What is the diagnosis and treatment plan for an adult patient with a history of adrenal insufficiency, presenting with low DHEA-S levels and abnormal DST results?

Diagnosis: Primary Adrenal Insufficiency

This patient has confirmed primary adrenal insufficiency based on the extremely low DHEA-S of 36 µg/dL and requires immediate initiation of lifelong glucocorticoid and mineralocorticoid replacement therapy—treatment should not be delayed for additional testing. 1, 2, 3

Interpretation of Laboratory Results

DHEA-S Level of 36 µg/dL:

• A DHEA-S level this low in the context of suspected adrenal insufficiency is highly diagnostic, as DHEA-S is markedly decreased in both primary and secondary adrenal insufficiency 4, 5
• In primary adrenal insufficiency specifically, DHEA-S levels are characteristically low because the entire adrenal cortex is affected 1, 3
• A normal age- and sex-adjusted DHEA-S level practically rules out adrenal insufficiency, but this patient's level is far below normal 4

DST (Dexamethasone Suppression Test) Result:

• The mention of "DST 1.8 with dexamethasone 286" appears to reference cortisol levels, but this test is not the appropriate diagnostic procedure for adrenal insufficiency 1, 2
• The dexamethasone suppression test is used to diagnose Cushing's syndrome (adrenal hyperfunction), not adrenal insufficiency 6
• If this represents a baseline cortisol of 1.8 µg/dL (or 50 nmol/L), this is diagnostic of adrenal insufficiency when paired with the low DHEA-S 1, 3

Distinguishing Primary vs. Secondary Adrenal Insufficiency

This presentation is consistent with PRIMARY adrenal insufficiency because:

• DHEA-S is severely suppressed, which occurs in both primary and secondary AI, but the degree of suppression combined with the clinical context suggests primary disease 4, 5
• To definitively confirm primary AI, you must measure paired morning (8 AM) cortisol and ACTH levels 1, 2, 3
• Primary AI will show: low cortisol (<250 nmol/L or <9 µg/dL) with elevated ACTH 1, 2, 3
• Secondary AI would show: low cortisol with low or inappropriately normal ACTH 2, 3

Immediate Treatment Protocol

Glucocorticoid Replacement:

• Start hydrocortisone 15-25 mg daily in divided doses immediately 1, 7, 8, 3
• Typical regimen: 10 mg upon waking, 5 mg at noon, 2.5-5 mg at 4 PM 2, 7
• The first dose must be taken immediately after waking, and the last dose at least 6 hours before bedtime to mimic physiological cortisol rhythm 7
• Alternative: cortisone acetate 25-37.5 mg daily or prednisone 3-5 mg daily, though hydrocortisone is strongly preferred 1, 7, 8

Mineralocorticoid Replacement (for Primary AI only):

• Start fludrocortisone 0.05-0.1 mg daily as a single morning dose 1, 7, 8, 3
• Typical maintenance range: 50-200 µg daily, adjusted based on blood pressure, salt cravings, and plasma renin activity 2, 7, 3
• Encourage unrestricted sodium salt intake 2

Essential Diagnostic Workup to Complete

Confirm the Diagnosis:

• Measure paired morning (8 AM) serum cortisol and plasma ACTH before starting treatment if the patient is stable 1, 2, 3
• If cortisol <250 nmol/L (<9 µg/dL) with elevated ACTH, primary AI is confirmed 1, 2
• If cortisol is 250-400 nmol/L (9-14 µg/dL) with elevated ACTH, perform cosyntropin stimulation test: give 0.25 mg (250 µg) IV or IM, measure cortisol at 30 and 60 minutes—peak <500 nmol/L (<18 µg/dL) confirms AI 1, 2, 3

Determine Etiology:

• Measure 21-hydroxylase (anti-adrenal) autoantibodies first, as autoimmune disease causes ~85% of primary AI in Western populations 1, 2
• If antibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tuberculosis, fungal infections, metastatic disease, or adrenoleukodystrophy 1, 2
• In males with negative antibodies, assay very long-chain fatty acids (VLCFA) to screen for adrenoleukodystrophy 1, 2

Check for Associated Conditions:

• Measure TSH and free T4 (autoimmune thyroid disease commonly coexists) 1, 2
• Check serum electrolytes: hyponatremia is present in 90% of cases, hyperkalemia in ~50% 1, 2, 3
• Screen for other autoimmune conditions annually: diabetes, pernicious anemia (vitamin B12), celiac disease (tissue transglutaminase antibodies) 2

Critical Patient Safety Measures

Emergency Preparedness:

• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 7, 8, 3
• Provide written stress-dosing guidelines: double or triple usual dose during fever, illness, vomiting, or physical stress 1, 7, 8, 3
• Order medical alert bracelet or necklace stating "adrenal insufficiency" 1, 7, 8, 3
• Provide steroid emergency card to carry at all times 1, 7

Patient Education:

• Teach recognition of adrenal crisis symptoms: severe weakness, confusion, vomiting, hypotension, abdominal pain 1, 3
• Instruct to seek immediate medical attention if unable to take oral medications or if symptoms worsen despite stress dosing 1
• Emphasize that this is a lifelong condition requiring permanent replacement therapy—never attempt to discontinue treatment 2

Monitoring and Follow-Up

Initial Monitoring (First 3 Months):

• Assess clinical response: resolution of fatigue, nausea, weight stabilization 1
• Check blood pressure (supine and standing), serum sodium and potassium every 2-4 weeks initially 1, 7
• Adjust fludrocortisone based on orthostatic hypotension, salt cravings, edema, and plasma renin activity 2, 7

Long-Term Monitoring (Annual):

• Review health, well-being, weight, blood pressure, and serum electrolytes 1, 7
• Screen for glucocorticoid over-replacement: weight gain, hypertension, hyperglycemia, osteoporosis 1, 7
• Monitor bone mineral density every 3-5 years 2, 7
• Screen annually for new autoimmune disorders (thyroid, diabetes, celiac disease) 2

Common Pitfalls to Avoid

• Never delay treatment in suspected adrenal crisis while waiting for diagnostic test results—mortality is high if untreated 1, 2
• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—hyperkalemia is present in only ~50% of cases 1, 2, 3
• Do not start thyroid hormone replacement before adequate glucocorticoid replacement in patients with concurrent hypothyroidism—this can precipitate adrenal crisis 2, 8
• Avoid dexamethasone for chronic maintenance therapy as it lacks mineralocorticoid activity and cannot be easily adjusted 2, 8
• Do not attempt diagnostic testing while the patient is on corticosteroids—exogenous steroids suppress the HPA axis and confound results 2

When to Refer to Endocrinology

• Arrange early endocrinology referral concurrently with treatment initiation for comprehensive patient education, stress-dosing protocols, and long-term management optimization 8
• Immediate endocrine consultation is mandatory for: severe symptomatic hypocortisolism requiring stress-dose therapy, pre-operative planning, recurrent adrenal crises, or diagnostic uncertainty 2, 8