Crushing Syndrome/ disease

Question 1

What is Cushing’s syndrome

Answer 1

Cushing’s syndrome is the condition resulting from increased free circulating glucocorticoids (cortisol), regardless of the cause

Question 2

What is Cushing’s disease?

Answer 2

Cushing’s disease is when the increased cortisol levels are caused by a functioning pituitary adenoma (ACTH-secreting)

Question 3

What is the most common cause of cortisol excess?

Answer 3

Iatrogenic
(exogenous steroids)

Question 4

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

Answer 4

Cushing’s disease is due to a pituitary adenoma, while Cushing’s syndrome includes all causes of cortisol excess

Question 5

What are the ACTH-dependent causes of Cushing’s?

Answer 5

(1) Pituitary adenoma
(Cushing’s disease)

(2) Ectopic ACTH
(small cell lung cancer)

(3) Ectopic CRH

Question 6

What are the ACTH-independent causes of Cushing’s? - Exogenous steroids

Answer 6

(1) Adrenal adenoma or carcinoma

(2) Adrenal cortical nodular hyperplasia

(3) False positive (pseudocushings)
= severe depression + severe alcoholism

Question 7

What are key clinical features of Cushing’s?

Answer 7

1. Moon face
2. Buffalo hump
3. Central obesity
4. Striae
5. Hypertension
6. Thin skin
7. Osteoporosis
8. Diabetes

Question 8

What test confirms cortisol excess?
= crushing syndrome

Answer 8

Overnight 1mg dexamethasone suppression test

Normal: cortisol <50 nmol/l the next morning

Abnormal: cortisol >130 nmol/l
= have to check ACTH levels, high-dose dexamethasone test

Question 9

What is the first-line diagnostic test for Cushing syndrome?

Answer 9

Low-dose dexamethasone suppression test. 2mg dexamethasone for 2 days

(1) Normal
= cortisol <50 nmol/l after 6 hours

(2) Cushing’s
= cortisol >130 nmol/l after 6 hours

Question 10

How do you interpret the Dexamethasone suppression test results? low, high

Answer 10

Low dose
(1) Supressed > confirms crushing syndrome likely dependent cause
Not supressed> confirms crushing syndrome likely independent

High dose (8mg) to differentiate causes
(2) Suppressed by high dose
= Cushing’s disease (pituitary adenoma)
Not supressed> adrenal

(3) Not suppressed by high or low dose = Ectopic ACTH production
(small cell lung cancer).

Question 11

What test differentiates ACTH-dependent from ACTH-independent Cushing’s?

Answer 11

Serum ACTH levels

(1) Low ACTH
= Adrenal adenoma/carcinoma, exogenous steroids = independent

(2) High ACTH
= Cushing’s disease or ectopic ACTH = dependent

Question 12

What is the first-line treatment for Cushing’s disease?

Answer 12

Transsphenoidal hypophysectomy (pituitary surgery)

Question 13

What imaging is used based on ACTH levels?

Answer 13

Low ACTH → Adrenal CT/MRI
= ACTH-independent Cushing’s syndrome

High ACTH → Pituitary MRI + biochemical tests
= ACTH-dependent Cushing’s syndrome

Question 14

What is the treatment for adrenal adenoma causing Cushing’s?

Answer 14

Adrenalectomy
= removal of the adrenal gland

Question 15

How is ectopic ACTH treated?

Answer 15

(1) Remove the source (eg, carcinoma)

(2) Bilateral adrenalectomy if not surgically feasible.

Question 16

What drugs control cortisol excess if surgery fails?

Answer 16

1. Metyrapone
2. Ketoconazole
3. Pasireotide

Question 17

What is the first step if Cushing’s is due to exogenous steroids?

Answer 17

Reduce steroid dose gradually

Question 18

How is cortisol excess established?

Answer 18

(1) Overnight 1mg dexamethasone suppression test
= Normal - cortisol <50 nmol/l the next morning
Abnormal - cortisol >130 nmol/l

(2) 24hr urine free cortisol:
= Normal - <250 nmol/24hr Cortisol/creatinine ratio <25

(3) Diurnal cortisol variation
= Loss of diurnal variation (suspicious of Cushing’s)

Question 19

What is the first line treatment for Cushing’s disease in the majority of cases?

Answer 19

Trans-sphenoidal surgery

Question 20

How is an overnight dexamethasone suppression test performed?

Answer 20

1mg oral Dexamethasone taken at midnight followed by a 9am cortisol blood test

Question 21

What is the common type of lung malignancy that gives rise to Cushing’s syndrome?

Answer 21

Small cell lung cancer

Question 22

What is the name given to pituitary driven ACTH excess?

Answer 22

Cushing’s disease

Question 23

What is the name given to the type of leg weakness that makes going up and down stairs difficult?

Answer 23

Proximal myopathy

Question 24

A 54-year-old woman is reviewed on the general medical ward after being admitted with cellulitis following a cut on her leg. She has recently been diagnosed with hypertension and type 2 diabetes mellitus. On examination, she has central obesity, a plethoric round face, bruising on her arms and proximal muscle weakness.

What is the next best investigation to screen for the most likely cause of these clinical findings?

Answer 24

Low dose dexamethasone suppression test

Question 25

A 76-year-old male presents to the GP with weight gain, depression, and proximal weakness. On examination, he has purple abdominal striae. The GP suspects Cushing's syndrome. What is the most common underlying cause of Cushing's syndrome?

Answer 25

Oral corticosteroids = Exogenous

Question 26

When would the answer be Nelsons Syndrome in regards to crushing syndrome

Answer 26

When a bilateral adrenalectomy has been mentioned

Question 27

A 55-year-old man is reviewed in the endocrinology clinic. He has a 3-month history of lethargy and weight gain. He has recently been diagnosed with hypertension and commenced on amlodipine but has no other past medical history. He smokes 20 cigarettes per day and drinks a bottle of wine each evening. On examination, he has a plethoric, round face, central obesity and proximal muscle weakness. 24-hour urinary cortisol and a random serum adrenocorticotropic hormone (ACTH) are both elevated. Midnight and early morning cortisol levels demonstrate normal diurnal variation in cortisol level. What is the most likely explanation for this patient’s physical findings and investigation results and explain why?

Answer 27

Chronic alcoholism = This is a case of pseudo-Cushing’s syndrome

Question 28

A 36-year-old woman presents to the GP with weight gain and low mood. She has a history of rheumatoid arthritis, diagnosed 3 years ago, and this has been well controlled with methotrexate and prednisolone. On examination, she has central obesity, proximal muscle weakness and purple abdominal striae. Thyroid function is normal and other routine blood tests are unremarkable. Pregnancy test is negative. What is the best next step in the management of this patient and why isn't it organising low and high dose dexamethasone suppression tests?

Answer 28

Wean prednisolone therapy = Patient presents with crushing syndrome with the most likely cause, steroids. Therefore, you have to wear them off her Organising low and high dose dexamethasone suppression tests would be unhelpful given that this patient is already on long-term steroid therapy and therefore further steroid to suppress cortisol levels will not give us additional information

Question 29

What are Low-dose dexamethasone and high-dose dexamethasone used for?

Answer 29

1. Used to diagnose Cushing’s syndrome 2. Used to differentiate between the causes of Cushing’s syndrome. It differentiates between a pituitary adenoma and an ectopic ACTH-producing tumor

Question 30

How does cortisol production respond to high-dose dexamethasone in Cushing’s disease (pituitary adenoma)?

Answer 30

Cortisol production is suppressed

Question 31

Where is crushing disease found

Answer 31

High dose dexamethasone - pituitary adenoma

Question 32

How does cortisol production respond to high-dose dexamethasone in Cushing’s syndrome due to an ectopic ACTH-producing tumor? (eg, small cell)

Answer 32

Cortisol production is not suppressed

Question 33

Why is cortisol not suppressed by high-dose dexamethasone in ectopic ACTH-producing tumors?

Answer 33

The ectopic tumor is not responsive to negative feedback from dexamethasone

Question 34

A patient develops red cheeks, a round face, hypertension, anxiety, easy bruising, fatigue, central obesity and amenorrhoea after being on a long-term medication. What medication may have caused this? and what disease is this describing?

Answer 34

Prednisolone = Crushing's syndrome

Question 34

Why is cortisol suppressed by high-dose dexamethasone in Cushing’s disease?

Answer 34

The pituitary tumor is still sensitive to the feedback from dexamethasone

Question 35

What is the purpose of the low-dose dexamethasone suppression test (LDDST)?

Answer 35

Screen for Cushing’s syndrome. If cortisol is not suppressed, Cushing’s syndrome is likely

Question 36

How does the high-dose dexamethasone suppression test (HDDST) help differentiate causes of Cushing’s syndrome?

Answer 36

(1) Suppression of cortisol suggests Cushing’s disease (pituitary adenoma) (2) No suppression suggests ectopic ACTH production (eg, small cell lung cancer) or an adrenal tumour

Question 37

A patient undergoes a high-dose dexamethasone suppression test (8mg overnight). Their cortisol levels are: Before dexamethasone: 600 nmol/L After dexamethasone: 150 nmol/L (75% suppression) What is the most likely diagnosis?

Answer 37

Cushing’s disease (pituitary adenoma) = cortisol suppression (>50%) suggests a pituitary source

Question 38

A 37-year-old man presents with unexplained weight gain over the last 6 months as well as low energy and irritability over the last 1 month. On physical examination, the patient has significant truncal obesity, a rounded face, a dorso-cervical hump as well as abdominal striation. What is the most common endogenous cause of this clinical presentation? and why isn't it steroid use?

Answer 38

Pituitary adenoma = crushing disease steroid use is exogenous (originating outside the body)

Question 39

You review a 52-year-old man who is being investigated for weight gain, impotence and hypertension. On examination, you recorded a blood pressure of 180/110 mmHg and noticed purple striae around his abdomen. He also has some difficulty getting up from a chair and you observe generalised decreased muscle strength. Routine bloods are ordered. Given the likely underlying diagnosis, what are the urea and electrolytes most likely to show?

Answer 39

Hypokalaemic metabolic alkalosis

Question 40

In a patient with Cushing's disease, how would the high-dose dexamethasone suppression test appear if bitemporal hemianopia is present?

Answer 40

If bitemporal hemianopia is present, both ACTH and cortisol would be suppressed with high-dose dexamethasone The bitemporal hemianopia is a sign of a pituitary tumour pressing on the optic chiasm, which can cause visual disturbances = always leading to decrease ACTH levels