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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
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
Define impaired glucose tolerance?
Fasting BM <7mmol/l
but post OGTT ~7.8-11.1mmol/l
Define Impaired fasting Glucose?
Fasting Glucose ~6.1-6.9mmol/l
Post OGTT <7.8mmol/l
- Absolute insulin deficiency
- no GLUT4 induction → hyperglycaemia
Outline the Pathology of T1DM
- Autoimmune origin → pancreatic beta cell destruction
- HLA DR3/4
Outline the CF of T1DM?
- Acute onset
- BMI <25
- PMH/ FH of autoimmune disease
- rapid weigt loss
- Polyuria & Polydipsia
- Profound lethargy
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
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
What are the complications of T1DM?
- Peripheral vascular disease
insulin resisitance + progressive insulin secretory defect
Give 5 RF for T2DM
- Central Obesity
- Sedentary lifestyle
- Impaired glucose tolerance
- Impaired flasting glucose
- South asian or afro-carribean ethnicity
- FH → genetic factors
For Metformin give;
- Decr hepatic glucose production, decr GI glucose absorption, incr target cell insulin sensitivity
- Lactic acidosis
- Take w meals
- Stop during illness → lactic acidosis
For Sulphonylurea [Gliclazide] give
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
For Thiazolidinediones [TZDs] such as Pioglitazone give
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
Outline the Hypothalamic Pituitary Thyroid Axis?
Give 5 CF of Hypothyroidism & 2 causes?
- weight gain
- heavy periods
- peripheral oedema
- Congenital → picked up on guthrie card
- Post ablation → radio-iodine or surgery
- Auto immune → hashimotos thyroiditis
What would the TFT results of a hypothyroid patient be?
What would the AntiTPO result be? Why?
- Thyroid Peroxidase
- Anti TPO in Hashimotos, cause of hypothyroid
What is the Tx for Hypothyroidism?
- Thyroxine [T4]
- Converted to T3
- 125mg daily
What are the CF of thyrotoxicosis?
What are the causes of Thyrotoxicosis?
- 3 Ts of thyrotoxicosis
- Also → weight loss, amenorrhoea, diarrhoea, moderate goitre w bruit
- Autoimmune → graves disease [Stimulatory TSH-r Ab]
- Thyroid Adenoma → goitre
- ^^TSH drive → Pituitary adenoma, hCG cross react w TSHr
What Ix would you perform for suspected Thyrotoxicosis?
- TFTs → low TSH, ^^fT3/T4
- TSH receptor antibody
- Iodine uptake scan → radiolabelled iodine
How is Thyrotoxicosis treated?
Carbimazole → 40mg daily
Radioactive Iodine → thyroid destruction
What features of thyroid eye diseas are specific to Graves?
- Graves eye disease
- Conjunctival oedema
- Periorbital oedema
Lid lag & retraction are not specific to Graves.
How does Amiodarone cause hypothyroidism?
What would the O/E be?
- Amiodarone has ^^Iodine
- Wolff-Chaikoff effect
- ^^I → reactionary hypothyroidism
- Thyroid just wants to chill
- Weight loss
- Fast AF
- Small goitre
- No bruit
Outline the histology of the Adrenal Gland
- Outer cortex [GFR]
- Zona Glomerulosa → minerallocorticoids [Aldosterone]
- Zona Fasciculata → Glucocorticoids [Cortisone]
- Zona Reticularis → Androgens
Inner cortex → catecholamines
What is Hyperaldosteronism?
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]
How would you investigate Hyperaldosteronism?
- 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
How is the hyperaldosternoid Pt managed?
- Spironalactone [aldosterone antagonist]
- Multiple antihypertensives
- Unilateral adrenalectomy [30% remain HBP]
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
What are the CF of Addisons Disease?
'Unforgiving master of non-specificity & disguise'
- Hyperpigmentation of buccal mucosa & palmar creases [ACTH cross reaction w melanin receptors]
- Postural hypotension
- Vague symptoms [weightloss, dizzy fainting low mood diarrhoea etc]
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
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
What are the CF of Cushings Syndrome?
- Bufallo Hump
- Peripheral muscle wasting
- Easy bruise
- Moon face
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
What are the hormones secreted by the Anterior Pituitary?
Draw the control loop of Growth hormone release?
What is Acromegaly?
Give 5 CF of this disease!!!!!
Growth hormone excess [HODOR!]
- ^interdental spacing
- Excessive sweating
- Coarse facial features
- spade like hands
- Wrist pain → carpal tunnel