The Adrenal Glands & Adrenal disorders

Question 1

Where are the adrenal glands located ?

Answer 1

Above the kidneys

Question 2

What are the two different issues found in the adrenal gland and what are their embryological origin ?

Answer 2

1. Adrenal medulla - originates from neural crest cells

2. Adrenal cortex - mesoderm

Question 3

Outline the three different structures of the adrenal cortex & a mneumonic to remember their functions

Answer 3

OUTER : Zona glomerulosa ( aldosterone secretion)

MIDDLE : Zona fascicluta ( Cortisol )

INNER : Zona retricularis ( androgens & small amounts of glucocorticoids )

SALT
SUGAR
SEX

‘ the deeper you go , the sweeter it gets ‘

Question 4

What is the umbrella term used to describe the hormones secreted by the adrenal cortex ?

Answer 4

Corticosteroids

Question 5

Mineralcorticoid secreted from adrenal cortex

Answer 5

Aldosterone

Question 6

Glucocorticoids secreted from adrenal cortex

Answer 6

Cortisol

Corticosterone

Question 7

Androgens secreted by the adrenal cortex function

Answer 7

• Androgens are secreted by the inner most layer known as atheist Zona reticular is. The androgens are : DHEA and androstenedione.
• in males the DHEA is converted into testosterone in testes , and in females the adrenal androgens promote libido and are converted to oestrogen by other tissues.
• after menopause , this is the only source of oestrogen.
• Androgens promote axiallary and pubic hair growth in both sexes.

Question 8

What are the main type of cells found in the adrenal medulla and what do they secrete ?

Answer 8

Chromaffin cells and they selectee noradrenaline and adrenaline

Chromaffin cells in adrenal medulla lack axons but act as postganglionic nerve fibres that release hormones into blood (80% adrenaline and 20% noradrenaline )

Question 9

Where are steroid hormones derived from ?

Answer 9

Cholesterol

Question 10

Outline the mechanism of action of how corticosteroids bind to their receptors

Answer 10

Because corticosteroids are steroid hormones - they are therefore lipid soluble.

They diffuse across the plasma membrane.

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Question 11

What is the main carrier protein for aldosterone ?

Answer 11

Serum albumin - because they are lipid soluble they cannot move passively in the blood.

Question 12

What is the main function of aldosterone ?

Answer 12

Plays a central role in regulation of plasma Na+ , K+ and arterial blood pressure.

Main actions in distal tubules and collecting ducts of nephrons where it promotes expression of Na+/K+ pump promoting reabsorption of Na+ and excretion of K+ thereby increasing water retention as if more Na+ is moving into the blood , water will follow. Therefore blood volume increases , thus blood pressure.

Question 13

What role does aldosterone play in the RAAS ( renin-Angiotensin aldosterone system) in periods of hypokalaemia/ hypotension ?

Answer 13

1. When there in hypotension / hypovolaemia , there will be a decrease in renal perfusion + an increased sympathetic tone from baroreceptors will lead to renin release from thr kidneys.
2. Renin then causes angiotensin to be cleaved into angiotensin 1.
3. ANgiotension converting enzyme ( ACE) them coverts Ang1 into Ang2.
4. Ang11 then stimulates the release of aldosterone from the Zona glomerulosa which leads to the increase expression of the Na+/K+ pump in the collecting duct and distal tubules which leads to increased rebaosotion of Na+ , thus water into blood.

Question 14

Define hyperaldoesteronism

Answer 14

Too much aldosterone produced

Question 15

What are the two general causes in hyperaldoesteronsim?

Answer 15

PRIMARY - Defect in Adrenal cortex : Bilateral idiopathic adrenal hyperplasia , Aldosterone secreting adrenal adenoma ( Conns syndrome).

Secondary - Due to over activity of RAAS : renin producing tumour , renal artery stenosis.

Question 16

What is the best way to distinguish between primary and secondary hyperalldoesteronism?

Answer 16

Primary - there are low renin levels. ( high aldosterone : renin levels )

secondary : High renin levels ( low aldosterone : renin ratio )

Question 17

What are clinical presentation symptoms of hyperaldosteronism?

Answer 17

1. High blood pressure
2. Left ventricular hypertrophy because the left side of the heart will have a greater after load as it will be working much harder due to the high blood pressure.
3. Stroke
4. Hypernatraemia ( a lot more Na+ is moving into the blood from kidney nephron )
5. Hypokalaemia ( a lot more K+ is being excreted by the kidneys from the Na+/K+ pump)

Question 18

What is treatment for Hyperaldosteronism?

Answer 18

1depends of the type of hyperaldosterinism

For example , if you have a primary cause eg Aldosterone - producing adenoma ( also known as Conns syndrome ) then it will be removed by surgery.

Medication wise - you can give Spironolactone. This is a mineralcorticoid receptor antagonist.

Question 19

What is the main carrier protein for cortisol I be blood ?

Answer 19

Transcortin

Question 20

What are the functions of Cortisol ?

Answer 20

It’s release is influenced by both CRH + ACTH - involved in the negative feedback loop.

1. Increased protein breakdown in muscle
2. Increased lipolysis in fat : causes re distrusting of fat especially in abdomen , supraclavicular fat pads , Dorso -cervical fat pad , buffalo hump, and on face ( moon face ).
3. Increase gluconeogenesis in the liver
4. Resistance to stress ( increased supply of glucose , raised blood pressure by making vessels more sensitive to vasoconstrictors)
5. Has anti-inflammatory effects by suppressing the immune system by inhibiting macrophage activity and mass call degranulation. (
6. Depression of immune response

Question 21

Why is cortisol useful for medication in Allergic reactions ?

Answer 21

Because is has anti-inflammatory effects as it inhibits macrophage activity and mast cell degranulation.

Question 22

What is Cushing’s syndrome ?

Answer 22

Chronic excessive exposure to cortisol

Question 23

What are the two causes of Cushing’s syndrome - and which one is more rare / common ?

Answer 23

External causes : prescribed glucocorticoids which is the most common cause .

Endogenous causes ( more rare ) : Benign Pitutary Adenoma secreting ACTH. This is called Cushing’s disease. Excess cortisol produced by an adrenal tumour , this is called Adrenals Cushing. Also , a non-pitutary adrenal tumour producing ACTH /CRH E.g. small cell lung cancer ( this is VERY RARE).

Question 24

What are signs and symptoms of Cushing’s disease ?

Answer 24

1. Due to the excess in breakdown of fat and redistribution of fat - people will present with :

• Buffalo hump
• Purple striae
• Acute weight gain
• plethoric moon faced shape
• hypertension
• hyperglycaemia ( due to more glucose being made in the liver by gluconeogensis)

Question 25

What are the two main steroid drugs ?

Answer 25

Prednisolone Dexamethasone

Question 26

What are steroid drugs often used to treat ?

Answer 26

``` Inflammatory disorders such as asthma Inflammatory bowel disease Rheumatoid arthritis Other auto - immune conditions Also used to suppress immune reaction in organ translation. ```

Question 27

What are side effects of anti-inflammation drugs ?

Answer 27

The same effects of higher levels of cortisol

Question 28

How would you proceed to remove someone of anti-inflammatory drugs ?

Answer 28

Steroid dosage should be reduced gradually and not stopped suddenly

Question 29

What is Addison’s disease ?

Answer 29

Chronic adrenal insufficiency- decreased cortisol levels below normal. Now mainly due to autoimmune disease. Original cases had TB of the adrenal glands now it is rare to find someone with Addison’s disease to have TB.

Question 30

What sex does Addison’s disease affect more ?

Answer 30

Affects more women than men

Question 31

What are common signs and symptoms of Addison’s disease ?

Answer 31

Postural hypotension Lethargy Weight loss Anorexia Increased Skin pigmentation Hypoglycaemia

Question 32

What is the mechanism behind why there is hyper pigmentation is Addison’s disease ?

Answer 32

1. Due to the decrease in cortisol 2. There will a negative feedback response on the anterior pituitary gland which would INCREASE ACTH secretion and production. ACTH is produced from a precursor protein known as ‘ POMC’ , once this is cleaved into ACTH. ACTH contains fragments of MSH.Which would increase melanin synthesis. Also ACTH itself can also activate melanocortin receptors on melanocytes so will contribute to hyperpigmentation. Predominantly occurs in the hands , lips , gums ,

Question 33

What is an Addisonian crisis ? And what precipipates it ?

Answer 33

A life threatening emergency due to adrenal insufficiency It is precipitated by : severe stress , salt depravation , infection , trauma , cold exposure , over exertion , ABRUPT STEROID WITHDRAWAL.

Question 34

What are symptoms of Addisonian crisis ?

Answer 34

Nausea Vomiting Pyrexia Hypotension Vascular collapsE

Question 35

How to treat an Addisonian crisis ?

Answer 35

Fluid replacement IV Cortisol Correct hypoglycaemia But for life long replacement : prescribe hydrocortisone.

Question 36

What is an Phaeochromocytoma?

Answer 36

A chromaffin celltumour This is a rare catecholamines secreting tumour ( mainly noradrenaline). May precipitate life thirsting hypertension Characteristics : severe hypertension , palpitations , excessive sweating , anxiety , weight loss , elevated blood glucose levels.

Question 37

How can you distinguish between the three possible causes of Cushing’s syndrome from when high levels of ACTH are detected ? ( whether it is An Adrenal adenoma , pituitary adenoma or non-pituitary/Adrenal adenoma ?

Answer 37

If there are high levels of ACTH detected , then you need to do a ‘ high dosage dexamethasone’ test. Dexamethasone is a synthetic glucocorticoid. If you give a high dosage of Dexamethasone you would expect ACTH levels to drop , thus cortisol levels will also drop. If this happens , then we know the cause is from the Pituitary gland - thus a benign pituitary adenoma. If ACTH levels do not drop , thus cortisol does not drop too .. then the elevated cortisol levels (+ ACTH levels ) must be caused by a Non-adrenal/Pituitary adenoma for example small cell lung cancer.

Question 38

What will be th cause of Cushing’s syndrome if ACTH levels are NOT high ?

Answer 38

Exogenous cause cause - mainly being prescribed glucocorticoids. This is because glucocorticoids will increase levels of cortisol. And because of the negative feedback effect - ACTH levels will therefore be low. Endogenous cause : if corticosteroids have not been prescribed , then the elevated cortisol levels must be due to a Adrenal tumour ( Adrenal Cushing’s).

Question 39

If taken a full blood count of someone with potential Addison’s disease , what will you detect ?

Answer 39

- Low Na+ levels ( due to mineralcorticoid effects low ) - high potassium levels ( due to mineralcorticoid effects low) - Cortisol levels very low - glucose levels lower than normal - ACTH levels higher - urea very high ( because of hypovolemia , there would be a reduced glomerular filtration rate which would decrease renal plasma flow)

Question 40

Why in Cushing’s syndrome or someone who is taking high dosage of anti-inflammatory medications will you often see a high Na+ conc and low K+ ?

Answer 40

This is because when cortisol levels reach Avery high concentration , they often influence mineralcorticoids too.

Question 41

If there is suspected excess / too little cortisol in the blood , what test will you carry out ?

Answer 41

If you suspect excess cortisol - you will take a blood sample at midnight because this is where blood cortisol levels should be at their lowest. If it is high at midnight then you know there is a potential abnormality. If you suspect low cortisol in the blood then you would carry out a blood test at 9 am in the morning where cortisol levels are at their highest - if they are low here then you know there is a suspected problem,

Question 42

What is congenital adrenal hyperplasia ( CAH ) ?

Answer 42

A very rare , but inherited important disorder. It is an autosomal recessive condition. This is where a child is presented with ambiguous genitalia caused by a block in the adrenal cortex pathway. This leads to a low cortisol and aldosterone levels. But high levels of androgens. Child will be : Hyperkalaemic , Hypotensive , Hyponatraemia , hypoglycaemic. Treatment : determination of sex of baby , corrective surgery ,