Central Precocious Puberty As A Sole Manifestation Of Suprasellar Arachnoid Cyst [puberdade Precoce Central Como única Manifestação De Cisto Aracnoide Supraselar]

Objective: Arachnoid cysts (AC) are a rare finding; 10% of them are suprasellar and occur almost exclusively in children. They are frequently associated with neurological and visual manifestations. Central precocious puberty as a sole manifestation is uncommon.Case description: Girl evaluated at the age of two years and seven months. She started breast development at the age of one year and eight months, pubic and axillary hair at the age of two years, with growth velocity acceleration (13cm/year) and increased bone age (seven years and one month). On exam: weight: 22.6kg (Z+4.0), height: 106cm (Z+3.5) and puberal stage of B3P2. The GnRH stimulus test was performed (basal LH 8.3 IU/L, at 30 minutes 94.3 IU/L; FSH basal=10.1 IU/L, at 30 minutes 29.5 IU/L). Nuclear Magnetic Resonance of the skull showed a suprasellar arachnoid cyst. Others stimulation tests were performed and excluded pituitary deficiencies. Treatment with a GnRH analog was started. At the age of four years and three months, she was B3P2, with normal growth velocity and neurologic development. Comments: Central precocious puberty can be the only manifestation of AC. It is essential to establish early diagnosis and treatment. A prolonged follow up is recommended, since late pituitary dysfunctions can occur.291126129Parent, A.S., Rasier, G., Gerard, A., Heger, S., Roth, C., Mastronardi, C., Early onset of puberty: Tracking genetic and environmental factors (2005) Horm Res, 64, pp. 41-47Trivin, C., Couto-Silva, A.C., Sainte-Rose, C., Chemaitilly, W., Kalifa, C., Doz, F., Presentation and evolution of organic central precocious puberty according to the type of CNS lesion (2006) Clin Endocrinol, 65, pp. 239-245Starzyk, J., Kwiatkowski, S., Urbanowicz, W., Starzyk, B., Harasiewicz, M., Kalicka-Kasperczyk, A., Suprasellar arachnoidal cyst as a cause of precocious puberty--report of three patients and literature overview (2003) J Pediatr Endocrinol Metab, 16, pp. 447-455Herter, L.D., Golendziner, E., Flores, J.A., Becker Jr., E., Spritzer, P.M., Ovarian and uterine sonography in healthy girls between 1 and 13 years old: Correlation of findings with age and pubertal status (2002) AJR Am J Roentgenol, 178, pp. 1531-1536Güzel, A., Trippel, M., Ostertage, C.B., Suprasellar arachnoid cyst: A 20-year follow-up after stereotactic internal drainage: Case report and review of the literature (2007) Turk Neurosurg, 17, pp. 211-218Ichiyama, T., Hayashi, T., Nishikawa, M., Furukawa, S., Optic nerve hypoplasia with hypopituitarism and an arachnoid cyst (1996) Brain Dev, 18, pp. 234-235Huang, H.P., Tung, Y.C., Tsai, W.Y., Kuo, M.F., Peng, S.F., Arachnoid cyst with GnRH- dependent sexual precocity and growth hormone deficiency (2004) Pediatr Neurol, 30, pp. 143-145Longas, A.F., Mayayo, E., Labarta, J.L., Congenital growth hormone deficiency arising from central cranial malformations: Experience in KIGS (1999) Growth Hormone Therapy In KIGS - 10 Years' Experience, pp. 135-146. , In: Ranke M, Wilton P, editors, Leipizig: JAB VerlagMohn, A., Schoof, E., Fahlbusch, R., Wenzel, D., Dörr, H.G., The endocrine spectrum of arachnoid cysts in childhood (1999) Pediatr Neurosurg, 31, pp. 316-321Adan, L., Bussières, L., Dinand, V., Zerah, M., Pierre-Kahn, A., Brauner, R., Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst (2000) Eur J Pediatr, 159, pp. 348-355Rivarola, M.A., Belgorosky, A., Mendilaharzu, H., Vidal, G., Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty (2001) Acta Paediatr, 90, pp. 751-756Golash, A., Mitchell, G., Mallucci, C., May, P., Pilling, D., Prenatal diagnosis of suprasellar arachnoid cyst and postnatal endoscopic treatment (2001) Childs Nerv Syst, 17, pp. 739-742Fujimura, J., Shima, Y., Arai, H., Ogawa, R., Fukunaga, Y., Management of a suprasellar arachnoid cyst identified using prenatal sonography (2006) J Clin Ultrasound, 34, pp. 92-94Ersahin, Y., Kesikci, H., Rüksen, M., Aydin, C., Mutluer, S., Endoscopic treatment of suprasellar arachnoid cysts (2008) Childs Nerv Syst, 24, pp. 1013-1020Dodd, R.L., Barnes, P.D., Huhn, S.L., Spontaneous resolution of a prepontine arachnoid cyst. Case report and review of the literature (2002) Pediatr Neurosurg, 37, pp. 152-157Shim, K.W., Lee, Y.H., Park, E.K., Park, Y.S., Choi, J.U., Kim, D.S., Treatment option for arachnoid cysts (2009) Childs Nerv Syst, 25, pp. 1459-1466Oberbauer, R.W., Haase, J., Pucher, R., Arachnoid cysts in children: A European co-operative study (1992) Childs Nerv Syst, 8, pp. 281-28

46,xx Dsd And Antley-bixler Syndrome Due To Novel Mutations In The Cytochrome P450 Oxidoreductase Gene [dds 46,xx E Síndrome De Antley-bixler Causada Por Novas Mutações No Gene Da Enzima P450 Oxidorredutase]

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively. © ABEM todos os direitos reservados.568578585Miller, W.L., Minireview: Regulation of steroidogenesis by electron transfer (2005) Endocrinology, 146, pp. 2544-2550Scott, R.R., Gomes, L.G., Huang, N., Van Vliet, G., Miller, W.L., Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency (2007) J Clin Endocrinol Metab, 92, pp. 2318-2322Auchus, R.J., Lee, T.C., Miller, W.L., Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer (1998) J Biol Chem, 273, pp. 3158-3165Flück, C.E., Tajima, T., Pandey, A.V., Arlt, W., Okuhara, K., Verge, C.F., Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome (2004) Nat Genet, 36, pp. 228-230Arlt, W., Walker, E.A., Draper, N., Ivison, H.E., Ride, J.P., Hammer, F., Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: Analytical study (2004) Lancet, 363, pp. 2128-2135Scott, R.R., Miller, W.L., Genetic and clinical features of P450 oxidoreductase deficiency (2008) Horm Res, 69, pp. 266-275Polusani, S.R., Kar, R., Riquelme, M.A., Masters, B.S., Panda, S.P., Regulation of gap junction function and connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR) (2011) Biochem Biophys Res Commun, 411, pp. 490-495Tomalik-Scharte, D., Maiter, D., Kirchheiner, J., Ivison, H.E., Fuhr, U., Arlt, W., Impaired hepatic drug and steroid metabolism in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency (2010) Eur J Endocrinol, 163, pp. 919-924(2012) Human Gene Mutation Database, , http://www.hgmd.cf.ac.uk/ac/index.php, Available at, Accessed on: Nov 17Flück, C.E., Pandey, A.V., Clinical and biochemical consequences of P450 oxidoreductase deficiency (2011) Endocr Dev, 20, pp. 63-79Krone, N., Reisch, N., Idkowiak, J., Dhir, V., Ivison, H.E., Hughes, B.A., Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency (2012) J Clin Endocrinol Metab, 97, pp. E257-E267Sambrook, J., Fristsch, E.F., Maniatis, T.E., (1989) Molecular Cloning: A laboratory manual, , Cold Spring Harbor, NY: Cold Spring Harbor Laboratory PressXia, C., Panda, S.P., Marohnic, C.C., Martásek, P., Masters, B.S., Kim, J.J., Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency (2011) Proc Natl Acad Sci U S A, 108, pp. 13486-13491Idkowiak, J., O'Riordan, S., Reisch, N., Malunowicz, E.M., Collins, F., Kerstens, M.N., Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency (2011) J Clin Endocrinol Metab, 96 (3), pp. E453-E462Hamdane, D., Xia, C., Im, S.C., Zhang, H., Kim, J.J., Waskell, L., Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450 (2009) J Biol Chem, 284 (17), pp. 11374-11384Xia, C., Hamdane, D., Shen, A.L., Choi, V., Kasper, C.B., Pearl, N.M., Conformational changes of NADPH-cytochrome P450 oxidoreductase are essential for catalysis and cofactor binding (2011) J Biol Chem, 286, pp. 16246-16260Herkert, J.C., Blaauwwiekel, E.E., Hoek, A., Veenstra-Knol, H.E., Kema, I.P., Arlt, W., A rare cause of congenital adrenal hyperplasia: Antley-Bixler syndrome due to POR deficiency (2011) Neth J Med, 69, pp. 281-283Fukami, M., Hasegawa, T., Horikawa, R., Ohashi, T., Nishimura, G., Homma, K., Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: Diagnostic value of urine steroid hormone analysis (2006) Pediatr Res, 59, pp. 276-280Flück, C.E., Miller, W.L., P450 oxidoreductase deficiency: A new form of congenital adrenal hyperplasia (2006) Curr Opin Pediatr, 18, pp. 435-441Homma, K., Hasegawa, T., Nagai, T., Adachi, M., Horikawa, R., Fujiwara, I., Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency: Implication for the backdoor pathway to dihydrotestosterone (2006) J Clin Endocrinol Metab, 91, pp. 2643-2649But, W.M., Lo, I.F., Shek, C.C., Tse, W.Y., Lam, S.T., Ambiguous genitalia, impaired steroidogenesis, and Antley-Bixler syndrome in a patient with P450 oxidoreductase deficiency (2010) Hong Kong Med J, 16, pp. 59-62Iijima, S., Ohishi, A., Ohzeki, T., Cytochrome P450 oxidoreductase deficiency with Antley-Bixler syndrome: Steroidogenic capacities (2009) J Pediatr Endocrinol Metab, 22, pp. 469-475Ko, J.M., Cheon, C.K., Kim, G.H., Yoo, H.W., A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene (2009) Eur J Pediatr, 168, pp. 877-880Sahakitrungruang, T., Huang, N., Tee, M.K., Agrawal, V., Russell, W.E., Crock, P., Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients (2009) J Clin Endocrinol Metab, 94, pp. 4992-5000Adachi, M., Tachibana, K., Asakura, Y., Yamamoto, T., Hanaki, K., Oka, A., Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome (2004) Am J Med Genet A, 128, pp. 333-339New, M.I., Nonclassical congenital adrenal hyperplasia and the polycystic ovarian syndrome (1993) Ann NY Acad Sci, 687, pp. 193-205Rosa, S., Duff, C., Meyer, M., Lang-Muritano, M., Balercia, G., Boscaro, M., P450c17 deficiency: Clinical and molecular characterization of six patients (2007) J Clin Endocrinol Metab, 92, pp. 1000-1007Shima, M., Tanae, A., Miki, K., Katsumata, N., Matsumoto, S., Nakajima, S., Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia (2000) Eur J Endocrinol, 142, pp. 274-279Belgorosky, A., Pepe, C., Marino, R., Guercio, G., Saraco, N., Vaiani, E., Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterozygote for two new point mutations of the CYP19 gene (2003) J Clin Endocrinol Metab, 88, pp. 5127-5131Fukami, M., Horikawa, R., Nagai, T., Tanaka, T., Naiki, Y., Sato, N., Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: Molecular and clinical studies in 10 patients (2005) J Clin Endocrinol Metab, 90, pp. 414-426Grondahl, C., Hansen, T.H., Marky-Nielsen, K., Ottesen, J.L., Hyttel, P., Human oocyte maturation in vitro is stimulated by meiosis-activating sterol (2000) Hum Reprod, 15 (SUPPL. 5), pp. 3-1

Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1 [seguimento De Longo Prazo Em Um Menino De 8 Anos De Idade Com Insulinoma Como Primeira Manifestação De Neoplasia Endócrina Múltipla Tipo 1]

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling. © ABE&M todos os direitos reservados.548754760Carling, T., Multiple endocrine neoplasia syndrome: Genetic basis for clinical management (2005) Curr Opin Oncol, 17, pp. 7-12Guang-Wen, Z., Yao, W., Xi, C., Xiao-Hua, J., Xiao-Ying, L., Guang, N., Diagnosis and surgical treatment of multiple endocrine neoplasia (2009) Chin Med J, 122, pp. 1495-1500Brandi, M.L., Gagel, R.F., Angell, A., Bilczikian, J.P., Beck-Peccoz, P., Bordi, C., Consensus: Guidelines for diagnosis and therapy of MEN type 1 and type 2 (2001) J Clin Endocrinol Metab, 86, pp. 5658-5671Newey, P.J., Jeyabalan, J., Walls, G.V., Christie, P.T., Gleeson, F.V., Gould, S., Nonfunctioning tumors in children with MEN1 (2009) J Clin Endocrinol Metab, 94, pp. 3640-3646Corbetta, S., Pizzocaro, A., Beck-Peccoz, P.P., Faglia, G., Spada, A., Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types (1997) Clin Endocrinol, 47, pp. 507-512Yoshimoto, K., Saito, S., Clinical characteristics in multiple endocrine neoplasia type 1 in Japan: A review of 106 patients (1991) Nippon Naibunpi Gakkai Zasshi, 67, pp. 764-774Marx, S.J., Spiegel, A.M., Skarulis, M.C., Doppman, J.L., Collins, P.S., Liotta, L.A., Multiple endocrine neoplasia type 1: Clinical and genetic topics (1998) Ann Intern Med, 129, pp. 484-494Chandrasckharappa, S.C., Guru, S.C., Manickan, P., Olufemi, S.E., Collins, P.S., Emmert-Buck, M.R., Positional cloning of the gene for multiple endocrine neoplasia-type 1 (1997) Science, 276, pp. 404-407Franchi, G.M., Villa, V.V., Carrera, P., Sartorio, S.M., Maffi, P., Bosi, E., A new mutation in the MEN1 gene (2009) Cancer Genet Cytogenet, 192, pp. 199-201Kim, H., Lee, J.R., Cho, E.J., Liu, J.O., Youn, H.D., Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with mSln3A-histonic deacctylase complex (2003) Cancer Res, 63, pp. 6135-6139Falchetti, A., Marini, F., Brandi, M.L., Multiple endocrine neoplasia (2010) GeneReviews, , http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=men1, Available at, Accessed at: 27 Jul 2010Geerdink, B.A.M., van der Luijt, R.B., Lips, C.J.M., Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening? (2003) Eur J Endocrinol, 149, pp. 577-582Falchetti, A., Brandi, M.L., Multiple endocrine neoplasia type I variants and phenocopies: More than a nosological issue? (2009) J Clin Endocrinol Metab, 94, pp. 1518-1520Marx, S.J., Nieman, L.K., Aggressive pituitary tumours in MEN1: Do they refute the two-hit model of tmorigenesis? (2002) J Clin Endocrinol Metab, 87, pp. 453-456Sambrook, J., Fritsch, E.F., Maniatis, T.E., Molecular cloning, a laboratory manual (1989), New York: Cold Spring HarborLourenço Jr., D.M., Coutinho, F.L., Toledo, R.A., Montenegro, F.L., Correia-Deur, J.E., Toledo, S.P., Early-onset, progressive, frequent, extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (2010) J Bone Miner Res, 25 (11), pp. 2382-2391Ruszniewski, P., Fave, G.D., Cadiot, G., Komminoth, P., Chung, D., Kos-Kudla, B., Well-differentiated gastric tumors/carcinomas (2006) Neuroendocrinology, 84, pp. 158-164Schussheim, D.H., Skarulis, M.C., Agarwal, S.K., Simonds, W.F., Burns, A.L., Spiegel, A.M., Multiple endocrine neoplasia type 1: New clinical and basic findings (2001) Trends Endocrinol Metab, 12, pp. 173-178Rix, M., Hertel, N.T., Nielsen, F.C., Jacobsen, B.B., Hoejberg, A.S., Brixen, K., Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1 (2004) Eur J Endocrinol, 151, pp. 709-715Correa, P., Lundgren, E., Rastad, J., Åkerström, G., Westin, G., Carling, T., Multiple endocrine neoplasia type 1 polymorphism D418D is associated with sporadic primary hyperparathyroidism (2002) Surgery, 132, pp. 450-455Toledo, R.A., Lourenço, D.M., Coutinho, F.L., Quedas, E., Mackowiack, I., Machado, M.C., Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (2007) Clin Endocrinol, 67, pp. 377-384Lourenço, D.M., Toledo, R.A., Coutinho, F.L., Margarido, L.C., Siqueira, S.A., dos Santos, M.A., The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1 (2007) Clinics (Sao Paulo), 62, pp. 465-476Stratakis, C.A., Shussheim, D.H., Freedman, S.M., Keil, M.F., Pack, S.D., Agarwal, S.K., Pituitary macroadenoma in 5-year-old: An early expression of multiple endocrine neoplasia type 1 (2000) J Clin Endocrinol Metab, 85, pp. 4776-4780Kontogeorgos, G., Kapranos, N., Tzavara, I., Thalassinos, N., Rologis, D., Monossomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1 (2001) Clin Endocrinol, 54, pp. 117-120Johnston, L.B., Chew, S.L., Trainer, P.J., Reznck, R., Grossman, A.B., Besser, G.M., Screening children at risk of developing inherited endocrine neoplasia syndromes (2000) Clin Endocrinol, 52, pp. 127-136Johnston, L.B., Chew, S.L., Lowe, D., Reznck, R., Monsom, J.P., Savage, M.O., Investigating familial endocrine neoplasia syndromes in children (2001) Horm Res, 55, pp. 31-35Lourenço, D.M., Toledo, R.A., Mackowiak, I.I., Coutinho, F.L., Cavalcanti, M.G., Correia-Deur, J.E., Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile (2008) Eur J Endocrinol, 159, pp. 259-274Görtz, B., Roth, J., Speel, E.J.M., Krähemmann, A., de Krieger, R.R., Matias-Guiu, X., MEN1 gene mutation analysis of sporadic adrenocortical lesions (1999) Int J Cancer, 80, pp. 373-379Kishi, M., Tsukada, T., Shimizu, S., Hosono, K., Ohkubo, T., Kosuge, T., A novel splicing mutation (894-9 G-A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1 (1999) Cancer Letters, 142, pp. 105-110Bassett, J.H., Forbes, S.A., Pannett, A.A., Lloyd, S.E., Christie, P.T., Wooding, C., Characterization of mutations in patients with multiple endocrine neoplasia type 1 (1998) Am J Hum Genet, 62, pp. 232-24