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.     

子痫前期合并腹腔间隔室综合征的诊治

世界腹腔间隔室综合征协会将腹腔间隔室综合征(ACS)定义为腹内压持续>20mmHg(伴或不伴腹腔灌注压<60mmHg,1mmHg=0.133kPa),同时合并有新发的器官功能障碍或衰竭。ACS是子痫前期的严重并发症,其临床表现与重度子痫前期有重叠,通过临床症状和体征进行诊断有相当大的难度,其诊断主要依靠腹内压的测量。ACS的治疗应个体化,包括"非手术管理"和外科减压。     

Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka

AIM: To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women with strictly defined disease. METHODS: A phenotyping database of 180 nulliparous women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were recruited for a study into genetics of pre-eclampsia was analyzed. RESULTS: Women who developed pre-eclampsia had significantly higher systolic blood pressure (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered at <34 weeks, at 34-36 weeks, and at term, respectively. 78% required a cesarean section. Complications included SBP > or = 160 mmHg (75.5%); DBP > or = 110 mmHg (83.8%); proteinuria > or =3 + (150 mg/dL) in the urine protein heat coagulation test (87%); renal failure requiring dialysis (2%); platelet counts <100 x 10(9)/L (13%); > or =70 U/L in aspartate and/or alanine aminotransaminase (15%); placental abruption (4%); eclampsia (9%); and one maternal death. Maternal complications indicative of severe disease, apart from the incidence of SBP > or = 160 mmHg and DBP > or = 110 mmHg, were not significantly different in early and late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48% of babies were small for gestational age. Only 80 of 135 babies of women with pre-eclampsia whose condition could be confirmed at 6 weeks post-partum were alive. CONCLUSIONS: Pre-eclampsia in Sinhalese women is associated with severe maternal morbidity and fetal morbidity and mortality, suggesting that modification of the Western diagnostic criteria and/or guidelines for medical care may be necessary. There is an urgent need to improve neonatal intensive care services in Sri Lanka.     

Does endothelial cell activation occur with intrauterine growth restriction?

It is possible that in fetal growth restriction without pre-eclampsia endothelial cell activation does not occur. This might be either because there is no release of 'factor X' or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre-eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre-eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E-selectin) and three cytokines [tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and -8 (IL-8)]. The levels of the markers of endothelial cell activation were raised in both pre-eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF-α, IL-6 and IL-8 were significantly raised in pregnancies complicated by pre-eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre-eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre-eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre-eclampsia.     

辅助生殖妊娠并发子痫前期相关因素研究进展

子痫前期是严重影响母婴健康、造成母婴死亡的主要原因之一。辅助生殖技术(assisted reproductive technology,ART)是子痫前期的危险因素。随着不孕症患者逐年增多,通过辅助生殖治疗获得妊娠的比例不断增加,子痫前期发生率也随之增加。近年国内外研究发现子宫内膜异位症、多囊卵巢综合征、肥胖、多胚胎移植、冷冻胚胎移植、卵母细胞捐赠妊娠、着床期雌二醇峰值升高以及孕早期低浓度的人绒毛膜促性腺激素是子痫前期的危险因素,而孕激素是子痫前期的保护因素。这些因素单一或联合作用于子痫前期的发生发展。早期识别子痫前期危险因素、早期预防和早期干预是降低子痫前期发病率、改善母婴不良结局的关键。综述辅助生殖妊娠并发子痫前期的相关因素,为今后的辅助生殖妊娠围生期保健提供重要参考依据。     

5,10 methylenetetrahydrofolate reductase polymorphism in black South African women with pre-eclampsia

The polymorphic C677T mutation in the gene encoding 5,10 methylenetetrahydrofolate reductase has been shown to be a risk factor for pre-eclampsia in Japanese and European women when inherited as a homozygous trait. We attempted to verify these findings in a black African population with a high incidence of pre-eclampsia. No difference in frequency of the T-allele was observed in 105 women with pre-eclampsia, compared with 110 healthy pregnant normotensive women. Only one woman with pre-eclampsia was TT homozygous, suggesting that methylenetetrahydrofolate reductase polymorphism is not an important factor in the pathogenesis of pre-eclampsia in black South African women.     

5,10 methylenetetrahydrofolate reductase polymorphism in black South African women with pre-eclampsia.

The polymorphic C677T mutation in the gene encoding 5,10 methylenetetrahydrofolate reductase has been shown to be a risk factor for pre-eclampsia in Japanese and European women when inherited as a homozygous trait. We attempted to verify these findings in a black African population with a high incidence of pre-eclampsia. No difference in frequency of the T-allele was observed in 105 women with pre-eclampsia, compared with 110 healthy pregnant normotensive women. Only one woman with pre-eclampsia was TT homozygous, suggesting that methylenetetrahydrofolate reductase polymorphism is not an important factor in the pathogenesis of pre-eclampsia in black South African women.     

Blood coagulation profile in Indian patients with pre-eclampsia and eclampsia.

Twelve Indian patients with pre-eclampsia, 15 with eclampsia and 15 with normal pregnancy in the third trimester were investigated. A systemic bleeding diathesis was encountered in two patients with eclampsia and in none with pre-eclampsia; two patients with pre-eclampsia, however, had excessive uterine haemorrhage. Coagulation studies showed statistically significant prolongation of thrombin time, elevation of serum fibrinogen degradation products (FDP) and hypofibrinogenaemia in patients with pre-eclampsia as well as eclampsia. In patients with eclampsia, significant thrombocytopenia also occurred. Euglobulin lysis time showed no significant change in patients with pre-eclampsia and eclampsia. There was no significant difference in the coagulation profile between patients with eclampsia and pre-eclampsia, except for more hypofibrinogenaemia in the former. The laboratory findings suggest the occurrence of intravascular coagulation in patients with pre-eclampsia and eclampsia.     

Vitamin C as an antioxidant supplement in women's health: a myth in need of urgent burial

Epidemiological data suggest that diets rich in antioxidants protect against diseases associated with free radical damage, including cancer, cardiovascular disease and diabetes. Early observations also suggested that vitamin supplements with antioxidant properties, like vitamins C and E, could also prevent or ameliorate pre-eclampsia, but most large randomized clinical trials have failed to show any benefit. Vitamin C given orally, even at high doses, does not achieve sustained serum levels that might be required for effective antioxidant activity. This may explain the failure of the numerous clinical trials involving its use in pre-eclampsia, cancers, cardiovascular diseases, etc. Vitamin C supplementation to stave off pre-eclampsia, cancer and other diseases is a ‘nutraceutical’ industry-driven myth which should be abandoned. We do not dispute a role for oxidative stress in the pathophysiology of pre-eclampsia, nor the possibility of amelioration of the disease by an anti-oxidant given at the right time and in the correct dosage. We simply wish to make a case that the massive and expensive clinical trials of vitamins C and E should cease until further rigorous scientific research is undertaken.     

Improving placental blood flow in pre-eclampsia with prostaglandin A1.

Prostaglandin A1 is a potent hypotensive, peripheral vasodilator, a weak oxytocic, antiplatelet aggregator. It improves the renal hemodynamics. Its effect on placental circulation was evaluated (expressed as systolic/diastolic ratio and umbilical artery resistance index) in 20 women with severe pre-eclampsia and 10 normotensive pregnant women, by using the Doppler technique. Moreover, another 10 women with severe pre-eclampsia received dextrose 5% as a placebo for comparative purposes. Significant improvements in both parameters studied were observed in the women with severe pre-eclampsia. The beneficial changes differed significantly from the recorded values when using dextrose in pre-eclampsia or prostaglandin A1 in normotensive subjects. Such promising data add another important perspective to prostaglandin A1 in severe pre-eclampsia and may open up new avenues for its use in other situations with compromised placental flow.     

Hemodynamic and hemorheological profiles in women with proteinuric hypertension of pregnancy and in pregnant controls

Summary We obtained blood samples from 52 patients with pre-eclampsia and from 40 pregnant controls for measurement of plasma urate levels, hematocrit, white cell count and various hemorheoligical parameters (see Table 3). We also used impedance cardiography to measure cardiac output in both groups and from the results derived values for total peripheral resistance and oxygen transport. Central venous pressure was measured with a superior vena cava catheter in patients with pre-eclampsia but not in controls. Women with pre-eclampsia had significantly lower cardiac output and central venous pressure when compared with a control group. A modest correlation was observed between central venous pressure and cardiac output. The majority of pre-eclamptic patients had significantly raised hematocrit, leucocyte count, uric acid and red cell aggregation. Red cell deformability was significantly decreased in patients with pre-eclampsia. Most patients with severe pre-eclampsia (BP diast. >100 mmHg) had a low Antithrombin III and colloid osmotic pressure level. The leucocyte count was raised when compared with the women with moderate pre-eclampsia. Oxygen delivery was reduced in patients with pre-eclampsia because of impaired rheological properties of their blood.     

Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes

Objectiveto explore knowledge of pre-eclampsia and opinions on potential screening tests for pre-eclampsia in women with type 1 diabetes.Designa qualitative study using semi-structured interviews of women planning a pregnancy, currently pregnant or post-partum with experience of pre-eclampsia.Setting, Participants and Methodseleven women with type 1 diabetes were recruited from a pre-pregnancy planning clinic or antenatal clinic. Semi-structured interviews were conducted with the women, asking a series of open-ended questions about their current knowledge of pre-eclampsia and their views on screening for pre-eclampsia. Data analysis was conducted using inductive thematic analysis.Findingsfour main themes were identified: Information, sources of stress, awareness and acceptability of screening. Generally, women's knowledge of pre-eclampsia was limited. Most did not appear to be aware of their increased risk of developing the disease. Similarly, the majority of women were unaware as to why their blood pressure and urine were checked regularly. The introduction of a screening test for pre-eclampsia was favoured, with only a small number of women raising concerns related to the screening tests.Conclusionshealth care professionals need to raise awareness of pre-eclampsia in this high risk group. The introduction of a screening test for pre-eclampsia appears to be acceptable in this population, however, further research is required to validate these findings and also to explore the views of women in other high risk groups.     

Risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism.

OBJECTIVES: To investigate the incidence and risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism. METHODS: A retrospective cohort study was performed on 1499 pregnant women with abnormal glucose metabolism at Peking University First Hospital from January 1995 to December 2004. RESULTS: The overall prevalence of pre-eclampsia in women with abnormal glucose metabolism was 9.4% (141/1499). The prevalence of pre-eclampsia in women diagnosed with diabetes mellitus prior to pregnancy was higher than that of gestational diabetes mellitus and gestational impaired glucose tolerance patients (29.1% vs 8.7% and 7.8%, P<0.01). Pre-pregnancy body mass index was significantly higher in women with pre-eclampsia than in those without. A higher rate of pre-eclampsia was found in women with chronic hypertension and those with poor glucose control. The independent risk factors for pre-eclampsia were chronic hypertension and elevated pre-pregnancy body mass index. CONCLUSIONS: The type of diabetes, chronic hypertension, and elevated pre-pregnancy body mass index are high risk factors for pre-eclampsia in pregnant women with abnormal glucose metabolism.     

Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: comparison with pre-eclampsia

Objective 1.To evaluate the activation profile of the endothelium in pregnancies complicated by small for gestational age fetuses compared with pre-eclampsia and normal pregnancy, by measuring the plasma levels of soluble adhesion molecules soluble E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1. 2. To determine whether soluble adhesion molecules were related to the severity of small for gestational age fetuses and pre-eclampsia.
Design Observational study.
Participants Sixteen women with small for gestational age fetuses; 15 women with pre-eclampsia and 15 healthy primigravidae were recruited as controls.
Methods Plasma levels of soluble E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 were measured by ELISA.
Results Compared with the healthy controls, soluble E-selectin was significantly increased in both small for gestational age fetuses and pre-eclampsia, whereas intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 were increased only in pre-eclampsia. In the small for gestational age fetuses group, soluble E-selectin correlated inversely with the ratio between birthweight and the expected normal birthweight (r=-0.4, P =0.007). In the pre-eclampsia group, a significant correlation was observed between vascular cell adhesion molecule-1 and blood pressure (r=0.54, P =0.039).
Conclusions Endothelial activation, reflected by raised levels of soluble E-selectin, is a feature of small for gestational age fetuses and is correlated with the severity of the disease. Differences in the profile of soluble cell adhesion molecules suggest variations in the degrees of endothelial activation between pre-eclampsia and small for gestational age fetuses.     

Metastin levels in pregnancies complicated by pre-eclampsia and their relation with disease severity

Aims: To evaluate the role of metastin levels in the pathophysiology of pre-eclampsia and to determine whether there is a relationship between the severity of the disease and Doppler velocimetry measurements. Methods: This cross-sectional study included 89 pregnant women (50 healthy normotensive pregnant women, 15 patients with mild pre-eclampsia, and 24 patients with severe pre-eclampsia) at the third trimester of pregnancy. The maternal levels of plasma metastin were determined by enzyme-linked immunosorbent assay. The umbilical artery and uterine artery blood flow velocities were measured by transabdominal color and pulsed Doppler ultrasound. Results: Plasma metastin levels were lower in patients with pre-eclampsia than those in the normotensive pregnant women. Four patients with mild pre-eclampsia and seven patients with severe pre-eclampsia had abnormal Doppler velocimetry findings. Metastin levels of pre-eclamptic patients with abnormal Doppler velocimetry findings were significantly lower than those in patients with normal Doppler velocimetry findings. Plasma metastin levels negatively correlated with proteinuria in 24 hours and with mean arterial pressure in the cases of pre-eclampsia. Conclusions: The findings suggest that decreased maternal concentrations of plasma metastin may be involved in the pathogenesis of pre-eclampsia. Plasma metastin levels may be useful in the assessment of the severity of pre-eclampsia. However, further trials are needed to clarify the role of metastin in pre-eclampsia.     

Impaired antioxidant activity in women with pre-eclampsia.

OBJECTIVE: To investigate antioxidant activity of sera and the plasma blood levels of two potent antioxidant in women with pre-eclampsia and normotensive pregnancies. STUDY DESIGN: The antioxidant activity of sera and the blood levels of ascorbic acid and alpha-tocopherol were assayed in women with normal pregnancies (n = 33), mild pre-eclampsia (n = 8), and severe pre-eclampsia (n = 16) between 20 and 40 weeks' gestation. Ascorbic acid and alpha-tocopherol concentrations were analyzed by high-performance liquid chromatography. Antioxidant activity of sera was measured as the percent inhibition of spontaneous autoxidation of a standard brain homogenate. RESULTS: Plasma levels of ascorbic acid in women with mild and severe pre-eclampsia were significantly lower than normal pregnancies (P < 0.05). Sera alpha-tocopherol levels were significantly decreased only in severe pre-eclampsia (P < 0.05). Sera antioxidant activity were significantly decreased in mild (73%) and severe (51%) pre-eclampsia compared with normal (86%) pregnancies (P = 0.02, P = 0.000, respectively). CONCLUSIONS: In women with pre-eclampsia, sera antioxidant activity and antioxidant level of plasma are decreased when compared with normotensive pregnancies. Impaired antioxidant activity and the reduction of antioxidant levels which increase the level of lipid peroxidation products may cause peroxidative damage of vascular endothelium and result in clinical symptoms of pre-eclampsia.     

子痫前期患者内皮素受体A基因G-231A多态性的研究

目的:探讨内皮素受体A(EDNRA)G-231A基因多态性与子痫前期有无关联。方法:用聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP),对成都地区220例子痫前期患者(其中轻度71例,重度149例)和270例健康对照组孕妇EDNRA基因G-231A多态性进行检测。结果:子痫前期组和正常孕妇组EDNRA基因G-231A位点A等位基因频率分别为35.9%、31.3%,两组之间等位基因频率分布无显著差异(P>0.05);重度子痫前期组与轻度子痫前期组比较,A等位基因频率分别为36.3%、35.2%,二者无显著差异(P>0.05)。此外,子痫前期组和正常孕妇组不同基因携带者收缩压和舒张压水平无统计学差异(P>0.05)。结论:本研究未发现EDNRA基因G-231A多态性与子痫前期发病有关联。     

Plasma 5'-nucleotidase activities and uric acid levels in women with pre-eclampsia

The present study investigated plasma activity of 5'-nucleotidase, a key enzyme in the production of adenosine, in pre-eclampsia, and evaluated the relationship between changes in 5'-nucleotidase activity, and levels of uric acid, endproduct of the purine metabolism, and the severity of pre-eclampsia. We measured plasma 5'-nucleotidase activities and uric acid levels in women with 18 normal pregnancies, mild and severe pre-eclampsia. In mild and severe pre-eclampsia, plasma 5'-nucleotidase activities and uric acid levels were significantly increased compared with those in normal pregnancy (p < 0.05). Plasma 5'-nucleotidase activity increased according to increases in uric acid levels and the severity of pre-eclampsia. These results suggest that increased plasma 5'-nucleotidase activity may, at least in part, be related to changes in purine metabolism in pre-eclampsia.     

Dyslipidemia in early second trimester is mainly a feature of women with early onset pre-eclampsia

Objective To investigate whether hypertriglyceridemic dyslipidemia is a risk factor for either early or late onset pre-eclampsia.
Design Prospective cohort study and nested case–control study.
Setting Aker Hospital: a university hospital with all levels of obstetric care.
Participants 2157 Caucasian pregnant women.
Methods Blood samples were obtained from non-fasting subjects at 18 weeks of gestation. All samples were analysed for triglycerides, total-cholesterol, high density lipoproteins cholesterol and non-high density lipoproteins cholesterol. ApoB-100 were analysed in pre-eclamptic women and in 3:1 matched controls. The cohort data were analysed by multiple logistic regression and the case–control data by conditional logistic regression.
Main outcome measures Adjusted odds ratios of early and late onset pre-eclampsia according to early second trimester serum concentration levels of lipids and ApoB-100.
Results Eighteen women developed early onset pre-eclampsia and 53 women developed late onset pre-eclampsia. In the cohort model, women with triglycerides above 2.4mmol/L had increased risk (OR 5.1; 95% CI 1.1–23.1) of early onset pre-eclampsia compared with those with triglycerides levels ≤ 1.5mmol/L. For women with high triglycerides: non-high density lipoproteins cholesterol ratios (>90 centile) the OR (95% CI) for early onset pre-eclampsia was 7.1 (2.3–22.0) compared with those with low ratios (≤ 50 centile). Similar associations were found in the case control model. We found no associations between plasma lipids and risk of late onset pre-eclampsia.
Conclusions Hypertriglyceridemic dyslipidemia before 20 weeks of gestation is associated with the risk of developing early but not late onset pre-eclampsia, giving support to the contention that these two variants of the disease are at least partly pathogenically different.     

Significantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia.

Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease.