My Endocrinology

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My Endocrinology
2012-01-26 12:14:11
adrenal diabetes

HPA axis, liver
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  1. Describe the enzymes commonly measured in LFTs
    • ALT: Found in hepatocytes and leaks in acute liver damage
    • AST: Found in RBCs, muscle and hepatocytes - also used as a cardiac marker
    • ALP: Lines biliary ducts- rises in cholestasis, bile duct obstruction and Paget's (found in bone)
    • gGT: Found in liver- shows cholestatic damage and even sub-clinical liver dysfunction. Especially used in chronic alcohol toxicity
  2. What are the three zones of the adrenal cortex, and what do they produce?
    • Z. Glomerulosa: Mineralocorticoids, especially aldosterone
    • Z. Fasciculata: Glucocorticoids, especially cortisol
    • Z. Reticularis: Precursor androgens in women/children
  3. Outline investigations of glucocorticoid production
    • Basal levels: ACTH and cortisol measured
    • Suppression: Dexamethasone given = CRH inhibition = Cortisol inhibition unless uncontrolled (e.g. Cushing's)
    • Stimulation: Synacthen given = cortisol production unless destruction
    • Imaging
  4. Outline investigations of mineralocorticoid production
    • Basal levels: Aldosterone-renin ratio
    • Suppression: Saline/fludrocortisone given = aldosterone suppression
    • U+Es for hypokalaemia
    • Urinalysis for excess excretion despite hypokalaemia
  5. Outline investigations of catecholamine production
    • Urinary catecholamines: 4hr collection to exclude excess
    • Resting plasma catecholamines
    • Imaging
  6. Outline causes of adrenal insufficiency
    • Primary: Addison's
    • Secondary: Long term steroid therapy = endogenous supperssion. H-P dysfunction.
  7. Outline the pathogenesis, pathophysiology and complications of Addison's
    • Pathogenesis: Destruction of adrenal cortex (e.g. AI or tb)
    • Pathophysiology: Reduced mineralo/glucocorticoid and androgen production
    • Complications: 'Addisonian crisis'; Hypoglycaemia, hypotension, hyponaetremia, hyperkalaemia, dehydration.
  8. Outline some major adverse effects of steroid therapy
    • Adrenal/pituitary suppression
    • Hypertension
    • Psychosis
    • Hyperglycaemia/diabetes/weight gain
    • Infection (with absent clinical features)
  9. What are the main causes of hyperaldosteronism?
    • Adrenal adenoma in zona glomerulosa (Conn's)
    • Ideopathic
    • Excessive renin production
  10. Outline the pathogenesis and pathophysiology of Cushing's syndrome
    • Pathogenesis: Increase in circulating ACTH (Cushing's disease) due to adenoma (usually pituitary). Or zona fasciculata adenoma
    • Pathophysiology: Hypertension, obesity, MI, infection and HF
  11. How are the causes of Cushing's syndrome managed?
    • Cushing's disease: Surgery or pitiuitary irradiation
    • Cortisol-inhibitors given prior to therapy
  12. What is a pheochromocytoma, and what does it cause?
    • Tumour of the sympathetic nervous system, usually in the adrenals.
    • Releases noadrenaline and adrenaline
    • Causes anxiety, hypertension, tachycardia, glycosuria, and any related damage
  13. What are the criteria for diagnosing diabetes?
    • Symptoms + random plasma glucose >11.1mmol/L
    • Fasting plasma glucose >7mmol/L
    • 2 hour post oral glucose tolerance >11.1mmol/l
    • HbA1c >6.5%
    • Confirmed on repeat testing
  14. Outline the pathophysiological mechanisms of diabetes
    • Hyperglycaemia
    • Microvascular complications
    • Cardiovascular disease
    • Acute decompensation (hyperosmolality, hyperglycaemia)
  15. What are the criteria for diagnosing metabolic syndrome?
    • 3/5 of:
    • Increased wast circumference
    • Increased triglycerides
    • Reduced HDL cholesterol
    • Increased blood pressure
    • Elevated fasting glucose
  16. What is the main cause of morbidities seen in chronic diabetes?
    • Microangiopathy is the cause of most complications in chronic diabetes
    • High plasma glucose causes increased endothelial intake of glucose
    • Glycoprotein formation occurs, thickening and weakening the basement membrane
  17. What changes occur in diabetic nephropathy?
    • Nephrotic syndrome and glomerulosclerosis
    • Glomerular fibrosis filtration membrane disruption and protein leakage (proteinuria)
    • Reduced filtration also leads to hypertension, oedema and reduced plasma oncotic pressure
  18. What is the cause of diabetic retinopathy?
    • Microangiopathy in the retina cause pericyte and endothelial cell damage
    • Blood-retinal barrier becomes permeable, while reducing blood supply
  19. Why are macrovascular changes seen in diabetes?
    • High blood sugar causes production of advanced glycation end products
    • Leads to inflammation and free radical production, endothelial damage and lipid deposition
  20. How is diabetic ketoacidosis acutely managed?
    • IV fluids; isotonic NaCL/lactated ringer's
    • IV/IM short acting insulin
    • IV KCl
    • NaCO3 (given if severe acidosis + hypokalaemia treated)
    • Underlying disease treatment
  21. Outline the long term management of type 2 diabetes
    • Lifestyle
    • Intensive hypertension treatment
    • Intensive dyslipidaemia treatment
    • Intensive glycaemia treatment
    • Antiplatelets if appropriate
  22. Describe the 'basal' insulin regimen
    • Mimics insulin release when controlling blood glucose during fasting
    • Given at bedtime
    • Intermediate/long acting insulin also prescribed
  23. Describe the 'biphasic' insulin regimen
    • Aims to provide fasting and post-prandial coverage
    • Given before breakfast and dinner
    • Requires a routine lifestyle and snacking
    • Glucose control not optimal
  24. Describe the 'basal bolus' insulin regimen
    • Aims to mimim insulin release as closely as possible
    • Basal insulin with a short acting given before meals
    • Requires multiple injections with snacking
    • Very flexible
  25. Describe 'insulin pump' therapy
    • Continuous subcutaneous insulin infusion
    • Has an adjustable basal rate given by an in vivo catheter
    • Can be programmed for nocturnal/early morning glucose changes
    • Useful for unpredictable livestyles and recurrent hyperglycaemia
  26. What is the mechanism of action of metformin?
    • Potentiates any residual insulin
    • Increases glucose uptake by skeletal muscle, inhibits gluconeogenesis and GI absorption
    • Also causes anorexia and weight loss
    • Risk of lactic acidosis
  27. What is the mechanism of action of thiazolidinediones?
    • Bind to a nuclear receptor in adipose and skeletal muscle cells
    • Increase insulin receptor expression
  28. What is the mechanism of action of sulphonylureas?
    • Activate a nuclear receptor in pancreatic beta cells
    • Reduce ATP sensitivity = increase insulin secretion
    • Can cause hypoglcaemia, increased appetite and weight gain
  29. Why is insulin used in T2DM?
    • Given when there is a high risk of CVD as well as a HbA1c >7%
    • Controls post-prandial hyperglycaemia
  30. What investigations are useful in Conn's syndrome?
    • Biochemistry: hypokalaemia/hyponaetremia/elevated aldosterone:renin ratio
    • Urinalysis: >30mmol potassium with hypokalaemia
    • Imaging: CT/MRI to localise adenoma
  31. What are the clinical features of Addison's disease?
    • Hyperpigmentation (increased ACTH production)
    • Postural hypertension
    • Anorexia/wasting
    • Low SBP
    • Hyponaetremia/hypokalaemia
    • General symptoms (malaise, weakness etc)
  32. How is Addison's disease managed?
    • Hydrocortisone
    • Prednisolone
    • Fludrocortisone
    • Treatment of underlying condition (stop steroid medication, AI etc)
    • Steroid warning bracelet
  33. What is the pathogenesis and pathophysiology of acromegaly and gigantism?
    • GH excess causes gigantism (before epiphyseal fusion) and acromegaly
    • Almost always due to pituitary tumour = increased GH and IGF-1
    • Soft tissue growth, arthropathy and sweat/sebaceous hypertrophy
  34. Outline some clinical features of acromegaly
    • Weight gain and limb size increase
    • Thick oily skin
    • Hyperhydrosis
    • Interdental separation/macroglossia
    • Hirsutism
  35. What investigations are useful in acromegaly?
    • Serum GH: if normal, acromegaly excluded
    • Serum IGF-1: Always raised in acromegaly
    • Glucose tolerance: glucose suppresses GH release
    • Diagnostic imaging
  36. How can acromegaly be managed?
    • Surgery/radiotherapy of adenoma
    • Dopamine agonists; lower serum GH
    • Octreotide; somatostatin analogue
    • Pegvisomant; competitive GH receptor antagonist
  37. Describe the appearance of the adrenals on imaging, including if an adenoma present
    • Upside down Y in transverse/coronal imaging
    • Low density unless IV contrast used, due to lipid content
    • Adenomas have greater lipid content, giving them a lower density (most incidentalomas)
  38. Describe the appearance of the pituitary on imaging
    • Central structure, with infundibulum attaching it to hypothalamus
    • Sits in pituitary sella
    • Found next to optic chiasm
    • Calcification occurs with aging
  39. Briefly outline the production of T3 and T4
    • I- taken up from blood via Na/I symporter
    • I- excreted into colloid
    • Thyroglobulin produced by ER and transported into colloid (very large molecule)
    • Tyrosines on thyroglobulin oxidised, then iodinised, then T1 and T2 attachements conjugate.
    • Whole molecule endocytosed into thyrocyte and proteolysed, creating T3 and T4, then excreted
  40. What investigations are useful when assessing thyroid function?
    • 123I can be used to show iodine intake and thyroid activity
    • Plasma TSH
    • Free thyroxine and total thyroxine (99% of thyroxine protein bound)
  41. Outline some common features of hyperthyroidism
    • Weight loss
    • Bone thining
    • Tachycardia/arrhythmia
    • Amenorrhea
    • Tremor
    • Sore eyes
  42. What investigations can detect hyperthyroidism and hypothyroidism?
    • Hyperthyroidism: Low TSH, TSH receptor antibody (Grave's), Thyroid peroxisomal antibody
    • Hypothyroidism: Thyroid peroxisomal antibody (again), high TSH, low free T4
  43. Outline some causes of hyperthyroidism
    • Thyroiditis: Destruction causes release and so high levels, then deficit
    • Grave's
    • Thyroid adenoma
    • Pituitary adenoma
  44. Outline some clinical features of hypothyroidism
    • Weight gain
    • Heavy periods
    • Peripheral oedema
    • Hair loss
    • Bradycardia
  45. How does amidarone cause thyroid disease?
    • Amidarone an anti-arrhythmic with a high iodone content
    • High iodine exposure causes 'Woll-chaikoff' effect, reducing thyroid iodine intake after large exposures
    • Type 1: Autoimmune thyrotoxicosis
    • Type 2: Destructive thyroiditis