HPA axis Flashcards
What are the effects of glucocorticoids?
maintenance of homeostasis during stress e.g. haemorrhage, infection, anxiety.
anti-inflammatory
energy metabolism - increase or maintain glucose conc.
formation of bone and cartilage.
regulation of blood pressure.
cognitive function, memory, conditioning.
Compare the levels of cortisol throughout the day
rise during early morning
peak just prior to awakening
fall during the day
low in the evening
Hormones are released in what fashion and rhythm?
pulsatile in an ultradian rhythm
What is the pathogenesis and causes of Cushing’s syndrome?
excess cortisol: pituitary adenoma - ACTH-secreting cells adrenal tumour - adenoma (or carcinoma) ectopic ACTH - carcinoid, paraneoplastic iatrogenic - steroid treatment
What are the clinical features of Cushing’s syndrome?
Central obesity with thin arms and legs, fat deposition over upper back
Rounded ‘moon’ face, thin skin with easy bruising, pigmented striae
Hirsutism
Hypertension, diabetes
Psychiatric manifestations
Osteoporosis
What is the pathogenesis of Addison’s disease?
Primary adrenal insufficiency:
usually autoimmune in UK.
rare: metastases or TB, secondary to pituitary disease.
decreased production of all adrenocortical hormones.
Other causes of hypoadrenalism:
iatrogenic - patients on high dose, long term steroid, suddenly stopped at a time of stress.
What are the clinical features of Addison’s?
Malaise, weakness, anorexia, weight loss
Increased skin pigmentation
Hypotension / postural hypotension
Hypoglycaemia
What are the features and common phenotypes of autoimmune polyendocrine syndromes type 1?
Rare, onset in infancy.
AIRE gene.
common phenotype: Addison’s disease, hypoparathyroidism, candidiasis.
What are the features and common phenotypes of autoimmune polyendocrine syndromes type 2?
Commoner, infancy to adulthood, polygenic.
common phenotype: Addison’s disease, T1 diabetes,
autoimmune thyroid disease.
How is the HPA axis assessed?
Basal:
blood - cortisol, ACTH, timing - circadian rhythm, ultradian rhythm, stress.
urine - cortisol, 24-hour collection, ‘area under curve’.
saliva - cortisol, timing, no stress.
Dynamic tests:
stimulated - ACTH, CRH, stress - hypoglycaemia.
suppressed - dexamethasone - synthetic glucocorticoid
How is Cushing’s syndrome managed?
Surgical (depending on cause): transphenoidal adenectomy, adrenalectomy.
pituitary radiotherapy.
How is Addison’s disease managed?
Steroid hormone replacement therapy: hydrocortisone (sometimes prednisolone).
Patients with primary adrenal insufficiency also need mineralocorticoid replacement therapy (fludrocortisone).
secondary adrenal insufficiency often requires other hormone replacement therapy (do not need fludrocortisone).
Outline the HPA axis
hypothalamus releases CRH and AVP.
this causes pituitary to release ACTH.
target organ then releases cortisol which inhibits ACTH and CRH secretion.
What are the clinical implications of autoimmune polyendocrine syndromes?
High index of suspicion for additional autoimmune endocrine disorders. consider screening in patients with T1 DM and/or Addison’s disease:
coeliac screen
TFTs (esp in pregnancy / post-partum)
Which tests are done if someone is suspected to have too much cortisol?
24 hour urinary free cortisol - area under curve.
Midnight cortisol (blood / saliva) - trough.
9 a.m. ACTH (with paired cortisol) - determines where the cortisol comes from due to negative feedback e.g. pituitary, adrenal, ectopic.
Dexamethasone suppression - absent negative feedback at pituitary in Cushing’s.
