8 adrenal disease

Question 1

define stress

Answer 1

a state of threatened homeostasis or dysharmony;

Question 2

how does the body respond to stress to re establish homeostasis?

Answer 2

• arousal, alertness, vigilance
• Redirection of energy:
  
  • Increased CV tone, ventilation
  • Increase glucose availability
  • Decrease energy consuming activities (digestion and reproduction)

Question 3

what is a stressor?

Answer 3

stimulus that induces state of stress

• psychological / emotional – anxiety, fear
• physiological - pain, fever, hypoglycaemia, injury, fluid deprivation, heavy exercise, etc.

Question 4

stress response system of SNS

Answer 4

intergrated response

• ↑ cardiac output and ventilation
• Diversion of blood flow to muscles and heart
• Mobilisation of glycogen and fat stores

“fight or flight”

synergistic with CRH-ACTH-cortisol

Question 5

stress response system of CRH-ACTH-cortisol

Answer 5

• Shift from protein & fat stores in favour of expanded glycogen stores and plasma glucose availability
• Amino acids available for tissue repair if physical damage

cortisol has permissive action on adrenaline and noradrenaline

synergistic with SNS & adrenaline

Question 6

stress response system of RAS, ADH, GH

Answer 6

decreased thyroid hormones

Question 7

how does cortisol have a protective function in stress activated immune responses

Answer 7

cortisol has an anti inflammatory effect to prevent over activation of immune defence mechanisms

Question 8

Answer 8

Question 9

effects of chronic stress with prolonged elevated cortisol levels (4)

Answer 9

• muscle wasting
• hyperglycaemia
• GI ulcers (increased susceptibility) : decreased production of prostaglandins in gut, responsible for mucus secretion that protect from gastric acid secretions - less protection
• impaired immune response

Question 10

what is cushing’s syndrome?

Answer 10

excess glucocorticoid activity

Question 11

what is cushing’s disease?

Answer 11

ACTH- secreting anterior pituitary tumour

Question 12

cushing’s syndrome

Answer 12

Question 13

why are both ACTH and cortisol levels high in an ectopic tumour of ACTH- producing cells

Answer 13

ectopic tumour cells lack feedback mechanism

Question 14

why do ACTH levels stay high in cushing’s syndrome?

Answer 14

tumour cells have impaired responsiveness to negative feedback from high cortisol levels

Question 15

what are the levels of CRH in cushing’s syndrome and why?

Answer 15

decreased due to negative feedback from increased ACTH levels

Question 16

what are signs and symptoms of cushing’s syndrome?

Answer 16

• altered fat distribution- truncal obesity, buffalo hump, red round face
• excess adrenal androgens - acne, female frontal balding and hirtuism, menstrual irregularities, testicular atrophy
• breakdown of protein, muscle wasting, loss of collagen- thin arms and legs, muscle weakness, thin skin, purple striae
• immunosuppressant- poor wound healing, easy bruising, infections
• mental changes- cognitive difficulties, emotional instability, depression, sleep disturbances
• altered bone metabolism- osteoporosis
• hypertension (excess mineralocorticoid actiivty- sodium retention hypokalemia)
• diabetes

Question 17

what is cushing syndrome’s effect on parathyroid hormone?

Answer 17

increased secretion due to decreased bone formation, intestinal calcium formation and increased urinary calcium excretion

Question 18

what does excess glucocorticoids in childhood cause?

Answer 18

growth retardation

Question 19

what is the diagnosis of cushing’s syndrome?

Answer 19

elevated plasma cortisol levels confirm diagnosis

loss of diurnal cortisol rhythm

• 24h urine free cortisol
• ACTH measurements
• dynamic tests- dexamethasone and CRH tests

Question 20

explain the diagnosis of CS using DEX tests

Answer 20

1. Low dose: confirms cushing’s syndrome (cortisol remains high or in normal range suggests CS as low dose should cause suppression)
2. 2^nd test High dose test to confirm the cause of cushing’s syndrome
   
   1. Cushing’ disease low cortisol (supression of ACTH)
   2. Adrenal gland tumour low ACTH and high/ normal cortisol
   3. Ectopic ACTH tumour- high ACTH and high/ normal cortisol

Question 21

what are the cortisol levels of serum cortisol 9am, midnight and 24h urine cortisol tests in CS?

Answer 21

serum 9am: N or increased

serum midnight: increased

24h urine: increased

Question 22

what is CRH stimulation test used for?

Answer 22

determine pituitary- dependent Cushing’s and ectopic source of ACTH

in adrenal or ectopic ACTH syndrome- no response to CRH- cortisol and ACTH levels are flat

pituitary- dependent: N or increased cortisol

Question 23

how would you locate these tumours?

1. ant pituitary
2. adrenal
3. bronchial
4. ACTH secreting tumour

Answer 23

1. MRI
2. abdominal x ray
3. chest x ray
4. octrescan

Question 24

what are some treatments of cushing’s syndrome?

Answer 24

surgery or radiotherapy

drugs to inhibit steroidogenesis (pre-operative or pallative, not long term therapy)

Question 25

what is Conn's syndrome? what is the common cause?

Answer 25

primary hyperaldosteronism tumour

Question 26

what are the clinical findings of conn's syndrome?

Answer 26

hypokalemia and weakness chronic hypokalemia- rena; dysfunction-\> polyuria **hypertension** is main clinical finding

Question 27

what is the treatment of Conn's syndrome?

Answer 27

surgery, aldosterone receptor antagonist e.g. spironolactone

Question 28

what is addison's disease? what type of condition is this?

Answer 28

primary adrenal insufficiency (apparent when 90% of adrenal cortex is destroyed) rare and chronic condition- failure of adrenal glands

Question 29

What are some causes of destruction of adrenal tissue in Addison's?

Answer 29

autoimmune, HIV or TB

Question 30

what are the levels of alosterone, cortisol, androgens and ACTH in Addison's?

Answer 30

low except high ACTH due to minimal negative feedback loops

Question 31

what are some symptoms of Addison's?

Answer 31

* postural hypotension * muscle weakness, fatigue, lethargy * hyponatraemia, hyperkalaemia * increased pigmentation * ACTH production increased, and MSH melanocyte stimulating hormone: share same POMC precursor as ACTH * Increased melanin content in skin * Hyperpigmentation in skin creases, old scars, gums and inside of the cheek * weight loss, anorexia * nausea and vomitting

Question 32

what are some tests of addison's/ adrenal failure?

Answer 32

* cortisol (decreased) and ACTH levels (increased) * ACTH stimulation test * adrenal auto-antibodies (if suspect auto-immune disease)

Question 33

treatment of addison's

Answer 33

life- long hormone replacement **Glucocorticoid** hydrocortisone to mimic diurnal variation (two doses, AM and PM) **Mineralocorticoid** fludrocortisone (daily) Higher doses of glucocorticoids during times of illness or major stress (e.g. surgery)

Question 34

what is secondary adrenal insufficiency? what are the clinical findings?

Answer 34

lack of ACTH production low cortisol, normal aldosterone (RAAS intact)

Question 35

what are the causes of adrenal insufficiency?

Answer 35

1. tumour, damage to pituitary 2. secondary adrenal suppression-\> exogenous glucocorticoid use - supression of ACTH levels-\> supression atrophy of adrenal cortex

Question 36

when should you suspect excess glucocorticoid use?

Answer 36

cushingoid apperance

Question 37

what happens if there is a sudden withdrawal of glucocorticoid use?

Answer 37

symptoms of acute adrenal insufficiency - lack of cortisol activity (weight loss, fatigue, N&V)

Question 38

what is an adrenal crisis?

Answer 38

= Acute adrenal insufficiency expressed when patient is under stress (e.g. infection) **→** hypotension, circulatory failure, death Urgent treatment (iv fluids, hydrocortisone, (iv then oral)) medical emergency

Question 39

what is congenital adrenal hyperplasia?

Answer 39

inherited defect in an enzyme involved in the production of cortisol and aldosterone \>90% of CAH due to deficiency of 21β-hydroxylase

Question 40

what happens in severe and less severe cases of CAH?

Answer 40

severe: females born with ambiguous genitalia- incorrect gender assignment less severe: children- precocious puberty females: virilisation (male characteristics)

Question 41

what are some clinical findings of CAH?

Answer 41

low cortisol and aldosterone build up of androgens decreased negative feedback inhibition-\> excess ACTH Prolonged ACTH hyperstimulation results in hyperplasia of the adrenals

Question 42

treatment of CAH

Answer 42

hormone replacement plastic surgery (androgens)