended treatment option. Its main limitation is optimal timing of the procedure in late first trimester or early second trimester to prevent spontaneous termination of pregnancy. We describe our experience and management of a 39-year-old patient with uncontrolled hypertension at 25 weeks gestation which was later diagnosed as ACTH independent Cushing's syndrome and had a favourable pregnancy outcome. The role of medical therapy and its challenges, as well as its impact on pregnancy outcomes, were explored by a literature search conducted through Pubmed and Medline databases. A total of 12 patients with Cushing's syndrome during pregnancy were reported to have been managed with metyrapone, with ketoconazole being studied to a significant degree in three cases. Of these women, 53% delivered close to term and 20% developed pre-eclampsia. Despite two neonatal deaths and one stillborn reported, medical management appeared effective in controlling hypercortisolemia during pregnancy with strict monitoring of blood pressure and foetal surveillance. It remains the only active management in the setting of pregnancy-induced Cushing's syndrome, and has shown to be a viable option in controlling serum cortisol levels especially as an adjunct to surgery as reflected in four cases. A multidisciplinary approach towards an individualised management process is warranted with medical management to ensure a safe maternal and foetal outcome.

Pregnancy‐induced Cushing’s syndrome in recurrent pregnancies: Case report and literature review

Pregnancy in women with Cushing's syndrome (CS) is uncommon. It is associated with significant maternal and fetal complications. Pregnancy-induced Cushing's syndrome is exceptionally rare with fewer than ten cases reported in the world literature and none in Australia or New Zealand. We describe a woman with possible recurrent pregnancy-induced CS complicating five pregnancies over a 7-year period. We discuss the changes in the hypothalamic-pituitary-adrenal axis during normal pregnancy together with the diagnosis, aetiology and management of CS in pregnancy.

Case Report: Adrenal LH/hCG Receptor Overexpression and Gene Amplification Causing Pregnancy-Induced Cushing’s Syndrome

Transient pregnancy-induced Cushing's syndrome (CS) is extremely rare, with only several cases reported in the literature. Ectopic LH/hCG-receptors (LHCGR) in the adrenal gland have been suggested to be involved in the pathogenesis of this condition. We report the clinical, molecular, and genetic features of a patient with pregnancy-induced CS. A 29-year-old female patient developed CS during multiple pregnancies, leading to repeated miscarriage. Signs and symptoms of hypercortisolism resolved soon after delivery or abortion, only to recur in subsequent pregnancies. In the non-pregnant state, hCG stimulation testing resulted in elevated cortisol levels. Serum cortisol was not suppressible with dexamethasone. The adrenals exhibited bilateral adrenal cortical nodular hyperplasia. Quantitative RT-PCR revealed a 2-fold increase in LHCGR and progesterone receptor mRNA expression and decreased estrogen receptor-beta expression in the patient's adrenal tissue relative to normal adrenals. Higher intensity of immunostaining for LHCGR was observed, particularly within the nodular lesions, compared to controls. Quantitative PCR revealed a LHCGR-to-beta-actin ratio of 1.5 in genomic DNA from adrenal and peripheral leukocytes, suggesting the presence of a germline duplication of the LHCGR gene. LHCGR overexpression resulting from germline gene duplication may be a potential pathogenic mechanism underlying this case of pregnancy-induced CS.

Pregnancy-induced Cushing's syndrome in multiple pregnancies

Pregnancy-induced Cushing's syndrome in multiple pregnancies

297. Pregnancy-induced Cushing's syndrome

297. Pregnancy-induced Cushing's syndrome