What is precocious puberty, its causes, diagnosis, treatment options, and management in children?

Precocious Puberty: Comprehensive Overview

Definition and Age Criteria

Precocious puberty is defined as the appearance of secondary sexual characteristics before age 8 years in girls or age 9 years in boys. 1, 2

• In girls, the first sign of true precocious puberty is breast development (thelarche), NOT isolated pubic or axillary hair, which represents adrenarche and should not be confused with true precocious puberty 1
• In boys, testicular enlargement (volume ≥4 mL or length ≥25 mm) marks the onset 3

Classification and Pathophysiology

Central Precocious Puberty (CPP) - Gonadotropin-Dependent

This is the most common form, resulting from premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. 4, 3

Causes include:

• Idiopathic (most common in girls) - though genetic discoveries have reduced "idiopathic" cases 4
• CNS pathology (more common in boys) - hypothalamic hamartomas, gliomas, arachnoid cysts, physical injuries 1, 4
• Genetic mutations - MKRN3, DLK1, KISS1, KISS1R genes 4, 3
• Familial constitutional variants 2

Peripheral Precocious Puberty (PPP) - Gonadotropin-Independent

This results from sex hormone production independent of the HPG axis. 3

Causes include:

• McCune-Albright syndrome 3
• Congenital adrenal hyperplasia 3
• Functioning ovarian or testicular tumors/cysts 1, 3
• Exogenous sex steroid exposure 2, 3
• Profound primary hypothyroidism (pseudo-precocious puberty) 3

Risk Factors and Epidemiology

• Clear female predominance (CPP occurs more frequently in girls) 4
• International adoption increases risk 4
• Obesity and endocrine disruptors are associated factors 5, 4
• Boys have higher likelihood of identifiable organic pathology 6

Diagnostic Evaluation

Initial Clinical Assessment

Evaluate for progressive versus nonprogressive precocious puberty, as nonprogressive cases do not require treatment. 5

• Tanner staging to assess degree of pubertal development 1
• Growth parameters - height, weight, growth velocity (accelerated growth is characteristic) 1, 5
• Family history of pubertal timing and potential exogenous hormone exposure 1
• Neurological symptoms - severe headaches, visual changes, seizures (mandate MRI) 1

Laboratory Testing

Measure baseline LH, FSH, and estradiol levels to differentiate central from peripheral precocious puberty. 1, 2

• GnRH stimulation test is the gold standard for confirming CPP: peak LH >10 IU/L indicates HPG axis activation 1
• Prolactin level - normal range rules out hyperprolactinemia, which occurs in 65% of true pituitary pathology cases 1
• Thyroid function tests to exclude hypothyroidism 3

Radiologic Assessment

Obtain bone age X-ray in all cases - bone age exceeds chronologic age in precocious puberty. 1, 5

Brain MRI with gadolinium contrast of the sella and hypothalamic-pituitary axis is indicated for confirmed CPP, especially:

• All girls under age 6 years (highest risk of CNS abnormalities) 1, 2
• Girls aged 6-8 years based on clinical presentation (2-7% likelihood of CNS lesion) 1
• Any patient with neurological symptoms 1
• MRI is superior to CT for parenchymal tissue visualization 1

Pelvic ultrasound to rule out ovarian tumors or cysts in girls 1

Treatment Approach

Central Precocious Puberty

GnRH analogs (long-acting depot formulations) are the standard treatment for progressive CPP. 1, 7

Treatment goals:

• Preserve final adult height (primary concern as CPP causes accelerated bone maturation and reduced stature) 1, 7
• Delay further pubertal progression and menarche 1
• Optimize development of secondary sex characteristics 1
• Address psychosocial consequences 8

Mechanism: GnRH analogs desensitize gonadotrophs through continuous stimulation, reducing LH release and halting gonadal stimulation 1

Treatment duration: Continue until normal age of puberty 1

Evidence for efficacy: All published evidence in girls with progressive precocious puberty indicates gain in adult height over predicted height before treatment or untreated historical controls 7

Important caveat: In girls with puberty onset at ages 8-10 years (lower half of normal distribution), GnRH agonist trials show no benefit 7

Peripheral Precocious Puberty

Treatment targets the underlying cause:

• Congenital adrenal hyperplasia: Glucocorticoids to suppress adrenal androgen secretion 3
• McCune-Albright syndrome: Third-generation aromatase inhibitors (anastrozole, letrozole) are more potent 3
• Tumors: Surgical intervention as indicated 3

Nonprogressive Precocious Puberty

Follow-up every 3-6 months between ages 6-7 years to assess for progression rather than initiating treatment. 5

Referral Criteria

Refer to pediatric endocrinology after obtaining baseline LH, FSH, and estradiol if Tanner stage 2 breast development occurs before age 8 years in girls. 1

Long-term Complications and Monitoring

Early puberty is associated with increased risk of behavioral problems, obesity, metabolic disorders, and breast cancer in long-term follow-up. 1, 8, 4

Psychosocial support and mental health monitoring:

• Early intervention with psychosocial support is crucial before psychiatric disorders develop 8
• Monitor for behavioral problems and mood symptoms during pubertal transition, even with treatment 8
• Mood symptoms often follow a predictable developmental course around puberty in at-risk youth 8

Fertility considerations:

• Provide contraceptive counseling as appropriate, since fertility may be present despite young age 1

Common Pitfalls to Avoid

• Do not confuse isolated adrenarche (pubic/axillary hair) with true precocious puberty - true CPP begins with breast development in girls 1
• Do not treat nonprogressive precocious puberty - reassess within several months if diagnosis is uncertain 5
• Do not skip brain MRI in girls under 6 years with CPP - they have the highest risk of CNS abnormalities 1, 2
• Do not overlook the need for contraceptive counseling in treated patients 1