From the Guidelines
A low cortisol level combined with high DHEAS is indeed concerning for adrenal dysfunction and warrants a comprehensive adrenal workup, specifically suggesting primary adrenal insufficiency (Addison's disease) rather than secondary adrenal insufficiency. This pattern is indicative of adrenal cortex damage, leading to decreased cortisol production, while the elevated DHEAS occurs due to increased ACTH stimulation from the pituitary attempting to compensate for low cortisol 1.
Diagnostic Approach
The next step should be an ACTH stimulation test (Cosyntropin test), where synthetic ACTH is administered and cortisol levels are measured at baseline, 30 minutes, and 60 minutes post-administration. A failure to adequately increase cortisol levels confirms adrenal insufficiency. Additional testing should include:
- Morning ACTH levels
- Aldosterone
- Renin
- Electrolytes
Management
Patients may need immediate treatment with hydrocortisone (typically 15-20 mg daily in divided doses) if symptomatic with fatigue, weight loss, hypotension, or electrolyte abnormalities. It's essential to complete the diagnostic workup before initiating long-term therapy unless the patient is in adrenal crisis, which would require immediate intervention with IV hydrocortisone and fluid resuscitation 1.
Key Considerations
- All patients need education on stress dosing for sick days, use of emergency steroid injectables, when to seek medical attention for impending adrenal crisis, and a medical alert bracelet for adrenal insufficiency to trigger stress dose corticosteroids by EMS 1.
- Endocrine consultation should be part of planning before surgery or high-stress treatments to ensure appropriate stress-dose planning 1.
- The relationship between ACTH and cortisol can distinguish primary and secondary adrenal insufficiency, guiding management decisions 1.
From the Research
Adrenal Insufficiency Diagnosis
- A low cortisol level and elevated Dehydroepiandrosterone sulfate (DHEAS) may not be more indicative of adrenal insufficiency, as the diagnosis of adrenal insufficiency is complex and requires a combination of biochemical tests and clinical evaluation 2.
- Baseline measurements of serum cortisol are helpful only when they are very low (≤ 5 μg/dL) or clearly elevated, whereas baseline plasma adrenocorticotropic hormone levels are helpful only when primary adrenal insufficiency is suspected 2.
- Measurements of baseline serum DHEA-S levels are valuable in patients suspected of having adrenal insufficiency, but a low level of this steroid is not sufficient by itself for establishing the diagnosis 2.
DHEA-S Levels in Adrenal Insufficiency
- A normal age- and sex-adjusted serum DHEA-S level practically rules out the diagnosis of adrenal insufficiency 2.
- Patients with impaired hypothalamic-pituitary-adrenal (HPA) function have a more severe loss in DHEA secretion than that of glucocorticoids 3.
- Measurements of serum DHEA levels during low-dose cosyntropin stimulation provide additional valuable information that improves the diagnostic accuracy of the test in patients suspected to have central adrenal insufficiency 3.
Clinical Evaluation and Testing
- Many patients require dynamic biochemical studies, such as the 1-μg cosyntropin test, to assess adrenal function 2.
- Careful clinical evaluation is required to determine the requirement for replacement in patients with 10.0 µg/dL ≤ the peak cortisol < 17.5 µg/dL, even in combination with baseline DHEA-S 4.
- A single measurement of plasma ACTH or measurement of ACTH response to corticotropin-releasing hormone is not enough to screen for asymptomatic cortisol-producing adrenal adenoma (ASCA) 5.
- Dexamethasone suppression test is essential in identifying ASCA, and a single determination of serum DHEA-S may be useful for the screening of ASCA in adrenal incidentalomas in young and middle-aged subjects 5.