Constitutional delayed puberty

Constitutional delayed puberty (CDP) traditionally has been considered a variant of normal growth with delay of onset of puberty and eventual normal secretion of reproductive system hormones resulting in normal physical development and fertility. In boys, pubertal delay is most commonly associated with CDP, while pubertal delay in girls is much more likely to stem from a pathological cause. Historically CDP has been a diagnosis of exclusion, assumed when there was no evidence of a pathologic cause, but confirmed only after years when reproductive function is within the adult range. However, gradually over recent years, the perception that CDP is simply a normal variant has been questioned. This change in perception is based on studies of adult CDP with a history of showing lack of attainment of genetically expected adult height, evidence of subfertility, and comparatively low bone mineral density. Further evidence is provided by the finding that some patients previously diagnosed as having permanent hypogonadotropic hypogonadism (HH) have been noted to develop endogenous hormone secretion as late as the third decade of life suggesting an extreme form of CDP in which normal fertility is spontaneously established. In addition, patients with CDP have functional abnormalities and are suggested by the co-occurrence of CDP and HH within the same kindred, and the evidence that gene variants (such as polymorphisms) whose mutations are known to result in permanent HH are also present in those with CDP. While genetic differences between these groups are being investigated, the approach to patients with CDP, including short-term hormonal therapy and long-term follow-up, remains unchanged, but with the understanding that CDP may actually reflect a disordered physiology rather than being merely a benign variant of normal.