9. Adrenal Glands Flashcards
Outline the structure of the adrenal glands.
Outer capsule surrounding the cortex, central medulla.
What are the 3 regions of the cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What is secreted by the zona glomerulosa?
Mineralocorticoids - aldosterone
What is secreted by the zona reticularis?
Androgens - dihydroepitestosterone (DHEA) and androstenedione
What is secreted by the zona fasciculata?
glucocorticoids - cortisol
What is the role of the adrenal medulla?
contains chromaffin cells that synthesise adrenaline (80%) and noradrenaline (20%)
What are the precursors for corticosteroid synthesis?
Cholesterol
How do corticosteroids exert their effects?
Bind to cytoplasmic receptor, chaperone proteins dissociate and complex translocated to nucleus, dimerisation and binding to glucocorticoid response elements (GREs).
How is aldosterone transported in the blood?
Albumin mainly, some by transcortin
What is the main role of aldosterone?
Regulating electrolytes to maintain blood pressure and volume
What is the main action of aldosterone?
Promotes expression of the Na+/K+ pump in distal tubules and collecting ducts of nephron tubules.
How does increased expression of Na+/K+ transporter alter blood volume?
Increases uptake of Na+ and water. Increases K+ excretion.
What is the difference between primary and secondary hyperaldosteronism?
Primary - defect in adrenal cortex
Secondary - over activity of RAAS
What are possible causes of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia (most common)
Aldosterone secreting adrenal adenoma
What is the name given to an Aldosterone secreting adrenal adenoma?
Conn’s syndrome
What can cause secondary hyperaldosteronism?
Renin producing tumour (rare)
Renal artery stenosis
What is a useful marker to distinguish between primary and secondary hyperaldosterone?
Renin levels.
Low in primary hyperaldosteronism, High in secondary hyperaldosteronism.
What clinical signs would you see in hyperaldosteronism?
High blood pressure LV hypertrophy Stroke Hypernatraemia Hypokalaemia
What drug can be used to treat hyperaldosteronism?
Spironolactone - mineralocorticoid receptor antagonist
What hormone is released by the anterior pituitary to stimulate cortisol release from adrenal glands?
ACTH
What carrier protein is bound to cortisol in the blood?
Transcortin
What hormone is released by the hypothalamus to stimulate ACTH release from the pituitary gland?
CRH - corticotropin releasing hormone
What are the main catabolic actions that cortisol causes?
Increased proteolysis in muscle
Increased gluconeogenesis in liver
Increased lipolysis
What stimulates the hypothalamus to release CRH?
Stress - pain, fever, low bp, hypoglycaemia
How does cortisol exert an anti-inflammatory response?
Inhibits macrophage activity and mast cell degranulation
Depresses immune response
Due to it’s anti-inflammatory effects, when can cortisol be prescribed?
After organ transplant
What disease is characterised by raised cortisol exposure?
Cushing’s disease
What is a common exogenous cause of Cushing’s syndrome?
Prescribed glucocorticoids
What are possible endogenous causes of Cushing’s?
- Benign pituitary adenoma secreting ACTH
- Adrenal tumour secreting cortisol
- Non-pituitary-adrenal tumours secreting ACTH
What is the name given to the condition caused by benign pituitary adenoma secreting ACTH?
Cushing’s DISEASE
What is the name given to raised cortisol as a result of an adrenal tumour?
Adrenal cushing’s
What non-pituitary-adrenal tumour has been known to secrete ACTH?
Small cell lung cancer
What are the signs and symptoms of Cushing’s disease?
Moon-shaped face Buffalo hump Abdominal obesity Purple striae Acute weight gain Hyperglycaemia Hypertension
By what mechanism does cortisol function to raise blood pressure?
Increases blood vessel sensitivity to vasoconstrictors.
Give 2 examples of steroid drugs frequently prescribed.
Prednisolone
Dexamethasone
What are steroid drugs often prescribed to treat?
Inflammatory disorders - asthma, IBD, RA, auto-immunity, organ transplant
What is it important to remember about taking a patient off steroid drugs?
Dose must be reduced GRADUALLY to avoid crisis
What is Addison’s disease characterised by?
Chronic adrenal insufficiency - decreased production of aldosterone, cortisol, and dehydroepiandrosterone
What is the common cause of Addison’s disease?
Auto-immune destruction of the adrenal cortex
Is Addison’s disease more common in men or women?
Women
What are the signs and symptoms of Addison’s disease?
Postural hypotension Lethargy Weight loss Anorexia Skin pigmentation Hypoglycaemia
Why is hyperpigmentation caused by Addison’s disease?
If cortisol levels are low,negative feedback will encourage more ACTH release from the hypothalamus. ACTH is derived from POMC, which also synthesises alpha-MSH. MSH stimulates melanin synthesis.
ACTH itself can also directly activate melanocortin receptors.
What is an addisonian crisis?
Life threatening acute emergency due to adrenal insufficiency.
What factors can trigger an addisonian crisis?
Severe stress, infection, trauma, cold exposure, over-exertion, salt deprivation, abrupt steroid withdrawal
What are the symptoms of addisonian crisis?
nausea, vomiting, hypotension, vascular collapse, pyrexia
How is addisonian crisis treated?
Fluids
Cortisol
Which enzyme does the adrenal medulla use to convert noradrenaline to adrenaline?
N-methyl transferase
20% chromatin cells lack this enzyme and secrete NA.
What is the name given to a chromatin cell tumour?
Phaeochromocytoma
Why can a pheochromocytoma lead to life-threatening hypertension?
Massive adrenaline and noradrenaline release causing vasoconstriction
What are the characteristics of phaeochromocytoma?
Severe hypertension Headaches Palpitations Anxiety Weight loss Raised blood glucose
If a patient has Cushing’s syndrome but their ACTH is suppressed, what does this tell you about the cause?
ACTH independent
Exogenous cushings - glucocorticoids taken
Adnrenal tumour secreting cortisol
If a patient presents with Cushing’s syndrome and their ACTH is raised, what test can you do to help determine the cause?
Dexamethasone (corticosteroid) suppression test
How does the dexamethasome suppression test work?
Dexamethasone should reduce ACTH by negative feed back to hypothalamus, thus reducing cortisol levels.In Cushing’s syndrome cortisol would not be supressed by a low dose of dexamethasone.
If dexamethasone does lower cortisol levels, what is the likely cause of the Cushing’s?
Benign pituitary adenoma secreting ATCH
If dexamethasone doesn’t lower cortisol levels, what is the likely cause of the Cushing’s?
Ectopic tumour producing ACTH
Which disease is casued by an aldosterone secreting adrenal adenoma?
Conn’s disease
Explain why purple striae are often seen in Cushing’s syndrome?
Central obesity from redistribution of fat stretches skin.
Increased proteolysis makes skin weaker and thinner
Which time of day would be best to take a blood sample for cortisol measurement if Cushing’s syndrome is suspected?
Midnight - usually lowest cortisol levels.
Name the synthetic analogue of ACTH used in an ACTH stimulation test.
Synacthen
What is the ACTH stimulation test used for?
Test for Addison’s disease.
Synacthen would normally increase plasma cortisol. A normal response usually excludes Addison’s disease.
Why might creatinine and urea levels be raised in a patient with Cushing’s disease?
Increased proteolysis
How would you treat a patient with addison’s disease?
Prescribe glucocorticoids - hydrocortisone
Explain why cortisol can have mineralocorticoid and androgen-like effects when present in high concentrations.
Steroid receptor hormology- all contain the same regions, so cortisol will bind with low affinity to the mineralocorticoid receptor at high levels.
What enzyme is most commonly deficient in congenital adrenal hyperplasia?
21-hydroxylase - pathway producing both glucocorticoids and mineralocorticoids.
Why does a deficiency in 21-hydroxylase lead to genital ambiguity in female infants?
Substrate for 21-hydroxylase is diverted to androgen synthesis, causing increased levels of DHEA and androstenedione.
