Embarazo ectópico roto con fracción beta de la hormona gonadotropina coriónica humana negativa: reporte de caso / Ruptured ectopic pregnancy with negative human chorionic gonadotropin hormone beta fraction: case report

Resumen El embarazo ectópico roto es una emergencia quirúrgica cuyo diagnóstico, gracias a la interrelación de la cuantificación de la fracción beta de la hormona gonadotropina coriónica humana (HCG-β) y los hallazgos ultrasonográficos, se ha hecho más preciso. Sin embargo, el diagnóstico se vuelve difícil cuando clínicamente se encuentran datos sugestivos de embarazo ectópico con una HCG-β negativa. Presentamos el caso de una mujer de 25 años acude a valoración por referir 12,2 semanas de retraso menstrual, asociado a sangrado transvaginal y signos de irritación peritoneal, que cuenta con HCG-β negativa (< 5 mUI/ml). Se realizó un rastreo ultrasonográfico encontrando abundante líquido libre en cavidad, sin evidencia de embarazo intrauterino. Ante la alta sospecha de embarazo ectópico se realizó laparotomía exploradora, encontrando hallazgos sugestivos de embarazo ectópico roto, y se realizó salpingectomía. Finalmente, en el estudio posoperatorio se confirmó por histopatología un embarazo ectópico roto. Existen muy pocos reportes en la literatura internacional de pacientes con características clínicas de embarazo ectópico roto, con HCG-β negativa. Es importante la difusión de este tipo de casos con la finalidad de mejorar los abordajes diagnósticos y no restar importancia ante la sospecha clínica, a pesar de presentar una HCG-β negativa.

Abstract Broken ectopic pregnancy is a surgical emergency that due to the relation between the serum quantification of the of the beta subunit of human chorionic gonadotropin (β-HCG) and the ultrasonographic findings, there have been improvements to reach a precise diagnosis. However, there are very few reported cases in the literature where a broken ectopic pregnancy is described with negative serum results in β-HCG. We present a case report of a 25-year-old patient came to the evaluation for referring 12.2 weeks of menstrual delay, associated with transvaginal bleeding and data of peritoneal irritation, she had a negative β-HCG fraction (< 5 mIU/ml). A scan was performed ultrasound finding abundant free fluid in the cavity, without evidence of intrauterine pregnancy. Given the high suspicion of ectopic pregnancy, an exploratory laparotomy was performed, finding findings suggestive of a ruptured ectopic pregnancy, a salpingectomy was performed. Finally, in the postoperative study, a ruptured ectopic pregnancy was confirmed by histopathology. There are very few reported internationally were found a patient with clinical characteristics of broken ectopic pregnancy, with a β-HCG negative. It is important the scientific diffusion of this type of cases with the purpose of improving the diagnostic approaches and not underestimating importance to the clinical suspicion, despite presenting negative β-HCG results.

Qualitative Determination of Human Chorionic Gonadotropin in Vaginal Washings for the Early Diagnosis of Premature Rupture of Fetal Membranes / Determinação qualitativa de gonadotrofina coriônica humana no lavado vaginal para o diagnóstico precoce de ruptura prematura de membranas fetais

Abstract Purpose This study aimed to evaluate and validate the qualitative human chorionic gonadotropin β subunit (β-hCG) test of the vaginal fluid washings of pregnant women with premature rupture of fetal membranes (PROM). Methods Cross-sectional study of pregnant women between gestational weeks 24 and 39 who underwent consultations in one of our institutions. They were divided into two groups: group A (pregnant women clinically diagnosed with PROM) and group B (pregnant women without loss of amniotic liquid). The patients were subjected to a vaginal fluid washing with 3 mL of saline solution, which was aspirated subsequently with the same syringe. The solution was immediately sent to the laboratory to perform the vaginal β-hCG test with cut-off points of 10 mIU/mL (β-hCG-10) and/or 25 mIU/mL (β-hCG-25). Results The β-hCG-10 test of the vaginal secretion was performed in 128 cases. The chi-squared test with Yates' correction showed a statistically significant difference between the 2 groups (p = 0.0225). The sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy parameters were 77.1%, 43.6%, 52.3%; 70.4%; and 58.6% respectively. The β-hCG-25 test of the vaginal washing was performed in 49 cases. The analysis by Fisher's exact test showed a statistically significant difference between the groups (p = 0.0175). The sensibility, specificity, PPV, NPV, and accuracy parameters were 44.4%, 87.1%, 66.6%; 72.9%; and 71.4% respectively. Conclusions The β-hCG-25 test showed better accuracy for the diagnosis of PROM, and can corroborate the early diagnosis of PROM because it is a simple and quick exam.

Resumo Objetivo Este estudo objetivou validar o exame qualitativo da subunidade β da gonadotrofina coriônica humana (β-hCG) em lavado vaginal de gestantes com ruptura prematura de membranas (RPM) fetais. Métodos Estudo transversal de gestantes com 24 a 39 semanas atendidas em um hospital de Maringá divididas em 2 grupos: grupo A (clinicamente diagnosticadas com RPM) e grupo B (gestantes sem perda de liquido amniótico). As pacientes foram submetidas a lavado vaginal com 3 mL de soro fisiológico, que logo em seguida foi aspirado de volta na mesma seringa e imediatamente enviado ao laboratório para a realização do exame de β-hCG vaginal com pontos de corte de 10 mIU/mL (β-hCG-10) e/ ou 25 mIU/mL (β-hCG-25). Resultados O teste de β-hCG-10 na secreção vaginal foi realizado em 128 casos, e o teste do qui-quadrado com correção de Yates mostrou diferença significante entre os dois grupos (p = 0,0225). Os parâmetros de sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN) e acurácia foram respectivamente 77,1%; 43,6%; 52,3%; 70,4%; e 58,6%. O teste de β-hCG-25 na secreção vaginal foi realizado em 49 casos, e a análise pelo teste exato de Fisher mostrou diferença significativa entre os grupos (p = 0,0175). Os parâmetros de sensibilidade, especificidade, VPP, VPN e acurácia foram respectivamente 44,4%; 87,1%; 66,6%; 72,9%; e 71,4%. Conclusões O β-hCG-25 apresentou melhor acurácia para o diagnóstico de RPM, e pode corroborar o diagnóstico precoce de RPM por se tratar de um exame simples e rápido.

Análise comparativa da acurácia in vitro de testes de detecção de hCG urinário / Comparative analysis of the accuracy of urinary hCG tests in vitro

OBJETIVO: Identificar se os pontos de corte de sensibilidade anunciados por três testes de gravidez na urina são compatíveis com os anunciados pelo fabricante e descrever os seus desempenhos diagnósticos. MÉTODOS: A urina de um voluntário masculino foi usada para diluir β-hCG recombinante em concentrações definidas de 0; 6,25; 12,5; 25; 50; e 100 mUI/mL. As amostras foram codificadas e cegamente analisadas para a positividade em três diferentes lotes dos testes hCG Strip Test Plus®, BioEasy® e Visitect Pregnancy®. O tamanho da amostra foi calculado para um erro alfa de 5 por cento, com um poder de 99 por cento. RESULTADOS: As três marcas apresentaram sensibilidade de 100 por cento na detecção do β-hCG nos três lotes analisados, com 100 por cento de valor preditivo negativo, usando somente controles negativos e amostras com concentrações iguais ou superiores ao limite do teste (n = 180/marca). A acurácia dos testes foi 83 por cento (BioEasy®), 84 por cento (Visitect®) e 91 por cento (Strip Test Plus®). O Strip Test Plus® apresentou o melhor desempenho para a razão de probabilidade positiva (52,5), enquanto que o produto Visitect® teve a melhor razão de probabilidade negativa (zero). CONCLUSÃO: Os três produtos analisados têm a sensibilidade dos pontos de corte anunciados. O produto Strip Test Plus® tem o melhor desempenho para identificar concentrações urinárias de β-hCG > 12,5 mUI/mL, consequentemente, confirmando gravidez, enquanto que o Visitect® tem o melhor desempenho para descartar a presença de β-hCG na urina (probabilidade pós-teste negativo: zero).

OBJECTIVE: To identify whether cutoff for sensitivity advertised by three pregnancy tests in urine are compatible to those reported by the manufacturer and to describe their diagnostic performance. METHODS: The urine of a male volunteer was used to dilute recombinant β-hCG at defined concentrations of 0, 6.25, 12.5, 25, 50, and 100 mIU/mL. The tubes containing each of the concentrations were coded and blindly assessed for positivity in three different lots of hCG tests: Strip Test Plus®, BioEasy®, and Visitect Pregnancy®. The sample size was calculated for an alpha error of 5 percent, with a power of 99 percent. RESULTS: All three brands, in their three lots analyzed, had 100 percent of sensitivity for detecting β-hCG, with 100 percent negative predictive value, using only negative controls and samples with concentrations equal or higher than the test cutoff (n = 180/brand). The accuracy of the tests was 83 percent (BioEasy®), 84 percent(Visitect®) and 91 percent (Strip Test Plus®). Strip Test Plus® had the best positive likelihood ratio (52.5), while Visitect® had the best negative likelihood ratio (zero). CONCLUSION: The three brands have adequate sensitivity for the advertised cutoffs. The Strip Test Plus® test had the best performance to identify urinary concentrations of β-hCG > 12.5 mIU/mL, and consequently, to confirm pregnancy, while Visitect® had the best performance to exclude β-hCG in urine (negative post-test probability: zero).

Dermatomiositis asociada a cáncer testicular mixto en paciente joven: reporte de un caso y revisión de la literatura / dermatomyositis associated with testicular cancer in young patient: a case report and literature review

La dermatomiositis se caracteriza por su compromiso cutáneo y muscular, siendo rara su asociación a cánceres seminomatosos y no seminomatosos en un mismo paciente. Se presenta el caso de un paciente de sexo masculino, de 31años, con tres meses de mialgias y eritema heliotropo en cara acompañado de erupción máculo-papular en áreas fotoexpuestas y yuxta-articulares, asociado a un aumento de volumen testicular izquierdo. La CK, beta-HCG, GOT, GPT, LDH, y alfa-feto proteína estaban elevadas. La biopsia muscular informó miositis intersticial y el estudio histopatológico testicular evidenció un cáncer testicular mixto con seminoma, teratocarcinoma y carcinoma embrionario. No presentó metástasis. Se trató con prednisona y orquiectomía, constatándose disminución progresiva del compromiso cutáneo en los meses siguientes a la cirugía. Los reportes publicados enfatizan medir alfa-feto proteína y beta-HCG, y examinar los testículos en pacientes jóvenes con dermatomiositis. Todos los casos publicados presentaron una evolución rápida. La sobrevida está relacionada con el volumen tumoral y la elevación de marcadores. La resolución del cuadro dermatológico dependerá de la sospecha precoz y el oportuno tratamiento de la patología de base.

Dermatomyositis is characterized for skin and muscular involvement, being rare its association with seminomatous and non seminomatous germ cell cancers, both in the same patient. The clinical case is a male patient 31 years old, with a story of three months of mialgies and heliotrope rash in face, and maculopapular lesions in photoexposed and juxta-articular areas, associated with left testicle increased in size. CK, beta-HCG, GOT, GPT, LDH, and alpha-fetoprotein were elevated. Muscular biopsy informed interstitial myositis; the histopathological study of a testicle tissue biopsy showed mixed testicular cancer with seminoma, teratocarcinoma, and embryonal carcinoma. No metastasis were found. He was treated with prednisone and orchiectomy, watching a progressive decrease of the cutaneous involvement over the next months after surgery. Literature reports remark to measure alpha-fetoprotein and beta-HCG, and to exam both testicles in young patients with dermatomyositis. All published cases had a rapid evolution. Survival is related with tumor size and elevation of serum markers. Resolution of the dermatologic features will depend on clinical suspicious and opportune treatment of the cancer.

[Diagnostic value of prolactin and B-HCG levels of vaginal fluid in diagnosis of premature rupture of membranes]

The aim of this study was diagnosis of premature rupture of membranes in suspected patients by measurement of prolactin and B-hCG levels in vaginal washing in order to reduce perinatal mortality and morbidity. The study included 211 pregnant women who were referred to the emergency of Imam Hossein Hospital at 28-38 weeks of pregnancy for leakage or prenatal care from April, 2007 to April 2008. The expulsion of fluid from the cervix was evaluated and fern and nitrazin tests were done. B-hCG and prolactin levels of vaginal washing fluid were measured. The presence of 2 of 3 parameters of fern test, nitrazin and cervical fluid was defined as absolutely premature rupture of membranes. Man-Withney U-test was used for analysis. The Roc curve was calculated. There were 132 patients in PROM group and 79 patient in the control group. The average age in the PROM and control groups was 26.9 +/- 6.08 and 26.2 +/- 4.84 years, respectively [P=0.074]. Both groups were matched for parity and gravidity. Prolactin levels in PROM group were 2930 +/- 3737 mIU/l versus 23.18 +/- 120mIU/l in the control group [P=0.000]. B-hCG was 439.78 +/- 1867mIU/l in PROM and 17.72 +/- 30mIU/l in control group [p=0.000]. Sensitivity and specificity of prolactin according to cut-off of 16.0mIU/l was 79.41% and 96%, respectively. Sensitivity and specificity for B-hCG with cut-off point of 12.5 was 69.85% and 69.33%, respectively. The measurement of prolactin and B-hCG levels in patients with suspected premature rupture of membranes can help in decision-making and treatment

Comparison of single and multidose of methotrexate in medical treatment of ectopic pregnancy

The purpose of this study was to compare the efficacy and safety of two regimens of methotrexate for medical treatment of ectopic pregnancy. In this prospective randomized clinical trial 100 women clinically suspected to have un ruptured ectopic pregnancy were randomly [One by one] treated with single [50mg/m2] and multi dose [1mg/kg MTX+ 0.1mg/kg folinic acid] Methotrexate [50 cases in each group]. Results of two groups were compared. The overall success rate of treatment was 94%. The use of single dose was associated with a greater chance of response to medical management than multi dose. [97% versus 91%]. The single dose regimen was associated with greater side effects. Women who experienced side effects were more likely to have successful treatment regardless of regimen. Three percent of patients had serum B hCG >10000IU/ml and in 5% of cases fetal heart reported in adnexal mass. Both these groups were much more responsive to single dose treatment. Efficacy of single dose in medical treatment of Ectopic pregnancy is better than multi dose regimen

Epidemiología de embarazo ectópico en el Hospital Central de San Cristóbal “Dr. José María Vargas” 2000-2005 / Epidemiology of ectopic pregnancy at the Hospital Central of San Cristóbal “Dr. José María Vargas” 2000-2005

El Embarazo Ectópico es la implantación del óvulo fecundado en un sitio diferente al endometrio. Se realizó un estudio retrospectivo, descriptivo y longitudinal, para conocer el comportamiento de algunas variables clínico-epidemiológicas relacionadas con el Embarazo Ectópico durante los años 2000-2005 en el Hospital Central de San Cristóbal “Dr. José María Vargas”. El estudio estuvo compuesto por 200 pacientes ingresadas con diagnóstico de Embarazo Ectópico. El antecedente ginecológico encontrado más frecuente fue aborto incompleto (34,5 por ciento) seguido del uso de dispositivos intrauterinos (12 por ciento). La clínica más llamativa fue el dolor abdominal (46 por ciento). El método paraclínico predominante la ecografía (75 por ciento). A la mayoría de las pacientes se les diagnóstico Embarazo Ectópico en su forma accidentada (95,93 por ciento) y localización ampollar (0,29 por ciento).

Comparación de dos métodos para la evaluación de la gonadotrofina coriónica en suero / Comparison of two methods for the evaluation of the chorionic gonadotrophin in serum

El uso de los anticuerpos (Ac) monoclonales específicos dirigidos contra la sub-unidad beta de la gonadotrofina coriónica (hCG-beta) es un prerrequisito para los tests de embarazo con un alto nivel de sensibilidad. Sin embargo, el diseño de inmunoensayos cada vez más sensibles y específicos no se ha visto reflejado en la comparabilidad de los resultados de los distintos métodos. Objetivos: a) Principal: evaluar la concordancia entre dos inmunoensayos (EIA VIDAS Y AxSYM) para la determinación cuantitativa de la hormona gonadotrofina coriónica humana (hCG) sub-unidad beta en suero. b) Secundario: evaluar la correlación e intercambiabilidad de ambos ensayos y c) plantear las dificultades inherentes a su utilización a través de nuestra experiencia. Material y métodos: se recolectaron 106 muestras consecutivas de suero de pacientes que concurrieron al Consultorio de Procreación Responsable y embarazadas de edades gestacionales entre 3 y 12 semanas extraídas para la determinación de hCG o hCG-beta. Las muestras fueron analizadas por dos metodologías de EIA: 1. AxSYM betahCG total (Lab. Abbott). 2. Vidas hCG (Lab. Biomerieux). Conclusiones: a pesar de la complejidad de la bioquímica y la fisiopatología de la hCG, los recientes avances han mejorado la estandarización del ensayo de esta hormona. Para el caso específico del diagnóstico precoz del embarazo, (donde los resultados obtenidos son cercanos a cero o bajos) la concordancia entre los métodos permite el uso indistinto de uno u otro. Para valores por encima de 20.000 mU/ml, los resultados obtenidos están demasiado separados entre sí y, por consiguiente, los métodos no serían intercambiables, lo que implica la necesidad de realizar las mediciones seriadas de una misma paciente con un mismo equipo de diagnóstico.

Adverse pregnancy outcomes after a false-positive second trimester serum screen for Down syndrome in Thai pregnant women.

OBJECTIVE: To determine whether a false-positive second trimester serum screen for Down syndrome in Thai pregnant women is predictive of adverse pregnancy outcomes. MATERIAL AND METHOD: The relationship between adverse pregnancy outcomes in women and a false-positive screening for Down syndrome was investigated in a case-control study. The Double-marker maternal serum screening for Down syndrome (alpha-fetoprotein and free beta-hCG) was performed on Thai pregnant women between 14 and 21 weeks 'gestation at Charoenkrung Pracharuk Hospital from March 1998 to August 2002. The pregnancy outcomes of 165 women having false positive serum screening (risk ratio at least 1.270; study group) were compared to the outcomes of 165 control patients having negative serum screening results (control group). The outcome indices analyzed were preterm delivery, low birth weight newborn, small-for-gestational age newborn, preeclampsia, placenta previa, and fetal death. RESULTS: The incidence of adverse pregnancy outcomes was 18.2% in the study group and 15.2% in the control group (odds ratio = 1.244; 95% confidence interval = 0.696, 2.225; p = 0.46). Women in the study group delivered at a significantly lower birth weight of newborns than women in the control group did (3088.1 +/- 543.9 versus 3229.1 +/- 454.6 g, respectively; p = 0.011). No significant differences in adverse outcomes was discovered after the comparisons between the study group and the control group. preterm delivery 11 of 165 (6.6%) versus 5 of 165 (3%), p = 0.124; low birth weight newborn 11 of 165 (6.6%) versus 6 of 165 (3.6%), p = 0.213; small for gestational age newborn 4 of 165 (2.4%) versus 0 of 165 (0%), p = 0.123; preeclampsia 16 of 165 (9.7%) versus 12 of 165 (7.3%), p = 0.429; placenta previa 4 of 165 (2.4%) versus 4 of 165 (2.4%), p=1; fetal death 1 of 165 (0.6%) versus 0 of 165 (0%), p=1. CONCLUSION: The present findings revealed no apparent increase in the adverse pregnancy outcomes analyzed in women with false positive Down syndrome screening test.

Ultra-sonografia transvaginal com Doppler colorido na conduta expectante da gravidez ectópica íntegra / Color Doppler ultrasound in the expectante management of unruptured ectopic pregnancy

OBJETIVO: Avaliar a importância da ultra-sonografia transvaginal com Doppler colorido com os resultados da conduta expectante na gravidez ectópica íntegra. PACIENTES E MÉTODOS: Vinte pacientes foram incluídas no estudo. Os critérios de inclusäo foram: estabilidade hemodinâmica, massa anexial menor ou igual a 5,0 cm, queda dos títulos de beta-hCG superior a 15 por cento num intervalo de 24 horas, desejo de gravidez futura e consentimento por escrito para participar do estudo. Foram excluídas as pacientes que apresentaram à ultra-sonografia embriäo com batimentos cardíacos. O acompanhamento foi realizado com dosagens seriadas de beta-hCG se negativo. As pacientes foram classificadas em três grupos conforme a US com Doppler colorido: elevado risco (fluxo trofoblástico acometendo mais de 2/3 da massa anexial), médio risco (quando o fluxo trofoblástico compromete de 1/3 a 2/3 do anel tubário) e de baixo risco (fluxos que acometem menos de 1/3 da massa anexial). RESULTADOS: Dos 20 casos submetidos a conduta expectante, todos evoluíram com sucesso, e em nenhuma paciente foi observado Doppler de elevado risco. CONCLUSäO: A ultra-sonografia transvaginal com Doppler colorido de médio e baixo risco säo situaçöes favoráveis para o tratamento clínico, porém estes resultados devem sempre ser analisados em conjunto com a curva de evoluçäo dos títulos de beta-hCG.

Study of the relationship between free B-subunit of human chorionic gonadotropin, estradiol and thyroid function in hyperemsis gravidarum

This study was carried out on 40 pregnant women who presented at less than 16 weeks of gestation. They were divided into 2 groups. Group I included 10 normal pregnant women as controls, group II included 30 pregnant women with hyperemesis gravidarum. Results showed a significant elevation of hCG, free beta-subunit of hCG, total T4, total T3, T3 resin uptake, free T4 index, free T3 index and estradiol was found in group II compared with the controls. While, there was a significant decrease in TSH level in group II compared with group I. It was concluded that, hCG and its free beta-subunit play a role in the etiology of hyperemesis, the associated biochemical hyperthyroidism and the elevated serum estradiol