Early-onset primary hypogonadism revealed by serum anti-Müllerian hormone (AMH) determination during infancy and childhood in trisomy 21

GRINSPON ROMINA; BEDECARRÁS P; GERMÁN IÑÍGUEZ; ANA ROCHA; ELISABETE A. MANTOVANI RODRIGUES RESENDE; VINICIUS N BRITO; CARLOS MILANI; TERESA SIR-PETERMANN; FIGUEROA GACITUA V.; MARÍA JOSÉ RIAL; SERGIO RECABARREN; ANDREA FORRESTER; ANA CHIESA; KESELMAN A.; GOTTLIEB S.; PATRICIA PAPENDIECK; ANDREA ARCARI; HAMILTON CASSINELLI; BERGADÁ , IGNACIO; GRYNGARTEN MIRTA; MARINA TROIANO; CLEMENT FLORENCIA; SOLEDAD RODRIGUEZ PRIETO; ROSA ENACÁN; VIVIANA OSTA; JEAN-YVES PICARD; MARIA DE FÁTIMA BORGES; MARIA G. ROPELATO; VÉRONIQUE GARZINO; JOSSO N; ETHEL CODNER; REY RA

Glasgow

Congreso; 50th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE); 2011

European Society for Paediatric Endocrinology (ESPE)

P2-d2-662 Gonads and Gynaecology 1 Early-onset primary hypogonadism revealed by serum anti-Müllerian hormone (AMH) determination during infancy and childhood in trisomy 21 Romina Grinspon1; Patricia Bedecarrás1; María Gabriela Ballerini1; German Iñiguez2; Ana Rocha2; Elisabete Mantovani Rodrigu3; Vinicius N. Brito4; Carlos Milani5; Teresa Sir-Petermann2; Verónica Figueroa Gacitúa6; María José Rial6; Sergio Recabarren7; Andrea Forrester6; Ana Chiesa1; Ana Keselman1; Silvia Gottlieb1; Patricia Papendieck1; Andrea Arcari1; Andrea Arcari1; Hamilton Cassinelli1; Ignacio Bergadá1; Mirta Gryngarten1; Marina Troiano1; Florencia Clément1; María Soledad Rodriguez Prieto1; Rosa Enacán1; Viviana Osta8; Jean-Yves Picard9; Maria de Fátima Borges3; María Gabriela Ropelato1; Véronique Garzino10; Nathalie Josso9; Ethel Codner11; Rodolfo Rey1 1Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), División de Endocrinología, Buenos Aires, Argentina; 2Universidad de Chile, IDIMI, Santiago, Chile; 3Universidade Federal do Triângulo Mineiro, Hospital Escola, Uberaba, Minas Gerais, Brazil; 4Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, São Paulo, Brazil; 5Instituto de Análisis Clínicos Dr. ?Héctor A. Milani?, Endocrinología, Junín, Argentina; 6Hospital de Niños Pedro de Elizalde, Departamento de Endocrinología, Buenos Aires, Argentina; 7Universidad de Concepción, Facultad de Ciencias Veterinarias, Chillán, Chile; 8Hospital de Niños R. Gutiérrez, Laboratorio central, Buenos Aires, Argentina; 9Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud, Unité Mixte de Recherche, Clamart, France; 10Immunotech, Beckman-Coulter Co., Marseilles, France; 11Universidad de Chile and Hospital Clínico San Borja Arriarán, Instituto de Investigaciones Materno Infantil (IDIMI), Facultad de Medicina, Santiago, Chile Background: Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ cell failure. Scarce information is available in trisomy 21, a frequent autosomal aneuploidy. Objective and hypotheses: We asked whether trisomy 21 presents with pubertal-onset, germ cell-specific, primary hypogonadism, or whether the hypogonadism is established earlier and affects other testicular cell populations. Methods: We assessed the pituitary-testicular axis functional status, especially Sertoli cell function. To compare with an adequate control population, we established reference levels for AMH in 357 normal males using a recently developed ultrasensitive assay. Results: In normal males, AMH increased from birth to 2-3 yr, then decreased to a plateau until pubertal onset, and further decreased until adulthood. The main fall was between Tanner stages 1 and 3, in coincidence with a significant increase in testis volume and serum testosterone. Serum AMH was above assay sensitivity at all ages (Table). In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy (Table). :::*^ FSH was elevated in 100% of patients <0.5 yr, 41% aged 0.5-2.9 yr, 18% aged 3-8.9 yr, 13% >9 yr G1, 50% G2, 50% G3, 88% G4 and 100% G5. Testosterone was within the normal range, but LH was elevated in 75% of patients <0.5 yr, 6% 0.5-2.9 yr, 13% 3-8.9 yr, 0% >9 yr G1, 17% G2, 50% G3, 71% G4 and 50% G5, indicating a mild Leydig cell dysfunction. Conclusions: In trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.