Cushings Syndrome

Question 1

what is the def of CS

Answer 1

chronic inappropriate elevation of free circulating cortisol

Question 2

what is the aetiology of CS

Answer 2

1. ACTH dependent (80%)
   - excess ACTH from a pituitary adenoma (Cushings disease) (80%)
   - ACTH secreted from ectopic source (small-cell lung carcinoma, pulmonary carcinoid tumours) (20%)
2. ACTH independent (20%)
   - excess cortisol from benign adrenal adenoma (60%)
   - excess cortisol from adrena carcinoma (40%)

Question 3

what is the epi of CS

Answer 3

rare
endogenous CS more common in females
20-40yrs peak incidence

Question 4

history of CS

Answer 4

increasing weight & fatigue
muscle weakness & myalgia
thin skin
easy bruising

hirsutism, acne, oligo/amenorrhoea, depression

Question 5

examination findings in CS

Answer 5

facial fullness, facial plethora (redness), interscapular fat pad
proximal muscle weakness
thin skin
bruising
central obesity
pink/purple striae on abdomen, breast, thighs
HTN
ankle oedema due to salt & water retention as a result of mineralocorticoid effect of excess cortisol
pigmentation in ACTH depedent cases

Question 6

what investigations would be performed in suspected CS

Answer 6

bloods
-non-specific changes such as low K (esp. in ectopic Cushings) & high glucose
initial high-sensitivity tests:
1 urinary free cortisol
2 late-night salivary cortisol
3 overnight dexamethasone suppression test
4 low dose dexmethasone suppression test
- in CS, 48h after first dose of dexamethasone fails to suppress cortisol below 50nmol/l
tests to determine underlying cause
1 ACTH-independent (adrenal adenoma/carcinoma)
-low plasma ACTH
-CT/MRI of adrenals
2 ACTH dependent (pituitary adenoma)
-high plasma ACTH
-pituitary MRI
3 ACTH depedent (ectopic)
-if lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT scan
-radiolabelled octreotide to detect carcinoid tumours as they express somatostatin receptors

Question 7

what is the management for iatrogenic CS

Answer 7

discontinue administration
lower steroid dose
use of an alternative steroid sparing agent if possible

Question 8

what is the management for CS

Answer 8

medical
-pre-operatively/if unfit for surgery
-inhibit cortisol synthesis with metyrapone/ketoconazole
surgical
-pituitary adenomas - resection
-adrenal adenoma/carcinoma - resection plus mitotane for carcinoma
-ectopic ACTH production - treatment directed at tumour
radiotherapy
-in those not cured
-in those with persistant hypercortisolaemia after trans-sphenoidal resection of tumour

Question 9

what are the complications in CS

Answer 9

diabetes
osteoporosis
HTN
pre-disposition to infections
complications of surgery & radiotherapy (small increased risk of intracranial tumours/stroke)

Question 10

what is Nelson’s syndrome

Answer 10

may develop from bilateral adrenalectomy

locally aggressive pituitary tumour causing skin pigmentation due to excessive ACTH secretion

Question 11

what is the prognosis in CS

Answer 11

5yr survival is 50% if untreated

depression often persists for many years after treatment