Cushing's Syndrome

Question 1

What is the definition of Cushing’s syndrome? [2]

Answer 1

chronic glucocorticoid excess / and inappropriate elevated levels of circulating cortisol

Question 2

What is the definition of Cushing’s disease? [2]

Answer 2

specifically refers to excess glucocorticoids / resulting from inappropriately increased ACTH secretion due to a pituitary adenoma

Question 3

What is the brief overview of the causes of Cushing’s syndrome? [3]

Answer 3

1. chief cause is oral steroids
2. 80% of endogenous causes due to increased ACTH / and of these a pituitary adenoma (Cushing’s disease) is the most common

Question 4

What are the 4 causes of Cushing’s syndrome? [4]

Answer 4

ACTH-dependent causes =

1. Cushing’s disease
2. ectopic ACTH production

ACTH-independent causes =

3. adrenal adenoma/cancer
4. iatrogenic e.g. ingestion of excess glucocorticoid

Question 5

What is the pathophysiology of Cushing’s disease? [3]

Answer 5

ACTH-secreting pituitary adenoma / causes bilateral adrenal hyperplasia / and excess cortisol secretion

Question 6

What is the pathophysiology of ectopic ACTH production? [2]

Answer 6

ACTH-producing tumour elsewhere in the body / especially small cell lung cancer and carcinoid tumours

Question 7

What is the pathophysiology of adrenal adenomas/cancer? [2]

Answer 7

Tumour of the adrenal glands / that releases excess cortisol

Question 8

What is the pathophysiology of iatrogenic causes? [2]

Answer 8

ingesting excess glucocorticoids / e.g. prednisolone

Question 9

What are the symptoms of Cushing’s syndrome? [5]

Answer 9

1. increased weight and obesity
2. mood changes (depression, lethargy, irritability, psychosis)
3. proximal weakness
4. gonadal dysfunction (irregular periods and erectile dysfunction)
5. acne

Question 10

What are the signs of Cushing’s syndrome? [10]

Answer 10

1. central obesity and wasted limbs (“lemon on stick” appearance
2. moon face
3. buffalo hump
4. supraclavicular fat distribution
5. skin and muscle atrophy
6. purple abdominal striae
7. osteoporosis
8. hypertension
9. hyperglycaemia
10. infection prone

Question 11

What is the first step of diagnosis? [3]

Answer 11

random plasma cortisol / if high then process to low dose dexamethasone suppression test / may mislead however due to infection, time of day or stress

Question 12

What is the second step of diagnosis? [5]

Answer 12

1. dexamethasone suppression test
2. in healthy patients, dexamethasone should send negative feedback and result in decreased ACTH secretion and cortisol
3. in Cushing’s disease - low dose has no effect on plasma cortisol but high dose does
4. in ectopic ACTH production, - even high dose fails to suppress cortisol production
5. in adrenal adenoma/cancer - any dose won’t suppress cortisol as the tumour is autonomous

Question 13

What is the treatment for iatrogenic causes? [1]

Answer 13

stop steroid medications if possible

Question 14

What is the treatment for Cushing’s disease? [3]

Answer 14

1. selective surgical removal of pituitary adenoma (trans-sphenoidal surgery)
2. or bilateral adrenalectomy if source unlocatable or recurrence post-op / complications include increase skin pigmentation from increased ACTH as adrenalectomy removes negative feedback

Question 15

What is the treatment for adrenal adenoma/carcinoma? [2]

Answer 15

1. adrenalectomy for adenomas

2. radiotherapy and adrenolytic drugs / e.g. mitotane for carcinoma

Question 16

What is the treatment for ectopic ACTH? [2]

Answer 16

1. surgery if tumour is located and hasn’t spread

2. drugs that inhibit cortisol synthesis / e.g. metyrapone, ketaconazole, fluconazole

Question 17

What are the complications of Cushing’s syndrome? [2]

Answer 17

1. untreated Cushing’s syndrome has increased vascular mortality
2. if treated, prognosis good but myopathy, increased blood pressure, osteoporosis, obesity and diabetes mellitus remain