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Chemistry

Stimulation/Suppression

Dynamic endocrine testing, through stimulation or suppression, helps assess gland function by challenging the normal feedback loops and observing the hormonal response

Principles of Stimulation/Suppression Testing

  • Purpose: To evaluate the functional reserve of an endocrine gland or to assess the autonomy of hormone production
  • Dynamic Assessment: Unlike static hormone measurements, these tests measure the gland’s response to a challenge
  • Types of Tests
    • Stimulation Tests: Used to assess hormone deficiency by stimulating hormone release and measuring the gland’s capacity to respond
    • Suppression Tests: Used to assess hormone excess by suppressing hormone production and measuring the gland’s ability to be inhibited
  • General Procedure
    1. Baseline Sample Collection: One or more baseline blood samples are collected to measure initial hormone levels
    2. Administration of Stimulatory or Suppressive Agent: A specific agent is administered to stimulate or suppress hormone production
    3. Serial Sample Collection: Blood samples are collected at specified intervals after the agent is administered to monitor the hormone response
    4. Interpretation: Hormone levels are measured and compared to established reference ranges to determine if the endocrine gland is functioning normally

Common Stimulation Tests

ACTH Stimulation Test (Cosyntropin Test)

  • Purpose: To assess adrenal gland function and diagnose adrenal insufficiency
  • Principle: Synthetic ACTH (cosyntropin) is administered to stimulate cortisol production by the adrenal glands
  • Procedure
    1. Baseline cortisol level is measured
    2. Cosyntropin (250 μg) is administered intravenously or intramuscularly
    3. Cortisol levels are measured 30 and 60 minutes post-injection
  • Interpretation
    • Normal Response: Cortisol level increases by at least 20 μg/dL from baseline and reaches a peak value of at least 20 μg/dL
    • Primary Adrenal Insufficiency: Minimal or no increase in cortisol levels, indicating adrenal gland dysfunction
    • Secondary Adrenal Insufficiency: Delayed or subnormal response, indicating pituitary dysfunction
  • Special Considerations
    • Patient should be off any glucocorticoid medications prior to the test
    • False-positive results can occur in patients with acute illness or stress

Insulin Tolerance Test (ITT)

  • Purpose: To assess growth hormone (GH) and ACTH reserve
  • Principle: Insulin-induced hypoglycemia stimulates the release of GH and ACTH
  • Procedure
    1. Baseline GH and cortisol levels are measured
    2. Regular insulin (0.05-0.15 U/kg) is administered intravenously to induce hypoglycemia
    3. GH and cortisol levels are measured at 30, 60, and 90 minutes post-injection
    4. Blood glucose levels are monitored throughout the test to ensure adequate hypoglycemia (glucose < 40 mg/dL)
  • Interpretation
    • Normal GH Response: GH level increases to at least 5-10 ng/mL
    • Normal Cortisol Response: Cortisol level increases by at least 7 μg/dL from baseline and reaches a peak value of at least 20 μg/dL
    • Abnormal Response: Failure to achieve adequate hypoglycemia or failure of GH and/or cortisol to increase appropriately
  • Special Considerations
    • ITT is contraindicated in patients with coronary artery disease, seizures, or known adrenal insufficiency
    • Test should be performed under close medical supervision due to the risk of severe hypoglycemia

TRH Stimulation Test

  • Purpose: To assess pituitary TSH reserve and diagnose thyroid disorders
  • Principle: TRH (thyrotropin-releasing hormone) stimulates the release of TSH from the pituitary gland
  • Procedure
    1. Baseline TSH level is measured
    2. TRH (200-500 μg) is administered intravenously
    3. TSH levels are measured at 30 and 60 minutes post-injection
  • Interpretation
    • Normal Response: TSH level increases by at least 5 μIU/mL from baseline
    • Primary Hypothyroidism: Elevated baseline TSH with an exaggerated response to TRH
    • Secondary Hypothyroidism: Low or normal baseline TSH with a blunted or absent response to TRH, indicating pituitary dysfunction
    • Tertiary Hypothyroidism: Low or normal baseline TSH with a delayed response to TRH, indicating hypothalamic dysfunction
  • Special Considerations
    • Patient should be off any thyroid hormone medications prior to the test
    • Certain medications (e.g., glucocorticoids, dopamine) can affect TSH secretion and interfere with the test results

Common Suppression Tests

Dexamethasone Suppression Test (DST)

  • Purpose: To diagnose Cushing’s syndrome and differentiate its causes
  • Principle: Dexamethasone, a synthetic glucocorticoid, suppresses ACTH production by the pituitary gland, which in turn suppresses cortisol production by the adrenal glands
  • Types of DST
    • Low-Dose DST: Used to screen for Cushing’s syndrome
    • High-Dose DST: Used to differentiate between pituitary-dependent Cushing’s disease and ectopic ACTH-secreting tumors
  • Procedure
    • Low-Dose DST
      1. Baseline cortisol level is measured
      2. Dexamethasone (1 mg) is administered orally at 11 PM
      3. Cortisol level is measured at 8 AM the following morning
    • High-Dose DST
      1. Baseline cortisol and ACTH levels are measured
      2. Dexamethasone (8 mg) is administered orally at 11 PM
      3. Cortisol and ACTH levels are measured at 8 AM the following morning
  • Interpretation
    • Low-Dose DST
      • Normal Suppression: Cortisol level is suppressed to < 1.8 μg/dL
      • Lack of Suppression: Cortisol level remains elevated, indicating Cushing’s syndrome
    • High-Dose DST
      • Pituitary-Dependent Cushing’s Disease: Cortisol level is suppressed by at least 50% from baseline
      • Ectopic ACTH-Secreting Tumor: Cortisol level is not suppressed
      • Adrenal Tumor: Cortisol level is not suppressed
  • Special Considerations
    • Certain medications (e.g., phenytoin, carbamazepine) can increase the metabolism of dexamethasone and interfere with the test results
    • False-positive results can occur in patients with depression, alcoholism, or chronic stress

Oral Glucose Suppression Test

  • Purpose: To diagnose acromegaly
  • Principle: Glucose normally suppresses growth hormone (GH) secretion
  • Procedure
    1. Baseline GH level is measured
    2. Patient drinks a standard glucose solution (75 g)
    3. GH levels are measured at 30, 60, 90, and 120 minutes post-ingestion
  • Interpretation
    • Normal Suppression: GH level is suppressed to < 1 ng/mL
    • Lack of Suppression: GH level remains elevated, indicating autonomous GH secretion characteristic of acromegaly
  • Special Considerations
    • Certain medications (e.g., beta-blockers) can interfere with the test results
    • False-positive results can occur in patients with renal failure or liver disease

General Precautions and Considerations

  • Patient Selection: Ensure that the patient is an appropriate candidate for the test and that there are no contraindications
  • Medication Review: Review the patient’s medication list and determine if any medications need to be withheld prior to the test
  • Informed Consent: Obtain informed consent from the patient after explaining the purpose, procedure, and potential risks of the test
  • Adverse Reactions: Be prepared to manage potential adverse reactions to the stimulatory or suppressive agent
  • Standardized Procedures: Follow standardized procedures for test administration, sample collection, and hormone measurement
  • Quality Control: Implement rigorous quality control procedures to ensure the accuracy and reliability of hormone measurements
  • Reference Ranges: Use appropriate reference ranges for the specific test and patient population
  • Clinical Correlation: Interpret test results in the context of the patient’s clinical presentation and other laboratory findings

Key Terms

  • Stimulation Test: A test used to assess hormone deficiency by stimulating hormone release
  • Suppression Test: A test used to assess hormone excess by suppressing hormone production
  • ACTH Stimulation Test: A test used to assess adrenal gland function
  • Insulin Tolerance Test (ITT): A test used to assess growth hormone and ACTH reserve
  • TRH Stimulation Test: A test used to assess pituitary TSH reserve
  • Dexamethasone Suppression Test (DST): A test used to diagnose Cushing’s syndrome
  • Oral Glucose Suppression Test: A test used to diagnose acromegaly
  • Dynamic Testing: Assessing endocrine function by measuring the response to a challenge
  • Baseline Sample: A blood sample collected prior to the administration of a stimulatory or suppressive agent
  • Reference Range: The range of values found in healthy individuals