Transcript Precocious Puberty

GANGGUAN PUBERTAS
Dr Eka Agustia Rini Sp AK
Sub Bagian Endokrinologi Ilmu Kesehatan
Anak
FK-UNAND / RS Dr M. Djamil Padang
PRECOCIOUS PUBERTY
Hypothalamus - Pituitary – Gonad
axis
INTRODUCTION
Epidemiology
– Frequency : girls > boys
– Girls: most have a benign central cause
– Boys: 50% pathologic peripheral cause.
 all boys with precocious puberty should
undergo detailed investigation, but in
girls additional investigation can be
based on the clinical impression
Profiles of Girls with Precocious Puberty
(N=438)
Age of onset
between 7-7.9 year olds
6 year olds
< 6 years old.
Etiology
Gonadotropin Dependent
Gonadotropin independent
Neurogenic abnormalities
(MR/CT skull)
59.6%
22.4%
18%
97.7%
2.3%
18.4%
Cisternino M, Arrigo T, Pasquino AM, et al. Etiology and Age Incidence of Precocious Puberty in Girls:
Precocious Puberty
Definition
– Appearance of
secondary sexual
characteristics : boys
< 9 years and girls <
8 years old (- 2SD)
Sex steroid 
– Estrogen: female
– Testosterone:male
Effect of sex steroid
Estrogen 
–Accelerated bone maturation and early
epiphyseal fusion (tall child but short
adult)
–Uterus, mammary gland
Testosterone
–Genital, Hirsutism, acne, male habitus
General:sexual behavior, aggressiveness
Classification
GnRH dependent (central) :
– premature reactivation hypothalamuspituitary-gonad axis  increased
gonadotropin  increased sex steroids
(dependent)
– Usually idiopathic
GnRH independent (peripheral):
– autonomous sex steroid secretion, 
depressing the hypothalamus-pituitary-gonad
axis
Classification
Variant
–premature thelarche
–premature adrenarche
–gynecomastia
Etiology GDPP
idiopathic
CNS
– tumor
– non-tumor: post infection, radiation,
trauma, congenital
iatrogenic
Delayed diagnosis of GIPP
Clinical manifestation GDPP
Always isosexual
Normal sequence of puberty
Hormonal profile: increased
gonadotropin and sex steroid
Etiology GIPP - male
Isosexual
– adrenal: tumor, CAH
– testes : cell Leydig tumor, familial
testotoxicosis
– gonadotropin-secreting tumor:
non CNS: hepatoma, germinoma, teratoma
CNS: germinoma, adenoma (LH secreting)
heterosexual
Increased peripheral aromatization
Etiology GIPP - female
Isosexual)
– McCune Albright
– Severe
hypothyroid
heterosexual
– adrenal: tumor,
CAH
– tumor ovarium:
arrhenoblastoma
Mc Cune Albright Syndrome
Trias
– Precocious puberty /
endocrine
hyperactivity
– Fibrodysplasia
– Café au lait
Clinical manifestation GIPP
Isosexual or heterosexual (late onset
CAH, tumor adrenal)
Disconcordant of sexual characteristics
(testes volume inappropriate with pubertal
stage - smaller)
Low or normal gonadotropin and
increased sex steroid
Benign Premature Adrenarche
self-limited condition occurring before six
years of age
characterized by the appearance of pubic
and no further secondary sexual
development.
normal growth patterns
Benign Premature Adrenarche
Normal bone age
Slight elevation of serum DHEA
Normal adrenal steroid hormone levels
Normal sex hormone levels
ACTH stimulation test: to exclude lateonset CAH
GnRH test: prepubertal pattern
Normal imaging studies
No specific treatment required
Premature Adrenarche
Excude virilization
– clitoral enlargement, advanced bone
age, acne, rapid growth, and voice
change.
– rapid progression
If virilization present
– measure testosterone, 17-OHP and
DHEA
– USG: adrenal or ovarian tumor
– 17-OHP or DHEA: CAH
Benign Premature Thelarche
Isolated appearance of unilateral or
bilateral breast aged 6 months to 3 years
No other signs of puberty or evidence of
excessive estrogen effect (thickening of
the vaginal secretions or bone age
acceleration).
Ingestion or application of estrogencontaining compounds must be excluded
as etiology
Benign Premature Thelarche
Normal growth rate and bone age
Normal levels of gonadotropins and
estradiol
USG: normal ovaries, prepubertal uterus
Usually resolves spontaneously and
requires no treatment
re-evaluation at intervals of 6-12 months to
ensure that premaure thelarche is not the
beginning of isosexual precocious puberty
Gynecomastia
Breast enlargement in males
common in teenage years, lasting 2 years
differentiate with obese boys
– lipomastia
– no mammae disk
Pathological causes must be sought
Pubertal Gynecomastia
Incidence: 50-60% of boys during early
adolescence
breast tissue usually asymmetric and often
tender.
If history and physical examination,
including palpation of the testicles, are
unremarkable, reassurance and periodic
reevaluation are all that is necessary. Most
cases resolve in one to two years.
Gynecomastia
Drugs
– sex steroids, hCG,
psychoactive (phenotiazine),
antituberculosis,
testosterone antagonist
(ketoconazole, cimetidine,
spironolactone)
Malnutrition
Idiopathic (most common)
Tumor producing disease
– hepatoma, adrenal, testes, LH
and hCG producing tumors
Pubertal Gynecomastia
Familial gynecomastia
– X-linked recessive trait or a sex-limited
dominant trait
– unless associated with hypogonadism no
further evaluation in an otherwise normal boy
– If severe, gynecomastia  cosmetic surgery.
Pathologic gynecomastia
– Klinefelter's syndrome: high risk for breast
cancer
– prolactin-secreting adenomata
Pubertal Gynecomastia
Pathologic gynecomastia
– hormone-secreting tumors (testes,
hepatoma), cirrhosis, hypo- and
hyperthyroidism.
– Drug induced (marijuana, phenothiazines,
opiates, amphetamines, digitalis, estrogens,
ketoconazole, spironolactone, isoniazid,
tricyclic antidepressants, cimetidine, etc).
If worsens and associated with psychologic
morbidity  bromocriptine, tamoxifen
reduction mammoplasty rarely indicated.
Diagnostic work up
Gonadotropin dependent or independent?
Etiology?
Hypothalamus
GnRH
(-)
Pituitary
LH/FSH
Gonad
E2 or T
H-P-G axis
Hypothalamus
GnRH
(-)
Pituitary
LH/FSH
Gonad
Sex steroid 
H-P-G axis in GDPP
Primary
Hypothalamus
GnRH
(-)
Pituitary
LH/FSH
Gonad
Extra Gonadal
Sex steroid 
H-P-G axis in GIPP
Diagnostic work up
History
age of onset, progressivity, family history,
growth, symptoms extragonadal cause
(adrenal), CNS complaints, gelactic laughter
(hamartoma), previous history: encephalitis,
meningitis TB
Physical examination
pubertal stage, signs of virilisation, height,
testes size (small indicative of perpheral
cause), CNS signs, skin (acne, café au lait),
Diagnostic work up
Laboratory
gonadotropin, bHCG, 17-OHProgesterone
(CAH), cortisol (Cushing syndrome,
adrenal tumor)
Imaging
Bone age, pelvic ultrasound, skull x-ray,
CT/MRI, bone survey (McCune Albright),
Therapy
According to the etiology
GDPP idiopathic: GnRH agonis
GIPP : medroxy-progesteron,
ketoconazole, dll
Variant: observation
Prognosis
According to etiology
GDPP idiopathic: GnRH agonis
– Final height = potential genetic height
– Preserved fertility
– Psychosocial minimal, regression of
secondary sex
GIPP : medical
– Potential genetic height 
– Regression of secondary sex  
Conclusion
Not all pubertal disorders are pathologic
Early increase of sex steroid should be
thoroughly investigated
GnRH agonist = drug of choice for
GDPP
DELAYED PUBERTY
Definisi
Pubertas terlambat bila tidak adanya
tanda-tanda pubertas
– laki-laki pada usia 14 tahun
– perempuan pada usia 13 tahun
Klasifikasi
– hipergonadotropik hipogonadism
– hipogonadotropik hipogonadism
Ammenorrhoe primer
Ammenorrhoe sekunder
Hipergonadotropik hipogonadism
Hipotalamus
LHRH
LH/FSH
Hipofisis
(-)
Target Organ
(gonad)
Primary defect
Sex Steroid
Hipergonadotropik hipogonadism
Dengan kelainan kromosom
– Dysgenesis gonad
Sindrom Turner
Pure gonadal dysgenesis
– Sindrom Klinefelter
– Androgen Insensitivity Syndrome *
Hipergonadotropik hipogonadism
Tanpa kelainan kromosom
– kongenital
gangguan biosintesis steroid adrenal
(P450c17,P450scc,3bHSD) dan
gonad (17-KS, P450 aromatase)
anorchia, ovary resistant syndrome,
LH resistance
– didapat
radiasi, chemotherapy, proses
autoimun
Hipogonadotropik
Hipotalamus
hipogonadism
LHRH
Primary defect
Hipofisis
LH/FSH
(-)
Target Organ
(gonad)
Sex Steroid
Hipogonadotropik hipogonadism
Constitutional delay
Kelainan Susunan Syaraf Pusat
– Tumor (craniopharyngioma, germinoma,
optic glioma, histiocytosis X)
– Struktural (mid line defect)
– Sindrom Kallmann
– hipopituitarism idiopathic
– pasca tindakan (radiasi, khemoterapi
inflamasi, infiltrasi - hemosiderosis)
Hipogonadotropik hipogonadism
Penyakit kronis
– endokrin, malnutrisi/anorexia nervosa,
kelainan sistemik
Aktivitas fisik berlebihan
Sindrom-sindrom
– Prader-Willi; Laurence-Moon-Biedl
Hypothalamic and pituitary causes of
pubertal failure-low gonadotrophins
Congenital defects
– Kalmann syndrome
– Congenital adrenal hypoplasia
– Septoptic dysplasia
– Development defect of pituitary
Tumors, direct effects or following
radiotherapy or surgery
Haemochromatosis
Thalassemia and endocrinopathy. A
multicenter study (N=3092)
4% 3%
7%
6%
80%
Delayed puberty
IDDM
Others
Hypothyroidism
Hypoparathyroidism
Italian Working Group on Endocrine Complication in nonendocrine diseases, 1993
Delayed puberty in Thalassamia patient
Italian Multicenter Thalassemia study
1993, (29 centers), 3092 patients :
Puberty failure:
males 41 %
females 39,5 %
All patient with hemachromatosis need
periodic careful endocrine evaluation
Tatalaksana
Anamnesis
Pemeriksaan fisik
Pemeriksaan penunjang
Terapi
Anamnesis
Riwayat perkembangan pubertas di dalam
keluarga
Data pertumbuhan & perkembangan
Riwayat penyakit/pengobatan dahulu
Fungsi penciuman
Pemeriksaan fisik
Pemeriksaan fisik secara umum
Pemeriksaan neurologis (funduskopi) d
Antropometri (TB, BB, rasio segmen atas
dan bawah, rentang lengan)
Status pubertas
Stigmata suatu sindrom (pendek, obese,
retardasi mental, webbed neck dll)
Pemeriksaan Penunjang
Pencitraan:
– usia tulang, CT scan/MRI kepala & USG
genitalia interna (atas indikasi),
Hormonal (basal/ uji GnRH)
– LH,FSH,Prolactin, Estrogen atau testosterone
Dan lain-lain
– analisis kromosom (atas indikasi)
– uji fungsi penciuman
Pubertal Delay
Any signs of puberty?
YES
NO
Check
• height, FSH/LH, T4/TSH,
• Prolactin, Karyotype (girls)
Psychological distress?
NO
YES
Low FSH/LH
High FSH
GnRh /
sex steroids
sex steroids
oxandrolone /
sex steroids
Monitor growth & pubertal
progress
Hormonal replacement
Discrepancies exist concerning
– the age of initiation
– dosage
Some authors : postponing treatment until
the age when arrested sexual maturation
in easily diagnosed
Early treatment supporters: Insist on the
psychological benefits treatment
Sexual development should be induce at
an appropriate age
Recommended hormone replacement
When to wait watchfully and when to test
and refer are part of the art of medicine
– Female patients
chronological age > 13-14 years
bone age > 11 years
– Male patients
chronological age > 14-15 years
bone age > 12 years
Hormonal replacement
Females :
– start ŵ estrogen 0,25 mg daily (6-9
months)
– after 9 MOs cyclic therapy ŵ estrogen
for 1st 21 days
Males:
– testosterone enanthate 50 mg IM/
monthly
– after 6-9 MOs, dose gradually increased
to 200 mg/3 weeks (2-3 years)
KESIMPULAN
Pubertas berlangsung menurut stadium,
umur tertentu
Pubertas harus selalu menjadi perhatian
orangtua / tenaga kesehatan
Setiap tenaga kesehatan dapat
mendeteksi kelainan pubertas secara
dini dan segera melakukan rujukan