What is the best course of action for a patient with normal cortisol levels and salt cravings, potentially indicating adrenal insufficiency or hormonal imbalance?

Salt Craving with Normal Cortisol: Evaluate for Mineralocorticoid Deficiency

Salt craving in the presence of normal cortisol levels strongly suggests inadequate mineralocorticoid replacement or undiagnosed primary adrenal insufficiency, and warrants immediate clinical evaluation including assessment of blood pressure (supine and standing), serum electrolytes, and consideration of fludrocortisone therapy. 1

Understanding the Clinical Significance

Salt craving is a cardinal symptom of mineralocorticoid deficiency and serves as a key clinical marker for assessing adequacy of replacement therapy in primary adrenal insufficiency (PAI). 1 The presence of salt craving despite "normal" cortisol levels indicates that:

• Mineralocorticoid deficiency can exist independently of glucocorticoid status - Normal cortisol does not exclude aldosterone deficiency in primary adrenal insufficiency 1
• Salt craving specifically indicates mineralocorticoid under-replacement, which is common and sometimes compensated for by over-replacement of glucocorticoids 1
• This symptom should never be dismissed, as under-replacement predisposes patients to recurrent adrenal crises 1

Immediate Clinical Assessment Algorithm

Step 1: Confirm the Diagnosis Context

If the patient has established primary adrenal insufficiency:

• Salt craving indicates inadequate fludrocortisone dosing 1
• Evaluate clinically by measuring blood pressure in supine and standing positions 1
• Check for lightheadedness upon standing (orthostatic symptoms) 1
• Assess for peripheral edema (suggests over-replacement if present) 1

If adrenal insufficiency has NOT been diagnosed:

• Normal cortisol alone does NOT exclude primary adrenal insufficiency - approximately 10% of patients with confirmed PAI present with normal cortisol concentrations 2
• Salt craving combined with other symptoms (fatigue, weight loss, hypotension) warrants full evaluation for adrenal insufficiency 3, 4
• Measure morning cortisol AND ACTH together - high ACTH with even "normal" cortisol can indicate early PAI 3, 2

Step 2: Laboratory Evaluation

Essential tests to order:

• Serum sodium and potassium - Hyponatremia occurs in 90% of newly diagnosed adrenal insufficiency cases, but hyperkalemia is present in only ~50% 3
• Plasma renin activity (PRA) - Elevated in mineralocorticoid deficiency 1
• Morning cortisol AND ACTH (if diagnosis not established) - High ACTH with normal cortisol suggests early primary adrenal insufficiency 3, 2
• 21-hydroxylase autoantibodies - Identifies autoimmune etiology in ~85% of Western PAI cases 3

Critical pitfall to avoid: Do not rely solely on electrolyte abnormalities - hyponatremia may be only marginally reduced and hyperkalemia is absent in ~50% of cases 3

Step 3: Assess Current Mineralocorticoid Replacement (If Applicable)

For patients already on fludrocortisone:

• Under-replacement is common and the most likely explanation for persistent salt craving 1
• Typical fludrocortisone dosing is 50-200 µg daily, but doses up to 500 µg daily may be needed in children, younger adults, or during late pregnancy 1
• Unrestricted sodium salt intake is essential - patients should be advised to eat sodium salt and salty foods without restriction and avoid potassium-containing salts 1

Drug interactions that may necessitate dose adjustment: 1

• Avoid: Diuretics, acetazolamide, carbenoxolone, liquorice, NSAIDs
• May need more fludrocortisone: Drospirenone-containing contraceptives
• Potentiate mineralocorticoid effect (avoid): Liquorice and grapefruit juice

Treatment Algorithm

If Primary Adrenal Insufficiency is Established:

Optimize fludrocortisone dosing: 1, 5

• Start with 0.1 mg daily (usual dose) 5
• Increase to 0.15-0.2 mg daily if salt craving persists 1, 5
• Maximum dose may reach 0.5 mg daily in younger adults or special circumstances 1
• Monitor response by: Resolution of salt craving, normalization of orthostatic blood pressure, absence of peripheral edema 1

Ensure adequate sodium intake: 1

• Advise unrestricted sodium salt and salty foods 1
• This is "an important third component of substitution therapy" alongside glucocorticoid and mineralocorticoid replacement 1

Check for glucocorticoid over-replacement: 1

• Under-replacement of mineralocorticoids is sometimes compensated for by over-replacement of glucocorticoids 1
• Review hydrocortisone dosing (typical: 15-25 mg daily in divided doses) 1, 4

If Adrenal Insufficiency is NOT Yet Diagnosed:

Proceed with diagnostic workup: 3, 4

• Measure morning (8 AM) cortisol, ACTH, and DHEAS 3, 4, 6
• Basal cortisol <250 nmol/L (<9 µg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency 3
• Normal cortisol with clearly elevated ACTH (>300 pg/mL) can indicate early PAI 3, 2
• If cortisol is 140-400 nmol/L (5-15 µg/dL), perform cosyntropin stimulation test 3

Cosyntropin stimulation test protocol: 3

• Administer 0.25 mg (250 µg) cosyntropin IV or IM 3
• Measure cortisol at baseline and 30 minutes post-administration 3
• Peak cortisol <500 nmol/L (<18 µg/dL) confirms adrenal insufficiency 3

Special Considerations

Pregnancy

• Fludrocortisone dose often needs to be increased during late pregnancy due to anti-mineralocorticoid effects of progesterone 1
• PRA is not a good parameter for dose adjustment in pregnancy - rely on salt craving assessment, blood pressure, and serum electrolytes 1

Essential Hypertension in PAI Patients

• Treat with a vasodilator, NOT by stopping mineralocorticoid replacement 1
• Consider fludrocortisone dose reduction but do not discontinue 1

Critical Safety Points

Never delay treatment if adrenal crisis is suspected: 3

• Unexplained hypotension, collapse, or GI symptoms warrant immediate IV hydrocortisone 100 mg and 0.9% saline infusion 3
• Do not wait for diagnostic test results if the patient is clinically unstable 3

Before starting or increasing thyroid hormone in suspected central hypothyroidism: 3

• Always rule out adrenal insufficiency first 3
• Start corticosteroids before levothyroxine to prevent precipitating adrenal crisis 3

Patient education essentials: 3, 4

• All patients with confirmed adrenal insufficiency need stress-dosing education 3, 4
• Should wear medical alert identification 3, 4
• Carry emergency injectable hydrocortisone 100 mg IM kit 3