What will a cortisol level test reveal about a 40-year-old female patient's adrenal function, particularly if she has a history of pituitary tumors and symptoms such as weight gain, hypertension, and fatigue?

What a Cortisol Level Will Tell You

A cortisol level, when measured alongside ACTH, will definitively distinguish between primary adrenal insufficiency (low cortisol with high ACTH), secondary adrenal insufficiency (low cortisol with low/normal ACTH), and ACTH-dependent hypercortisolism from a pituitary or ectopic source (high cortisol with detectable/elevated ACTH). 1

Critical Context for Your Patient

Given this patient's history of pituitary tumors with weight gain, hypertension, and fatigue, the cortisol level serves two essential diagnostic purposes:

1. Screening for Subclinical Cushing's Disease

• Pituitary tumors can cause subclinical Cushing's disease in approximately 4.8% of cases, presenting with metabolic disorders (hypertension, obesity, glucose intolerance) without classic Cushingoid features. 2
• Morning basal cortisol should be measured alongside ACTH to identify ACTH-dependent hypercortisolism—elevated cortisol with detectable or elevated ACTH indicates either pituitary or ectopic ACTH production. 3
• If basal cortisol is elevated with non-suppressed ACTH, perform a 1 mg overnight dexamethasone suppression test—failure to suppress cortisol below 1.8 μg/dL (50 nmol/L) suggests autonomous cortisol production. 4
• Confirm with 24-hour urinary free cortisol excretion, which provides integrated assessment of cortisol production. 4
• Midnight serum cortisol >5.0 μg/dL further supports the diagnosis of Cushing's syndrome by demonstrating loss of normal circadian rhythm. 2

2. Evaluating for Adrenal Insufficiency

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in the presence of acute illness is diagnostic of primary adrenal insufficiency. 1
• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH suggests secondary adrenal insufficiency, which is relevant given her pituitary tumor history. 1
• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases, but absence of hyperkalemia cannot rule out the diagnosis as it occurs in only ~50% of cases. 1
• If morning cortisol is indeterminate (neither clearly normal nor clearly low), proceed with cosyntropin stimulation test: administer 0.25 mg intramuscularly or intravenously, measure cortisol at 30 minutes, with peak cortisol <500 nmol/L (<18 μg/dL) diagnostic of adrenal insufficiency. 1

Algorithmic Approach to Interpretation

Step 1: Measure morning (8 AM) cortisol AND ACTH simultaneously 1

Step 2: Interpret the pattern:

• High cortisol + High/Normal ACTH → ACTH-dependent Cushing's syndrome (pituitary vs. ectopic source) 3

  • Proceed with high-dose dexamethasone suppression test and pituitary MRI 3
  • If MRI negative or equivocal, bilateral inferior petrosal sinus sampling is gold standard to confirm pituitary source 3
  • Central-to-peripheral ACTH ratio ≥2:1 before stimulation and ≥3:1 after CRH/desmopressin confirms pituitary origin 3

• Low cortisol + High ACTH → Primary adrenal insufficiency 1

  • Check 21-hydroxylase autoantibodies (positive in ~85% of autoimmune cases) 1
  • If negative, obtain adrenal CT to evaluate for hemorrhage, tumor, or infiltrative disease 1

• Low cortisol + Low/Normal ACTH → Secondary adrenal insufficiency 1

  • Highly relevant given pituitary tumor history
  • Requires glucocorticoid replacement but NOT mineralocorticoid replacement 1

• Normal cortisol → Does not exclude subclinical Cushing's disease; proceed with dexamethasone suppression test if clinical suspicion remains high 2

Critical Pitfalls to Avoid

• Never rely on a single random cortisol measurement—cortisol has marked diurnal variation, and timing of collection is essential. 1
• Do not delay treatment of suspected adrenal crisis for diagnostic testing—if the patient is clinically unstable with unexplained hypotension, give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion. 1
• Exogenous steroids (including inhaled fluticasone) suppress the HPA axis and confound results—ensure the patient is not on any corticosteroid therapy when testing. 1
• Absence of hyperkalemia does not rule out primary adrenal insufficiency—it is present in only ~50% of cases. 1
• Hyponatremia with hypo-osmolality requires excluding adrenal insufficiency before diagnosing SIADH—both conditions present identically, and the cosyntropin stimulation test is medically necessary to distinguish them. 1

Treatment Implications Based on Results

If Cushing's disease is confirmed:

• First-line treatment is transsphenoidal surgical resection of the pituitary adenoma. 3, 5
• Medical management with ketoconazole 400-1200 mg/day is most commonly used for residual disease due to relatively tolerable toxicity profile. 4, 3, 5
• Postoperative corticosteroid supplementation is required until HPA axis recovery. 4, 3

If adrenal insufficiency is confirmed:

• Primary adrenal insufficiency requires both glucocorticoid (hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoid (fludrocortisone 0.05-0.1 mg daily) replacement. 1
• Secondary adrenal insufficiency requires only glucocorticoid replacement since the renin-angiotensin-aldosterone system remains intact. 1
• All patients need education on stress dosing, medical alert identification, and emergency injectable hydrocortisone kit. 1