Adrenal steroids

Question 1

What happens in a glucocorticoid deficiency?

Answer 1

Decreased Na, hypotension and decreased glucose

Loss of cortisol effects on vascular tone - hypotentsion - low blood pressure decreases GFR, therefore less water excreted.

Cortisol inhibits ADH - and inhibition of cortisol results in increased ADH production - more reabsorption of water -> decreased Na by dilution.

You would also get hypoglycaemia because of reduced hepatic gluconeogenesis (decreased glucose)

Question 2

What does aldosterone (mineralocorticoid) deficiency cause?

Answer 2

Decreased NA, Increased K+ and metabolic acidosis

Hyponatraemia - It is am ECF regulator, induces the reabsorption of Na from the urine. Loss of aldosterone causes loss of Na in urine and water follows. This can result in production of ADH when 8% of intravascular volime -> vasoconstrictor and retain more water that dilutes Na levels.

Hyperkalaemia from reduced renal K+ excretion and reduced H+ excretion causes metabolic acidosis.

Question 3

How is aldosterone produced and what does it do?

Answer 3

The juxtaglomerular apparatus senses low Na and produces renin, which is converted to angiotensin I and then to angiotensin II by ACE. Angiotensin II stimulates the adrenal cortex to produce aldosterone. Aldosterone increases Na and subsequently H20 reabsorption and it increases the intravascular volume.

Question 4

What are the causes of adrenal failure?

Answer 4

Primary (adrenal gland) - means that the issue is at the adrenal gland

Secondary/tertiary (pituitary/hypothalamus)

Question 5

What regulates the production of cortisol?

Answer 5

Hypothalamus produces corticotrophin releasing factor, which sitimulates the pituitary t produce ACTH (adrenocorticotrophic hormone). ACTH stimulates the adrenal cortex to produce cortisol.

Cortisol has negative feedback to the pituitary and to the hypothalamus.

Question 6

How is ACTH made and what is the consequence?

Answer 6

ACTh is a peptide product of POMC (proopiomelanocoritin).

As POMC is cleaved it produces 3 melanocyte stimulating hormones.

ACTH contains an alpha MSH.

Thus, increase POMC cleavage to make ACTH results in increased MSH which cause a tan.

Any primary adrenal problem, with loss of negative feedback for ACTH and thus adensoine production will result in a tan.

The tan occurs most apparently in the skin flextures, buccal mucosa, old scars, freckles, nails.

Question 7

What regulates cortisol?

Answer 7

ACTH is regulated by cortisol and is independent of the mineralocorticoid axis

Question 8

When is obesity of pathological cause?

Answer 8

Glucocorticoid excess causes profound growth failure and obesity. It increases the breakdown of muscle into glucose and promotes the deposition of fat. It also causes fat redistribution.

Short fat kid = problem

Fast change in weight

Check the children’s growth charts - they will stop growing if they are pathologically obese. Simple obesity drives growth but they enter puberty earlier and may end a similar height as their parents.

Look for change of look.

Adult glucocorticoid excess leads to truncal obesity

Childhood flucocorticoid excess leads to generalised obesity

Glucocorticoid excess causes;
Moon face, thinning skin (stretch marks, bruising)
Androgen excess - prodcued on the way to producing cortisol (sexual hair [hirsutism], amenorrhoea)
Myopathy (proximal weakness)
Glucose intolerance (diabetes mellitus)
Hypertension
Osteoporosis

Question 9

What do you test for when looking for pathological obesity?

Answer 9

24 hour urinary free cortisol significantly high

Normal Na, Low potassium, low renin

The high levels of cortisol are stimulating the mineralocorticoid receptors and actibg like aldosterone -> increase in Na reabsorption and loss of K+. Negative regulation is reducing renin levels.

Question 10

What is cushings syndrome?

Answer 10

Glucocorticoid excess and probable androgen excess.

Caused by a tumour in the pituitary making more ACTH.

Primary functional adrenal tumour

ACTH secreting tumour in places other than the pituitary.

Exogenous glucocorticoid.

Question 11

What can excess cortisol do to the mineralocorticoid receptor?

Answer 11

Can bind it and activate it. This only happens when there is excess corticoid. Usually it is metabolised before this can happen.

Question 12

What would happen with partial loss of the glucocorticoid receptor?

Answer 12

This would stimulate the production of CRF and ACTH to produce more cortisol because of reduced negative feedback. This would result in the cortisol stimulating the mineralocorticoid receptor. This would cause mineralocorticoid excess, which may cause hypertension of low potassium.

Would not be able to produce cortisol when sick. Bioproducts of cortisol production is the androgens, which cause hirsutism.

Overall:
Increased cortisol
Secondary mineralocorticoid effects - alkolosis, hypokalaemia, hypertension.
Hyperandrogenism (amenorrhoea, hirsutism).
Fatigue/tirdness (cortisol insensitivity)

Question 13

What do you get with loss of function of the mineralocorticoid receptor?

Answer 13

Would look like aldosterone deficiency but would be high levels of aldosterone (pseudohypoaldosteronism.

High aldosterone and renin levels
Depleted ECF
high K+ and low Na+

Question 14

What happens with ACTH receptor loss of function mutation?

Answer 14

No cortisol - adrenal crisis
Low blood pressure - collapse and die.

In this case, the adrenal glands are small and non-functioning.

Hypotension
Low Na
Hypoglcaemia

Question 15

What is the function of cortisol?

Answer 15

It inhibits ADH.

Increases vascular tone - hypertentsion

Cortisol inhibits ADH - and inhibition of cortisol results in increased ADH production - more reabsorption of water -> decreased Na by dilution.

Question 16

What does high levels of 17 OH progesterone indicate in an infant?

Answer 16

It is a byproduct in making cortisol and androgens. It suggests a defect in cortisol synthesis.

The low cortisol will also lead to high ACTH levels with secondary stimulation of the adrenal cortex and excess production of adrenal precursors and adrenal hyperplasia. Can cause very high levels of testosterone, and make a girl highly mascularized. They thought she was a man but had a uterus.

Congenital adrenal hyperplasia

Question 17

What is congenitial adrenal hyperplasia?

Answer 17

It is when the adrenal glands are not able to produce cortisol. This causes the pituitary to increae the production of ACTH and this has a secondary stimulation on the adrenals resulting in hyperplasia.

The disrupted production of cortisol can resulting in androgens being produced. If this is a female then they become hypervirulized and develop external male genitalia. If they are a male it can cause increased growth can cause a large penis, tall and dark.

Lack of cortisol causes an increase in the ADH, hypotension and loss of glucose

Boy aged 4 with a very large penis, very tall for age and for parents, dark skin relative to parents, pubic hair present, non-pubertal testis (has to be adrenal problem)
Hypertension, low K, normal Na.

Bone age of 11
Small testis
High blood pressure
Reduced K+
Making lots of MSH

Question 18

What is precocious puberty?

Answer 18

Will have descended testis in boys and that is how you differentiate from other testosterone excess disorders.

Question 19

What is Addison’s disease?

Answer 19

AKA acute adrenal insufficiency

Not producing cortisol or aldosterone

Abdominal pain, weakness/apathy, nausea/vomiting, hypoglycaemia, seizures, hypotension, cardiovascular collapse, decreased Na, decreased Cl, increased K and academia

Fluid and electrolyte resuscitation, hydrocortisone replacement, inotropic support