Update on central precocious puberty: from etiologies to outcomes

ABSTRACT

Introduction: Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold standard for the treatment of central precocious puberty (CPP) and have an impressive record of safety and efficacy. However, ongoing refinements in diagnosis and management continue to lead to important advancements in clinical care.

Areas covered: The aim of this review is to cover current considerations and controversies regarding the diagnosis of CPP, as well as new findings in regards to etiology and treatment modalities.

Expert opinion: There is emerging evidence of monogenic etiologies of CPP and significant progress in the expansion of newer formulations of GnRHas. Despite these exciting developments, areas of uncertainty in the diagnosis and treatment of CPP remain. While long-term outcomes of patients treated for CPP are encouraging, only short-term follow-up is available with respect to the newer extended release GnRHa preparations, and how they compare with historically used formulations is unknown. A particular shortage of information exists pertaining to CPP in boys and regarding the psychological implications of PP in girls, and more research is needed. Continued investigation will yield new insights into the underlying genetics and optimal treatment strategies for CPP.

KEYWORDS:

• Central precocious puberty
• etiology
• treatment
• genetics
• outcomes

Article highlights

• The majority of girls have idiopathic CPP whereas boys are more likely to have a pathological cause.

• The diagnosis of CPP requires a combination of clinical and biochemical factors, as well as imaging studies in selected cases.

• A brain MRI should be obtained in all boys with CPP; MRI in girls is more controversial, with earlier age more clearly necessitating brain MRI.

• Identification of genetic causes of CPP is exciting but is at the beginning of its journey.

• Girls <6 years old benefit most from the treatment. Less data exists for boys but treatment should be considered in boys <9 years old.

• The gold-standard treatment for CPP is GnRHas which provide sustained high levels of GnRH, resulting in suppression of the HPG axis.

• Multiple formulations of GnRHas are available and they are equally effective in terms of the clinical aspects of CPP. There are some minor differences observed in gonadotropin levels.

• Long-term concerns of children treated with GnRHas for CPP include an increase in BMI, PCOS and decrease in BMD. However, results to date are reassuring.

This box summarizes key points contained in the article.

Declaration of interest

EA Eugster participates in clinical trials sponsored by Abbvie and Tolmar/Orphan Reach. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.