Basal Ultrasensitive LH Assay: A Useful Tool in the Early Diagnosis of Male Pubertal Delay?

Abstract

The aim of this study was to evaluate the usefulness of basal measurements of gonadotropins in distinguishing between constitutionally delayed puberty (DP) and hypogonadotropic hypogonadism (HH), comparing its diagnostic efficiency with that of the dynamic GnRH infusion test (0.83 microg/min during 120 min). We studied 20 males, chronological age (CA) 14-18 years, with a final diagnosis of DP (n = 8), partial HH (n = 5) and complete HH (n = 7), confirmed by follow-up. We also evaluated basal samples of ultrasensitive LH and FSH in 117 healthy control males (CA 2-19 yr), classified according to Tanner stage. In the control group, ROC plot analysis showed a cutoff to differentiate prepuberty from puberty of 0.65 IU/l for LH (sensitivity: 91%, specificity: 98%). Differences were found (p < 0.05) in basal LH and in maximal responses to GnRH in complete HH in relation to DP and partial HH. The diagnostic efficiency of the GnRH infusion test was 85%. For basal LH, a cut-off limit of 0.65 IU/l showed a diagnostic efficiency of 85% for complete HH and 100% for partial HH and DP. We conclude that, in our experience, basal LH levels above 0.65 IU/l measured by ultrasensitive assay would rule out a complete deficiency. It was not possible to differentiate DP from partial HH, either in basal samples or with the infusion test.

Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys

“…[7][8][9][10] Pharmacological stimulation of gonadotropins by GnRH also showed overlapping gonadotropin serum concentrations. 7,10,11 In contrast, pharmacological stimulation of gonadotropins by GnRH agonists (GnRHa) showed a significantly higher discriminatory potential. GnRH agonists have longer half-lives than GnRH and a stronger affinity for the GnRH receptor, causing a supraphysiological and sustained stimulation of the gonadotropic cells.…”

“…Current laboratory studies have examined basal or stimulated concentrations of gonadotropins and basal or stimulated testosterone concentrations, as well as basal inhibin B and AMH concentrations . Basal serum gonadotropin concentrations were shown to be poor discriminators except in one study . Pharmacological stimulation of gonadotropins by GnRH also showed overlapping gonadotropin serum concentrations .…”

Gonadotropin Secretion in Girls with Turner Syndrome Measured by an Ultrasensitive Immunochemiluminometric Assay

“…The above-mentioned studies [7,8,9,10,11,12,13] as well as other studies [14, 15] were performed using radioimmunoassays with low sensitivity and a detection limit higher than prepubertal levels. The development of new assays with higher sensitivity has recently provided useful information on the regulation of gonadotropins in prepubertal children and offered improved diagnosis of many pubertal disorders [16,17,18,19,20]. In addition, these assays have demonstrated that normal prepubertal levels of LH and FSH are much lower than previously thought.…”

Recent advances in the understanding and management of delayed puberty

“…Grinspon et al 8 had shown a 100% diagnostic specificity of basal FSH <1.2 IU/L for IHH in boys with delayed puberty, but the study consisted of only a very small number with CDGP. Sequera et al 38 showed exclusion of severe IHH with LH >0.65 IU/L, but did not identify thresholds to differentiate between partial IHH and CDGP. Although lower basal gonadotrophin levels on average have been demonstrated in IHH compared with CDGP, there is substantial overlap between the groups 37.…”