What are the implications and management of elevated late salivary cortisol levels, specifically 290 and 275, potentially indicating Cushing's syndrome?

Elevated Late Salivary Cortisol Levels: Implications and Management

Late salivary cortisol levels of 290 and 275 strongly suggest Cushing's syndrome and require further diagnostic evaluation and appropriate management. 1, 2

Diagnostic Significance

• Late-night salivary cortisol is a key screening test for Cushing's syndrome, with normal values typically below 3.6 nmol/L (approximately 0.13 μg/dL) 3
• Values of 290 and 275 (presumed units: nmol/L) are significantly elevated and highly suggestive of Cushing's syndrome with loss of normal circadian rhythm of cortisol secretion 1, 4
• Late-night salivary cortisol has excellent diagnostic accuracy for Cushing's syndrome with sensitivity of 92-100% and specificity of 93-100% 4
• These elevated values represent a failure of the normal nocturnal nadir in cortisol production, which is a hallmark of Cushing's syndrome 1

Recommended Diagnostic Algorithm

1. Confirm Cushing's syndrome diagnosis with additional tests 1:

   • 24-hour urinary free cortisol (UFC) measurement for 3 consecutive days
   • Low-dose dexamethasone suppression test (LDDST)
   • Consider measuring dexamethasone levels during LDDST to improve test interpretability 2

2. Determine ACTH dependency 2:

   • Measure morning plasma ACTH levels
   • ACTH >5 ng/L suggests ACTH-dependent Cushing's syndrome
   • ACTH <5 ng/L suggests ACTH-independent Cushing's syndrome

3. Localize the source based on ACTH status 1, 2:

   • For ACTH-dependent disease:
     • Pituitary MRI
     • CRH stimulation test
     • Bilateral inferior petrosal sinus sampling (BIPSS) if MRI is inconclusive
   • For ACTH-independent disease:
     • Adrenal CT or MRI scan

Management Approach

• Treatment depends on the cause 1, 5:

  • Cushing's disease (pituitary source): transsphenoidal surgery
  • Adrenal adenoma: laparoscopic adrenalectomy
  • Adrenal carcinoma: open adrenalectomy with possible adjuvant therapy
  • Ectopic ACTH: surgical removal of the source when possible

• Medical therapy options when surgery is contraindicated or unsuccessful 1:

  • Adrenal steroidogenesis inhibitors (ketoconazole, mitotane)
  • Pituitary-directed medications for Cushing's disease
  • Bilateral adrenalectomy for refractory cases

Clinical Implications and Complications

• Untreated Cushing's syndrome leads to significant morbidity and mortality 5, 6:

  • Cardiovascular: hypertension, increased risk of heart disease and stroke
  • Metabolic: diabetes, obesity, dyslipidemia
  • Musculoskeletal: osteoporosis, fractures, proximal muscle weakness
  • Immunologic: increased susceptibility to infections
  • Psychiatric: depression, anxiety, cognitive impairment

• Specific symptoms to monitor 1, 6:

  • Central obesity, "moon face," buffalo hump
  • Proximal muscle weakness
  • Wide purple striae, easy bruising
  • Hypertension, hyperglycemia
  • Growth failure in children and adolescents

Important Considerations

• False positive results can occur with 1, 2:

  • Severe obesity
  • Alcoholism
  • Depression
  • Disrupted sleep-wake cycles
  • Sample contamination (particularly by topical corticosteroids)

• In children and adolescents, Cushing's syndrome typically presents with weight gain combined with growth failure (decreased height velocity), which distinguishes it from simple obesity 1

• For patients with suspected cyclic Cushing's syndrome, periodic repeated testing may be necessary as cortisol levels can fluctuate between normal and elevated 1, 4