Puberty in 24 patients with Klinefelter syndrome

Abstract

Abstract. Twenty four boys with Klinefelter syndrome, 18 of whom were diagnosed prepubertally, were observed until adulthood. Onset of puberty, as judged from testicular enlargement and pubic hair development, occurred between 11 to 14 years in the above 18 patients. By the age of 17 pubic hair, penile length and height had reached the adult stage in all patients, but arrest of testicular growth was noted at midpuberty, 13 years, with maximal mean (+_ SD) volume attained being 3.5 4-1.5 ml. The first conscious ejaculation was reported to have occurred between 13 to 16 years in 10 patients and in the remaining 4 between 17 to 18 years of age. Sperm counts obtained after the age of 18 revealed azospermia or severe oligospermia in all patients except one, who had a sperm count of 30 • 106/ml. The hypothalamic-pituitary-gonadal axis, assessed by LH-RH and hCG stimulation tests, was found to be normal in prepuberty and during early pubertal stages. From mid-puberty the basal levels of plasma FSH and the response to LH-RIt showed a gradual increase above the normal. Towards late puberty (> 15 years) basal and peak levels of LH were above normal with a concomitant decrease in the basal level of testosterone and its response to hCG.These findings indicate that during childhood and early puberty function of the hypothalamic-pituitary-gonadal axis is normal in Klinefelter syndrome, allowing the onset of pubertal signs at the appropriate age, and that until late puberty there is a relative preservation of function in the testicular Leydig cells, permitting the normal sequential development of the androgen-dependent pubertal signs. The measurement of testicular testosterone reserve by means of hCG stimulation constitutes a useful aid in determining when and if testosterone replacement therapy should be instituted. Key words: Klinefelter syndrome -PubertyThe clinical, hormonal and histological picture of Klinefelter syndrome has been given wide attention in the literature since the original description published in 1942 [13]. Histological studies indicate that testicular damage is already present in the perinatal and prepubertal periods [15,21]. The progression of these changes during puberty has been found to lead to faulty spermatogenesis [10] as well as a decrease in testosterone production and secretion by the testes [14,31] with signs of hypovirilization in most of these patients [8].Reprint requests to: Prof. Z. Laron, Institute of Pediatric and Adolescent Endocrinology, Beilinson Medical Center, Petah Tikva 49 100, Israel Presented here are the findings made during long-term follow-up in 24 patients with Klinefelter syndrome, most of whom had been diagnosed before puberty. It was the aim of this study to investigate the sequence of the clinical and hormonal changes taking place and their inter-relationships, before and during puberty. Patients and MethodsThe patient material comprised 24 patients in all of whom the diagnosis of Klinefelter syndrome was confirmed by chromosomal studies. In 18, diagnosis was made before ...

Klinefelter syndrome: an unusual diagnosis in pediatric patients

“…Do ponto de vista hormonal, pacientes com SK apresentam valores pré-puberais normais de T, LH, FSH, inibina B e hormônio antimülleriano, com resposta normal da T ao teste de estímulo com gonadotrofina coriônica humana 9,10,20,21 . Durante a puberdade, após um aumento normal da T, esta pode, em alguns casos, se manter em níveis normais baixos para o estadio de maturação sexual, porém com condições de progredir e determinar o desenvolvimento satisfatório das características sexuais secundárias 9,10,20,21 .…”

“…Do ponto de vista hormonal, pacientes com SK apresentam valores pré-puberais normais de T, LH, FSH, inibina B e hormônio antimülleriano, com resposta normal da T ao teste de estímulo com gonadotrofina coriônica humana 9,10,20,21 . Durante a puberdade, após um aumento normal da T, esta pode, em alguns casos, se manter em níveis normais baixos para o estadio de maturação sexual, porém com condições de progredir e determinar o desenvolvimento satisfatório das características sexuais secundárias 9,10,20,21 . A partir da metade da puberdade, em geral, os pacientes com SK já começam a apresentar um aumento gradual do FSH (refletindo a disfunção dos túbulos seminíferos e das células de Sertoli) e do LH (refletindo a disfunção das células de Leydig), sendo que o aumento do FSH em geral precede (cerca de 1 ano antes) e é mais intenso do que o de LH; tais dados podem, a partir deste momento, auxiliar na suspeita diagnóstica, como verificado no presente estudo.…”

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

“…However, from around midpuberty the testicular deterioration occurs, as evidenced by a regression of testicular volume (5,41) (Fig. 3) and levelling off in the serum concentrations of testosterone and INSL3, both of which remain in the low-normal range through puberty (17,36,37,39). Concomitantly, a dramatic decline is observed in inhibin B concentrations, which are most often undetectable at the end of puberty in Klinefelter patients (17,38,39).…”

“…In childhood, KS boys are characterized by normal concentrations of testosterone, FSH, LH, anti-Mü llerian hormone (AMH), inhibin B, and insulin-like factor 3 (INSL3) until the onset of puberty (17,18,36,37,38,39,40,41,42,43). KS boys usually enter puberty at the expected age with an initial normal increase in testicular volume (Fig.…”

“…At midpuberty, a relative hypogonadism is usually evident by increasing LH and FSH concentrations to hypergonadotropic levels. FSH increases earlier and more markedly than LH (5,36,37,41). Adults with KS are characterized by hypergonadotropic hypogonadism with highly elevated serum concentrations of FSH and LH.…”