What is the diagnostic workup for premature adrenarche?

Diagnostic Workup for Premature Adrenarche

The diagnostic workup for premature adrenarche should include measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, 17-hydroxyprogesterone, and exclusion of other causes of androgen excess through targeted laboratory testing and imaging when indicated. 1, 2

Definition and Clinical Presentation

• Premature adrenarche is defined as the appearance of clinical signs of androgen action before the age of 8 years in girls or 9 years in boys, associated with adrenal androgen precursor concentrations higher than expected for prepubertal chronological age 1, 3
• Clinical signs include:
  • Pubic and/or axillary hair (most pronounced sign) 1
  • Adult-type body odor (present in almost all cases) 4
  • Acne/comedones 2
  • Greasy hair 2
  • Accelerated statural growth 1, 2

Initial Evaluation

• Detailed history focusing on:

  • Timing and progression of androgen-related symptoms 4
  • Growth pattern (accelerated growth may indicate pathology) 2
  • Family history of similar presentation 4
  • Medication exposure (exogenous androgens) 1

• Physical examination should assess:

  • Height, weight, and BMI (PA children are often overweight and taller than peers) 1
  • Tanner staging of pubic/axillary hair 3
  • Presence of other signs of androgen excess 2
  • Blood pressure (to screen for conditions like congenital adrenal hyperplasia) 3
  • Signs of central puberty (breast development in girls, testicular enlargement in boys) 2

Laboratory Investigations

• First-line laboratory tests:

  • Serum DHEAS (best marker of adrenal androgen secretion) 1, 2
  • Androstenedione 2, 5
  • Testosterone 2, 5
  • 17-hydroxyprogesterone (to exclude congenital adrenal hyperplasia) 3
  • Bone age assessment (X-ray of left hand and wrist) 3

• Additional tests if clinically indicated:

  • ACTH stimulation test (measuring 17-hydroxyprogesterone response) if congenital adrenal hyperplasia is suspected 3
  • Serum electrolytes and blood pressure measurement 3
  • Fasting glucose, insulin levels (to assess for insulin resistance) 5
  • Lipid profile (to assess metabolic risk) 5

Imaging Studies

• Adrenal ultrasonography if:

  • Rapid progression of symptoms 3
  • Markedly elevated androgen levels 3
  • Signs of virilization (clitoromegaly, voice deepening) 2
  • Accelerated bone age advancement (>2 years) 3

• Advanced imaging (CT or MRI) only if:

  • Adrenal tumor is suspected based on clinical presentation or laboratory findings 2
  • Ultrasonography reveals abnormal adrenal morphology 3

Differential Diagnosis to Exclude

• Congenital adrenal hyperplasia (particularly non-classical form) 1, 2
• Androgen-producing tumors (adrenal or gonadal) 1
• Precocious puberty 1
• Exogenous source of androgens 1
• Cushing syndrome 3

Follow-up Recommendations

• Most cases of premature adrenarche are benign and require no specific treatment 3
• Regular follow-up is recommended for:
  • Children with additional risk factors (obesity, insulin resistance, low birth weight) 1, 5
  • Monitoring for progression to central puberty 3
  • Assessing for development of metabolic abnormalities 5

Special Considerations

• In cases with low birth weight and insulin resistance, consider metabolic monitoring 5
• For bilateral adrenal findings, consider measuring serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 6
• In populations with higher risk, monitor for progression to polycystic ovarian syndrome in girls 1, 5

Common Pitfalls to Avoid

• Failing to distinguish between benign premature adrenarche and pathological causes of androgen excess 4
• Overinvestigation of a typically benign condition 4
• Missing non-classical congenital adrenal hyperplasia, which can present similarly 3
• Neglecting metabolic risk assessment in children with additional risk factors 5