1. Precocious puberty M. Šnajderová
Pediatrická klinika, 2. LF UK a FN Motol, Praha
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2. Precocious puberty
Acceleration of any sign of puberty >2.5 SD above mean range of normal population (Goldfarb, 1985):
Girls < 8 yr
Boys < 9 yr
Incidence: 0.6% children

3. Early puberty (constitutional acceleration)
2 – 2.5 SD from the mean of population range (Rallison, 1986)
Girls : 8 – 9 yr (B2)
Boys : 9 – 9.5 yr (testes length >2.5 cm, volume > 4 cm3)
Early puberty: ???
Pathology x variation of normal development ???

4. Variants of normal development
Incomplete forms of sexual precocity
Premature pubarche
Premature thelarche

5. Pubarche (adrenarche precox)
Age (frequently ≤ 7 years in both girls and boys) BA
Growth velocity
DHEAS, A-dion …cortisol level in normal range
Exclude blocks adrenal steroidogenesis (US, gynecology, ACTH test?)
Follow up

6. Precocious puberty Gonadotropin - dependent Gonadotropin- independent
central peripheral

7. Precocious puberty: classification

8. DIAGNOSTICS  THERAPY

9. GnRH test: diagnostics and monitoring in CPP
GnRHa
HYPOTHALAMUS GnRH
PITUITARY  LH,  FSH
   LH,   FSH
GONADS  E2  T

10.           p<0,01  p<0,001 ICPP: idiopathic CPP
OCPP: organic CPP
 p<0,  p<0,001

11. Menstrual cycle after therapy
USG: ovaries – no pathological findings
11.5% some girls after short interval after menarche
10%
1 OCPP (NF 1) menarche after induction 3.5 yrs after therapy, at present induction of menarche
in another 2 OCPP girls

12. Not to treat premature telarche, pubarche
familial early onset of puberty (slow progressive)

13. Therapy to stop the progression of puberty
to preclude or attempt to reclaim
compromised growth potential

14. CPP - treatment GnRH agonists : depot i.m. , s.c. 11.25 mg trp
GnRH antagonists : ?
Monitoring : hormonal levels,
growth, development

15. Effect of therapy: CPP Start of therapy: BA ≤ 11 r
End of therapy: BA 12 – 13 r
Recovery of hormonal secretion after discontinuation
Adult height is close to target height
Bone age

16. Idiopathic slow progressive CPP
non treated

17. Therapy organic CPP : if there is an underlying treatable cause –
therapy should be given
BA acceleration, younger age, growth prognosis
Gonadotropin-independent:
adrenal suppression in CAH …

18. Peripheral precocious puberty PPP
Sex steroids: not after activation of reproductive axis hypothalamus – pituitary - gonads.
Isosexual or heterosexual.
Congenital
Secondary CPP
Postnatal
Exogenous endogenous
MAS
FMPP
CAH
Anabolic steroids Tumors
COC Adrenal gland
Gel (T) granulosa cells Cosmetics Leydig cells
tumor producing hCG
ovarian cysts

19. PPP heterosexual CAH 21-OHD,11beta-OHD,3beta-OHSD Ovarian tumors
Adrenal tumors

20. PPP isosexual Exogenous sex steroids or gonadotropins
McCune-Albright syndrome
Ovarian tumors
Adrenal tumors
Limited or reversible forms
(chronic primary hypothyroidism, exogenous sex steroid or gonadotropins, ovarian cysts)

21. MAS (girls and boys)
Somatic activating mutation GNAS (gene encoding stimulation of Gsα in intracelular cascade_ endocrine and other tissues). Mutation in mosaic form, heterogenous clinical spectrum.
Clinical signs: fractures, Cushing syndrome, sublinical hypothyroidism. Frequently precocious puberty at the age 2-6 yrs. Vaginal bleeding, breasts enlargement (not in any case). Bleeding migt be present repeatedly, fluctuation in breasts enlargemen. Ovarian cysts – production of estrogen.
Triad
PPP
café au lait
Fibrous bone dysplasia

22. FMPP Familial male-limited precocious puberty
Heterozygous activating mutation LHR+
Not so frequent comparred with MAS, positive family history
Mutation AD or de novo
Female: asymptomatic (LH and FSH is necessary for ovarian steroidogenesis)
Male: early virilisation at 2 yrs (penis, PH, acné, body odour), small testicles

23. MAS: therapy Girls Aromatase inhibitors (dBA, growths): Letrozol
Tamoxifen
No surgery!!!
Boys
Prespective study: missing
Good results: antiandrogens

24. FMPP therapy Antiandrogen and/or aromatase inhibitor
Testolacton and spironolacton
Prospect in combination:
Antiandrogen: bicalutamid
Aromatase inhibitor: anastrozol

25. Secondary CPP
Primary PPP – after elimination of negative feedback when on therapy
Start of CPP in children with BA acceleration
Frequent in girls with breast enlargement treated for PPP
In boys with progresssion of testicular volume
LH levels
GnRHa therapy