Endocrine 1 (adrenals and pituitary) Flashcards
1
Q
Structure/ anatomy of adrenals?
A
- The adrenal glands are bilateral and sit superior and medial to the upper pole of the kidneys (4-5g each)
- They are composed of an outer cortex and inner medulla
- The cortex secretes glucocorticoids, mineralocorticoids and androgens
- The medulla secretes catecholamines (adrenaline)
2
Q
3 zones of the adrenal cortex? What does each secrete and what controls it?
A
- Zona glomerulosa is the outer most layer and secretes aldosterones under control of RAAS
- Zona fasciculata is the middle layer and secretes cortisol/ glucocorticoid under control by pituitary-hypothalamic axis
- Zona reticularis is the inner most layer and secretes androgens under control by the pituitary-hypothalamic axis
3
Q
Main actions of cortisol?
A
- Cortisol actions: increases alertness, inhibits the immune system, inhibits bone formation, raises the blood glucose, increases metabolism
4
Q
Explain what primary hypoadrenalism is/ addisons?
A
- This is usually due to auto-immune destruction of the adrenal gland – layers are usually destroyed in a stepwise fashion so the zona reticularis is often spared
- Other causes of primary failure include metastatic spread to adrenals and TB destruction
- Can be confusion as some people use the term Addison’s disease to refer to all adrenal insufficiency and some just to the auto-immune form
5
Q
3 causes of primary hypoadrenalisms?
A
autoimmune destruction (most commonly)
TB destruction
metastatic destruction
6
Q
Who gets primary adrenal insufficiency?
A
- The auto-immune form is more common in females
- Auto-immune form is associated with 21-hydroxylase antibodies
- Also associated with other auto-immune diseases such as vitiligo, pernicious anaemia, type 1 diabetes and coeliac disease
7
Q
Presentation of addisons?
A
- Anorexia and weight loss
- Fatigue and lethargy
- Dizziness and low blood pressure
- Abdominal pain
- Nausea and vomiting
- Salt craving
- Skin hyperpigmentation and buccal pigmentation (this is because there is excess ACTH trying to stimulate the failing adrenals and this reacts with melanocytes to increase melanin)
- Amenorrhoea in women
8
Q
Investigations for addisons?
A
- Hyponatraemia is often key electrolyte abnormality
- Hyperkalaemia
- Hypoglycaemia
- Sometimes hypercalcaemia
- Metabolic acidosis
- Adrenal antibodies (21-hydroxylase) present in 90%
- Plasma renin is high due to low aldosterone
- Single cortisol level is generally of little value, but a high reading can help as this suggests the diagnosis is very unlikely
- Definitive diagnosis can be made with the short synacthen test- this is where you give synthetic ACTH and monitor response, if no cortisol is released in response to this there is primary adrenal insufficiency
- May do imaging to look for structural pathology of the adrenals if this was suspected
- May do MRI of pituitary of suspecting secondary insufficiency
9
Q
Diagnostic test for addisons?
A
- Definitive diagnosis can be made with the short synacthen test- this is where you give synthetic ACTH and monitor response, if no cortisol is released in response to this there is primary adrenal insufficiency
10
Q
Explain electrolyte abnormalities in addisons?
A
- Most are caused by deficiency of aldosterone
- Aldosterone action = retention of sodium and water with excretion of potassium and H+
- If you are deficient in aldosterone you secrete more sodium and water, and retain more potassium and hydrogen ions
- This results in metabolic acidosis, hyperkalaemia and hyponatraemia
11
Q
Management of addisons?
A
- Glucocorticoid replacement with hydrocortisone tablets
- Fludrocortisone is used as mineralocorticoid replacement
- Patients need educated about steroids including increasing doses when ill, carrying a steroid card and wearing a medical alert bracelet
12
Q
Describe adrenal crisis?
A
- If suspected this should be treated straight away, as wrongly treating someone is unlikely to cause harm
- Hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia, dehydration, hyperpigmentation
- Either an initial presentation or with a precipitating event e.g. infection, trauma
- Need hydrocortisone IM or IV and IV saline infusion
13
Q
What is cushing syndrome?
A
- Clinical state of increased free circulating cortisol
- Cushing’s disease refers specifically to Cushing’s Syndrome that is caused by pituitary disease
14
Q
Explain the causes of cushings syndrome?
A
- The majority are due to a pituitary adenoma (Cushing’s disease) – pituitary secretes excess ACTH
- Second commonest cause is a benign adenoma of the adrenal gland secreting excess cortisol
- Another cause is ectopic ACTH production from tumours e.g. in small cell lung cancer or in pancreatic tumours
- Prolonged administration of glucocorticoids for conditions such as rheumatoid arthritis or asthma etc. can sometimes cause iatrogenic Cushing syndrome – in these cases patients need their medication gradually reduced otherwise there is a risk of causing an adrenal crisis as usually the adrenal cortex has become atrophic
CAPE
Cushings disease, adrenal adenoma, paraneoplastic, exogenous steroids
15
Q
Presentation of cushings syndrome?
A
- Thin skin, easy bruising, poor wound healing, skin pigmentation and abdominal striae
- Proximal myopathy – may struggle to do things like walk up stairs or hang washing
- Frontal balding in women
- Osteoporosis – this helps with diagnosis as usually a patient does not have osteoporosis if they are overweight so the combination of obesity plus osteoporosis heavily hints that this could be Cushings
- Central obesity
- Round “moon” face
- In conditions where there is excess ACTH e.g. pituitary adenoma secreting ACTH or ectopic ACTH production from a cancer, there can be hyperpigmentation as the ACTH reacts with melanocytes
16
Q
Investigations for cushings syndrome?
A
- Screening test = look for raised urinary or salivary cortisol
- Definitive Test = Overnight dexamethasone suppression test – in normal individuals cortisol levels should decrease in response to administration of dexamethasone
- Then may need to do imaging to determine the cause of the Cushings e.g. CT and MRIs to look for the tumours
17
Q
Management of cushings syndrome?
A
- In pituitary adenomas: trans-sphenoidal removal of the tumour is treatment of choice
- In adrenal adenomas: laparoscopic resection
- In adrenal carcinomas: treatment more complicated as these are usually highly aggressive and generally have surgery plus medical management
- In cases of other cancers secreting ACTH: if possible remove the tumours
- Medical therapy can be used to control cortisol hypersecretion in unclear cases or whilst a patient waits for treatment e.g. metyrapone (block cortisol steroidgenesis)
18
Q
Explain what a phaeochromocytoma is?
A
- A rare adrenal medulla tumour composed of chromaffin cells
- If the tumour is extra medulla and in the sympathetic chain it is called a paraganglioma
- Note: you mainly get chromaffin cells in your adrenals but you also find them in some ganglia
19
Q
Who gets phaeochromocytoma?
A
- 25% are associated with a familial syndrome e.g. MEN-2 and VHL and Neurofibromatosis
- Usually presents in those age 30-50
- About 10% are bilateral and 10% are malignant (there isn’t a clear cut between malignant and benign, it can be difficult to predict behaviour but majority are benign)
20
Q
Presentation of phaeochromocytoma?
A
- The catecholamine excess is often intermittent resulting in intermittent symptoms
- Classic triad: hypertension, headache and sweating
- Other symptoms: palpitations, breathlessness, constipation, anxiety and weight loss
21
Q
Classic triad of phaeochromocytoma?
A
headaches, sweating, hypertension
22
Q
Explain physiological control and release of adrenaline?
A
- Adrenaline is released mainly through the activation of nerves connected to the adrenal glands, which trigger the secretion of adrenaline and thus increase the levels of adrenaline in the blood
- This process happens relatively quickly, within minutes of the stressful event being encountered
- When the stressful situation ends, the nerve impulses to the adrenal glands are lowered meaning that the adrenal glands stop producing adrenaline
- Stress also stimulates the release of ACTH from the pituitary gland which promotes the production of the steroid hormone cortisol from the cortex of the adrenal glands
23
Q
Investigations for phaeochromocytoma?
A
- Screening test = Measurement of urinary catecholamines and metabolites (normal results on 3 x 24 hour collection essentially excludes the diagnosis)
- Plasma metanephrine is generally raised – if can measure at time of symptoms
- Identify the tumour – MRI, MIBG (nuclear imaging test), PET scan
- Can be difficult to histologically predict behaviour
- All those with a confirmed phaeochromocytoma should have genetic testing done
