title: Early onset of primary hypogonadism revealed by serum anti-Müllerian hormone determination during infancy and childhood in trisomy 21.
abstract: 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 on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.
authors.affiliation: División de Endocrinología, Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. rgrinspon@cedie.org.ar
authors.forename: R P
authors.initials: RP
authors.lastname: Grinspon
authors.forename: P
authors.initials: P
authors.lastname: Bedecarrás
authors.forename: M G
authors.initials: MG
authors.lastname: Ballerini
authors.forename: G
authors.initials: G
authors.lastname: Iñiguez
authors.forename: A
authors.initials: A
authors.lastname: Rocha
authors.forename: E A
authors.initials: EA
authors.lastname: Mantovani Rodrigues Resende
authors.forename: V N
authors.initials: VN
authors.lastname: Brito
authors.forename: C
authors.initials: C
authors.lastname: Milani
authors.forename: V
authors.initials: V
authors.lastname: Figueroa Gacitúa
authors.forename: A
authors.initials: A
authors.lastname: Chiesa
authors.forename: A
authors.initials: A
authors.lastname: Keselman
authors.forename: S
authors.initials: S
authors.lastname: Gottlieb
authors.forename: M F
authors.initials: MF
authors.lastname: Borges
authors.forename: M G
authors.initials: MG
authors.lastname: Ropelato
authors.forename: J-Y
authors.initials: JY
authors.lastname: Picard
authors.forename: E
authors.initials: E
authors.lastname: Codner
authors.forename: R A
authors.initials: RA
authors.lastname: Rey
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications / Q000503:physiopathology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D007223:Infant; D007231:Infant, Newborn; D007985:Leydig Cells / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size; D012708:Sertoli Cells / Q000502:physiology; D013737:Testis / Q000033:anatomy & histology; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone