Cushings disease Flashcards
what causes cushings syndrome?
excess cortisol
what general biochemical changes does cushings syndrome cause?
protein loss altered carbohydrate/lipid metabolism - diabetes, obesity altered psyche - depression, psychosis excess mineralocorticoid excess androgen
what does protein loss cause in cushings?
myopathy, wasting osteoporosis, fractures thin skin striae bruising
what does the excess mineralocorticoid in cushings cause?
hypertension
oedema
what does excess androgen in cushings cause?
virilism
hirsutism
acne
oligo/amenorrhoea
what features distinguish cushings from obesity?
thin skin proximal myopathy frontal balding in women conjunctival oedema (chemosis) osteoporosis
what is the most common test for cushings?
exogenous oral high dose steroid (dexamethasone)
- should cause low serum cortisol
describe dexamethasone suppression test?
overnight 1mg dexamethasone
- normal = cortisol <50 nmol the nest mornine
- cushings = >100 nmol/L
what other tests can screen for cushings?
4 hr urine free cortisol
- should be <250
diurinal cortisol variation(midnight/8am)
what is the definitive test for cushings?
low dose dexamethasone suppression test
- 2 day 2mg/day dexamethasone suppression test
- cortisol <50 = normal
- cortisol >130 = definitely cushings
what are the 2 types of cushings?
cushings disease (pituitary) cushings syndrome
what can cause cushings syndrome?
adenoma of adrenal glands (benign/cancer) ectopic (thymus, lung, pancreas) pseudo - alcohol and depression - steroid medication
how do pituitary, adrenal and ectopic cushings differ in test results?
pituitary = abnormal dexa test, ACTH <300, high dose dexa suppression = 50% adrenal = abnormal dexa test, ACTH <1, no high dose dexa suppression ectopic = abnormal dexa test, ACTH >300, no high dose dexa suppression
what does CRH test show in cushings DISEASE?
50% increase in ACTH
20% increase in cortisol
how is pituitary cushings disease managed?
hypophysectomy and external radiotherapy if it recurs
bilateral adrenalectomy
how is adrenal cushings managed?
adrenalectomy
how is ectopic cushings managed?
remove source
or
bilateral adrenalectomy
how can cushings be managed pharmacologically?
metyrapone (if other treatments fail or waiting for radiotherapy to work)
ketoconazole (hepatotoxic)
pasireotide LAR (somatostatin analogue)
what are the features of pan hypopituitarism?
GH = growth failure TSH = hypothyroid LH/FSH = hypogonadism ACTH = hypoadrenal Prolactin = no effects
what are the features of pan hypopituitarism in posterior pituitary?
diabetes insipidus
what can cause hypopituitarism?
primary tumours secondary metastatic tumours local brain tumours granulomatous disease (TB, sarcoidosis etc) vascular disease trauma hypothalamic disease iatrogenic autoimmune (sheenan) infection (meningitis)
what are the symptoms of anterior hypopituitarism in females?
menstrual irregularities infertility, impotence abdo obesity loss of axillary and pubic hair dry skin and hair hypothyroid faces growth retardation (in children)
what are the symptoms of anterior hypopituitarism in males?
infertility, impotence gynaecomastia abdo obesity loss of facial hair loss of axillary and pubic hair dry skin and hair hypothyroid faces growth retardation (in children)
what are the best tests for checking the steroid axis (cortisol etc)?
synacthen
insulin tolerance
what replacement therapy is used for hypopituitarism?
thyroxine (100-150 mcg/day) hydrocortisone (10-25 mg/day) ADH (desmospray or tablets) GH (nightly SC GH) sex steroids (HRT/oestrogen/progesterone pill for female, testosterone for males)
what does GH do in adults?
improves well being and quality of life decreased abdo fat increases muscle mass, strength, exercise capacity and stamina improves cardiac function decreases cholesterol and increases LDL increases bone density given daily by SC injection
how can testosterone replacement be delivered?
IM injection every 3-4 weeks (sustanon) skin gel (testogel, tostran) prolonged IM injection 10-14 weeks (nebido) oral tablets (restandol)
what are the risks of testosterone replacement?
prostate enlargement - doesn't cause prostate cancer but can increase size of it polycythaemia - monitor FBC hepatitis (only oral tablets) - monitor LFTs
what can cause cranial diabetes insipidus?
familial (isolated, DIDMOAD)
acquired (idiopathic, trauma)
rare causes (tumour, sarcoid, radiation, meningitis)
what test is used for diabetes insipidus?
water deprivation test
describe the water deprivation test
no drinking for 8-12 hrs
check serum and urine osmolalities for 8hr and then 4h after intra muscular DDAVP
- urine/serum osmol ratio >2 = normal
- urine/serum osmol ratio <2 = diabetes insipidus
how can the water deprivation test indicate the source of diabetes insipidus?
if urine/serum osmolality improves after DDAVP then it is due to cranial diabetes insipidus (i.e DDAVP deficiency)
how is diabetes insipidus managed?
desmospray
desmopressin oral tablets
desmopressin injection
