What are the initial steps and tests for adrenal blood testing in patients suspected of having adrenal disorders?

Initial Steps and Tests for Adrenal Blood Testing in Suspected Adrenal Disorders

The initial adrenal blood testing should include morning cortisol and ACTH levels, serum electrolytes, aldosterone-to-renin ratio in hypertensive patients, and plasma free metanephrines for all patients with suspected adrenal disorders. 1, 2

Diagnostic Algorithm for Adrenal Testing

Step 1: Initial Laboratory Evaluation

• Morning serum cortisol and plasma ACTH - The cornerstone tests for evaluating adrenal function 1, 3
• Basic metabolic panel - To assess for electrolyte abnormalities (hyponatremia, hyperkalemia) 1
• Plasma free metanephrines - To screen for pheochromocytoma regardless of symptoms 2
• Aldosterone-to-renin ratio (ARR) - For patients with hypertension and/or hypokalemia 1, 2

Step 2: Confirmatory Testing Based on Initial Results

For Suspected Primary Adrenal Insufficiency:

• If morning cortisol is <250 nmol/L with elevated ACTH, this is diagnostic of primary adrenal insufficiency 1
• If results are equivocal, perform ACTH stimulation test (Synacthen test):
  • Administer 0.25 mg ACTH (tetracosactide) IV or IM
  • Measure serum cortisol at baseline and 30-60 minutes post-administration
  • Peak cortisol <500 nmol/L confirms adrenal insufficiency 1

For Suspected Cortisol Excess:

• 1 mg overnight dexamethasone suppression test:
  • Administer 1 mg dexamethasone at 11 PM
  • Measure serum cortisol at 8 AM the next morning
  • Interpretation:
    • <50 nmol/L excludes cortisol hypersecretion
    • 51-138 nmol/L suggests possible autonomous cortisol secretion

    • 138 nmol/L indicates cortisol hypersecretion 1, 2

For Suspected Primary Aldosteronism:

• If ARR is elevated (>20 ng/dL per ng/mL/hr), proceed with confirmatory testing:
  • Saline suppression test or salt loading with 24-hour urine aldosterone measurement 1

For Suspected Pheochromocytoma:

• If plasma free metanephrines are >2x upper limit of normal, this strongly suggests pheochromocytoma 1, 2

Etiology-Specific Testing

For Suspected Autoimmune Adrenal Insufficiency:

• 21-hydroxylase (21OH) autoantibodies - Positive results confirm autoimmune etiology 1

For Suspected Non-Autoimmune Adrenal Insufficiency:

• Adrenal CT scan - To identify tumors, calcifications (tuberculosis), hemorrhage, or infiltrative disease 1
• Very long-chain fatty acids (VLCFA) - In males to screen for adrenoleukodystrophy 1

For Suspected Adrenal Tumors:

• DHEAS, testosterone - Elevated in adrenocortical carcinoma or virilizing tumors 1
• Additional hormones if clinically indicated:
  • 17-OH progesterone
  • Androstenedione
  • 17-beta-estradiol (in men and postmenopausal women) 2

Important Clinical Considerations

• Never delay treatment of suspected acute adrenal insufficiency for diagnostic testing - Immediate administration of hydrocortisone and IV fluids is life-saving 1

• Testing conditions matter:

  • For ARR testing: Patient should be out of bed for 2 hours and seated for 5-15 minutes, potassium-replete, and off interfering medications 1
  • Morning cortisol samples should be collected between 8-9 AM 3

• Common pitfalls to avoid:

  • Failure to screen for pheochromocytoma before any intervention can cause life-threatening crisis 2
  • Exogenous steroid use (including inhaled steroids) may confound interpretation of cortisol levels 1
  • Patients with adrenal insufficiency may have mildly elevated TSH (4-10 IU/L) due to lack of cortisol's inhibitory effect on TSH production 1
  • 21OH antibodies may become negative over time in previously positive patients, so absence doesn't exclude autoimmune etiology 1

• Special considerations:

  • In children and elderly patients, 21OH antibodies are often absent even in autoimmune adrenal insufficiency 1
  • Perioperative hydrocortisone replacement is mandatory for patients with autonomous cortisol secretion 2

By following this systematic approach to adrenal blood testing, clinicians can efficiently diagnose adrenal disorders and prevent potentially life-threatening complications.