| What is Cushing's syndrome? | Symptoms and signs associated with prolonged exposure to high cortisol, including all causes of high cortisol (endogenous and exogenous)
Iatrogenic Cushing's is common (long term cortisol therapy), endogenous Cushing's include (Adrenal adenoma, pituitary or ectopic)
Cushing's disease is pituitary dependent Cushing's syndrome (rare, 5-6/million, more common in women [in addition to adrenal adenomas])
Ectopic ACTH like bronchogenic carcinoma (more common in men) |
| What are the clinical features of Cushing's syndrome? | Weight gain, menstrual irregularity, hirsutism, psychiatric dysfunction (psychosis), HTN, diabetes, osteoporosis, moon face, plethora, red-puprle striae, bruising, ankle edema |
| What are the comorbidities associated with Cushing's? | Infections (reactivated TB, fungal infections, wound infections and poor wound healing)
Metabolic features (glucose intolerance -->overt DM, increased TGs and cholesterol, hypokalemic alkalosis, cortisol swamps in kidney HSD11B2 acted from cortisol as aldosterone, supressed LH, FSH, TSH, GH)
Eye (raised intraocular pressure, exophthalmos (increased retrorbital fat), cataracts |
| What are the classifications of causes of Cushing's? | ACTH-dependent (pituitary dependent, ectopic ACTH, Ectopic CRH, macronodular adrenal hyperplasia, iatrogenic (tx with 1-24 ACTH)
ACTH independent (Adrenal adenoma and carcinoma, primary pigmented nodular adrenal hyperplasia and Carney's syndrome, MacCune-Albright, aberrant receptor expression, iatrogenic cortisol)
Pseudo Cushing's (alcoholism, depression and obesity) |
| What is pituitary ACTH disease? | 70% of Cushing's, pituitary adenoma, majority is pituitary microadenomas (<1cm), larger macroadenomas may occur and be invasive in 10% of cases. |
| What is ectopic ACTH syndrome? | 15% of Cushing's, occurs in highly malignant tumors like small cell carcinoma, indolent cases (neuroendocrine tumors) |
| What is ectopic CRH syndrome? | Very rare, bronchail carcinoid, medullary thyroid or prostate carcinoma producing CRH. |
| What is macronodular adrenal hyperplasia? | 10-40% of pt with Cushing's, bilateral hyperplasia with one or more nodules, older patients and symptoms for a longer time, caused by long standing stimulation by ACTH -->autonomous adrenal adenoma) thus become hypersensitive for ACTH, where it becomes relatively low. |
| What is cortisol-secreting adrenal adenoma and carcinoma? | Adenoma 10% of Cushing's carcinoma less than 5%.
more common in peds (65% of children with Cushing's)
rapid onset in carcinoma and gradual in adenoma, in carcinoma may produce aldosterone or androgens as well, female causes hirsutism and virilization
May be subclinical (incidentaloma) 10% of cases. |
| What is primary pigmented nodular adrenal hyperplasia? | bilateral small pigmented adrenal nodules, 2-4mm, present younger than 30 yrs part of Carney's |
| What is Carney's complex? | Familial autodominant PKA mutation, causes pigmented nodules, cardiac myxoma, skin myxoma, lentiginosis, testicular and breast duct adenomas. |
| What is cyclic Cushing's syndrome? | periods of excess cortisol and periods of normal cortisol, mostly ACTH dependent |
| What is pseudo-Cushing's? | Some or all clinical features of Cushing's, resolution of underlying cause results in disappearance of the features |
| What is alcohol Cushing's? | Chronic liver disease causes impaired cortisol metabolism so increased cortisol secretion rate |
| What is depression Cushing's? | When cause of Cushing's in unknown, can be correlated with a psychiatric issue. |
| What is obesity Cushing's? | Mildly increased cortisol secretion rate, increased peripheral metabolism and cortisol clearance lead to activated HPA axis/ |
| What is iatrogenic Cushing's? | depends on dose of corticosteroid given, ACTH rarely prescribed but if long term can cause cushingoid features |
| How is the screening for Cushing's? | midnight serum or salivary cortisol, 24-hour urine cortisol or low-dose dexamethasone supression 1mg at 11pm then get cortisol at 1 am |
