HPA axis - clinical aspects Flashcards
How is cholesterol mobilised into the adrenal cortex?
Via activation of ACTH
In the adrenal medulla, what is cholesterol covered into?
Either Aldosterone, Cortisol or Androgens
Which hormone helps the conversion of cholesterol into aldosterone?
Angiotensin II
Which hormones maintain homeostasis during stress (bleeding, infection, etc)?
Glucocorticoids
What are the main affects of glucocorticoids?
Maintain homeostasis
Anti-inflammatory
Energy balance/metabolism
Form bone + cartilage
Regulate blood pressure
Cognitive function, memory, conditioning
What two dynamic tests can be done to assess the adrenal axis?
Stimulation to check for deficit - synacthen, glucagon stimulation, insulin stress test
Suppression to check for excess - ONDST, LDDST, HDDST
What are the two types of Cushing’s syndrome?
ACTH dependent Cushings
ACTH Independent Cushings
What causes ACTH Dependent Cushing’s syndrome? Would the ACTH level be high or low?
Pituitary tumour
Ectopic ACTH secretion
High ACTH level
What causes ACTH Independent Cushing’s syndrome? Would the ACTH level be high or low?
Adrenal tumour
Long term steroid therapy
Low ACTH level
What signs and symptoms do patients present with, in glucocorticoid excess?
Pigmentation occurs in which type of Cushings and why?
ACTH Dependent Cushing’s syndrome.
Occurs due to high ACTH levels.
What is the preferred testing method for glucocorticoid excess?
Overnight dexamethasone test
If cortisol can be suppressed on a low dose dexamethasone test, is the glucocorticoid excess caused by the adrenal or pituitary gland?
Adrenal
If cortisol can be suppressed on a high dose dexamethasone test, is the glucocorticoid excess caused by the adrenal or pituitary gland?
Pituitary
Which type of imaging should be done if a pituitary cause is suspected in glucocorticoid excess?
MRI
In adrenal imaging, when would a malignancy be suspected?
> 4cm
Heterogenous = calcification and necrosis
Extending out of capsule = invasive
What medications can be used to treat glucocorticoid excess?
Adrenal gland - Ketoconazole. Mifepristone (approved for those with cushings + T2DM).
Pituitary - Somatostatin analogues or dopamine agonist therapy.
What types of surgery can treat glucocorticoid excess?
Transsphenoidal adenectomy
Adrenalectomy
What are the two types of glucocorticoid deficiency?
Primary adrenal insufficiency
Secondary adrenal insufficiency
What can cause both primary and secondary adrenal insufficiency?
Autoimmune conditions
Infiltrative e.g. sarcoidosis
Infections e.g. TB, Fungal, AIDS
Vascular e.g. haemorrhage/infarction
Drugs
Metastatic deposition
What causes are specific to primary adrenal insufficiency?
CAH - Congenital Adrenal Hyperplasia
Adrenoleucodystrophy
Can head trauma cause primary or secondary adrenal insufficiency?
Secondary
Is there both glucocorticoid and mineralocorticoid deficiency in primary and secondary adrenal insufficiency?
No, both in primary.
Glucocorticoid deficiency only in secondary.
What is the most common cause of primary adrenal insufficiency?
Autoimmune adrenalitis
Which antibody is associated with autoimmune adrenalitis?
21- hydroxylase
What age does primary adrenal insufficiency typically occur at?
30-50 years
How much of the Adrenal cortex is destroyed before symptoms of primary adrenal insufficiency occur?
90%
What is the MOA of ketoconazole?
Decreases cortisol synthesis.
What is the MOA of Rifampicin?
Increases cortisol metabolism.
Which drugs can cause glucocorticoid insufficiency?
Ketoconazole
Rifampicin
What are the clinical features of adrenal insufficiency?
Pigmentation of the skin occurs in what type of adrenal insufficiency and why?
Primary.
Increased ACTH due to reduced cortisol levels. ACTH and Melanocytes have the same precursor molecule.
What is the difference between primary and secondary adrenal insufficiency?
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.
What tests can be done to diagnose adrenal insufficiency?
9am cortisol
ACTH levels
Na+, K+, pH
Renin (high), Aldosterone (Low)
Adrenal antibodies
What is the dynamic testing used to confirm adrenal insufficiency and how is this done?
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.
What does it mean if the levels of cortisol 30minutes post synacthen test are >420nmol/L?
No adrenal insufficiency as cortisol is being produced from the ACTH.
What does it mean if the levels of cortisol 30minutes post synacthen test are <420nmol/L, but >420nmol/L at 60minutes?
A slow/delayed adrenal response.
What is adrenal crisis?
An emergency caused by a lack of cortisol.
What is the management of adrenal crisis?
IV Hydrocortisone
IVI
Hypoglycaemic management
Mineralocorticoid replacement once daily glucocorticoid dose <50mg/24hours (primary adrenal insufficiency only). - Fludrocortisone 100mcg OD.
What is the long term management of adrenal crisis?
Replacement - steroids. Mineralocorticoid if primary.
Education.
Home emergency hydrocortisone injection.
Steroid card
What are the sick day rules in adrenal insufficiency?
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.
How does exogenous steroids affect the adrenal cortex?
Causes atrophy of zona fasciculate and zona reticularis.
Zona glomerulose spared due to RAAS.
What is the equivalent dose of Prednisolone 5mg into Hydrocortisone and Dexamethasone?
What is autoimmune polyglandular syndrome?
Deficiencies in the function of several endocrine glands.
Circulating autoantibodies and lymphocytic filtration of the affected multiple tissues.
In autoimmune polyglandular syndrome, which conditions may occur together?
What are the four types of autoimmune polyglandular syndromes?
If someone with T1DM presents with weight loss, hypoglycaemia and fatigue, what should be checked?
9am cortisol
If someone with T1DM presents with Gi symptoms, what should be checked?
Markers for coeliac disease.
If someone with T1DM also has Addison’s disease, what should be checked?
TFTs
Coeliac screen
What should be asked when taking an endocrine history?
What should be examined in an endocrine examination?
