24-Hour Urine Collection for Cortisol in Secondary Hypertension Workup
Yes, 24-hour urine collection for free cortisol is a reasonable and guideline-recommended diagnostic test for patients with suspected secondary hypertension and potential Cushing's syndrome. 1
Guideline Support for This Test
The 2020 International Society of Hypertension and 2024 ESC guidelines explicitly list 24-hour urinary free cortisol as an appropriate further diagnostic test for secondary hypertension when Cushing's syndrome is suspected. 1 This test should be pursued when:
- Resistant hypertension is present (blood pressure uncontrolled on 3+ medications including a diuretic) 1
- Strong clinical clues suggest Cushing's syndrome, such as central obesity, proximal muscle weakness, wide purple striae, easy bruising, or facial plethora 1, 2
- Early onset hypertension (<30 years) without typical risk factors 1
- Sudden deterioration in previously controlled blood pressure 1
Diagnostic Algorithm for Cushing's Syndrome Screening
Initial Screening Tests (Choose 2-3)
The Endocrine Society recommends using at least two different screening tests to confirm hypercortisolism: 2, 3
- 24-hour urinary free cortisol (sensitivity >90%, though lowest among the three main tests) 2, 3
- Late-night salivary cortisol (sensitivity 92-100%, specificity 93-100%, abnormal threshold >3.6 nmol/L) 2, 4
- Overnight 1-mg dexamethasone suppression test (sensitivity >90%, abnormal if cortisol ≥1.8 μg/dL at 8 AM) 2, 3
Critical Collection Requirements for 24-Hour UFC
Obtain at least 2-3 separate 24-hour collections before making diagnostic decisions, as intra-patient variability can reach 50% between collections. 2, 5 Each collection must include:
- Complete 24-hour urine volume with documented start/stop times 1
- Total creatinine excretion to verify collection completeness 1
- Avoidance of copper contamination in collection containers 5
Diagnostic threshold: Values >100 μg/24 hours (1.6 μmol/24 hours) are typically diagnostic of Cushing's syndrome in symptomatic patients, though 40 μg/24 hours represents a better sensitivity threshold. 5
If Screening Tests Are Positive
Measure morning (08:00-09:00h) plasma ACTH to determine if Cushing's syndrome is ACTH-dependent or ACTH-independent: 2, 6
- ACTH >5 ng/L: ACTH-dependent (pituitary or ectopic source) → proceed to pituitary MRI 2, 6
- ACTH >29 ng/L: 70% sensitivity and 100% specificity for Cushing's disease 2
- ACTH low/undetectable: ACTH-independent (adrenal source) → proceed to adrenal CT or MRI 2, 6
Common Pitfalls to Avoid
False Positives in 24-Hour UFC
Several conditions can cause mildly elevated urinary cortisol without true Cushing's syndrome (pseudo-Cushing's states): 2, 5
- Severe obesity (very common in hypertensive patients) 2
- Uncontrolled diabetes mellitus 2
- Depression or psychiatric disorders 2
- Alcohol use disorder 2
- Polycystic ovary syndrome 2
Collection Issues That Invalidate Results
- Incomplete 24-hour collection (verify with creatinine excretion) 1, 5
- Renal impairment or polyuria (makes UFC unreliable; use late-night salivary cortisol instead) 2
- Oral estrogen/contraceptives (increase cortisol-binding globulin, falsely elevating total cortisol but not UFC) 2, 5
Cyclic Cushing's Syndrome
Cyclic disease can produce weeks to months of normal cortisol secretion interspersed with hypercortisolism, leading to false-negative results. 2, 5 If clinical suspicion remains high despite normal initial testing, repeat collections during symptomatic periods over 3-6 months. 2
Relative Strengths Compared to Other Tests
24-hour UFC is less ideal as a first-line screening test compared to late-night salivary cortisol or dexamethasone suppression testing due to: 7
- Collection difficulties and frequent patient non-compliance 7
- Lower sensitivity for mild or cyclic Cushing's syndrome 7
- High intra-patient variability requiring multiple collections 2, 7
However, strikingly elevated UFC levels (>4x upper limit of normal) are highly specific for Cushing's syndrome and provide strong confirmatory evidence. 7
When to Refer to Specialist Center
The 2020 ISH guidelines recommend referring patients with suspected secondary hypertension to specialist centers with appropriate expertise and resources for: 1