1 PREPUBERTAL BLEEDING WITHOUT SECONDARY SIGNS OF PUBERTY

• Puberty in female is a process of biologic change and physical development after which sexual
reproduction becomes possible.
• Sequence of events : THELARCHE - PUBARCHE OR ADRENARCHE - RAPID GROWTH SPURT -
MENARCHE

1 PRECOCIOUS PUBERTY
• Appearance of any signs of secondary sexual maturation at an early speci c age
more than 2.5 standard deviation below the mean.

2 RARE CAUSES OF PRECOCIOUS PUBERTY

3 Vaginal bleeding & McCune-Albright syndrome
• Classic triad :
◦Cafe-au-lait spots
◦Abnormal bone lesion
◦Precocious puberty
• Present with prepubertal bleeding along with thelarche. Rarely, a child may present with bleeding
and No breast budding

2 DIFFERENTIAL DIAGNOSIS OF PREPUBERTAL BLEEDING WITHOUT ANY BREAST

DEVELOPMENT
• Foreign object
• Genital trauma
• Genital abuse
• Lichen sclerosus
• Infectious vaginitis (especially from shigella)
• Urethral prolapse
• Breakdown of labial adhesions
• Friable genital warts or vulvar lesions
• Vaginal tumor
• Rare presentation of McCune-albright syndrome (typically has breast development)
• Isolated menarche (controversial)

—-H/H
FOREIGN BODIES
• Classic symptom :
◦Foul, bloody vaginal discharge
◦Discharge is often purulent and may be without blood
• May be inserted in children because genital area is pruritic or when naturally curious children are
exploring their bodies
• TOILET TISSUE - Most common caginal foreign body in pre-adolescent female

URETHRAL PROLAPSE
• Most common presentation isPREPUBERTAL BLEEDING. Not urinary symptomatology.
• Often sharp increase in abdominal pressure (such as coughing), precedes urethral prolapse
• The distal aspect of urethral mucosa may be prolapsed along the entire 360 degree of the urethra
• Red donut-like structure
• Treatment : conservative and non-interventional
VAGINAL TUMORS : SARCOMA BOTRYOIDES & ENDODERMAL SINUS TUMORS
• Almost all cases of sarcoma botryoides of the vagina in prepubertal children occur prior to age 5
and endodermal sinus tumors prior to age 2.
• Although these tumors are extremely rare causes of prepubertal bleeding, they must be
considered in every child. Both are aggressive malignancies and prompt diagnosis is critical.
• In young children with no evident cause of prepubertal bleeding, a VAGINOSCOPY should be
done to rule out these malignancies

SEXUAL ABUSE
• Indications of sexual molestation in a child with pre-menarcheal vulvovaginitis :
◦(+) identi cation of trichomonas infection, gonorrhea, or chlamydia
• Complete transections of the hymen between 3 & 9 o’clock positions are not congenital but could
be from abuse or by inserting objects

GENITAL TRAUMA
• Most common cause of genital trauma during childhood is an accidental fall
◦STRADDLE INJURIES
• Accidental genital trauma often produces extreme pain and overwhelming anxiety for the child
and her parents.
◦Gynecologist may underestimate the extent of anatomic injuries
◦Examine the child under general anesthesia

3 OVARIAN TUMORS
• Constitute approximately 1% of all neoplasms in pre-menarcheal children
• Benign and malignant ovarian tumors are usually unilateral
• Biopsy of the contralateral ovary should be avoided
◦Possible exceptions to this rule are :
‣ Dysgerminoma
‣ Immature teratoma
• Pre-adolescent ovarian neoplasm necessitating surgery :
◦Most common:
‣ Benign cystic teratoma
‣ Malignant germ cell tumor
◦2 goals of Surgical therapy :
‣ Removal of NEOPLASM
‣ Preservation of future fertility
Optional Readings : Not included in PPT/ Lecture
Summarized version of PRECOCIOUS PUBERTY from Comprehensive Gynecology Book

1 PRECOCIOUS PUBERTY
• Appearance of any signs of secondary sexual maturation at an early age.
• Complete evaluation should be carried out at 8 years old
• 2 Primary concerns of parents and children :
◦Social stigma - child being physically di erent from peers
◦Diminished height
‣ premature closure of epiphyseal growth centers
‣ Early course : girls are taller and heavier than chronologic peers
‣ Late course : eventual adult height will be shorter than normal because of premature closure of epiphyses.
‣ 50% will not reach height of 5ft.

• Types of disorders :
◦GnRH DEPENDENT (Complete or True)
◦GnRH INDEPENDENT (Incomplete or Pseudo)
‣ Feminizing (isosexual)
‣ Virilizing (heterosexual)
• Pathophysiology :
◦GnRH dependent with integrated HPO Axis - Normal physiologic
◦GnRH Independent without HPO axis integration - Abnormal physiology

Add table :
• GnRH DEPENDENT PRECOCIOUS PUBERTY
◦Premature maturation of HPO Axis
◦Normal menses, ovulation
◦Possibility of pregnancy
◦Bone age is advanced (except in hypothyroidism)
◦70% of cases
• GnRH INDEPENDENT PRECOCIOUS PUBERTY
◦Premature female sexual maturation —> estrogen induced uterine stimulation —> bleeding without any normal follicular activity
• BOTH have INCREASED ESTROGEN levels

2 TYPES OF DISORDERS
Table : p. Thelarche vs p. Adrenarche
PREMATURE THELARCHE
• Isolated unilateral or bilateral breast development
• NOT accompanied by other pubertal development
• Estrogen levels are NORMAL
• Benign self-limiting ; No treatment required
• Often regresses
• Normal linear growth and bone age

PREMATURE PUBARCHE OR ADRENARCHE

• Isolated development of pubic hair without other signs of secondary sexual maturation
• Girls do not have clitoral hypertrophy
• Cause is poorly understood but related to increased androgen production (DHEA, DHEAS)
• Many cases evolve to PCOS
◦measurement of testosterone and 17-hydroxyprogesterone should be carried out

3 CENTRAL PRECOCIOUS PUBERTY (GnRH DEPENDENT)

H/H
IDIOPATHIC
• 80% of cases
• No genital abnormalities except early development
• FOLLICULAR OVARIAN CYST forms due to increased pituitary gonadotrophin levels
• Diagnosis :
◦LH >5mlU/mL
◦GnRH stimulation test- give GnRH Agonist followed by measurement of LH & FSH after 3 Hours.

CNS LESIONS
• 20% of cases
• Warrants careful evaluation by imaging
• Common Symptoms :
◦Headache
◦Visual disturbances
• Unusual symptoms :
◦Seizure with inappropriate laughter - GELASTIC SEIZURES
• Pathophysiology: Poorly understood
• HAMARTOMA - may secrete GnRH ; this secretion is not subject to normal physiological inhibition.

PRIMARY HYPOTHYROIDISM
• Untreated hypothyroidism results in GnRH dependent precocious puberty
• Usually seen in Hashimoto thyroiditis
• Only cause of precocious puberty where BONE AGE IS RETARDED
• VAN WYK-GRUMBACH SYNDROME
◦Diminished negative feedback of thyroxine resulting to :
‣ Increased production of TSH
‣ Increased production of gonadotrophins

3 PERIPHERAL (GnRH-INDEPENDENT) PRECOCIOUS PUBERTY

• Aka incomplete or Pseudo- precocious puberty
• Most common cause :
◦ESTROGEN SECRETING OVARIAN CYST
◦LARGE FUNCTIONING FOLLICLE
H/H
Granulosa cell tumors
• Most common type of soild ovarian cell tumor causing precocious puberty
• Larger than 8cm
• Can be palpated abdominally

Adrenocortical neoplasms
• May produce isosexual (feminizing) or heterosexual (virilizing) precocious puberty

McCune-albright syndrome
• Leads to constant stimulation of LH, FSH, TSH, GH
• First sign : Vaginal bleeding
• Classic triad :
◦Cafe-au-lait spots
◦Abnormal bone lesion
◦Precocious puberty

Iatrogenic / Factitious precocious puberty

• Occurs when young girl used hormone creams or ingests adult medications (estrogen or birth control pills

2 DIAGNOSTIC EVALUATION
• History and PE
• Imaging of brain (CT, MRI) - check for Hamartoma
• Laboratory:
◦Serum E2
◦LH
◦Thyroid function test
◦Adrenal androgen (DHEAS) - elevated
• Bone age determination: HAND-WRIST FILMS
◦Done since acceleration of growth is the earliest clinical feature of precocious puberty
• Ultrasound, CT, MRI of abdomen and pelvis - to evaluate ovaries, uterus and adrenal gland
• GnRH Stimulation test

2 TREATMENT
• dependent on cause, extent and progression of disease
• Goals :
◦Reduce ginadotrophin secretion
◦Reduce or counteract peripheral actions of sex steroids
◦Decrease growth rate to normal
◦Slow skeletal maturation (to allow development of maximal adult height)
• Drug of choice : GnRH Agonist (ex. Leuprolide)
◦Given monthly or trimonthly injections or rarely intranasally
◦Most e ective in 4-6 year olds; continuous treatment until 11 years old
◦Reverses ovarian cycle and changes growth pattern
• McCune-albright syndrome Treatment :
◦Aromatase inhibitors (anastrozole, letrozole) - prevent conversion of biologically active estrogens
◦Fulvestrant - “pure” ER Antagonist ; most promising
• Intensive counseling