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 59.6%
6 year olds 22.4%
< 6 years old. 18%
Etiology
Gonadotropin Dependent 97.7%
Gonadotropin independent 2.3%
Neurogenic abnormalities 18.4%
(MR/CT skull)
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 hypothalamus-pituitary-
gonad axis increased gonadotropin increased
sex steroids (dependent)
Usually idiopathic
GnRH independent (peripheral):
autonomous sex steroid secretion, depressing
the hypothalamus-pituitary-gonad axis
Usually pathologic
 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
Caf 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 late-
onset 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 estrogen-
containing 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
Primary
(-) Pituitary

LH/FSH

Gonad

Sex steroid
H-P-G axis in GDPP
 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, caf 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

Hipofisis LH/FSH

(-)
Target Organ Primary defect
(gonad)

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 hipogonadism

Hipotalamus 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)
7%
4% 3%
6%

80%

Delayed puberty Hypothyroidism

IDDM Hypoparathyroidism
Others
Italian Working Group on Endocrine Complication in non-
endocrine 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
Psychological distress?
height, FSH/LH, T4/TSH,
Prolactin, Karyotype (girls)

NO YES

Low FSH/LH High FSH

oxandrolone /
sex steroids
GnRh /
sex steroids 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 estrogen 0,25 mg daily (6-9
months)
after 9 MOs cyclic therapy 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