MEH - The Adrenal Glands Flashcards
What are the three layers of the adrenal glands?
Within the capsule and cortex what layers are there and what do each produce?
What des the medulla produce? What cells are here?
G Salt
F Sugar
R Sex
CAPSULE: Zona glomerulosa - Mineralocorticoids - Aldosterone
CORTEX: Zona fasiculata - Glucocorticoids - Cortisol
Zona reticularis - Androgens + Glucocorticoids
Adrenaline (80%), NA(20%), chromatin cells
What are DHEA and androstenedione precursors of?
- Testosterone male
- Oestrogen women
What are the three glucocorticoids?
Cortisol
Cortisone
Corticosterone
What is an important mineralocorticoid?
Aldosterone
What are steroid hormones synthesised from and where?
Cholesterol in adrenal glands and gonads
How do they exert their action?
Lipid soluble - Bind to nuclear receptors and modulate gene transcription
What exerts a faster action and why? Steroids or catecholamines?
Steroids as its takes time to modulate gene transcription and new protein synthesis
How do corticosteroid exert their action in the cell?
Diffuse across cell membrane
Binding causes chaperone proteins to dissociate from glucocorticoid receptor (e.g. heat shock protein 90)
Receptor ligand translocates to nucleus
Binds to GREs (glucocorticoid response elements) or other transcription factors
What are GREs (glucocorticoid reposes elements)?
Areas in a promotor region of a gene that can turn on transcription when glucocorticoid-receptor binds
Where is aldosterone synthesised exactly?
In the zona glomerulosa of the adrenal cortex
Which 2 proteins carry aldosterone in serum? Which is the main one?
Albumin - most
Transcortin
Where is the aldosterone receptor and why?
Intracellular as it exerts its actions by regulating gene transcription
What are the broad roles of aldosterone?
Na K homeostasis - reabsorption of Na excretion of K, absorption of H2O (by increasing expression of NaK pump)
BP balance
Where is ACE made and where does ang I get cleaved to ang II?
Primarily in lung endothelial cells
What is the primary role of ADH?
Translocation of aquaporins in collecting tubule to increase H2O reabsorption
What happens in hyperaldosterone (6 - 3 primary, 3 secondary) vs hypo?
Hyper -
Primary - LOW renin (high aldosterone): Most common is bilateral idiopathic adrenal hyperplasia,Conns syndrome (aldosterone secreting adrenal adenoma) -> increased BP, low K+ arrhythmias, hypernatraemia, LVH
Secondary - HIGH renin (low aldosterone), also renin producing tumours e.g. of juxta glomerular, renal artery stenosis
Hypo - Congenital adrenal hyperplasia - lack of enzyme leads to low cortisol and aldosterone and high androgens (male hormones)
What can cause hyperaldosteronism? (primary vs secondary) What are signs and treatments?
Primary - LOW RENIN - defect in adrenal cortex
Most common is bilateral idiopathic adrenal hyperplasia
Conns syndrome
Secondary - HIGH RENIN - Over activation of RAAS
Juxtaglomerular tumour
Renal Artery Stenosis
Signs/Symptoms are: High BP Hypernatraemia Hypokalaemia LVH Stroke
Treatment: Aldosterone antagonist - Spironolactone. Surgery if aldosterone secreting tumour
What is Conn’s syndrome?
Aldosterone secreting adrenal adenoma
Where exactly is cortisol synthesised? What it’s major carrier protein?
Zona fasiculata in response to ACTH
Transcortin
Are cortisol main actions catabolic or anabolic?
Catabolic
What are 6 important actions of cortisol?
Gluconeogenesis Proteolysis Lipolysis Increase BP - via increased glucose (increases sensitivity of blood to vasoconstrictors) Anti-inflammatory Depression of immune reponse
What is cortisols effect on gluconeogenesis and where?
Increase glucose production leads to increased insulin which leads to increased glycogen stores in the liver.
What is cortisol effect on muscle?
Inhibits GLUT4 receptor so reduces uptake of glucose by muscles having a glucose sparing effect
What is cortisol effect on fat?
Decreased glucose utilisation, decreased sensitivity to insulin, increased lipolysis
Also redistribution of fat especially in abdomen, supraclavicular fat pads (buffalo hump), and on face (moon)
What are symptoms of Cushings syndrome? Why do you get striae? What are 4 causes of Cushings syndrome?
Moon face Buffalo hump Hyperglycaemia Hypertension Acute weight gain 1) Prescribed glucocorticoids 2) Pituitary ACTH secreting adenoma -Cushings DISEASE 3) Adrenal secreting cortisol adenoma 4) Non pituitary-adrenal tumours secreting ACTH e.g. small cell lung cancer (rate)
Name two steroid drugs, what kinds of disorders are they used to treat? What are the side effects like? Why should you reduce steroids gradually and not stop suddenly?
Prednisolone
Dexamethasone
Inflammatory - e.g. asthma, IBD, RA
Side effects similar to higher levels of cortisol plus can have mineralocorticoid effects
Must reduce slowly as get adrenal insufficiency (adrenals reduce steroid synthesis whilst you’re on steroids) - would get similar to addison’s crisis
What is the most common cause of Addisons?
Autoimmune destructive atrophy of adrenal cortex.
Who is more likely to get Addisons men or women
Women (autoimmune tends to be)
What are symptoms of Addisons?
Postural hypotension Lethargy Weight loss Anorexia Increased skin pigmentation - brown Hypoglycaemia
Why is there more POMC in Addisons? What is the side effect of this?
Because ACTH is low, so negative feedback to ant pit reduced, so more POMC is required to synthesis ACTH
Side effect is POMC contains gamma-MSH (melanocyte stimulating hormone) which produces melanin in skin –> colouration
How else is melanin and skin pigmentation increased in Addison’s other than POMC?
ACTH contains alpha-MSH which acts on melanocortin receptors on melanocytes to increase hyper pigmentation
What is Addisonian crisis? What is it precipitated by? Symptoms? Treatment?
Life threatening emergency due to adrenal insufficiency
Caused by stress, salt depravation Infection Trauma Cold Exposure Over exertion Abrupt steroid drug withdrawal
Symptoms are nausea, vomitting, pyrexia, hypotension, vascular collapse
Treatment: Fluid replacement, cortisol
Explain how the adrenal medulla is a modified sympathetic ganglion of ANS
It receives pre-ganglionic sympathetic input via:
Splanchnic nerves –> celiac ganglia –> chromaffin cells
Chromaffin cells lack axons but release hormones into blood: Adrenaline (80%), Nor adrenaline (20%)
Why do 80% chromaffin cells release adrenaline and 20% NA?
Because 20% of chromaffin cells lack the enzyme N-Methyl transferase
What are NA and adrenaline derived from?
Tyrosine
How does tyrosine become DA, NA, Adrenaline? Which enzyme converts NA to adrenaline?
Tyrosine —> Levodopa —> Dopamine —-> NA —> via N-methyl transferase —> Adrenaline
How does hormonal adrenaline increase HR?
Binds to beta 1 adrenergic receptors (GPCR) G alpha S pathway
1) Activating PKA that phosphorylates L type Ca2+ channels
2) cAMP - phosphorylates HCN channels increasing funny current
3) PKA - also phosphorylates HCN channels increasing funny current
Potentiates opening
Therefore increasing upslope of the action potential
What is pheochromocytoma? What happens?
Catecholamine secreting tumour (normally NA)
Can lead to life threatening hypertension
Other symptoms: Palpitations Hyperglycaemia Headaches Anxiety Weight loss Excessive sweating
Are there any ill-effects from lack of adrenal catecholamines? Compared to corticosteroids?
No ill effects from catecholamines
Lack of Corticosteroids is life threatening - must receive cortisol aldosterone (e.g. similar to Addisons disease).
What tests would you do for Cushings syndrome and what would you see?
Blood test: Midnight cortisol, should be low will be high
Suppression test - Give a steroid drug e.g. dexamethasone for a few days then test cortisol levels should be low but in cushings will stay high.
24hr urine - cortisol levels will be high in Cushings
What would you expect to see in tests for Aldosterone insufficiency (e.g. Congenital Adrenal Hyperplasia)? Compared to low ACTH?
High K
Low Na
Low ACTH alone will have Low Na with normal K
What would you expect to see on tests for aldosterone excess e.g. Conns, renin secreting juxtaglomerular tumours etc?
High BP
High Na
Low K
CT/MRI/MIBG/PET scan - tumours etc
How would you test for increased catecholamines? Why avoid things like coffee, coke, bananas before? What might high levels indicate?
24hr Urine - catecholamines or metanephrines
Plasma metanephrines - more sensitive than 24hr urine
Because they affect results
Pheochromocytoma
What are metanephrines?
Metabolites of adrenaline and NA
Apart from Addisons what two other causes of reduced cortisol is there?
Secondary adrenal failure from hypopituitism - reduced ACTH
Steroid induced hypoadrenalism - ACTH suppression
Apart from autoimmune what other causes of primary adrenal failure is there?
Infection - TB Drugs Malignancy Vascular - infarct etc Infiltration - amyloidosis etc
What is the treatment for Addisons? Why would they have to carry a steroid card?
Lifelong:
Glucocortioids - hydrocortisone, prednisolone
Mineralocorticoids - fludrocortison
To ensure health professionals know about crisis that can occur if steroids are stopped suddenly –> gives similar to addison crisis. As ACTH suppressed with long-term steroids so on removal can cause hypo adrenal crisis
why would Secondary adrenal failure from hypopituitism - reduced ACTH when compared with Addisons not:
- Cause pigmentation
- Not cause hyperkalaemia
- Cause hyponatraemia
- No ACTH so no gamma-MSH stimulating melanin
- No mineralocorticoid deficiency unlike can get in addisons
- Dilutional hyponatraemia (due to absence of normal effect of cortisol on free water excretion)
3 causes of Cushings syndrome? State their effects on ACTH
Pituitary tumour - increased ACTH
Adrenal Tumour - increased cortisol - reduced ACTH due to negative feedback
Ectopic ACTH - e.g. some small cell lung cancers secrete ACTH
Sometimes adrenal tumours causing Cushings also affect androgens - what kinds of symptoms might you see? How would you treat an adrenal tumour?
Hirtuism (excessive hair growth in some areas of body) Acne Greasy skin Clitoromegaly Deep voice Androgenic alopecia
Adrenalectomy
What is the commonest cause of endocrine hypertension?
Primary hyperaldosteronism e.g. Conns or bilateral idiopathic adrenal hyperplasia - can see hypertension at a young age
High BP low K - what is the clinical suspicion?
Hyperaldosteronism
Low Na high K - what is the clinical suspicion?
Hypoaldosteronism
Low Na normal K
ACTH deficiency
What is Congenital adrenal hyperplasia? What enzyme? What is the treatment?
Rare autosomal recessive disorder - Lack of enzyme 21-hydroxylase causes: Low cortisol Low aldosterone High male hormones (androgens)
Causes genitalia abnormalities and adrenal crisis (Hypotension, hyponatraemia, hyperkalaemia, hypotension, hypoglycaemia, virilisation (development of male characteristics) -
Treat adrenal crisis, determine sex of baby
Corrective surgery may be needed and long term glucocorticoids and mineralocorticoids
What is the difference between pheochromocytoma and paraganglioma? What three characteristics make it more likely to be genetically inherited. What are the symptoms of both? What are the investigations? (Type of urine/blood tests/imaging and what is the neuroendocrine marker?)
Both catecholamine secreting hormones
Pheo - from adrenal medulla (90%)
Para - extra adrenal tumour (10%)
Genetic if:
Extra adrenal
Malignant
Bilateral
Symptoms are same as anxiety attack - sympathetic surge –> sweating, palpitations, high or low BP, collapse
24hr urine metanephrines
Plasma metanephrines
Neuroendocrine marker is - Chromogranin A (a tumour marker)
CT/MRI/PET
What is the treatment for pheochromocytoma and paraganglioma? Why must you alpha block first?
alpha antagonists - phenoxybenzamine
beta blockers - bisoprolol
surgery
Must alpha block first because otherwise get unopposed alpha antagonism and this can lead to an pheo crisis.
What is phenoxybenzamine?
Adrenergic Alpha antagonist
What are MEN-2 VHL NF1 and SDHB/SDHD
Familial causes of pheochromocytoma and paraganglioma
