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Are Adolescent Boys with Klinefelter Syndrome Androgen Deficient?« Back to Volume 22, Issue 4, December 2006 - Table of Contents Wikström and colleagues followed 14 non mosaic 47,XXY boys with Klinefelter syndrome (KS) prospectively for 4–25 months (median 18 months) beginning at a median age of 11.5 years (range 10–13.9 years). The median bone age at the start of the study was also 11.5 years (range 7.5–14.5 years). The subjects were examined every 4 to 6 months and puberty was staged and serum taken for hormone measurements. Body mass index (BMI) was calculated as were width and length of the testes. Testicular volume was calculated, bone age was assessed annually, and gonadotropin-releasing hormone (GnRH) stimulation test performed. Hormones evaluated included testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), prostrate-specific antigen (PSA), and leptin. For comparison for serum T and E2 levels, a control group of recently published reference values from 55 healthy Swedish boys was used. The longitudinal changes in the other hormones were compared to values obtained in healthy, untreated Finnish boys with constitutional delay of puberty. Bone age, rather than chronologic age, was used for the comparison. In the boys with KS, both the onset and progression of puberty fell within the normal range for Finnish boys. However, there was an arrest in testicular growth during puberty and testicular volumes never exceeded 4.5 mL. Mean testicular volume of 2.0 mL was used to indicate the clinical onset of puberty which occurred at a median age of 12.6 years. During follow-up, gynecomastia occurred in 11 boys with KS; this was reversible in 5 boys. Only 1 of the 11 boys had reached Tanner Stage III puberty. No significant delay in skeletal maturation was seen during puberty in these boys. The longitudinal changes in serum testosterone were not different from that seen in the controls. However, some of the older boys displayed hypergonadotropism, as evidenced by elevated serum LH levels. Before the age of 12, the KS boys had higher serum estradiol levels than the controls. No tendency appeared for higher estradiol levels or higher E2/T ratios among KS boys with gynecomastia compared to those without. Serum SHBG levels in KS boys decreased with levels remaining in the normal range. Both the timing and the magnitude of the rise in serum PSA in the KS boys were normal. Serum leptin levels decreased during puberty, but were on average higher in the KS group than in the controls; mean BMI did not differ between the 2 groups. LH and FSH responses to gonadotropin releasing hormone (GnRH) were pathologically elevated beginning in mid puberty at the age of 13 to 14, with FSH responses being exaggerated earlier. The authors concluded that the rate of pubertal progression in KS boys is normal, as is the timing of onset of puberty. Testicular growth however was impaired. There is no phenotypic evidence for androgen deficiency during early and mid puberty, as skeletal maturation fell within the normal range for healthy Finnish boys. Impaired testosterone secretion was not evident during early to mid puberty. Since the testosterone concentrations do not necessarily reflect androgen activity, the SHBG, PSA, and leptin level concentrations were determined. These hormones are regulated to some extent by androgens and can be a marker of testosterone action. There was no evidence of diminished androgen activity at the cellular level. The KS boys did have higher leptin and higher leptin/BMI ratios than the controls, suggesting some type of diminished androgen action in adipose tissue. The authors concluded that the KS boys have sufficient testosterone to allow normal progression of puberty and adequate androgen action until mid puberty. Thus there is no indisputable evidence that androgen supplementation during early puberty would be of significant benefit. However, neurodevelopmental and psychosocial evaluations were not performed during this study. Thus it is unclear whether these factors may benefit from early androgen supplementation. Editor’s CommentThis is a very interesting longitudinal study which presents important information for endocrinologists, geneticists, and pediatricians who provide care for boys with KS. The authors have demonstrated that the onset and initial progression of puberty occurs normally in these boys, and there is no evidence of androgen deficiency at the cellular level before mid puberty. Thus the degeneration of seminiferous tubules which occurs in these adolescents does not appear to be a result of diminished androgen action at least in early puberty. The authors pointed out that they have not performed, or at least not reported, on neurological and psychological outcomes and whether or not these may be affected by early androgen administration. Such studies are clearly needed in order to make recommendations for hormonal replacement. Collaboration between endocrinologists and neuropsychologists is clearly needed to better understand how to help these children. William L. Clarke, MD
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
