HPA axis Flashcards
What are the 3 layers of the adrenal gland?
Capsule
Cortex
Medulla
What are the layers of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What is produed in the zona glomerulosa?
Mineralocorticoids- aldosterone/ progesterone
What is produced in the zona fasciculata?
Corticosteroids - cortisold
small amounts of androgens
What is produced in the zona reticularis?
Androgens eg DHEA and small amount of corticosteroids
What is the venous and arterial supply of the adrenal glands?
Venous:
R: inf. vena cava
L: l renal vein
Arterial:
Sup, mid, inf adrenal artery
What is produced in the adrenal medulla?
Chromaffin cells produce catecholamines, epinephrine, norepinephrine
Describe the HPA axis
Hypothalamus -> CRH (corticotropin releasing hormone)
Ant. pit -> ACTH (adrenocorticotropin hormone)
Cortex of adrenal gland -> glucocorticoids (androgens and cortisol)
What are the normal physiological actions of cortisol?
Gluconeogenesis
Lipolysis in adipose tissue
Protein and fat metabolism
Anti-inflam
Immunosupression
What are the actions of glucocorticoids?
affect carc, fat, protein metabolism `
What are the actions of mineralocorticoids?
control sodium and potassium balance (aldosterone)
What is the action of CRF?
Corticotropin releasing factor acts on ant pit -> ACTH to act on adrenal cortex to release androens and cortisol
What type of hormones does the adrenal cortex produce
steroid hormones
What is Cushing’s syndrome?
Abnormal persistent elevated glucocorticoid levels with loss of circadian cortisol secretion and loss of normal negative feedback
What is Cushing’s disease?
Pituitary adenoma causing excessive ACTH secretion causing bilateral adrenal hyperplasia causing excessive cortisol production
What are the ACTH dependent causes of cushings syndrome?
- Cushing’s disease - pit adenoma
- Ectopic ACTH production eg small cell lung cancer and carcinoids
What are the ACTH independent causes of Cushing’s syndrome?
Adrenal carcinoma
Iatrogenic - steroid use
What are the signs for Cushing’s syndrome?
Round moon face
Central obesity
Back buffalo hump
Purple abdo striae
Hyperglycaemia/ hypertension/ osteoporosis
Thin skin
What are the symptoms for Cushing’s syndrome?
Weight gain
Acne
Peripheral weakness
Mood change- irritable/ depression/ psychosis
Gonadal dysfunction- erectile dysfunction/ irregular periods
What is the men to women prevalence of cushing disease?
equal
What age do people usually present with Cushing’s?
30-50 yrs
What is the main investigation for Cushing syndrome?
dexamethasone suppression test
How is dexamethasone used to diagnose Cushings
Acts as glucocorticoid steroid to suppress ACTH production
Sees if cortisol production is reduced
What are the results for the first line dexamethasone test for Cushings?
Suppressed ACTH and high cortisol with low dose (1mg) of dexa.
Given at night, measured in the morning
What are the results for the second dexamethasone test for cushing’s?
Cushing’s disease = suppressed ACTH and cortisol
Ectopic ACTH = high ACTH and cortisol
Adrenal adenoma = suppressed ACTH and high cortisol
What is the treatment for iatrogenic Cushing’s syndrome ?
stop medication
What is the treatment for Cushing’s disease
Pituitary adenoma removal
What is the treatment for Cushing’s syndrome caused by ectopic ACTH?
Surgery
What is the treatment for Cushing’s syndrome caused by adrenal adenoma?
Adrenalectomy (nelsons syndrome as a complication)
What are the conditions for the dexamethasone suppression test?
Overnight 12am given then 8am measurement
What is primary adrenal insufficiency?
Destruction of the adrenal cortex resulting in deficiency in mineralocorticoids, glucocorticoids and androgens
What is Addison’s disease?
Primary adrenal insufficiency caused by autoimmune destruction of the adrenal cortex resulting in deficiency of mineralocorticoids, glucocorticoids and androgens
Describe the pathophysiology of Addison’s disease
Autoimmune destruction of adrenal cortex by 21-hydroxylase adrenal autoantibodies
What are the ACTH levels in Addisons and why and what symptom does this cause?
High due to low cortisol levels which results in negative feedback to pit gland
causes hyperpigmentation
Describe the epidemiology of Addison’s
Rare- 0.8/100,000
More common in women
What is the main cause of primary adrenal insufficiency in the UK
Addisons disease
What is the main cause of primary adrenal insufficiency worldwide?
TB
Describe the clinical presentation of Addison’s disease
Fatigue
Tanned
Hyperpigmentation- palmar, sun-exposed areas, waist
GI: wt loss, abdo pain, nausea, vomiting, loss appetite
CVS: postural hypotension, hypoglycaemia
MSK: joint pain, muscle cramps
Depressed/ anxious/ psychosis
Tanned, Tearful, Tired, Toned,
What are the investigations and results for Addison’s disease?
ACTH stimulation test: low cortisol
U&E: High K+ and low Na+ (lack aldosterone)
Serum ACTH: High ACTH and low cortisol= primary
Low ACTH and cortisol = secondary
21-hydroxylase adrenal autoantibodies positive
What is the ACTH stimulation test and what is it used for?
Used to diagnose Addison’s disease
Measure baseline cortisol
Give ACTH and measure cortisol 30 min after
Addisons= low cortisol (adrenal destruction)
What is the managment of Addison’s?
Oral hydrocortisone to replace steroids
Fludrocorticosone to replace aldosterone
What are the Na and K ion levels for Addison’s disease and why?
Low Na+ and high K+ due to lack of aldosterone
What are the complications of Addison’s disease?
Adrenal crisis
- life threatening
What are the symptoms of an adrenal crisis?
Reduced conciousness
Hypoglycaemia, hypotension
What is the management for an adrenal crisis?
Immediate treatment
IV fluids
Steroids
Glucose
Intensive monitoring
What is secondary adrenal insufficiency?
Lack of ACTH production from the pit gland causing deficiency in cortisol
What is the common cause in secondary adrenal insufficiency?
Iatrogenic- long term steroid use disturbs the pit. adrenal axis
How is primary adrenal insufficiency different to hypothalamic-pituitary disease?
Deficiency in mineralocorticoids which aren’t controlled by the pituitary
