The Road to Diagnosis: Labs, Imaging, and Guidelines

Diagnosing Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) or Bilateral Macronodular Adrenal Disease (BMAD) is a two-part process. Your medical team must first confirm that your adrenal glands are producing cortisol on their own (autonomy) and then use detailed imaging to confirm the presence of multiple large nodules on both glands ^[1][2].

Current guidelines from the European Society of Endocrinology (ESE) provide a clear roadmap for this process, ensuring that mild cases are caught even if you don’t have obvious physical symptoms ^[3].

The Diagnostic Cornerstone: The 1-mg DST

The most important test for diagnosing adrenal cortisol issues is the 1-mg overnight dexamethasone suppression test (DST).

• The Procedure: You take a 1-mg tablet of dexamethasone (a synthetic steroid) at 11:00 PM and have your blood drawn for cortisol the following morning between 8:00 AM and 9:00 AM ^[1].
• The Logic: In a healthy person, the brain senses the dexamethasone and tells the adrenal glands to stop making cortisol. In PBMAH, the adrenal glands ignore this signal and keep pumping out cortisol anyway ^[1][4].
• The Threshold: According to the 2023 guidelines, if your morning cortisol level is greater than 1.8 µg/dL (50 nmol/L), it suggests Mild Autonomous Cortisol Secretion (MACS) ^[3][5]. This is a screening threshold, not a standalone diagnosis of PBMAH. The test must be interpreted carefully, as results can be altered by estrogen (like birth control), acute illness, and exposure to exogenous steroids (like joint injections, asthma inhalers, or skin creams) ^[6][3].

Note: Your doctor may check your dexamethasone levels in the same blood sample to make sure your body processed the pill correctly ^[6][3].

Confirming Adrenal Independence

Once a high cortisol reading is found, your doctor must prove the problem is in the adrenals and not the brain (pituitary).

1. ACTH Levels: This hormone, made by the pituitary, should be very low (suppressed) because the brain is trying to shut down the excess cortisol ^[1]. While there is no single “magic number,” an ACTH level below 10 pg/mL often points toward the adrenal glands as the source ^[7].
2. DHEAS Levels: DHEAS is another hormone made by the adrenal glands. It is often lower than normal in people with PBMAH because the excess cortisol production suppresses the pathways that make DHEAS ^[8][9].

What to Look for on Imaging

Imaging (usually a CT scan) is used to see the “macronodules” that give the disease its name.

• Size: By definition, macronodules are larger than 1 cm (0.4 inches) ^[10][11]. In PBMAH, these nodules are found on both the left and right adrenal glands.
• Appearance: Doctors look at Hounsfield Units (HU), a measure of density on a CT scan.
  • Benign (Non-Cancerous): A score of 10 HU or less suggests the nodule is “lipid-rich” (full of fat), which is common in benign adrenal growths ^[3][10].
  • Washout: If a nodule is higher than 10 HU, doctors may use a “washout” study with contrast dye. Most PBMAH nodules show “good washout,” meaning the dye leaves the nodule quickly ^[10][12].
    However, suspicious size, heterogeneity, or growth requires specialist multidisciplinary review rather than relying on HU or washout alone to rule out malignancy or pheochromocytoma.

Ruling Out “Look-Alikes”

Because you have nodules on both sides, your doctor must ensure they aren’t causing other problems. You will likely have blood or urine tests to rule out:

• Pheochromocytoma: A rare tumor that produces adrenaline-like hormones ^[1][13].
• Primary Aldosteronism: A condition where the glands make too much aldosterone, leading to very high blood pressure and low potassium ^[14][15].

These tests are selected based on your specific imaging, hypertension, and local guideline criteria; not every patient needs every test.

Completeness Checklist

To ensure an accurate diagnosis, your medical report should ideally include the following information. You can use this list to review your results with your doctor:

• [ ] Hormone Results: Cortisol level after 1-mg DST (is it >1.8 µg/dL?).
• [ ] ACTH Level: Is it low or suppressed?
• [ ] DHEAS Level: Is it below the normal range for your age?
• [ ] Nodule Details: Number, side (left, right, or both), and size (in cm) of all nodules.
• [ ] Density (HU): Are the nodules 10 HU or less?
• [ ] Other Adrenal Tests: Results for metanephrines (to rule out pheochromocytoma) and aldosterone-renin ratio (to rule out primary aldosteronism), if indicated.
• [ ] Comorbidity Check: Documentation of your blood pressure, blood sugar (A1c), and bone density ^[3].