Hypofunction of adrenal glands

Question 1

what are three causes of adrenal disorders through hypofunction?

Answer 1

adrenal dysgenesis (uncommon)
impared steroidgenesis (uncommon)
adrenal destruction

Question 2

what are causes of primary adrenal insufficiency?

Answer 2

addisons disease

adrenal enzyme defects

Question 3

what are causes of addisons disease?

Answer 3

Immune destruction (auto)
Invasion
Infiltration
Infection
Infarction
Iatrogenic

Question 4

what is an example of an adrenal enzyme defect?

Answer 4

congenital adrenal hyperplasia (most commonly 21-hydroxylase deficiency)

Question 5

what is the incidence of autoimmune addisons disease?

Answer 5

> 85% UK cases of adrenal failure

Question 6

what antibodies are commonly found in autoimmune addisons disease?

Answer 6

+ve adrenal autoantibodies (to 21-OHase) in 70% cases

lymphocytic infiltrate of adrenal cortex

Question 7

what are associated autoimmune diseases to addisons disease?

Answer 7

thyroid disease (20%)
Type 1 diabetes mellitus (15%)
premature ovarian failure (15%)

Question 8

what are common symptoms associated with primary adrenal failure?

Answer 8

Weakness, fatigue, anorexia, weight loss 100%

Skin pigmentation or vitiligo 92%

Hypotension 88%

Unexplained vomiting or diarrhoea 56%

Salt Craving 19 %

Postural symptoms 12%

Question 9

why is skin pigmentation and vitiligo associated with primary adrenal failure?

Answer 9

There is not enough cortisol in the feedback loop to the hypothalamus so it produced more CRH which increases ACTH which is formed from precursor POMC - breaks down into acth and msh

Msh pigment goes into pigments in skin and causes increased pigmentation, darkening of the skin particularly in areas not exposed to the sun

Question 10

what are possible clues to the diagnosis of adrenal failure?

Answer 10

Disproportion between severity of illness & circulatory collapse / hypotension / dehydration

Unexplained hypoglycaemia

Other endocrine features (hypothyroidism, body hair loss, amenorrhoea)

Previous depression or weight loss

Question 11

how is adrenal insufficiency diagnosed?

Answer 11

Routine bloods: U&E (low sodium, high pottasium), glucose, FBC

Random cortisol
>450 nmol/l (not Addison’s)
<450 nmol/l (adrenal status uncertain)

Synacthen test (and basal ACTH)
If suspicion high & patient unwell, treat with steroids and do Synacthen test later

Question 12

what is the synacethen test?

Answer 12

uses a special chemical (synacthen) to test how well the adrenal glands make cortisol

Question 13

describe the method of a short synacthen test?

Answer 13

METHOD
0900h: take 7 ml blood for cortisol (red top Vacutainer) and ACTH (purple top, on ice to lab immediately).
Give 250micrograms tetracosactrin IM (ideally) or IV.
0930h: Take 7 ml blood for cortisol.
1000h: Take 7 ml blood for cortisol. (optional)

For the diagnosis of congenital adrenal hyperplasia the samples taken for cortisol are also analysed for 17-OH progesterone to exclude 21-hydroxylase deficiency. In some cases 17-OH pregnenolone is measured to differentiate between 21-OH and 3ß-HSD deficiency.

INTERPRETATION
Normal response if test done at 0900h (considerable diurnal variation):
Stimulated plasma cortisol >500 nmol/l
Incremental rise of at least 200 nmol/l

If impaired cortisol response, and ACTH >200 ng/l then diagnosis is primary adrenal failure.

If ACTH <10ng/l then diagnosis is secondary adrenal failure
Response of 17-OH progesterone in suspected 21-hydroxylase deficiency (cryptic): marked rise after ACTH stimulation, which varies according to whether the patient is homozygous or heterozygous. Reference for nomogram: New et al., JCEM 57, 320-326 (1983).

Question 13

if an adrenocortical insufficiency is suspected what test should be done?

Answer 13

Rapid ACTH
Stimulation
test

Question 14

if the rapid stimulation test abnormal what does this indicate?

Answer 14

Adrenocortical
insufficiency

Question 15

if Adrenocortical insufficiency is confirmed what should be done?

Answer 15

Plasma ACTH

Question 16

if Plasma ACTH is supressed what does that indicate?

Answer 16

Secondary adrenocortical insufficiency

Question 17

if plasma ACTH is elevated what does that indicate?

Answer 17

Primary adrenocortical insufficiency

Question 18

if the rapid ACTH stimulation test is normal what does that indicate?

Answer 18

Excludes primary adrenocortical insufficiency

Question 19

describe the stages of diagnosing adrenocortical insufficiency?

Answer 19

Question 20

if addisons disease is suspected what should be done?

Answer 20

adrenal antibodies should be checked

Question 21

if adrenal antibodies are negative in men and women what should be done?

Answer 21

men - check VLCFA
if postive (adrenoleucodystrophy)
if negative adrenaal imaging

women - adrenal imaging
if positive - adrenal infiktration, infarction, haemorrage, infection
if negative - look for rare causes of addisons disease

Question 22

how should glucocorticoid replacement be given?

Answer 22

Usual total daily doses & relative potencies
Hydrocortisone 20-30mg =
Prednisolone 7.5mg =
Dexamethasone 0.75mg

Given in divided doses to ‘mimic normal diurnal variation’
eg HC 20mg at 08.00h & 10mg at 18.00h

Question 23

how should mineralocorticoid replacement be given?

Answer 23

Synthetic steroid, fludrocortisone

Binds to mineralocorticoid (aldosterone) receptors

50-300 micrograms daily

Adjust dose according to:
clinical status (postural BP, oedema)
U&E
plasma renin level

Question 24

how should dose of Mineralocorticoid replacement dose be adjusted according to?

Answer 24

clinical status (postural BP, oedema)
U&E
plasma renin level

Question 25

what is it important that patients undergoing steroid treatment have?

Answer 25

Question 26

who needs special care whilst on steroids?

Answer 26

Hypoadrenal patients on replacement steroids

Patients on steroids in doses sufficient to suppress the pituitary adrenal axis (>7.5mg prednisolone daily, or equivalent)

Patients who have received such treatment during the previous 18/12 (HPA axis may still be suppressed)

Question 27

what action should be taken while ill or stressed on steroids?

Answer 27

Minor short-lived illness or stress
double glucocorticoid dose

Major illness or operation
(especially if nil by mouth or GI upset)
100mg hydrocortisone iv stat
50-100mg HC iv 8-hourly
as stress abates, reduce HC by 50% per day until back on usual replacement dose

Question 28

what are three important ‘self-care’ rules for patients on steroids?

Answer 28

Never miss steroid doses

Double the hydrocortisone dose in event of intercurrent illness (eg flu, UTI)

If severe vomiting or diarrhoea, call for help without delay
(likely to need IM hydrocortisone - some patients or their partners are taught to inject)