MET3 Revision: Endocrine I Flashcards
Name three infective organisms that can cause hypoadrenalism [3]
TB
Fungal infections (E.g. candidiasis)
Neisseria meningitidis; Pseudomonas aeruginosa and Haemophilus influenzae causing WATERHOUSE-FRIDERICHSEN Syndrome .
Describe the pathophysiology of Waterhouse-Friderichsen syndrome [1]
blood vessels in the adrenal gland rupture during a severe bacterial infection, turning the adrenal glands into sacks of blood
(Blood clots occur during an infection, due to the toxins produced by the bacteria having pro-coagulant nature. This forms septic emboli. Adrenal vessels are small, so often get stuck there. Causes ischaemia and necrosis of the adrenal glands. Risk of adrenal crisis)
Name an iatrogenic cause of hypoadrenalism [1]
Ketoconazole: antifungal but suppresses the adrenals
Name 4 causes of hypoadrenalism [4]
- Addison’s–autoimmuneadrenalitis
- Infections: TB/fungal
- Waterhouse-Friedrichson syndrome –adrenal haemorrhage due to meningococcal infection
- Congenital adrenal hyperplasia
- Drugs: long term steroids suppressing adrenals. Ketoconazole
What are signs of Addison’s disease? [5]
- anorexia & weight loss
- fatigue, generalised weakness,
- increased pigmentation - particularly in mouth, scars and skin creases
- dizziness on standing
-
nausea & vomiting
(Remember Addison’s is due to decreased cortisol and aldosterone)
State 5 signs of Addison’s disease [5]
(Addison’s disease refers specifically to when the adrenal glands have been damaged, resulting in reduced cortisol and aldosterone secretion)
Postural hypotension (>10 mmHg)
Vitiligo (came up in CBL)
Depression & pyschosis
Abodominal pain (w/ n & v)
Flu like myalgias
Pigmentation – buccal, scars, skin crease
How may an Addisonian crisis present? [5]
Acute presentation of severe adrenal insufficiency, where the absence of steroid hormones (cortisol and aldosterone) leads to a life-threatening emergency. They may present with:
- Reduced consciousness
- Hypotension
- Abdominal pain
- Nausea and vomiting
- Hypoglycaemia
- Hyponatraemia and hyperkalaemia
- Pigmentation – buccal, scars, skin crease
When taking blood tests, what would hypoadrenalism have? [6]
- Na & K levels
- Urea levels
- Glucose levels
- Type of anaemia
- Ca levels
- Effect on leukocytes
Low Na; High K
High urea (increased salt and water loss / dehydration)
Low glucose
Normocytic anaemia
Eoisinophilia
Mild hypercalcemia
Aside from running blood tests, what would you test for with a patient you suspect of having hypoadrenalism? [4]
- Short synthetic ACTH [synacthen] test
- If synacthen test not available: Random cortisol and ACTH: 9am ATCH raised
- 21 hydroyxlase adrenal antibodies positive in 80% patients
- Abdomen x-ray (if TB has caused calcification of adrenal glands)
Describe the diagnostic test of choice for hypoadrenalism? [1]
Short synthetic ACTH [synacthen] test:
-The blood cortisol is measured at baseline, 30 and 60 minutes after administration.
- The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol.
- The cortisol level should at least double in response to synacthen.
- A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).
Describe the method of conducting a short synthetic ACTH [synacthen] test
- A dose of Synacthen, (synthetic ACTH).
- The blood cortisol is checked before and 30 and 60 minutes after the dose.
- The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol.
- The cortisol level should at least double.
- A failure of cortisol to double indicates either:
- Primary adrenal insufficiency (Addison’s disease)
- Very significant adrenal atrophy after a prolonged absence of ACTH in secondary adrenal insufficiency
Autoantibodies directed at the adrenal cortex to the autoantigens [] and [] can be seen in 70% of patients with idiopathic or primary Addison’s disease
Autoantibodies directed at the adrenal cortex to the autoantigens 21-hydroxylase and 17 alpha hydroxylase can be seen in 70% of patients with idiopathic or primary Addison’s disease
Management of Addisonian crisis;
Acute treatment? [2]
Long term treatment? [2]
Acute treatment:
* 0.9% saline
* IV hydrocortisone 100mg bolus stat; then IM doses until can take tablets
Long term treatment:
* Oral hydrocortisone – usually 10mg/5mg/5mg
* Oral fludrocortisone (mineralocorticoid) - 100 / 200 mg
Long term management of Addisonian crisis is:
Oral hydrocortisone
Oral fludrocortisone
What are the doses and dosing regimen like? [2]
Oral hydrocortisone – usually 10mg/5mg/5mg(reduce dose during the day so can sleep at night (cortisol is lowest at midnight))
Oral fludrocortisone - once daily; first thing at morning. Dose is titrated around BP; normally 100 - 200 mg dose
What blood results would you expect to see a ptx with Cushings syndrome? [3]
Hypokalaemia: due to excess cortisol having a mineralocorticoid effect (acts on aldostorone receptors)
Hyperglycaemia
High white blood cell count: Polycythaemia, Neutrophilia, Lymphopenia
Name and explain the diagnostic test of choice for Cushing’s syndrome
Normal: dexamethasone suppresses cortisol release from adrenal glands
Cushings: cortisol levels are high despite dexamethasone suppressing cortisol release
State 4 reasons that can cause increase in cortisol, which would give false positive results in a dexamethasone suppression test [4]
depression
alcohol excess
obesity
acute illness
What would differing ACTH levels indicate about the whether Cushings is ACTH dependent or independent?
ACTH elevated: more likely to be pituitary ectopic disease causing an increase in ACTH and therefore more cortisol - ACTH dependent
ACTH suppressed: more likely to be adrenal disease causing more cortisol - ACTH independent
How would you differ imaging to determine whether Cushings was ACTH dependent or ACTH independent? [2]
If ACTH-dependent: Pituitary vs ectopic
- MRI image of the pituitary
If ACTH-independent:
- imaging of adrenals/chest
Ectopic ACTH dependent Cushings is often caused by which type of cancer? [1]
ectopic ACTH: small cell lung cancer
What are the 3 arteries that supply the adrenal glands? [3]
Which arteries do they come from? [3]
Superior adrenal artery – arises from the inferior phrenic artery
Middle adrenal artery – arises from the abdominal aorta.
Inferior adrenal artery – arises from the renal arteries.
What is release of aldosterone stimulated by? [2]
rising K+ [1]
fall in blood volume/BP [1]
Explain effect of aldosterone on RAAS system
Renin converts angiotensin -> ANG1
ANG1 converted to ANGII by ACE (from lungs) ANG II:
Causes direct vasoconstricton + binding to ANG II receptors in ZG
ZG cells produce aldosterone: causes vasoconstriction + remodelling - (ininflammation in heart + vasculature).
Second effect of aldosterone: ‘sodium savour’: Na reabsorption + water reabsorption : Have to exchange K+ at the ENAC channels on the distal tubule.
mineralocorticoid receptor is activated by which two substrates? [2]
Why is that important? [1]
mineralocorticoid receptor: activated by cortisol AND aldosterone
So in cells where aldosterone is active, cortisol is deactivated otherwise receptor would be overwhelmed