Cushing's syndrome

Question 1

Define Cushing’s syndrome.

Answer 1

Clinical manifestation of pathological hypercortisolism from any cause.

Question 2

Who is affected?

Answer 2

· More common in women.
· No ethnic disparities in prevalence.
· Majority of adults are diagnosed between the ages of 20-50.

Question 3

What is the pathophysiology of Cushing’s syndrome?

Answer 3

· The clinical manifestations result from excess tissue exposure to cortisol.
· The degree of symptoms is based on the degree of cortisol excess.

Question 4

What is the prognosis for Cushing’s syndrome?

Answer 4

· Untreated disease has a poor survival rate of 50% at 5 years.
· Increased mortality from CVD.

Question 5

What are the most common aetiologies of Cushing’s?

Answer 5

1. ATCH-secreting pituitary adenomas.
2. Autonomous adrenal cortisol over-production.
3. Ectopic ACTH-secreting tumours.
4. To exclude as a cause that causes physiological hypercortisolism:
   · Pregnancy.
   · Malnutrition.
   · Alcoholism.
   · Physiological stress.

Question 6

List the possible risk factors.

Answer 6

· Exogenous corticosteroid use. 
· Pituitary adenoma - vast majority of these are non-secretory and don't cause Cushing's disease.
· Adrenal adenoma. 
· Adrenal carcinoma. 
Neuroendocrine tumours.

Question 7

What are the typical presenting signs and symptoms?

Answer 7

· Facial plethora.
· Facial rounding. 
· Supraclavicular fullness. 
· Pathological fractures (especially vertebrae and ribs).
· Weight gain and central obesity. 
· Acne. 
· Striae. 
· Menstrual irregularities. 
· Depression.
· HTN. 
· Glucose intolerance or diabetes. 
· Premature osteoporosis or unexplained fractures. 
· Easy bruising. 
· Proximal muscle weakness.

Question 8

What investigations would you do to help diagnose Cushing’s?

Answer 8

· Urine pregnancy test.

· Serum glucose.

· 1st line - Late-night salivary cortisol - elevated.

· 1mg overnight dexamethasone suppression test - morning cortisol >50nm/L.

· 24hr urinary free cortisol - >50mcg/24 hours.

· 48hr 2mg dexamethasone suppression test - morning cortisol >50nm/L.

· Pituitary MRI.

Question 9

Suggest some differentials.

Answer 9

· Obesity.

· Metabolic syndrome.

Question 10

What is the treatment option for an ACTH-secreting pituitary tumour?

Answer 10

1st line - Trans-sphenoidal pituitary adenomectomy - – removes the causative pituitary adenoma:
· Medical therapy before surgery.
· Post-surgical corticosteroid replacement therapy.

2nd line - Repeat trans-sphenoidal pituitary adenomectomy:
· Medical therapy before surgery.
· Post-surgical corticosteroid replacement therapy.
· Post-surgical non-corticosteroid pituitary hormone replacement therapy.

3rd line - Pituitary radiotherapy.

4th line - Bilateral adrenalectomy.

Question 11

What is the treatment option for an ectopic ACTH-secreting tumour?

Answer 11

1st line - Surgical resection of tumour and metastases.
· Chemotherapy/Radiotherapy.

2nd line - Bilateral adrenalectomy.

Question 12

What is the treatment option for an adrenal carcinoma?

Answer 12

· 1st line - Unilateral adrenalectomy.

· Chemotherapy/Radiotherapy.

Question 13

What are the most common complications of Cushing’s?

Answer 13

· Adrenal insufficiency secondary to adrenal suppression. 
· CVD. 
· HTN.
· Diabetes.
· Osteoporosis.