Cushing's disease and syndrome Flashcards
What is Cushing’s syndrome?
general term referring to chronic excessive and inappropriate elevated levels of circulating CORTISOL whatever the cause
What is Cushing’s disease?
specifically refers to:
bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma
Where is cortisol secreted.
zona fasciculata (middle) of adrenal cortex
what are the functions of cortisol?
- ↑ carb + protein catabolism (breakdown)
- ↑ deposition of fat + glycogen
- Na+ retention
- ↑ renal K+ loss
- Diminished host response to infection
Explain the pattern in which cortisol is released?
Since CRH is released according to circadian rhythm and in response to stress:
- highest levels in morning
- lowest at midnight
What type of hormone is cortisol
glucocorticoid
What can the causes be divided into?
ACTH dependent
ACTH independent
What are ACTH dependent causes
- Cushings disease
2. Ectopic ACTH production - small cell lung cancer, carcinoid tumours
What are ACTH independent causes?
- Iatrogenic - administration of a glucocorticoid e.g. pred
2. Adrenal adenoma/carcinoma
Explain pathophysiology behind ACTH dependent causing Cushings
XS ACTH stimulates XS cortisol release
Explain pathophysiology behind ACTH independent causing Cushings
neoplasms in adrenals stimulate zona fasciscularis to release more cortisol
OR
ingesting XS glucocorticoid itself
What are the sx?
Obese
Mood: depression, lethargy, irritability, psychosis
Proximal weakness - muscle atrophy
Gonadal dysfunction - irregular periods + ED
Acne
Recurrent Achilles tendon rupture
What are the signs?
Central obesity Plethoric Moon face Buffalo hump - fat pad on back Skin + muscle atrophy Abdo striae Osteoporosis HTN Hyperglycaemia Inf prone
What causes muscle and skin atrophy?
protein catabolic effects of cortisol
what investigations would u do to confirm Cushing’s syndrome?
- Overnight dexamethasone suppression test - 1mg at 00:00, measure serum cortisol at 8am. Normal - suppression <50nmol/L, Cushing’s S - no suppression
- 24hr urine free cortisol - normal <280nmol/24hr
What tests would u do to localise the source of Cushings? How would u interpret the results?
Measure plasma ACTH
If ACTH is undetectable - adrenal tumour (ACTH independent cause)
If ACTH detectable - distinguish pituitary cause from ectopic ACTH + do high dose suppression test or CRH test
How wold u interpret CRH stimulation test?
If there is a pituitary source - cortisol rises - Cushing’s disease
If ectopic/adrenal - no change
What is the treatment of iatrogenic Cushings syndrome?
stop steroids!
What is rx of Cushings w adrenal cause?
- Adenoma - adrenalectomy
2. Carcinoma - radiotherapy + adrenolytic drug (mitotane)
What is rx of Cushings due to ectopic ACTH
Surgery
Drugs inhibiting cortisone synthesis - metyrapone, ketoconazole, fluconazole
What is the rx of Cushing’s disease?
selective removal of pituitary adenoma
if cant find pituitary source - bilateral adrenalectomy
What is a complication of a bilateral adrenalectomy? How is it treated?
Nelsons syndrome:
Increase skin pigmentation due to significantly increased ACTH from an enlarging pituitary tumour as the adrenalectomy will remove the negative feedback
rx: radiotherapy to pituitary
What is the major cause of mortality in pts w Cushing’s syndrome?
CVD
What are complications?
CVD
HTN
DM
Osteoporosis
Why does Cushings increase risk of osteoporosis?
Glucocorticoids cause decreased osteoblast activity and increased osteoclast activity - DO PERIODIC BONE ASSESSMENTS
