cushing's syndrome

Question 1

definition

Answer 1

cushing’s syndrome = hypercortisolism
cushing’s disease = hypercortisolism due to ACTH secreting pituitary adenoma (most common cause of endogenous cushing’s syndrome)

Question 2

aetiology

Answer 2

can be exogenous or endogenous
exogenous is the most common cause

exogenous: by corticosteroid exposure, e.g. drugs
endogenous: by something within the pituitary-adrenal axis (e.g. pituitary adenomas, adrenal adenomas)

also can be caused by ectopic ACTH secretion from neuroendocrine tumours

can be classified as ACTH-dependent or ACTH-independent cushing’s

Question 3

signs and symptoms

Answer 3

• facial plethora
• violaceous striae
• menstrual irregularities
• linear growth deceleration in children
• hypertension
• glucose intolerance or DM
• premature osteoporosis / unexplained fractures
• weight gain / central obesity
• acne
• psychiatric symptoms (depression, anxiety mood changes)
• decreased libido
• easy bruisability
• proximal myopathy (weakness)
• facial rounding
• “camel pads” (dorsocervical fat pads)
• unexplained nephrolithiasis (renal stones)
• hirsutism

Question 4

risk factors

Answer 4

• exogenous corticosteroid use
• pituitary adenoma
• adrenal adenoma
• adrenal carcinoma
• neuroendrocrine tumours
• thoracic or bronchogenic carcinoma, especially SCLC (ectopic ACTH syndrome)

Question 5

investigations

Answer 5

1st investigations:

• urine pregnancy test (rule out pregnancy as a cause!!)
• serum glucose
• late night salivary cortisol
• 24hr urinary free cortisol
• 1mg overnight dexamethasone suppression test (to confirm diagnosis of cushing’s)
• 48hr 2mg dexamethasone suppression test

others:

• plasma DHEAS level (if elevated then points to adrenal carcinoma)
• morning plasma ACTH (differentiate pituitary vs adrenal cause)
• high dose dexamethasone suppression test (differentiate pituitary vs adrenal cause)
• pituitary MRI
• adrenal CT
• inferior petrosal sinus sampling (to compare central vs peripheral ACTH levels to confirm pituitary and not ectopic ACTH production)
• CT chest, abdo pelvis (localise ectopic tumour)
• MRI chest (localise ectopic tumour)
• PET (localise ectopic tumour)
• octreotide scan (localise ectopic tumour)

Question 6

treatment

Answer 6

cushing’s disease:
1. transphenoidal pituitary adenomectomy
+ medical therapy before surgery to shrink adenoma: ketoconazole/metyrapone (steroidogenesis inhibitors)
+ post-surgery corticosteroid replacement: hydrocortisone
+ post-surgery non-corticosteroid pituitary hormone replacement: levothyroxine + testosterone transdermal/testosterone cipionate/estradiol/conjugated oestrogens/medroxyprogresterone + somatropin + desmopressin

2. medical therapy alone without surgical resection – metyrapone/ketoconazole
3. pituitary radiotherpay
4. bilateral adrenalectomy

ectopic ACTH or corticotrophin-releasing hormone syndrome:
1. surgical resection/ablation of tumour and mets
+ medical therapy (keto/metyr)
+ chemo/radiotherapy for primary tumour

ACTH-independent cushing’s due to adrenal adenoma/carcinoma/hyperplasia (just no chemo/radio in hyperplasia)
1. adrenalectomy or tumour resection
+ medical therapy before urgery (SAME AS BEFORE)
+ chemo/radio

Question 7

complications

Answer 7

• adrenal insufficiency after adrenal suppression treatment
• cardiovascular disease (due to hypertension, DM etc. associated with cushing’s, could also be to excess cortisol itself)
• hypertension
• DM
• osteoporosis
• nephrolitiasis
• nelson’s syndrome after bilateral adrenalectomy (develop macroadenomas that secrete ACTH due to the lack of feedback of steroid hormones after removal of adrenals)

treatment/surgery related:

• central hypothyroidism
• growth hormone deficiency
• adrenal insufficiency
• hypopituitarism
• hyponatraemia (complication of pituitary surgery) (due to development of SIADH)
• hypogonadism
• DI

Question 8

prognosis

Answer 8

usually really bad if left untreated, 50% in 5 years. mostly Cardiovascular causes