Adrenal Insufficiency Flashcards
What hormone is produced by zona glomerulosa
Aldosterone
What controls aldosterone production
RAAS
What hormone is produced by zona fasciculate
Cortisol
What hormone is produced by zona reticularis
Androgen precursors
What controls androgen precursors production
HPA
What controls cortisol production
HPA
What is the HPA axis
CRH then ACTH then cortisol
When is ACTH the highest
8 in the morning
When is ACTH the lowest
Midnight
What hormone does the adrenal medulla produce
Catecholamines
What controls catecholamines production
Sympathetic nervous system
What determines the hormone being produced
The enzyme in the specific zone
How does RAAS work
Low blood pressure cause renin release from juxtaglomerular apparatus of the kidney that splits angiotensinogen into angiotensin 1 and ACE in the lungs covert it to angiotensin 2 that triggers release of aldosterone.
Aldosterone cause vasoconstriction increasing blood pressure & triggers release of ADH from pituitary & cause salt retention & therefor water retention
What also stimulate aldosterone
High potassium levels
ACTH
Steroid hormone production pathway
DIAGRAM
What is 7 biochemical actions of cortisol
Increase protein catabolism
Increase hepatic glycogen synthesis
Increase hepatic gluconeogenesis
Maintain blood pressure
Initiation of diuretics
Inhibit inflammatory & immune response
Inhibits bone formation
What is 3 actions of cortisol in stress response
Increase availability of fuel substance
Act on pancreas to decrease insulin & increase glucagon to promote glucose availability
Increase of enhance catecholamines activation
What is 2 molecular actions of cortisol
Increase transcription of glucocorticoid
Inhibit inflammatory gene expression
What is congenital adrenal hyperplasia
Autosomal recessive metabolic disorder
What is the epidemiology of 21-hydroxylase deficiency
Most of CAH (90%)
What is the epidemiology of 11-OH deficiency
5-10% of CAH
What is the epidemiology of 17-OH deficiency
Less than 5% of CAH
What is the epidemiology 3 21-BHSD deficiency
Rare
What pathophysiology does all CAH have in common
Decrease GC that decrease negative feedback that increase ACTH leading to adrenal hyperplasia
What is the pathophysiology of 21-OH deficiency
Decreased GC
Decreased MC causing salt wasting
Increase androgens causing over virilisation in female
What is the diagnostic precursor in 21-OH deficiency
Increase 17-OH progesterone
What is the treatment of 21-OH deficiency
Cortisol & fludrocortisone
What is monitoring for 21-OH deficiency
17-OHP
Androgens
What is the 3 stages of severity in 21-OH deficiency
- Severe salt losing:
Severe enzyme defect w/ potential adrenal crisis
Hypotension, shock & hyperK
Virilisation but males at risk - Simple virilisation form:
Mild enzyme defects w/ adequate cortisol & androgen production
Accumulation of 17 OHP & excessive androgens
Over virilisation of female & male - Non-classical form:
Very mild enzyme defect
No neonatal masculinization& young female menstrual irregularity, infertility & hirsutism
What is the pathophysiology of 3-BHSD deficiency
Decreased GC
Decreased MC causing salt wasting
Decrease androstenedione that decreases testosterone causing under virilisation in male
Increased DHEA over virilisation in females
What is the diagnosis used for 3- BHSD deficiency
Increase pregnenolone, 17a-hydroxypregnenlone, DHEA & renin
What is the pathophysiology of 11-OH deficiency
Decreased GC
Decreased aldosterone but increased deoxycorticosterone leading to hypertension & hypoK
Increase androgens causing over virilisation in females
What is the diagnostic precursor in 11-OH deficiency
Increase 11-deoxycortisol & 1-OH progesterone
What is the pathophysiology of 17-OH deficiency
Decreased GC
Decreased cortisol but increased corticosterone
Increased MC precursors leading to low renin hypertension w/ hypoK & metabolic acidosis
Decrease androgens causing under virilisation in males & delayed puberty in females
What is Addison disease
Impaired capacity of cortisol & aldosterone secretion
What is Addison disease
Primary adrenal hypofunction
What is 7 causes of Addison disease
Autoimmune
Adrenal haemorrhage
Meningococcal septicaemia
Infection
Neoplastic infiltration
Amyloidosis
Adrenoleukodystrophy
What is secondary adrenal hypofunction
Rapid withdrawal of prolonged steroid therapy
Lack of ACTH causing a cortisol deficiency & intact aldosterone
What is 9 clinical features of Addison disease
Orthostatic hypotension
Dehydration
Hypoglycaemia
Pigmentation (excess ACTH)
Fatigue
Muscle weakness
Weight loss
Anorexia
Addisonian crisis
What is Addisonian crisis
Hypotension, shock & abdominal pain
What is the biochemical feature of aldosterone & cortisol deficiency
Aldosterone deficiency
Na & water loss in urine
HypoNa & hyperK
Metabolic acidosis
Cortisol deficiency:
Hypoglycaemia
What is the 3 imaging investigation of adrenal insufficiency
CT adrenal or pituitary
MRI of pituitary
CXR
What is the 3 auto-Ab investigation of adrenal insufficiency
Anti-adrenal
Anti-thyroid
Anti-Islet cell
What is the blood test for investigation of adrenal insufficiency
Cortisol, ACTH & aldosterone
What is the blood results of primary adrenal insufficiency
Decrease aldosterone, cortisol & increase ACTH
What is the blood results of secondary adrenal insufficiency
Decreased ACTH & cortisol
What is a stimulation test
Evaluating the ability of adrenal to respond to stimulation of ACTH
What is primary adrenal insufficiency response to stimulation test
Unable tor respond
What is secondary adrenal insufficiency response to stimulation test
Respond after longer period of stimulation
What is the short ACTH stimulation test
One dose of synacthen measuring cortisol before & 30 minutes after
What is the long ACTH stimulation test
Synacthen for 3 days
Measuring before, 1,2,4,8 & 24 hrs after last dosage
What is the interpretation of short ACTH stimulation test
Normal: cortisol increase more than 550
Subnormal response: primary or secondary adrenal insufficiency
What is the interpretation of long ACTH stimulation test
Normal: rising cortisol levels peak at 4-8 hrs
Primary adrenal insufficiency: no/poor response
Secondary: slowly developing response with a peak at 24 hrs
What is the insulin tolerance test
Induce hypoglycaemia to stimulate ACTH in stress response
What is the insulin tolerance test interpretation
Normal: increase to more than 550
Subnormal: primary or secondary adrenal insufficiency
What is the metyraprone stimulation test
Inhibits 11B-OH & reduce cortisol concentration that reduce negative feedback on HPA that increase ACTH & 11-DOC
What is the metyraprone stimulation test interpretation
Normal: ACTH & 11-DOH increase
Subnormal: 11 DOC decrease due to primary or secondary adrenal insufficiency
