Primary Testicular Dysfunction Is a Major Contributor to Abnormal Pubertal Development in Males with Prader-Willi Syndrome

Hirsch, Harry J.; Eldar‐Geva, Talia; Benarroch, Fortu; Rubinstein, Orit; Gross‐Tsur, Varda

doi:10.1210/jc.2008-2760

Cited by 62 publications

(66 citation statements)

References 36 publications

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“…Hypogonadotropic hypogonadism was found in more than 25% of the participants in our study, while in males with PWS, severe gonadotropin deficiency is a rare cause of hypogonadism (6,(8)(9)(10). The dissimilarity in hypothalamic-pituitary function between males and females with PWS might be explained by the divergence in the regulation of FSH secretion between normal males and females.…”

Section: Discussionmentioning

confidence: 47%

“…We found that pubertal development in PWS females, as in males, is characterized by normal adrenarche followed by pubertal arrest. Most females with PWS had variable hypothalamic dysfunction and a unique pattern of ovarian dysfunction characterized by extremely low or undetected inhibin B along with normal AMH levels, resembling the findings of the primary testicular defect in PWS males (10). A small subgroup of women, however, showed detectable inhibin B levels, albeit subnormal for their age, which might be compatible with partial ovarian follicular development.…”

Section: Discussionmentioning

confidence: 78%

“…Clinical features, attributed mainly to hypothalamic dysfunction (2, 5-7), include severe hypotonia and feeding difficulties in infancy, an insatiable appetite leading to severe obesity in childhood, short stature, and hypogonadism as well as dysmorphic features and variable degrees of mental retardation (2)(3)(4). Although hypogonadism has often been attributed to hypothalamic dysfunction, some studies show that a primary testicular defect contributes to the hypogonadism in PWS males (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Hypogonadism in females with Prader–Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction

Eldar‐Geva

Hirsch

Benarroch

et al. 2010

European Journal of Endocrinology

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Objective: The variable hypogonadism in Prader-Willi syndrome (PWS) has generally been attributed to hypothalamic dysfunction. Recent studies have documented primary testicular dysfunction in PWS males. Our aims were to characterize sexual development and reproductive hormones in PWS females and to investigate the etiology of hypogonadism. Design: A cross-sectional study. Methods: Physical examination was performed on 45 PWS females (aged 6 weeks to 32 years) and blood samples were obtained for hormonal analyses. Results: Age of onset and progression of puberty varied; most adults had incomplete sexual development. Spontaneous menarche was reported in four (aged 15-30 years) but all had subsequently developed secondary amenorrhea or oligomennorrhea. Anti-Mullerian hormone levels were within the normal range in all age groups. Inhibin B was consistently low or undetectable; only five women had levels in the low-normal range (20-54 pg/ml). LH was normal in most children, but low (!1.0 IU/l) in 9 of 15 adults. FSH was within the normal range for age in most children, but low (!0.5 IU/l) in 10 and high in four adults. Estradiol levels were normal-low and androgen levels were normal in the majority. Conclusions: Pubertal development in PWS females, as in males, is characterized by normal adrenarche, pubertal arrest, and hypogonadism due to variable combinations of a unique primary gonadal defect and hypothalamic dysfunction.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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Hypogonadism in females with Prader–Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction

Eldar‐Geva

Hirsch

Benarroch

et al. 2010

European Journal of Endocrinology

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“…Although the hypogonadism in PWS has long been believed to be entirely hypothalamic, resulting in low gonadotropins and subsequent low gonadal hormones, recent studies have suggested that there is a combination of hypothalamic and primary gonadal deficiencies. [30][31][32] That conclusion was largely based on absence of hypogonadotropism and abnormally low inhibin B in both sexes. In a recent study, all 20 individuals with PWS who were evaluated had brain abnormalities that were not found in 21 sibs or 16 individuals with early-onset morbid obesity who did not have PWS.…”

Section: Other Endocrine Issuesmentioning

confidence: 99%

Prader-Willi syndrome

Cassidy

Schwartz

Miller

et al. 2012

Genetics in Medicine

1,134

1,193

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“…Boys and adolescents present normal/low AMH, low inhibin B, normal/low testosterone and normal/high FSH and LH (43)(44)(45).…”

Section: Primary Hypogonadism With Germ Cell-specific Dysfunctionmentioning

confidence: 99%

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker

Grinspon

Rey

2011

Arq Bras Endocrinol Metab

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SUMMARYSertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHb mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis. Arq Bras Endocrinol Metab. 2011;55(8):512-9 Keywords Hypogonadotrophic hypogonadism; hypergonadotrophic hypogonadism; testis; anorchia; cryptorchidism; disorders of sex development SUMáRioAs células de Sertoli são a população de células mais ativa nos testículos durante a primeira e segunda infância. Neste período, o hipogonadismo só pode ser evidenciado sem o uso de testes estimulatórios se a função das células de Sertoli for avaliada. O AMH é um marcador útil do nú-mero e da atividade das células de Sertoli no período pré-puberal. A concentração sérica de AMH é alta da metade da vida fetal até a metade da puberdade. A produção de AMH pelos testículos aumenta em resposta ao FSH e é potencialmente inibida por androgênios. O AMH sérico não é detectável em pacientes anorquídicos. No hipogonadismo central ou primário afetando a gônada inteira, ou estabelecido na vida fetal ou infância, a concentração de AMH sérica é baixa. Por outro lado, quando o hipogonadismo afeta apenas as células de Leydig (por exemplo, nas mutações, LHb, defeitos do receptor de LH/CG ou das enzimas esteroidogênicas), a concentração de AMH sé-rico é normal ou alta. Em meninos púberes com hipogonadismo central, a concentração de AMH é baixa para o estágio na escala de Tanner (refletindo a falta de estímulo pelo FSH), mas alta para a idade (indicando a falta do efeito inibidor da testosterona). O tratamento com FSH provoca um aumento do AMH sérico, enquanto a administração de hCG aumenta os níveis de testosterona, que fazem a downregulation do AMH. Em conclusão, a concentração sérica de AMH é útil na avaliação da função gonadal, excluindo a necessidade de testes estimulatórios, e direciona o diagnóstico et...

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Primary Testicular Dysfunction Is a Major Contributor to Abnormal Pubertal Development in Males with Prader-Willi Syndrome

Abstract: Pubertal development in PWS is characterized by normal adrenarche, variable hypothalamic dysfunction, and hypogonadism due to a unique testicular defect. Primary testicular dysfunction is a major component of hypogonadism in PWS.

Cited by 62 publications

References 36 publications

Hypogonadism in females with Prader–Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction

Hypogonadism in females with Prader–Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction

Prader-Willi syndrome

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker

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