About This Page
This is a clinician-written, evidence-based guide aligned to the MCC Examination Objectives. It is structured by clinical presentation — the way the MCCQE tests and the way patients actually present. Management reflects current Canadian guidelines (CMA, CFPC, CPS). Always cross-reference with institutional protocols and clinical judgment.
Key points
- Exogenous glucocorticoids are the most common cause; always ask about oral, inhaled, topical, injected, and traditional/over-the-counter preparations
- Screen only when clinical suspicion is meaningful; obesity and diabetes alone are not enough
- First-line screening options include 1 mg overnight dexamethasone suppression, late-night salivary cortisol, or 24-hour urinary free cortisol
- After confirming hypercortisolism, ACTH separates adrenal from pituitary/ectopic causes
- Cushing syndrome increases infection, VTE, osteoporosis, diabetes, hypertension, psychiatric morbidity, and perioperative risk
Approach to the Presentation
Cushing features are tested as a pattern-recognition presentation. Many features overlap with common obesity and metabolic syndrome, so the discriminators are proximal myopathy, easy bruising, wide purple striae, facial plethora, thin skin, unexplained osteoporosis, hypokalemia, and severe early-onset cardiometabolic disease. The first diagnostic move is medication history because exogenous glucocorticoids are common and may be hidden in injections, inhalers, creams, or supplements. If endogenous Cushing syndrome is suspected, screen with an accepted first-line test, confirm abnormal results, then use ACTH and imaging selectively rather than jumping directly to CT.
Differential Diagnosis
| diagnosis | likelihood | key features | distinguishing test |
|---|---|---|---|
| Exogenous Glucocorticoid Exposure | must-not-miss | History of prednisone, dexamethasone, steroid injections, inhaled steroids, potent topical steroids, or supplements; cushingoid appearance with adrenal suppression | Medication reconciliation; low endogenous ACTH/cortisol depending timing; do not abruptly stop chronic steroids |
| Ectopic ACTH Syndrome | must-not-miss | Rapid severe hypercortisolism, muscle weakness, hypokalemic metabolic alkalosis, hyperpigmentation, weight loss, smoking history or malignancy | Very high ACTH/cortisol; failure to suppress; CT chest/abdomen after biochemical confirmation |
| Adrenocortical Carcinoma | must-not-miss | Rapid Cushing features with virilisation/feminisation, abdominal pain, large adrenal mass, constitutional symptoms | ACTH low, adrenal androgen excess, suspicious adrenal imaging |
| Pituitary Cushing Disease | common | Gradual central weight gain, facial plethora, proximal weakness, striae, menstrual irregularity, mood change; may have headache/visual symptoms if macroadenoma | Elevated/inappropriately normal ACTH after confirmed hypercortisolism; pituitary MRI and specialist dynamic testing |
| Pseudo-Cushing States | common | Alcohol use disorder, severe depression, poorly controlled diabetes, severe obesity, obstructive sleep apnea can cause mild cortisol abnormalities | Clinical context; repeat or specialist testing after addressing driver |
| Polycystic Ovary Syndrome | common | Hirsutism, acne, oligomenorrhea, obesity, insulin resistance; lacks proximal myopathy and wide purple striae | Androgen profile, menstrual history, ovarian criteria; cortisol screening normal |
| Simple Obesity / Metabolic Syndrome | common | Central adiposity, hypertension, dyslipidemia, insulin resistance without catabolic skin/muscle signs | No abnormal first-line cortisol screening |
| Adrenal Adenoma causing Cortisol Excess | less common | Cushing features or autonomous cortisol secretion with hypertension, diabetes, osteoporosis; adrenal incidentaloma may be present | Low ACTH with adrenal lesion and abnormal dexamethasone suppression |
| Congenital Adrenal Hyperplasia | rare | Androgen excess, menstrual irregularity, infertility, adrenal enlargement; may mimic some Cushing features | 17-hydroxyprogesterone and endocrine assessment |
Red Flags & Key History
Symptoms
Rapid onset severe weakness, infection, psychosis, VTE symptoms, or uncontrolled hypertension/diabetes
Proximal muscle weakness, easy bruising, thin skin, wide purple striae, facial plethora
Hypokalemia with hypertension — ectopic ACTH or mineralocorticoid excess
Virilisation, severe androgen excess, or abdominal pain — adrenal carcinoma concern
History of any glucocorticoid formulation including injections, inhalers, creams, or supplements
Weight gain, mood change, insomnia, menstrual irregularity, reduced libido
Fragility fracture or early osteoporosis
Signs
Proximal myopathy: difficulty rising from chair or climbing stairs
Wide purple abdominal striae, easy bruising, thin skin, poor wound healing
Facial plethora, dorsocervical fat pad, supraclavicular fullness
Hypertension, oedema, or signs of heart failure
Hirsutism, acne, virilisation, or testicular atrophy depending cause
Signs of infection may be muted despite severe illness
Approach to Investigation
First-line
Medication and exposure historyAsk explicitly about oral, inhaled, nasal, topical, intra-articular, epidural, and complementary steroid exposure
One accepted screening test1 mg overnight dexamethasone suppression, late-night salivary cortisol, or 24-hour urinary free cortisol; choose according to availability and context
Basic complication assessmentBP, A1c/glucose, lipids, electrolytes, CBC, renal function, and fracture risk
Second-line
Repeat/confirm abnormal screeningCushing diagnosis should not rest on a single borderline abnormal result unless presentation is severe
ACTH after confirmed hypercortisolismLow ACTH suggests adrenal source; normal/high ACTH suggests pituitary or ectopic ACTH
DHEA-S/androgens and potassiumHelpful when adrenal carcinoma or ectopic ACTH is suspected
Specialist
Pituitary MRI or adrenal CTOnly after biochemical confirmation and ACTH-directed localisation
Inferior petrosal sinus samplingSpecialist test when ACTH-dependent Cushing source is unclear
Endocrinology referralAll suspected endogenous Cushing syndrome or complex steroid taper/adrenal suppression
Management Principles
Endocrine Society diagnostic approach adapted to Canadian specialist practice1
First step
- Look for exogenous glucocorticoid exposure before ordering extensive endocrine tests
- If chronic steroid exposure is present, do not stop abruptly; assess adrenal suppression risk and taper plan
2
Screening and confirmation
- Use one recommended screening test when pre-test probability is meaningful
- Repeat or confirm abnormal results and avoid testing during acute severe illness where possible
- After confirmed endogenous hypercortisolism, measure ACTH to direct imaging
3
Complication management
- Treat hypertension, diabetes, infection risk, osteoporosis, psychiatric symptoms, and VTE risk
- Refer for definitive pituitary, adrenal, or ectopic tumour management
- Provide perioperative steroid planning and patient education about adrenal insufficiency risk
Complications & Pitfalls
- Missing exogenous steroids: Steroid injections, inhalers, creams, and supplements can all cause Cushingoid features
- Screening every patient with obesity: Low pre-test probability creates false positives
- Imaging before biochemistry: Incidental pituitary or adrenal lesions can mislead the workup
- Stopping steroids abruptly: Chronic exposure can suppress the HPA axis and cause adrenal crisis
- Ignoring complications: Infection, VTE, osteoporosis, diabetes, and psychiatric risk drive morbidity
MCCQE1 Exam Tips
- 1Exogenous steroids are the most common Cushing cause — medication history is the exam-saving step
- 2Discriminating signs are proximal myopathy, wide purple striae, bruising, and thin skin
- 3Do screening test first, ACTH second, imaging third
- 4Low ACTH = adrenal source; high/normal ACTH = pituitary or ectopic ACTH
- 5Pseudo-Cushing states include alcohol use disorder and severe depression
- 6Do not abruptly stop long-term glucocorticoids
- 7Cushing syndrome causes osteoporosis and infection risk even in younger patients
Put your reading into practice
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