What is the next step in managing a patient with potential cortisol dysregulation based on abnormal lab results, including DST, ACTH, urine, and salivary cortisol levels?

Interpretation of Your Lab Results

Your results do not indicate Cushing's syndrome—the dexamethasone suppression test shows appropriate cortisol suppression (2.2 μg/dL), the ACTH is normal, and both 24-hour urinary free cortisol and late-night salivary cortisol values are well within normal limits.

Analysis of Your Specific Results

Dexamethasone Suppression Test (DST)

• Post-dexamethasone cortisol of 2.2 μg/dL represents normal suppression, as the diagnostic threshold for abnormal suppression is ≥1.8 μg/dL (≥50 nmol/L), and values >5 μg/dL indicate overt Cushing's syndrome 1
• Your dexamethasone level of 584 ng/mL confirms adequate drug absorption and metabolism, ruling out false-negative results from abnormal dexamethasone clearance 2, 1
• This result effectively excludes autonomous cortisol secretion 2

ACTH Level

• ACTH of 22 pg/mL is within the normal range and appropriate for your suppressed cortisol state 1
• This normal ACTH with adequate cortisol suppression confirms intact hypothalamic-pituitary-adrenal (HPA) axis regulation 2

24-Hour Urinary Free Cortisol (UFC)

• Your UFC of 29.2 μg/24h is well below the diagnostic threshold of 40 μg/24h for normal cortisol excretion 1
• Values >100 μg/24h would be required to suggest Cushing's syndrome in symptomatic patients 1
• The creatinine-adjusted value of 21.7 μg/g creatinine further confirms normal cortisol excretion 1

Late-Night Salivary Cortisol (LNSC)

• Both evening measurements (11:20 PM: 0.05 and 11:35 PM: 0.03) are well below the abnormal threshold of >3.6 nmol/L (approximately >0.13 μg/dL when converted) 1
• Your morning values (9:20 AM: 0.18 and 0.29) show preserved circadian rhythm with appropriate morning elevation 1
• These results demonstrate normal cortisol circadian rhythm, which is lost in true Cushing's syndrome 2

Clinical Recommendation: No Further Workup Needed

Based on concordant normal results across all four screening modalities, no additional testing for hypercortisolism is warranted 2. The 2021 Endocrine Society consensus guidelines emphasize that:

• Multiple concordant normal screening tests effectively exclude Cushing's syndrome 2
• Your results show appropriate cortisol suppression, normal ACTH regulation, normal 24-hour cortisol excretion, and preserved circadian rhythm 2, 1

Important Considerations

If Symptoms Persist Despite Normal Testing

• Consider pseudo-Cushing's states such as depression, severe obesity, polycystic ovary syndrome, or alcohol use disorder, which can cause mild clinical features resembling Cushing's without true hypercortisolism 2
• These conditions typically produce UFC values <3-fold above normal (i.e., <120 μg/24h), which is not present in your case 2

Cyclic Cushing's Syndrome

• If clinical suspicion remains extremely high despite these normal results, cyclic Cushing's syndrome could theoretically be considered, where patients have alternating periods of normal and elevated cortisol secretion 2
• However, this would require 3-6 months of serial testing during symptomatic periods, and is only justified with compelling clinical features 2

Critical Pitfall to Avoid

• Do not pursue further invasive testing (such as inferior petrosal sinus sampling) based on these normal screening results, as IPSS should never be used to diagnose hypercortisolism 2
• Avoid unnecessary imaging or specialist referrals that could lead to incidental findings and cascade of additional testing 2