4.4 - The Adrenal Gland

Question 1

Where are the adrenal glands?

Answer 1

• above the kidneys
• right and left adrenal glands

Question 2

How many arteries and veins does each adrenal gland have?

Answer 2

• both adrenals have many arteries but only one vein each
• right and left adrenal veins
• e.g. abdominal aorta, adrenal arteries, middle adrenal arteries, inferior adrenal arteries

Question 3

Where do the left and right adrenal veins drain into?

Answer 3

• left adrenal vein drains into renal vein
• right adrenal vein drains into IVC (inferior vena cava)

Question 4

What is the microanatomy of the adrenal glands?

Answer 4

• outer layer - zona glomerulosa
• middle layer (thickest) - zona fasciculata
• inner layer - zona reticularis
• zona glomerulosa, fasciculata and reticularis together form the adrenal cortex
• the adrenal medulla is found at the centre (inner to zona reticularis)
• capsule –> zona glomerulosa –> zona fasciculata –> zona reticularis –> medulla

Question 5

What hormones does the adrenal cortex produce and which zonas produce what?

Answer 5

Corticosteroids:

• mineralocorticoids - key one is aldosterone –> produced by zona glomerulosa
• glucocorticoids - cortisol –> produced by zona fasciculata and reticularis
• small amount of sex steroids - androgens and oestrogens –> produced by zona fasciculata and reticularis

Question 6

What are the steroid hormones synthesised from?

Answer 6

• all steroids synthesised from cholesterol
• it has 27 carbons

Question 7

What are the key steps of synthesis for aldosterone?

Answer 7

1. cholesterol side chain cleavage forms pregnenolone
2. 3-beta-hydroxysteroid dehydrogenase oxidises 3rd carbon in pregnenolone to form progesterone
3. 21 hydroxylase adds OH group to carbon 21 of progesterone to form 11-deoxycorticosterone
4. 11 hydroxylase adds OH group to carbon 11 to form corticosterone
5. 18 hydroxylase adds OH group to carbon 18 to form aldosterone

Question 8

What are the key steps of synthesis for cortisol?

Answer 8

1. cholesterol side chain cleavage forms pregnenolone
2. 3-beta-hydroxysteroid dehydrogenase oxidises 3rd carbon in pregnenolone to form progesterone
3. 17 hydroxylase adds OH group to carbon 17 of progesterone to form 7-hydroxyprogesterone
4. 21 hydroxylase adds OH group to carbon 21 to form 11-deoxycortisol
5. 11 hydroxylase adds OH group to carbon 11 to form cortisol

Question 9

What hormones does the adrenal medulla produce?

Answer 9

• neuroendocrine/chromaffin cells of the medulla produce catecholamines:
• adrenaline aka epinephrine (80%)
• noradrenaline aka norepinephrine (20%)
• dopamine

Question 10

How does aldosterone work?

Answer 10

• major net effect is to conserve body sodium by stimulating its reabsorption, and controlling BP
• binds to receptors in kidney and stimulates Na+ reabsorption in distal convoluted tubule and cortical collecting duct (and in sweat glands, gastric glands, colon)
• also stimulates K+ and H+ secretion in distal convoluted tubule and cortical collecting duct
• aldosterone switches on sodium-potassium ATPase which helps you reabsorb sodium and lose potassium (which goes into the urine)
• increased sodium reabsorption causes water absorption too, which increases blood volume and therefore increases blood pressure

Question 11

How is aldosterone regulated?

Answer 11

• in kidney, the juxtaglomerular apparatus (JGA) is always monitoring blood pressure
• decreased renal perfusion pressure (normally associated with decreased arterial BP), decreased Na+ load to top of loop of Henle (macula densa cells), and increased renal sympathetic activity (direct to JGA cells) = JGA release renin into blood
• the liver makes angiotensinogen protein which renin converts into angiotensin I
• angiotensin converting enzyme (ACE) in lungs converts angiotensin I –> angiotensin II, which works on zona glomerulosa to produce aldosterone (and other effects e.g. vasoconstriction)
• at zona glomerulosa, angiotensin II activates side chain cleavage, 3-hydroxysteroid dehydrogenase, 21, 11, 18 hydroxylases = more aldosterone produced

Question 12

What are the physiological effects of cortisol?

Answer 12

• normal stress response
• weak mineralocorticoid effects
• metabolic effects:
• peripheral protein catabolism
• hepatic gluconeogenesis
• increased BGC
• fat metabolism (lipolysis in adipose tissue)
• enhanced effects of glucagon and catecholamines
• renal and cardiovascular effects - excretion of water load, increased vascular permeability

Question 13

How is cortisol secretion regulated?

Answer 13

• cortisol, ACTH (adrenocorticotrophic hormone) and CRH (corticotrophin releasing hormone) have a negative feedback system
• increased cortisol means less CRH and ACTH secreted from hypothalamus and pituitary gland, and vice versa

Question 14

What is the effect of ACTH on the adrenals?

Answer 14

Activation of:

• side chain cleavage enzyme
• 3-hydroxysteroid dehydrogenase
• 17, 21, 11 hydroxylase
• results in cortisol production

Question 15

What kind of rhythm does cortisol have?

Answer 15

• diurnal rhythm
• increase starts at 12:30am and peaks at 8:30am, then decreases pretty much evenly to 12:30am again
• daily cycles - increase in ACTH = increase in cortisol - graphs mirror each other

Question 16

Where is the adrenal medulla derived from?

Answer 16

Ectodermal neural crest

Question 17

What are the steps for forming adrenaline and noradrenaline?

Answer 17

1. tyrosine (precursor for Adr&NA synthesis) has O2 added to make dopa
2. dopa has CO2 removed to form dopamine
3. dopamine then converted to noradrenaline
4. methyl donor group added to noradrenaline to form adrenaline

Question 18

Where are catecholamines stored and how are they released?

Answer 18

• stored in cytoplasmic granules
• released in response to ACh from preganglionic sympathetic neurones

Question 19

What is the role of catecholamines?

Answer 19

• fight or flight response e.g. tachycardia, sweating, increased BGC, alertness, vasoconstriction
• noradrenaline and adrenaline bound to albumin
• degraded by two hepatic enzymes: monoamine oxidase and catechol-O-methyl transferase

Question 20

What happens in Addison’s disease?

Answer 20

• primary adrenal failure
• autoimmune disease where the immune system decides to destroy the adrenal cortex –> cortisol and aldosterone deficiency
• salt loss
• TB of the adrenal glands is commonest cause worldwide
• pituitary starts secreting lots of ACTH and hence MSH (melanocyte-stimulating hormone)
• eventual death due to low BP

Question 21

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

Answer 21

• increased pigmentation of skin / hyperpigmentation
• autoimmune vitiligo may coexist (white patches in skin)
• no cortisol or aldosterone = low blood pressure
• adrenal crisis - syncope, fever, convulsions, hypoglycaemia, hyponatremia, severe vomiting and diarrhoea
• GI - nausea, vomiting, constipation, abdominal pain
• weakness
• weight loss

Question 22

Why do patients with Addison’s disease have a good tan (hyperpigmentation)?

Answer 22

• POMC (pro-opio-melanocortin) is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
• people who have pathologically high levels of ACTH will also have levels of MSH and may become tanned

Question 23

How do you treat Addison’s disease?

Answer 23

• rehydrate with normal saline
• give dextrose to prevent hypoglycaemia which could be due to glucocorticoid deficiency
• give hydrocortisone / another glucocorticoid

Question 24

What happens in Cushing’s syndrome?

Answer 24

• occurs due to an excess of cortisol or other glucocorticoid
• too much cortisol = metabolism changes and weight gain happens

Question 25

What are four possible causes of Cushing’s syndrome?

Answer 25

• taking steroids by mouth (common)
• pituitary dependent Cushing’s disease (pituitary adenoma)
• ectopic ACTH (lung cancer)
• adrenal adenoma / carcinoma

Question 26

What are the clinical signs and symptoms of Cushing’s syndrome?

Answer 26

• thin skin
• proximal myopathy - weakness of upper limbs
• centripetal obesity (lemon on sticks)
• diabetes, hypertension and osteoporosis
• immunosuppression (reactivation of TB)
• moon face
• striae (stretch marks)
• fat pads on back of neck
• poor wound healing and easy bruising