The Adrenal Glands & Disorders

Question 1

Where are the adrenal glands located?

Answer 1

Pyramidal structure, on top of the kidneys

Question 2

Describe the anatomical division of the adrenal gland in terms of the different layers of the cortex

Answer 2

Capsule: surrounds gland

Cortex: (GFR) zona glomerulosa (aldosterone) zona fasiculata (cortisol) zona reticularia (androgens) SALT, SUGAR, SEX

Medulla: chromaffin cells (NA, A)

Question 3

Name the hormones produced by the different layers of the adrenal cortex

Answer 3

Glomerulosa: mineralocorticoids (aldosterone SALT)

Fasiculata: glucocorticoids (SUGAR)

Feticularis: androgens (SEX)

Question 4

Describe in general terms the structure and functions of the steroid hormones

Answer 4

Synthesised from cholesterol in AG, lipid soluble (can diffuse PM), bind nuclear receptors to modulate gene transcription

Question 5

What hormones do the class ‘steroid’ include?

Answer 5

Glucocorticoids (cortisol)

Mineralocorticoids (aldosterone)

Androgens

Oestrogen

Progestins

Question 6

What are the 3 endogenous causes of cushings?

Answer 6

Pit

Ectopic

Tumour

Question 7

What type of receptors do steroid hormones bind?

Answer 7

Nuclear

Question 8

What is the role of 21-hydroxylase?

Answer 8

cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones - in the adrenal cortex.

Def = low glucocorticoids/mineralocorticoids, high = androgens

Question 9

Explain how the steroid hormones affect their target tissues

Answer 9

Nuclear receptor = modulate gene transcription. Diffuse PM, bind receptor, dissociation of chaperone protein, receptor ligand to nucleus, dimerisation, receptor binds GREs or transcription factors = reg gene transcription

Question 10

Explain how cortisol secretion is controlled by ACTH and CRH

Answer 10

HPA axis: CRH by hypo to AP, ACTH by AP to AG, AG prod cortisol

-ve feedback of cortisol and ATCH

Question 11

Explain how ACTH can lead to increased pigmentation in certain areas of the body

Answer 11

Adrenal insufficiency

Decreased cortisol

-ve feedback on AP reduced

More POMC required to synthesise ACTH

High ACTH = raised melanocyte stim hormone MSH = affects melanocytes

Question 12

What are the signs of chronic high cortisol?

Answer 12

Re-distribution of fat (abdo, buffalo hump, moon face)

Acute weight gain

Purple striae

Hyperglycaemia

Hypertension

Question 13

What are the causes of cushings syndrome?

Answer 13

External = prescribed glucocorticoids (MOST COMMON)

Endogenous = benign pit adenoma secreting ACTH, excess cortisol from adrenal tumour, not pit/adrenal tumours prod ACTH/CRH

Question 14

What is cushings disease?

Answer 14

benign pit adenoma secreting ACTH

Question 15

What are purple striae indicative of and why are they formed?

Answer 15

Cushings = proteolysis of skin

Question 16

What is cushings SYNDROME?

Answer 16

Chronic excessive exposure to cortisol

Question 17

What is the most abundant corticosteroid?

Answer 17

cortisol

Question 18

Describe the main actions of cortisol.

Answer 18

Increased protein breakdown

Increase gluconeogenesis and glycogen storage

Increased lipolysis

Anti-inflam

Immune depression

Question 19

What signals to the hypothalamus stim CRH release?

Answer 19

Pain, fever, hypoglycaemia, low BP

Question 20

How does cortisol fluctuate?

Answer 20

Highest in morning/lowest at night

Question 21

What is the function of aldosterone?

Answer 21

Reg gene transcription

Reg plasma Na, K+, arterial blood pressure

Promotes Na+/K+ pump expression = promotes reabsorption of Na and excretion of K+

Central role on RAAS

Question 22

What is hyperaldosteronism?

Answer 22

High aldosterone

Primary = defect in adrenal cortex: bilateral idiopathic adrenal hyperplasia (high aldosterone:renin ratio)

Secondary = over activity of RAAS: tumour, renal artery stenosis (low aldosterone:renin ratio)

Question 23

What are the signs of hyperalsosteronism?

Answer 23

High BP, hypernatriaemia, hypokalaemia

Question 24

What protein transports cortisol and aldosterone?

Answer 24

transcortin

Question 25

What is the treatment for hyperaldosteronism?

Answer 25

Spironolactone = mineralocorticoid receptor antagonist

Question 26

What is Addisons disease?

Answer 26

Chronic adrenal insufficiency

Cause = autoimmune atrophy

Increased skin pigmentation

Question 27

What is an addisonian crisis?

Answer 27

Symptom of severe adrenal insufficiency = hypotension, vascular collapse, pyrexia

Treat = fluids, cortisol

Question 28

Describe in general terms the structure and functions of adrenaline

Answer 28

Made from tyrosine

Flight and flight = heart B1 increased HR/contractility, lungs B2 bronchodilation, blood vessels A1 con + B2 dil

Question 29

Explain how adrenaline exerts its effects on target cells

Answer 29

GPCR: alpha 1 + 2, beta 1 + 2

Question 30

Describe the components and overall function of the renin angiotensin aldosterone system

Answer 30

Slide picture

Question 31

What are the inputs and outputs of RAAS?

Answer 31

In = hypotension, hypovolaemia.

Out = increased blood pressure, increased blood vol

Question 32

Outline pheochromocytoma

Answer 32

Chromaffin cell tumour

Rare NA secreting tumour = severe hypertension

Question 33

Describe tests of adrenal cortical function

Answer 33

CT, MRI, functional PET

Suspect Def = aldosterone def (low Na+, high K), ACTH def (low Na+, K+ norm, if no glucocorticoids taken = adrenal tumour, if taken = exogenous cushings), SynACTHen test (cort low)

Suspect Exc = aldosterone (low K+), cortisol (midnight, 24hr urine = high), dex supress: Low dose (low cortisol/ATCH), high dose (ACTH high in ectopic, low in pit adenoma)

Question 34

Explain how cortisol can have weak mineralocorticoid and androgen effects

Answer 34

Aldosterone and cortisol (a glucosteroid) have similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids.