Precocious Puberty 10.03.2011

8/3/2019 Precocious Puberty 10.03.2011

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Patrick Shea MD PGY3


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The patient is a 6 year old girl, previously healthy,with normal growth and development. She presentsto clinic with 1 week of bilateral breast enlargementand tenderness. Exam findings are normal except forTanner 2 breast development bilaterally. There is nodischarge, and the area is minimally tender. She has

no axillary or pubic hair and a normal pre-pubertalGU exam. PCP reassures mom that this is most likelybenign premature thelarche.

Case: HPI


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The patient comes back into the PCP 2 weeks laternow with a 2-day history of vaginal bleedingrequiring 2-3 pads per day.

Continued


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Differential?


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Physical exam: Large coast of Maine caf -au-lait maculeon lower back

Labs: FSH


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Mutation of GNAS gene de novo in utero (oftenmosaic)G-protein becomes constitutively activatedCan cause multiple endocrine autonomoushyperfunctionClassic triad: Fibrous bone dysplasia, precociouspuberty, caf-au-lait macules (Coast of Maine)

McCune-Albright

Syndrome


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Precocious puberty caused by McCune-Albright will NOTrespond to Leuprolide (because the G-protein isautoactivated)SERMs: Faslodex, Tamoxifen (block end-organ estrogeneffects)Some studies with aromatase inhibitors(Testolactone>newer kinds like Anastrozole)

Higher risk for fractures, pituitary tumors, bony tumorsCan be disfiguring depending on bony involvementShort stature, generally ending up below mid-parentalheight in adulthood (premature growth plate fusion).

Treatment/Prognosis


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McCune-Albright

Syndrome


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Before age 8 in girls or before age 9 in boys.In boys: testicular enlargement, then adrenarche, then

penile enlargement and voice change, then growth spurt.In girls: thelarche, then adrenarche, then growth spurt,then menarche (~2 cm growth left after menarche).In boys, precocity is more likely pathological than delay

(constitutional)In girls, precocity is more likely constitutional, whereasdelay is more likely pathological.

Precocious Puberty


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CENTRAL: GnRH pulse generator in thehypothalamus is activated

PERIPHERAL: Endogenous or exogenous source ofexposure to sex steroids, without stimulation by thehypothalamus.

Differential?


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Intracranial damage to inhibitory systems: trauma,radiation, infection

Hypothalamic hamartomas: produce pulsatile GnRHOther neoplasms that affect thehypothalamus/pituitary systemLangerhans Cell Histiocytosis

Central Precocity


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McCune-Albright SyndromeCongenital Adrenal Hyperplasia (steroid shunting)Germ cell tumorsAdrenal tumorsGonadal tumors

Controversial: Endocrine disruptors, obesity (maybe bidirectional depending on gender)

Peripheral causes


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Complete history particularly of exposures to anysort of exogenous steroids, tea tree oil, lavender oil.

Thorough physical exam w/ Tanner stagingLabs: FSH, LH, Estradiol, Testosterone, DHEA-S,beta-hCG, CMP, CBC, (salivary cortisol)Imaging: bone age XR, (brain MRI)

Work-up


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Depends on the causeLeuprolide is a GnRH agonist that works to shutdown the pulse generator. (Treatment for CENTRALPP).If the cause is neoplastic, referral to oncologyAromatase inhibitors for MASRemove exogenous sources.

Treatment


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Growth failure, short statureMarker for neoplastic diseasesSocial problems: aggression in boys, unwantedsexual attention for girlsHigher risk for breast cancer for girls later in life.Social risk for girls: Prospective study in Green

Journal showed higher rates of criminality, substanceabuse, high-risk sexual behavior, and depression.

Clinical and Social

Importance


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1. Copeland, et.al. Outcomes of Early Pubertal Timing in Young Women: A Prospective Population-Based Study Am J Psychiatry 2010; 167:1218-12252.2. Antoniazzi, F; Zamboni, G (2004). "Central precocious puberty: current treatment options". Paediatricdrugs 6 (4): 21131.3. McKenna, Ph il (2007-03-05). "Childhood obesity brings early puberty for girls" . New Scientist.Archived from the original on 2008-04-19.http://web.archi ve.org/web/20080419072722/http://www.newscientist.com/article/dn11307-childhood-obesity-brings-early-puberty-for-girls.html. Retrieved 2010-05-22 .4. Cooney, Elizabeth (2010-02-1 1). "Pube rty gap: Obesity splits boys, girls. Adolescent males at top ofthe BMI chart may be delayed" . MSNBC. http://www.msnbc.msn.com/id/35332881/ns/health-kids_and_parenting/ . Retrieved 2010-05-225. "Early-Onset Puberty Puts Girls at Risk of Medical Problems" . redorbit.com. 2007-09-17.http://www.redorbit.com/news/health/1067387/earlyonset_puberty_puts_girls_at_risk_of_medical_ problems/index.html . Retrieved 2009-12-15.

6. Garn, SM. Physical growth and development. In: Friedman SB, Fisher M, Schonberg SK. , editors.Comprehensive Adolescent Health Care. St Louis: Quality Medical Publishing; 19927. Sarafoglou, Kyriakie; Hoffman, and Roth: Pediatric Endocrinology and Inborn Errors of Metabolism. Sixthedition: 2009.

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Precocious Puberty 10.03.2011

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