Wy Bikin Suryawan/Md Arimbawa

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: A Multicentric Study. J Pediatr Endocrinol Metab. 2000;13(suppl 1):695-701

 Definition

Appearance of secondary

sexual characteristics : boys < 9 years and girls < 8 years old (- 2SD)
Sex

steroid

Estrogen: female Testosterone:male

 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

 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

 Variant

premature thelarche premature adrenarche gynecomastia

 idiopathic CNS

tumor non-tumor: post infection, radiation, trauma,

congenital
iatrogenic Delayed

diagnosis of GIPP

 Always

isosexual Normal sequence of puberty Hormonal profile: increased gonadotropin and sex steroid

 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

 Isosexual)

McCune Albright
Severe hypothyroid
heterosexual

adrenal: tumor, CAH

tumor ovarium:

arrhenoblastoma

 Trias

Precocious puberty /

endocrine hyperactivity Fibrodysplasia Caf au lait

 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

 self-limited

condition occurring before six years of age characterized by the appearance of pubic and no further secondary sexual development. normal growth patterns

 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

 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

 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

 Normal Normal

growth rate and bone age 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

 Breast

enlargement in males common in teenage years, lasting 2 years differentiate with obese boys
lipomastia no mammae disk
Pathological

causes must be sought

 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.

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

 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

 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.

 Gonadotropin Etiology?

dependent or independent?

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

 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),

 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),

 According

to the etiology GDPP idiopathic: GnRH agonis GIPP : medroxy-progesteron, ketoconazole, dll Variant: observation

 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

 Not

all pubertal disorders are pathologic Early increase of sex steroid should be thoroughly investigated GnRH agonist = drug of choice for GDPP