Secondary Adrenal Insufficiency Diagnosis and Presentation

Clinical Presentation

Secondary adrenal insufficiency characteristically presents with hyponatraemia without hyperkalaemia or metabolic acidosis, because aldosterone secretion remains intact through the preserved renin-angiotensin-aldosterone system 1, 2
Hyponatraemia is present in 90% of newly diagnosed adrenal insufficiency cases, including secondary adrenal insufficiency, due to cortisol deficiency impairing free water clearance and causing inappropriately elevated vasopressin 3, 1
The clinical picture of secondary adrenal insufficiency can be nearly identical to SIADH, making it essential to exclude adrenal insufficiency before diagnosing SIADH 1

The American College of Physicians recommends measuring morning cortisol and ACTH, with low cortisol and low or inappropriately normal ACTH indicating secondary adrenal insufficiency 1, 4
Morning cortisol <250 nmol/L with low ACTH is diagnostic of secondary adrenal insufficiency 4
A cosyntropin stimulation test with peak cortisol <500 nmol/L confirms the diagnosis of secondary adrenal insufficiency 1, 4

The absence of hyperkalaemia cannot rule out adrenal insufficiency—it is present in only 50% of primary cases and is typically absent in secondary adrenal insufficiency 3, 1
Never diagnose SIADH in a patient with hyponatraemia without first performing a cosyntropin stimulation test to exclude adrenal insufficiency 1

A baseline serum cortisol level is obtained before administering the synthetic ACTH analogue (cosyntropin) 5.
The standard stimulation dose is 0.25 mg (250 µg) of cosyntropin given intravenously or intramuscularly 5.
Post‑injection serum cortisol samples are drawn at 30 minutes and 60 minutes to assess adrenal response 5.

A cortisol increase to ≥ 500 nmol/L (≈ 14–15 µg/dL) after stimulation indicates normal adrenal reserve 5.
A cortisol level that remains < 500 nmol/L after stimulation is diagnostic of adrenal insufficiency 5.
Simultaneous measurement of plasma ACTH helps differentiate primary adrenal insufficiency (high ACTH) from secondary adrenal insufficiency (low/normal ACTH) 5.

Clinicians integrate the post‑stimulation cortisol response, ACTH level, and the patient’s clinical presentation to confirm the diagnosis 5.
When adrenal insufficiency is confirmed, further evaluation to identify the underlying cause is undertaken, and glucocorticoid replacement therapy is typically initiated 5.