Elevated Random Luteinizing Hormone is an Unreliable Indicator for Pubertal Suppression in Girls Treated with Monthly Leuprolide for Idiopathic Central Precocious Puberty

Abstract

Objective:Longitudinal data regarding random luteinizing hormone (LH) concentrations in patients with idiopathic central precocious puberty (ICPP) during treatment are limited. Therefore, we sought to evaluate random LH and estradiol concentrations during monthly leuprolide injection and their associations with pubertal progression and final adult height (FAH) in girls with ICPP.Methods:Medical records of 27 girls with ICPP who had attained FAH were reviewed. Patients’ height, weight, Tanner stage, growth rate (GR), bone age, random LH measured by both immunoradiometric and immunochemiluminescent methods, follicular-stimulating hormone (FSH) and estradiol levels were monitored until FAH.Results:Treatment was started at a mean (±standard deviation) age of 8.1±0.6 years with mean duration of 3.9±0.2 years. At six months of follow-up, random LH (p=0.048), FSH (p<0.001) and estradiol (p=0.023) concentrations were decreased compared with baseline. Thereafter, random LHs were well suppressed. GRs gradually decreased to prepubertal norm by month 12. Seventeen patients (63%) exhibited pubertal LH concentrations at least once during treatment visits. Furthermore, 43 of a total 116 (37%) LH measurements were found elevated. However, those patients with elevated random LH did not show signs of pubertal progression. After treatment, mean FAH was greater than predicted adult height (p<0.0001) and target height (p=0.03). At no time points of treatment did random LH, FSH and estradiol correlate with GRs or FAH.Conclusion:Elevated random LH is commonly found in ICPP girls during monthly leuprolide treatment. However, these elevations were not associated with clinical progression of puberty or decreased FAH, suggesting that it is not a reliable method for CPP monitoring.

Elevated Pre-injection Basal Luteinizing Hormone Concentrations are Common in Girls Treated for Central Precocious Puberty

“…One study in girls treated with a 50 mg histrelin implant suggested that continuous low-concentration LH secretion tapered off over time as basal LH concentrations decreased during the course of therapy ( 14 ). We did not observe this temporal decline in LH concentrations, similar to findings in another study using leuprorelin 3.75 mg ( 9 ). Whether the shorter half-life of leuprorelin 3.75 mg allows breakthrough gonadotropic activity at GnRHa trough concentrations towards the next injection remains speculative.…”

“…Thus, elevated concentrations of LH did not indicate insufficient pituitary suppression as the girls never showed signs of breast tissue development, BA advancement or had increased growth velocity. In line with this report, Wiromrat and Panamonta ( 9 ) found that in spite of pubertal basal LH concentrations during GnRHa treatment, clinical measures such as Tanner stage, BA and decreased growth velocity indicated sufficient pituitary suppression. Other smaller studies in girls treated with a 50 mg histrelin implant have also reported elevated LH concentrations during treatment ( 14 , 15 ).…”

“…We, like others ( 9 , 14 , 15 ), question the advantage of including routine basal LH concentrations as a monitoring strategy for pituitary suppression during GnRHa therapy. Consecutive clinical assessment assisted by growth velocity and BA is likely superior as a first line strategy.…”

“…However, there is still no consensus on how to monitor the pituitary suppression during GnRHa treatment ( 8 ). It has been suggested that increased basal luteinizing hormone (LH) concentrations indicate lack of suppression ( 8 , 9 , 10 ). In case basal LH concentrations provide the same information as a GnRH stimulation test, monitoring would be less time consuming, costly and less invasive for the patients ( 11 ).…”