Adrenal glands and conditions Flashcards
What is the adrenal cortex divided into?
3 layers:
- Zona glomerulosa (outer)
- Zona fasciculata (middle)
- Zona reticularis (inner)
Which hormones are produced in the adrenal cortex and whereabouts?
- Aldosterone- golmerulosa
- Cortisol and corticosteroids- Fasciculata
- Androgens- Reticularis
What hormones are produced in the adrenal medulla?
Epinephrine and norepinephrine
What are all corticosteroids derived from and how?
Cholesterol- is converted to pregnenelone and then a series of enzymatic reactions occur to produce different steroid molecules
What are the categories of corticosteroid hormones?
- Mineralcorticosteroids- e.g. aldosterone
- Gluticorticoids e.g. cortisol
- Sex hormones e.g. dihydroepiandrosterone
What is the role of aldosterone?
Aldosterone is a major mineralocorticoid that acts on the distal tubule and collecting ducts of the kidney:
- Promotes Na+ reabsorption in the kidney
- Increases K+ and H+ excretion in the urine
- sodium retention leads to water retention causing an increase in volume of the extracellular fluid
Long-term this increases blood pressure
What increases aldosterone secretion?
- Aldosterone secretion is increased by activation of the renin
angiotensin aldosterone system - or direct stimulation of the adrenal cortex by a rise in plasma [K]
What is the role of cortisol?
Cortisol is a major glucocorticoid
- Role in metabolism to increase blood glucose concentration at the expense of protein and fat stores:
Stimulates hepatic gluconeogenesis
Inhibits glucose uptake by the tissues
Stimulates protein breakdown in muscles
stimulates lipolysis in adipose tissue- provides store of fatty acids rather than using up glucose
- Influence the action of other hormones
e.g. need sufficient cortisol for catecholamines to induce vasoconstriction
Lack of cortisol could lead to circulatory shock in a
stressful situation where need acute vasoconstriction - Role in adaption to stress
Stress increases cortisol secretion- acts in flight or flight to produce immediate source of energy in terms of glucose, aa and fatty acids - Anti-inflammatory/immunosuppressive effects
Cortisol inhibits pro-inflammatory cytokines, phagocytosis, neutrophil recruitment, fibroblast proliferation
How is cortisol secretion controlled?
- In response to stress, the hypothalamus releases ‘ Corticotrophin releasing hormone’ (CRH)
- CRH stimulates the anterior pituitary to relax ACTH (Adrenalcorticotrophic hormone)
- ACTH then acts on the adrenal cortex to cause the release of cortisol. Cortisol goes on to act on the liver, immune system, adipose tissue and muscle
- Reduction of cortisol production is then governed by a negative feedback loop
How do levels of cortisol change throughout the day?
Cortisol has a diurnal rhythm meaning the levels are highest in the morning and lowest at night.
- it is related to the sleep-wake cycle so a shift worker will have a different rhythm
- important in determining times of day to take bloods and to perform surgery (cortisol helps us respond to stress)
What increases the secretion of cortisol?
Stress increases cortisol production proportionally to the magnitude of stress:
- Can be physical stress e.g. hypoglycaemia, trauma, surgery, infection, pain
- or psychological stress e.g. anxiety, fear, stress
causes:
- protein catabolism
- gluconeogenesis
- inhibits glucose uptake by tissues
- stimulates lipolysis to fatty acids
- inhibits inflammation and immune responses
- inhibits non-essential functions e.g. reproduction, growth etc
Give some examples fo corticosteroids used in therapy
Prednisolone
Beclometasone
Fluticasone
Hydrocortisone
used for three anti-inflammatory and immunosuppressive effects
What can lead to hyper secretion of aldosterone?
- A tumour that is made from aldosterone-secreting cells
- High activity of the renin-angiotensin aldosterone system e.g. arteriosclerosis causing narrowing of the blood vessels
What is the effect of aldosterone hypersecretion?
Hypernatraemia- high sodium in the blood
Hypokalaemia- low potassium in the blood
High blood pressure- due to sodium and water retention
What is the process of increased secretion of aldosterone from the renin-angiotensin aldosterone (RAAS) system?
- Juxtaglomerular cells in the afferent arteriole of the kidney detect a low blood pressure and secrete renin
- The liver secretes angiotensinogen which is converted into angiotensin I by renin
- Angiotensin I is then converted to angiotensin II in the lungs by angiotensin converting enzyme (ACE)
- angiotensin II stimulates the release of aldosterone from the adrenal glands
What is Conn’s syndrome and its causes?
Conn’s syndrome is primary hyperaldosteronism- the adrenal glands produce too much aldosterone. Can be caused by:
- Adrenal adenoma- an aldosterone secreting tumour
- Bilateral adrenal hyperplasia
- familial hyperaldosteronism
- adrenal carcinoma
How is primary and secondary hyperaldosteronism diagnosed?
Calculation of the renin:aldosterone ratio
- If low renin but high aldosterone= primary
- if high renin and high aldosterone= secondary
- Will also likely have high blood pressure (aldosterone increases sodium and water in blood)
- serum electrolyes- likely to have hypokalaemia
- can use CT/MRI scans to check for adrenal tumours
What is the treatment for Conn’s syndrome (aldosterone hypersecretion)?
- Usually use aldosterone antagonists e.g. Spironolactone
- and treat the underlying cause with surgery to remove the tumour/adrenal gland
What is the condition associated with cortisol hypersecretion?
Cushing’s syndrome
What causes Cushing’s syndrome?
Caused by having too much cortisol in the body
- this can be due to excess ACTH or corticotrophin-releasing hormone or adrenal tumours secreting excess cortisol
What are the symptoms of Cushing’s syndrome?
- excess glucose- hyperglycaemia
- abnormal fat distribution- ‘buffalo’ hump on the back of the neck or moon face
- thin and fragile skin
- osteoporosis
- Hirtuism- excess facial hair
- Hypertension
- Psychosis
- Depression
- Poor wound healing
- Increased susceptibility to infection
- Thin arms
- fatigue
What are the most obvious symptoms of Cushing’s syndrome?
- Moon face
- Buffalo hump
What can cause Cushing’s syndrome?
- Use of exogenous steroids e.g. prednisolone over a long period of time
- Pituitary adenomas producing excess ACTH
- Adrenal adenoma
What are the treatment options for Cushing’s syndrome?
- For tumours- radiotherapy or surgery
Pharmacological treatments: Corticosteroid inhibitors:
- Metyrapone- competitive inhibitor of 11B-hydroxylation in the adrenal cortex
- Ketoconazole- An imidazol derivative that acts as a potent inhibitor of cortisol and aldosterone synthesis
- Carbenexone- inhibits hydrocortisone conversion too cortisol
if Cushing’s syndrome was caused by steroid therapy, gradual reduction or withdrawal may be appropriate
What is the condition associated with a cortisol and aldosterone deficiency?
Addison’s disease
What is Addison’s disease?
A deficiency in both glucocorticoids and mineral corticoids- a cortisol and aldosterone deficiency due to atrophy of the adrenal cortex (wasting or thinning)
What are the symptoms of Addison’s disease?
- Lethargy
- Depression
- Anorexia
- Weight loss
- Increased thirst
- low mood
What is an Addisonian crisis?
This is a medical emergency caused by a dramatic fall in cortisol levels which can be fatal. People should watch out for the following symptoms:
Vomiting
abdominal pain
weakness
hypotension
hyperpigmentation
can cause a coma
What is the demographic of Addison’s disease?
- Most commonly diagnosed in ages 30-50
- More common in women
- About 300 cases per year in the uk
What is the treatment of Addisonian crisis?
100mg of IV hydrocortisone every 6-8 hours
What is the treatment for Addison’s disease?
Lifelong steroid replacement:
- Hydrocortisone- replaces cortisol
20-30 mg given daily- divided into a larger dose in the morning to mimic diurnal variations in normal cortisol levels- e.g. 10mg OM, 5mg LU and 5mg ON
- Fludrocortisone- replaces aldosterone
- given 50-300mcg once daily
- should carry a steroid card!!
