Lecture 24: Endocrine disorders Flashcards
Where do the adrenal glands sit?
On top of kidneys
What is the outer layer of the adrenal gland called?
Cortex - makes up around 80% of the glands mass
What is the inner core of the adrenal gland called?
Adrenal medulla
What are the layers of the adrenal glands called?
- Outer layer: Zona glomerulosa
- Middle layer: Zona fascicilata
- Inner layer: Zona reticularis
What is the collective name for the hormones produced by the adrenal glands?
Adrenocorticoids - name refers to site of origin - adrenal cortex and the chemical class they belong to - steroids.
What are the two types of adrenocorticoids?
- Mineralocorticoids
- Glucocorticoids
Where are the mineralocorticoids excreted from?
Cells in the zona glomerulosa
What is the function of mineralocorticoids?
Regulates Na reabsoprtion and K excretion in kidneys
What is the name of the mineralocorticoid hormone?
Aldosterone
What is the name of the glucocorticoid?
Cortisol
Where are the glucocorticoids secreted?
Zona fasciculata
What is the function of cortisol?
Regulates the bodys response to stress
What is the name of the sex hormone?
Androgen
Where is androgen secreted?
Zona reticularis
What is the function of androgens?
Regulate reproductive function
What does the adrenal medulla secrete?
Catecholamines
What are the catecholamines?
80% Adrenaline, 20% noradrenaline
What controls cortsiol secretion?
Hypothalmic pituitary adrenal axis
How is cortisol released by the adrenal cortex?
- Hypothalamus secretes corticotrophin releasing hormone
- This acts on the anterior pituitary to secrete adrenocorticotrophic hormone
- This acts on the adrenal cortex to release cortisol
When does cortisol peak?
When you wake up
What are the cellular actions of cortisol?
- Increase circulating glucose levels
- Maintain the normal responsiveness of blood vessels to vasocontrictive stimuli
- Have effects on the immune system, nervous system and kidneys
- Also an anti inflammatory immunosuppressant
What is the primary action of glucocorticoids?
To maintain normal concentrations of the enzymes necessary for the breakdown of proteins, fats and glycogen and the conversion of amino acids to glucose in the liver - increases plasma levels of glucose, fatty acids and amino acids
What is the effect of cortisol on many tissues?
- Decrease glucose uptake
- Decrease amino acid uptake
What is the effect of cortisol on many tissues?
- Decrease glucose uptake
- Decrease amino acid uptake
What is the effect of cortisol in adipose tissue?
Stimulate lipolysis which raises plasma levels of fatty acids and glycerol
What is the effect of cortisol in muscles and other tissues?
- Stimulate protein breakdown
- Inhibit protein synthesis
What is the effect of cortisol on the liver
Stimulate gluconeogensis
What is the cellular action of cortisol
Regulates genes controlling development, metabolism and immune response
Where is the glucocorticoid receptor found?
In the cytoplasm in its inactive form
How does cortisol have its action?
- Cortisol is an agonist for the glucocorticoid receptor, which is present in its inactive form in the cytoplasm. The inactive form forms a complex with heat shock proteins
- When the cortisol binds to the receptor, the heat shock proteins disocciate from the receptor and the glucocorticoid receptor travels to the nucleus of the cell where it has its effect
- In the nucleus, the glucocorticoid receptor regulates the transcriptional activity of glucoroticoid responsive genes, positively and negatively
- The glucocorticoid receptor is involved in transactivation, it forms a homodimer. It binds to DNA responsive elements on the gene and activates gene transciption
- It is also involved in transrepression - In the abscence of the activated glucocorticoid receptor, other transcription factors such as NF kappa B are able to activate target genes.
What is addisons disease?
Destruction or dysfunctional of the entire adrenal cortex. It affects both glucorticoid and mineralocorticoud function
What are the symptoms of addisons disease?
- Darkening areas of the skin (hyperpigmentation)
- Extreme fatigue
- Unintentional weight loss and decreased appetite
- Low blood pressure (light headedness and fainting)
- Gastrointestinal disturbance (nausea, vomiting, and abdominal pain)
- Salt craving
- Low blood glucose (hypoglycaemia)
What causes addisons disease?
- Autoimmune destruction of the gland
- Infections - TB, HIV, Syphilis, Cryptococci
- Invasion eg neoplastic conditions
- Haemorrhage - Waterhouse friderchsen syndrome
What causes hyperpigmentation of the skin in addisons disease?
The decreased secrtion of cortisol causes a lack of negative feedback, so an increased secetion of corticotrophin releasing hormone and adrenocotrophic hormone - this stimulates the malanocytes to produce malanin whoch leads to darkening of the skin.
What is the treatment for addisons disease?
Need glucocorticoid replacement - hydrocortisone, longer acting such as prednisolon or dexamethason
For mineralocorticoid 0 fludricortisone is used
What is the dosage for hydrocortisone?
15-30mg, given as divided doses to resemble the natural cortisol production
What should you do to adjust a patients dose if they are ill (infections)?
May require an increased glucocorticoid dose.
What is secondary adrenal insufficiency?
The adrenal glands still work but they just don’t t get appropriate signals to stimulate the release of adrenal hormones. Lack of adrenocorticotrophic hormone secretion from the pituitary
What is tertiary adrenal insufficiency?
Lack of corticotrophin releasing hormone secretion from the hypothalamus
What can cause secondary adrenal insufficiency?
Long term glucorticoid drug use can supress the hypothalamus adrenal pituitary axis.
Also if corticosteroid medication is stopped too abrptly
How do you treat secondary adrenal insufficiency?
With glucocorticoid. But mineralocorticoid is unnecessary because the adrenal gland works fine.
What do glucorticoid drugs do?
Suppress the hypothalamus and anterior pituitary
What is the rate of withdrawal for short term ( <3 weeks) courses of oral corticosteriouds?
Can be stopped abruptly
When should gradual withdrawal be considered?
- More than 3 weeks of treatment
Received repeated courses - Received more than 40mg prednisolone daily for more than 1 week
What is an adrenal crisis?
Sudden severe worsening of adrenal insufficiecy symptoms.
What are the symptoms of adrenal crisis?
- Sudden, severe pain in the lower back, abdomen or legs
- Severe vomiting and diarrhoea
- Dehydration
- Low blood pressure
- Loss of consciousness
What is cushings syndrome?
Hypersecretion of cortisol
What causes cushings syndrome?
- Prolonged exposule to elevated levels of cortisols - may be due to exogenous use of glucocorticoids or body produces too much
- Pituitary tumour - leading to increased secretion of adrenocorticotrophic hormone. This is called cushings disease
- Adrenocortical tumour
- Tumours external to hypothalmic pituitary adrenal axis - other parts of the body produce ectopic adrenocorticoptrophic hormone
What are the effects of cushings syndrome?
- Moon face
- Bruisability
- Red striation
- Fat in abdomen
- Poor wound healing
- Hypertension
- Red cheeks
- Thin arms and legs
- Excessive bone resoption
- Type 2 diabted
What are the 2 classes of cushings syndrome?
- Adrenocorticotrophic (ACTH) dependent - body makes too much adrenocorticotrophic hormone so too much cortisol is produced. This may be due to a pituoatry tumour ( Cushings disease) or an ectopic tumour produces too much ACTH
- Adrenocorticotrophic (ACTH) independent ACTH level is low Adrenal glands are making too much cortisol Due to adrenal tumour or adrenal hyperplasia
What drugs cause cushings syndrome?
- Glucocorticoids
- Drug interactions, drugs that inhibit CYP450 enzymes ( itraconazole, ritonavir, a number of antidepressants) because glucorticoids are metabolised by CYP450 enzymes
What is the treatment of cushings syndrome?
- Surgery: Remove the pituitary gland/ adrenal glands
- When drug induced: gradual withdrawal of the causative drug
- Mifepristone: glucocorticoid recptor antagonist. Doesnt reduce cortisol level, prevents the action of cortisol
What is metyrapone?
A drug that inhibits the enzyme 11 beta hydroxylase. This enzyme converts 11 deoxycortisol to cortisol. By inhibiting this enzyme, inhibits cortisol production
