Diagnosing and managing CPP

Here are some tips practitioners can use in assessing, monitoring, and treating precocious puberty.

What is central precocious puberty?

Central precocious puberty (CPP) is a condition where puberty is triggered well before the “normal” range of 8 to 13 in girls and 9 to 14 in boys. For girls with this condition, signs of puberty can appear before age 8, and in boys before age 9. Between 1 in 5,000 to 1 in 10,000 girls are affected by this condition, and an even smaller number of boys.¹

Signs of central precocious puberty typically include:

• Development of pubic hair
• Development of axillary hair
• Rapid height increases
• Acne
• Underarm odor
• Breast development in girls
• Menarche in girls
• Penile and testes growth in boys
• Deepening voice in boys

The condition can run in families, and is passed down as an autosomal dominant genetic mutation. The MKRN3 gene is the gene most commonly involved in CPP, because a protein produced by this gene plays an important role in triggering the start of puberty. Puberty normally begins when the hypothalamus is stimulated to release gonadotropin-releasing hormone (GnRH). GnRH then triggers the release of other hormones that play a role in sexual development.

In most adolescents, the protein made by the MKRN3 gene blocks this release of GnRH until a certain point. In children with CPP, experts believe this doesn’t happen, and GnRH is released early in spurts, triggering the puberty process.

Monitoring precocious puberty

The diagnosis of precocious puberty begins with a physical exam that confirms early growth of pubic hair in both boys and girls, as well as early breast growth in girls and penile/testicle growth in boys. The Tanner scale is the recommended tool for this assessment, but findings can also be confirmed with blood testing to check levels of hormones like:²

1. L hormone [LH]
2. Follicle-stimulating hormone [FSH])
3. Estradiol
4. Testosterone
5. Dehydroepiandrosterone sulfate (DHEAS)
6. Thyroid hormones
7. Gonadotropin-releasing hormone agonist (GnRHa) stimulation tests
8. 17-hydroxyprogesterone to test for congenital adrenal hyperplasia

Bone scans are another common diagnostic tool, since bone age can provide a lot of information about pubertal timing and growth. Other assessments may include ultrasound to examine the structure and function of the gonads or magnetic resonance imaging to study the brain and pituitary glands.

Treating CPP

The standard treatment for CPP is the use of GnRH agonists, says Katherine Kutney, MD, a pediatric endocrinologist at Rainbow Babies and Children’s Hospital in Cleveland. These work by preventing the release of hormones like PH and FSH from the pituitary gland.

“Pulses of GnRH cause gonadotropin release, while tonic GnRH receptor activation prevents gonadotropin release,” Kutney explains, adding that premature adenarche alone is not generally treated.

Additional options for treatment have become available in more recent years, Kutney adds. These include:

1. Subcutaneous leuprolide (Lupron Depot)
2. Long-acting 1-month intramuscular leuprolide (Lupron Depot)
3. Long-acting 3-month intramuscular leuprolide (Lupron Depot)
4. Long-acting 6-month intramuscular triptorelin (Triptodur)
5. Long-acting 6-month subcutaneous leuprolide acetate (Fensolvi)
6. Long-acting 1-year implantable histrelin acetate (Supprellin)

These options mainly offer a variety of route and frequency options that could increase compliance, but experts suggest that the extremely high cost of GnRHa’s developed for use in children is one of the biggest factors in the use of these medications.³

Kutney adds that during the assessment, clinicians also want to check for alternative causes of CPP, such as adrenal tumors or conditions like congenital adrenal hyperplasia (CAH) or McCune Albright Syndrome. These conditions are treated separately, for example with surgery in the case of adrenal tumors and with medications like glucocorticoids for CAH.

References

1. Central Precocious Puberty. Medlineplus.gov. Updated August 18, 2020. https://medlineplus.gov/genetics/condition/central-precocious-puberty/#inheritance
2. How Do Healthcare Providers Diagnose Precocious Puberty & Delayed Puberty? NICHD.NIH.gov. Updated June 21, 2021. https://www.nichd.nih.gov/health/topics/puberty/conditioninfo/diagnosed
3. Eugster EA. Treatment of Central Precocious Puberty. Journal of the Endocrine Society. May 2019;3(6):965-972. doi:10.1210/js.2019-00036.