Cushing's disease and Cushing's syndrome

Question 1

Define Cushing’s syndrome and Cushing’s disease, while explaining the difference between the two

Answer 1

• Cushing syndrome: This is an excessive production of cortisol hormone
• Cushing disease: is a type of Cushing syndrome where the cause is a pituitary tumour producing ACTH that results in excessive hormone

Question 2

Describe the epidemiology of Cushing’s syndrome

Answer 2

• Women are 3x more likely to develop it

Question 3

What are the main risk factors for developing Cushing’s syndrome

Answer 3

1. ) Being female
2. ) Being on oral steroids for a chronic condition such as rheumatoid arthritis and asthma
3. ) Spontaneous endogenous cause is rare: 80% of these are due to a pituitary adenoma

Question 4

Explain the main causes of Cushing’s syndrome

Answer 4

1. ) ACTH independent cause: Exogenous steroids that produce all the clinical features of the syndrome (basically noting changes with the levels of hormones involved in producing cortisol)
2. ) ACTH independent cause: adrenal adenoma/carcinoma (adrenal cortex specifically) which causes the gland to produce excess cortisol
3. ) Ectopic Cushing’s syndrome: due to paraneoplastic syndrome e.g. small cell lung cancer producing ACTH
4. ) Cushing’s disease: a pituitary adenoma that causes excess ACTH. Get bilateral adrenal hyperplasia due to ACTH hypersecretion by pit adenoma

Question 5

Describe the pathology of Cushing’s syndrome

Answer 5

• Excess cortisol can result from:
• Excess ACTH which then stimulates excess cortisol production
• Neoplasma in adrenals, stimulating the zona reticularis to produce more cortisol
• Ingesting excess glucocortiocids e.g. prednisolone

Question 6

What are the clinical features of excess cortisol

Answer 6

• Inhibits the immune system: leads to weaker immune system, so person will get frequent infections
• Inhibition of bone formation: leads to osteoporosis and weak, brittle bones
• Raises blood glucose: can lead to type 2 diabetes
• Stimulates metabolism

Question 7

What are the main signs and symptoms of Cushing’s syndrome?

Answer 7

SIGNS

1. ) Buffalo hump
2. ) Moon face
3. ) Central obesity
4. ) Acne
5. ) Hirsutism: unwanted male pattern hair growth on woman
6. ) Fatigue
7. ) Easily bruising skin/thin skin
8. ) Muscle wastage/thin arms-> from osteoporosis

SYMPTOMS: CUSHING MNENOMIC

C - cataracts
U - ulcers
S - striae
H - hypertension and hyperglycaemia
I - increased risk of infection
N - necrosis
G - glucosuria

+ in women, get amenorrhoea

Question 8

Investigations and diagnosis

Answer 8

1. ) Blood test: high levels of cortisol
   - 1st line: overnight dexamethasone suppression test: dexamethasone usually supresses cortisol level. Failure to suppress is enough to diagnose the symptom
   - This can be:
2. ) Low dose dexamethasone: most relaible + normal people will suppress cortisol to <50nmol 2 hours after last dose of dexa
3. ) High dose: Cushing’s disease patients will suppress plasma cortisol by 48 hours. Failure of this will suggest an ectopic source of ACTH or an adrenal tumour
   - After this 1st line test, check 24 hour urinary free cortisol measurement: if normal levels are present, probs not Cushing

2nd line test: try a 48 hours dexamethasone test
- Plasms ACTH
1.) Low: adrenal imaging. Supression will be a pit adenoma. MRI will find lesion
2.) High: distinguish pituitary and ectopic cause
- No suppression by high dose need to look for ectopic. Would do a
1.) IV contrast CT chest, abdo, pelvis
2.) MRI of neck, thorax, abdo
3.) CXR to look at lung for SCLC
OR
CRH test
- if cortisol increases = pituitary disease
- if cortisol doesn’t increase = ectopic

3.) CT or MRI: for adenoma identification

Question 9

Treatment

Answer 9

1. ) If exogenous: reducing levels of steroids to manage symptoms
2. ) Cushing’s disease: get transphenoidal removal of pituitary adenoma
3. ) Adrenal adenoma: adrenalectomy (can cause nelson’s syndrome) or radiotherapy
4. ) Adrenal carcinoma: adrenalectomy + RT and adrenolytic drugs e.g. mitotane
5. ) Ectopic ACTH: surgery to remove tumour if location is unknown

Question 10

What could be a differential diagnosis of Cushing’s syndrome

Answer 10

Pseudo- Cushing’s syndrome: caused by excess alcohol, will resolve after 1-3 weeks of alcohol abstinence