Proceed with ACTH Stimulation Testing to Confirm or Exclude Adrenal Insufficiency
Your patient's morning cortisol of 7.8 µg/dL with ACTH of 20 pg/mL falls into the indeterminate "gray zone" that requires cosyntropin stimulation testing to definitively rule in or rule out adrenal insufficiency. 1 This is not a diagnosis you can make or exclude based on these baseline values alone.
Why These Results Are Indeterminate
Morning cortisol 7.8 µg/dL is neither clearly normal nor clearly diagnostic. Cortisol <5 µg/dL with elevated ACTH would be diagnostic of primary adrenal insufficiency, while cortisol 5-10 µg/dL with low-normal ACTH suggests secondary adrenal insufficiency—but neither pattern is definitive without stimulation testing. 2
ACTH of 20 pg/mL is inappropriately low-normal for this cortisol level. In primary adrenal insufficiency, you would expect ACTH >63 pg/mL (often >100 pg/mL), while in secondary adrenal insufficiency, ACTH would be frankly low (<7 pg/mL). 3, 2 This intermediate ACTH suggests either early/partial adrenal dysfunction or secondary insufficiency, but cannot distinguish between them or confirm the diagnosis. 1
The clinical picture strongly supports testing further. Her symptoms (chronic nausea in 20-62% of AI cases, weight loss in 43-73%, post-surgical hypotension suggesting inability to mount stress response) combined with Hashimoto's disease (increasing autoimmune AI risk) make this a high pretest probability scenario. 3, 2
The Cosyntropin Stimulation Test Protocol
Administer 0.25 mg (250 mcg) cosyntropin intramuscularly or intravenously, with cortisol measurements at baseline, 30 minutes, and 60 minutes post-administration. 3, 1
Interpretation Criteria
Peak cortisol <500 nmol/L (<18 µg/dL) at either 30 or 60 minutes is diagnostic of adrenal insufficiency. 3, 1
Peak cortisol >550 nmol/L (>18-20 µg/dL) is normal and excludes adrenal insufficiency. 1, 2
The test should be performed in the morning, though this is not strictly mandatory. 1
Critical Considerations Before Testing
Do not delay testing for diagnostic procedures if the patient is clinically unstable or you suspect adrenal crisis. If she develops hypotension, altered mental status, severe vomiting, or shock, give hydrocortisone 100 mg IV immediately plus 0.9% saline infusion at 1 L/hour without waiting for test results. 3, 1
Ensure she is not taking exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) as these suppress the HPA axis and confound interpretation. 3, 1 If she has been on steroids, wait for adequate washout before testing—hydrocortisone requires 24 hours, other steroids require longer. 1
What the Test Will Tell You
If Peak Cortisol <500 nmol/L (<18 µg/dL): Adrenal Insufficiency Confirmed
Distinguish primary from secondary based on the baseline ACTH you already have:
High ACTH (>63 pg/mL) = Primary adrenal insufficiency (Addison's disease). Proceed with etiologic workup: measure 21-hydroxylase autoantibodies (positive in ~85% of autoimmune cases), and if negative, obtain adrenal CT imaging to evaluate for hemorrhage, tuberculosis, metastases, or adrenoleukodystrophy (check very long-chain fatty acids in males). 3, 1
Low or low-normal ACTH (<20 pg/mL) = Secondary adrenal insufficiency. Consider MRI brain with pituitary/sellar cuts to evaluate for pituitary adenoma, hemorrhage, hypophysitis, or other structural lesions. 1, 4
Treatment Implications of Confirmed Diagnosis
Initiate glucocorticoid replacement therapy immediately:
For mild-moderate symptoms: Start hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) to approximate physiological cortisol secretion. 3, 1, 2
For primary adrenal insufficiency: Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement, as aldosterone deficiency causes the hypotension and salt craving. 3, 1, 2 Secondary AI does not require mineralocorticoid replacement since the renin-angiotensin-aldosterone system remains intact. 1
Patient education is mandatory: All patients need instruction on stress dosing (doubling or tripling doses during illness, fever, or physical stress), emergency injectable hydrocortisone 100 mg IM kit with self-injection training, and medical alert bracelet indicating adrenal insufficiency. 3, 1, 2
If Peak Cortisol >550 nmol/L (>18-20 µg/dL): Adrenal Insufficiency Excluded
This normal response excludes adrenal insufficiency and you must look elsewhere for the cause of her symptoms. 1, 2 Consider alternative diagnoses for chronic nausea, weight loss, and anxiety (gastroparesis, celiac disease, hyperthyroidism from Hashimoto's thyroiditis transitioning to hypothyroidism, psychiatric disorders). 1
Common Pitfalls to Avoid
Do not rely on electrolyte abnormalities to make or exclude the diagnosis. Hyponatremia is present in 90% of newly diagnosed AI cases, but hyperkalemia occurs in only ~50% of primary AI cases—its absence does not rule out the diagnosis. 3, 1
Do not assume a "normal range" morning cortisol excludes AI in a symptomatic patient. Cortisol 5-10 µg/dL may fall within laboratory reference ranges but is inappropriately low for peak morning levels and inadequate for stress response. 3, 1
If treating concurrent hypothyroidism from Hashimoto's, always start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis. 1, 4 Thyroid hormone increases cortisol metabolism and can unmask or worsen adrenal insufficiency. 1
Never attempt diagnostic testing in patients already on corticosteroid replacement therapy—the diagnosis is already made. Morning cortisol measurements in patients taking hydrocortisone, prednisone, or other steroids are not diagnostic because the assay measures both endogenous and therapeutic steroids. 1