Cushings disease

Question 1

what causes cushings syndrome?

Answer 1

excess cortisol

Question 2

what general biochemical changes does cushings syndrome cause?

Answer 2

protein loss
altered carbohydrate/lipid metabolism - diabetes, obesity
altered psyche - depression, psychosis
excess mineralocorticoid
excess androgen

Question 3

what does protein loss cause in cushings?

Answer 3

myopathy, wasting
osteoporosis, fractures
thin skin
striae
bruising

Question 4

what does the excess mineralocorticoid in cushings cause?

Answer 4

hypertension

oedema

Question 5

what does excess androgen in cushings cause?

Answer 5

virilism
hirsutism
acne
oligo/amenorrhoea

Question 6

what features distinguish cushings from obesity?

Answer 6

thin skin
proximal myopathy
frontal balding in women
conjunctival oedema (chemosis)
osteoporosis

Question 7

what is the most common test for cushings?

Answer 7

exogenous oral high dose steroid (dexamethasone)

- should cause low serum cortisol

Question 8

describe dexamethasone suppression test?

Answer 8

overnight 1mg dexamethasone

• normal = cortisol <50 nmol the nest mornine
• cushings = >100 nmol/L

Question 9

what other tests can screen for cushings?

Answer 9

4 hr urine free cortisol
- should be <250
diurinal cortisol variation(midnight/8am)

Question 10

what is the definitive test for cushings?

Answer 10

low dose dexamethasone suppression test

• 2 day 2mg/day dexamethasone suppression test
• cortisol <50 = normal
• cortisol >130 = definitely cushings

Question 11

what are the 2 types of cushings?

Answer 11

cushings disease (pituitary)
cushings syndrome

Question 12

what can cause cushings syndrome?

Answer 12

adenoma of adrenal glands (benign/cancer)
ectopic (thymus, lung, pancreas)
pseudo
- alcohol and depression
- steroid medication

Question 13

how do pituitary, adrenal and ectopic cushings differ in test results?

Answer 13

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

Question 14

what does CRH test show in cushings DISEASE?

Answer 14

50% increase in ACTH

20% increase in cortisol

Question 15

how is pituitary cushings disease managed?

Answer 15

hypophysectomy and external radiotherapy if it recurs

bilateral adrenalectomy

Question 16

how is adrenal cushings managed?

Answer 16

adrenalectomy

Question 17

how is ectopic cushings managed?

Answer 17

remove source
or
bilateral adrenalectomy

Question 18

how can cushings be managed pharmacologically?

Answer 18

metyrapone (if other treatments fail or waiting for radiotherapy to work)
ketoconazole (hepatotoxic)
pasireotide LAR (somatostatin analogue)

Question 19

what are the features of pan hypopituitarism?

Answer 19

GH = growth failure
TSH = hypothyroid
LH/FSH = hypogonadism
ACTH = hypoadrenal
Prolactin = no effects

Question 20

what are the features of pan hypopituitarism in posterior pituitary?

Answer 20

diabetes insipidus

Question 21

what can cause hypopituitarism?

Answer 21

primary tumours
secondary metastatic tumours
local brain tumours
granulomatous disease (TB, sarcoidosis etc)
vascular disease
trauma
hypothalamic disease
iatrogenic
autoimmune (sheenan)
infection (meningitis)

Question 22

what are the symptoms of anterior hypopituitarism in females?

Answer 22

menstrual irregularities
infertility, impotence
abdo obesity
loss of axillary and pubic hair
dry skin and hair
hypothyroid faces
growth retardation (in children)

Question 23

what are the symptoms of anterior hypopituitarism in males?

Answer 23

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)

Question 24

what are the best tests for checking the steroid axis (cortisol etc)?

Answer 24

synacthen

insulin tolerance

Question 25

what replacement therapy is used for hypopituitarism?

Answer 25

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)

Question 26

what does GH do in adults?

Answer 26

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

Question 27

how can testosterone replacement be delivered?

Answer 27

IM injection every 3-4 weeks (sustanon)
skin gel (testogel, tostran)
prolonged IM injection 10-14 weeks (nebido)
oral tablets (restandol)

Question 28

what are the risks of testosterone replacement?

Answer 28

prostate enlargement
- doesn't cause prostate cancer but can increase size of it
polycythaemia
- monitor FBC
hepatitis (only oral tablets)
- monitor LFTs

Question 29

what can cause cranial diabetes insipidus?

Answer 29

familial (isolated, DIDMOAD)
acquired (idiopathic, trauma)
rare causes (tumour, sarcoid, radiation, meningitis)

Question 30

what test is used for diabetes insipidus?

Answer 30

water deprivation test

Question 31

describe the water deprivation test

Answer 31

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

Question 32

how can the water deprivation test indicate the source of diabetes insipidus?

Answer 32

if urine/serum osmolality improves after DDAVP then it is due to cranial diabetes insipidus (i.e DDAVP deficiency)

Question 33

how is diabetes insipidus managed?

Answer 33

desmospray
desmopressin oral tablets
desmopressin injection