What is ACTH (Adrenocorticotropic Hormone) plasma?

ACTH Plasma: Diagnostic Role in Endocrine Disorders

Plasma ACTH (Adrenocorticotropic Hormone) is a critical diagnostic marker that helps differentiate between primary and secondary adrenal disorders, with normal morning values ranging from 5-60 ng/L (1.1-13.2 pmol/L). 1

What is ACTH?

ACTH is a hormone produced by the anterior pituitary gland that regulates cortisol production through the hypothalamic-pituitary-adrenal (HPA) axis. It functions in a negative feedback mechanism where:

• Rising cortisol levels inhibit ACTH secretion
• Falling cortisol levels stimulate ACTH secretion
• ACTH stimulates the adrenal cortex to produce cortisol

Normal ACTH Values and Diurnal Variation

• Morning (8:00-9:00 AM) plasma ACTH: 5-60 ng/L (1.1-13.2 pmol/L)
• Evening/night levels are typically lower (approximately 50% of morning values)
• ACTH follows a circadian rhythm with peak levels occurring around 6 AM and lowest levels around midnight 2

Diagnostic Applications of ACTH Measurement

1. Differentiating Types of Adrenal Insufficiency

• Primary adrenal insufficiency: Markedly elevated ACTH (>100 ng/L) with low cortisol due to lack of cortisol feedback 3
• Secondary adrenal insufficiency: Low or inappropriately normal ACTH with low cortisol due to pituitary dysfunction 3

2. Diagnosing Cushing's Syndrome

ACTH measurement helps determine the etiology of hypercortisolism:

• ACTH-dependent Cushing's syndrome (pituitary origin/Cushing's disease):

  • Normal or elevated ACTH (>5 ng/L or >1.1 pmol/L) 3
  • Using a cut-off of 29 ng/L (6.4 pmol/L), ACTH has 70% sensitivity and 100% specificity for diagnosing Cushing's disease 3

• ACTH-independent Cushing's syndrome (adrenal tumor):

  • Suppressed or undetectable ACTH levels 3

• Ectopic ACTH syndrome:

  • Typically very high ACTH levels 4

3. Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

• Plasma ACTH levels during critical illness can be variable (low, normal, or high)
• Guidelines suggest against using ACTH levels for routine diagnosis of CIRCI due to complexity of measurement and insufficient turnaround time 3

Testing Considerations

• Morning samples (8:00-9:00 AM) are preferred due to diurnal variation
• Samples should be collected in plastic tubes and processed rapidly to prevent ACTH degradation
• ACTH measurement is often paired with cortisol measurement for proper interpretation
• Dynamic testing (CRH stimulation, dexamethasone suppression) may be required for definitive diagnosis 3

Clinical Pitfalls and Caveats

• ACTH has a short half-life (22-30 minutes) in plasma, requiring proper sample handling 5
• Multiple forms of ACTH exist (including "big ACTH" with low biological activity), which may affect interpretation in certain conditions like lung carcinoma 6
• Stress, illness, and medications can affect ACTH levels
• ACTH levels should always be interpreted in the context of clinical presentation and cortisol levels
• Cyclical Cushing's disease may show variable ACTH levels, requiring repeated measurements 3

Specialized Testing

For cases where standard ACTH measurement doesn't provide a definitive diagnosis:

• Bilateral inferior petrosal sinus sampling (BSIPSS): Recommended for patients with ACTH-dependent Cushing's syndrome without identified pituitary adenoma on MRI 3
  • A central-to-peripheral ACTH ratio ≥2:1 before CRH/desmopressin and ≥3:1 after stimulation confirms pituitary source 3
  • Should only be performed in specialized centers by experienced interventional radiologists 3

Remember that ACTH measurement is just one component of a comprehensive endocrine evaluation and should be interpreted alongside other clinical and biochemical parameters.