Cushings SYNDROME

Question 1

What is the aetiology in cushings?

Answer 1

excess cortisol

Question 2

The 2 Subdivisions? and causes?

Answer 2

It can be divided into ACTH Dependent (80%) and ACTH Independent (20%)

ACTH Dependent;

• Excess ACTH from a pituitary adenoma (Cushing’s disease)
• Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)

ACTH Independent;

• Benign adrenal adenoma
• Adrenal carcinoma

Question 3

Invx for cushings?

Answer 3

Bloods
○ U&Es - hypokalaemia due to mineralocorticoid effect
○ BM - high glucose

• Initial High-Sensitivity Tests
○ 24hr Urinary free cortisol - above 50
○ Late-night salivary cortisol - high
○ Overnight dexamethasone suppression test (1mg)
   -morning cortisol above 50nmol

○ Low dose dexamethasone suppression test (LDDST)
• Give 0.5 mg dexamethasone orally every 6 hrs for 48 hrs
• In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose of dexamethasone fails to suppress below 50 nmol/L

ACTH-independent (adrenal adenoma/carcinoma)- tumour producing cortisol;
• Low plasma ACTH
• CT or MRI of adrenals

 ACTH-dependent (pituitary adenoma)
• High plasma ACTH
• Pituitary MRI
• High-dose dexamethasone suppression test
• Inferior petrosal sinus sampling

Question 4

How does one differentiate between a pituitary and ectopic source of acth?

Answer 4

Inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone suppression test)
• Central: peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s disease

• so if ratio is 2:1 you know its pituitary adenoma.
  and;

high dose dexamethasone suppression test (2mg)
- positive test - suppresses (means pituitary source)

Question 5

ivx for ACTH-dependent (ectopic) cushings?

Answer 5

• If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
• Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors

Question 6

what is cushings disease?

Answer 6

cushings casued by pituitary adenoma

Question 7

Management of cushings caused by pituitary adenoma (cushings disease)?

Answer 7

1st;

• Transphenoidal adenoma resection
  Adjuncts;
• Ketoconazole or metyrapone before surgery
• Hydrocortisone Post surgery for corticosteroid
  replacement
• Other pituitary hormones given for replacement

2nd;
- Medical therapy alone - Ketoconazole or metyrapone

3rd;
- Pituitary radiotherapy (if re-operation wont benefit)

4th;
- Bilateral adrenalectomy

Question 8

Management of cushings caused by ectopic acth ?

Answer 8

1st;

• Surgery to resect or ablation of tumour + mets
• Ketoconazole or metyrapone

2nd;
Bilateral adrenalectomy

3rd;
Medical only; Ketoconazole or metyrapone

Question 9

Management of ACTH independent cushings - bilateral adrenal tumours?

Answer 9

1. Bilateral adrenalectomy

2. Medical only; Ketoconazole or metyrapone

Question 10

Management of ACTH independent cushings - unilateral adrenal tumours?

Answer 10

1. unilateral tumour resection

2. Medical only; Ketoconazole or metyrapone