Endocrine: Cushings

Question 1

Most common cause of cushings disease?

Answer 1

A benign pituitary tumour that secretes ACTH

Question 2

Cushings disease vs Cushings syndrome

Answer 2

Cushing’s disease is a subtype of Cushing’s syndrome

Cushings disease: caused by an ACTH secreting pituitary adenoma

Question 3

Causes of cushings?

Answer 3

Iatrogenic: corticosteroid therapy
ACTH-dependent causes:
- Cushing’s disease (a pituitary adenoma → ACTH secretion)
- Ectopic ACTH secretion secondary to a malignancy
ACTH-independent causes:
- Adrenal adenoma producing too much cortisol

Question 4

Clinical features of cushings?

Answer 4

Weight Gain Central Obesity buffalo hump, moon face, striae
Bone/Muscle Affects: Proximal myopathy, osteopenia and osteoporosis
Derm affects: Hirsutism, Acne vulgaris, thin skin bruising and poor wound healing
Endocrine: Diabetes, Oligomenorrhea or amenorrhea
Other: Depression, sleep disturbance,h ypertension

Question 5

Investigation for cushings?

Answer 5

Overnight (low-dose) dexamethasone suppression test:
- patients with Cushing’s syndrome do not have their morning cortisol spike suppressed

24 hr urinary free cortisol
- two measurements are required

Bedtime salivary cortisol
-two measurements are required

Question 6

Investigations to localise the cause of cushings? How does it work?

Answer 6

High-dose dexamethasone suppression test:
9am and midnight plasma ACTH and cortisol levels

Question 7

High dose dexamethasone suppression test results:
- cortisol suppressed
- ACTH suppressed

Answer 7

Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)

Question 8

High dose dexamethasone suppression test results:
- cortisol not suppressed
- ACTH suppressed

Answer 8

Cushing’s syndrome due to other causes (e.g. adrenal adenomas)

Question 9

High dose dexamethasone suppression test results:
- cortisol not suppressed
- ACTH not suppressed

Answer 9

Ectopic ACTH syndrome

Question 10

Management of cushings?

Answer 10

First-line = trans-sphenoidal removal of pituitary tumour
Second-line = repeat trans-sphenoidal surgery, pituitary radiotherapy
Third-line = bilateral adrenalectomy

Question 11

Complications of bilateral adrenalectomy?

Answer 11

1) Hypoadrenal crisis - requires life-long glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) replacement
2) Nelson’s syndrome - low/no endogenous cortisol following bilateral adrenalectomy causes massive increase in ACTH production by pituitary gland (via negative feedback) which causes rapid pituitary enlargement (mass effects) and skin hyperpigmentation.