Differential diagnosis between constitutional delay of growth and puberty, idiopathic growth hormone deficiency and congenital hypogonadotropic hypogonadism: a clinical challenge for the pediatric endocrinologist

Abstract

Differential diagnosis between constitutional delay of growth and puberty (CDGP), partial growth hormone deficiency (pGHD) and congenital hypogonadotropic hypogonadism (cHH) may be difficult. All these conditions usually present with poor growth in pre- or peri-pubertal age and they may recur within one familial setting, constituting a highly variable, but somehow common, spectrum of pubertal delay. Narrative review of the most relevant English papers published between 1981 and march 2020 using the following search terms "constitutional delay of growth and puberty," "central hypogonadism," "priming," "growth hormone deficiency," "pituitary," "pituitary magnetic resonance imaging," with a special regard to the latest scientific acquisitions. CDGP is by far the most prevalent entity in boys and recurs within families. pGHD is a rare, often idiopathic and transient condition, where hypostaturism presents more severely. Specificity of pGHD diagnosis is increased by priming children before growth hormone stimulation test (GHST); pituitary MRI and genetic analysis are recommended to personalize future follow-up. Diagnosing cHH may be obvious when anosmia and eunuchoid proportions concomitate. However, cHH can either overlap with pGHD in forms of multiple pituitary hormone deficiencies (MPHD) or syndromic conditions either with CDGP in family pedigrees, so endocrine workup and genetic investigations are necessary. The use of growth charts, bone age, predictors of adult height, primed GHST and low dose sex steroids (LDSS) treatment are recommended. Only a step-by-step diagnostic process based on appropriate endocrine and genetic markers together with LDSS treatment can help achieving the correct diagnosis and optimizing outcomes.