6 - ENDOCRINE DISORDERS: THE ADRENAL GLAND

Question 1

CRH

Answer 1

Corticotropin Releasing Hormone

Question 2

ACTH

Answer 2

AdrenoCortico Tropic Hormone

Question 3

Adrenal cortex layers

Answer 3

• zona glomerulosa
• zona fasciculata
• zona reticularis

Question 4

zona glomerulosa

Answer 4

secreting aldosterone, control of renin from kidney.
Na rabsorption.
Production of mineralcorticoids

Question 5

zona fasciculata

Answer 5

glucocorticoid secretion - cortisol

Question 6

zona reticularis

Answer 6

secretion of sex hormones - androgen.
Precursor for testosterone and oestrogen.
Produces DHEA (precursor to androgens)

Question 7

adrenal cortex

Answer 7

all hormones synthesised from cholesterol.

Has lots of LDL receptors to combine cholesterol and can act as store to synthesise hormones rapidly.

Question 8

ALDOSTERONE

Answer 8

• Regulates Na and K homeostasis
• Secreted in response to low blood pressure/volume
• Promotes Na reabsorption and K+ excretion in the kidney

Question 9

Cortisol

Answer 9

• Raises blood glucose
• Increases lipid and protein breakdown
• Resistance to stress
• Immune response depression
• Bound by cortisol binding protein in the blood
• Highest levels 8am, lowest midnight.

Question 10

DHEA

Answer 10

produced from zona reticularis

- precursor to androgens, tested for adrenal gland function

Question 11

ANDROGENS

Answer 11

made from Dehydroepiandrosterone (DHEA)
Converted to testosterone in circulation, converted to oestrogen in ovaries if female
Secondary sexual characteristics
Prepubertal growth spurt

Question 12

THE ADRENAL MEDULLA

Answer 12

• Produces adrenaline, noradrenaline (CATECHOLAMINES) from chromaffin cells in response to nervous stimulation.
• Fight/flight response
Not under control of ACTH from anterior pituitary.

Question 13

Catecholamines (epinephrine and norepinephrine)

Answer 13

Line blood vessels, increase heart rate, force and pressure, increase glucose levels.

Question 14

COMT (catechol-o-methyltransferase)

Answer 14

enzyme that breaks down catecholamines and Metabolises into metanephrine and normethanephrine.

• broken down products seen in urine
• assess quantity of adrenaline
• cannot measure adrenaline as broken down too quick

Question 15

Assess Adrenal function

Answer 15

Competitive ELISA - cortisol, aldosterone, DHEA, metanephrine
OR
2-site ELISA - plasma ACTH

Question 16

Competitive ELISA
(cortisol, aldosterone, DHEA, metanephrine)

Answer 16

• Antibody attached to well (specific for hormone X)
• Patient’s serum added PLUS HRP labelled hormone X
• TMB subsrate added
• Yellow Colour development
• This e.g. = low patient hormone X as few binding sites filled, high colour absorbance

Question 17

2-site ELISA

Measure plasma ACTH

Answer 17

1. Antibody to ACTH in well.
2. Serum added.
3. C-terminal of ACTH binds to antibody in well.
4. Antibody added to bind to N-terminal, linked to HRP enzyme.
5. TMB substrate added, yellow colour change.
6. High absorbance = more colour change. Directly proportional.

Question 18

Dexamethasone (glucocorticoid) suppression test

Answer 18

Looks like cortisol to body. Tests if cortisol production is regulated by negative feedback.
- dexamethasone inhibits ACTH release in healthy people, -ve feedback.
- If no decrease in cortisol, ACTH and CRH is still being released.
Pituitary tumour or ectopic ACTH source. Produced from tumour instead of anterior pituitary.

Question 19

Stress hormone pathway

Answer 19

Corticotropin-releasing hormone (hypothalamus),
Adrenocorticotropic hormone (ACTH) (anterior pituitary),
cortisol (adrenal gland).

Question 20

Synacthen test

Answer 20

Tests if adrenal gland responds to ACTH.

• give patient IV synacthen, looks like ACTH
• should stimulate cortisol production in adrenal gland.
• measure cortisol, if no rise then suspect adrenal insufficiency.

Question 21

Adrenal cortical insufficiency

Answer 21

not producing enough hormones, aldosterone.

Question 22

Addison’s disease

Answer 22

destruction of both adrenal glands by autoimmune disease or infection.

Question 23

Adrenal cortical insufficiency symptoms

Answer 23

muscle weakness, tiredness, skin pigmentation, vomiting, sweating, hypotension, low blood Na.
High K causes cardia arythmias.
High ACTH to increase cortisol levels.
Precursor to ACTH causes pigmented skin.

Question 24

DIAGNOSTIC FINDINGS OF ADRENAL CORTICAL INSUFFICIENCY

Answer 24

Plasma ACTH higher than normal range
Plasma cortisol less than normal range
Synacthen test (ACTH analogue) – little, if any, increase in cortisol

If aldosterone production is decreased too:
Hyponatraemia (serum sodium low)
Hyperkalaemia (serum potassium high)
Uraemia – high levels of urea in blood (dehydrated)

Question 25

HYPERADRENALISM

Answer 25

excess cortical hormone secretione.g. Cushing's syndrome

Question 26

Hyperadrenalism (Cushing's syndrome) symptoms

Answer 26

muscle weakness, hypertension (cortisol stimulates mineralcorticoid leading to aldosterone effects), hirsutism (unwanted hair), central obesity, osteoporosis.

Question 27

Conn's Syndrome (hyperaldosteronism)

Answer 27

Aldosterone in response to low blood pressure, cause water retention by reabsorption of Na. symptoms: 1. Hypertension 2. Hypokalemia 3. metabolic alkalosis 4. decreased renin secretion

Question 28

SOME CAUSES OF HYPERADRENALISM

Answer 28

* Adrenal cortical hyperplasia * Adrenal cortical adenoma * Adrenal cortical carcinoma

Question 29

Adrenal cortical hyperplasia

Answer 29

Increase in cell number Increased ACTH stimulation, maybe tumour in pituitary gland. Diagnosis = dexamethasone suppression test shows raised cortisol with no negative feedback

Question 30

Adrenal cortical adenoma

Answer 30

``` • May secrete excess cortisol (Cushing’s) or aldosterone (Conn’s) • Yellow cut surface- stored cholesterol • Diagnosis: ACTH not detectable • If cortisol-secreting: - Cortisol increase • If aldosterone-secreting - Plasma aldosterone high - Serum Na high - Serum K low - Urine K high ```

Question 31

Adrenal cortical carcinoma

Answer 31

``` • Yellow/white tumour • Often secrete cortisol - Cushing’s • Often secrete androgens - hirsutism • Diagnosis: - Cortisol increase - DHEA increase ```

Question 32

PHEOCHROMOCYTOMA – ADRENAL MEDULLA TUMOUR

Answer 32

• Symptoms: sweating, headaches, palpitations, hypertension… • Diagnosis: - Increase in adrenaline/noradrenaline breakdown products (metanephrine and normetanephrine)