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OBJECTIVE: To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS). DESIGN: In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population. METHODS: Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer. RESULTS: Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E2) concentrations started to increase during puberty and inhibin B and anti-Müllerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P<0.01), FSH (7.1 vs 2.5 U/l, P<0.001), testosterone (18.7 vs 15.6 nmol/l, P<0.01) and E2(66 vs 46 pmol/l, P<0.001) levels and lower AMH (33 vs 65 pmol/l, P<0.01) and inhibin B (median 108 vs 187 pg/ml, P<0.01) levels than the reference population. CONCLUSIONS: In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To test the clinical usefulness of sensitive commercial immunoassays for determination of low 17β-estradiol concentrations in children. METHODS: The lower limit of detection and clinical usefulness (functional sensitivity) of three commercial estradiol immunoassays were validated by use of 500 sera from prepubertal and pubertal children and 55 pooled sera. The three immunoassays consisted of two modified direct immunoassays; one RIA (Spectria Estradiol RIA) and one time-resolved fluoroimmunoassay (AutoDELFIA Estradiol), both with increased serum volume in relation to antibody concentration and extended incubation time. In the third method, serum was purified and concentrated using diethyl ether extraction prior to measurement by the modified Spectria Estradiol RIA. RESULTS: The lower limits of detection and clinical usefulness were 9 and 30 pmol/l for the direct RIA, 11 and 50 pmol/l for the AutoDELFIA, and 4 and 6 pmol/l for serum determined by extraction RIA. When measuring the serum pool originating from girls at breast stages 1–2, the direct RIA and AutoDELFIA resulted in significantly higher 17β-estradiol concentrations when compared with the extraction RIA (+58 and +267%, P<0.001). We found a significant difference in 17β-estradiol concentrations between girls at breast stages 1 (median 6 pmol/l) and 2 (median 16 pmol/l), when quantified by the extraction RIA (P<0.0001) but no difference when quantified with the direct RIA (median values 12 and 14 pmol/l respectively). CONCLUSION: For determination of low serum 17β-estradiol concentrations in children, an extraction step prior to commercial immunoassay is needed to achieve clinically useful results. [ABSTRACT FROM AUTHOR]