Endocrine: Cushing Syndrome

Question 1

what is Cushing syndrome?

Answer 1

clinical manifestation of pathological hypercortisolism (excess levels of cortisol) from any cause

Question 2

what three groups can hypercortisolism be classified into?

Answer 2

1. ACTH-dependent.
2. ACTH-independent.
3. Exogenous.

Question 3

what causes ACTH-dependent hypercortisolism?

Answer 3

Caused by conditions that have high or inappropriately normal ACTH levels stimulating adrenal cortisol overproduction e.g. ACTH-secreting tumours.

Question 4

what causes ACTH-independent hypercortisolism?

Answer 4

caused by excessive cortisol secretion by the adrenal glands despite a suppressed ACTH level.

Question 5

what is Exogenous hypercortisolism?

Answer 5

Patients taking exogenous corticosteroids for any reason may develop features of Cushing syndrome.

Question 6

what is ACTH?

Answer 6

adrenocorticotrophic hormone

Question 7

which hormone stimulates the adrenal cortex to produce cortisol?

Answer 7

adrenocorticotrophic hormone (ACTH)

nb: too much ACTH - too much cortisol (Cushing’s syndrome)

Question 8

what are some risk factors for Cushing’s syndrome?

Answer 8

• exogenous corticosteroid use
• pituitary adenoma (producing ACTH)
• Adrenal adenoma or carcinoma (producing cortisol - subclinical Cushing syndrome)

Question 9

what hormone does the hypothalamus secret which acts on the anterior pituitary gland to produce ACTH?

Answer 9

corticotrophin releasing hormone

NB: Patients who use any dose of exogenous glucocorticoid can stimulate the production of ACTH (and thus cortisol) more = Cushing’s syndrome

Question 10

what are some symptoms of Cushing’s syndrome?

Answer 10

• weight gain
• change of appearance
• depression
• insomnia
• amenorrhoea/ oligomenorrhoea
• poor libido
• easy bruising
• hair growth
• acne
• muscular weakness
• growth arrest in children
• backpain
• polyuria
• polydipsia
• psychosis

Question 11

what are some signs of Cushing’s syndrome?

Answer 11

• moon face
• skin infection
• acne
• bruising
• hypertension
• osteoporosis/pathological fractures
• ‘buffalo hump’
• central obesity
• proximal myopathy

Question 12

which conditions present in a similar way to Cushing’s syndrome?

Answer 12

Obesity.
Metabolic syndrome.

nb: both usually lack facial plethora, unexplained bruising and proximal muscle weakness

Question 13

what investigations would you conduct to confirm a diagnosis of Cushing’s syndrome?

Answer 13

• late night salivary cortisol. result: elevated.
• 1mg overnight dexamethasone suppression test. Result: morning cortisol >50 nanomol/L (>1.8 micrograms/dL).
• 24-hour urinary free cortisol: Result: >50 micrograms/24 hour.

Question 14

what is the late night salivary cortisol test?

Answer 14

• saliva sample collected between 11pm/midnight

- two swabs should be taken to improve sensitivity

Question 15

what is the 1mg overnight dexamethasone suppression test?

Answer 15

Patient is given 1 mg of dexamethasone at 11 p.m., and a plasma cortisol level is obtained the following morning at 8 a.m.

Question 16

why should a serum glucose investigation be considered in a patient with suspected Cushing syndrome?

Answer 16

Cushing syndrome commonly leads to diabetes and glucose intolerance.

Result: elevated

Question 17

what is the treatment for Cushing syndrome?

Answer 17

find the cause then treat accordingly:

• ACTH tumour (resect)
• Stop taking corticosteroids
• If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the patient replacement steroid hormones for life.

Question 18

In a patient with hypercortisolism, drug therapy is important for normalising cortisol levels whilst awaiting surgery - what drugs would you use?

Answer 18

Metyrapone, ketoconazole and mitotane can all be used to lower cortisol levels by directly inhibiting synthesis and secretion in the adrenal gland – only short acting