Cushing's

Question 1

How might a patient with Cushing’s present in PACES and how would you structure the station?

Answer 1

Typically station 2 or 5

Could be counselling station re: weaning off steroids and switching to other immunosuppression.

PC
- issues with weight gain
- issues managing blood sugars / complications from diabetes (i.e. peripheral neuropathy, may be an undiagnosed diabetes i.e. polyuria, polydipsia)
- bumping into things / issues with driving (i.e. field defect from tumour)
- symptoms of uncontrolled hypertension (headaches, visual problems - hypertensive retinopathy)
- change in facial appearance
- oligo/amenorrhoea
- muscle weakness
- easy bruising
- fatigue
- loss of libido
- acne/hirsutism
- depression/ other personality change
- symptoms of associated disease i.e. SOB in COPD or resp complication of autoimmune disease, joint problems in RA/SLE, Raynaud’s in systemic sclerosis, swallowing problems or indigestion
- atypical fracture

Established Cushing’s should be a spot diagnosis so history can then be focused to that after exploring the presenting complaint.

• History to cover above symptoms
• Differentiating from other functioning pituitary adenomas i.e. prolactinoma (lactation infertility, erectile dysfunction), acromegaly (large extremities, paraesthesia at extremities), TSH (symptoms of hyperthyroidism - weight loss, anxiety, tremor, impaired concentration, heat intolerance)
• Differentiating from phaeochromocytoma (if concern is hypertension - palpitations, anxiety, headaches, sweating)
• malignancy risk factors if history indicating Cushing’s syndrome (usually bronchial, SCLC, thymus, pancreatic neuroendocrine)

PMHx & DHx
- conditions for exogenous steroids

FHx
MEN 1 (patient may be jaundiced or have evidence of scar from pancreatic tumour resection/ neck from parathyroid) - could ask about symptoms of hypercalcaemia if this is the case

SHx
- Smoking/alcohol (risk factors associated with problems with Cushing’s, alcohol related to pseudo-Cushing’s)
- Impact on the patient, any driving concerns

Exam: (start with where the history has guided you/patient’s main concern)
- Visual fields if indicated from hx
- Offer fundoscopy
- Blood pressure
- Proximal myopathy
- Buffalo hump
- Skin folds for bruising
- Hands for joint deformity as part of condition requiring steroids
- Chest if indicated by HPC
- Abdo if IBD indicated from hx, also mouth for ulcers, red painful eye, jaundice

Question 2

What investigations would you do in a patient with suspected Cushing’s syndrome?

Answer 2

Bedside:
- BP if not already done (ideally ABPM/24h BP), Bloods checking electrolytes, BM, HbA1c, lipids, calcium and vit d for osteoporosis risk factors and management urine dip for glucose
- ECG for LVH (refer for echo)
- Check for effects of hypercortisolism on other major endocrine functions i.e. TSH

If strong suspicion for exogenous, generally we wouldn’t check for below.

Confirm hypercortisolism
- preferred is overnight dexamethasone suppression test
- can do 24h urinary cortisol but this is cumbersome for patient and ideally needs x2, can also use overnight saliva cortisol x2

+ second confirmatory test i.e. LDDST

Can also check ACTH at the offset or after confirming hypercortisolism (high = ACTH secreting tumour or ACTH pituitary adenoma; low = adrenal adenoma)

Locating the lesion:
- MRI pituitary fossa
- CT adrenal
- whole body CT

Bilateral inferior petrosal sinus sampling (gold standard for locating pituitary vs ectopic ACTH)

Question 3

How is an overnight dexamethasone suppression test carried out and how are the results interpreted?

Answer 3

1mg dex at 11pm

Cortisol measured at 9am

If <50 - normal suppression

Question 4

How is a low dose dexamethasone suppression test carried out and how are results interpreted?

Answer 4

8 doses of 0.5mg dexamethasone PO are given over 48h (9am, 3pm, 9pm, 3am, 9am, 3pm, 9pm, 3am)

ACTH and cortisol is measured at 9am (T=0) and again at 9am (T=48h)

Suppression <50 is normal suppression at 48h

Question 5

What is bilateral inferior petrosal sinus sampling and how are results interpreted?

Answer 5

Interventional radiological test

Sample blood from peripheral vein as well as both inferior petrosal sinuses pre and post desmopressin.

Inject desmopressin.

If IPS:P ACTH 2:1, confirms pituitary source of ACTH.

Question 6

What are important considerations pre-dexamethasone suppression testing?

Answer 6

Patients on enzyme inducing drugs can metabolise dexamethasone leading to false positives. Ideally patient should be off them, but this isn’t always possible.
i.e. anti-epileptics, St John’s Wort, rifampicin,

Oestrogens COCP, pregnancy, HRT can induce cortisol binding globulin - need to be off for 6 weeks pre-test

Question 7

What are the treatment options for Cushing’s?

Answer 7

Exogenous - weaning off steroids and switching to steroid sparing immunosuppression

Cushing’s syndrome
- surgical i.e. trans-sphenoidal approach for pituitary tumour
- adrenalectomy for adrenal tumour

Would need metyrapone pre-surgery to reduce hypercortisolism

Pituitary irradiation post surgery

Question 8

What is the prognosis of untreated Cushing’s syndrome?

Answer 8

50% mortality at 5 years due to accelerated ischaemic heart disease secondary to diabetes and hypertension.