Detection Of Metabolic Syndrome Features Among Childhood Cancer Survivors: A Target To Prevent Disease

Along with the growing epidemic of obesity, the risk of atherosclerosis, cardiovascular disease morbidity, and mortality are increasing markedly. Several risk factors for cardiovascular disease, such as visceral obesity, glucose intolerance, arterial hypertension, and dyslipidemia commonly cluster together as a condition currently known as metabolic syndrome. Thus far, insulin resistance, and endothelial dysfunction are the primary events of the metabolic syndrome. Several groups have recommended clinical criteria for the diagnosis of metabolic syndrome in adults. Nonetheless, in what concerns children and adolescents, there are no unified definitions, and modified adult criteria have been suggested by many authors, despite major problems. Some pediatric disease states are at risk for premature cardiovascular disease, with clinical coronary events occurring very early in adult life. Survivors of specific pediatric cancer groups, particularly acute lymphocytic leukemia, central nervous system tumors, sarcomas, lymphomas, testicular cancer, and following bone marrow transplantation, may develop metabolic syndrome traits due to: hormonal deficiencies (growth hormone deficiency, thyroid dysfunction, and gonadal failure), drug or radiotherapy damage, endothelial impairment, physical inactivity, adipose tissue dysfunction, and/or drug-induced magnesium deficiency. In conclusion, some primary and secondary prevention remarks are propose in order to reduce premature cardiovascular disease risk in this particular group of patients. © 2008 Siviero-Miachon et al, publisher and licensee Dove Medical Press Ltd.44825836Adan, L., Trivin, C., Sainte-Rose, C., GH deficiency caused by cranial irradiation during childhood: Factors and mukers in young adults (2001) J Clin Endocrinol Metab, 86, pp. 5245-5251Ahmet, A., Blaser, S., Stephens, D., Weight gain in craniopharyngioma -a model for hypothalamic obesity (2006) J Pediatr Endocrinol Metab, 19, pp. 121-128Alberti, K.G.M.M., Zimmet, P.Z., World Health Organisation (WHO)-Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation (1998) Diabet Med, 15, pp. 539-553National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (1992) Pediatrics, 89 (PART 2), pp. 525-584. , American Academy of PediatricsType 2 diabetes in children and adolescents (2000) Diabetes Care, 23, pp. 381-389. , American Diabetes AssociationArgüelles, B., Barrios, V., Buño, M., Anthropometric parameters and their relationship to serum growth hormone-binding protein and leptin levels in children with acute lymphoblastic leukemia: A prospective study (2000) Eur J Endocrinol, 143, pp. 243-250Baker, K.S., Ness, K.K., Steinberger, J., Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: A report from the Bone Marrow Transplantation Survivor Study (2007) Blood, 109, pp. 1765-1772Balkau, B., Charles, M.A., European Group for the Study of Insulin Resistance (EGIR) - Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (1999) Diabet Med, 16, pp. 442-443Barker, D.J., Fetal origins of coronary heart disease (1995) BMJ, 311, pp. 171-174Brydøy, M., Fosså, S.D., Dahl, O., Gonadal dysfunction and fertility problems in cancer survivors (2007) Acta Oncol, 46, pp. 480-489Bülow, B., Link, Y., Ahren, B., Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment (2004) Clin Endocrinol (Oxf), 61, pp. 683-691Chatterjee, R., Palla, K., MeGarrigle, H.H., Syndrome "X" in adult female recipients of bone marrow transplantation for haematological malignancies (2005) Bone Marrow Transplant, 35, pp. 209-210Colao, A., Di Somma, C., Rota, F., Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: A prospective study after GH withdrawal and restarting GH replacement (2005) J Clin Endocrinol Metab, 90, pp. 2659-2665Cook, S., Weitzman, M., Auinger, P., Prevalence of a metabolic syndrome phenotype in adolescents: Findings from the third National Health and Nutrition Examination Survey, 1988-1994 (2003) Arch Pediatr Adolesc Med, 157, pp. 821-827Cruz, M.L., Weigensberg, M.J., Huang, T.T., The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity (2004) J Clin Endocrinol Metab, 89, pp. 108-113Dalton, V.K., Rue, M., Silverman, L.B., Height and weight in children treated for acute lymphoblastic leukemia: Relationship to CNS treatment (2003) J Clin Oncol, 21, pp. 2953-2960DeFerranti, S.D., Gauvreau, K., Ludwig, D.S., Prevalence of the metabolic syndrome in American adolescents (2004) Circulation, 110, pp. 2494-2497Einhom, D., Reaven, G.M., Cobin, R.H., The American College of Endocrinology - American College of Endocrinology position statement on the insulin resistance syndrome (2003) Endocr Pract, 9, pp. 237-252Florin, T.A., Fryer, G.E., Miyoshi, T., Physical inactivity in adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2007) Cancer Epidenziol Biomarkers Prev, 16, pp. 1356-1363Genuth, S., Alberti, K.G., Bennett, P., Follow-up report on the diagnosis of diabetes mellitus. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Diabetes Care, 26, pp. 3160-3167Gleeson, H.K., Shalet, S.M., The impact of cancer therapy on the endocrine system in survivors of childhood brain tumors (2004) Endocr Relat Cancer, 11, pp. 589-602Grundy SM, Brewer Jr HB, Cleeman JI, et al. 2004. Definition of metabolic syndrome. Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation, 109:433-8Guo, C.Y., Halton, J.M., Barr, R.D., Hypomagnesemia associated with chemotherapy in patients treated for acute lymphoblastic leukemia: Possible mechanisms (2004) Oncol Rep, 11, pp. 185-189Gurney, J.G., Ness, K.K., Sibley, S.D., Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia (2006) Cancer, 107, pp. 1303-1312Harish, K., Dharmalingam, M., Himanshu, M., Study protocol: Insulin and its role in cancer (2007) BMC Endocr Disord, 7, p. 10Harz, K.J., Müller, H.L., Waldeck, E., Obesity in patients with craniopharyngioma: Assessment of food intake and movement counts indicating physical activity (2003) J Clin Endocrinol Metab, 88, pp. 5227-5231Heikens, J., Ubbink, M.C., Van der Pal, H.P.J., Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease (2000) Cancer, 88, pp. 2116-2121Hickman, T.B., Briefel, R.R., Carroll, M.D., Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: Data from the Third National Health and Nutrition Examination Survey (1998) Prev Med, 27, pp. 879-890Higgins, K., Noon, C., Cartwright, V., Features of the metabolic syndrome present in bone marrow transplantation in adulthood (2004) Bone Marrow Transplant, 33 (SUPPL. 1), pp. S216-S217Hodgkinson, E., Neville-Webbe, H.L., Coleman, R.E., Magnesium depletion in patients receiving cisplatin-based chemotherapy (2006) Clin Oncol (R Coll Radiol), 18, pp. 710-718Hoffman, K.E., Derdak, J., Bernstein, D., Metabolic syndrome traits in long-term survivors of pediatric sarcoma (2008) Pediatr Blood Cancer, 50, pp. 341-346Hsu, I.R., Kim, S.P., Kabir, M., Metabolic syndrome, hyperinsulinemia, and cancer (2007) Am J Clin Nutr, 86, pp. S867-S871Hu, G., Qiao, Q., Tuomilehto, J., Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women (2004) Arch Intern Med, 164, pp. 1066-1076. , for the DECODE Study Group(2006) The IDF consensus worldwide definition of the metabolic syndrome, , http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf, online, Accessed on January 10, 2008. URLJaniszewski, P.M., Oeffinger, K.C., Church, T.S., Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia (2007) J Clin Endocrinol Metab, 92, pp. 3816-3821Jarfelt, M., Lannering, B., Bosaeus, I., Body composition in young adult survivors of childhood acute lymphoblastic leukaemia (2005) Eur J Endocrinol, 153, pp. 81-89Jones, K.L., The dilemma of the metabolic syndrome in children and adolescents: Disease or distraction? (2006) Pediatr Diabetes, 7, pp. 311-321Kavey RE, Allada V, Daniels SR, et al. 2006. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Sciencethe Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Diseaseand the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation, 114:2710-38Kourti, M., Tragiannidis, A., Makedou, A., Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy (2005) J Pediatr Hematol/Oncol, 27, pp. 499-501Link, K., Moëll, C., Garwicz, S., Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood (2004) J Clin Endocrinol Metab, 89, pp. 5003-5012Lustig, R.H., Autonomic dysfunction of the β-Cell and the pathogenesis of obesity (2003) Rev Endocr Metab Disord, 4, pp. 23-32Lustig, R.H., Post, S.R., Srivannaboon, K., Risk factors for the development of obesity in children surviving brain tumors (2003) J Clin Endocrinol Metab, 88, pp. 611-616Mertens, A.C., Yasui, Y., Neglia, J.P., Late mortality experience in five-year survivors of childhood and adolescent cancer: The Childhood Cancer Survivor Study (2001) J Clin Oncol, 19, pp. 3163-3172Mohamed-Ali, V., Pinkney, J.H., Coppack, S.W., Adipose tissue as an endocrine and paracrine organ (1998) Int J Obes, 22, pp. 1145-1158Moser, E.C., Noordijk, E.M., Carde, P., Late non-neoplastic events in patients with aggressive non-Hodgkin's lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials (2005) Clin Lymphoma Myeloma, 6, pp. 122-130National Center for Health Statistics. 2000 CDC Growth Charts: United States [updated 2007 February 12cited 2007 November 08] [online]. Accessed on January 10, 2008. URL: http://www.cdc.gov/ growthcharts[NCEP-ATP III] National Cholesterol Education Program Adult Treatment Panel III - Expert panel on the detection, evaluation, and treatment of high blood cholesterol in adults. 2001. Executive summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285:2486-97National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. 1996. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics, 98:649-58National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. 2004. Fourth report of the Task Force on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children. Pediatrics, 114:555-76Neville, K.A., Cohn, R.J., Steinbeck, K.S., Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: Prevalence and risk factors (2006) J Clin Endocrinol Metab, 91, pp. 4401-4407Nuver, J., Smit, A.J., Postma, A., The metabolic syndrome in long-term cancer survivors, an important target for secondary preventive measures (2002) Cancer Treat Ver, 28, pp. 195-214Nuver, J., Smit, A.J., Wolffenbuttel, B.H., The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer (2005) J Clin Oncol, 23, pp. 3718-3725Oeffinger, K.C., Buchanan, G.R., Eshelman, D.A., Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia (2001) J Pediatr Hematol/Oncol, 23, pp. 424-430Oeffinger, K.C., Mertens, A.C., Sklar, C.A., Obesity in adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2003) J Clin Oncol, 21, pp. 1359-1365Oeffinger, K.C., Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of cardiovascular disease? (2008) Pediatr Blood Cancer, 50, pp. 462-467Pollak, M.N., Insulin, insulin-like growth factors, insulin resistance, and neoplasia (2007) Am J Clin Nutr, 86, pp. S820-S821Razzouk, B.I., Rose, S.R., Hongeng, S., Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma (2007) J Clin Oncol, 25, pp. 1183-1189Reaven, G.M., Banting lecture 1988: Role of insulin resistance in human disease (1988) Diabetes, 37, pp. 1595-1607Reilly, J.J., Kelly, A., Ness, P., Premature adiposity rebound in children treated for acute lymphoblastic leukemia (2001) J Clin Endocrinol Metab, 86, pp. 2775-2778Ross, J.A., Oeffinger, K.C., Davies, S.M., Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2004) J Clin Oncol, 22, pp. 3558-3562Roth C, Wilken B, Hanefeld F, et al. 1998. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol, 138-89-91Rutter, M.M., Rose, R.S., Long-term endocrine sequelae of childhood cancer (2007) Curr Opin Pediatr, 19, pp. 480-487Saini, A., Al-Shanti, N., Stewart, C.E., Waste management - cytokines, growth factors and cachexia (2006) Cytokine Growth Factor Rev, 17, pp. 475-486Sarti, C., Gallagher, J., The metabolic syndrome: Prevalence, CHD risk, and treatment (2006) J Diabetes Compl, 20, pp. 121-132Shalitin, S., Phillip, M., Stein, J., Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence (2006) Bone Marrow Transplant, 37, pp. 1109-1117Shoelson, S.E., Lee, J., Goldfine, A.B., Inflammation and insulin resistance (2006) J Clin Invest, 116, pp. 1793-1801Siviero-Miachon, A.A., Spinola-Castro, A.M., Tosta-Hernandez, P.D.C., Leptin assessment in acute lymphocytic leukemia survivors: Role of cranial radiotherapy? (2007) J Ped Hematol/Oncol, 29, pp. 776-782Sklar, C.A., Mertens, A.C., Walter, A., Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: Role of cranial irradiation (2000) Med Pediatr Oncol, 35, pp. 91-95Sklar, C.A., Mertens, A.C., Mitby, P., Premature menopause in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (2006) J Natl Cancer Inst, 98, pp. 890-896Soares, D.V., Spina, L.D., de Lima, Oliveira Brasil, R.R., Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement (2005) Metabolism, 54, pp. 321-329Srinivasan, S., Ogle, G.D., Garnett, S.P., Features of the metabolic syndrome after childhood craniopharyngioma (2004) J Clin Endocrinol Metab, 89, pp. 81-86Szczepaniska-Kostro, J., Tolwinska, J., Urban, M., Cardiac mass and function, carotid artery intima media thickness, homocysteine and lipoprotein levels in children and adolescents with growth hormone deficiency (2004) J Pediatr Endocrinol Metab, 17, pp. 1405-1413Talvensaari, K.K., Lanning, M., Tapanainen, P., Long-term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome (1996) J Clin Endocrinol Metab, 81, pp. 3051-3055Taskinen, M., Lipsanen-Nyman, M., Tiitinen, A., Insufficient growth hormone secretion is associated with metabolic syndrome after allogeneic stem cell transplantation in childhood (2007) J Pediatr Hematol/ Oncol, 29, pp. 529-534Trimis, G., Moschovi, M., Papassotiriou, I., Early indicators of dysmetabolic syndrome in young survivors of acute lymphoblastic leukemia in childhood as a target for preventing disease (2007) J Ped Hematol/ Oncol, 29, pp. 309-314Waychenberg, B.L., Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome (2000) Endocr Rev, 21, pp. 697-738Weiss, R., Dziura, J., Burgett, T.S., Obesity and the metabolic syndrome in children and adolescents (2004) N Engl J Med, 350, pp. 2362-2374Zimmet P, Alberti G, Kaufinan F, et al. on behalf of the International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes. 2007. The metabolic syndrome in children and adolescents. Lancet, 369:2059-61Zhou JR, Blackburn GL, Walker WA. 2007. Symposium introduction: metabolic syndrome and the onset of cancer. Am J Clin Nutr, 86: S817-S81

The Use Of Growth Hormone To Treat Endocrine-metabolic Disturbances In Acquired Immunodeficiency Syndrome (aids) Patients [o Papel Do Hormônio De Crescimento No Tratamento Dos Distúrbios Endócrino-metabólicos Do Paciente Com A Síndrome Da Imunodeficiência Adquirida (aids)]

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART ) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions. copyright© ABE&M todos os direitos reservados.525818832(2007) Unaids. Aids Epidemic Update, , http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf, December. Disponível emSecretaria de Vigilância em Saúde. Programa Nacional de DST e Aids (2007) Boletim Epidemiológico Aids-DST, (1). , Ministério da Saúde, Brasília: Ministério da Saúde, ano IVLeonard, E.G., McComsey, G.A., Metabolic complications of antiretroviral therapy in children (2003) Pediatr Infect Dis J, 22, pp. 77-84Hirschfeld, S., Use of human recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection (1996) Horm Res, 46, pp. 215-221Mulligan, K., Grunfeld, C., Hellerstein, M.K., Neese, R.A., Schambelan, M., Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection (1993) J Clin Endocrinol Metab, 77, pp. 956-962Mynarcik, D.C., Frost, R.A., Lang, C.H., DeCristofaro, K., McNurlan, M.A., Garlick, P.J., Insulin-like growth factor system in patients with HIV infection: Effect of exogenous growth hormone administration (1999) J Acquir Immune Defic Syndr, 22, pp. 49-55Hardin, D.S., Rice, J., Doyle, M.E., Pavia, A., Growth hormone improves protein catabolism and growth in prepubertal children with HIV infection (2005) Clin Endocrinol (Oxf), 63, pp. 259-262Gelato, M., McNurlan, M., Freedland, E., Role of recombinant human growth hormone in HIV-associated wasting and cachexia: Pathophysiology and rationale for treatment (2007) Clin Ther, 29, pp. 2269-2288Viganò, A., Mora, S., Manzoni, P., Schneider, L., Beretta, S., Molinaro, M., Effects of recombinant growth hormone on visceral fat accumulation: Pilot study in human immunodeficiency virus-infected adolescents (2005) J Clin Endocrinol Metab, 90, pp. 4075-4080Kotler DP, Muurahainen N, Grunfeld C, Wanke C, Thompson M, Saag M, et al. Effects of growth hormone on visceral adipose tissue and dyslipidemia in HIV, an erratum. J Acquir Immune Defic Syndr. 2006;43:378-80Falutz, J., Therapy insight: Body-shape changes and metabolic complications associated with HIV and highly active antiretroviral therapy (2007) Nat Clin Pract Endocrinol Metab, 3, pp. 651-661Tesselaar, K., Miedema, F., Growth hormone resurrects adult human thymus during HIV-1 infection (2008) J Clin Invest, 3, pp. 844-847Lo, J.C., Mulligan, K., Noor, M.A., Schwarz, J.M., Halvorsen, R.A., Grunfeld, C., The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation (2001) J Clin Endocrinol Metab, 86, pp. 3480-3487Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe (2004) Aids, 18, pp. 1443-1451. , European Paediatric Lipodystrophy GroupMinistério da Saúde. Brasil 2004. Secretaria de Vigilância em Saúde. Programa Nacional de DST e Aids Brasília (PN DSTAids). Série Manuais no 60. [atualizaç ão não disponívelacesso em 2008 Apr 28]. Disponível em: http://www.aids.gov.brZidovudine, didanosine, and zalcitabine in the treatment of HIV infection: Meta-analyses of the randomised evidence (1999) Lancet, 353, pp. 2014-2025. , HIV Trialists' Collaborative GroupChantry, C., Byrd, R., Englund, J., Baker, C.J., McKinney Jr, R.E., Pediatric Aids Clinical Trials Group Protocol 152 Study Team. Growth, survival and viral load in childhood HIV infection (2003) Pediatr Infect Dis J, 22, pp. 1033-1039Wanke, C., Kotler, D., The HIV wasting collaborative consensus committee. Collaborative recommendations. The approach to diagnosis and treatment of HIV wasting (2004) J Acquir Immune Defic Syndr, 37 (SUPPL. 5), pp. S284-S288Burgoyne, R.W., Tan, D.H., Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART ): A balancing act (2008) J Antimicrob Chemother, 61, pp. 469-473Dreimane, D., Nielsen, K., Deveikis, A., Bryson, Y.J., Geffner, M.E., Effect of protease inhibitors combined with standard antiretroviral therapy on linear growth and weight gain in human immunodeficiency virus type 1-infected children (2001) Pediatr Infect Dis J, 20, pp. 315-316Verweel, G., Van Rossum, A.M.C., Hartwig, N.G., Wolfs, T., Scherpbier, H.J., de Groot, R., Treatment with highly active antiretroviral therapy in human immunodeficiency virus type-1-infected children is associated with a sustained effect on growth (2002) Pediatrics, 109, pp. E25Sterne, J.A., Hernán, M.A., Ledergerber, B., Tilling, K., Weber, R., Sendi, P., Swiss HIV cohort study. Long-term effectiveness of potent antiretroviral therapy in preventing Aids and death: A prospective cohort study (2005) Lancet, 366, pp. 378-384Patel, K., Hernán, M.A., Williams, P.L., Seeger, J.D., McIntosh, K., Van Dyke, R.B., Pediatric Aids Clinical Trials Group 219/219C Study Team. Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: A 10-year follow-up study (2008) Clin Infect Dis, 46, pp. 507-515Scevola, D., DiMatteo, A., Giglio, O., Uberti, F., HIV infection-related cachexia and lipodystrophy (2006) Cachexia and wasting: A modern approach, pp. 407-428. , Mantovani G, editor, Milan: Springer;revised classification system for human immunodeficiency virus infection in children less than 13 years of age (1994) MMWR Morb Mortal Wkly Rep. 1994, 43, pp. 1-10. , Centers for Disease Control and PreventionMangili, A., Murman, D.H., Zampini, A.M., Wanke, C.A., Nutrition and HIV infection: Review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort (2006) Clin Infect Dis, 42, pp. 836-842Leonard, E.G., McComsey, G.A., Antiretroviral therapy in HIV-infected children: The metabolic cost of improved survival (2005) Infect Dis Clin North Am, 19, pp. 713-729Polo, R., Gómez-Candela, C., Miralles, C., Locutura, J., Alvarez, J., Barreiro, F., SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA. Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient (2007) Nutr Hosp, 22, pp. 229-243Chantry, C.J., Frederick, M.M., Meyer 3rd, W.A., Handelsman, E., Rich, K., Paul, M.E., Endocrine abnormalities and impaired growth in human immunodeficiency virus-infected children (2007) Pediatr Infect Dis J, 26, pp. 53-60Valente, A.M.M., Reis, A.F., Machado, D.M., Succi, R.C.M., Chacra, A.R., Alterações metabólicas da síndrome lipodistrófica do HIV. (2005) Arq Bras Endocrinol Metab, 49, pp. 871-881Saint-Marc, T., Partisani, M., Poizot-Martin, I., Bruno, F., Rouviere, O., Lang, J.M., A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy (1999) Aids, 13, pp. 1659-1667Lundgren, J.D., Battegay, M., Behrens, G., De Wit, S., Guaraldi, G., Katlama, C., EACS Executive Committee. European Aids Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV (2008) HIV Medicine, 9, pp. 72-81Laue, L., Pizzo, P.A., Butler, K., Cutler Jr., G.B., Growth and neuroendocrine dysfunction in children with acquired immunodeficiency syndrome (1990) J Pediatr, 117, pp. 541-545Matarazzo, P., Palomba, E., Lala, R., Ciuti, E., Altare, F., de Sanctis, L., Growth impairment, IGF I hyposecretion and thyroid dysfunction in children with perinatal HIV-1 infection (1994) Acta Paediatr, 83, pp. 1029-1034Panamonta, O., Kosalaraksa, P., Thinkhamrop, B., Kirdpon, W., Ingchanin, C., Lumbiganon, P., Endocrine function in Thai children infected with human immunodeficiency virus (2004) J Pediatr Endocrinol Metab, 17, pp. 33-40Rondanelli, M., Caselli, D., Aricò, M., Maccabruni, A., Magnani, B., Bacchella, L., Insulin-like growth factor I (IG F-I) and IG F-binding protein 3 response to growth hormone is impaired in HIV-infected children (2002) Aids Res Hum Retroviruses, 18, pp. 331-339Fliers, E., Unmehopa, U.A., Manniesing, S., Vuijst, C.L., Wiersinga, W.M., Swaab, D.F., Decreased neuropeptide Y (NPY) expression in the infundibular nucleus of patients with nonthyroidal illness (2001) Peptides, 22, pp. 459-465Eledrisi, M.S., Verghese, A.C., Adrenal insufficiency in HIV infection: A review and recommendations (2001) Am J Med Sci, 321, pp. 137-144Tovo, P.A., de Martino, M., Gabiano, C., Cappello, N., D'Elia, R., Loy, A., Prognostic factors and survival in children with perinatal HIV infection (1992) Lancet, 339, pp. 1249-1253Nachman, S.A., Lindsey, J.C., Pelton, S., Mofenson, L., McIntosh, K., Wiznia, A., Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy (2002) Arch Pediatr Adolesc Med, 156, pp. 497-503Congote, L.F., Monitoring insulin-like growth factors in HIV infection and aids (2005) Clin Chim Acta, 361, pp. 30-53Meininger, G., Grinspoon, S., Regulation of the growth hormone/ insulin-like growth factor-I axis in HIV disease (2001) Endocrinologist, 11, pp. 188-195Frost, R.A., Fuhrer, J., Steigbigel, R., Mariuz, P., Lang, C.H., Gelato, M.C., Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system (1996) Clin Endocrinol (Oxf), 44, pp. 501-514Heijligenberg, R., Sauerwein, H.P., Brabant, G., Endert, E., Hommes, M.J., Romijn, J.A., Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome (1996) J Clin Endocrinol Metab, 81, pp. 4028-4032Rondanelli, M., Solerte, S.B., Fioravanti, M., Scevola, D., Locatelli, M., Minoli, L., Circadian secretory pattern of growth hormone, insulin-like growth factor type I, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone and prolactin during HIV infection (1997) Aids, 13, pp. 1243-1249Stanley TL, Grinspoon SK. GH/GHRH axis in HIV lipodystrophy. Pituitary. 2008 Feb 13 [Epub ahead of print]Viganò, A., Mora, S., Brambilla, P., Schneider, L., Merlo, M., Monti, L.D., Impaired growth hormone secretion correlates with visceral adiposity in highly active antiretroviral treated HIV- infected adolescents (2003) Aids, 17, pp. 1435-1441Van Rossum, A.M.C., Gaaker, M.I., Verweel, G., Hartwig, N.G., Wolfs, T.F., Geelen, S.P., Endocrinology and immunologic factors associated with recovery of growth in children with human immunodeficiency virus type 1 infection treated with protease inhibitors (2003) Pediatric Infect Dis J, 22, pp. 70-76Schambelan, M., Mulligan, K., Grunfeld, C., Daar, E.S., LaMarca, A., Kotler, D.P., Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group (1996) Ann Intern Med, 125, pp. 873-882Krentz, A.J., Koster, F.T., Crist, D.M., Finn, K., Johnson, L.Z., Boyle, P.J., Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in Aids and Aids-related complex (1993) J Acquir Immune Defic Syndr, 6, pp. 245-251McNurlan, M.A., Garlick, P.J., Steigbigel, R.T., DeCristofaro, K.A., Frost, R.A., Lang, C.H., Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease (1997) J Clin Invest, 100, pp. 2125-2132Waters, D., Danska, J., Hardy, K., Koster, F., Qualls, C., Nickell, D., Recombinant human growth hormone, insulin-like growth factor 1, and combination therapy in Aids-associated wasting: A randomized, double-blind, placebocontrolled trial (1996) Ann Intern Med, 125, pp. 865-872Esposito, J.G., Thomas, S.G., Kingdon, L., Ezzat, S., Growth hormone treatment improves peripheral muscle oxygen extraction-utilization during exercise in patients with human immunodeficiency virus-associated wasting: A randomized controlled trial (2004) J Clin Endocrinol Metab, 89, pp. 5124-5131Moyle, G.J., Daar, E.S., Gertner, J.M., Kotler, D.P., Melchior, J.C., O'Brien, F., Serono 9037 Study Team. Growth hormone improves lean body mass, physical performance, and quality of life in subjects with HIV-associated weight loss or wasting on highly active antiretroviral therapy (2004) J Acquir Immune Defic Syndr, 35, pp. 367-375Storer, T.W., Woodhouse, L.J., Sattler, F., Singh, A.B., Schroeder, E.T., Beck, K., A randomized, placebocontrolled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment (2005) J Clin Endocrinol Metab, 90, pp. 4474-4482Wanke, C., Gerrior, J., Kantaros, J., Coakley, E., Albrecht, M., Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV (1999) Aids, 13, pp. 2099-2103Zeitler, P.S., Travers, S., Kappy, M.S., Advances in the recognition and treatment of endocrine complications in children with chronic illness (1999) Adv Pediatr, 46, pp. 101-149Napolitano, L.A., Schmidt, D., Gotway, M.B., Ameli, N., Filbert, E.L., Ng, M.M., Growth hormone enhances thymic function in HIV-infected adults (2008) J Clin Invest, 118, pp. 1085-109

Short Stature In Chronic Kidney Disease: Physiopathology And Treatment With Growth Hormone [baixa Estatura Na Doença Renal Crônica: Fisiopatologia E Tratamento Com Hormônio De Crescimento]

Growth failure is frequent and a clinically important issue in children with chronic kidney disease (CKD). Many factors contribute to impaired growth in these children, including abnormalities in the growth hormone (GH) - insulin-like growth factor 1 (IGF-1) axis, malnutrition, acidosis, renal bone disease and glucocorticoid associated treatment. The management of growth failure in children with CKD is complicated by the presence of other-disease related complications requiring medical intervention. Despite evidence of GH efficacy and safety in this population, this therapy is still underutilized. This review shows the impact, the causes and the treatment of growth failure in children with CKD. copyright© ABE&M todos os direitos reservados.525783791K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification (2002) Am J Kidney Dis, 39 (2 SUPPL. 1), pp. S1-266. , National Kidney FoundationChesney, R.W., Brewer, E., Moxey-Mims, M., Watkins, S., Furth, S.L., Harmon, W.E., Report of NIH task force on research priorities in chronic kidney disease in children (2006) Pediatr Nephrol, 21, pp. 14-25NAPRTCS Annual Report, , https://web.emmes.com/study/ped/annlrept/annlrept2005.pdf, acesso em 2005, Disponível emSeikaly, M.G., Salhab, N., Warandy, B.A., Stablein, D., Use o hrGH in children with chronic kidney disease: Lessons from NAPRTCS (2007) Pediatr Nephrol, 22, pp. 1195-1204Mahesh, S., Kaskel, F., Growth hormone axis in chronic kidney disease (2008) Pediatr Nephrol, 23, pp. 41-48Gorman, G., Frankenfield, D., Linear growth in pediatric hemodialysis patients (2008) Pediatr Nephrol, 23, pp. 123-127Ulinski, T., Cochat, P., Longitudinal growth in children following kidney transplantation: From conservative to pharmacological strategies (2006) Pediatr Nephrol, 21, pp. 903-909Vimalanchandra, D., Hodson, E.M., Willis, N.S., Craig, J.C., Cowell, C., Knight, J.F., Growth hormone for children with chronic kidney disease (Cochrane Review) (2006) Cochrane Database Syst Rev, 19. , CD003264Williams, R., Growth hormone underutilized in pediatric hemodialysis population (2006) Nat Clin Pract Nephrol, p. 2. , Disponível em: doi:10.1038/ncpneph0081Mahan, J.D., Warady, B.A., Assessment and treatment of short stature in pediatric patients with chronic kidney disease: A consensus statement (2006) Pediatr Nephrol, 21, pp. 917-930Lewis, M., Shaw, J., Reid, C., Evans, J., Webb, N., Verrier-Jones, K., Growth in children with established renal failure: A registry analysis (2007) Nephrol Dial Transplant, 22, pp. 76-180Tom, A., McCauley, L., Bell, L., Rodd, C., Espinosa, P., Yu, G., Growth during maintenance hemodialysis: Impact of enhanced nutrition and clearance (1999) J Pediatr, 134, pp. 464-471Roth, K.S., Duncan, L.L., Chan, J.C., The role of nutrition in chronic renal insufficiency of childhood: How much do we know? (2005) Crit Rev Food Sci Nutr, 45, pp. 259-263Jarkovská, Z., Hodková, M., Sazamová, M., Rosická, M., Dusilová-Sulková, S., Marek, J., Plasma levels of active and total ghrelin in renal failure: A relationship with GH/IGF-1 axis (2005) Growth Horm IGF Res, 15, pp. 369-376Mak, R.H., Cheung, W., Cone, R.D., Marks, D.L., Orexygenic and anorexygenic mechanisms in the control of nutrition in chronic kidney disease (2005) Pediatr Nephrol, 20, pp. 427-431Rees, L., Shaw, W., Nutrition in children with CRF and on dialysis (2007) Pediatr Nephrol, 22, pp. 1689-1702Graf, L., Candelaria, S., Doyle, M., Kaskel, F., Nutrition assessment and hormonal influences on body composition in children with chronic kidney disease (2007) Adv Chronic Kidney Dis, 14, pp. 215-223Uauy, R.D., Hogg, R.J., Brewer, E.D., Reisch, J.S., Cunningham, C., Holliday, M.A., Dietary and growth in infants with chronic renal insufficiency: A report from the Southwest Pediatric Nephrology Study Group and the University of California, San Francisco (1994) Pediatr Nephrol, 8, pp. 45-50Lane, P.H., Puberty and chronic kidney disease (2005) Adv Chronic Kidney Dis, 12, pp. 372-377Hokken-Koelega, A.C., Saenger, P., Cappa, M., Greggio, N., International Workshop on Management of Puberty for Optimum Auxological Results. Unresolved problems concerning optimal therapy of puberty in children with chronic renal diseases (2001) J Pediatr Endocrinol Metab, 14 (SUPPL. 2), pp. 945-952Langman, C.B., Renal osteodystrophy: A pediatric perspective, 2005 (2005) Growth Horm IGF Res, 15 (SUPPL. A), pp. 42-47Santos, F., Carbajo-Pérez, E., Rodríguez, J., Fernández-Fuente, M., Molinos, I., Amil, B., Alterations of the growth plate in chronic renal failure (2005) Pediatr Nephrol, 20, pp. 330-334Rabkin, R., Sun, D.F., Chen, Y., Tan, J., Shaefer, F., Growth hormone resistance in uremia: A role of impaired JAK/STAT signaling (2005) Pediatr Nephrol, 20, pp. 313-318Roelfsema, V., Clark, R.G., The growth hormone and insulin-like growth factor axis: Its manipulation for the benefit of growth disorders in renal failure (2001) J Am Soc Nephrol, 12, pp. 1297-1306Tonshoff, B., Kiepe, D., Ciarmatori, S., Growth hormone/insulin-like growth factor system in children with chronic renal failure (2005) Pediatr Nephrol, 20, pp. 279-289Smink, J.J., Buchholz, I.M., Hamers, N., van Tilburg, C.M., Christis, C., Sakkers, R.J., Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis (2003) Osteoarthritis Cartilage, 11, pp. 864-871Jux, C., Leiber, K., Hügel, U., Blum, W., Ohlsson, C., Klaus, G., Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes (1998) Endocrinology, 139, pp. 3296-3305Klaus, G., Jux, C., Fernandez, P., Rodriguez, J., Himmele, R., Mehls, O., Suppression of growth plate chondrocyte proliferation by corticosteroids (2000) Pediatr Nephrol, 14, pp. 612-615Koedam, J.A., Hoogerbrugge, C.M., van Buul-Offers, S.C., Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone (2000) J Endocrinol, 165, pp. 557-567Smink, J.J., Koedam, J.A., Koster, J.G., van Buul-Offers, S.C., Dexamethasone-induced growth inhibition of porcine growth plate chondrocytes is accompanied by changes in levels of IGF axis components (2002) J Endocrinol, 174, pp. 343-352Oliveira, J.C., Machado Neto, F.A., Morcilo, A.M., Oliveira, L.C., Belangero, V.M.S., Gelonese Neto, B., Insuficiência renal crônica e hormônio de crescimento: Efeitos no eixo GH-IGFe na leptina. (2005) Arq Bras Endocrinol Metab, 49, pp. 964-970Mehls, O., Himmele, R., Hömme, M., Kiepe, D., Klaus, G., The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells (2001) J Pediatr Endocrinol Metab, 14 (SUPPL. 6), pp. 1475-1482Jonsson, K.B., Ljunghall, S., Karlström, O., Johansson, A.G., Mallmin, H., Ljunggren, O., Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts (1993) Biosci Rep, 13, pp. 297-302Klare, B., Strom, T.M., Hahn, H., Engelsberger, I., Meusel, E., Illner, W.D., Remarkable long-term prognosis and excellent growth in kidney-transplant children under cyclosporine monotherapy (1991) Transplant Proc, 23, pp. 1013-1017Shampiro, R., Scantlebury, V.P., Jordan, M.L., Vivas, C., Ellis, D., Lombardozzi-Lane, S., Pediatric renal transplantation under tacrolimus-based immunosuppression (1999) Transplantation, 67, pp. 299-303Mehls, O., Ritz, E., Skeletal growth in experimental uremia (1983) Kidney Int, 21 (SUPPL.), pp. 53-62Haffner, D., Schaefer, F., Does recombinant growth hormone improve adult height in children with chronic renal failure? (2001) Semin Nephrol, 21, pp. 490-497Fine, R.N., Stablein, D., Long-term use of recombinant growth hormone in pediatric allograft recipients: A report from the NAPTRCS Transplant Registry (2005) Pediatr Nephrol, 20, pp. 404-408Crompton, C.H., Australian and New Zeland Paediatric Nephrology Association. Long-term recombinant human growth hormone use in Australian children with renal disease (2004) Nephrology (Carlton), 9, pp. 325-330Andre, J.L., Bourquard, R., Guillemin, F., Krier, M.J., Briancon, S., Final height in children with chronic renal failure who have not received growth hormone (2003) Pediatr Nephrol, 18, pp. 685-689Mehls, O., Lindberg, A., Nissel, R., Wühl, E., Schaefer, F., Tönshoff, B., Growth hormone treatment in short children with chronic kidney disease (2007) Growth hormone therapy in pediatrics, pp. 407-421. , Ranke MB, Price DA, Reiter EO, editores, Basel: Karger;Guest, G., Berard, E., Crosnier, H., Chevallier, T., Rappaport, R., Broyer, M., Effects of growth hormone in short children after renal transplantation. French Society of Pediatric Nephrology (1998) Pediatr Nephrol, 12, pp. 437-446Fine, R.N., Ho, M., Tejani, A., Blethen, S., Adverse events with hrGH treatment of patients with chronic renal insufficiency and end-stage renal disease (2003) J Pediatr, 142, pp. 539-545Fine, R.N., Stablein, D., Cohen, A.H., Tejani, A., Kohaut, E., Recombinant human growth hormone post-renal transplantation in children: A randomized controlled study of the NAPRTCS (2002) Kidney Int, 62, pp. 688-69

The Use Of Fluorescence In Situ Hybridization In The Diagnosis Of Hidden Mosaicism: Apropos Of Three Cases Of Sex Chromosome Anomalies [o Uso Da Hibridação In Situ Com Fluorescência No Diagnóstico De Mosaicismo Oculto: A Propósito De Três Casos De Anomalias De Cromossomos Sexuais]

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. © ABEM todos os direitos reservados.568545551Nielsen, J., Wohlert, M., Sex chromosome abnormalities found among 34,910 newborn children: Results from a 13-year incidence study in Arhus, Denmark (1990) Birth Defects Orig Artic Ser, 26 (4), pp. 209-223Li, X., Sex chromosomes and sex chromosome abnormalities (2011) Clin Lab Med, 31 (4), pp. 463-479Sørensen, K., Nielsen, J., Jacobsen, P., Rølle, T., The 48, XXYY syndrome (1978) J Ment Defic Res, 22 (3), pp. 197-205Kleczkowska, A., Fryns, J.P., Van den Berghe, H., X-chromosome polysomy in the male. The Leuven experience 1966-1987 (1988) Hum Genet, 80 (1), pp. 16-22Linden, M.G., Bender, B.G., Robinson, A., Intrauterine diagnosis of sex chromosome aneuploidy (1996) Obstet Gynecol, 87 (3), pp. 468-475Ottesen, A.M., Aksglaede, L., Garn, I., Tartaglia, N., Tassone, F., Gravholt, C.H., Increased number of sex chromosomes affects height in a nonlinear fashion: A study of 305 patients with sex chromosome aneuploidy (2010) Am J Med Genet A, 152 A (5), pp. 1206-1212Tartaglia, N., Ayari, N., Howell, S., D'Epagnier, C., Zeitler, P., 48, XXYY, 48, XXXY and 49, XXXXY syndromes: Not just variants of Klinefelter syndrome (2011) Acta Paediatr, 100 (6), pp. 851-860Oliveira, R.M., Verreschi, I.T., Lipay, M.V., Eça, L.P., Guedes, A.D., Bianco, B., Y chromosome in Turner syndrome: Review of the literature (2009) Sao Paulo Med J, 127 (6), pp. 373-378Barros, B.A., Maciel-Guerra, A.T., De Mello, M.P., Coeli, F.B., Carvalho, A.B., Viguetti-Campos, N., The inclusion of new techniques of chromosome analysis has improved the cytogenetic profile of Turner syndrome (2009) Arq Bras Endocrinol Metab, 53 (9), pp. 1137-1142Ogata, T., Matsuo, N., Turner syndrome and female sex chromosome aberrations: Deduction of the principal factors involved in the development of clinical features (1995) Hum Genet, 95, pp. 607-609Tsuchiya, K.D., Fluorescence in situ hybridization (2011) Clin Lab Med, 31 (4), pp. 525-542Sallai, A., Sólyom, J., Dobos, M., Szabó, J., Halász, Z., Ságodi, L., Y-chromosome markers in Turner syndrome: Screening of 130 patients (2010) J Endocrinol Invest, 33 (4), pp. 222-227Wiktor, A.E., Van Dyke, D.L., Detection of low level sex chromosome mosaicism in Ullrich-Turner syndrome patients (2005) Am J Med Genet A, 138 (3), pp. 259-261Garcia-Quevedo, L., Blanco, J., Sarrate, Z., Català, V., Bassas, L., Vidal, F., Hidden mosaicism in patients with Klinefelter's syndrome: Implications for genetic reproductive counselling (2011) Hum Reprod, 26 (12), pp. 3486-3493Westlander, G., Ekerhovd, E., Granberg, S., Hanson, L., Hanson, C., Bergh, C., Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: A prospective study of possible predictive factors for successful sperm recovery (2001) Fertil Steril, 75, pp. 1102-1105Schoubben, E., Decaestecker, K., Quaegebeur, K., Danneels, L., Mortier, G., Cornette, L., Tetrasomy and pentasomy of the X chromosome (2011) Eur J Pediatr, 170 (10), pp. 1325-1327Shouman, N., Pabst, B., Arslan-Kirchner, M., Eckardt, A., Schönweiler, R., Ptok, M., Search for deletion 22q11.2 in interphase nuclei of buccal mucosa of patients ascertained by isolated cleft palate: A new diagnostic approach (2003) Int J Oral Maxillofac Surg, 32 (2), pp. 198-200Mendonca, B.B., Domenice, S., Arnhold, I.J., Costa, E.M., 46, XY disorders of sex development (DSD) (2009) Clin Endocrinol (Oxf), 70 (2), pp. 173-187Rocha, V.B., Guerra-Júnior, G., Marques-de-Faria, A.P., de Mello, M.P., Maciel-Guerra, A.T., Complete gonadal dysgenesis in clinical practice: The 46, XY karyotype accounts for more than one third of cases (2011) Fertil Steril, 96 (6), pp. 1431-1514Hawkins, J.R., Taylor, A., Goodfellow, P.N., Migeon, C.J., Smith, K.D., Berkovitz, G.D., Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis (1992) Am J Hum Gen, 51, pp. 979-984Ferraz-de-Souza, B., Lin, L., Achermann, J.C., Steroidogenic factor-1 (SF-1, NR5A1) and human disease (2011) Mol Cell Endocrinol, 336 (1-2), pp. 198-205Soardi, F.C., Coeli, F.B., Maciel-Guerra, A.T., Guerra-Junior, G., Mello, M.P., Complete XY gonadal dysgenesis due to p. D293N homozygous mutation in the NR5A1 gene: A case study (2010) J Appl Genet, 51, pp. 223-224Cools, M., Drop, S.L., Wolffenbuttel, K.P., Oosterhuis, J.W., Looijenga, L.H., Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers (2006) Endocr Rev, 27 (5), pp. 468-484Bondy, C.A., Turner Syndrome Study Group. Care of girls and women with Turner syndrome: A guideline of the Turner Syndrome Study Group (2007) J Clin Endocrinol Metab, 92, pp. 10-25Lindhardt Johansen, M., Hagen, C.P., Rajpert-De Meyts, E., Kjærgaard, S., Petersen, B.L., Skakkebæk, N.E., 45, X/46, XY mosaicism: Phenotypic characteristics, growth, and reproductive function-A retrospective longitudinal study (2012) J Clin Endocrinol Metab, 97 (8), pp. E1540-E1549Bettio, D., Venci, A., Rizzi, N., Negri, L., Setti, P.L., Clinical and molecular cytogenetic studies in three infertile patients with mosaic rearranged Y chromosomes (2006) Hum Reprod, 21 (4), pp. 972-975Hsu, L.Y., Phenotype/karyotype correlations of Y chromosome aneuploidy with emphasis on structural aberrations in postnatally diagnosed cases (1994) Am J Med Genet, 53, pp. 108-140Nazarenko, S.A., Timoshevsky, V.A., Sukhanova, N.N., High frequency of tissue-specific mosaicism in Turner syndrome patients (1999) Clin Genet, 56 (1), pp. 59-65Spencer, D.A., Eyles, J.W., Mason, M.K., XYY syndrome, and XYY/XXYY mosaicism also showing features of Klinefelter's syndrome (1969) J Med Genet, 6, pp. 159-165Stochholm, K., Juul, S., Gravholt, C.H., Diagnosis and mortality in 47, XYY persons: A registry study (2010) Orphanet J Rare Dis, 5, p. 15Tartaglia, N., Davis, S., Hench, A., Nimishakavi, S., Beauregard, R., Reynolds, A., A new look at XXYY syndrome: Medical and psychological features (2008) Am J Med Genet A, 146 (12), pp. 1509-1522Hook, E.B., Exclusion of chromosome mosaicism: Tables of 90 percent, 95 percent and 99 percent confidence limits and comments on use (1977) Am J Hum Genet, 29, pp. 94-97McCorquodal, M.M., Bowdle, F.C., Two pregnancies and the loss of the 46, XX cell line in a 45, X/46, XX Turner mosaic patient (1985) Fertil Steril, 43, pp. 229-233Gravholt, C.H., Friedrich, U., Nielsen, J., Chromosomal mosaicism: A follow-up study of 39 unselected children found at birth (1991) Hum Genet, 88, pp. 49-52Schad, C.R., Kuffel, D.G., Wyatt, W.A., Zinsmeister, A.R., Jenkins, R.B., Dewald, G.W., Application of fluorescent in situ hybridization with X and Y chromosome specific probes to buccal smear analysis (1996) Am J Med Genet, 66 (2), pp. 187-19