Cushing's syndrome

Question 1

What is the difference between Cushing’s disease and Cushing’s syndrome?

Answer 1

Cushing’s syndrome is the clinical manifestation of hypercortisolism from any cause.

Cushing’s disease is one cause of Cushing’s syndrome characterised by increased secretion of ACTH from the anterior pituitary (secondary hypercortisolism).

Question 2

What is the endocrine axis associated with Cushing’s?

Answer 2

Question 3

What is the most likely diagnosis? What is the most common cause?

Answer 3

Cushing’s

Most common causes:

Exogenous cause:

1. Prolonged use of glucocorticoids → Cushing’s syndrome
2. Secretion of ectopic ACTH - small-cell lung Ca

Endogenous cause:

1. 80% Pituitary tumour → cortisol excess Cushing’s disease.
2. 10% adrenal adenomas
3. 1% adrenal carcinomas

Question 4

Who does Cushing’s disease usually affect?

Answer 4

Women between 30-50yrs

Question 5

What are the classical characteristics of Cushing’s syndrome?

Answer 5

Cushing described a syndrome characterized by:

• truncal obesity,
• hypertension,
• fatigability and weakness,
• amenorrhoea,
• hirsutism,
• purplish abdominal striae,
• oedema,
• glycosuria,
• osteoporosis
• a basophilic tumour of the pituitary.

Most common signs and symptoms:

• Typical habitus 97%
• Increased body weight 94%
• Fatigability and weakness 87%
• Hypertension ( >150/90) 82%
• Hirsutism 80%
• Amenorrhoea 77%
• Cutaneous striae 67%
• Personality changes 66%
• Ecchymoses 65%
• Oedema 62%
• Polyuria and polydipsia 23%
• Hypertrophy of clitoris 19%

Question 6

What tests are used for the diagnosis of Cushing’s?

Answer 6

Main initial findings are usually low potassium, metabolic alkalosis, high glucose and hypertension (low aldosterone excluding Conn’s)

Diagnostic tests:

1. Overnight dexamethasone suppression test
   
   1. OR 24hr urine free cortisol
2. Inferior petrosal sinus sampling (IPSS) -?pituitary or ectopic

Other tests: help localise lesions

• Insulin stress test - Cushing’s vs pseudo-Cushing’s
• CRH stimulation - as above
• pituitary MRI
• abdominal CT

NB: High dose dexamethasone suppression test (HDDST) is no longer used because most are pituitary dependent anyway and the test has high false +ve. Results below.

Question 7

What is the management of Cushing’s syndrome?

Answer 7

1st line: pituitary cause:

• Transsphenoidal pituitary adenomectomy (1st line)
  
  • +/- Preceded with medical therapy: somatostatin analogue, DA (carbegoline) etc.
  • +/- Followed by hydrocortisone replacement or other hormone replacement.

Adrenal cause:

• Unilateral/bilateral adrenalectomy or tumour resection
  
  • +/- Preceded with medical therapy e.g. steroidogenesis inhibitors like ketoconazole
  • +/- chemo/ radiotherapy

Question 8

What are the complications of Cushing’s syndrome?

Answer 8

• Adrenal insufficiency secondary to adrenal suppression
• CVD
• Osteoporosis - excessive bone exposure to glucocorticoids
• Nephrolithiasis - calcium renal stones
• Nelson’s syndrome
• Hypopituitarism
• Hyponatraemia after surgery

Question 9

What is Nelson’s syndrome?

Answer 9

Progression of a pituitary adenoma after bilateral adrenalectomy

May be so large as to cause mass effect, and elevated ACTH.

Question 10

What is the prognosis with Cushing’s when untreated/treated?

Answer 10

• If left untreated - condition worsens and survival at 5yrs is 50%
• In first year of effective therapy, many of the characteristic features resolve

Question 11

What causes hypertension in Cushing’s?

Answer 11

Cortisol at high concentrations acting on MR receptors

The enzyme that usually stops this is saturated and so HTN occurs

Question 12

What is a serious consequence of stopping steroids suddenly?

Answer 12

Addisonian crisis