CLINICAL PRESENTATION AND ETIOLOGY
OF CENTRAL PRECOCIOUS PUBERTY IN
CHILDREN
Bùi Phương Thảo1, Vũ Chí Dũng1, Nguyễn Ngọc Khánh1,
Cấn Thị Bích Ngọc1, Nguyễn Thị Hoàn1, Lê Ngọc Duy1,
Nguyễn Phú Đạt2,
1 Bệnh viện Nhi Trung ương
2 Trường Đại học Y Hà Nội
Introduction
Central precocious puberty (CPP): early
sexual symptoms, increased growth
velocity, advanced bone age
CPP: Activation of hypothalamus-pituitarygonads axis
Puberty: < 8 years in girls, < 9 years in
boys
Psychological impact
D Mul I and A Hughes
Reduce final height
Introduction
Teimann 2005 (Denmark): CPP prevalence in
girls (0.2%) 10 times higher than that in boys
(0.05%)
Limited studies on CPP
Goal:


To find etiology of CPP
To describe clinical presentation and investigation of
CPP
Method and subjects
Patients diagnosed of CPP in NHP from 1996 to
2013
Inclusion criteiria




Puberty : < 9 years in boys, < 8 years in girls
Bone age-Chronological age: > 1 year
Testosteron > 1 nmol/L in boys, E2 > 60 pmol/L in
girls
Testicular volume: > 4 ml in boys
Exclusion criteria

Abdominal tumor (adrenal, ovarian)
Method and subjects
Method



Cross-sectional study
Each patient has medical record about clinical
presentation, investigation, treatment
Clinical presentation:
Breast, pubic hair, menstruation in girls
Acne, deepened voice, pubic hair, penile length, testicular
volume in boys




Bone age according to Greulich-Pyle
Physical development evaluation: on Vietnamese
data 2003
FSH, LH, E2 or Testosteron
Brain CT/MRI, abdomen ultrasound
Result and discussion
187 patients
diagnosed of CPP
Distribution of patients
according to diagnosis
age (months)
Age: 83.5±29.3
months

Common age: 60-100
months
20
40
60
80
Age in months
100
120
Result and discussion
Female /male ratio
Male/femele ratio:
Boys 25/186 (13.4%)
Girls 162/186
(86.6%)
Male
13.4%
Female
86.6%
Result and discussion
Chemaitilly 2001 (Thailand): 256 CPP
patients (26 boys, 230 girls)
Soriano 2010 (Spain): 250 CPP patients
(24 boys, 226 girls)
Result and discussion
Etiology according to gender
Etiology
Boys
(n,%)
Idiopathic 12 (48%)
Girls
(n,%)
Total (n,%)
154 (95.1%)
166 (88.8%)
Brain
tumor
7 (28%)
6 (3,7%)
(6 hamartoma, 1 (3 hamartoma, 1
pituitary tumor)
astrocytoma, 1
germinoma, 1
pituitary tomor)
13 (6.9%)
CAH
6 (24%)
1 (0.6%)
7 (3.8%)
Rathke
cyst
0
1 (0.6%)
1 (0.5%
Result and discussion
Idiopathic: 95.1% in girls, higher than in
boys (48%)
Brain tumor: 28% in boys, higher than in
girls (3.73)
Carel 2008:


Brain tumor in boys: 40-90%
Bain tumor in girls: 8-33%
In our study: CPP caused by CAH
Kết quả và bàn luận
CPP could be symptom of CNS disease
CNS disease:



8% in asymptomatic girl
40% in asymptomatic in boys
Brain CT/MRI: boys, girls?
Chalumeau M, Hadjiathanasiou, Cisternino M, De Sanctis V, et al
Result and discussion
Bone age accelerated than chronological age of:
36.9±19.9 months
Carel 2004:



CPP -> increase growth velocity > 6cm/yeas, BA>CA
Untreated final height: 151-156 cm in man, 20 cm
below normal range
Untreated final height: 150-154 cm in female, 12 cm
below normal range
Result and discussion
Clinical presentation in boys
Penile length: 6,9±1,0cm (5->9 cm)
Testicular volume: 6,8±3,1 ml (4->15ml)
Pubic hair: 17/21 (80,9%) have pubic hair
2->P5





P1: 4 (19,0%)
P2: 10 (47,6%)
P3: 5 (23,8)
P4: 1 (4,8)
P5: 1 (4,8)
Result and discussion
Clinical presentation in girls
Breast:


No breast development: 1 patient (0,6%)
Breat development: 161 BN (99,4%)
B2: 28,4%; B3: 51,3%; B4: 17,9%; B5: 1,8%
Pubic hair


No pubic hair: 97 patients (59,9%)
Pubic hair: 65 patients (40,1%)
P2: 30,2%; P3: 8,6%; P4: 1,2%
Menstruation:


39 patients have no menstruation (63,9%)
22 patients have menstruation (36,1%)
Nguyễn Văn Đ, 1 year old, CPP due to
hypothalamic hamartoma
Đào Thị Hồng A, 2.5 years old, CPP due
to hypothalamic hamartoma dưới đồi
Result and discussion
Investigation
FSH and LH after GnRH
stimulation (25 cases)
Basal FSH, LH


FSH: 4,6 ± 3,6
LH: 2,5 ± 2,4

IU/l
20
40
20
0
10
FSH sau GnRH
0
IU/l
60
30
80
100
40

FSH: 23,6 ± 18,7
LH: 12,9 ± 9,0
FSH
LH
LH sau GnRH
Result and discussion
Investigation
Estradiol: median 103 pmol/L (25%, 75%: 39,
187pmol/L)
Testosteron: median 5.7 nmol/L (25%, 75%: 2.5 và
8.2 nmol/L)
Result and discussion
Basal FSH, LH: high specificity, low
sensitivity
FSH, LH after GnRH stimulation: in CPP,
FSH, LH in pubertal range
CPP boys: testosteron usually in pubertal
range
CPP girls: Estradiol has low sensitivity
Theo Carel 2008
Result and discussion
Treatment by GnRH analogue
Short-term benefit: stop puberty in girls

Early menstruation: related risk
Long-term: improve final height,
psychological issue
Early indication of GnRH
Rare: in combination with GH or
oxandrolone
D Mul and I A Hughes
Discussion
Treatment by GnRH analogue
CPP girls < 6 years old: most beneficial

GnRH improve final height
CPP < 6 yrs: 9-10 cm improvement in final height
CPP 6-8 yrs: 4.5-7.2 cm improvement in final
height
Indication for CPP girls > 6 tuổi:
individualisation
D Mul and I A Hughes
Discussion
Treatment by GnRH analogue
When to stop GnRH?



Achieve final height
Prefer to have puberty like peers
After improvemetn of psychological impact
Age to stop: 10.6->11.6 tuổi
Stop when BA11 yrs and CA 12 yrs:
maximal FH
Arrigo T, Cisternino M, Lahlou N, Carel JC, et al
Result and discussion
GnRH: mild and transient side effects
Stop GnRH: Complete recovery of
hyphothalamus-pituitary-gonad axis



To have menstruation: after 2-61 months
Ovarian cycle: happen in 60%-96% of
patients, no different compared to normal
women
No infertility
Pasquino AM, Cassio A, Feuillan PP, Arrigo T, Heger S, et al
Thank you