Pathophysiology

Question 1

Definition of irregular menstrual cycles

Answer 1

normal in the first year post menarche as part of the pubertal transition
● > 1 to < 3 years post menarche: < 21 or > 45 days
● > 3 years post menarche to perimenopause: < 21 or > 35 days or < 8 cycles per year
● > 1 year post menarche > 90 days for any one cycle
● Primary amenorrhea by age 15 or > 3 years post thelarche (breast development)

Question 2

Precocious puberty: classification by aetiology?

Answer 2

1. Central - early activation of hypothalamic-pituitary-gonadal axis
2. Peripheral - gonadotropin hormone-independent secretion of sex hormones
3. Benign pubertal variants

Question 3

Benign variants of precocious puberty?

Answer 3

Isolated thelarche
Premature adrenarche/pubarche
Benign prepubertal vaginal bleeding
Nonprogressive precocious puberty

Question 4

Causes of peripheral precocious puberty?

Answer 4

1. Gonadal
   a) Inherited
   -Familial male-limited precocious puberty
   -McCune-Albright syndrome
   b) Acquired
   -Ovarian cysts/tumour
   -Leydig cell tumour
   -HCG secreting germ cell tumour
   -Primary hypothyroidism
2. Adrenal - CAH, virilising adrenal tumour
3. Exogenous sex steroids

Question 5

Laboratory testing for precocious puberty?

Answer 5

1. Establish if central or peripheral
   - FSH, LH, oestradiol and/or testosterone
   - LH >0.3 U/L suggests central
   - FSH has limited diagnostic utility but is typically suppressed in peripheral precocity
2. Possible further evaluation
   - GnRH stimulation test helps distinguish between central and peripheral precocity
   - Imaging - consider MRI for central, and testicular or pelvic ultrasound for peripheral
   - Evaluation of serum adrenal androgens (DHEAS, androstenedione), adrenal gland imaging

Question 6

GnRH stimulation test - procedure and indications?

Answer 6

To help distinguish between central and peripheral precocity if baseline investigations and clinical picture do not match up. GnRH stimulation will cause a heightened LH response in patients with CPP.
GnRH (100mcg) or a GnRH agonist (eg leuprolide acetate 20mcg/kg) may be used.
LH measured 30-40 minutes post GnRH or 60 minutes post-GnRH agonist, with or without FSH, or testing of E2/testo 24 hours later.
Peak stimulated LH, LH:FSH ratio or stimulated serum E2/testo may be used. Exact cut-offs not well-established and assay dependent.