Would the 8am cortisol level be elevated or suppressed in a patient with a 3mm pituitary microadenoma (adenoma affecting the pituitary gland)?

8AM Cortisol in Pituitary Microadenoma Evaluation

In a patient with a pituitary microadenoma causing Cushing's disease, the 8AM cortisol level will be elevated, not suppressed. This reflects the fundamental pathophysiology of ACTH-dependent hypercortisolism from a pituitary source.

Pathophysiologic Basis

• Pituitary microadenomas autonomously secrete ACTH, which drives bilateral adrenal cortisol overproduction, resulting in elevated morning cortisol levels 1
• The normal circadian rhythm of cortisol is lost in Cushing's disease, but morning levels remain elevated (or become even more elevated) rather than suppressed 2, 3
• Morning (8AM-9AM) cortisol measurement is the standard reference point for diagnostic evaluation because it represents the physiologic peak of the diurnal rhythm 1

Expected Laboratory Findings

In microadenomas causing Cushing's disease, you will find:

• Morning plasma ACTH levels are normal to elevated (typically 45-52 ng/L in microadenomas, compared to 134 ng/L in macroadenomas) 4, 5
• Morning serum cortisol is elevated (mean ~22.6 μg/dL or 624.7 nmol/L in microadenomas) 4
• Any detectable ACTH level >5 ng/L in the presence of hypercortisolism indicates ACTH-dependent disease, ruling out adrenal sources where ACTH would be suppressed 1, 3

Diagnostic Algorithm for Microadenomas

When evaluating a suspected 3mm pituitary microadenoma:

1. Confirm hypercortisolism first with 24-hour urinary free cortisol and/or late-night salivary cortisol 3
2. Measure morning (8AM) plasma ACTH to determine ACTH-dependency 1, 3
   • ACTH >5 ng/L = ACTH-dependent (pituitary or ectopic source)
   • ACTH low/undetectable = ACTH-independent (adrenal source)
3. Perform low-dose dexamethasone suppression test (cortisol >1.8 μg/dL after 1mg overnight = abnormal) 1
4. If microadenoma <6mm on MRI, proceed to bilateral inferior petrosal sinus sampling (BIPSS) to confirm pituitary source 1

Critical Distinctions by Adenoma Size

Microadenomas (like your 3mm lesion) differ from macroadenomas:

• Microadenomas show more preserved circadian variation (62% nycthemeral variation vs. 28% in macroadenomas) 4
• Better suppression with high-dose dexamethasone (61% suppression vs. 30% in macroadenomas) 4
• Lower absolute ACTH levels but still elevated above normal 4, 5
• Higher cortisol-to-ACTH ratio (12 vs. 7 in macroadenomas), suggesting more efficient cortisol production per unit of ACTH 4

Common Pitfalls to Avoid

• Do not confuse ACTH-dependent with ACTH-independent Cushing's syndrome - only in adrenal adenomas (ACTH-independent) would you see suppressed ACTH and elevated cortisol 2, 1
• Microadenomas ≤2mm are frequently invisible on MRI (sensitivity only 63%), so normal imaging does not exclude the diagnosis 1
• Timing matters - afternoon ACTH measurements are unreliable because levels are physiologically lower and don't correspond to established diagnostic thresholds 1
• Even after successful microadenoma resection, cortisol may remain elevated if there is concurrent corticotroph hyperplasia, which is invisible on imaging 6

When BIPSS is Required

For a 3mm microadenoma, BIPSS is indicated because:

• Lesions <6mm require BIPSS to definitively distinguish pituitary from ectopic ACTH sources 1
• Central-to-peripheral ACTH ratio ≥2:1 at baseline or ≥3:1 after CRH/desmopressin confirms pituitary source with 96-100% sensitivity 1
• MRI misses approximately one-third of ACTH-secreting microadenomas, making biochemical confirmation essential 1

Clinical Context

• Microadenomas account for 98% of Cushing's disease cases and are the most common cause 1
• Patients typically present with classic Cushingoid features (central obesity, moon facies, proximal weakness, wide purple striae) despite small tumor size 3, 7
• The diagnosis is often delayed (median 1.5 years for microadenomas) because symptoms develop gradually 4