What are the typical lab findings in congenital adrenal hyperplasia (CAH)?

Laboratory Findings in Congenital Adrenal Hyperplasia

The hallmark laboratory finding in CAH is markedly elevated 17-hydroxyprogesterone (17-OHP), typically accompanied by elevated ACTH, low cortisol, and elevated androgens, with additional electrolyte abnormalities in salt-wasting forms. 1

Primary Diagnostic Markers

17-Hydroxyprogesterone (17-OHP)

• Dramatically elevated 17-OHP is the diagnostic marker for 21-hydroxylase deficiency, which accounts for >95% of CAH cases 1, 2
• In classical CAH, baseline 17-OHP is markedly elevated at presentation 1
• In non-classical CAH, 17-OHP may be moderately elevated or normal at baseline, but ACTH stimulation testing reveals levels typically >30 nmol/L (above normal response) 1
• 21-deoxycortisol is emerging as a more specific marker than 17-OHP, as it is not elevated in premature infants or other forms of CAH 3

Cortisol and ACTH

• Serum cortisol is low or inappropriately normal for the clinical state 4
• Plasma ACTH is clearly elevated due to lack of negative feedback from cortisol deficiency 4
• ACTH stimulation test shows inadequate cortisol response, with peak cortisol <500 nmol/L (or <18 μg/dL) diagnostic of adrenal insufficiency 4, 5

Electrolyte Abnormalities (Salt-Wasting Form)

Sodium and Potassium

• Hyponatremia is present due to aldosterone deficiency, impaired free water clearance from cortisol deficiency, and increased vasopressin/angiotensin II 4
• Hyperkalemia results from aldosterone deficiency, impaired glomerular filtration, and acidosis 4
• Important caveat: In the presence of severe vomiting, hypokalemia and alkalosis may paradoxically be present instead 4

Other Electrolyte Findings

• Metabolic acidosis is common 4
• Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 4

Androgen Markers

Testosterone and Related Androgens

• Elevated testosterone (>2.5 nmol/L in females) is characteristic 4
• Elevated androstenedione (>10.0 nmol/L) may be present 4
• Elevated DHEAS (age-dependent thresholds: >3800 ng/mL for ages 20-29, >2700 ng/mL for ages 30-39) 4

Mineralocorticoid Axis

• Plasma renin activity (PRA) is increased in salt-wasting forms 4
• Serum aldosterone is low despite elevated renin 4

Additional Laboratory Findings

Hematologic and Metabolic

• Mild eosinophilia and lymphocytosis may be present 4
• Anemia can occur 4
• Increased liver transaminases are sometimes observed 4
• Hypoglycemia is more common in children but can occur in adults, potentially causing seizures 4

Thyroid Function

• TSH levels may be mildly elevated (typically 4-10 IU/L) due to lack of cortisol's inhibitory effect on TSH production 4

Enzyme-Specific Patterns in Rare CAH Forms

11-Beta-Hydroxylase Deficiency

• Elevated deoxycorticosterone (DOC), 11-deoxycortisol, and androgens distinguish this from 21-hydroxylase deficiency 6, 7
• Hypertension with hypokalemia is characteristic, unlike the salt-wasting seen in 21-hydroxylase deficiency 6, 7

3-Beta-HSD Deficiency

• Impaired both adrenal and gonadal steroid biosynthesis very early in the pathway 7
• May present with salt wasting or delayed puberty in both sexes 7

17-Hydroxylase Deficiency

• Estrogen deficiency in females leads to immature pubertal development and primary amenorrhea 7
• 46,XY disorders of sex development frequently observed in males 7

Critical Clinical Pitfall

Never delay treatment in suspected acute adrenal crisis to perform diagnostic testing - collect baseline cortisol and ACTH samples immediately, then start treatment without waiting for results 4, 5