The adrenal glands play a crucial role in maintaining hormonal balance by producing hormones like cortisol, aldosterone, and androgens. When adrenal function is impaired, it can lead to various clinical disorders such as Addison's disease, Cushing's syndrome, and adrenal hyperplasia. Laboratory tests measuring cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone (DHEA) are essential to evaluate adrenal health.
What Are Adrenal Function Tests?
Adrenal function tests assess the hormones produced by the adrenal glands and their regulatory pathways to diagnose disorders related to either adrenal insufficiency or excess.
Key Adrenal Hormones Tested
1. Cortisol
Cortisol is the primary glucocorticoid produced by the adrenal cortex. It regulates metabolism, immune response, and stress adaptation. Cortisol secretion follows a diurnal rhythm, peaking in the early morning and lowest at midnight.
- Indications: Suspected Cushing's syndrome, Addison’s disease, adrenal insufficiency, or stress response evaluation.
- Sample: Blood (serum), saliva, or 24-hour urine.
2. ACTH (Adrenocorticotropic Hormone)
ACTH is secreted by the pituitary gland and stimulates the adrenal cortex to produce cortisol. Measuring ACTH alongside cortisol helps differentiate between primary adrenal disorders (adrenal gland failure) and secondary/tertiary causes (pituitary or hypothalamic dysfunction).
- Indications: Evaluation of adrenal insufficiency, differentiating causes of cortisol excess.
- Sample: Blood (plasma), usually drawn in the morning.
3. DHEA and DHEA-S (Dehydroepiandrosterone and its Sulfate)
DHEA and DHEA-S are adrenal androgens important for secondary sexual characteristics and serve as precursors to testosterone and estrogen. Abnormal levels can indicate adrenal tumors, congenital adrenal hyperplasia, or androgen excess.
- Indications: Evaluation of androgen excess, hirsutism, ambiguous genitalia, or adrenal tumors.
- Sample: Blood (serum).
Reference Ranges for Adrenal Hormones
| Test | Normal Range | Notes |
|---|---|---|
| Serum Cortisol (8 AM) | 6 – 23 µg/dL | Varies with stress, illness |
| Serum Cortisol (4 PM) | 3 – 15 µg/dL | Lower than morning values |
| Plasma ACTH (8 AM) | 10 – 60 pg/mL | Higher in primary adrenal insufficiency |
| Serum DHEA-S | 35 – 430 µg/dL (varies by age & sex) | Higher in young adults, males |
How To Interpret Adrenal Function Tests
Interpretation depends on the combination of test results:
- High cortisol + low ACTH: Suggests adrenal (primary) cortisol excess (e.g., adrenal adenoma).
- High cortisol + high ACTH: Indicates pituitary cause (Cushing’s disease) or ectopic ACTH production.
- Low cortisol + high ACTH: Suggests primary adrenal insufficiency (Addison’s disease).
- Low cortisol + low ACTH: Suggests secondary or tertiary adrenal insufficiency due to pituitary or hypothalamic dysfunction.
- Elevated DHEA-S: May indicate adrenal tumor or congenital adrenal hyperplasia.
Common Clinical Conditions Diagnosed
- Addison's Disease: Autoimmune destruction of adrenal cortex causing deficiency of cortisol and aldosterone.
- Cushing's Syndrome: Excess cortisol production from adrenal or pituitary tumors.
- Congenital Adrenal Hyperplasia: Enzyme deficiencies causing impaired cortisol synthesis and androgen excess.
- Adrenal Tumors: Overproduction of adrenal hormones leading to various syndromes.
Additional Tests for Adrenal Disorders
- Dexamethasone Suppression Test (DST) to confirm Cushing’s syndrome
- 24-hour Urinary Free Cortisol
- Aldosterone and Renin levels for mineralocorticoid disorders
- Imaging studies: CT or MRI of adrenal glands and pituitary
FAQs
Q1. When is the best time to measure cortisol and ACTH?
The ideal time is early morning (7-9 AM) when cortisol and ACTH peak naturally.
Q2. Can stress affect cortisol levels?
Yes, physical or emotional stress can increase cortisol secretion temporarily.
Q3. What is the difference between DHEA and DHEA-S?
DHEA is the active form, whereas DHEA-S is a sulfated, more stable circulating form used commonly for lab testing.
Conclusion
Adrenal function tests including cortisol, ACTH, and DHEA are fundamental for diagnosing and managing disorders of the adrenal glands. Proper interpretation requires understanding their physiology, timing of tests, and clinical correlation.
Tags: Adrenal Function Tests, Cortisol Test, ACTH, DHEA, Addison’s Disease, Cushing Syndrome, Endocrinology, Lab Tests

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