EDITORIAL April 01, 2020 April 01, 2020

Challenges in monitoring GnRH analog treatment in central precocious puberty

DOI: 10.20945/2359-3997000000241

Central precocious puberty (CPP) results from an early activation of the hypothalamic-pituitary-gonadal (HPG) axis (,). The causes of CPP are heterogeneous, with central nervous system abnormalities being of special interest in boys, while idiopathic etiology is more prevalent among girls (). In the last decade, however, the number of idiopathic cases has diminished thanks to the discovery of mutations in different genes, including KISS1, KISS1R, MKRN3 , and DLK1 (,).

GnRH analogs (GnRHa) are the mainstay of treatment for this endocrine pediatric condition (,). These drugs act by causing a transient downregulation and suppression of the HPG axis. An impressive expansion in the amount of extended-release GnRHa formulations has occurred in the last years. These include leuprolide acetate 3-month depot, triptorelin 3-month depot, triptorelin 6-month depot, and histrelin subcutaneous implant replaced annually (). These forms are reported to be safe and provide sustained gonadotropin suppression, slowing puberty progression and improving predicted adult height. Notably, the treatment with GnRHa has been considered successful if pubertal progression is halted and if growth velocity and the rate of skeletal maturation are slowed (,). However, there are no homogeneous consensus regarding the optimal strategy for monitoring treatment in CPP beyond auxological parameters and periodic bone age X-rays. The HPG axis can be evaluated by measuring unstimulated or stimulated (following GnRH or GnRHa administration) serum LH and sex steroids. It is known that unstimulated LH concentrations above the prepubertal range do not necessarily indicate a lack of suppression, while concentrations within the prepubertal range likely indicate suppression (). GnRHa stimulation test should be performed for definitive information. However, the lack of correlation between biochemical measurements during treatment and adult height outcomes does not support routine biochemical testing in all patients (). Therefore, the assessment and management of CPP remain challenging for pediatric endocrinologists.

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