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17 Cards in this Set
- Front
- Back
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Three classes of corticosteroids produced by adrenals |
Mineralocorticoids Glucocorticoids Adrenal androgen precussors(Dihydroepiandrosterone) |
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What are some triggers for CRH release by the hypothalamus |
Physical stress Emotional Fever Hypoglycemia Hypotension |
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Circadian pattern of CRH and ACTH release |
Starts to rise early in the morning hours peaks around 8:30 am and low levels in the evening with a nadir at 12 midnight |
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Action of dexamethasone |
Potent synthetic glucocorticoid which suppresses CRH/ACTH by binding HP glucocorticoids receptors leading to down regulation of endogenous cortisol synthesis |
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Action of cortisol |
Increases glucose output by the liver and decreases intake by muscles and adipose Reduces insulin sensitivity Decreases immune activity Negative feedback of ACTH Increase alpha one receptor production and sensitivity to catecholamines |
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What is Cushing's syndrome |
A constellation of clinical features that results from chronic exposure to excess glucocorticoids of any etiology |
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Cushing's disease |
Refers to Cushings syndrome caused by pituitary corticotrope adenoma |
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Most common cause of Cushing's syndrome |
Medical use of glucocorticoids for immunosuppression or for treatment of inflammatory disorders |
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What gene mutation leads to Cushings disease |
Deubiquitinase USP8 |
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Types of ectopic ACTH |
Bronchial or pancreatic carcinoid tumors Small cell lung cancer Medullary thyroid carcinoma Pheochromocytoma |
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ACTH independent causes of Cushing's |
Adrenocortical adenoma Adrenocortical carcinoma Macronodular adrenal hyperplasia Primary pigmented nodular adrenal disease McCune-Albright Syndrome |
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Clinical manifestations |
Facial plethora Thin brittle skin Easy bruising Hirsutism, stretch marks, acne Central obesity Weight gain Rounded face Fat pad on neck Muscle atrophy and weakness Osteopenia, osteoporosis, decrease in linear growth Irritability, depression, emotional lability Hypertension, hypokalemia, edema, atherosclerosis Increased susceptibility to infections, increased WBC, hypercoagulation increasing risk of DVT and PE Glucose intolerance or diabetes Dyslipidemia Decreased libido, amenorrhoea, Hypothyroidism |
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What are the more specific features of Cushings |
Fragility of skin Easy bruising and broad >1cm purish striae Signs if proximal myopathy |
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Tests used to screen or confirm Cushings |
24 hour urinary free cortisol excretion increased above 3 times normal Dexamethasone overnight test(plasma cortisol >50nmol/L at 8-9am after 1mg Dexa at 11pm) Midnight plasma cortisol >130nmol/L Further: Low dose Dex test(plasma cortisol >50nmol after 0.5mg dexa q6h for 2 days) |
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Factors that can affect confirmation tests |
Incomplete 24 hr urine collection Concurrent intake of CYP3A4 inducing drugs. such as antiepileptics rifampicin Concurrent OCP use raising CBG thus increasing total cholesterol Pseudocushings syndrome Cyclic Cushings |
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What is high dose Dexamethasone test |
Cortisol suppression >50% after q6h 2mg dexam for 2 days |
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Drugs used in treatment of Cushings |
Mitotane Ketoconazole Metyrapone |
