The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

A. Lucas-herald; S. Bertelloni; A. Juul; J. Bryce; J. Jiang; M. Rodie; Richard Sinnott; M. Boroujerdi; M. Lindhardt Johansen; O. Hiort; P. M. Holterhus; M. Cools; G. Guaragna-filho; G. Guerra-junior; N. Weintrob; S. Hannema; S. Drop; T. Guran; F. Darendeliler; A. Nordenstrom; I. A. Hughes; Carlo Acerini; R. Tadokoro-cuccaro; S. F. Ahmed

doi:10.1210/jc.2016-1372

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

A. Lucas-herald, S. Bertelloni, A. Juul, J. Bryce, J. Jiang, M. Rodie, Richard Sinnott, M. Boroujerdi, M. Lindhardt Johansen, O. Hiort, P. M. Holterhus, M. Cools, G. Guaragna-filho, G. Guerra-junior, N. Weintrob, S. Hannema, S. Drop, T. Guran, F. Darendeliler, A. NordenstromI. A. Hughes, Carlo Acerini, R. Tadokoro-cuccaro, S. F. Ahmed

Institut for Klinisk Medicin

44 Citationer (Scopus)

Abstract

Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16years)and22years (range,16to52years), respectively.Ofthe cohort,29men(56%)had20different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P=.004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. (J Clin Endocrinol Metab 101: 3959-3967, 2016).

Originalsprog	Engelsk
Tidsskrift	The Journal of Clinical Endocrinology & Metabolism
Vol/bind	101
Udgave nummer	11
Sider (fra-til)	3959-3967
ISSN	0021-972X
DOI	https://doi.org/10.1210/jc.2016-1372
Status	Udgivet - nov. 2016

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10.1210/jc.2016-1372

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Lucas-herald, A., Bertelloni, S., Juul, A., Bryce, J., Jiang, J., Rodie, M., Sinnott, R., Boroujerdi, M., Lindhardt Johansen, M., Hiort, O., Holterhus, P. M., Cools, M., Guaragna-filho, G., Guerra-junior, G., Weintrob, N., Hannema, S., Drop, S., Guran, T., Darendeliler, F., ... Ahmed, S. F. (2016). The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene. The Journal of Clinical Endocrinology & Metabolism, 101(11), 3959-3967. https://doi.org/10.1210/jc.2016-1372

Lucas-herald, A, Bertelloni, S, Juul, A, Bryce, J, Jiang, J, Rodie, M, Sinnott, R, Boroujerdi, M, Lindhardt Johansen, M, Hiort, O, Holterhus, PM, Cools, M, Guaragna-filho, G, Guerra-junior, G, Weintrob, N, Hannema, S, Drop, S, Guran, T, Darendeliler, F, Nordenstrom, A, Hughes, IA, Acerini, C, Tadokoro-cuccaro, R & Ahmed, SF 2016, 'The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene', The Journal of Clinical Endocrinology & Metabolism, bind 101, nr. 11, s. 3959-3967. https://doi.org/10.1210/jc.2016-1372

@article{0902d320a62046ca861ae8de7a6af16b,

title = "The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene",

abstract = "Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16years)and22years (range,16to52years), respectively.Ofthe cohort,29men(56%)had20different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P=.004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. (J Clin Endocrinol Metab 101: 3959-3967, 2016).",

author = "A. Lucas-herald and S. Bertelloni and A. Juul and J. Bryce and J. Jiang and M. Rodie and Richard Sinnott and M. Boroujerdi and {Lindhardt Johansen}, M. and O. Hiort and Holterhus, {P. M.} and M. Cools and G. Guaragna-filho and G. Guerra-junior and N. Weintrob and S. Hannema and S. Drop and T. Guran and F. Darendeliler and A. Nordenstrom and Hughes, {I. A.} and Carlo Acerini and R. Tadokoro-cuccaro and Ahmed, {S. F.}",

year = "2016",

month = nov,

doi = "10.1210/jc.2016-1372",

language = "English",

volume = "101",

pages = "3959--3967",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "11",

}

TY - JOUR

T1 - The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

AU - Lucas-herald, A.

AU - Bertelloni, S.

AU - Juul, A.

AU - Bryce, J.

AU - Jiang, J.

AU - Rodie, M.

AU - Sinnott, Richard

AU - Boroujerdi, M.

AU - Lindhardt Johansen, M.

AU - Hiort, O.

AU - Holterhus, P. M.

AU - Cools, M.

AU - Guaragna-filho, G.

AU - Guerra-junior, G.

AU - Weintrob, N.

AU - Hannema, S.

AU - Drop, S.

AU - Guran, T.

AU - Darendeliler, F.

AU - Nordenstrom, A.

AU - Hughes, I. A.

AU - Acerini, Carlo

AU - Tadokoro-cuccaro, R.

AU - Ahmed, S. F.

PY - 2016/11

Y1 - 2016/11

N2 - Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16years)and22years (range,16to52years), respectively.Ofthe cohort,29men(56%)had20different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P=.004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. (J Clin Endocrinol Metab 101: 3959-3967, 2016).

AB - Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. Results: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16years)and22years (range,16to52years), respectively.Ofthe cohort,29men(56%)had20different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P=.004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. Conclusions: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management. (J Clin Endocrinol Metab 101: 3959-3967, 2016).

U2 - 10.1210/jc.2016-1372

DO - 10.1210/jc.2016-1372

M3 - Journal article

C2 - 27403927

SN - 0021-972X

VL - 101

SP - 3959

EP - 3967

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 11

ER -

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

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