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Cushings syndrome
1. CUSHINGS
GR EXCESS
• Cushing disease is caused by pituitary problem and cushing syndrome is caused by ectopic
acth
• cushings disease is seen in 2 to 3 in million
• cushings disease is more common in women
• ectopic acth is more common in men
CAUSES
• exogenous steroids as inhalants , injection , tablets , creams
• ritonavir decreases steroid clearance
clinical features ::
• obesity , plethora , moon face and hirsutism
• fat deposits seen on spine , supra clavicular fossa , temporal regions & epidural space
• menstrual irregularities
• loss of libido
• vellus hypertrichosis
• hypogonadotrophic hypogonadism
• agitated depression , lethargy , paranoia and overt psychosis
• osteoporotic vertbral collapse
• osteonecrosis of femoral and humeral heads
• renal caliculi
• skin thinning , liddle sign & easy bruising
• acne and papular lesions over face chest & back
• myopathy of lower limbs & shoulder girdle
• myopathy tested by crouching position
• hypertension
• reactivation of tb
• skin and nails fungal infections
• bowel perforation
• wound infections
• glucose intolerance
• increased cholesterol and triglyceride levels
• hypokalemic alkalosis(ectopic acth)
• decreased GH secretion
• increased intraocular pressure
PHYSIOLOGICAL HYPERCORTISOLISM WITH FEATURES OF CS
• pregnancy
• obesity
• psychological stress
• poorly controlled diabetes
• aloholism
CREATED BY -Dr.GOPALA KRISHNAM RAJU
@
D
r_gkr
2. CUSHINGS
PHYSIOLOGICAL HYPERCORTISOLISM WITHOUT FEATURES OF CS
• physical stress
• malnutrition
• intense chronic exercise
• hypothalamic amenorrhea
• high CBG
• GR resistance
classification
• ACTH dependant
• ACTH independent
ACTH dependant
• 70% cases are due to this
• ZF & ZR widening seen
• 85 to 90% cases are due to monoclonal pituitary adenoma
• basophil hyperplasia seen in 9 to 33 % cases
• majority of tumors are microadenomas and 10% are macroadenomas
• hallmark feature is resistant ACTH secretion to normal GR inhibition
• increasedACTH pulse amplitude with loss of normal circadian rhythm
• 15 % cases are due to non pituitary tumors
• may be due to bronchus cancer and carcinoids and pancreas cancer
• ACTH and cortisol are very high
• bronchial medullary and prostate cancer produces CRH and ACTH
• due to high ACTH there is MAH confusing as primary adrenal tumor
ACTH independent
• 65% of childrens with cushings have adrenal cause
• adenomas cause gradual course but carcinoma causes rapid course
• patients complain of abdominal or loin pain
• females show virilisation , hirsutism , clitoromegaly , breast atrophy , deep voice , temporal
recession , and severe acne
• in pure cortisol secreting tumors there is no hirsutism
• primary pigmented nooduular adrenal hyperplasia
• mc cune albright syndrome
• AIMAH
• exogenous GR
CREATED BY -Dr.GOPALA KRISHNAM RAJU
@
D
r_gkr
3. CUSHINGS
INVESTIGATIONS
• LATE NIGHT SALIVARY CORTISOL
• URINARY FREE CORTISOL
• LOW DOSE DEXA SUPPRESSION TEST
• for low index of suspicion we do either 24hr UFC or LDSST
• for high index of suspicion we do 2 tests
• women with hypothalamic amenorrhea has high 24hr UFC
• men doing intense exercise have high cortisol and ACTH levels
• 24hr UFC is a inegrated measure of serum free cortisol
• Salivary cortisol increase with age cardiovascular disorders and in diabetes
• LDDST – 1mg at 11pm and cortisol at 8am should be <1.8/50
• 8am cortisol and 0.5mg dexa QID for 2 days and again cortisol at 8am should be <1.8/50
• phenytoin and rifamapicin decreases dexa clearance
• patients with adrenal incidentalomas have normal urine cortisol but high salivary cortisol
• late night cortisol > 7.5 is CS
• in pregnancy 24hr UFC or late night salivary cortisol is best
• adrenal incidentalomas 1mg DST best
• in renal patients 1mg DST best
CREATED BY -Dr.GOPALA KRISHNAM RAJU
@
D
r_gkr