Disorders of the adrenal cortex

Question 1

Explain how cortisol secretion is controlled by ACTH & CRH?

Answer 1

HPA axis (hypothalamus-pituitary-adrenal axis)
hypothalamus --> CRH --> pituitary --> ACTH --> adrenal --> cortisol

Question 2

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

Answer 2

POMC (released after eating) is the precursor to ACTH & MSH
MSH is within ACTH sequence in POMC
so ACTH has some MSH like activity when present in excess

(MSH normally leads to pigmentation), ACTH stimulates adrenal glands - produce cortisol (steroid hormone)

Question 3

Describe the main action of cortisol

Answer 3

increase muscle proteolysis
increase lipogenesis
disturbance in Ca2+ metabolism & loss of bone matrix protein
can have mineralocorticoid effects

Question 4

Explain how cortisol can have weak mineralocorticoid & androgen effects?

Answer 4

cortisol effect on target tissue through binding to receptors in cytoplasm / nucleus
all steroid hormone receptors have similar basic structure (contains both hormone & DNA binding domain)
hormone binding domain of mineralocorticoid & androgen receptors have over 60% sequence homology
therefore cortisol can bind to these receptors to a limited extent

Question 5

Which is the best test for adrenal cortical function?

Answer 5

best test for Cushing’s is when patient is sleeping as cortisol should be lowest, so if cortisol is high when patient is sleeping then they have Cushing’s
cortisol levels max in morning - 9am test

Question 6

what is a biochemical test to test out corticosteroid deficiency?

Answer 6

synacthen test
give synthetic ACTH (synACTHen), blood test at 0 & 30mins, if above certain no. of cortisol then fine - see if adrenal cortex responds to ACTH

Question 7

What’s a way of testing ACTH levels?

Answer 7

ACTH should increase with stress & hypoglycaemia OR insulin stress test (pituitary ACTH deficiency)

insulin tolerance test - lowers glucose, ACTH should increase

Question 8

Explain the effects of over secretion of cortisol

how does it lead to ‘steroid diabetes’?

Answer 8

increase muscle proteolysis: increase hepatic gluconeogenesis –> hyperglycaemia leading to polydipsia & polyuria leading to steroid diabetes

steroid = cortisol

Question 9

How does excess cortisol secretion affect muscles?

Answer 9

increase muscle proteolysis –> wasting of proximal muscles –> thin arms & legs ‘muscle weakness’

loss of tissue protein = negative nitrogen balance

Question 10

How does excess cortisol secretion affect the skin?

Answer 10

catabolic effect on protein structures in the skin = purple striae in the lower abdomen, upper arms & thighs –> easy bruising due to thinning of skin & subcutaneous tissue

Question 11

How does excess cortisol secretion affect fat of the body?

Answer 11

increases lipogenesis - deposit fat in abdomen, face, neck: weight gain & moon shaped face

Question 12

How does excess cortisol secretion affect Ca2+?

Answer 12

disturbance in Ca2+ metabolism & loss of bone matrix proteins –> osteoporosis –> back pain & collapse of ribs

Question 13

What does the weak mineralocorticoid effect of cortisol lead to?

Answer 13

hypertension from Na+ & fluid retension

Question 14

What causes Addison’s?

Answer 14

low cortisol with high ACTH
decrease cortisol secretion due to AUTOimmune destruction of adrenal gland (loss of mineralocorticoids - Addisonian crisis (emergency)
chronic debilitating disorder - Addison’s disease

Question 15

What are the initial non-specific symptoms of Addison’s?

Answer 15

tiredness, extreme muscle weakness, dehydration, anorexia, vague abdominal pain, weight loss, dizziness

Question 16

What are more specific signs of Addison’s?

Answer 16

increased pigmentation esp. exposed areas of body, scars, points of creases/friction (ACTH mediated melanocyte stimulation)
decrease BP: Na+ & fluid depletion not enough Na+ & H2O in cell
hypoglucaemia episodes esp. fasting
decrease vascular tone (contraction of vessels to maintain BP)
postural hypotension (reduced systolic BP) from fluid depletion

Question 17

How do you treat Addisons?

Answer 17

with intra-venous cortisol & fluid replacement (5% dextrose - replace glucose)

Question 18

functions & actions of adrenaline

Answer 18

released in fight/flight: stress response
cardiac muscle: increase cardiac output, increase blood to muscle
CNS: increase mental awareness
liver: increase lipid metabolism, gluconeogenesis
skeletal muscle: carbohydrate metabolism: increase glycogenolysis

Question 19

What is mineralocorticoid and what is it’s function?

Answer 19

Na+ & water in cell, K+ out of cell (Sodium-K+ pump)
deficiency of M: low Na+ into cell, leading to dehydration, high K+ in cell
EXCESS: high Na+ in cell, cell swells, hypertension, low K+ in cell

Question 20

What is Glucocorticoid’s action?

Answer 20

increase glucose production, breakdown of protein (proteolysis), redistribution of fat (tissue specific enzyme)
DEFICIENCY: low glucose, weight loss, underweight, nausea, hyPOtension
EXCESS: increase glucose, weight gain, increase appetite, hypertension, cushingnoid (signs of cortisol hormone)

Question 21

What are androgens?

Answer 21

sex steroids: increase BP, decrease glucose
reproduction & development of sex characteristics e.g. breast tissue, testosterone produced by adrenal gland in women

Question 22

What are the different layers of the adrenal cortex and what do they each secrete? from outermost to inner

Answer 22

outer: zona glomerulosa - secrete mineralocorticoids e.g. aldosterone regulate Na+ & H2O
zona fasiculata: secretes cortisol, regulate carbohydrate metabolism, glucose
CORE: zona reticularis: secretes glucocorticoids & androgens (small amounts) - sex hormones

Question 23

Explain how the steroid hormones affect their target tissues

Answer 23

act on intracellular receptors
enter nucleus & alter DNA transcription (to mRNA)
(different to peptide hormones which have cell surface receptors