Week 12 - Endocriology

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mewinstanley@googlemail.com
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131385
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Week 12 - Endocriology
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2012-01-29 17:26:07
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Endocrinology
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DM, Thyroid & Adrenals
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  1. Define Diabetes Mellitus [WHO 1999]
    • Metabolic disorder of multiple aetiology
    • Characterised by → chronic hyperglycemia & disturb of carb, fat & prot metabolism
    • Resulting from defects in insuling secretion, action or both
  2. What are teh diagnostic criteria for DM?
    Based on threshold values for micro-vascular disease

    Symptoms + random BM >11.1mmol/l

    Fasting Plasma Glucose >7mmol/l

    2hours post oral GTT >11.1mmol/l

    HbA1c >6.5%
  3. Define impaired glucose tolerance?
    Fasting BM <7mmol/l

    but post OGTT ~7.8-11.1mmol/l
  4. Define Impaired fasting Glucose?
    Fasting Glucose ~6.1-6.9mmol/l

    Post OGTT <7.8mmol/l
  5. Define T1DM
    • Absolute insulin deficiency
    • no GLUT4 induction → hyperglycaemia
  6. Outline the Pathology of T1DM
    • Unclear
    • Autoimmune origin → pancreatic beta cell destruction
    • HLA DR3/4
  7. Outline the CF of T1DM?
    • Acute onset
    • BMI <25
    • PMH/ FH of autoimmune disease
    • rapid weigt loss
    • Polyuria & Polydipsia
    • Profound lethargy

    ?DKA
  8. What is Diabetic Ketoacidosis?
    How does insulin deficiency lead to DKA?
    DKA = Severe uncontrolled hyperglycaemia, acidosis & electrolyte imbalance

    • Lack of insulin leads to hyperglycaemia
    • ^gluconeogenesis & glycogenolysis
    • Reduced peripheral uptake [no GLUT4]

    • Lack of insulin → ^ lipolysis
    • ^^glycerol & FFA in portal circulation
    • FFA → ketone bodies [hepatic mitochondria] → ketosis & Acidosis

    • ^^blood glucose → osmotic diuresis
    • loss of fluid & electrolytes [Na, K & Mg]
    • acidosis displaces intracellular K
  9. Outline the Management of DKA?
    Replace Insulin → 6u/hr, maintain BM 9-14mmol/l

    Fluid replacement → FAST, 1l saline

    Replace K → serum ^^, total body K = low

    Supportive → ABCs, ECG, NGT, DVT-prophylaxis
  10. What are the complications of T1DM?
    • Microvascular
    • Retinopathy
    • Nephropathy
    • Neuropathy

    • Macrovascular
    • CVD
    • Peripheral vascular disease
  11. Define T2DM?
    insulin resisitance + progressive insulin secretory defect
  12. Give 5 RF for T2DM
    • Central Obesity
    • Sedentary lifestyle
    • Impaired glucose tolerance
    • Impaired flasting glucose
    • ^Age
    • South asian or afro-carribean ethnicity
    • FH → genetic factors
  13. For Metformin give;
    -MoA
    -Indications
    -A/E
    -PK/PD
    -WWJD?
    • MoA
    • Decr hepatic glucose production, decr GI glucose absorption, incr target cell insulin sensitivity

    • Indications
    • T2DM 1st line

    • A/E
    • Diarrhoea
    • Flatulence
    • Lactic acidosis

    • PK/PD
    • Short half life

    • WWJD?
    • Take w meals
    • Stop during illness → lactic acidosis
  14. For Sulphonylurea [Gliclazide] give
    -MoA
    -Indications
    -A/E
    -PK/PD
    -WWJD?
    MoA → act on beta cells ^^release of insulin

    Indications → intolerant to Metformin

    A/E → weight gain, hypoglycaemia

    PK/PD → short t1/2

    WWJD? → dont take if pregnant/ lactating
  15. For Thiazolidinediones [TZDs] such as Pioglitazone give
    -MoA
    -Indications
    -A/E
    -PK/PD
    -WWJD?
    MoA → improves target cell resp to glucose, decr gluconeogenesis

    Indications → 2nd line + SU

    A/E → concerns re: safety, ^ankle swelling, ^risk of osteoporosis

    PK/PD → prodrug, req hepatic metabolism

    WWJD? → heart failure
  16. Outline the Hypothalamic Pituitary Thyroid Axis?
  17. Give 5 CF of Hypothyroidism & 2 causes?
    • CF
    • weight gain
    • tired
    • heavy periods
    • constipation
    • peripheral oedema
    • Bradycardic
    • Goitre

    • Causes
    • Congenital → picked up on guthrie card
    • Post ablation → radio-iodine or surgery
    • Auto immune → hashimotos thyroiditis
  18. What would the TFT results of a hypothyroid patient be?
    What would the AntiTPO result be? Why?
    • TFT
    • ^^TSH, low fT4/T3

    • TPO
    • Thyroid Peroxidase
    • Anti TPO in Hashimotos, cause of hypothyroid
  19. What is the Tx for Hypothyroidism?
    • Thyroxine [T4]
    • Converted to T3
    • 125mg daily
  20. What are the CF of thyrotoxicosis?
    What are the causes of Thyrotoxicosis?
    • CF
    • 3 Ts of thyrotoxicosis
    • Tired
    • Tachycardic
    • Tremors
    • Also → weight loss, amenorrhoea, diarrhoea, moderate goitre w bruit

    • Causes
    • Autoimmune → graves disease [Stimulatory TSH-r Ab]
    • Thyroid Adenoma → goitre
    • ^^TSH drive → Pituitary adenoma, hCG cross react w TSHr
  21. What Ix would you perform for suspected Thyrotoxicosis?
    • TFTs → low TSH, ^^fT3/T4
    • TSH receptor antibody
    • Iodine uptake scan → radiolabelled iodine
  22. How is Thyrotoxicosis treated?
    Carbimazole → 40mg daily

    Radioactive Iodine → thyroid destruction
  23. What features of thyroid eye diseas are specific to Graves?
    • Graves eye disease
    • exopthalmus
    • Conjunctival oedema
    • Periorbital oedema
    • Proptosis
    • Othalmoplegia

    Lid lag & retraction are not specific to Graves.
  24. How does Amiodarone cause hypothyroidism?
    What would the O/E be?
    • Pathophysiology
    • Amiodarone has ^^Iodine
    • Wolff-Chaikoff effect
    • ^^I → reactionary hypothyroidism
    • Thyroid just wants to chill

    • O/E
    • Weight loss
    • Fast AF
    • Small goitre
    • No bruit
  25. Outline the histology of the Adrenal Gland
    • Outer cortex [GFR]
    • Zona Glomerulosa → minerallocorticoids [Aldosterone]
    • Zona Fasciculata → Glucocorticoids [Cortisone]
    • Zona Reticularis → Androgens

    Inner cortex → catecholamines
  26. Outline the HPA axis?
  27. What is Hyperaldosteronism?
    Give examples?
    Hyperaldosteronism = mineralocorticoid excess assoc w ^^BP & low K [arrythmia, muscle weakness]

    • Primary → suppressed renin levels
    • e.g. Conns syndrome, bilateral adrenal hyperplasia, adrenal carcinoma

    • Secondary → to ^^^^^^renin
    • e.g. renal hypoperfusion [HF, cirrhosis, nephrotic syndrome]
  28. How would you investigate Hyperaldosteronism?
    • Biochem
    • U+Es → low K, ?renin [primary v secondary
    • Aldosterone renin ratio [raised = primary aldosteronism n.b ^^renin, ^^aldosterone]

    Adrenal Vein sampling [to check for aldosterone]

    MRI/CT → localise any adenoma
  29. How is the hyperaldosternoid Pt managed?
    • Medical
    • Spironalactone [aldosterone antagonist]
    • Multiple antihypertensives

    • Surgical
    • Unilateral adrenalectomy [30% remain HBP]
  30. What is hypoadreanilsim?
    a.k.a Adrenal insufficiency

    • Inadequate production of steroid hormomes by adrenals
    • Usually Cortisol [may include aldosterone]

    Primary acute → stress crisis/ rapid steroid withdrawal/ adreanl haemorrhage

    Primary Chronic → Addisons/ MTB infection

    Secondary → hypothalamic/ pituitary disease
  31. What are the CF of Addisons Disease?
    • Hyperpigmentation of buccal mucosa & palmar creases [ACTH cross reaction w melanin receptors]
    • Postural hypotension
    • Vague symptoms [weightloss, dizzy fainting low mood diarrhoea etc]

    'Unforgiving master of non-specificity & disguise'
  32. How do you test for adrenal insufficiency?
    • Short ACTH test [Synacthen]
    • Measure plasma [cortisol] befre & 30 mins after ACTH analogue has been given
    • Addisons excluded if 2n measure = >550mmol/l
  33. What is Cushings Syndrome?
    What are the differenct causes?
    Cushings = glucocorticoid excess

    • ACTH dependant causes [^ACTH]
    • Cushings Disease → pituitary adenoma secreting ACTH bilateral adrenal hyperplasia
    • Ectopic ACTH → Small cell lung cancer & carcinoid tumours
    • Ectopic CRH [Rare] → Prostate tumour

    • ACTH independant [low ACTH]
    • Iatrogenic → Steroid use
    • Adrenal Adenoma/Carcinoma
    • Adrenal nodular hyperplasia
  34. What are the CF of Cushings Syndrome?
    • Bufallo Hump
    • Peripheral muscle wasting
    • Easy bruise
    • Striae
    • Moon face
  35. How do you investigate Cushings Syndrome?
    • Overnight Dexamethasone Suppression test
    • Give Pt steroid at midnight
    • measure cortisol before & at 8am
    • in healthy negative feedback so no ^cortisol
    • In CS → ^ cortisol despite low ACTH
  36. What are the hormones secreted by the Anterior Pituitary?
    Girls Like FAT!

    • GH
    • LH
    • FSH
    • ACTH
    • TSH
  37. Draw the control loop of Growth hormone release?
  38. What is Acromegaly?
    Give 5 CF of this disease!!!!!
    Growth hormone excess [HODOR!]

    • CF
    • ^interdental spacing
    • Excessive sweating
    • Coarse facial features
    • spade like hands
    • Wrist pain → carpal tunnel

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