The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization / A associação incomum entre doença de Graves, urticária crônica idiopática e insuficiência ovariana prematura: relato de caso clínico e tipagem HLA

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA.

A urticária crônica idiopática, caracterizada pelo aparecimento de pápulas espontâneas e persistentes por pelo menos seis semanas, tem sido associada a doenças autoimunes. Apresentamos aqui o caso da associação incomum entre urticária crônica idiopática, doença de Graves e falência ovariana prematura. Foram conduzidos estudos de tipagem HLA. Uma mulher de 36 anos apresentou sinais e sintomas de hipertireoidismo por três meses. No mesmo período, a paciente queixou-se do aparecimento de pápulas urticariformes generalizadas que coçavam intensamente e não eram responsivas ao tratamento com anti-histamínicos. O hipertireoidismo foi confirmado bioquimicamente, e o tratamento com metimazol foi iniciado. Assim que os valores hormonais se normalizaram, observou-se uma melhoria significativa do quadro de urticária. No entanto, a paciente continuou a apresentar amenorreia. A avaliação endocrinológica, com a idade de 38 anos, mostrou falência ovariana prematura. Este é o primeiro caso de associação entre doença de Graves, urticária idiopática crônica e falência ovariana prematura. A base genética dessa associação incomum é representada por combinações específicas de haplótipos HLA.

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization.

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA.

Falla ovárica precoz: [revisión] / Premature ovarian failure: [review]

La falla ovárica precoz es una amenorrea secundaria que se presenta en una mujer antes de los 40 años, que conlleva a hipoestrogenismo, infertilidad y las consecuencias de la menopausia prematura, como osteoporosis, enfermedad cardiovascular, trastornos neurovegetativos, entre otros. Se presenta agotamiento folicular, por dotación insuficiente de folículos o destrucción acelerada de los ovocitos. Las causas son varias, pero predominan las genéticas, autoinmunes y las iatrogénicas. Entre las causas genéticas, son frecuentes las deleciones Xq y Xp, las translocaciones, aberraciones numéricas (47,XXX, 45,X0), premutaciones de X frágil, entre otros. Entre las enfermedades autoinmunes son de importancia la insuficiencia poliglandular tipo I y II. Las iatrogenias pueden ser quirúrgicas en ovarios o trompas y, con la presencia del cáncer de mama en mujeres jóvenes, el tratamiento oncológico puede destruir las células germinales, por lo que hoy se sugiere utilizar técnicas de preservación de la función ovárica y de la fertilidad. En el manejo de la falla ovárica precoz, una vez determinada la causa, se sugiere el uso de terapia estrogénica, aunque no se ha hecho investigación en el tipo de hormona a utilizar, dosis y consecuencias a largo plazo. Tener presente la prevención y manejo de la osteoporosis y la enfermedad cardiovascular. Con relación a la infertilidad, se está realizando criopreservación de embriones y ovocitos para autodonación, así como criopreservación de tejido ovárico cortical para autotrasplante posterior, con éxitos y limitaciones. Los agonistas de GnRH podrían actuar en proteger los ovarios en casos de quimioterapia. Se observa con atención la terapia génica experimental en casos de falla ovárica precoz.

Premature ovarian failure is characterized by secondary amenorrhea affectinga woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberrations (47,XXX, 45,X0), fragil X premutations are frequent. Type I and type II poliglandular insufficiency are important causes among autoimmune diseases. Iatrogenia may occur in surgery of the ovaries and Fallopian tubes and with oncologic treatment that destroys germinal cells in young women with breast cancer. Nowadays use of ovarian function and fertility preservation techniques are suggested. Once the cause is determined estrogens use is recommended although little research on hormone type, dosage and long term consequences has been done. Care must be placed in osteoporosis and cardiovascular disease prevention and treatment. In regards to infertility, there is already experience with embryos and oocytes cryopreservation for autodonation, and cortical ovarian tissue cryopreservation for posterior autotrasplantation, with success as well as limitations. GnRH agonists could protect the ovaries when chemotherapy is used. Attention is placed on experimental gene therapy in cases of premature ovarian failure.

Falla ovárica precoz / Premature ovarian failure

La falla ovárica precoz es una amenorrea secundaria que se presenta en una mujer antes de los 40 años, que conlleva a hipoestrogenismo, infertilidad y las consecuencias de la menopausia prematura, como osteoporosis, enfermedad cardiovascular, trastornos neurovegetativos, entre otros. Se presenta agotamiento folicular, por dotación insuficiente de folículos o destrucción acelerada de los ovocitos. Las causas son varias, pero predominan las genéticas, autoinmunes y las iatrogénicas. Entre las causas genéticas, son frecuentes las deleciones Xq y Xp, las translocaciones, aberraciones numéricas (47,XXX, 45,X0), premutaciones de X frágil, entre otros. Entre las enfermedades autoinmunes son de importancia la insuficiencia poliglandular tipo I y II. Las iatrogenias pueden ser quirúrgicas en ovarios o trompas y, con la presencia del cáncer de mama en mujeres jóvenes, el tratamiento oncológico puede destruir las células germinales, por lo que hoy se sugiere utilizar técnicas de preservación de la función ovárica y de la fertilidad. En el manejo de la falla ovárica precoz, una vez determinada la causa, se sugiere el uso de terapia estrogénica, aunque no se ha hecho investigación en el tipo de hormona a utilizar, dosis y consecuencias a largo plazo. Tener presente la prevención y manejo de la osteoporosis y la enfermedad cardiovascular. Con relación a la infertilidad, se está realizando criopreservación de embriones y ovocitos para autodonación, así como criopreservación de tejido ovárico cortical para autotrasplante posterior, con éxitos y limitaciones. Los agonistas de GnRH podrían actuar en proteger los ovarios en casos de quimioterapia. Se observa con atención la terapia génica experimental en casos de falla ovárica precoz

Premature ovarian failure is characterized by secondary amenorrhea affectinga woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberrations (47,XXX, 45,X0), fragil X premutations are frequent. Type I and type II poliglandular insufficiency are important causes among autoimmune diseases. Iatrogenia may occur in surgery of the ovaries and Fallopian tubes and with oncologic treatment that destroys germinal cells in young women with breast cancer. Nowadays use of ovarian function and fertility preservation techniques are suggested. Once the cause is determined estrogens use is recommended although little research on hormone type, dosage and long term consequences has been done. Care must be placed in osteoporosis and cardiovascular disease prevention and treatment. In regards to infertility, there is already experience with embryos and oocytes cryopreservation for autodonation, and cortical ovarian tissue cryopreservation for posterior autotrasplantation, with success as well as limitations. GnRH agonists could protect the ovaries when chemotherapy is used. Attention is placed on experimental gene therapy in cases of premature ovarian failure

Alpha-enolase: a novel autoantigen in patients with premature ovarian failure.

OBJECTIVE: Although controversial, the presence of circulating antiovarian antibodies (AOA) may be considered a marker of autoimmune premature ovarian failure (POF). The purpose of the present work was to evaluate the presence of AOA in POF patients, and to identify a possible autoantigen in order to develop a reliable diagnostic tool that might help to determine the real prevalence of autoimmune POF. DESIGN: Non-randomised study. Blood sampling for determination of circulating AOA. PATIENTS: One hundred and ten patients with POF and 60 normally menstruating women with no record of autoimmune diseases (controls). MEASUREMENTS: Presence of circulating AOA was assessed by Western-blot, using cytosolic fraction from human ovarian homogenate as antigen. RESULTS: Twenty-one of 110 women with POF presented circulating antibodies directed toward an antigen of approximately 50 kD. Sixty control subjects proved negative. After purification and analysis by mass spectrometry, the antigen was identified as alpha-enolase. CONCLUSION: Determination of the presence of circulating antialpha-enolase antibodies might be instrumental in identifying those patients who may present a putative defect in immunoregulation and therefore a possible autoimmune aetiolgy for POF.

Circulating immunoglobulins that inhibit the binding of follicle-stimulating hormone to its receptor: a putative diagnostic role in resistant ovary syndrome?

OBJECTIVE: To evaluate the presence of circulating immunoglobulins that inhibit FSH binding to its receptor (Ig-FSHR) in patients with premature ovarian failure (POF). DESIGN: Non-randomized study. Blood sampling for determination of circulating immunoglobulins. patients Two hundred and forty-seven patients with POF and 60 normally menstruating women (controls). measurements Circulating immunoglobulins that inhibit FSH binding to its receptor were assessed by FSH-binding inhibition assay. RESULTS: Twenty-three out of 247 women with POF presented circulating immunoglobulins that inhibit FSH binding to its receptor. These patients had been previously diagnosed as ROS. Sixty control subjects proved negative. CONCLUSION: Determination of the presence of circulating immunoglobulins that inhibit FSH binding to its receptor could be instrumental in diagnosing the gonadotropin resistance ovary syndrome.

Anti-corpus luteum antibody: a novel serological marker for ovarian dysfunction in systemic lupus erythematosus?

OBJECTIVE: To investigate the presence of autoantibodies directed to corpus luteum (CoL) in systemic lupus erythematosus (SLE) sera and its correlation with menstrual disturbances. METHODS: We evaluated 87 female patients with SLE, < 40 years old, and 23 women with normal menses as controls. Anti-corpus luteum antibody was detected by immunoblot technique. RESULTS: Reactivity to a bovine CoL antigen was found in 22% of SLE sera. Characterization of the target antigen revealed a 67 kDa glycoprotein highly enriched in corpus luteum, but nearly absent in total ovary extract. Similarly, target antigen was also weakly detectable in tissues that produce or metabolize steroids, such as testis, adrenal cortex, and liver, and it was absent in adrenal medulla or HEp-2 cells. Anti-CoL antibody was easily distinguished from other frequent reactivities of SLE sera, including anti-RNP, anti-Sm, anti-Ro/La, anti-dsDNA, or anticardiolipin. The observation of anti-67 kDa reactivity to human CoL suggests a possible pathogenic role in gonadal dysfunction. Indeed, we observed an inverse association of anti-CoL antibody with the duration of hypergonadotropic amenorrhea. Supporting this hypothesis, in patients with normal or irregular menses, the presence of this antibody was associated with elevated serum level of follicle stimulating hormone, an early and specific sign of ovarian lesion. CONCLUSION: Anti-CoL antibody seems to be associated with early stages of ovarian dysfunction in SLE. Moreover, since similar association of antiovarian antibodies has been observed in an experimental model of autoimmune oophoritis, our findings raise the possibility of autoimmune ovarian lesion in patients with SLE.