Cushing’s Syndrome

Question 1

What is Cushings Syndrome?

Answer 1

Cushing’s is a syndrome caused by over secretion of cortisol. It can be split into two main groups, ACTH independent (Primary) or ACTH dependant (Secondary). As cortisol is a corticosteroid the presentation is similar to that of the complication of long term steroid use.

Cortisol - Causes the production of glucose in the liver and increases metabolism of muscle and fat. Cortisol also helps the body regulate its response to stress. It decreases inflammation and decreases the immune system response.

Question 2

What are the causes of Cushings Syndrome?

Answer 2

Common – Exogenous steroid use, Cushing’s Disease (ACTH secreting pituitary adenoma)

Other - Ectopic ACTH secretion (Small cell lung cancer or bronchial carcinoma), Adrenal Adenoma

Question 3

What will you find on history taking of Cushings Syndrome?

Answer 3

Symptoms:
Hypertension (especially in younger people or treatment resistant hypertension)
Diabetes
Weight gain with central obesity
Osteoporosis (Fractures)
Menstrual irregularities/ Loss of libido/ Hirsutism (hair growth, deep voice)
Proximal muscle weakness
Thin skin/Easy Bruising
Physical Stigmata of Cushing’s - Moon face, Supraclavicular Fat pad, Buffalo Hump, Purple striae (caused by weight gain causing severe stretch marks)
Hyperpigmentation – Only if cause is increased secondary

Risk Factors:
Female

Specific Questions to ask about:
Make sure to exclude Exogenous corticosteroid use
Symptoms of underlying pituitary adenoma – Headache, bitemporal hemianopia, other pituitary hormones affected
Ask about lung cancer symptoms – Weight loss, cough, lethargy, haemoptysis

Differentials:
Obesity/Metabolic Syndrome - Lack of any other features of the disease
Pseudo-Cushing’s Syndrome – Same presentation as Cushing’s, but no Hypo-pituitary-adrenal axis changes. Can be caused by depression or alcoholism

Question 4

What will you find on examanination of Cushings Syndrome?

Answer 4

End of the bed:
Generalised Bruising without obvious trauma
Hands:
Progressive proximal muscle weakness
Hypertension
Face:
Moon Face 
Red Discolouration
Chest:
Supraclavicular fat pad
Buffalo Hump 
Abdomen:
Purple striae
Legs:
Progressive proximal muscle weakness

Question 5

What investigations will you order in Cushings Syndrome?

Answer 5

Bedside:
Pregnancy test – To rule out pregnancy as cause for weight gain and central adiposity

Bloods:
Glucose - Cushing’s commonly causes diabetes
FBC – Some Cushing’s will have a raised WCC
U&E – To look for any electrolyte abnormality’s (E.g. Cross reaction of cortisol at Aldosterone receptors causes Na+ exchange for K+ in the kidneys causing Hypokalaemia). If ectopic secretion from lung cancer is suspected will show any metastasise to the kidney
LFT - If ectopic secretion from lung cancer is suspected will show any metastasise to the liver
Ca2+ - Looking for a cancer if indicated
ACTH Levels – If ACTH levels are low it indicates Primary/ACTH Independent Cushing’s. However, if levels are normal or high a dexamethasone suppression test is required to differentiate between pituitary release of ACTH or ectopic release of ACTH.
ABG – Metabolic acidosis can be caused by the hypokalaemia

Imaging:
CXR – Looking for Heart Failure (Caused by long term hypertension) or to look for lung cancer
MRI pituitary gland/hypothalamus - Cushing’s disease bilateral adrenal hyperplasia
CT chest/abdo/pelvis – Looking ectopic ACTH secretion

Special Tests:
Late-night salivary cortisol - First line diagnostic test, taken between 11pm and 1am when levels should be lowest. If raised it indicates loss of diurnal variation, so order 24-hour urinary cortisol levels
24-hour urinary cortisol levels – Raised Free cortisol levels on 2 occasions is diagnostic.

Dexamethasone suppression test - Give dexamethasone (a cortisol analogue) at night and tests cortisol in the morning, which should have fallen. In a positive test the dexamethasone levels have no effect on serum cortisol levels (This is diagnostic of Cushing’s).
A high dose dexamethasone suppression test can be done if a secondary cause of Cushing’s is suspected – With very high doses of dexamethasone, the pituitary gland will reduce ACTH output, reducing cortisol levels by 50% in 48 hours (even though the pituitary is abnormally secreting ACTH and low doses had no effect), ectopic production will not be affected whatsoever.

Question 6

What is the treatment of Cushings Syndrome?

Answer 6

Medical:
Metyrapone (Glucocorticoid receptor antagonist) - Used in lead up to surgery or when surgery is contraindicated

Surgical:
Pituitary Adenoma - Trans sphenoidal pituitary adenectomy, radiotherapy can be used post operatively in non-curative or relapsing cases
Adrenal Adenoma - Adrenalectomy
Adrenal Carcinoma – Often palliative care required
Ectopic Production - Resection of tumour or adrenalectomy if resection of ectopic tumour not possible (As ectopic ACTH cannot cause problems if there is no adrenal gland)
After surgery patients may require hormone replacement therapy for other hormones affected e.g. Pituitary or adrenal hormones