T1 L9: Hypothalamic-pituitary-adrenal axis: clinical aspects

Question 1

describe the HPA axis?

Answer 1

Hypothalamus - CRH,AVP

Pituitary gland- ACTH

Adrenal gland = Cortisol

Question 2

what percentage of cortisol is bound to cortisol binding globulin (CBG) ?

Answer 2

90%

Question 3

what is the function of

11-beta-hydroxysteroid dehydrogenase

Answer 3

Interconverts cortisol and cortisone -active and inactive form

Question 4

what are the effects of glucocorticoids

Answer 4

Maintenance of homeostasis during stress
e.g. haemorrhage, infection, anxiety

Anti-inflammatory

Energy balance / metabolism
 / maintain normal [glucose]

Formation of bone and cartilage

Regulation of blood pressure

Cognitive function, memory, conditioning

Question 5

give some androgens

Answer 5

DHEAs and androstenediones

and estrone

Question 6

what type of scans are used for suspected pituitary swelling

Answer 6

MRI scan

Question 7

describe the circadian rhythm of cortisol (mean data)

Answer 7

rise during the early morning

peak just prior to awakening

fall during the day

are low in the evening

Question 8

where do we describe the cortisol release as pulsatile

Answer 8

when its individual data

Question 9

what is an ultradian rhythm

Answer 9

Spontaneous pulses of varying amplitude

Amplitude decreases in the circadian trough

Question 10

what enzyme causes the conversion of testosterone into Oestrogen

Answer 10

Aromatase

Question 11

what enzyme causes the conversion of testosterone into dihydrotestosterone

Answer 11

5-alpha-reductase

Question 12

if in vitro the mineralocorticoid receptor has the same affinity for aldosterone as cortisol why does aldosterone bind predominately to the receptor?

Answer 12

The 11-beta-HSD-2 in the kidney inactivates cortisol, enabling aldosterone to bind the MR

Question 13

what is cushings syndrome

Answer 13

Too much cortisol

Question 14

what are the possible causes for cushings syndrome

Answer 14

• Pituitary adenoma: ACTH-secreting cells (‘Cushing’s disease’)
• Adrenal tumour: adenoma (or carcinoma)
• ‘Ectopic ACTH’: carcinoid, paraneoplastic

Iatrogenic: steroid treatment (‘Cushingoid’)

Question 15

what are the clinical features of cushings syndrome

Answer 15

Hypertension

Diabetes

Central obesity with thin arms & legs

Fat deposition over upper back (‘buffalo hump’)

Question 16

what is Addison’s disease?

Answer 16

When there is too little cortisol

Question 17

what are the clinical features of addisons disease

Answer 17

Malaise, weakness, anorexia, weight loss

Increased skin pigmentation:
knuckles, palmar creases, around / inside the mouth, pressure areas, scars

Hypotension / postural hypotension

Hypoglycaemia

Question 18

what is the primary pathogenesis of addisons disease

Answer 18

Usually autoimmune in UK

Rare causes include metastases or TB

( Production of all adrenocortical hormones)

Question 19

what are the secondary causes to addisons disease

Answer 19

Secondary to pituitary disease (rare)

‘Iatrogenic’
patients on high dose, long term steroid Rx, which is suddenly stopped at a time of stress

Question 20

what are the differences between Type 1 and 2 AUTOIMMUNE POLYENDOCRINE SYNDROMES

Answer 20

T1:
Rare

Onset in infancy

Ar (AIRE gene)

Common phenotype:
Addison’s disease
Hypoparathyroidism
Candidiasis

t2:
Commoner (still rare!)

Infancy to adulthood

Polygenic

Common phenotype:
Addison’s disease
T1 diabetes M
Autoimmue thyroid disease

Question 21

Assessment of the HPAA axis

Answer 21

BASAL

• Blood-timing circadian rhythm
• -Cortisol
• -ACTH

Urine 24 hour-area under curve
-Cortisol

Saliva
-Cortisol

Dynamic tests

• stimulated -ACTH ,stress
• suppressed -

Question 22

explain the suppressed test

Answer 22

Dexamethane suppression test is when there should be a small amount of cortisol in theory but with cushings disease the cortisol is still high.

Question 23

what tests are performed for too much cortisol

Answer 23

24 hour urinary free cortisol
‘AREA UNDER THE CURVE’

Midnight cortisol (blood / saliva)
‘TROUGH’

9 a.m. ACTH (with paired cortisol)
PITUITARY / ADRENAL / ECTOPIC?
NEGATIVE FEEDBACK AT PITUITARY

DEXAMETHASONE SUPPRESSION
Sensitivity to GC negative feedback at pituitary

Question 24

what tests are done if there are too little cortisol

Answer 24

9 a.m. cortisol
‘PEAK’

SynACTHen test
Adrenal response to ACTH
Trophic effect ACTH on adrenals

Insulin tolerance test
Response to hypoglycaemic stress
Can be dangerous!

U & E (low Na, high K) in Addison’s disease
Due to mineralocorticoid deficiency
Can measure renin & aldosterone concentrations

low glucose

Question 25

always image patients with

Answer 25

Addison’s disease

Question 26

How do you treat Cushing’s syndrome

Answer 26

Surgical (depending on the cause)

• Transphenoidal adenectomy
• Adrenalectomy

Pituitary radiotherapy

Question 27

How do you manage Addison’s disease

Answer 27

Steroid hormone replacement therapy (‘glucocorticoid’):
Usually hydrocortisone (sometimes prednisolone)

Patients with primary adrenal insufficiency also need mineralocorticoid replacement therapy (fludrocortisone).

Patients with secondary adrenal insufficiency will often be taking other hormone replacement therapy (do not need fludrocortisone).

Question 28

On treating a patient with addissons disease their dose needs to be increased when

Answer 28

Intercurrent illnesses (e.g. ‘flu)