Jennifer Harrington1, Mark R Palmert. 1. Division of Endocrinology, The Hospital for Sick Children and Department of Pediatrics, The University of Toronto, Toronto, Canada M5G1X8. jennifer.harrington@sickkids.ca
Abstract
CONTEXT: 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. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSION: 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.
CONTEXT: 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. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSION: 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.
Authors: Andrea Salonia; Giulia Rastrelli; Geoffrey Hackett; Stephanie B Seminara; Ilpo T Huhtaniemi; Rodolfo A Rey; Wayne J G Hellstrom; Mark R Palmert; Giovanni Corona; Gert R Dohle; Mohit Khera; Yee-Ming Chan; Mario Maggi Journal: Nat Rev Dis Primers Date: 2019-05-30 Impact factor: 52.329
Authors: Ulrich Boehm; Pierre-Marc Bouloux; Mehul T Dattani; Nicolas de Roux; Catherine Dodé; Leo Dunkel; Andrew A Dwyer; Paolo Giacobini; Jean-Pierre Hardelin; Anders Juul; Mohamad Maghnie; Nelly Pitteloud; Vincent Prevot; Taneli Raivio; Manuel Tena-Sempere; Richard Quinton; Jacques Young Journal: Nat Rev Endocrinol Date: 2015-07-21 Impact factor: 43.330
Authors: T Todisco; S Mastromattei; L Chioma; G Ubertini; M G Pattumelli; D Fintini; M Cappa Journal: J Endocrinol Invest Date: 2022-07-28 Impact factor: 5.467
Authors: Diana L Cousminer; Jaakko T Leinonen; Antti-Pekka Sarin; Himanshu Chheda; Ida Surakka; Karoliina Wehkalampi; Pekka Ellonen; Samuli Ripatti; Leo Dunkel; Aarno Palotie; Elisabeth Widén Journal: PLoS One Date: 2015-06-01 Impact factor: 3.240