SERUM LUTEINIZING-HORMONE CONCENTRATIONS, AS MEASURED BY A SENSITIVE IMMUNORADIOMETRIC ASSAY, IN CHILDREN WITH NORMAL, PRECOCIOUS OR DELAYED PUBERTAL DEVELOPMENT

To determine the diagnostic potential of a highly sensitive immunoradiometric assay (IRMA) for LH in children with normal puberty or altered tempo of sexual maturation, we compared serum LH levels by IRMA (LH IRMA) and standard RIA (LH RIA) in children with idiopathic precocious thelarche (IPT; n = 6), idiopathic premature adrenarche (IPA; n = 14), central precocious puberty (CPP; n = 15), and constitutional delay of puberty (DP; n = 15), and 160 control children (79 males and 81 females). Subjects in the latter group were staged, according to their genital or breast development, as early prepubertal (P1E; age, < 8 yr), late prepubertal (P1L; 8-12 yr), or stage II-V (P2-P5; n = 22-34 for each subgroup). Serum LH IRMA levels in P1E, IPT, and IPA children were either undertectable (95% of subjects < 0.25 IU/L) or barely detectable (5% of subjects, greater-than-or-equal-to 0.5 IU/L). Serum LH IRMA levels were greater than 0.5 IU/L in 38% of P1L (mean +/- SD for the group, 1.0 +/- 1.3 IU/L) and 57% of P2 (1.4 +/- 1.3 IU/L); they were greater than 1.0 IU/L in 100% of P3 (2.6 +/- 1.3 IU/L), P4 (3.9 +/- 2 IU/L), and P5 (8.6 +/- 4 IU/L) children. Comparison of serum LH levels between contiguous pubertal stages showed significantly higher LH IRMA concentrations in P3 vs. P1E, P4 vs. P2, P5 vs. P4 (all P < 0.001), and P3 vs. P1L (P < 0.05). In contrast, LH RIA values were not significantly different in P1E (2.0 +/- 0.6 IU/L), P1L (2.3 +/- 0.6 IU/L), P2 (2.7 +/- 0.9 IU/L), P3 (3.2 +/- 1.3 IU/L), and P4 (3.7 +/- 2.2 IU/L), although they were higher in P5 (6.8 +/- 4 IU/L) than in P4 (P < 0.001). From P1E to P5 LH IRMA levels increased 38-fold in females and 21-fold in males, while LH RIA increased 4- and 2.1-fold, respectively. Serum LH IRMA correlated significantly with serum testosterone levels in boys from P1L to P5 (r = 0.76; P < 0.001), while LH RIA levels did not (r = 0.18). Serum LH IRMA concentrations were above the prepubertal range (> 0.5 IU/L) in 67% of children with CPP (group average, 1.8 +/- 1.4 IU/L) and 87% of children with DP (1.6 +/- 1.4 IU/L). In contrast, LH RIA levels were above prepubertal (> 3.7 IU/L) in 27% of children with CPP (3.1 +/- 1.3 IU/L) and 20% of children with DP (2.8 +/- 1.5 IU/L). In conclusion, 1) the high sensitivity of this LH IRMA and the steep increase in LH IRMA levels with puberty allow better separation of pubertal stages than a standard RIA; 2) there appears to be a continuum of LH IRMA levels between P1L and P2, with a clear-cut increase in P3 children; 3) serum LH IRMA, unlike LH RIA concentrations, correlate well with serum testosterone in late prepubertal and pubertal males and, therefore, appear to more closely reflect in vivo LH bioactivity; and 4) because of its greater ability (2.5- to 4.3-fold that of the RIA) to detect an increase in serum LH concentrations in children with CPP and DP, a random LH IRMA appears to be more useful screening test than a random LH RIA measurement in the initial evaluation of children with abnormal tempo of sexual maturation.