Clinical Presentation Checklist

 To help you organize your clinical approach or provide a guide for your students, here is a comprehensive troubleshooting checklist for identifying and diagnosing Cushing's Syndrome.

Clinical Presentation Checklist
Review these common "red flag" symptoms to distinguish Cushing's from simple obesity or metabolic syndrome.

[ ] Central Obesity: Weight gain primarily in the trunk and abdomen with thin arms and legs.
[ ] Dermatological Signs: * Wide (>1cm), purple/red striae (stretch marks) on the abdomen, thighs, or breasts.
Easy bruising and thin, fragile skin.
Slow wound healing.
[ ] Fat Redistribution: * "Moon Face" (rounded, plethoric face).
"Buffalo Hump" (supraclavicular and dorsocervical fat pads).
[ ] Musculoskeletal: Proximal muscle weakness (difficulty standing from a chair or climbing stairs).
[ ] Endocrine/Metabolic: New-onset hypertension, Type 2 Diabetes, or irregular menstrual cycles.

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Diagnostic Troubleshooting (The "First Tier" Tests)
If Cushing's is suspected, use at least two of these tests to confirm hypercortisolism. If results are discordant, further investigation is required.
[ ] 24-Hour Urinary Free Cortisol (UFC): Measures cumulative cortisol over a full day. (Requires at least two collections).
[ ] Late-Night Salivary Cortisol: Checks for the loss of normal diurnal rhythm (cortisol should be at its lowest at midnight).
[ ] Overnight Low-Dose Dexamethasone Suppression Test (LDDST): 1 mg of dexamethasone is taken at 11 PM; cortisol is measured at 8 AM.
Normal result: Cortisol suppresses to < 1.8 µg/dL.

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Differential Diagnosis: Determining the Source
Once hypercortisolism is confirmed, you must "troubleshoot" the source (Pituitary vs. Adrenal vs. Ectopic).
[ ] Check Plasma ACTH Levels:
Low ACTH (< 5 pg/mL): Likely Adrenal-dependent (tumor on the adrenal gland).
High/Normal ACTH (> 20 pg/mL): ACTH-dependent (Pituitary tumor or Ectopic source like lung cancer).
[ ] High-Dose Dexamethasone Suppression Test: Usually suppresses cortisol in Pituitary cases (Cushing's Disease) but not in Ectopic or Adrenal cases.
[ ] Imaging Protocols:
Pituitary MRI (if ACTH is high).
Adrenal CT (if ACTH is low).
Chest/Abdomen CT (if Ectopic ACTH is suspected).

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Common "False Positive" Pitfalls (Pseudo-Cushing's)
Ensure these factors aren't skewing your results:
[ ] Exogenous Steroids: Is the patient using creams, inhalers, or joint injections? (Most common cause).
[ ] Severe Stress/Depression: Can cause elevated cortisol without a primary tumor.
[ ] Alcoholism: Chronic heavy use can mimic the clinical and biochemical features of Cushing's.
[ ] High Estrogen: Pregnancy or oral contraceptives can elevate total cortisol levels (though free cortisol may remain normal).