Crushing Syndrome/ disease Flashcards
Adrenal Disorder
What is Cushing’s syndrome
Cushing’s syndrome is the condition resulting from increased free circulating glucocorticoids (cortisol), regardless of the cause
What is Cushing’s disease?
Cushing’s disease is when the increased cortisol levels are caused by a functioning pituitary adenoma (ACTH-secreting)
What is the most common cause of cortisol excess?
Iatrogenic
(exogenous steroids)
What is the difference between Cushing’s disease and Cushing’s syndrome?
Cushing’s disease is due to a pituitary adenoma, while Cushing’s syndrome includes all causes of cortisol excess
What are the ACTH-dependent causes of Cushing’s?
(1) Pituitary adenoma
(Cushing’s disease)
(2) Ectopic ACTH
(small cell lung cancer)
(3) Ectopic CRH
What are the ACTH-independent causes of Cushing’s? - Exogenous steroids
(1) Adrenal adenoma or carcinoma
(2) Adrenal cortical nodular hyperplasia
(3) False positive (pseudocushings)
= severe depression + severe alcoholism
What are key clinical features of Cushing’s?
- Moon face
- Buffalo hump
- Central obesity
- Striae
- Hypertension
- Thin skin
- Osteoporosis
- Diabetes
What test confirms cortisol excess?
= crushing syndrome
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
What is the first-line diagnostic test for Cushing syndrome?
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
How do you interpret the Dexamethasone suppression test results? low, high
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).
What test differentiates ACTH-dependent from ACTH-independent Cushing’s?
Serum ACTH levels
(1) Low ACTH
= Adrenal adenoma/carcinoma, exogenous steroids = independent
(2) High ACTH
= Cushing’s disease or ectopic ACTH = dependent
What is the first-line treatment for Cushing’s disease?
Transsphenoidal hypophysectomy (pituitary surgery)
What imaging is used based on ACTH levels?
Low ACTH → Adrenal CT/MRI
= ACTH-independent Cushing’s syndrome
High ACTH → Pituitary MRI + biochemical tests
= ACTH-dependent Cushing’s syndrome
What is the treatment for adrenal adenoma causing Cushing’s?
Adrenalectomy
= removal of the adrenal gland
How is ectopic ACTH treated?
(1) Remove the source (eg, carcinoma)
(2) Bilateral adrenalectomy if not surgically feasible.
What drugs control cortisol excess if surgery fails?
- Metyrapone
- Ketoconazole
- Pasireotide
What is the first step if Cushing’s is due to exogenous steroids?
Reduce steroid dose gradually
How is cortisol excess established?
(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)
What is the first line treatment for Cushing’s disease in the majority of cases?
Trans-sphenoidal surgery
How is an overnight dexamethasone suppression test performed?
1mg oral Dexamethasone taken at midnight followed by a 9am cortisol blood test
What is the common type of lung malignancy that gives rise to Cushing’s syndrome?
Small cell lung cancer
What is the name given to pituitary driven ACTH excess?
Cushing’s disease
What is the name given to the type of leg weakness that makes going up and down stairs difficult?
Proximal myopathy
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?
Low dose dexamethasone suppression test
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?
Oral corticosteroids
= Exogenous
When would the answer be Nelsons Syndrome in regards to crushing syndrome
When a bilateral adrenalectomy has been mentioned
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?
Chronic alcoholism
= This is a case of pseudo-Cushing’s syndrome
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?
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
What are Low-dose dexamethasone and high-dose dexamethasone used for?
- Used to diagnose Cushing’s syndrome
- Used to differentiate between the causes of Cushing’s syndrome. It differentiates between a pituitary adenoma and an ectopic ACTH-producing tumor
How does cortisol production respond to high-dose dexamethasone in Cushing’s disease (pituitary adenoma)?
Cortisol production is suppressed
Where is crushing disease found
High dose dexamethasone - pituitary adenoma
How does cortisol production respond to high-dose dexamethasone in Cushing’s syndrome due to an ectopic ACTH-producing tumor? (eg, small cell)
Cortisol production is not suppressed
Why is cortisol not suppressed by high-dose dexamethasone in ectopic ACTH-producing tumors?
The ectopic tumor is not responsive to negative feedback from dexamethasone
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?
Prednisolone
= Crushing’s syndrome
Why is cortisol suppressed by high-dose dexamethasone in Cushing’s disease?
The pituitary tumor is still sensitive to the feedback from dexamethasone
What is the purpose of the low-dose dexamethasone suppression test (LDDST)?
Screen for Cushing’s syndrome. If cortisol is not suppressed, Cushing’s syndrome is likely
How does the high-dose dexamethasone suppression test (HDDST) help differentiate causes of Cushing’s syndrome?
(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
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?
Cushing’s disease (pituitary adenoma)
= cortisol suppression (>50%) suggests a pituitary source
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?
Pituitary adenoma
= crushing disease
steroid use is exogenous
(originating outside the body)
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?
Hypokalaemic metabolic alkalosis
In a patient with Cushing’s disease, how would the high-dose dexamethasone suppression test appear if bitemporal hemianopia is present?
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
