Clinical And Molecular Spectrum Of Patients With 17β-hydroxysteroid Dehydrogenase Type 3 (17-β-hsd3) Deficiency [espectro Clínico E Molecular De Pacientes Com Deficiência De 17β-hidroxiesteroide Desidrogenase Tipo 2 (17-β-hsd3)]

The enzyme 17β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) catalyzes the conversion of androstenedione to testosterone in the testes, and its deficiency is a rare disorder of sex development in 46,XY individuals. It can lead to a wide range of phenotypic features, with variable hormonal profiles. We report four patients with the 46,XY karyotype and 17-β-HSD3 deficiency, showing different degrees of genital ambiguity, increased androstenedione and decreased testosterone levels, and testosterone to androstenedione ratio G novel mutation, and c.277+4A>T mutation, both located within the intron 3 splice donor site of the HSD17B3 gene, were identified in case 3. In addition, homozygosis for the missense p.Ala203Val, p.Gly289Ser, p.Arg80Gln mutations were found upon HSD17B3 gene sequencing in cases 1, 2, and 4, respectively. © ABEM todos os direitos reservados.568533539Andersson, S., Moghrabi, N., Physiology and molecular genetics of 17beta-hydroxysteroid dehydrogenases (1997) Steroids, 62, pp. 143-147Lukacik, P., Kavanagh, K.L., Oppermann, U., Structure and function of human 17beta-hydroxysteroid dehydrogenases (2006) Mol Cell Endocrinol, 248, pp. 61-71Labrie, F., Luu-The, V., Lin, S.X., Labrie, C., Simard, J., Breton, R., The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology (1997) Steroids, 62, pp. 148-158George, M.M., New, M.I., Tem, S., Sultan, C., Bhangoo, A., The clinical and molecular heterogeneity of 17aHSD3 enzyme deficiency (2010) Horm Res Paediatr, 74, pp. 229-240Boehmer, A.L., Brinkmann, A.O., Sandkuijl, L.A., Halley, D.J., Niermeijer, M.F., Andersson, S., 17beta-hydroxysteroid dehydrogenase-3 deficiency: Diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations (1999) J Clin Endocrinol Metab, 84, pp. 4713-4721Mendonça, B.B., Inacio, M., Arnhold, I.J., Costa, E.M., Bloise, W., Martin, R.M., Male pseudohermaphroditism due to 17beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management (2000) Medicine (Baltimore), 79, pp. 299-309Lee, Y.S., Kirk, J.M., Stanhope, R.G., Johnston, D.I., Harland, S., Auchus, R.J., Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls (2007) Clin Endocrinol (Oxf), 67, pp. 20-28Faienza, M.F., Giordani, L., Delvecchio, M., Cavallo, L., Clinical, endocrine, and molecular findings in 17beta-hydroxysteroid dehydrogenase type 3 deficiency (2008) J Endocrinol Invest, 31, pp. 85-91Andersson, S., Geissler, W.M., Wu, L., Davis, D.L., Grumbach, M.M., New, M.I., Molecular genetics and pathophysiology of 17 betahydroxysteroid dehydrogenase 3 deficiency (1996) J Clin Endocrinol Metab, 81, pp. 130-136Mendonca, B.B., Arnhold, I.J., Bloise, W., Andersson, S., Russell, D.W., Wilson, J.D., 17Beta-hydroxysteroid dehydrogenase 3 deficiency in women (1999) J Clin Endocrinol Metab, 84, pp. 802-804Prehn, C., Möller, G., Adamski, J., Recent advances in 17betahydroxysteroid dehydrogenases (2009) J Steroid Biochem Mol Biol, 114, pp. 72-77Hiort, O., Reinecke, S., Thyen, U., Jurgensen, M., Holterhus, P.M., Schon, D., Puberty in disorders of somatosexual differentiation (2003) J Pediatr Endocrinol Metab, 16 (SUPPL. 2), pp. 297-306Cohen-Kettenis, P.T., Gender change in 46, XY persons with 5alphareductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency (2005) Arch Sex Behav, 34, pp. 399-410Faisal Ahmed, S., Iqbal, A., Hughes, I.A., The testosterone: Androstenedione ratio in male undermasculinization (2000) Clin Endocrinol (Oxf), 53, pp. 697-702Ben Rhouma, B., Belguith, N., Mnif, M.F., Kamoun, T., Charfi, N., Kamoun, M., A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual ambiguity (2012) J Sex Med, , [Epub ahead of print]Neocleous, V., Sismani, C., Shammas, C., Efstathiou, E., Alexandrou, A., Ioannides, M., Duplication of exons 3-10 of the HSD17B3 gene: A novel type of genetic defect underlying 17g-HSD-3 deficiency (2012) Gene, 499, pp. 250-255Sambrook, J., Fritsch, E.F., Maniatis, T.E., (1989) Molecular cloning, a laboratory manual, , New York: Cold Spring HarborSaez, J.M., De Peretti, E., Morera, A.M., David, M., Bertrand, J., Familial male pseudohermaphroditism with gynecomastia due to a testicular 17-ketosteroid reductase defect. 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Comparative Study Of Transvaginal Sonography And Outpatient Hysteroscopy For The Detection Of Intrauterine Diseases [comparação Do Ultra-som Transvaginal E Da Histeroscopia Ambulatorial No Diagnóstico Das Doenças Intra-uterinas]

Introduction: Intrauterine diseases are common morbid disorders. Endometrial and endocervical polyps, myomas, synechiae, uterine malformations, endometrial hyperplasia and endometrial cancer are cited among intrauterine pathology. The investigations using transvaginal sonography and outpatient hysteroscopy had been a gold standard. Transvaginal sonography shows endometrial thickness and heterogeneous variations within the echogenecity of the endometrium uterine pathology. Transvaginal sonography is easy to apply for evaluation of intrauterine pathology and it has high sensitivy to diagnostic for intrauterine disorders. Hysteroscopy was used the gold standard control. It permited the better identification of intrauterine pathology but the histologic examination has been used for definitive diagnostic. Difficulty apprenticeship this technique had very decrease your access. Objectives: To evaluate the efficiency of transvaginal ultrasonography and outpatient hysteroscopy in the diagnosis of intrauterine pathology. Subjects and methods: The study conducted was a retrospective diagnostic-type test. They involved a total of 469 women underwent diagnostic hysteroscopy in 2006 in Campinas University. Seventy-nine women were excluded due to lack of ultrasound results in their medical charts. One-hundred and forty-seven premenopausal women and two-hundred and forty-three postmrnopausal women. For statistical analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy. The gold standard of the ultrasonography was the hysteroscopy and the gold standard of the hysteroscopy was the endometrium biopsy. Results: The mean age of postmenopausal women was 61±9.4 years. We observed 6.6% of endometrial hyperplasia and cancer and 54% of endometrial polyps. Ultrasonography had a sensitivity of 95.6%, a specificity of 7.4% and an accuracy of 53.7%, while hysteroscopy had a sensitivity of 95.7%, a specificity of 83% and an accuracy of 88.7%. The mean age of premenopausal women was 40±8.2 years. Endometrial cancer was not observed and two cases of endometrial hyperplasia were found. We observed 34% of endometrial polyps. Sensibility was 52.9%, specificity was 68.4% and the accuracy was 61.2% for polyps on ultrasonography while in hysteroscopy was 78.8%, 67.6% and 73.1% respectively. For myoma, sensitivily was 70.6% and 64.3%, specificity was 44.3% and 98.1% and accuracy was 63.3% and 91.2% in ultrasonography and hysteroscopy respectively. Conclusion: Hysteroscopy had better diagnostic accuracy than ultrasonography for the detection of intrauterine pathology.24SUPPL.26570Whitehead, M.I., Spencer, C.P., Endometrial assessment revisited (1999) Br Obstet Gynecol, 106, pp. 623-632Witt, B.R., Pelvic factors and infertility (1991) Infertil Reprod Med Clin North Am, 2, p. 371Batzer, F.R., Abnormal uterine bleeding: Imaging techniques for evaluation of the uterine cavity and endometrium before minimally invasive surgery - the case for transvaginal ultrasonography (2007) J Minimally Invasive Gynecol, 14, pp. 9-11Cepni, I., Ocal, P., Erkan, S., Comparison of transvaginal sonography, saline infusion sonography and hysteroscopy in the evaluationof uterine cavity pathologies (2005) Australian New Zealand J Obstet Gynecol, 45, pp. 30-35Goldastein, S.R., Zelster, I., Horan, C.K., Snyder, J.R., Schwartz, L.B., Ultrasonography based triage for perimenopausal patients with abnormal uterine bleending (1997) Am J Obstet Gynecol, 177, pp. 102-108Dijkhuizen, F.P.H.L.J., Brolman, H.A.M., Potters, A.E., Bongers, M.Y., Heintz, A.P.M., The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities (1996) Obstet Gynecol, 87, pp. 345-349Kremer, C., Duffy, S., Moroney, M., Patient satisfaction with outpatient hysteroscopy versus day case hysteroscopy: Randomized, controlled trial (2001) BMJ, 320, pp. 279-282Alborzi, S., Parsanezhad, M.E., Mahmoodian, S., Sonohysterography versus transvaginal sonography for screening of patients with abnormal uterine bleeding (2007) Int J Gyneco Obstet, 96, pp. 20-23Makris, N., Kalmantis, K., Skartados, N., Papadimitriou, A., Mantzaris, G., Antsaklis, A., Three-dimensional hysterosonography versus hysteroscopy for the detection of intracavitary uterine abnormalities (2007) Int J Gynecol Obstet, 97, pp. 6-9Gimpelson, R.J., Rappold, R.O., A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage (1988) Am J Obstet Gynecol, 158, pp. 489-492Bradley, L.D., Falcone, T., Magen, A.B., Radiographic imaging techniques for the diagnosis of abnormal uterine bleeding (2000) Obstet Gnecol Clin North Am, 27, pp. 245-246Bradley, L.D., Pasqualatto, E.B., Pricell, M.H., Hysteroscopic management endometrial polyps (2000) Obstet Gynecol, 4, pp. S23Gumus, I.I., Keskin, E.A., Kiliç, E., Aker, A., Kalalr, H., Turhan, N.O., Diagnostic value of hysteroscopy end hysterosonography in endometrial abnormalities in asymptomatic postmenopausal women (2008) Arch Gynecol Obstet, 278, pp. 241-244Timmermans, A., Gerritse, M.B.E., Opmeer, B.C., Jansen, F.W., Mol, B.W.J., Veersema, S., Diagnostic accuracy of endometrial thickness to exclude polyps in women with postmenopausal bleeding (2008) J Clinical Ultrasound, 36, pp. 286-290Tinelli, R., Tinelli, F.G., Cicinelli, E., Malvasi, A., Tinelli, A., The role of hysteroscopy with eye-directed biopsy in postmenopausal women with uterine bleeding and endometrial atrophy (2008) Menopause, 15, pp. 737-742Loverro, G., Bettochi, S., Cormio, G., Transvaginal sonography and hysteroscopy in postmenopausal uterine bleeding (1999) Maturitas, 33, pp. 139-144Garuti, G., Sambruni, I., Cellani, F., Garzia, D., Alleva, P., Luerti, M., Hysteroscopy and transvaginal ultrasonography in postmenopausal women with uterine bleeding (1999) Int J Gynecol Obstet, 65, pp. 25-33Kelekci, S., Kaya, E., Alan, M., Comparison of trnsvaginal sonography, saline infusion sonography, and office hysteroscopy in reproductive-aged women with or without abnormal uterine bleeding (2005) Fertil Steril, 84, pp. 682-686Towbin, N.A., Gviazda, I.M., March, C.M., Office hysteroscopy versus transvaginal ultrasonographyin the evaluation of patients with excessive uterine bleeding (1996) Am J Obstet Gynecol, 174, pp. 1678-1682Angioni, S., Loddo, A., Milano, F., Piras, B., Minerba, L., Melis, G.B., Detectionod benign intracavitary lesions in postmenopausal women with abnormal uterine bleeding: A prospective comparative study on outpatient hysteroscopy and blind biopsy (2008) J Minimally Invasive Gynecol, 15, pp. 87-91Machtinger, R., Korach, J., Padoa, A., Transvaginal ultrasound and diagnostic hysteroscopyas a predictor of endometrial polyps: Risk factors for premalignancy and malignancy (2005) Int J Gynecol Cancer, 15, pp. 325-32