PACES PATHFINDERS LEARNING LIBRARY

Approach to Progressive Weight Gain

Cushing Syndrome • Hypercortisolism • MRCP (UK) PACES

A structured MRCP (UK) PACES approach to a patient presenting with progressive weight gain. Learn how to recognise Cushing syndrome, identify features of hypercortisolism, investigate systematically, distinguish ACTH-dependent from ACTH-independent disease and explain management confidently.

12 min read Presenting Complaint Very High Yield

At a Glance

Presentation Progressive weight gain
Likely Diagnosis Cushing Syndrome
Underlying Disorder Hypercortisolism
Must Not Miss Exogenous corticosteroid use
Hallmark Feature Central obesity with proximal myopathy and purple striae
First Investigation Confirm hypercortisolism before localisation

Red Flags

Rapid weight gain Purple striae Easy bruising Proximal muscle weakness Resistant hypertension Visual symptoms

PACES Approach

① Confirm true weight gain ② Identify features of cortisol excess ③ Exclude exogenous steroid use ④ Confirm hypercortisolism ⑤ Localise the underlying cause

Endocrine Investigation Pathway

Clinical Suspicion
Progressive weight gain
Purple striae
Proximal weakness
Step 1
Confirm hypercortisolism
Step 2
Measure ACTH
Low ACTH
Adrenal CT/MRI
High ACTH
Pituitary MRI
MRI Equivocal
Inferior Petrosal Sinus Sampling

Overview

Progressive weight gain is a common presenting complaint, but the presence of central obesity, proximal muscle weakness, easy bruising, thin skin, violaceous striae, hypertension and diabetes should immediately raise suspicion of Cushing syndrome. In MRCP (UK) PACES, candidates should first exclude exogenous corticosteroid exposure, then confirm hypercortisolism using appropriate screening tests before determining whether the cause is ACTH-dependent or ACTH-independent.

Structured History

  • Duration and progression of weight gain
  • Distribution of weight gain (central or generalized)
  • History of prolonged corticosteroid use (oral, inhaled, topical, intra-articular or injectable)
  • Easy bruising, thinning of the skin or poor wound healing
  • Purple abdominal striae or increasing abdominal girth
  • Proximal muscle weakness affecting climbing stairs or rising from a chair
  • New-onset diabetes, hypertension or worsening glycaemic control
  • Menstrual irregularity, infertility or reduced libido
  • Mood changes, depression, anxiety or sleep disturbance
  • History suggestive of pituitary disease including headache or visual disturbance

Examination

  • Measure weight, BMI and waist circumference
  • Record blood pressure
  • Inspect for central obesity and facial fullness
  • Look for wide violaceous abdominal striae
  • Assess skin thinning, bruising and poor wound healing
  • Assess proximal muscle power
  • Look for hirsutism, acne and features of androgen excess
  • Examine for peripheral oedema
  • Assess visual fields if pituitary disease is suspected
  • Look for evidence of osteoporosis or vertebral tenderness

Differential Diagnosis

Exogenous Corticosteroid Therapy Pituitary Cushing Disease Adrenal Adenoma Adrenal Carcinoma Ectopic ACTH Syndrome Hypothyroidism Polycystic Ovary Syndrome Simple Obesity Pseudo-Cushing Syndrome

Investigations

  • 1 mg overnight dexamethasone suppression test
  • 24-hour urinary free cortisol
  • Late-night salivary cortisol
  • Morning plasma ACTH
  • Pituitary MRI if ACTH-dependent disease is suspected
  • CT or MRI of the adrenal glands if ACTH-independent disease is suspected
  • Inferior petrosal sinus sampling when indicated
  • HbA1c, fasting glucose and lipid profile
  • Serum electrolytes, especially potassium
  • Bone mineral density assessment if osteoporosis is suspected

Diagnosis

Progressive Weight Gain Secondary to Cushing Syndrome

The diagnosis is established by first confirming endogenous hypercortisolism using appropriate screening tests. Once confirmed, plasma ACTH distinguishes ACTH-dependent from ACTH-independent disease, allowing targeted imaging to identify the underlying cause. A careful drug history is essential to exclude exogenous corticosteroid exposure before proceeding with endocrine investigations.

Management

Initial Management Optimise blood pressure, diabetes, osteoporosis and cardiovascular risk while completing the endocrine evaluation.
Definitive Treatment Withdraw exogenous steroids where appropriate, pituitary or adrenal surgery, medical therapy or radiotherapy according to the underlying cause.
Long-term Follow-up Monitor endocrine recovery, recurrence, metabolic complications and bone health with specialist follow-up.

Explaining to the Patient

"Your symptoms suggest that your body may be producing too much cortisol, which is an important hormone made by the adrenal glands. We first need to confirm whether cortisol levels are genuinely raised using specialised hormone tests. If they are, further blood tests and scans will help identify the exact cause. Treatment depends on the underlying diagnosis and may involve adjusting steroid medication, surgery or medicines to reduce cortisol production."

Examiner's Corner

Differentiate Cushing Syndrome from Cushing Disease
  • Cushing Syndrome refers to cortisol excess from any cause.
  • Cushing Disease specifically refers to a pituitary ACTH-secreting adenoma causing hypercortisolism.
How do you investigate suspected Cushing Syndrome?
  • Confirm hypercortisolism using an overnight dexamethasone suppression test, late-night salivary cortisol or 24-hour urinary free cortisol.
  • Measure plasma ACTH.
  • Low ACTH suggests an adrenal source.
  • Normal or high ACTH suggests pituitary or ectopic ACTH production.
  • Pituitary MRI or adrenal CT/MRI is performed according to ACTH results.
  • Inferior petrosal sinus sampling is useful when pituitary imaging is inconclusive.
Common Viva Questions
  • What are the causes of Cushing syndrome?
  • How does exogenous steroid excess present?
  • What is pseudo-Cushing syndrome?
  • How do you distinguish ACTH-dependent from ACTH-independent disease?
  • When is inferior petrosal sinus sampling indicated?
  • What is Nelson syndrome?
  • What complications occur if Cushing syndrome is untreated?
Important Clinical Pearls
  • Always ask specifically about oral, inhaled, topical and injectable corticosteroids.
  • Confirm hypercortisolism before localisation.
  • Never stop long-term corticosteroids abruptly.
  • Treat diabetes, hypertension, osteoporosis and infections alongside definitive endocrine therapy.
  • Remember that obesity alone does not equal Cushing syndrome.

Pathfinder Pearls

Think exogenous steroids first Purple striae are highly suggestive Proximal myopathy is a key clinical clue Differentiate Cushing syndrome from Cushing disease Confirm hypercortisolism before imaging ACTH directs further investigations Remember pseudo-Cushing syndrome Treat cardiovascular risk aggressively

Common Pitfalls

  • Failing to ask about corticosteroid exposure.
  • Ordering pituitary MRI before confirming hypercortisolism.
  • Confusing Cushing disease with Cushing syndrome.
  • Missing pseudo-Cushing syndrome.
  • Ignoring metabolic complications such as diabetes and hypertension.
  • Stopping corticosteroids abruptly.
  • Focusing only on obesity while overlooking other clinical features.

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