What is the purpose of the Cushing's score in managing Cushing's syndrome?

The Purpose of Cushing's Score in Managing Cushing's Syndrome

The Cushing's score is not a standardized diagnostic tool in managing Cushing's syndrome, but rather diagnostic testing involves a sequential approach using multiple tests including dexamethasone suppression testing, 24-hour urinary free cortisol, and late-night salivary cortisol measurements to confirm hypercortisolism and determine its source. 1

Diagnostic Approach for Cushing's Syndrome

Initial Screening Tests

• Overnight 1-mg Dexamethasone Suppression Test (DST):

  • Procedure: 1 mg dexamethasone at 11 PM, cortisol measured at 8 AM next day
  • Failure to suppress morning cortisol suggests Cushing's syndrome
  • Measuring serum dexamethasone levels simultaneously improves specificity 1

• Late-Night Salivary Cortisol (LNSC):

  • Sensitivity >90%, specificity 100%
  • Useful for initial screening and monitoring cyclic Cushing's syndrome 1

• 24-hour Urinary Free Cortisol (UFC):

  • Reflects overall cortisol production
  • Supports diagnosis when other tests are positive 1

Determining Source of Hypercortisolism

1. Plasma ACTH Measurement:

   • Differentiates ACTH-dependent from ACTH-independent causes 1

2. Dynamic Testing:

   • High-dose dexamethasone suppression test (8 mg)
   • CRH stimulation test
   • Desmopressin test 1

3. Imaging Studies:

   • Pituitary MRI for suspected Cushing's disease
   • Adrenal imaging for ACTH-independent causes 1

4. Bilateral Inferior Petrosal Sinus Sampling (IPSS):

   • For ACTH-dependent cases with equivocal results
   • Central-to-peripheral gradient ≥2 basal or ≥3 post-stimulation confirms pituitary source 1

Clinical Presentation and Importance of Early Diagnosis

Key Clinical Features

• Weight gain with central obesity
• Facial plethora, purple striae, easy bruising
• Proximal muscle weakness
• Hypertension (highly prevalent, often >80%) 2
• Glucose abnormalities
• Mood disorders and cognitive changes 3

Pediatric Considerations

• Growth failure (subnormal growth velocity) with weight gain
• Male predominance in prepubertal cases (71%)
• Microadenomas account for 98% of pediatric cases 2

Screening Recommendation for Children

• Screen for Cushing's syndrome in children with obesity only if:
  • Weight gain is inexplicable AND
  • Combined with either decreased height SDS or height velocity 2

Comorbidities and Complications

• Cardiovascular: Hypertension, increased risk of myocardial infarction, cardiac failure, stroke 4
• Metabolic: Type 2 diabetes (up to 30% of patients), dyslipidemia 1
• Musculoskeletal: Osteoporosis, fractures, myopathy 1
• Neuropsychiatric: Cognitive deficits, depression, mania 4
• Immune: Immunosuppression during active disease, susceptibility to infections 4

Treatment Approach

1. First-line: Surgical resection of causal lesion 5

   • Transsphenoidal surgery for pituitary adenomas
   • Unilateral adrenalectomy for adrenal causes

2. Second-line options (if surgery fails or is contraindicated):

   • Medical therapy: Adrenal steroidogenesis inhibitors, pituitary-targeted drugs, glucocorticoid receptor blockers
   • Radiation therapy for pituitary tumors
   • Bilateral adrenalectomy 1, 3

3. Management of comorbidities:

   • Aggressive treatment of hypertension (mineralocorticoid receptor blockers like spironolactone may be particularly effective) 2
   • Treatment of metabolic abnormalities
   • Bone health management 1

Monitoring and Follow-up

• Regular clinical evaluation for disease activity and comorbidities
• Biochemical monitoring with late-night salivary cortisol, DST, or UFC
• Annual clinical screening for patients not managed surgically 1

Early diagnosis and effective treatment are crucial to reduce mortality, improve comorbidities, and enhance long-term quality of life in patients with Cushing's syndrome 5.