LH Measurements by in Vitro Bioassay and a Highly Sensitive Immunofluorometric Assay Improve the Distinction between Boys with Constitutional Delay of Puberty and Hypogonadotropic Hypogonadism

Abstract

ABSTRACT. The basal and gonadotropin-releasing hormone (GnRH) stimulated levels of LH were measured in 21 boys with delayed puberty using conventional RIA, mouse interstitial cell in vitro bioassay (B-LH), and a highly sensitive immunofluorometric method (F-LH). On the basis of subsequent clinical follow-up, the subjects were diagnosed as idiopathic constitutional delay of puberty (CD, n = 13) or hypogonadotropic hypogonadism (HH, n = 8). The basal RIA LH levels were similar in the two diagnostic groups (HH, 2.92 f 0.76, CD 3.53 -C 1.37 IU/L). In contrast, the mean basal B-LH was significantly lower in boys with H H than with CD (1.10 2 0.45 versus 2.91 & 1.23 IU/L; p < 0.01). A similar finding was made by F-LH measurements which were clearly lower in the H H than the CD group (0.073 f 0.04 versus 1.71 -C 0.97 IU/L, p < 0.01). Also upon GnRH stimulation (3.5 pg/kg i.v.), the distinction between the CD and H H groups was better with the B-LH and F-LH measurements. The basal B/I ratio of the CD group (0.90 f 0.43) was more than that of the H H group (0.42 f 0 . 2 5 ,~ < 0.01) and this ratio increased significantly (more than 2-fold, p c 0.01) during GnRH stimulation in the CD group, but not in the HH patients. Such differences were not found between the B/F ratios of the CD and H H groups. Measurements of basal and GnRH stimulated B-and F-LH levels clearly improved the distinction between CD and HH in comparison to the conventional RIA method, due to the low sensitivity and likely cross-reactions with some non-LH constituents of serum in the latter assay. This problem is, to a great extent, eliminated by better sensitivity and specificity of B-LH and F-LH measurements. For the same reasons, the difference in B/I ratios between the CD and H H samples, and the increased B/I ratio after GnRH stimulation in the CD group, were not observed in B/F ratios. In conclusion, the measurements of basal and GnRH-stimulated concentrations of serum B-LH and F-LH clearly improve the differential diagnostics between CD and HH. The discrepancies measured between the B/I and B/F ratios in these samples call for reevaluation of the bio/immuno ratios of circulating LH. (Pediatr Res 27: 211-214, 1990) Abbreviations B/F ratio, ratio of serum B-LH/F-LH concentrations B/I ratio, ratio of serum B-LH/I-LH concentrationsB-LH, bioactive LH CD, constitutional delay of puberty F-LH, immunoreactive LH measured by immunofluorometric assay GnRH, gonadotropin-releasing hormone hCG, human chorionic gonadotropin HH, hypogonadotropic hypogonadism I-LH, immunoreactive LH measured by radioimmunoassay CV. coefficient of variation CD and HH pose a diagnostic problem in pediatric endocrinology. This differentiation is important for prognostic reasons and to avoid too long androgen treatment of children with CD. No hormonal measurement has thus far proven to be absolutely reliable in discriminating the two conditions (1, 2). Basal levels of immunoreactive LH and FSH show no clear differences (3-5), and even after stimulation tests with GnRH and hCG some ...

Response of the Free Alpha-Subunit to GnRH Distinguishes Individuals with ‘Functional’ from Those with Permanent Hypogonadotropic Hypogonadism

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The human chorionic gonadotropin test is more powerful than the gonadotropin-releasing hormone agonist test to discriminate male isolated hypogonadotropic hypogonadism from constitutional delayed puberty

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Diagnostic difficulty in polycystic ovary syndrome due to an LH-beta-subunit variant

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