Clinical aspects of adrenal function

Question 1

What types of hormones are secreted by the adrenal cortex?

Answer 1

Steroid hormones

Question 2

What are steroid hormones derived from?

Answer 2

Cholesterol

Question 3

What are the hormones released by the adrenal cortex?

Answer 3

Glucocorticoids
Mineralocorticoids
Androgens

Question 4

What can happen when glucocorticoids are found in excess?

Answer 4

Can mineralocorticoid properties

Question 5

How do steroids affect target cells?

Answer 5

Enter the nucleus and affect gene transcription

Question 6

What is the function of mineralocorticoids?

Answer 6

Salt and water retention

Question 7

What effects do mineralocorticoids have when found in excess?

Answer 7

Glucocorticoid effects

Question 8

What controls androgen release from the adrenal cortex?

Answer 8

Puberty and pituitary gland

Question 9

Why do androgens released from the adrenal cortex have little effect?

Answer 9

The androgens have weak effects until they are metabolised peripherally into testosterone

Question 10

What types of hormones does the adrenal medulla release?

Answer 10

Catecholamines - amines

Question 11

What receptors to catecholamines bind to on target cells?

Answer 11

G-protein coupled receptors

Question 12

Why does a dysfunction in the adrenal medulla no affect the release of catecholamines to a large extent?

Answer 12

They are predominantly synthesized by the sympathetic nerve endings

Question 13

What area of the adrenal cortex is affected by Cushing’s?

Answer 13

Zona fasciculata

Question 14

What hormone is elevated in the blood in Cushing’s syndrome?

Answer 14

Cortisol

Question 15

What is the source of high cortisol in Cushing’s syndrome?

Answer 15

Three main causes:

1. Increase in production of ACTH from the pituitary gland = this is called Cushing’s disease and is caused by pituitary adenoma
2. Ectopic tissues producing ACTH - cancers (small cell lung cancer)
3. Steroid drugs for clinical use

Question 16

How do you diagnose Cushing’s syndrome?

Answer 16

1. Look for increased levels of glucocorticoids
2. Measure urinary metabolites of cortisol
3. Measure ACTH - distinguishes adrenal from pituitary source
4. Suppression test - Dexamethasone. Synthetic steroid with glucocorticoid excess - when injected in high quantities should suppress release of ACTH
5. Imaging - localise the source of ACTH via imaging or nuclear medicine scan -> label molecule that binds to ACTH receptor

Question 17

Treatment of Cushing’s syndrome

Answer 17

Surgery

Drugs

Question 18

What are possible side effects from Cushing’s disease treatment?

Answer 18

Removal of adrenal glands = Nelson’s disease

Pituitary gland loses its negative feedback

Grows in size = blindness

Increased production of ACTH = pigmentation. MSH (melanocortin stimulating hormone) is a precursor for ACTH

Question 19

What area of the adrenal medulla does Addison’s disease affect?

Answer 19

Zona fasciculate and glomerulosa

Question 20

What is characterised in Addison’s disease?

Answer 20

Inadequate secretion of hormones from the adrenal cortex

Question 21

What are the causes of Addison’s disease

Answer 21

1. Autoantibodies that attack the adrenal gland
2. Bad infection - rapid adrenal failure
3. Steroid drugs - if suddenly stops using. Since they have caused atrophy of the adrenal glands

Question 22

What diagnostic test can be performed to diagnose Addison’s

Answer 22

Inject ACTH. If the adrenal glands fail to respond - intrinsic adrenal disease/ atrophy

Question 23

Why does the use of steroid drugs cause the adrenal gland to atrophy?

Answer 23

Activates the negative feedback loop so there is a decrease in ACTH production

ACTH stimulates survival and growth of adrenal cortical cells

Suppression of ACTH therefore, leads to adrenal cortex atrophy

Question 24

What are the symptoms of Addison’s?

Answer 24

Salt and water wasting - low blood pressure
Low blood glucose
Fatigue
Weight loss

Question 25

What is congential adrenal hyperplasia?

Answer 25

A rare group of autosomal recessive conditions characterized by the mutation in production of steroid hormones The most common = mutation in 21 hydroxylase enzyme - turns precursors into mineralocorticoids and glucocorticoids

Question 26

What is characterised in congenital adrenal hyperplasia?

Answer 26

Increase in the production of sex hormones Low level of glucocorticoids and mineralocorticoids in the blood

Question 27

Why is there elevated sex hormone levels in the blood of congenital adrenal hyperplasia patients?

Answer 27

All the precursors that should become glucocorticoids and mineralocorticoids become sex hormones instead Sex hormones and glucocorticoids/mineralocorticoids share the same precursors

Question 28

What factors determine the symptomology of the patients?

Answer 28

Age and the level of blockage of metabolic pathways

Question 29

What are the symptoms of congenital adrenal hyperplasia?

Answer 29

In females If severe - birth, ambiguous genetalia If milder - childhood/ adolescence, accelerated growth and hair growth If mild - adulthood, infertility or menstrual problems In males If severe - problems producing glucocorticoids = salt and water retention, accelerated puberty and exaggerated growth

Question 30

What tests can be done to check if baby has congentil adrenal hyperplasia?

Answer 30

In the US - babies screened for 17 hydroxyprogesterone intermediate Elevated in congenital adrenal hyperplasia patients

Question 31

What is Pheochromocytoma?

Answer 31

Benign neuroendocrine tumours in the adrenal medulla

Question 32

What does Pheochromocytoma cause?

Answer 32

Excess secretion of catecholamines from the adrenal medulla

Question 33

How do you diagnose Pheochromocytoma?

Answer 33

1. Suspicious if patient does not respond to hypertensive drugs 2. Measure the metabolites of adrenaline in the urine 3. Nuclear medicine scans - look for areas secreting an excess of catecholamines

Question 34

What symptoms does Pheochromocytoma cause?

Answer 34

There is excess sympathetic activation This leads to excess noradrenaline and adrenaline metabolites in the urine Palpilations, weight loss, abdonminal pain, hypertension and anxiety

Question 35

How can you treat Pheochromocytoma?

Answer 35

Surgery | Drugs - alpha blockers to counteract hypertension problems

Question 36

What causes infertility?

Answer 36

Many problems 1. Local - sperm generation, pathology of uterine tubules 2. Adrenal related - Cushings in females leads to excess androgens/ congenital adrenal hyperplasia -> ambiguous genitalia 3. Conditions of the ovary - polycystic ovarian syndrome

Question 37

What does Aromatase do?

Answer 37

P450 enzyme In the ovary, converts androgens -> oestrogen