Myxedema ascites with elevated serum CA 125 concentration

We report a case of myxedema ascites and markedly elevated serum CA 125 concentration. The cause of ascites and elevated tumor markers in hypothyroidism remains unknown. Diagnosis was characterized by no evidence of malignancy seen by transvaginal ultrasonography or abdominal computed tomography and ascites resolution with serum CA 125 normalization after adequate hormonal treatment. Our data suggest that hypothyroidism should be considered in patients with ascites and elevated serum CA 125.     

Myxedema ascites with an extremely elevated CA125 Level: a case report

Carbohydrate antigen 125 (CA125) is a tumor-marker frequently associated with ovarian malignancies; however, benign gynecologic conditions (e.g. ovarian cysts) commonly cause a smaller increase in CA125 levels. This report describes an elderly Japanese woman with high CA125 levels and massive ascites caused by hypothyroidism. A 67-year-old woman presented herself with a weight gain of about 12 kg and abdominal distension. Her serum CA125 level was markedly elevated (822 U/ml) and abdominal CT revealed a right ovarian cyst and massive ascites. Hormonal laboratory data showed severe primary hypothyroidism with a serum TSH of 594 IU/L and a free thyroxin level of 0.05 ng/dl. Ascitic fluid was found to be exudate with a high protein content of 42 g/L. Cytological analysis and FDG-PET showed no evidence of malignancy. The ascites completely disappeared and serum CA125 normalized after adequate hormonal replacement therapy. These data suggest that hypothyroidism should be considered in patients with ascites and elevated serum CA125.     

Transient elevation of serum tumor markers in a patient with hypothyroidism

We report a case of a 66-year-old woman admitted to our hospital for examination and treatment of uterine and rectal prolapse, pleural and pericardial effusion, and ascites. On further examination, she was diagnosed with hypothyroidism. Test results showed markedly elevated concentrations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125). We consequently performed multiple imaging studies, none of which detected a malignancy. Hormonal replacement therapy with levothyroxine was started, and the pleural and pericardial effusion and ascites gradually abated. Concentrations of serum CEA and CA125 also decreased gradually after therapy with levothyroxine. These findings indicate that in patients with hypothyroidism, elevated CEA and CA125 levels do not necessarily indicate malignancy. Conversely, in any patient with elevated serum CEA and/or CA125, hypothyroidism should be considered in the differential diagnosis.     

Markedly elevated CA125 in hepatic cirrhosis: two case illustrations and review of the literature

CA125 is the most widely used tumor marker presently available for use in patients with epithelial ovarian cancer. Although elevated in a high percentage of patients with ovarian cancer, serum CA125 levels have also been detected in patients with numerous benign and malignant nongynecologic disorders, including various diseases of the liver. Despite this well-publicized fact, it has become apparent that the association between CA125 elevation, particularly the degree of elevation, and liver disease may not be as widely recognized as one would suspect. When marked CA125 elevations occur, diagnostic confusion is common. We describe two cases illustrative of this point. Both cases involve middle-aged women who presented with massive ascites and due to markedly elevated serum CA125 levels underwent exploratory laparotomy with hysterectomy and/or bilateral salpingo-oopherectomy before their referral to our center. Because preservation of a woman's reproductive organs is a significant concern, it is imperative that both primary care physicians and specialists are aware of such associations and the proper use of tumor markers.     

Elevation of serum and ascites cancer antigen 125 levels in patients with liver cirrhosis

BACKGROUND AND AIM: Serum cancer antigen (CA) 125 elevation has been reported in patients with liver disease, but it is poorly characterized. The present study aimed to evaluate the range of serum and ascitic CA 125 levels in patients with liver cirrhosis and to explore possible factors associated with CA 125 elevation. METHODS: A total of 70 patients were studied. Group I consisted of 30 patients with liver cirrhosis with or without ascites. Group II consisted of 30 patients with digestive malignant tumors with or without ascites. Group III consisted of 10 patients with benign ascites. The CA 125 levels were measured in the serum of all patients and also simultaneously in the ascitic fluid of 15 patients. RESULTS: Serum CA125 levels in 80% of (24/30) patients from group I were elevated, particularly in those with ascites, irrespective of the etiology of cirrhosis. Serum CA 125 levels were correlated with Child-Pugh scores (r = 0.38), but not significantly (P = 0.06). All patients from group II with ascites and from group III had elevated serum CA 125 levels, but there was no difference in the serum CA 125 levels between patients with ascites from group I (275 +/- 175 U/mL), group II (368 +/- 190 U/mL) or group III (396 +/- 287 U/mL), nor was there a significant difference in ascitic CA 125 levels (P > 0.05). The levels of serum CA 125 (198 +/- 108 U/mL) were lower than, but correlated with that of ascites (460 +/- 234 U/mL, r = 0.58, P = 0.026). The elevation of serum CA 125 accompanied by abnormalities of other tumor markers was more common in malignant ascites than in benign ascites (90% compared with 6%, P < 0.05). CONCLUSION: The elevation of serum CA 125 is common in patients with liver cirrhosis. It is related to the presence of ascites, and possibly to the insufficiency of liver function, but not the etiology of cirrhosis and ascites. Serum CA 125 probably comes from ascites. It usually predicts benign disease if the elevation of serum or ascites CA 125 is not accompanied by the abnormalities of other tumor markers.     

The importance of serum and ascites fluid alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, and CA 15-3 levels in differential diagnosis of ascites etiology

BACKGROUND/AIMS: Clinical usage of tumor markers is being limited due to low specificity. Elevated plasma levels of tumor markers may be seen in diseases other than malignancy, i.e., kidney, liver or circulatory disturbances. METHODOLOGY: In our study, we studied serum and ascites fluid alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, CA 15-3 levels in patients with chronic liver disease, spontaneous bacterial peritonitis, malignancy, tuberculous and congestive heart failure in a total of 76 patients. RESULTS: The sensitivity and specificity for ascites fluid alpha-fetoprotein levels were 28.5% and 100%, for serum alpha-fetoprotein levels 28.5% and 98.1%, for ascites fluid carcinoembryonic antigen levels 38.0% and 98.1%, for serum carcinoembryonic antigen levels 57.1% and 90.0%, for ascites fluid CA 19-9 levels 19.0% and 94.5%, for serum CA 19-9 levels 33.3% and 21.8%, for ascites fluid CA 15-3 levels 28.5% and 92.7%, and for serum CA 15-3 levels 47.6% and 81.8%, respectively. CONCLUSIONS: In conclusion, the sensitivity of serum and ascites fluid tumor markers was found to be low. High specificity may be due to low number of study participants. Serum and ascites fluid tumor markers are not found to be useful in the differential diagnosis of ascites etiology.     

A case of subclinical hypothyroidism developing marked pleural effusions and peripheral edema with elevated vascular endothelial growth factor

A 69-year-old woman was admitted for the treatment of marked pleural effusions and peripheral edema. Analytical studies of the pleural effusion revealed exudates. Culture for bacterial organisms and tuberculosis were negative, and cytology was normal. She had a mediastinal tumor at the age of 61 and regular follow-up showed no evidence of malignancy. She underwent the mediastinal tumor resection, because we thought this was the cause of her symptoms. However, her clinical symptoms persisted after surgery. Next, we noticed subclinical hypothyroidism, in which serum TSH level was elevated with concomitant normal thyroid hormone levels. In addition, serum vascular endothelial growth factor (VEGF) levels, which have been reported to be related to the pathophysiology of the extravascular volume overload, were elevated. Although her TSH level was slightly elevated (15.4 microU/ml), we started thyroid hormone replacement therapy. This therapy gradually ameliorated her clinical manifestation and abnormal laboratory data, including elevated VEGF levels. These observations indicate that even subclinical hypothyroidism may cause severe clinical manifestations. Furthermore, elevated VEGF may be a contributing factor in the pathogenesis of extravascular volume overload in hypothyroid patients.     

肿瘤标志物和血清腹水白蛋白梯度在恶性腹水诊断中的价值

目的 探讨肿瘤标志物和血清腹水白蛋白梯度(SAAG)在恶性腹水诊断中的应用价值.方法 回顾性研究2005年1月至2008年1月收治的114例腹水患者,根据腹水病因分为恶性腹水组39例和良性腹水组105例(其中结核性腹水12例、无菌性肝硬化腹水93例).分析腹水和血清癌胚抗原(CEA)、糖链抗原(cA)19-9、CA125和SAAG在良、恶性腹水中分布的差异,并构建受试者工作(ROC)曲线.结果 在恶性和良性腹水患者中均检出肿瘤标志物.恶性腹水患者的血清CEA和CA19-9、腹水CEA和CA19-9均明显高于良性腹水患者(P<0.05).恶性腹水患者的SAAG明显低于肝硬化腹水患者(P<0.05),而与结核性腹水患者差异无统计学意义(P>0.05).恶性腹水患者的血清和腹水CA125与良性腹水患者差异均无统计学意义(P>0.05).腹水CEA、CA19-9和SAAG的曲线下面积分别为0.79、0.82和0.85;准确度最高的临界值分别是1.45 U/L、19.50 U/L和13.50 g/L,敏感度和特异度分别是66.7%和78.1%、74.4%和84.8%及82.9%和84.6%.联合检测价值最好的组合为SAAG和腹水CA19-9,其敏感度和特异度为61.54%和97.14%.结论 通过ROC曲线寻找最佳的生化指标组合鉴别良、恶性腹水是可行的.     

A case of progressive systemic sclerosis complicated by massive pleural effusion with elevated CA125

A tumor marker, CA125, is known to increase in the serum or other body fluids in various malignancies such as ovarian cancer. Here we present a case of progressive systemic sclerosis (PSS) with massive pleural effusion, in which CA125 in the serum and pleural fluid were elevated. The serum level of CA125 decreased in accordance with the change of the pleural effusion. CA125 level may be an indicator for the activity of serositis in some cases with collagen vascular diseases.     

联合检测血清、腹水肿瘤标志物对良、恶性腹水的鉴别诊断价值

目的 探索肿瘤标志物对良、恶性腹水的鉴别诊断价值.方法 回顾性分析我院2008年12月～2013年2月收治的126例腹水患者的病历资料.根据病因将其分为恶性腹水组（58例）和良性腹水组（肝硬化腹水36例,结核性腹水32例）,比较血清和腹水中甲胎蛋白（AFP）、糖链抗原（CA） 19-9、CA125、CA72-4、癌胚抗原（CEA）在良恶性腹水患者的差异,并对有统计学意义的指标构建受试者工作特征曲线（ROC曲线）图,以期寻找最佳临界值.结果 恶性腹水患者血清及腹水中CA19-9、CA72-4、CEA含量均高于良性腹水患者,差异有统计学意义（P＜0.05）,良、恶性腹水患者腹水及血清中AFP、CA125含量差别均无统计学意义（P＞0.05）.血清CA72-4、腹水CA19-9、CA72-4和CEA的ROC曲线下面积分别为0.701、0.783、0.752和0.848,准确度最高时其临界值分别为4.03 U/ml、19.33 U/ml、1.895 U/ml和1.41 ng/ml,腹水和血清CA19-9、CA72-4、CEA 3项指标联合检测的敏感性均较单项检测指标高,差异有统计学意义（P＜0.05）,敏感性和特异性分别为48.28％、79.41％、71.43％和91.18％.结论 血清和腹水中CA19-9,CA72-4,CEA水平的检测有助于良恶性腹水的鉴别诊断,构建ROC曲线可为恶性腹水的诊断提供最佳生化指标的组合.     

Multiple myeloma presenting as massive ascites]

Ascites is a rare complication of multiple myeloma. We report a case of multiple myeloma with peritoneal involvement. An 80-year-old woman was admitted to our hospital because of massive ascites. Laboratory findings included an Hb of 7.8 g/dl, IgA of 2,160 mg/dl, and CA125 of 942 IU/ml. Immunoelectropheresis analysis detected a monoclonal component of IgA lambda in serum, and of BJP lambda in urine. Bone marrow aspirtion revealed normal cellularity with 32.7% atypical plasma cells. The ascites was characterized by an exudate with numerous atypical plasma cells and elevated IgA and CA125 levels. The IL-6 level was 22 pg/ml and 79 pg/ml in serum and ascites, respectively. A diagnosis of IgA lambda multiple myeloma with peritoneal involvement was made. Chemotherapy consisting of melphalan and prednisolone reduced the serum IgA and CA125 levels markedly, and alleviated the patient's ascites.     

慢性肾脏病患者血清肿瘤标志物的表达及其相关因素分析

目的验证非肿瘤的慢性肾脏病(CKD)患者是否存在血清肿瘤标志物表达的改变并分析影响其改变的相关因素。方法2005年3月至6月对复旦大学附属中山医院的232例肾内科住院患者,分别根据内生肌酐清除率(Ccr)、蛋白尿(Upro)和血清白蛋白(Salb)表达分组,采用单因素分析了解其与血清肿瘤标志物是否相关。利用多元回归分析了解年龄、Ccr、浆膜腔积液、Upro和Salb对血清肿瘤标志物是否存在独立影响。结果CEA、CA199、NSE和SCC表达在不同Ccr组间和CA199、CA125、NSE和SCC表达在不同Salb组间以及CA125、NSE和SCC表达在不同Upro组间,均值差异均有统计学意义。年龄为CEA和PSA表达升高的危险因素(RF);浆膜腔积液为CA125表达升高的RF;Ccr的下降为CA125和SCC升高的RF;Upro的增加为SCC升高的RF;Salb表达的下降分别为CA199、CA125和NSE升高的RF。结论CKD患者中根据血清肿瘤标志物诊断相应肿瘤时,须结合患者年龄及是否合并有大量蛋白尿、低蛋白血症、浆膜腔积液和肾功能不全等因素。     

类似进展期卵巢癌的老年女性结核性腹膜炎临床分析(附三例报告)

目的 探讨绝经后老年女性结核性腹膜炎与晚期卵巢癌的临床特点,并对相关文献进行复习.方法 回顾性分析了2003年1月至2009年9月卫生部北京医院收治的60岁以上老年女性被确诊为结核性腹膜炎的3例患者临床资料.并进行文献复习,探讨结核性腹膜炎的误诊原因及诊断方法.结果 3例患者均表现出类似晚期卵巢癌的临床症状:胸水、腹水、盆腹腔包块及腹胀,进行性消瘦,肿瘤抗原125(CA125)升高.其中2例患者接受了剖腹探查术,均未发现恶性肿瘤.3例患者均接受了抗结核治疗.其中2例患者在治疗中胸水、腹水消失.结论 结核性腹膜炎老年女性患者易被误诊为卵巢癌,从而接受手术治疗.腹腔镜活检是诊断结核性腹膜炎安全有效的方法.剖腹探查是不能行腹腔镜手术患者的另一选择.     

Subclinical hypothyroidism in the elderly: to treat or not to treat?

Patients with subclinical hypothyroidism (SCH) have normal concentrations of thyroid hormone and elevated thyrotropin (TSH) levels. These individuals may experience mild symptoms of hypothyroidism. Such symptoms are nonspecific and also can be associated with aging or nonthyroidal illness. SCH is not uncommon in the elderly, particularly in females with positive thyroid antibodies and in those who have undergone partial thyroidectomy or I131 treatment for Graves' disease. Patients with SCH with markedly increased TSH levels or high-titer thyroid antibodies are at higher risk of progressing to overt hypothyroidism. Management options include observation only, with long-term follow up, or substitution with thyroid hormone. Replacement will prevent the development of overt hypothyroidism when reliable follow-up cannot be assured and may improve subtle, nonspecific symptoms of thyroid hormone deficiency. If a decision in favor of replacement therapy has been made, the dose of thyroid hormone should be increased gradually with the objective of returning the TSH level to normal without inappropriately elevating the serum thyroxine concentration. The patient should be carefully observed to see if hypothyroid symptoms, mental status or cardiac function improve with therapy. Continued administration of thyroid hormone would serve prophylactic purposes even if improvement did not occur.     

慢性肾脏病患者血清肿瘤标志物的表达及其相关因素分析

目的验证非肿瘤的慢性肾脏病（CKD）患者是否存在血清肿瘤标志物表达的改变并分析影响其改变的相关因素。方法2005年3月至6月对复旦大学附属中山医院的232例肾内科住院患者，分别根据内生肌酐清除率（Ccr）、蛋白尿（Upro）和血清白蛋白（Salb）表达分组，采用单因素分析了解其与血清肿瘤标志物是否相关。利用多元回归分析了解年龄、Ccr、浆膜腔积液、Upro和Salb对血清肿瘤标志物是否存在独立影响。结果CEA、CA199、NSE和SCC表达在不同Ccr组间和CA199、CAm、NSE和SCC表达在不同Salb组间以及CA125、NSE和SCC表达在不同Upro组间，均值差异均有统计学意义。年龄为CEA和PSA表达升高的危险因素（RF）；浆膜腔积液为CA125表达升高的RF；Ccr的下降为CA125和SCC升高的RF；Upro的增加为SCC升高的RF；Salb表达的下降分别为CA199、CA125和NSE升高的RF。结论CKD患者中根据血清肿瘤标志物诊断相应肿瘤时，须结合患者年龄及是否合并有大量蛋白尿、低蛋白血症、浆膜腔积液和肾功能不全等因素。     

TSH DEPENDENT ELEVATION OF SERUM THYROGLOBULIN IN REVERSIBLE PRIMARY HYPOTHYROIDISM

Serum levels of thyroglobulin (Tg) were measured using immunoradiometric assay in 18 patients with primary hypothyroidism, whose serum levels of thyroid stimulating hormone (TSH) were higher than 40 mU/l and anti-Tg antibodies were negative. In 12 patients, serum Tg levels were extremely elevated above the upper limit of normal (30 ng/ml) and the levels were more than 800 ng/ml in 10 of them. In all of these 12 patients, thyroid function recovered spontaneously with only iodide restriction and the serum Tg levels declined concomitantly with the decrease in serum TSH concentrations, events suggesting the TSH dependency of this Tg elevation. In the other 6 patients without elevated Tg levels, thyroid function did not recover and replacement therapy with L-thyroxine had to be given. Data from our study show that the TSH dependent Tg secretion is observed in reversible type primary hypothyroidism and that it may proceed vigorously even though thyroid hormone production is subnormal. Measurement of serum Tg may be valuable for predicting the prognosis of primary hypothyroidism.     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

肿瘤标记物在细胞学阴性的恶性腹水中的诊断价值

目的 探讨肿瘤标志物CEA 、CA199、CA125在细胞学阴性的恶性腹水中的诊断价值.方法 检测189例腹水患者的血清和腹水肿瘤标记物,评估肿瘤标记物在细胞学阴性的恶性腹水中的诊断价值.结果 在预设的临界值,细胞学阴性的恶性腹水患者血清和腹水CEA 、CA19-9阳性率明显高于良性腹水组（P ＜0.05）;CA12-5两组比较,差异无统计学意义（P＞0.05）.血清CEA 、CA19-9诊断敏感性较低;腹水CEA 、CA19-9诊断敏感性明显提高,特异性相当.腹水CEA、CA19-9的ROC曲线下面积分别为0.94、0.88.结论 肿瘤标记物CEA、CA19-9有助于细胞学阴性恶性腹水的鉴别诊断,CA12-5无诊断价值;其中腹水CEA诊断价值较高.     

血清CA125在肝硬化患者中的临床意义及相关因素研究

目的 探讨血清CA125在肝硬化患者中的临床意义及相关因素.方法 回顾性分析130例肝硬化患者血清CA125水平,Child-Pugh分级、腹水程度的临床资料,并分析相关数据.结果 血清CA125水平在肝硬化患者中明显升高,其水平与Child-Pugh分级、腹水程度呈正相关性,与肝硬化病因无关.结论 CA125可能成为临床评价肝硬化患者肝功能损害和腹水的参考指标.     

Diagnosis of malignant versus tuberculous ascites using tumor markers and globulin ratios in serum and ascites: A Fisher discriminant model

Background and study aimsThis study was conducted to investigate the significance of tumor and biochemical markers in serum and ascitic fluid in the differential diagnosis of tuberculous and malignant ascites.Patients and methodsBased on findings from natural orifice transluminal endoscopic surgery and postoperative pathology or cytology of 63 patients, they were divided into the malignant group (31 patients) and the tuberculous group (32 patients). Levels of tumor markers, albumin, globulin, and lactate dehydrogenase were measured simultaneously. Data were statistically analyzed, and a Fisher discriminant model was established. The receiver operating characteristic curve was constructed to confirm the discriminant value.ResultsThe levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 19-9 (CA 19-9), and globulin in serum and ascitic fluid were different between the tuberculous and malignant ascites groups (P < .05). The ratios of ascites-to-serum levels of CEA, CA125, and CA 19-9, as well as the ratio of serum-to-ascites of globulin levels, were different between the two groups (P < .05). The Fisher discriminant model was established based on the ascites-to-serum ratios of CEA, CA125, and CA 19-9 levels and the serum-to-ascites ratio of globulin levels. The area under the curve was 0.908, the sensitivity was 0.838 (26/31), and the specificity was 0.875 (28/32).ConclusionA Fisher discriminant model can be established using serum and ascites tumor markers and globulin ratios, which is valuable in the differential diagnosis of tuberculous versus malignant ascites.