HPA axis - clinical aspects

Question 1

How is cholesterol mobilised into the adrenal cortex?

Answer 1

Via activation of ACTH

Question 2

In the adrenal medulla, what is cholesterol covered into?

Answer 2

Either Aldosterone, Cortisol or Androgens

Question 3

Which hormone helps the conversion of cholesterol into aldosterone?

Answer 3

Angiotensin II

Question 4

Which hormones maintain homeostasis during stress (bleeding, infection, etc)?

Answer 4

Glucocorticoids

Question 5

What are the main affects of glucocorticoids?

Answer 5

Maintain homeostasis
Anti-inflammatory
Energy balance/metabolism
Form bone + cartilage
Regulate blood pressure
Cognitive function, memory, conditioning

Question 6

What two dynamic tests can be done to assess the adrenal axis?

Answer 6

Stimulation to check for deficit - synacthen, glucagon stimulation, insulin stress test
Suppression to check for excess - ONDST, LDDST, HDDST

Question 7

What are the two types of Cushing’s syndrome?

Answer 7

ACTH dependent Cushings
ACTH Independent Cushings

Question 8

What causes ACTH Dependent Cushing’s syndrome? Would the ACTH level be high or low?

Answer 8

Pituitary tumour
Ectopic ACTH secretion
High ACTH level

Question 9

What causes ACTH Independent Cushing’s syndrome? Would the ACTH level be high or low?

Answer 9

Adrenal tumour
Long term steroid therapy
Low ACTH level

Question 10

What signs and symptoms do patients present with, in glucocorticoid excess?

Answer 10

Question 11

Pigmentation occurs in which type of Cushings and why?

Answer 11

ACTH Dependent Cushing’s syndrome.
Occurs due to high ACTH levels.

Question 12

What is the preferred testing method for glucocorticoid excess?

Answer 12

Overnight dexamethasone test

Question 13

If cortisol can be suppressed on a low dose dexamethasone test, is the glucocorticoid excess caused by the adrenal or pituitary gland?

Answer 13

Adrenal

Question 14

If cortisol can be suppressed on a high dose dexamethasone test, is the glucocorticoid excess caused by the adrenal or pituitary gland?

Answer 14

Pituitary

Question 15

Which type of imaging should be done if a pituitary cause is suspected in glucocorticoid excess?

Answer 15

MRI

Question 16

In adrenal imaging, when would a malignancy be suspected?

Answer 16

> 4cm
Heterogenous = calcification and necrosis
Extending out of capsule = invasive

Question 17

What medications can be used to treat glucocorticoid excess?

Answer 17

Adrenal gland - Ketoconazole. Mifepristone (approved for those with cushings + T2DM).
Pituitary - Somatostatin analogues or dopamine agonist therapy.

Question 18

What types of surgery can treat glucocorticoid excess?

Answer 18

Transsphenoidal adenectomy
Adrenalectomy

Question 19

What are the two types of glucocorticoid deficiency?

Answer 19

Primary adrenal insufficiency
Secondary adrenal insufficiency

Question 20

What can cause both primary and secondary adrenal insufficiency?

Answer 20

Autoimmune conditions
Infiltrative e.g. sarcoidosis
Infections e.g. TB, Fungal, AIDS
Vascular e.g. haemorrhage/infarction
Drugs
Metastatic deposition

Question 21

What causes are specific to primary adrenal insufficiency?

Answer 21

CAH - Congenital Adrenal Hyperplasia
Adrenoleucodystrophy

Question 22

Can head trauma cause primary or secondary adrenal insufficiency?

Answer 22

Secondary

Question 23

Is there both glucocorticoid and mineralocorticoid deficiency in primary and secondary adrenal insufficiency?

Answer 23

No, both in primary.
Glucocorticoid deficiency only in secondary.

Question 24

What is the most common cause of primary adrenal insufficiency?

Answer 24

Autoimmune adrenalitis

Question 25

Which antibody is associated with autoimmune adrenalitis?

Answer 25

21- hydroxylase

Question 26

What age does primary adrenal insufficiency typically occur at?

Answer 26

30-50 years

Question 27

How much of the Adrenal cortex is destroyed before symptoms of primary adrenal insufficiency occur?

Answer 27

90%

Question 28

What is the MOA of ketoconazole?

Answer 28

Decreases cortisol synthesis.

Question 29

What is the MOA of Rifampicin?

Answer 29

Increases cortisol metabolism.

Question 30

Which drugs can cause glucocorticoid insufficiency?

Answer 30

Ketoconazole Rifampicin

Question 31

What are the clinical features of adrenal insufficiency?

Answer 31

Question 32

Pigmentation of the skin occurs in what type of adrenal insufficiency and why?

Answer 32

Primary. Increased ACTH due to reduced cortisol levels. ACTH and Melanocytes have the same precursor molecule.

Question 33

What is the difference between primary and secondary adrenal insufficiency?

Answer 33

Primary - Adrenal glands don't make enough cortisol and aldosterone despite a normal/increased ACTH. Secondary - Pituitary gland doesn't make enough ACTH. ACTH controls the production of cortisol. Less ACTH = Less cortisol.

Question 34

What tests can be done to diagnose adrenal insufficiency?

Answer 34

9am cortisol ACTH levels Na+, K+, pH Renin (high), Aldosterone (Low) Adrenal antibodies

Question 35

What is the dynamic testing used to confirm adrenal insufficiency and how is this done?

Answer 35

Synacthen test. Synthetic ACTH at 9am. Measure Cortisol at 0, 30 and 60 minutes. Beware of steroids + only do if equivalent of 5mg prednisolone or less + omit on morning of test.

Question 36

What does it mean if the levels of cortisol 30minutes post synacthen test are >420nmol/L?

Answer 36

No adrenal insufficiency as cortisol is being produced from the ACTH.

Question 37

What does it mean if the levels of cortisol 30minutes post synacthen test are <420nmol/L, but >420nmol/L at 60minutes?

Answer 37

A slow/delayed adrenal response.

Question 38

What is adrenal crisis?

Answer 38

An emergency caused by a lack of cortisol.

Question 39

What is the management of adrenal crisis?

Answer 39

IV Hydrocortisone IVI Hypoglycaemic management Mineralocorticoid replacement once daily glucocorticoid dose <50mg/24hours (primary adrenal insufficiency only). - Fludrocortisone 100mcg OD.

Question 40

What is the long term management of adrenal crisis?

Answer 40

Replacement - steroids. Mineralocorticoid if primary. Education. Home emergency hydrocortisone injection. Steroid card

Question 41

What are the sick day rules in adrenal insufficiency?

Answer 41

Moderate illness (fever, infection etc) - Double daily steroid dose. Severe illness (vomiting GI illness, surgery, colonoscopy prep) - IV Hydrocortisone 100mg then 200mg/24hours. OR IM Hydrocortisone 100mg then 50mg every 60 hours.

Question 42

How does exogenous steroids affect the adrenal cortex?

Answer 42

Causes atrophy of zona fasciculate and zona reticularis. Zona glomerulose spared due to RAAS.

Question 43

What is the equivalent dose of Prednisolone 5mg into Hydrocortisone and Dexamethasone?

Answer 43

Question 44

What is autoimmune polyglandular syndrome?

Answer 44

Deficiencies in the function of several endocrine glands. Circulating autoantibodies and lymphocytic filtration of the affected multiple tissues.

Question 45

In autoimmune polyglandular syndrome, which conditions may occur together?

Answer 45

Question 46

What are the four types of autoimmune polyglandular syndromes?

Answer 46

Question 47

If someone with T1DM presents with weight loss, hypoglycaemia and fatigue, what should be checked?

Answer 47

9am cortisol

Question 48

If someone with T1DM presents with Gi symptoms, what should be checked?

Answer 48

Markers for coeliac disease.

Question 49

If someone with T1DM also has Addison's disease, what should be checked?

Answer 49

TFTs Coeliac screen

Question 50

What should be asked when taking an endocrine history?

Answer 50

Question 51

What should be examined in an endocrine examination?

Answer 51