Precocious Pseudopuberty Follow-up
- Author: Sunil Sinha, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Further Outpatient Care
After the initial diagnosis of peripheral precocious puberty and the determination of its etiology, most patients require continued monitoring.
- McCune-Albright syndrome (MAS): Closely follow the cases of patients with MAS for the occurrence of other endocrinopathies or associated pathology.
- Testotoxicosis: Treatment decisions of these patients are complex. The most extensive report followed 10 boys during 6 years of treatment, but none had reached final height. Thus, no firm recommendations for one particular form of therapy are currently available. Offer genetic counseling for families affected with this condition.
- Congenital adrenal hyperplasia (CAH): Classic simple virilizing CAH requires lifelong therapy with glucocorticoids in both males and females. Most males with late-onset nonclassic CAH do not require glucocorticoid treatment. Treat symptomatic girls with nonclassic CAH with low-dose glucocorticoids throughout their reproductive years.
- Testicular, ovarian, and adrenal tumors: These tumors are typically unilateral and should be surgically removed. Once removed, the remaining contralateral testis, ovary, or adrenal gland should recover from suppression and be adequate for normal function.
Further Inpatient Care
See the list below:
- No further inpatient care should be required in patients with precocious pseudopuberty.
Inpatient & Outpatient Medications
The treatment of peripheral precocious puberty depends on its etiology. Although therapy is rarely carried out by anyone other than a pediatric endocrinologist, the following list is included for completeness:
- MAS may be mild and slowly progressive; thus, no outpatient medical management is required. If the puberty is rapidly progressive or adult height is severely compromised, treatment may be indicated. Testolactone, an aromatase inhibitor, is the most commonly used medication for the treatment of MAS. Other drugs have included medroxyprogesterone acetate and, more recently, tamoxifen. A gonadotropin agonist may have an additional benefit but only if the bone age is so advanced that central precocious puberty has begun.
- The management of testotoxicosis is difficult and controversial. Testotoxicosis is often treated with ketoconazole, a nonspecific inhibitor of steroidogenesis. An alternative regimen has included spironolactone and testolactone. Gonadotropin agonists may be added as noted in the management of MAS.
- Treatment of CAH with near-physiologic replacement doses of hydrocortisone is used to suppress adrenal androgen production.
See the list below:
- If an experienced pediatric endocrinologist or appropriate surgical subspecialty support is not available, transferring the patient to another facility with experienced staff is highly encouraged.
See the list below:
- MAS: Long-term complications stem from the multiple endocrinopathies that these patients may develop. Patients may also develop extremely deforming and disabling polyostotic bone changes.
- Testotoxicosis: Complications are related to early sexual and physical maturation. Other complications are psychological and related to the early sexual and physical maturation.
- CAH: Complications from overtreatment with hydrocortisone (eg, poor growth, adrenal suppression, features of Cushing syndrome) may be observed. Undertreatment of females may result in irreversible virilization and polycystic ovarian syndrome. Young men with untreated or poorly treated classic CAH may develop testicular adrenal rests, responsive to glucocorticoid suppression. Subfertility may be associated with CAH in both men and women. Adrenal tumors are more common in patients with CAH than in the general population.
Prognosis varies with etiology.
- MAS: Prognosis varies with the number of endocrinopathies and the extent of the bone disease. Most girls have an excellent prognosis.
- Testotoxicosis: Prognosis is excellent with proper treatment.
- CAH: Prognosis is excellent with proper treatment.
- Ovarian granulosa cell tumors: Early recognition and diagnosis of ovarian granulosa cell tumors leads to improved cure rates and disease-free survival rates.
See the list below:
- Inappropriate societal expectations are often placed on these children based on the appearance of advanced maturity. Reminders of the chronologic age of the child are often necessary for school personnel, caregivers, and parents.
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].
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].
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].
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].
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].
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].
[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].
Acerini CL, Tasker RC. Traumatic brain injury induced hypothalamic-pituitary dysfunction: a paediatric perspective. Pituitary. 2007 Jun 15. [Medline].
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].
Cavanah SF, Dons RF. McCune-Albright syndrome: how many endocrinopathies can one patient have?. South Med J. 1993 Mar. 86(3):364-7. [Medline].
DiMeglio LA, Pescovitz OH. Disorders of puberty: inactivating and activating molecular mutations. J Pediatr. 1997 Jul. 131(1 Pt 2):S8-12. [Medline].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Kappy MS, Ganong CS. Advances in the treatment of precocious puberty. Adv Pediatr. 1994. 41:223-61. [Medline].
Kulin HE, Muller J. The biological aspects of puberty. Pediatr Rev. 1996 Mar. 17(3):75-86. [Medline].
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].
Low LC, Wang Q. Gonadotropin independent precocious puberty. J Pediatr Endocrinol Metab. 1998 Jul-Aug. 11(4):497-507. [Medline].
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].
Merke DP, Cutler GB Jr. Evaluation and management of precocious puberty. Arch Dis Child. 1996 Oct. 75(4):269-71. [Medline].
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].
The ovary and female sexual maturation. Rosenfield RL, Sperling MA, ed. Pediatric Endocrinology. 1996. 329-85.
Quigley CA, Pescovitz OH. Premature thelarche and precocious puberty. Curr Ther Endocrinol Metab. 1997. 6:7-13. [Medline].
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].
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].
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].
Styne DM. New aspects in the diagnosis and treatment of pubertal disorders. Pediatr Clin North Am. 1997 Apr. 44(2):505-29. [Medline].
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].
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].
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].