What is the role of gonadotropin testing in the diagnosis of precocious puberty?

Updated: Nov 30, 2020
  • Author: Paul B Kaplowitz, MD, PhD; Chief Editor: Robert P Hoffman, MD  more...
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Because of the development of more sensitive third-generation assays for LH, which can detect levels as low as 0.1 IU/L or below, random LH is now considered a good screening test for CPP, with levels of 0.3 IU/L or above considered diagnostic. However, many children with CPP have prepubertal basal LH levels but will respond to a challenge with GnRH with an increase to 5 IU/L or above, which is considered pubertal.

The immunochemiluminometric assay (ICMA) method for LH assessment seems more specific than the immunofluorometric assay (IFMA) method. An LH level of less than 0.1 IU/L is generally prepubertal, and one study suggested an upper reference range limit for IMCA-measured LH of 0.2 IU/L in both boys and girls, with no overlap between prepubertal and pubertal levels in boys and a 10% overlap in girls. [39]  Another study found that a basal LH level measured by two different ICMA assays was sufficient to document CPP in 90% of girls, with levels of more than 0.83 IU/L in all but one patient; 29 of 34 prepubertal girls had undetectable values (< 0.15 IU/L to < 0.2 IU/L). [40]

A study by Carel et al stated that the peak LH level measured by ICMA that defines CPP is 4.1 IU/L in boys and 3.3 IU/L in girls. [23]

Random follicle-stimulating hormone (FSH) levels do not discriminate between prepubertal and pubertal children. Suppressed levels of LH and FSH accompanied by highly elevated testosterone or estradiol levels suggest precocious pseudopuberty rather than CPP.

A definitive diagnosis of CPP may be confirmed by measuring LH and FSH levels 30-60 minutes after stimulation with GnRH at 100 mcg or with a GnRH analogue. Because native GnRH is no longer available, most centers are using the analogue leuprolide (aqueous form) at a dose of 20 mcg/kg, up to a maximum of 500 mcg. An increase in FSH levels much greater than the increase in LH levels suggests that the child is prepubertal.

Another study suggested that when the baseline LH level is prepubertal, an increase in LH level to 5 IU/L or more after leuprolide correlates well with progression of pubertal signs during a 6-month period of observation. [41]  No increase in LH and FSH levels after the infusion of GnRH suggests precocious pseudopuberty.

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