Cushing's Syndrome Flashcards
D?
Clinical syndrome of hypercortisolism, resulting from exogenous corticosteroid use or over-secretion of cortisol.
RF?
• Exogenous corticosteroid use
• Pituitary adenoma
Adrenal adenoma/carcinoma
DDx?
- Obesity
* Metabolic syndrome
Epidemiology?
Age: 20-50
Sex: Women 4:1
Ethnicity:
Prevalence:
Aetiology?
- Prolonged glucocorticoid therapy
- Primary-Overproduction of cortisol by the adrenal gland
- Eg
- Adrenal adenoma
- Adrenal carcinoma
- Macronodular adrenal hyperplasia
• Secondary-excess ACTH production
• Eg
• Cushing’s disease-pituitary adenoma secreting excess ACTH
• Paraneoplastic syndrome-ectopic ACTH production
○ Eg-small cell lung cancer and renal cell carcinoma
CP?
- Thin bruisable skin with purple abdominal striae
- Delayed wound healing
- Flushing of face
- Hirsutism
- Acne
- Hyperpigmentation-secondary
- Lethargy, depression, sleep disturbance and psychosis
- Osteopenia, osteoporosis, fractures, avascular necrosis of femoral head
- Insulin resistance
- Dyslipidaemia
- Central obesity, moon face, buffalo hump
- Low libido, irregular cycles
- Secondary HT
- Infections
- PUD
- Cataracts
CP steroid use?
• “CUSHINGOID” is the acronym for side effects ofcorticosteroids:C=Cataracts,U=Ulcers,S=Striae/Skinthinning,H=Hypertension/Hirsutism/Hyperglycemia,I= Infections,N=Necrosis(of femoralhead),G= Glucoseelevation,O=Osteoporosis/Obesity,I=Immunosuppression,D= Depression/Diabetes
Pathophysiology?
- Hypothalamus secretes CRH and stimulates pituitary gland to make ACTH, whcih travels to the adrenal cortex and stimulates cortisol synthesis in the zona fasciculata
- Cortisol/glucocorticoids are not soluble in water and are bound to cortisol-binding globulin and only a small fraction is free and biologically active
- Excess is filtered in the urine
- Free cortisol-circadian rhythm and increases gluconeogenesis, proteolysis and lipolysis in times of stress and sensitivity to catecholamines in BV/BP regulation, dampens inflammatory response
- Influences mood and memory
- NF mechanism of regulation
- Cushings-constantly high so exaggerated effects
Effects
• Proteolysis-atrophy and osteoporosis
• Elevated glucose-high insulin-activates LPL-accumulates more fat molecules in centre of body-central obesity
• HT-amplified catecholamine effect and cross reacts with mineralocorticoid receptors
• Inhibits GRH-disrupts fertility
• Dampens inflammatory response
• Impaired brain function
Causes
• Exogenous steroids
• Molecular structure of exogenous corticosteroids is so similar to cortisol that it mimics it and causes NF and atrophy of adrenal glands
• Endogenous
• Adrenal adenomas/carcinomas-cells in ZF divide abnormally ad secrete excess cortisol-NF suppresses CRH and ACTH-normal adrenal gland shrinks
• Pituitary adenoma-benign tumour of gland-cells don’t mets-grows in size and oversecretes ACTH-overstimulates ZF-excess cortisol
• Ectopic ACTH-somewhere else-no NF
I-first line?
Exam, Pregnancy test
• Serum glucose
• Late-night salivary cortisol
• Overnight dexamethasone suppression test
• 24-hr urinary free cortisol
• 48 hr 2mg dexamethasone suppression test
I-second line?
- DHEAS
- ACTH
- High-dose dexamethasone suppression test
- MRI, CT, PET octreotide
M-primary first line?
• Stop treatment
• Unilateral/bilateral adrenalectomy or resection or
Therapy-chemo/radio, CS replacement
M-second line?
- Medical therapy
* Chemo/radiotherapy
M-s-first line?
- Transsphenoidal pituitary adenectomy
- Therapy
- A somatostatin analogue (pasireotide), steroidogenesis inhibitor, or glucocorticoid receptor antagonist (mifepristone) is occasionally used for mild hypercortisolism, or short term for severe hypercortisolism, before other therapies are undertaken.
- Hormone replacement therapy
M-s-second line?
repeat or medical therapy alone
M-s-third line?
- Pituitary radiotherapy
- Medical therapy
- Hormone replacement therapy
