What presentation is most consistent with secondary adrenal insufficiency?

Secondary Adrenal Insufficiency: Most Consistent Presentation

The answer is D. Hyponatraemia is the most consistent presentation with secondary adrenal insufficiency.

Key Distinguishing Features

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. This is the critical distinguishing feature from primary adrenal insufficiency.

Why Each Option Applies or Does Not Apply:

A. Hyperpigmentation - INCORRECT

• Hyperpigmentation occurs only in primary adrenal insufficiency due to elevated ACTH levels stimulating melanocytes 3
• In secondary adrenal insufficiency, ACTH is low or inappropriately normal, so hyperpigmentation does not occur 1, 2

B. Hyperkalaemia - INCORRECT

• Hyperkalaemia results from aldosterone deficiency, which occurs in primary adrenal insufficiency 3
• Secondary adrenal insufficiency spares mineralocorticoid function because the renin-angiotensin system remains intact 1, 2
• The presence of hyponatraemia WITHOUT hyperkalaemia actually suggests secondary rather than primary adrenal insufficiency 1

C. Severe hypotension - INCORRECT (as a distinguishing feature)

• While hypotension can occur in both primary and secondary adrenal insufficiency, severe hypotension is more characteristic of primary adrenal insufficiency due to combined glucocorticoid and mineralocorticoid deficiency 3
• Secondary adrenal insufficiency typically presents with less severe hypotension because mineralocorticoid function is preserved 2

D. Hyponatraemia - CORRECT

• Hyponatraemia is present in 90% of newly diagnosed adrenal insufficiency cases, including secondary adrenal insufficiency 3, 1
• In secondary adrenal insufficiency, hyponatraemia occurs due to cortisol deficiency impairing free water clearance and causing inappropriately elevated vasopressin 3, 4
• The clinical picture can be nearly identical to SIADH, making it essential to exclude adrenal insufficiency before diagnosing SIADH 1, 4
• Importantly, hyponatraemia occurs WITHOUT the hyperkalaemia seen in primary adrenal insufficiency 1

E. Metabolic acidosis - INCORRECT

• Metabolic acidosis occurs in primary adrenal insufficiency due to aldosterone deficiency 3
• Secondary adrenal insufficiency does not cause metabolic acidosis because aldosterone secretion is preserved 2

Critical Clinical Pitfall

Never diagnose SIADH in a patient with hyponatraemia without first performing a cosyntropin stimulation test to exclude adrenal insufficiency 1. Both conditions present with:

• Euvolemic hypo-osmolar hyponatraemia
• Inappropriately elevated urine osmolality
• Elevated urinary sodium concentration 1

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.

Diagnostic Approach for Secondary Adrenal Insufficiency

• Measure morning cortisol and ACTH: low cortisol with low or inappropriately normal ACTH indicates secondary adrenal insufficiency 1, 5
• Morning cortisol <250 nmol/L (<9 μg/dL) with low ACTH is diagnostic 5
• Cosyntropin stimulation test with peak cortisol <500 nmol/L (<18 μg/dL) confirms the diagnosis 1, 5