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Cortisol (4:00 PM)

Immunity
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Report in 4Hrs

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No Fasting Required

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Cortisol plays a major role in Regulating metabolism, Managing immune response, Controlling blood pressure, Assisting in glucose regulation

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Cortisol (4:00 PM) - Comprehensive Medical Test Guide

  • Why is it done?
    • Measures the level of cortisol, a steroid hormone produced by the adrenal glands that regulates stress response, blood pressure, glucose metabolism, and immune function
    • Evaluates circadian rhythm disruption by measuring cortisol at its expected nadir (lowest point) in the late afternoon, as cortisol levels follow a daily pattern with highest levels in early morning and lowest levels in late afternoon/evening
    • Diagnoses Cushing's syndrome (excessive cortisol production) - typically ordered along with 8:00 AM cortisol for comparison
    • Screens for Addison's disease (adrenal insufficiency) when abnormally low values are present
    • Investigates symptoms such as fatigue, weakness, mood changes, weight gain, easy bruising, purple stretch marks, hypertension, or muscle weakness
    • Evaluates abnormal results from previous 8:00 AM cortisol or dexamethasone suppression tests
    • Typically performed in conjunction with morning cortisol tests to assess the appropriate daily decline in cortisol levels
  • Normal Range
    • Reference Range: 2.0-12.0 mcg/dL (or 50-320 nmol/L SI units)
    • Units of Measurement: mcg/dL (micrograms per deciliter) or nmol/L (nanomoles per liter)
    • What Normal Means: Values within the reference range indicate appropriate circadian cortisol decline with adequate suppression of cortisol in the afternoon, suggesting normal adrenal function and normal HPA (hypothalamic-pituitary-adrenal) axis regulation
    • High Values (>12.0 mcg/dL): Indicates inadequate suppression of cortisol in the afternoon; may suggest Cushing's syndrome, loss of normal circadian rhythm, or chronic stress
    • Low Values (<2.0 mcg/dL): May indicate adrenal insufficiency, Addison's disease, or hypopituitarism, though afternoon values are normally lower than morning values
    • Borderline Values: Values near the upper limit of normal (10-12 mcg/dL) may warrant repeat testing, comparison with morning cortisol levels, or additional diagnostic studies such as late-night salivary cortisol or dexamethasone suppression test
  • Interpretation
    • Elevated 4:00 PM Cortisol (>12.0 mcg/dL): Suggests loss of normal diurnal cortisol variation; abnormal afternoon suppression may indicate Cushing's syndrome (pituitary adenoma, ectopic ACTH secretion, adrenal carcinoma, or primary adrenal hyperplasia); particularly significant if 8:00 AM cortisol is also elevated
    • Normal 4:00 PM Cortisol (2.0-12.0 mcg/dL) with Elevated 8:00 AM Cortisol: Suggests normal circadian rhythm may be preserved; helps distinguish pseudoCushing's (stress, depression) from true Cushing's syndrome
    • Low 4:00 PM Cortisol (<2.0 mcg/dL): May indicate adrenal insufficiency, particularly if morning cortisol is also low; may occur with hypopituitarism, central adrenal insufficiency, or end-stage Addison's disease
    • Flattened Circadian Rhythm: When both 8:00 AM and 4:00 PM cortisol are elevated or when the normal morning-to-afternoon decline is absent, suggests disrupted HPA axis function; seen in Cushing's syndrome, depression, chronic stress, sleep disorders, shift work, or metabolic syndrome
    • Factors Affecting Results:
    • Physical or psychological stress (illness, pain, anxiety, depression)
    • Medications: estrogen, oral contraceptives, corticosteroids, phenytoin, rifampin, and other medications affecting cortisol metabolism
    • Time zone changes, shift work, or sleep disturbances causing circadian rhythm disruption
    • Obesity and metabolic conditions may alter cortisol levels
    • Pregnancy increases cortisol-binding globulin and may elevate total cortisol
    • Sample collection timing must be precise at 4:00 PM (±30 minutes) for accurate circadian rhythm assessment
  • Associated Organs
    • Primary Organ System: Endocrine system (specifically the hypothalamic-pituitary-adrenal axis)
    • Organs Directly Involved:
    • Adrenal glands (zona fasciculata) - produce cortisol
    • Pituitary gland (anterior lobe) - produces and secretes ACTH (adrenocorticotropic hormone)
    • Hypothalamus - produces CRH (corticotropin-releasing hormone)
    • Medical Conditions Associated with Abnormal Results:
    • Cushing's Syndrome - excess cortisol production caused by: pituitary adenoma (Cushing's disease), adrenocortical tumors, ectopic ACTH production (lung cancer, thymic tumors), or primary adrenal hyperplasia
    • Addison's Disease (Primary Adrenal Insufficiency) - autoimmune destruction of adrenal cortex, tuberculosis, fungal infections, adrenal hemorrhage, or metastatic cancer
    • Central Adrenal Insufficiency - pituitary tumors, pituitary apoplexy, hypopituitarism, or pituitary surgery affecting ACTH production
    • Pseudo-Cushing's Syndrome - depression, anxiety, eating disorders, chronic alcoholism, obesity, or poorly controlled diabetes causing elevated cortisol without true Cushing's pathology
    • Polycystic Ovary Syndrome (PCOS) - mild cortisol elevation may be present
    • Metabolic Syndrome - altered cortisol secretion may contribute to insulin resistance and abdominal obesity
    • Potential Complications or Risks with Abnormal Results:
    • Chronic hypercortisolism: osteoporosis, fractures, muscle weakness, hypertension, diabetes, cardiovascular disease, depression, and increased infection risk
    • Chronic adrenal insufficiency: hypotension, hypoglycemia, hyponatremia, hyperkalemia, shock, and risk of adrenal crisis
    • Circadian rhythm disruption: sleep disorders, mood disorders, cognitive impairment, metabolic dysfunction
  • Follow-up Tests
    • If Elevated 4:00 PM Cortisol Suggests Cushing's Syndrome:
    • 8:00 AM cortisol level - assess degree of hypercortisolism
    • Late-night salivary cortisol (11:00 PM or midnight) - most sensitive screening test for Cushing's; lack of normal nighttime suppression is highly specific
    • Low-dose dexamethasone suppression test (1 mg overnight or 2 mg/day for 2 days) - evaluates suppressibility of cortisol by exogenous glucocorticoids
    • 24-hour urinary free cortisol (UFC) - confirms excessive cortisol production; increased UFC is the gold standard for Cushing's diagnosis
    • ACTH level (morning) - distinguishes ACTH-dependent from ACTH-independent Cushing's; elevated ACTH suggests pituitary adenoma or ectopic ACTH; suppressed ACTH suggests adrenal tumor
    • High-dose dexamethasone suppression test - if ACTH is elevated; helps differentiate pituitary (Cushing's disease) from ectopic ACTH syndrome
    • MRI of pituitary - if pituitary adenoma is suspected
    • CT scan of abdomen/pelvis - if adrenal tumor is suspected
    • Chest CT or ACTH sampling - if ectopic ACTH syndrome is suspected
    • If Low 4:00 PM Cortisol Suggests Adrenal Insufficiency:
    • 8:00 AM cortisol - if also low, confirms adrenal insufficiency
    • ACTH level (morning) - high ACTH with low cortisol indicates primary adrenal insufficiency; low or normal ACTH with low cortisol indicates central insufficiency
    • ACTH stimulation test (cosyntropin/tetracosactide) - evaluates adrenal reserve and confirms primary adrenal insufficiency
    • TSH, free T4, LH, FSH, prolactin - if central insufficiency suspected to evaluate other pituitary function
    • MRI of pituitary and hypothalamus - if central insufficiency is suspected
    • Adrenal antibodies (21-hydroxylase antibodies) - if autoimmune Addison's disease is suspected
    • If Normal Result but Clinical Suspicion Remains:
    • Repeat testing - cortisol levels may fluctuate; repeat sampling may be needed for confirmation
    • Monitoring frequency - baseline testing establishes starting point; monitoring intervals depend on diagnosis and treatment
    • Typically repeat testing at 4-6 week intervals during treatment optimization or after medication changes
  • Fasting Required?
    • Fasting Required: No
    • Fasting Status: Cortisol testing does not require fasting; the patient may eat and drink normally before the test
    • Critical Timing Requirements: The sample must be collected at precisely 4:00 PM (±30 minutes maximum); accuracy of timing is essential for meaningful interpretation
    • Sample Collection Method: Blood draw (serum cortisol) from a peripheral vein; collection is typically done in a clinical laboratory or healthcare setting
    • Medications to Avoid or Report:
    • Corticosteroids (prednisone, dexamethasone, hydrocortisone) - discontinue 24-48 hours before test if possible (consult physician); these medications directly suppress or elevate cortisol
    • Estrogen therapy and oral contraceptives - report to laboratory; may increase cortisol-binding globulin and elevate total cortisol
    • Phenytoin (Dilantin) and rifampin - report to laboratory; these medications affect cortisol metabolism
    • Licorice and licorice-containing products - avoid for 24-48 hours before test; can elevate cortisol levels
    • Other Patient Preparation Requirements:
    • Avoid strenuous exercise or significant physical activity 24 hours before test; physical stress can elevate cortisol
    • Minimize psychological stress in the 24 hours before testing; acute stress can transiently elevate cortisol levels
    • Avoid caffeine and nicotine for 30 minutes before blood draw; these stimulants may elevate cortisol
    • Remain seated and relaxed for 5-10 minutes before blood draw to allow cortisol levels to stabilize
    • Inform healthcare provider of recent illnesses, surgeries, or hospitalizations; acute illness or trauma elevates cortisol
    • Report sleep schedule and any shift work or recent travel; circadian rhythm disruption affects cortisol secretion
    • Maintain normal daily routine day of test; unusual activities or stress can artificially elevate results

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