Medscape is available in 5 Language Editions – Choose your Edition here.


Precocious Pseudopuberty Workup

  • Author: Sunil Sinha, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
Updated: Oct 30, 2015

Laboratory Studies

See the list below:

  • Sex steroids: The common laboratory finding for all causes of precocious pseudopuberty consists of pubertal levels of sex steroids (ie, substances with either androgenic or estrogenic effects in the presence of low-basal luteinizing hormone [LH] and follicle-stimulating hormone [FSH] with the lack of a pubertal increase in LH and FSH concentrations in response to exogenous gonadotropin-releasing hormone [GnRH] stimulation).
  • LH and FSH levels
    • LH and FSH levels are in the prepubertal range.
    • LH and FSH levels are not increased in response to exogenous gonadotropin-releasing hormone.
  • Adrenal steroid precursors: Enzyme deficiencies in the pathway for cortisol synthesis lead to elevated cortisol precursors. The exact elevated precursor depends on the enzymatic deficiency.
    • 17α-hydroxyprogesterone: This steroid precursor is elevated in 21-hydroxylase deficiency and also in 11β-hydroxylase deficiency (see 17-Hydroxyprogesterone, Serum and 17-Hydroxyprogesterone, Urine).
    • 11-deoxycortisol and deoxycorticosterone: These steroid precursors are elevated in 11β-hydroxylase deficiency but should be either low or low-normal in patients with 21-hydroxylase deficiency.
    • Androstenedione: This precursor of testosterone is more stable and is not an acute phase reactant. Therefore, androstenedione may provide a more reliable marker of 21-hydroxylase deficiency than does the 17α-hydroxyprogesterone. An elevated androstenedione is not a specific cause of precocious puberty because androstenedione may be elevated in individuals with tumors and CAH.
  • Human chorionic gonadotropin (HCG): This is elevated in patients with HCG-secreting tumors.
  • Urinary 17-ketosteroids: The level of 17-ketosteroids in a 24-hour urine collection provides a means of quantifying the amount of adrenal androgens being produced. 17-ketosteroids tend to be markedly elevated in patients with tumors of the adrenal glands. Dehydroepiandrosterone (DHEA) and DHEA-sulfate and metabolites (eg, androstenedione) are the major constituents of this assay. Testosterone and dihydrotestosterone contribute less than 1% of total urinary 17-ketosteroids.
  • Estradiol: A random measurement of estradiol may not be elevated because secretion may be cyclic in individuals with McCune-Albright syndrome (MAS).
  • Testosterone: In FMPP, the levels of testosterone are pubertal with low-basal LH and FSH.
  • Thyroid function test: Serum thyroid-stimulating hormone (TSH) should be elevated markedly and the serum free thyroxine (T4) should be markedly decreased if the patient's sexual precocity is secondary to severe primary hypothyroidism.

Imaging Studies

See the list below:

  • The number of imaging studies that a clinician should obtain depends on the suspected diagnosis.
  • Ultrasonography is a sensitive test that aids in the evaluation of the ovaries, testes, and adrenal glands.
    • Ultrasonography of the ovaries and uterus can aid in determining the etiology of precocity. The uterus is sensitive to estrogen and is a good bioassay to determine the length of time and magnitude of estrogen exposure. In girls with MAS, the ovaries are frequently asymmetric secondary to the presence of large unilateral cysts. Ovarian tumors are also visible using ovarian ultrasonography.
    • Testicular ultrasonography may detect Leydig cell tumors that are not palpable on testicular examination.
    • Ultrasonography of the adrenal glands may help to establish the diagnosis of an adrenal tumor; however, abdominal CT scanning and MRI are more sensitive techniques for imaging the adrenal gland.
  • Many clinicians perform bone scanning in young girls suspected of having MAS.
    • Areas of fibrous dysplasia are positive on bone scan.
    • A skeletal survey may identify the presence of polyostotic fibrous dysplasia, which is observed in patients with MAS.
  • Brain MRI is indicated in males (and in select females at the discretion of the clinician) with sexual precocity and in any patient with neurologic signs or symptoms.
  • Pelvic MRI can be useful in the diagnosis and evaluation of females with precocious puberty. Uterine volume and evaluation of the different uterine layers can be well visualized on MRI. In premenarchal girls, the uterine corpus is small, and the cervical length is greater than that of the uterine body until about age 13 years. The ovarian tumors have characteristic MRI findings and may assist in the diagnosis of ovarian neoplasms.

Other Tests

See the list below:

  • GnRH stimulation test: Administer a standardized dose of GnRH (3.5 mcg/kg intravenously; not to exceed 100 mcg) after obtaining baseline LH/FSH levels. Then, obtain FSH and LH levels at 30, 60, and 90 minutes (or an abbreviated test may be performed with sampling at 30 min only). In the case of gonadotropin-independent precocious puberty, no increase over basal levels is observed. FSH and LH response is termed flat.
  • Leuprolide acetate stimulation test: GnRH has been difficult to obtain; an alternative to the GnRH stimulation test is GnRH agonist Leuprolide acetate stimulation test. Administer leuprolide acetate [20 µg/kg2] Obtain a baseline LH, estradiol and testosterone are optional. Measure the LH level at 3 hours after injection. Measure estradiol or testosterone 24 hours after injection. An LH level of more than 8 IU/L is consistent with central precocious puberty (CPP). If the estradiol stimulates to 50 pg/mL or greater this is consistent with CPP. If the estradiol levels are 25-50 pg/mL this is consistent with early CPP.[4] Sathasivam et al, however, demonstrate a baseline serum level of LH greater than or equal to 0.3 U/L and a stimulated (peak) LH level greater than or equal to 5 U/L with the leuprolide-stimulation test accurately predicting pubertal progression.[5]
  • Bone age: Perform a bone age assessment for any patient who presents with clinical signs of early puberty.[6] Bone age is advanced (>2 standard deviations above the mean for age) in children who have had significant sex steroid exposure over an extended time, regardless of etiology.
  • Genetic testing: Genetic testing can be used to confirm the diagnosis and provide genetic counseling for different types of CAH (including the most common form, 21-hydroxylase deficiency), gain-of-function mutations in the GNAS gene for MAS, and gain-of-function mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR) for FMPP.
Contributor Information and Disclosures

Sunil Sinha, MD Assistant Professor, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Sunil Sinha, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.


Cydney L Fenton, MD Director, Center for Diabetes and Endocrinology, Akron Children's Hospital

Cydney L Fenton, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Merrily P M Poth, MD Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Received grant/research funds from Eli Lilly for pi; Received grant/research funds from NovoNordisk for pi; Received consulting fee from NovoNordisk for consulting; Partner received consulting fee from Onyx Heart Valve for consulting.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.


Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

  1. Bajpai A, Menon PS. Contemporary issues in precocious puberty. Indian J Endocrinol Metab. 2011 Sep. 15 Suppl 3:S172-9. [Medline]. [Full Text].

  2. Mamun AA, Hayatbakhsh MR, O'Callaghan M, Williams G, Najman J. Early overweight and pubertal maturation--pathways of association with young adults' overweight: a longitudinal study. Int J Obes (Lond). 2009 Jan. 33(1):14-20. [Medline].

  3. de Sousa G, Wunsch R, Andler W. Precocious pseudopuberty due to autonomous ovarian cysts: a report of ten cases and long-term follow-up. Hormones (Athens). 2008 Apr-Jun. 7(2):170-4. [Medline].

  4. Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, Larsen L, et al. Efficacy and Safety of Leuprolide Acetate 3-Month Depot 11.25 Milligrams or 30 Milligrams for the Treatment of Central Precocious Puberty. J Clin Endocrinol Metab. 2012 Feb 16. [Medline].

  5. Sathasivam A, Garibaldi L, Shapiro S, Godbold J, Rapaport R. Leuprolide stimulation testing for the evaluation of early female sexual maturation. Clin Endocrinol. Sept 2010. 73(3):375-81. [Medline].

  6. Martin DD, Meister K, Schweizer R, Ranke MB, Thodberg HH, Binder G. Validation of automatic bone age rating in children with precocious and early puberty. J Pediatr Endocrinol Metab. 2011. 24(11-12):1009-14. [Medline].

  7. Leschek EW, Jones J, Barnes KM, et al. Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. J Clin Endocrinol Metab. 1999 Jan. 84(1):175-8. [Medline].

  8. [Guideline] American Academy of Pediatrics: Committee on Psychosocial Aspects of Child and Family Health and Committee on Adolescence. Sexuality education for children and adolescents. Pediatrics. 2001 Aug. 108(2):498-502. [Full Text].

  9. Acerini CL, Tasker RC. Traumatic brain injury induced hypothalamic-pituitary dysfunction: a paediatric perspective. Pituitary. 2007 Jun 15. [Medline].

  10. Agboola-Abu CF, Aligwekwe PK, Olowu AO, Kuku SF. Congenital adrenal hyperplasia due to 11-hydroxylase enzyme deficiency in three siblings. A brief report. West Afr J Med. 1999 Apr-Jun. 18(2):80-6. [Medline].

  11. Cavanah SF, Dons RF. McCune-Albright syndrome: how many endocrinopathies can one patient have?. South Med J. 1993 Mar. 86(3):364-7. [Medline].

  12. DiMeglio LA, Pescovitz OH. Disorders of puberty: inactivating and activating molecular mutations. J Pediatr. 1997 Jul. 131(1 Pt 2):S8-12. [Medline].

  13. Garibaldi LR, Aceto T Jr, Weber C, Pang S. The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test. J Clin Endocrinol Metab. 1993 Apr. 76(4):851-6. [Medline].

  14. Haddad N, Eugster E. An update on the treatment of precocious puberty in McCune-Albright syndrome and testotoxicosis. J Pediatr Endocrinol Metab. Jun 2007. 20:653-661. [Medline].

  15. Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997 Apr. 99(4):505-12. [Medline].

  16. Holland FJ, Kirsch SE, Selby R. Gonadotropin-independent precocious puberty ("testotoxicosis"): influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab. 1987 Feb. 64(2):328-33. [Medline].

  17. Ibanez L, Potau N, Zampolli M, et al. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab. 1994 Jan. 78(1):30-5. [Medline].

  18. Isguven P, Yoruk A, Adal E, et al. Adult type granulosa cell tumor causing precocious pseudopuberty in a 6year-old girl. J Pediatr Endocrinol Metab. 2003 Apr-May. 16(4):571-3. [Medline].

  19. Josan VA, Timms CD, Rickert C, Wallace D. Cerebellar astrocytoma presenting with precocious puberty in a girl. Case report. J Neurosurg. 2007 Jul. 107(1 Suppl):66-8. [Medline].

  20. Kalfa N, Patte C, Orbach D, et al. A nationwide study of granulosa cell tumors in pre- and postpubertal girls: missed diagnosis of endocrine manifestations worsens prognosis. J Pediatr Endocrinol Metab. 2005 Jan. 18(1):25-31. [Medline].

  21. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics. 1999 Oct. 104(4 Pt 1):936-41. [Medline].

  22. Kappy MS, Ganong CS. Advances in the treatment of precocious puberty. Adv Pediatr. 1994. 41:223-61. [Medline].

  23. Kulin HE, Muller J. The biological aspects of puberty. Pediatr Rev. 1996 Mar. 17(3):75-86. [Medline].

  24. Laue L, Kenigsberg D, Pescovitz OH, et al. Treatment of familial male precocious puberty with spironolactone and testolactone. N Engl J Med. 1989 Feb 23. 320(8):496-502. [Medline].

  25. Low LC, Wang Q. Gonadotropin independent precocious puberty. J Pediatr Endocrinol Metab. 1998 Jul-Aug. 11(4):497-507. [Medline].

  26. Mastorakos G, Mitsiades NS, Doufas AG, Koutras DA. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid. 1997 Jun. 7(3):433-9. [Medline].

  27. Merke DP, Cutler GB Jr. Evaluation and management of precocious puberty. Arch Dis Child. 1996 Oct. 75(4):269-71. [Medline].

  28. Outwater EK, Wagner BJ, Mannion C, et al. Sex cord-stromal and steroid cell tumors of the ovary. Radiographics. 1998 Nov-Dec. 18(6):1523-46. [Medline].

  29. The ovary and female sexual maturation. Rosenfield RL, Sperling MA, ed. Pediatric Endocrinology. 1996. 329-85.

  30. Quigley CA, Pescovitz OH. Premature thelarche and precocious puberty. Curr Ther Endocrinol Metab. 1997. 6:7-13. [Medline].

  31. Rosenfield RL. Does a Primary Acceleration of LH Pulse Frequency Underlie an Association between Central Precocious Puberty and Polycystic Ovary Syndrome?. Commentary on Escobar ME et al: Acceleration of LH Pulse Frequency in Adolescent Girls with a History of Central Precocious Puberty with versus without Hyperandrogenism (Horm Res 2007;68:278-285). Horm Res. 2007 Jun 20. 68(6):286-287. [Medline].

  32. Siklar Z, Ocal G, Adiyaman P, Ergur A, Berberoglu M. Functional ovarian hyperandrogenism and polycystic ovary syndrome in prepubertal girls with obesity and/or premature pubarche. J Pediatr Endocrinol Metab. 2007 Apr. 20(4):475-81. [Medline].

  33. Stratakis CA, Vottero A, Brodie A, et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metab. 1998 Apr. 83(4):1348-57. [Medline].

  34. Styne DM. New aspects in the diagnosis and treatment of pubertal disorders. Pediatr Clin North Am. 1997 Apr. 44(2):505-29. [Medline].

  35. Tanaka YO, Tsunoda H, Kitagawa Y, et al. Functioning ovarian tumors: direct and indirect findings at MR imaging. Radiographics. 2004 Oct. 24 Suppl 1:S147-66. [Medline].

  36. Toma HS, Tan PL, McKusick VA, Katsanis N, Adams NA. Bardet-Biedl Syndrome in an African-American patient: should the diagnostic criteria be expanded to include hydrometrocolpos?. Ophthalmic Genet. 2007 Jun. 28(2):95-9. [Medline].

  37. Yesilkaya E, Cinaz P. Neuroendocrine tumor of the pancreas resulting in precocious puberty. J Pediatr Surg. 2007 Jul. 42(7):1314; author reply 1314-5. [Medline].

Graph represents the prevalence of breast development at Tanner stage 2 or greater by age and race.
Graph represents the prevalence of pubic hair at Tanner stage 2 or greater by age and race.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.