Puberty

Summary

Normal puberty is a physiological process marking the transition to sexual maturity, typically lasting 2–5 years and occurring between ages 8–13 in girls. It involves sequential hormonal changes, beginning with adrenarche and gonadarche, followed by thelarche, pubarche, and culminating in menarche. Tanner staging is used to assess pubertal development based on breast and pubic hair growth. Precocious puberty refers to early onset of these changes—before age 8 in girls—classified as central (gonadotropin-dependent) or peripheral (gonadotropin-independent). Diagnosis involves hormonal testing and imaging, and treatment targets the underlying cause, with GnRH agonists for central forms and hormone antagonists for peripheral types.

Normal puberty

• Definition: Puberty is the physiological process of sexual maturation involving the development of secondary sexual characteristics, reproductive capability, and the transition from childhood to adulthood.
  

  Parameter	Girls	Boys
  Normal age range	8–13 years	9–14 years
  ★ Average onset	11 years	13 years
  Duration	2–5 years	2–5 years
  Menarche age	10–16 years (mean: 13)	N/A

• Pubertal physiology:
  1. Adrenarche (First Phase)
     • Definition: Activation of adrenal androgen production
     • Age of onset: 6-8 years (both sexes)
     • Clinical features:
       • Axillary and pubic hair growth
       • Body odor (apocrine gland activation)
       • Acne development
       • Oily skin
     • Key Point: Independent of hypothalamic-pituitary-gonadal axis
  2. Gonadarche (HPG Axis Activation)
     • Definition: Activation of hypothalamic-pituitary-gonadal axis
     • Mechanism: Pulsatile GnRH secretion → ↑FSH and LH → gonadal hormone production
     • Hormonal changes:
       • Girls: ↑Estradiol from ovaries
       • Boys: ↑Testosterone from testes
  3. Thelarche (Girls) / Testicular Enlargement (Boys)
     • Girls - Thelarche:
       • ★ First sign of puberty in girls
       • Age: 8-11 years (average 10.5)
       • Breast bud development (Tanner stage 2)
     • Boys - Testicular enlargement:
       • ★ First sign of puberty in boys
       • Age: 9-14 years (average 11.5)
       • Testicular volume >4 mL (normal prepubertal: 1-3 mL)
  4. Growth Spurt
     • Peak height velocity:
       • Girls: 11.5 years (6-12 cm/year)
       • Boys: 13.5 years (7-14 cm/year)
     • Mechanism: Estrogen → ↑Growth hormone → ↑IGF-1
     • Duration: ~2 years
  5. Pubarche
     • Definition: Onset of pubic hair growth
     • Age: Usually follows thelarche/testicular enlargement by 6-12 months
     • Hormone: Primarily androgen-dependent
  6. Menarche (Girls) / Voice Changes (Boys)
     • Girls - Menarche:
       • Age: 10-16 years (mean: 13 years)
       • Timing: Usually 2-3 years after thelarche
       • Important: Initial cycles often anovulatory for 6-18 months
     • Boys - Voice changes:
       • Age: 13-15 years
       • Mechanism: Testosterone → laryngeal growth
• Female: adrenarche → gonadarche → thelarche → growth spurt→ pubarche → menarche

Pubertal changes -Tanner stage-

Precocious puberty

• Definition: A condition in which onset of pubertal development begins earlier than normal population — typically before age 8 in girls and before age 9 in boys.
• Classification:
  • Central precocious puberty:
    • Pathophysiology
      • Gonadotropin-dependent precocious puberty
      • Early activation of hypothalamic-pituitary-gonadal axis → ↑GnRH → ↑LH/FSH → ↑sex hormones
    • Causes: idiopathic (most common), CNS lesions (25%, most commonly is craniopharyngioma), systemic condition like (tuberous sclerosis, neurofibromatosis).
      • Note: most common cause in girls is idiopathic (85-90%) while in boys is CNS lesions (60%)
    • Clinical picture: normal symmetric development of secondary sexual characteristics but at an early age.
    • Diagnosis:
      • Lab:
        • Serum LH and FSH: increased
        • GnRH stimulation test (gold standard, increase in LH levels after GnRH administration)
        • Estradiol level: increased
      • Imaging:
        • X-ray of the nondominant hand and wrist (increase bone age)
        • MRI/CT of the brain with contrast if increased LH is confirmed (to rule out CNS lesions).
    • Treatment:
      • GnRH agonist (e.g., leuprolide, buserelin, goserelin).
      • Treat underlying cause
  • Peripheral precocious puberty
    • Pathophysiology
      • Gonadotropin-independent precocious puberty, peripheral pseudopuberty
      • Autonomous sex hormone production → negative feedback → ↓LH/FSH
    • Causes: HCG-producing tumors (granulosa cell tumors and follicular cysts), congenital adrenal hyperplasia, McCune Albright syndrome (increase estrogen production), and exogenous estrogen exposure
    • Clinical picture: not following the normal secondary sexual development.
    • Diagnosis:
      • Lab:
        • FSH and LH decreased
        • GnRH stimulation test (no increase in LH levels after GnRH administration)
      • Imaging:
        • X-ray (accelerated bone growth)
        • Pelvic/abdominal ultrasound
        • Adrenal CT/MRI if indicated
      • Treatment:
        • Treat underlying cause
        • Androgen or estrogen antagonist therapy.
        • Surgical intervention: For tumors

Delayed puberty

• Definition: Absent breast development by age 13 OR absent menstruation by age 14 OR within 3 years of breast development
• Causes:
  • Constitutional delay of puberty (most common cause, physiological cause)
  • Genetic disorders (ex. Turner syndrome)
  • Hypergonadotropic hypogonadism
  • Hypogonadotropic hypogonadism (ex. Kallman syndrome “genetic cause”)
  • Certain chronic disorders (eg, diabetes mellitus, inflammatory bowel disorders, renal disorders, CF, anemia)
  • Autoimmune disorders (eg, Hashimoto thyroiditis)
• Basic Pathophysiology
  

  Delayed Puberty: Levels of Dysfunction
  Level of Dysfunction	Mechanism	LH/FSH Levels	Sex Hormone Levels
  Constitutional Delay	Normal but delayed HPG axis maturation	Low (prepubertal)	Low
  Hypogonadotropic	Hypothalamic/pituitary dysfunction	Low	Low
  Hypergonadotropic	Primary gonadal failure	High	Low

• Diagnosis:
  • Best initial test: Bone age X-ray (left hand/wrist)
  • Most important labs: LH, FSH, estradiol (girls), genetic testing
  • Initial Laboratory Workup
    

    Hormonal Evaluation in Delayed Puberty
    Test	Purpose	Normal Values	Interpretation
    ★ LH, FSH	Classify hypo vs hypergonadotropic	Prepubertal: <2 IU/L	High = primary gonadal failure
    Testosterone (boys)	Assess gonadal function	Prepubertal: <50 ng/dL	Low with high LH/FSH = primary failure
    Estradiol (girls)	Assess ovarian function	Prepubertal: <20 pg/mL	Low with high LH/FSH = ovarian failure
    Prolactin	Rule out prolactinoma	<25 ng/mL	Elevated suggests pituitary adenoma
    TSH, T4	Rule out hypothyroidism	TSH: 0.5–5.0 mIU/L	Hypothyroidism can delay puberty

• Treatment:
  • Constitutional delay of puberty: reassurance
  • Treat the underlying cause
  • May include hormone therapy (e.g., testosterone, estrogen)