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ACTH (Adreno Corticotropic Hormone)

Hormone/ Element
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Details

Assesses pituitary secretion of ACTH, regulating cortisol production; used in Cushing’s or Addison’s disease.

7751,950

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ACTH (Adrenocorticotropic Hormone) - Comprehensive Test Guide

  • Why is it done?
    • Test Purpose: Measures the level of adrenocorticotropic hormone produced by the anterior pituitary gland to evaluate the function of the pituitary-adrenal axis and diagnose disorders affecting cortisol production
    • Suspected Cushing's Syndrome: Evaluates patients with symptoms of excessive cortisol including central obesity, purple stretch marks, muscle weakness, and mood disorders
    • Suspected Addison's Disease: Assesses patients with symptoms of adrenal insufficiency including fatigue, hypotension, hyperpigmentation, and electrolyte abnormalities
    • Pituitary Disorders: Evaluates anterior pituitary function and helps diagnose pituitary adenomas or secondary adrenal insufficiency
    • Cortisol Abnormalities: Assists in differentiating between various causes of abnormal cortisol levels and ectopic ACTH syndrome
    • Timing: Typically performed in the early morning (6-8 AM) as ACTH exhibits circadian rhythm with higher levels in the morning and lower levels in the evening
  • Normal Range
    • Reference Range (Morning): 10-50 pg/mL (picomoles per liter), with most laboratories using 7.2-36.0 pmol/L as standard reference
    • Reference Range (Evening): Less than 10 pg/mL, typically 3-13 pg/mL due to natural diurnal variation
    • Units of Measurement: pg/mL (picograms per milliliter) or pmol/L (picomoles per liter); conversion factor is 1 pg/mL = 0.22 pmol/L
    • Normal Results Indicate: Proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis with appropriate cortisol regulation and normal adrenal gland response
    • Elevated Values: Above normal range, often >50 pg/mL, suggest Cushing's syndrome, ectopic ACTH production, or primary adrenal insufficiency
    • Decreased Values: Below normal range, often <5 pg/mL, indicate secondary adrenal insufficiency or pituitary dysfunction with reduced hormone secretion
    • Interpretive Note: ACTH levels must be interpreted in conjunction with serum cortisol levels and clinical context, as results vary by laboratory methodology and individual circadian rhythm variations
  • Interpretation
    • Elevated ACTH (>50 pg/mL) with Elevated Cortisol: Suggests Cushing's syndrome due to pituitary adenoma (central) or ACTH production from non-pituitary sources (ectopic ACTH syndrome)
    • Elevated ACTH with Normal/Low Cortisol: Indicates primary adrenal insufficiency (Addison's disease) where the adrenal glands fail to respond to ACTH stimulation
    • Low ACTH (<5 pg/mL) with Low Cortisol: Indicates secondary adrenal insufficiency from pituitary disease, including pituitary adenoma, hypopituitarism, or prior pituitary surgery/radiation
    • Low ACTH with Normal/Elevated Cortisol: Suggests Cushing's syndrome from primary adrenal disease (adrenal tumor or carcinoma) with suppressed ACTH through negative feedback
    • Ectopic ACTH Syndrome: Characterized by markedly elevated ACTH (often >100 pg/mL) with elevated cortisol from non-pituitary tumors, typically small cell lung cancer or carcinoid tumors
    • Factors Affecting Results: Time of collection (circadian rhythm), stress level, physical activity, medications (corticosteroids, phenytoin), pregnancy, obesity, and acute illness can all influence ACTH levels
    • Circadian Variation Impact: ACTH levels peak at 6-8 AM and reach minimum levels at 11 PM-midnight; loss of normal circadian rhythm may indicate pathology even with normal absolute values
    • Clinical Significance: ACTH testing is essential for accurate diagnosis and differentiation of adrenal and pituitary disorders; misinterpretation can delay treatment and lead to serious complications
  • Associated Organs
    • Primary Organ Systems: Endocrine system, specifically the hypothalamus, anterior pituitary gland, and adrenal cortex (zona fasciculata)
    • Cushing's Syndrome: Excess cortisol production affecting metabolic, cardiovascular, and psychiatric systems; complications include hypertension, diabetes, osteoporosis, mood disorders, and increased infection risk
    • Addison's Disease (Primary Adrenal Insufficiency): Characterized by adrenal cortex destruction (autoimmune, tuberculosis, or other causes); complications include electrolyte imbalances, hypotension, shock, and reduced stress response capacity
    • Pituitary Adenomas: Benign tumors producing excess ACTH; can cause visual field defects, headaches, and hypopituitarism if large; most common cause of Cushing's syndrome
    • Ectopic ACTH Syndrome: Non-endocrine tumors (lung, thymus, pancreas) producing ACTH; associated with malignancy and carries poor prognosis; severe metabolic complications
    • Secondary Adrenal Insufficiency: Results from pituitary or hypothalamic disease; causes inadequate ACTH production affecting cortisol secretion and stress response
    • Adrenal Cortex Tumors: Benign adenomas or malignant carcinomas can produce autonomous cortisol independently of ACTH, leading to ACTH-independent Cushing's syndrome
    • Potential Complications of Abnormal ACTH: Hypertensive crisis, acute adrenal crisis (in insufficiency), cardiovascular disease, cerebrovascular accident, severe infections, electrolyte-related cardiac arrhythmias, and psychiatric emergencies
  • Follow-up Tests
    • Serum Cortisol: Essential companion test collected simultaneously; must be interpreted with ACTH to differentiate cause of abnormality
    • 24-Hour Urinary Free Cortisol: Confirmatory test for Cushing's syndrome; measures total cortisol excretion in urine; may be repeated if initial results are borderline
    • Dexamethasone Suppression Test (DST): Assesses pituitary-adrenal axis response; low-dose DST (overnight or 2-day) screens for Cushing's syndrome; high-dose DST differentiates pituitary from ectopic ACTH sources
    • Corticotropin-Releasing Hormone (CRH) Stimulation Test: Distinguishes pituitary (ACTH responds) from adrenal or ectopic causes (no response); measures ACTH and cortisol response 15-30 minutes after CRH injection
    • Pituitary MRI: Indicated if ACTH is elevated with high cortisol; visualizes pituitary for adenomas or structural abnormalities; may show normal results even with microadenomas
    • Adrenal Imaging (CT or MRI): Ordered if ACTH is suppressed with elevated cortisol; evaluates for adrenal tumors, nodules, or bilateral hyperplasia
    • Chest CT Scan: Performed if ectopic ACTH syndrome is suspected; screens for small cell lung cancer or carcinoid tumors; may require additional imaging if initial CT is negative
    • ACTH Stimulation Test (Cosyntropin Test): Evaluates adrenal function reserve in suspected adrenal insufficiency; assesses cortisol response 30-60 minutes after synthetic ACTH injection
    • Insulin Tolerance Test (ITT): Evaluates overall pituitary function including ACTH response to hypoglycemia; less commonly used but gold standard for assessing adrenal reserve
    • ACTH Monitoring Frequency: For diagnosed conditions: baseline levels, then 4-6 weeks after treatment initiation, then periodically based on clinical response; varies per condition and treatment modality
    • Plasma Midnight Cortisol: Screening test for Cushing's syndrome; loss of normal circadian rhythm is highly suggestive; often combined with late-night salivary cortisol
  • Fasting Required?
    • Fasting Status: No - fasting is NOT required for ACTH testing; food intake does not significantly affect ACTH levels
    • Timing Requirements: Specimen must be collected between 6-8 AM for optimal diagnostic accuracy due to circadian rhythm; early morning timing is critical, NOT fasting-related
    • Patient Preparation: Patient should be seated or recumbent for 30 minutes before blood draw; ensure minimal stress during collection as stress elevates ACTH
    • Medications to Hold/Adjust: Corticosteroids (prednisone, dexamethasone) should be held if possible before testing; phenytoin, vasopressin, and estrogen can affect results; consult physician regarding medication timing
    • Specimen Handling: Blood collected in EDTA (lavender-top) tube or plasma separator tube; must be transported on ice immediately to laboratory; sample degradation occurs at room temperature
    • Physical Activity: Avoid strenuous exercise for 24 hours before testing; light activity is acceptable but intense exercise can elevate ACTH
    • Stress Avoidance: Minimize physical and emotional stress before collection; relaxation techniques may help; notify physician of recent acute illness, surgery, or trauma
    • Sleep Considerations: Ensure adequate sleep night before test; sleep deprivation can affect circadian rhythm and ACTH levels
    • Special Instructions: Inform laboratory if patient works night shift or has irregular sleep schedule; consider 24-hour adapted collection time; coordinate with physician for optimal timing

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