Cushing's Syndrome In Pregnancy Research Articles

Diverse presentations of Cushing's syndrome during pregnancy - A case series.

Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

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.

Cushing Syndrome in Pregnancy: A Case Presentation and Review of Literature

: The Cushing syndrome typically presents with abdominal obesity, wide purple striae, glucose intolerance, hypertension, easy bruising, and muscle weakness, a rare disorder interfering with ovulation, making the combination of Cushing syndrome and pregnancy less common. Nevertheless, Cushing syndrome has been reported in pregnancy. Here we report another case of pregnancy with Cushing syndrome, which presents merely with obesity, hypertension, and glucose intolerance, using a literature review at the end.

ODP621 Hypertension with Hypokalemia in Pregnancy? Think "Cushing's Syndrome"

Abstract Introduction Pregnancy is uncommon in women with Cushing's syndrome (CS) as hypercortisolism and hyperandrogenism suppress gonadotropins leading to anovulatory cycles. Such pregnancies carry a higher rate of fetal morbidity and mortality. Therefore, it is of paramount importance to diagnose and treat CS in pregnancy. The diagnosis of CS in pregnancy is challenging due to the physiologic changes of the hypothalamic-pituitary-adrenal axis during pregnancy. We describe a case of CS in pregnancy that was a successfully treated with surgery. Case description An asymptomatic 39-year-old pregnant female patient with gestational hypertension was admitted to the hospital after she was found to have uncontrolled hypertension (while on 3 anti-hypertensive medications) and severe hypokalemia with potassium level of 2.8 mEq/L. She was 14 weeks pregnant at the time. She has a family history of primary aldosteronism in her father successfully treated with adrenalectomy at the age of 60. Her work up included blood work (done at 13: 42) which showed sodium level of 146 mEq/L, plasma aldosterone concentration of <1 ng/dL, plasma renin activity of 1.0 ng/mL/hr, total testosterone of 46 ng/dL, DHEA-S of 31 mcg/dL, plasma metanephrines <50 pg/mL, 24-hour urine metanephrines 70 ug, 24-hour urine normetanephrines 164 ug/24 hrs, ACTH 5 pg/mL, and cortisol 28.2 mcg/dl. MRI abdomen without contrast showed a 3.5×3.0×4.2 cm left adrenal nodule consistent with adenoma. Patient was diagnosed with non-ACTH dependent subclinical CS based on her elevated cortisol and low ACTH levels. She underwent left laparoscopic adrenalectomy and was discharged on oral hydrocortisone. Pathology showed adrenal cortical adenoma. Her blood pressure normalized shortly after surgery and her anti-hypertensive medications were stopped. Discussion Pregnancy is associated with multiple changes in the hypothalamic-pituitary-adrenal axis making diagnosis of CS in pregnancy challenging. Those changes include increased Cortisol binding globulin production leading to increased serum cortisol level and lack of suppression with Dexamethasone beside placental production of CRH and ACTH, all leading to increased salivary and urinary free cortisol levels, as well. This case of hypertension and hypokalemia in pregnancy presented a diagnostic dilemma. Furthermore, the clinical presentation was confounded by a family history of primary aldosteronism. However, the low serum ACTH level highly suggested the diagnosis of CS. Unfortunately, there are no pregnancy-specific guidelines for the diagnosis of CS. The dexamethasone suppression test is not recommended as it often yields false-positive results. The use of urinary free cortisol and late-night salivary cortisol is recommended, and the diagnosis is established when results are three to four times the upper limit of normal. ACTH levels <10 pg/ml are suggestive of adrenal CS. MRI without contrast can be used for imaging. To date, there have been over 260 reported cases of CS in pregnancy with more than half of them being. Presentation: No date and time listed

Cushing Syndrome Secondary to Ectopic ACTH Production in Pregnancy: A Case Report

Ectopic adrenocorticotropic hormone production is an extremely rare cause of Cushing syndrome in pregnancy and is associated with significant morbidity. A 37-year-old multiparous woman at 32 weeks’ gestation presented with hypertension, anasarca, hypokalemia, and fetal distress requiring an urgent cesarean section. Her adrenocorticotropic hormone and cortisol levels were elevated, and high-dose dexamethasone failed to suppress them, suggesting ectopic adrenocorticotropic hormone production. Multimodality imaging did not identify a source, and she had urgent bilateral adrenalectomy for refractory severe hypercortisolism. Ectopic Cushing syndrome in pregnancy requires a high index of suspicion for diagnostic testing and prompt treatment to minimize maternal and fetal complications.

Abstract #1143379: Hypertension with Hypokalemia in Pregnancy? Think “Cushing’s Syndrome”

Pregnancy is uncommon in women with Cushing's syndrome (CS) as hypercortisolism and hyperandrogenism suppress gonadotropins leading to anovulatory cycles. Such pregnancies carry higher rates of fetal morbidity and mortality. It is important to diagnose and treat CS in pregnancy.

Cushing syndrome in pregnancy, diagnosed after delivery

Cushing syndrome (CS) is rare in pregnancy, and few cases have been reported to date. Women with untreated CS rarely become pregnant because of the ovulatory dysfunction induced by hypercortisolism. It is difficult to diagnose CS in pregnancy because of its very low incidence, the overlap between the clinical signs of hypercortisolism and the physiological changes that occur during pregnancy and the changes in hypothalamus-pituitary-adrenal axis activity that occur during pregnancy and limit the value of standard diagnostic testing. However, CS in pregnancy is associated with poor maternal and fetal outcomes; therefore, its early diagnosis and treatment are important. Here, we report two patients with CS that was not diagnosed during pregnancy, in whom maternal and fetal morbidity developed because of hypercortisolism.

Approach to Cushing's syndrome in pregnancy: two cases of Cushing's syndrome in pregnancy and a review of the literature.

Cushing's syndrome (CS) rarely occurs during pregnancy. The primary aim of this article is to propose a therapeutic approach to CS in pregnancy. Here, we present two cases of CS in pregnancy and a literature review. This article proposes the early diagnostic points, especially the clinical approach to this medical condition, mainly for pregnant women without a previous diagnosis of CS. More importantly, we present therapeutic strategies for CS during pregnancy, especially glucocorticoid replacement for perioperative, postoperative, and perinatal periods in pregnant women with CS in order to minimize complications for both mother and fetus. At the same time, we also assess the anxiety status of patients. This article summarizes the approach to CS in pregnancy, not only with a physiological assessment but with a psychological assessment as well.

Cushing's disease: major difficulties in diagnosis and management during pregnancy

Pregnancy in women with a diagnosis of Cushing' syndrome (CS) is an extremely rare event and its diagnosis and treatment are a real medical challenge. During pregnancy, the hypothalamus-pituitary-adrenal axis undergoes major changes leading to a significant increase in plasma cortisol levels throughout gestation. The difficulties in diagnosis are related to the resemblance of symptoms of CS and those of pregnancy, and to the complex interpretation of the screening tests. Moreover, the diagnostic work up in the postnatal period may be difficult in the first weeks postpartum. Importantly, the etiology of CS in pregnancy differs from non-pregnant status. In pregnancy, the adrenal origin is the most frequent in up to 60% of the cases, in contrast to ACTH-secreting corticotroph adenomas of the pituitary gland, which account for 70% of the cases outside pregnancy. Nevertheless, maternal and fetal outcomes are severely affected in the context of CS whichever the etiology is, with high rates of maternal and fetal morbimortality, and with a rate of overall fetal loss of about 25% of the pregnancies. There is no consensus as to the most effective treatment in these circumstances in terms of improving maternal and fetal outcomes, as there are no studies comparing the different modalities of treatment for CS in pregnancy. However, evidence suggests that patients receiving treatment during pregnancy achieve better fetal outcomes than those who do not receive treatment. We aim to summarize in this review the major diagnostic and management difficulties during pregnancy.

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.

Cushing disease with pregnancy

Pregnancy occurs rarely in patients with Cushing syndrome (CS) due to hypercortisolism. So far, about 150 cases of CS in pregnancy have been reported in the literature. We describe a 22-year-old female who presented in pregnancy with clinical features of CS. She delivered at 34 weeks of gestation and baby had transient adrenal insufficiency in the neonatal period. Mother underwent transsphenoidal surgery 1 year postpartum and on follow up she is under remission. Neonatal hypoadrenalism should be anticipated in maternal CS.

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.

Cushing's syndrome in pregnancy with a severe maternal complication: A case report

Cushing's syndrome (CS) in pregnancy may be confused with a complication of pregnancy, such as pre-eclampsia or gestational diabetes. We managed a case of CS in pregnancy that was considered to be severe pre-eclampsia due to uncontrolled hypertension. The fetus was delivered via emergency cesarean section at 31 weeks' gestation because of severe pre-eclampsia and pulmonary edema. The parturient was admitted to the intensive care unit for severe maternal complications, including pulmonary hemorrhage, acute renal failure, disseminated intravascular coagulopathy, and congestive heart failure. A spine magnetic resonance image and 99m-technetium whole-body scan obtained postpartum showed multiple thoracolumbar spine compression fractures (Deleted; t-2,5,8,10,11, and -12; and L-1,2,3,4, and -5), multiple rib fractures, and a left iliac bone fracture due to osteoporosis. As a result of diagnosing CS after delivery, an adrenal cortical adenoma of the right adrenal gland was demonstrated and a laparoscopic adrenalectomy was successfully performed.

Cushing's syndrome in pregnancy: an overview

Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.

The Hypothalamic-Pituitary-Adrenal Axis in Pregnancy: Challenges in Disease Detection and Treatment

Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed. CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing's disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used. Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed.

Cushing’s Syndrome during Pregnancy: Personal Experience and Review of the Literature

Cushing's syndrome (CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing's syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing's syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy.

Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathy

Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur.

Cushing Syndrome in Pregnancy Secondary to an Adrenal Cortical Adenoma

Cushing syndrome in pregnancy is rare. This is explained by the syndrome's association with amenorrhoea, oligomenorrhoea, infertility and abortions. Cushing syndrome commonly presents with hypertension, weight gain, diabetes, striae or truncal obesity, all of which can be consistent with pregnancy in women without Cushing syndrome. We describe a case of Cushing syndrome in pregnancy secondary to an adrenal cortical tumour which was discovered after an abnormal glucose tolerance test. The woman developed classical features of Cushing syndrome including gestational diabetes and hypertension and was managed successfully to term after a unilateral adrenalectomy at 23 weeks. The case is reported not only because of its rarity but also because the diagnosis was made after a routine screening test for gestational diabetes. Early diagnosis and treatment of adrenal adenoma causing Cushing syndrome in pregnancy reduces maternal and fetal morbidity and mortality.