T1 L7: The Hypothalamic-pituitary adrenal axis

Question 1

What protein is 90% of cortisol bound to?

Answer 1

Cortisol binding globulin (CBG)

Question 2

What re some effects of glucocorticooids?

Answer 2

• Maintenance of homeostasis during stress
• Inti-inflammatory
• Energy balance
• Formation of bone and cartilage
• Regulation of blood pressure
• Cognitive function, memory, conditioning

Question 3

When are cortisol levels at the lowest and highest?

Answer 3

Highest just prior to waking up and lowest in the evening

Question 4

What is an ultradian rhythm?

Answer 4

A recurrent period or cycle repeated throughout a 24-hour day

Question 5

What is the affinity of the mineralocorticoid receptor (MR) for aldosterone vs cortisol?

Answer 5

The same

But the 11-beta-HSD-2 enzyme in the kidneys inactivates cortisol allowing more aldosterone to bind to that receptor

Question 6

What is Cushing’s syndrome?

Answer 6

Too much cortisol

Question 7

What are some symptoms of Cushing’s syndrome?

Answer 7

• Weight gain
• Central obesity
• Hypertension
• Insulin resistance
• Neuropsychiatric problems like depression
• Osteoporosis

Question 8

What is the pathogenesis of Cushing’s syndrome?

Answer 8

Most common:
A pituitary adenoma affecting ACTH-secreting cells

Can also be caused by an adrenal tumour or by ‘ectopic ACTH’ caused by carcinoid tumours that secrete ACTH

Can be iatrogenic by steroid treatment

Question 9

What are some clinical presentations of Cushing’s syndrome?

Answer 9

• Central obesity with thin arms and legs
• Fat deposition over upper back (buffalo hump)
• Rounded face
• Thin skin with easy bruising. pigmented striae
• Hirsutism

-Hypertension, diabetes, psychiatric manifestations, and osteoporosis

Question 10

What is Pigmented Striae?

Answer 10

Stretch marks

Question 11

What is Hirsutism?

Answer 11

Excessive hair growth

Question 12

What is the pathogenesis of Addison’s disease?

Answer 12

Normally autoimmune in the UK but can be caused by metastases or TB which causes destruction of the adrenal glands

Can be secondary to pituitary disease (rare) or can be iatrogenic caused by high dose steroids which is suddenly stopped

Question 13

What are some clinical features of Addison’s disease?

Answer 13

-Malaise
-Weakness
-Anorexia
-Weight loss
Increased skin pigmentation on knuckles, palmar creases, around the mouth, pressure areas, scars
-Hypotension
-Hypoglycaemia

Question 14

What are type 1 autoimmune polyendocrine syndromes?

Answer 14

They’re rare and have an onset in infancy

Common phenotypes: Addison’s disease, Hypoparathyroidism, Candidiasis

Question 15

What are type 2 autoimmune polyendocrine syndromes?

Answer 15

They’re more common than type 1 but still rare and have an onset during infancy or adulthood
Common phenotype: Addison’s disease, T1 diabetes, autoimmune thyroid disease

Question 16

What are some autoimmune conditions that may happen together?

Answer 16

• T1 diabetes
• Autoimmune thyroid disease
• Coeliac disease
• Addison’s disease
• Pernicious anaemia
• Alopecia
• Vitiligo
• Hepatitis
• Premature ovarian failure
• Myasthenia gravis

Question 17

What is Myasthenia gravis?

Answer 17

When antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles

Question 18

What are some ways that the Hypothalamic-pituitary adrenal axis can be assessed?

Answer 18

Basal:
Blood cortisol and ACTH (Timing matters because of the circadian and ultraradian rhythm. It’s stressful)
Urine cortisol (A 24-hour collection is needed)
Salivary Cortisol (best to do because there is no stress so it just needs to be timed)

Dynamic tests:
Stimulated or suppressed tests

Question 19

Describe a stimulated test to asses the Hypothalamic-pituitary adrenal axis

Answer 19

ACTH or CRH is injected or the patient is made hypoglycaemic to induce stress within the body

All are done to see how the body responds

Question 20

Describe a supressed tests to asses the Hypothalamic-pituitary adrenal axis

Answer 20

Dexamethasone (a synthetic glucocorticoid) is administered to see what happens within the body

There wont be any suppression if the patient has Cushing’s syndrome

Question 21

Why shouldn’t someone be investigated for endocrine conditions unless they have signs and symptoms?

Answer 21

Because there is a risk of false positive results

Question 22

What imaging should be considered if someone has been confirmed to have Cushing’s syndrome?

Answer 22

Chest X-ray
MRI Pituitary
CT adrenals

Question 23

When should someone with Addison’s be considered for imaging?

Answer 23

When there in concern it’s TB or metastatic cancer

Question 24

What are some ways of managing Cushing’s syndrome?

Answer 24

Surgical:
Transsphenoidal adenectomy
Adrenalectomy

Or pituitary radiotherapy

Question 25

What are some ways of managing Addison’s disease?

Answer 25

• Steroid hormone replacement therapy
• Patients with primary adrenal insufficiency also needs mineralocorticoid replacement therapy like Fludrocortisone
• Patients with secondary adrenal insufficiency will often be taking other hormone replacement therapy

Question 26

When do steroid doses need to be increased when someone has Addison’s disease?

Answer 26

• During stress
• Operations/ post-operative period

Patients need IV of IM injections if they’re unable to take medication