RED Endocrine 8 Learning objectives PDF

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1. State the various hormones produced by the adrenal gland(cortex, medulla)Hormones of the adrenal gland Adrenal cortex – glucocorticoids (cortisol) – but cortisol has some mineralocorticoid activity as it is affects water and electrolyte balance like aldosterone - mineralocorticoids (aldosterone)-...

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1. State the various hormones produced by the adrenal gland (cortex, medulla) Hormones of the adrenal gland • Adrenal cortex – glucocorticoids (cortisol) – but cortisol has some mineralocorticoid activity as it is affects water and electrolyte balance like aldosterone – mineralocorticoids (aldosterone) – weak androgens (dehydroepiandrosterone, DHEA(S)) • Adrenal medulla – catecholamines (adrenaline, noradrenaline) 2. Regarding aldosterone and adrenal androgens, briefly describe the control of hormone release and their actions in the body Androgens include the DHEA/DHEAS and androstenedione and is regulated by ACTH. Androgens contribute to the auxillary and pubic hair growth in women Aldosterone the main mineralocorticoid is secreted when there is increased plasma potassium levels. Regulated by hyperkalaemia and angiotensin 2 ( RAAS). Aldosterone acts on the DCT and collecting ducts to promote sodium retention hence also water retention and potassium excretion into the urine by acting as a transcription factor with the mineralocorticoid receptor to increase expression of ATPase and selective sodium channels in the late DCT and CD. INDEPENDENT OF ACTH. In conns syndrome there is excess aldosterone present due to hyperaldosteronism and adrenal tumour. The excess aldosterone causes secondary hypertension due to excessive sodium and water retention and hypokalaemia as there is significant potassium loss in the urine.

3. Describe the hypothalamic-pituitary-adrenal axis (endocrine axis) The hypothalamus secretes corticotropin releasing hormone and this positively acts on the anterior pituitary to secrete adrenocorticotropic releasing hormone which positively acts on the adrenal cortex to stimulate cortisol, aldosterone and andgrogens release. However only cortisol is involved in feedback control. With the short negative feedback loop is there is inhibition of CRH release when there are high levels of ACTH detected. There is a long feedback loop with inhibition one and two levels above the arenal cortex. Administration of exogenous glucocorticoid steroids such as prednisolone and dexamethasone have a similar structure to cortisol therefore can also activate the long negative feedback loop by having a negative effect on the hypothalamus and the anterior pituitary. Get less CRH and ACTH hence supresses endogenous cortisol. Pred and dex are used in asthma, COPD, UC, RA, organ transplant.

Review the metabolic actions of cortisol on target tissues (muscle, adipose tissue and liver), and its immunosuppressive/ antiinflammatory actions

Actions of cortisol • Role in adaptation to stress • Permissive role in action of other endocrine hormones • Actions on other tissues

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Metabolic effects

In muscle and adipose tissue – catabolic opposes insulin. In adipose tissue get less glucose uptake and more protein breakdown to produce more amino acids. In adipose tissue there is also less glucose uptake and more lipolysis to produce more fatty acids and glyercol. Together these products increase gluconeogenesis in the liver whilst there is also increased glucose synthesis. In liver – stimulate gluconeogenesis, and glycogen storage. Glycogen storage is essential in order for us to deal with prolonged periods of stress as it provides readily available glucose faster than gluconeogenesis which takes too long. Overall, to elevate plasma glucose levels 

Anti-inflammatory/ immunosuppressive effects

Cortisol stimulates the production of lipocortin 1 (annexin1) – which inhibits PLA2, an enzyme that generates arachidonic acid, the precursor for prostanoids & leukotrienes. Cortisol also decreases the number and activation of T-lymphocytes and the production of cytokines (interleukins, TNF-D). It also stabilises lysosomes therefore phagocytosis doesn’t occur and decreases NO production.

4. Discuss the role of cortisol in the body’s stress response Stress is the state of threatened homeostasis and disharmony. Stress stimuli include anxiety, fear, fever, hypoglycaemia, injury and surgery There is an integrated response between the sympathetic nervous system and cortisol where there is a redirection of energy to provide increased CV tone and ventilation, more glucose availability and energy consuming activities such as digestion and reproduction are put on hold. There is also diversion of blood flow to the muscles and the heart. Cortisol ensures there is enhanced protein breakdown in the muscle to ensure there are amino

acids available for tissue repair if damage occurs and shifts protein and fat storage in favour of expanding glycogen stores and plasma glucose availability. There is also a stress activated immune response where cortisol protects the body against potential overactivation of immune defence mechanisms due to its immunosuppressive actions Chronic stress with prolonged elevated cortisol levels lead to muscle wasting, hyperglycaemia, GI ulcers ( loss of gastroprotective PGs) and impaired immune system

5. Describe the mechanisms underlying the main disorders of the adrenal cortex including Cushing's, Addison's and Conn's diseases. Briefly describe the main signs/ symptoms associated with these conditions and the principles of treatment of these disorders. (This is directed private study) Cushing’s syndrome -

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Excessive gucocorticiod activity- excess cortisol High dose or long term endogenous or exogenous steroid medication Main course is ACTH secreting anterior pituitary tumour- this is known as cushings disease and the disease causes cushings syndrome A primary cause of cushings syndrome is autonomous secretion of cortisol- causes negative feedback on ACTH CRH, therefore these levels are low Secondary causes are related to the pituitary (high cortisol and ACTH) and ectopic tumour causes ( High cortisol and ACTH) ( bronchial, pancreatic and ovarian) levels of ACTH are high due to impaired negative feedback Signs and symptoms o Truncal obesity – due to altered fat deposition o Buffalo humpo Thin skin o Acne o Female hirsutism- excess production of androgens o Muscle weakness- breakdown of protein and muscle wasting o Osteoporosis – excess mineralocorticoid activity, get altered bone metabolism o Hypertension o Diabetes o Female frontal balding o Depression o Bruises easily Diagnosis: o Cortisol measurements- loss of diurnal rhythm

o 24 hour urine free cortisol o ACTH measurement- primary ( low ACTH) , secondary ( high ACTH) o Low dose DEX- No change in cortisol levels if it is due to a pituitary ACTH tumour o High dose DEX- suppression of cortisol levels due to CRH and ACTH inhibition 

Treatment: o Localisation of tumour, MRI, abdominal CT o Surgery and radiotherapy to remove and destroy the tumour o Medical treatment such as drugs to inhibit steroidogenesis – CURATIVE

Addison’s disease

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Adrenal insufficiency – low aldosterone, cortisol and androgens but high ACTH and CRH Less cortisol therefore less negative feedback on CRH and ACTH Rare and chronic condition Primary adrenal insufficiency – gradual destruction of the adrenal tissue often autoimmune or HIV and TB Signs and symptoms due to lack of mineralocorticoid activity: o Postural hypotension o Muscle weakness o Hyponatraemia and hyperkalaemia o Weight loss o Increases pigmentation due to increased melanin in the skin- get in skin creases, scares and lips o Nausea and vomiting Tests for adrenal failure o Cortisol and ACTH leveks o Synacthen test o Andrenal antibodies if it is autoimmune Treatment: o Life long replacement – to be taken once daily o Glucocorticoid – hydrocortisone o Mineralocorticoid- fludrocortisone o Higher doses are given during times of illness or major stress ei surgery Secondnary adrenal suppression due to high dose glucocorticoid use ( low levels of ACTH and everything else- get atrophy of adrenal glands?)

Conn’s syndrome – primary hyperaldosteronism or adrenal tumour

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Excess aldosterone leads to hypokalaemia (increased elimination of potassium in the urine) and hypertension due to salt retention and water retention leading to increased circulatory volume hence increased blood pressure. Metabolic alkalosis as aldosterone stimulated hydrogen secretion in the I cells of the late DCT and DC.

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Treatment: o Surgery o Aldosterone receptor antagonist – spironolactone...