Disorders of Puberty

Normal Puberty - Hormonal Harmony

• HPG Axis Activation: Pulsatile GnRH ↑ → FSH/LH ↑ → gonadal steroidogenesis (estrogen/testosterone).
• Adrenarche: ↑ adrenal androgens (DHEA, DHEAS) → pubic/axillary hair, body odor.
• Sequence & Milestones:

  ⭐ Thelarche (breast development) is typically the first sign of puberty in girls, occurring between 8-13 years, followed by pubarche and then menarche.

  • Girls: Thelarche → Pubarche → Peak Height Velocity (PHV) → Menarche (10-15 yrs; ~2-3 yrs post-thelarche).
  • Boys: Testicular enlargement (≥4ml or 2.5cm; 9-14 yrs) → Pubarche → PHV → Spermarche.

Precocious Puberty - Too Soon Bloom

Puberty onset: Girls <8 yrs, Boys <9 yrs.

• Central (CPP; GnRH-dependent): Premature HPG axis activation.
  • Diagnosis: Pubertal LH response to GnRH (peak LH >5-8 mIU/mL). Brain MRI needed.
  • Causes:
    • Idiopathic (common, esp. girls ~90%).
    • CNS lesions (boys > girls): Hypothalamic hamartoma, glioma, hydrocephalus.
• Peripheral (PPP; GnRH-independent): Excess sex steroids; HPG axis suppressed.
  • Diagnosis: Prepubertal LH response to GnRH. Image adrenals/gonads.
  • Causes:
    • McCune-Albright Syndrome (MAS): PPP, café-au-lait spots, fibrous dysplasia.
    • Congenital Adrenal Hyperplasia (CAH).
    • Gonadal tumors (ovary, testis).
    • Adrenal tumors.
    • Exogenous steroids.
    • hCG-secreting tumors.

⭐ In girls with central precocious puberty, approximately 90% of cases are idiopathic, whereas in boys, an identifiable CNS pathology is much more common.

Delayed Puberty - Late Bloomer Blues

• Definition: No thelarche by age 13 in girls, or no testicular enlargement (≥4ml) by age 14 in boys.
• Etiology:
  • Constitutional Delay of Growth & Puberty (CDGP): Most common, often familial. Bone age < chronological age.

    ⭐ Constitutional Delay of Growth and Puberty (CDGP) is the most common cause of delayed puberty, especially in boys, and is often associated with a positive family history.

  • Hypogonadotropic Hypogonadism (↓FSH, ↓LH - Central):
    • Kallmann Syndrome (anosmia, GnRH deficiency)
    • CNS tumors (e.g., craniopharyngioma), chronic illness, malnutrition
  • Hypergonadotropic Hypogonadism (↑FSH, ↑LH - Peripheral/Gonadal):
    • Turner Syndrome (45,XO): girls; short stature, webbed neck.
    • Klinefelter Syndrome (47,XXY): boys; tall, gynecomastia, small testes.
    • Gonadal dysgenesis, autoimmune oophoritis, chemo/radiotherapy.
• Diagnostic Approach:

• Key Investigations: Bone age, FSH, LH, Estradiol/Testosterone, Karyotype.
• Management: Treat underlying cause. Reassurance for CDGP. Hormone Replacement Therapy (HRT) if permanent hypogonadism.

Key Syndromes - Puberty Puzzles

• McCune-Albright Syndrome: Precocious puberty (GnRH-independent), café-au-lait spots (coast of Maine), polyostotic fibrous dysplasia. 📌 Triad: PPP (Precocious Puberty, Pigmentation, Polyostotic fibrous dysplasia).
• Androgen Insensitivity Syndrome (AIS): 46,XY (genotype), female phenotype, absent uterus, testes present (often intra-abdominal), ↑Testosterone, ↑LH.

High‑Yield Points - ⚡ Biggest Takeaways

• McCune-Albright syndrome: Characterized by precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia.
• Kallmann syndrome: Presents with delayed puberty and anosmia/hyposmia due to GnRH deficiency.
• Turner syndrome (45,XO): Features delayed puberty, streak gonads, and often primary amenorrhea.
• Constitutional Delay (CDGP): Most common cause of delayed puberty in boys; bone age is delayed.
• Central Precocious Puberty (CPP): Results from early HPG axis activation; treated with GnRH agonists.
• Peripheral Precocious Puberty (PPP): GnRH-independent; caused by adrenal/gonadal tumors or CAH.
• Isolated premature thelarche/adrenarche: Usually benign variants; require careful observation and reassurance.