What are some key steps in evaluating children for early puberty?

Take a focused medical history1

Determine the annualized growth rate1,2

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Perform a direct physical examination3

Request a radiograph of left wrist to determine bone age1

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Children with features consistent with CPP should promptly be referred to a Pediatric Endocrinologist for further evaluation4

What is the incidence of central precocious puberty (CPP)?

CPP, a gonadotropin-dependent precocious puberty, is a rare condition.5,6

central precocious puberty symptoms
central precocious puberty symptoms CPP

What are the causes of CPP?

  • CPP is caused by early reactivation of the hypothalamic-pituitary-gonadal (HPG) axis8
  • CPP is most often idiopathic in girls, while boys are more likely to have organic causes8

What are the potential health implications of CPP?

Children with CPP may experience9-12:

  • Expression of secondary sexual characteristics that are inconsistent with their age group
  • Rapid bone maturation that results in shorter predicted adult height

How is CPP diagnosed?

If signs of early puberty are seen by the patient’s family or family physician, a complete physical examination should be performed including:

A focused medical history, including1:

  • The precise rate and timing of growth
  • A history of secondary sexual characteristic development
  • Behavioral changes related to puberty
  • A family history

An accurate plotting of growth and evaluation of growth velocity1,2

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A Physical Examination

Staging by using Tanner-Marshall protocol to evaluate pubertal development4,5,15

Tanner-Marshall stage ≥2 before age of 8 in girls

  • Evaluation of breast development: Palpitation helps differentiate breast tissue from adipose tissue

Tanner-Marshall stage ≥2 before age of 9 in boys

  • Evaluation of testicular development: A phallus length of 2.5 cm or more in flaccid state, or testicular volume of 4 mL or more is suggestive

Imaging Studies

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Left hand/wrist x-ray to determine bone age1,4

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Cranial MRI

  • May identify effects of hypothalamic hamartomas, optic nerve gliomas, hydrocephalus, arachnoidal cysts, and hypothalamic irradiation. These causes can be found in approximately 20% of CPP cases in girls and 65% of cases in boys16
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Possible pelvic ultrasound in girls

  • May help rule out CPP by identifying ovarian cysts, which may be associated with McCune-Albright syndrome or peripheral precocious (pseudo-) puberty (PPP)4
  • Can enable comparison of ovarian and uterine sizes with reference levels. Increased ovarian volume may indicate CPP4,8
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Children with features consistent with CPP should promptly be referred to a Pediatric Endocrinologist for further evaluation4

Laboratory Studies

The Healthcare Provider may perform ultra-sensitive hormonal assays to confirm the diagnosis of CPP, which include but are not limited to1:

  • Testosterone
  • Estradiol
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Thyroid-stimulating hormone (TSH)
  •  
  • Thyroxine (T4)
  • Human chorionic gonadotropin (hCG)

The Pediatric Endcrinologist may also perform a GnRH stimulation test.1,5

How is CPP treated?

GnRH agonists are standard of care for treatment of central precocious puberty (CPP)7,17

  • Since 1989, GnRH agonists have been used to suppress the hypothalamic-pituitary-gonadal (HPG) axis4,18
  • By desensitizing and downregulating GnRH receptors, GnRH agonists gradually inhibit gonadotropin release4,5,19
Always check with parents or caregivers to ensure that the Pediatric Endocrinologist is routinely monitoring their child
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Learn more about the efficacy of LUPRON DEPOT-PED for the treatment of CPP

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References: 1. Blondell RD, Foster MB, Dave KC.  Disorders of puberty. Am Fam Physician. 1999;60(1):209-218. 2. Cooke DW, Divall SA, Radovick S. Normal and aberrant growth. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 24. 3. Styne DM, Grumbach MM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 25.  4. Nebesio TD, Eugster EA. Current concepts in normal and abnormal puberty. Curr Probl Pediatr Adolesc Health Care. 2007;37(2):50-72. 5. Muir A. Precocious puberty. Pediatr Rev. 2006;26(10):373-381. 6. González ER. For puberty that comes too soon, new treatment highly effective. JAMA. 1982;248(10):1149-1151. 7. Nabhan ZM, Walvoord EC. Treatment of gonadotropin-dependent precocious puberty. In: Pescovitz OH, Walvoord EC, eds. When Puberty Is Precocious: Scientific and Clinical Aspect. Totowa, NJ: Humana Press; 2007:chap 16. 8. Imel EA, Bethin KE. Etiology of gonadotropin-dependent precocious puberty. In: Pescovitz O, Walvoord EC, editors. When Puberty Is Precocious: Scientific and Clinical Aspect. New Jersey: Humana Press; 2007. 9. Silverman L, Kaplowitz P and the PES/AAP-SoEn Patient Education Committees.  Precocious Puberty: A Guide for Parents and Patients. Available at: https://www.pedsendo.org/assets/patients_families/ Educational_Materials/PrecociousPuberty.pdf. Accessed August 23, 2016. 10. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44:291-303. 11. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970;45:13-23. 12. Kaplowitz PB. Precocious Puberty. Available at: http://emedicine.medscape.com/article/924002-overview. Accessed June 6, 2016. 13. Lipman K, Hench KD, Benyi T, et al. A multicenter randomized controlled trial of an intervention to improve the accuracy of linear growth measurements. Arch Dis Child. 2004;89:342-346. 14. Tanner JM, Davies PSW. Clinical longitudinal standards for height and velocity for North American children. J Pediatr. 1985;107:317‐329. 15. Herman-Giddens ME. Puberty is starting earlier in the 21st century. In: Pescovitz OH, Walvoord EC, eds. When Puberty Is Precocious: Scientific and Clinical Aspect. Totowa, NJ: Humana Press; 2007:chap 5. 16. Carel J-C, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update. 2004;10(2):135-147. 17. Carel JC, Eugster EA, Rogel A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123(4):e752-762. 18. LUPRON DEPOT-PED [package insert]. North Chicago, IL: AbbVie Inc. 19. Neely EK, Lee PA, Bloch CA, et al. Leuprolide acetate 1-month depot for central precocious puberty: hormonal suppression and recovery. Int J Pediatr Endocrinol. 2010;2010:398639. doi:10.1155/2010/398639 Epub 2011.