Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.
BACKGROUND
Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications.


OBJECTIVE
The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH.


METHODS
A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH.


RESULTS
Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups.


CONCLUSIONS
Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.
Division of Endocrinology, The Hospital for Sick Children and Department of Pediatrics, The University of Toronto, Toronto, Canada M5G1X8. jennifer.harrington@sickkids.ca
Jennifer
J
Harrington
Mark R
MR
Palmert
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006063:Chorionic Gonadotropin / Q000032:analysis; D003937:Diagnosis, Differential; D003955:Diagnostic Tests, Routine; D005260:Female; D005820:Genetic Testing; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006062:Gonadotropins / Q000097:blood; D006130:Growth Disorders / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000175:diagnosis*; D007223:Infant; D008297:Male; D011628:Puberty, Delayed / Q000175:diagnosis* / Q000209:etiology
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone