Session 9: Disorders of Adrenocortical Function Flashcards
What is Cushing’s syndrome.
An umbrella term of the increase of cortisol (excess of cortisol). It is the chronic excessive exposure to cortisol.
How can Cushing’s syndrome be subdivided? What is most common?
Into External causes and endogenous causes. External causes are most common.
Give an example of an external cause of Cushing’s syndrome.
Prescribed glucocorticoids causing an increase in cortisol.
Give examples of endogenous causes of Cushing’s syndrome.
Benign pituitary adenoma secreting ACTH called Cushing’s disease. Excess cortisol produced by adrenal tumour called Adrenal Cushing’s. Non pituitary-adrenal tumours producing ACTH and/or CRH like small cell lung cancer. (Ectopic tumours)
Signs of excess cortisol.
Increased muscle proteolysis and hepatic gluconeogenesis. Hyperglycaemia, polyuria and polydipsia called steroid diabetes. Immunosuppressive, anti-inflammatory and anti-allergic reactions reactions of cortisol can lead to increased susceptibility to bacterial infections and production of acne. Disturbance in calcium metabolism
Symptoms of Cushing’s syndrome.
Plethoric moon-shaped face Buffalo hump (back/neck) Abdominal obesity Purple striae (due to proteolysis (weakened skin structure) and acute weight gain) Acute weight gain Hyperglycaemia Hypertension Back pain Easily broken bones due to osteoporosis Easy bruising because of thinning of skin Thin arms and legs Muscle weakness Hyperglycaemia Polydipsia Polyuria Nocturia Hypernatraemia Hypokalaemia
Why might someone with chronic inflammatory condition develop Cushing’s syndrome?
Because of their chronic inflammatory condition like asthma, IBD, etc… they might be on constant steroidal treatment (glucocorticoids) e.g. hydrocortisone and prednisone. Chronic excessive exposure to cortisol can lead to Cushing’s syndrome.
Why would hypertension develop in Cushing’s syndrome?
Cortisol (glucocorticoids) can also bind to mineralocorticoid and also androgen receptors, however with a low affinity. But with high levels of cortisol this will occur more often causing increase in blood pressure.
If someone is on glucocorticoids for a chronic inflammatory condition and develops Cushing’s syndromes. How will you treat it?
Steroid dosage should be reduced gradually and not stopped suddenly.
Why would you not just stop the steroid treatment suddenly all together?
Because there is a down regulated expression of zone fasciculata synthesis of cortisol. If you stop it too abruptly the patient won’t be able to produce their own cortisol and can cause an addisonian crisis.
What is Addison’s disease?
Chronic adrenal insufficiency.
Causes of Addison’s disease.
Disease of adrenal cortex due to auto-immune destruction reducing glucocorticoids and mineralcorticoids. Was a complication of tuberculosis back in the days. Disorders in pituitary or hypothalamus that lead to decreased secretion of ACTH or CRH which affects the synthesis of glucocorticoids. More common in women than men. Other much rare causes include fungal infection, adrenal cancer and adrenal haemorrhage.
Signs and symptoms of Addison’s disease.
Non-specific symptoms such as: Tiredness Extreme muscular weakness Anorexia Vague abdominal pain Weight loss Occasional dizziness Dehydration Hyponatraemia Hyperkalaemia More specific symptoms: Increased skin pigmentation (hyperpigmentation) in areas such as points of friction, buccal mucosa, scars and palmar creases. Hypotension due to sodium and fluid depletion Postural hypotension Hypoglycaemia especially on fasting
What is a severe and life-threatening consequence of Addison’s disease?
Addisonian crisis This can be caused by stress such as trauma or severe infection. Can lead to nausea, vomiting, extreme dehydration, hypotension, fever and even coma. Addisonian crisis is a clinical emergency.
How do you treat addisonian crisis?
Intravenous hydrocortisone and fluid replacement
How do you test for adrenocortical function?
First off we want to test the cortisol levels. This is done by plasma cortisol. 24hr urinary excretion of cortisol and its breakdown products are used to investigate adrenocortical disease. In case of suspected Addison’s you also want to test cortisol levels when you expect them to in a normal individual to be at its highest which is at around 9 am. In case of suspected Cushing’s you want to test cortisol levels when you expect them to in a normal individual to be at its lowest which is at around 12 am (midnight). Also electrolyte sample to see levels of Na+ and K+ in the blood.
What would you expect the levels of Na+ and K+ to be in a patient with Addison vs. one with Cushing’s? (This is compared to a normal healthy individual).
High Na+ and low K+ in a patient with Cushing’s due to glucocorticoid binding to mineralcorticoid receptors and increasing expression of Na+/K+-ATPase leading to an increased reabsorption of Na+. Low Na+ and high K+ in patient with Addison’s. (In ACTH deficiency only Na+ is low but K+ is normal.)
We established that the patient has an excess of cortisol. Our diagnosis is Cushing’s syndrome. How do we further test to establish where the problem is?
We want to establish whether there is an increased level of ACTH or a decreased.
Why do we test ACTH?
Because an increased ACTH would tell us that there is probably nothing wrong with the adrenal glands themselves because if cortisol was raised, cortisol should by negative feedback stop the synthesis and release of ACTH. A decrease in ACTH would mean that for some reason there is an increased level of cortisol but still a low level of ACTH. So the negative feedback loop is working fine, but there is still production of cortisol somehow.
Dexamethasone suppression test comes back. ACTH remained high. What is the diagnosis? Explain why.
Ectopic tumour releasing ACTH or CRH like small cell bronchial carcinoma. This is because there is no functioning negative feedback loop going on in the ectopic tumour. An increased level of dexamethasone has no effect on the production of ACTH or CRH.
