HPA Axis

• Organs of the HPA axis

  • hypothalamus
  • pituitary
  • adrenals
• Pituitary is the key hormone-producing gland

  Under the control of the hypothalamus

  The pituitary is divided into two lobes

  • Anterior pituitary
  • Posterior pituitary

  These are controlled differently and have different functions
• The hypothalamus secretes hormones into the hypophyseal portal system

  These travel to the anterior pituitary where they cause the release of further hormones:
• The hypothalamus produces hormones and transports these to the posterior pituitary within neurones

  From here they are released directly into the blood stream:

  Oxytocin involved in lactation and social bonding/love

  ADH involved in maintaining blood pressure and fluid balance
• Growth hormone released by anterior pituitary in response to GnRH from the hypothalamus. Function: Bone and cartilage growth, increased protein synthesis, breakdown of fat
• Prolactin released by anterior pituitary in response to Prolactin releasing hormone from hypothalamus. Function: milk production
• Thyroid-stimulating hormone-releasing hormone In hypothalamus stimulates Thyroid stimulating hormone release from anterior pituitary. function: Thyroid gland produces more thyroxine
• Gonadotropin-releasing hormone (GnRH) Released by hypothalamus stimulates FSH and LH release from anterior pituitary. Function: Reproduction and androgen/oestrogen production
• Corticotropin releasing hormone (CRH) Release from the hypothalamus leads to the release of ACTH from the anterior pituitary. Function: Production of steroids from the adrenals
• ADRENAL GLAND HORMONES

  • mineralocorticoid - aldosterone and corticosterone
  • Glucocorticoid - cortisol and cortisone
  • Androgens - estrogens and testosterone
  • Catecholamines - adrenaline and noradrenaline
  • Peptides - somatostatin and substance P
• MINERALOCORTICOID

  • Key endogenous example is aldosterone (triggered by angiotensin II)
  • Key exogenous example is fludrocortisone
  • Named after its affect on minerals, chiefly sodium
  • Cause retention of sodium in the kidneys, which causes an increase in blood pressure.
  • Also causes a loss of potassium
• GLUCOCORTICOID

  • Key endogenous example is cortisol
  • Key exogenous example is hydrocortisone
  • Named after its affect on glucose
  • Released in response to stress and hypoglycaemiA
  • Causes many effects:
  • Increased blood sugar by increasing hepatic glucose production
  • Suppress the immune system
  • Breakdown of proteins (e.g. muscle wasting)
  • Inhibits sleep
• replacement mineralocorticoid - fludrocortisone

  replacement glucocorticoid - hydrocortisone
• Diurnal variation

  • Cortisol is lowest at night
  • Peaks mid-morning
  • Impact on inflammatory diseases?
• The adrenals produce corticosteroids

  Glucocorticoid (e.g. cortisol) – stress, immune, glucose

  Mineralocorticoid (e.g. aldosterone) – high BP, retain sodium, lose potassium

  They are controlled by the HPA

  Some key conditions of this system are Addison’s (low steroids) and Cushing’s (high steroids)
• Cortisol blood tests have to be taken at a specific time because of diurnal variation.
• Addison’s disease

  • primary hypoadrenalism
  • potential causes:
  • auto-immune destruction of the adrenals
  • tuberculosis infection of the adrenals
  • Haemorrhage
  • infiltration - malignancy/amyloid
  • result is low levels of both mineralocorticoid and glucocorticoid
  • Patients may present in crisis
• Addisons blood test - low sodium, high potassium, low glucose
• Effects of low aldosterone:

  • decreased blood Na+ levels
  • increased blood K+ levels
  • decreased blood pressure

  low aldosterone means can't hang on to sodium or get rid of potassium. Low cortisol means will make less glucose.
• Glucocorticoid side effects

  • Facial erythema
  • hypertrichosis
  • buffalo hump
  • acne
  • hypertension
  • Insomnia, mood disorders, psychosis
  • cataract, glaucoma
  • moon face
  • osteoporosis, osteopenia, avascular bone necrosis
  • myopathy
  • poor wound healing
  • purpura
  • striae
  • truncal obesity
• systemic and topical glucocorticoids side effects

  • skin atrophy/thinning
• inhaled glucocorticoids side effects

  • oral candidiasis
  • hoarseness
  • respiratory tract infections
• A 28-year-old Caucasian female presents to the emergency department with a history of increasing

  weakness, lethargy and new dizziness. She has been vomiting. On examination her blood pressure

  is 78/40 (low) and she has unusually tanned palmar creases and arms. She has a history of Type 1

  Diabetes and Hypothyroidism and on arrival to the emergency department has a blood sugar of 3.2

  (low) despite not having taken her insulin for some time. Temperature was normal.

  Addison's disease
• Emergency treatment for Addison's disease - IV hydrocortisone
• A 48-year-old woman with no past medical history presents to her GP with high blood pressure (180/75)

  which has not responded to two different anti-hypertensives. She reports gaining significant weight in

  her abdomen, face and upper back but has remarkably skinny legs and arms by comparison. She

  complains of unsightly stretch marks on her abdomen and insists she has been dieting to try to lose

  weight. She also feels tired all the time. Her blood sugar is elevated.

  Cushing's syndrome
• Cushing's syndrome

  • too much cortisol
  • can have a variety of causes
  • pituitary tumour secreting ACTH (Cushing's disease)
  • adrenal tumour producing cortisol
  • other tumours can produce ACTH too e.g. small cell lung cancer
  • giving someone too many steroids
• Signs and symptoms of Cushing's syndrome

  • high blood sugars/diabetes
  • high blood pressure
  • muscle wasting
  • abdominal weight gain
  • depression, fatigue
  • hair loss
  • moon face
  • thin skin/easy bruising with poor wound healing
  • osteoporosis
  • menstrual changes
• Cushing's syndrome blood test

  • High sodium
  • Low Potassium
  • high glucose

  High cortisol means we hang onto more sodium (hence high BP) and lose more potassium. Also leads to high gluconeogenesis - diabetes.
• • exclude exogenous glucocorticoid exposure as cause of Cushing's
  • increased urinary excretion of free cortisol
  • absence of cortisol suppression
  • evaluation of circadian cortisol secretion rhythm
  • midnight plasma or salivary cortisol levels
  • dexamethasone test with or without CRH test
• Adrenal gland causes of cortisol hypersecretion

  • ACTH low
  • No response to CRH test
  • No suppression in dexamethasone 8mg test
  • tumours (or rarely hyperplasia) seen on adernal CT or MRI
  • normal pituitary MRI
• Pituitary causes of cortisol hypersecretion

  • Normal or high ACTH level
  • Rare response on CRH test
  • Suppression on Dexamethasone 8mg test
  • Normal adrenal MRI/CT or hyperplasia
  • Microadenomas on pituitary MRI (60%)
• Ectopic secretion of cortisol

  • Normal or very high ACTH test
  • Rare response on CRH test
  • Rare suppression on dexamethasone 8mg test
  • normal adrenal CT/MRI or hyperplasia
  • normal pituitary MRI
• management of Cushing's depends on the cause:

  • adrenal tumour - remove
  • pituitary tumour - remove
  • lung tumour - hopefully remove
  • steroid prescription - reduce if possible
  • medication may be required to inhibit cortisol production