Endocrine Flashcards
Diabetes
Type 1 vs Type 2
Insulin release
Insulin action
Autoimmune destruction of pancreatic islet cells leading to reduced insulin
Hypersecretion of insulin by depleted beta cell mass. Increasing insulin resistance
Alpha cells: glucagon, beta cells: insulin
Glucose -> beta cell. Enters via GLUT-2. Increases ATP. ATP closes K+ channels which depolarise cell. VgCa channels open Ca to cell. Insulin released.
To peripheral muscle. Binds insulin receptor. Mobilises GLUT-4 to membrane. Glucose able to enter cell.
Increase glucose -> increased insulin
Increase uptake liver (200g) and muscles (150g) as glycogen
Suppresses gluconeogenesis, lipolysis, proteolysis, ketogenesis
Type 1 DM
Aetiology
Presentation
Complications
Genetic predisposition and autoimmune process (insulin/islet cell autoantibodies)
Family history of other autoimmune conditions HLA DR3/4
Polyuria, polydipsia, weight loss, lethargy, DKA problems… (dehydration, breathing, abdo pain)…
DKA
Type 2 DM
Who
RF
Pres
30+ obese, low physical activity
Obesity (trunk i.e. metabolic), lack of activity, PCOS, metabolic syndrome, family Hx (x2.4 > than T1DM), south Asian, pre-diabetes (impaired glucose tolerance/fasting glucose)
Polyuria, polydipsia, lethargy, prolonged/frequent/recurrent infections (e.g. vaginal thrush)
DM
Ix
Diagnosis criteria
Complication screening (3)
Urine dip, FPG, RPG, OGTT, HbA1c (n.b. this won’t be accurate in anaemic patients)
Symtomatic + one elevated FPG (≥7.0) or RPG (≥11.1)
Asymptomatic + two elevated FPG or RPG
HbA1c ≥48mmol/mol or 6.5%
Urine dip for protein
BP for HTN
Fasting lipid for hyperlipidaemia
Diabetic foot
Presentation (2)
Risk factors
Ulcers (neuropathic painless and punched out or arterial), loss of pulses
Charcot foot - Bone and joint degeneration -> deformity - Rockerbottom sole, claw toes, loss of transverse arch
Peripheral neuropathy, callus smoking, HTN, hypercholesterolaemia
Diabetic eye problems
Types
Process
Features (5)
Cataracts, retinopathy, maculopathy, glaucoma
Microvascular occlusion -> retinal ischaemia -> neovascularisation
Pericyte loss -> leakage -> haemorrhages or diffuse oedema
Microaneurysm - from physical weakness
Hard exudates - lipoproteins from leakage
Haemorrhages - rupture of weakened capillaries small dots, blots or flame
Cotton wool spots - build up of axonal debris
Neovascularisation
Diabetic eye problems
Presentation
Management
Emergency referrals (3)
Painless, gradual reduction of central vision
Haemorrhage - sudden onset dark, painless floater
Optimise glycaemic control Blood pressure control Lipid control Laser photocoagulation Or intravitreal steroids
Sudden LOV
Red eye
Retinal detachment
Annual review criteria (10)
Educate + modifiable RFs Check BMI Check complications: hypos, HOHS, DKA Assess CVS: BP, pulses, bruits Inspect injection sites - lipodystrophy Foot check - neuropathy and pulses Urine dip - protein, nitrites, ketones Check eyes - acuity and ophthalmoscopy -> refer opthalmology Ask erectile dysfunction Bloods: HbA1c and home capillary monitoring results, random lipids
Type II DM management
Single drug therapy ideally metformin
Target is 6.5%
Gradually increase over weeks to reduce GI SE
Dual drug therapy *only if HbA1c > 58mmol/mol or 7.5%
Target is 7% (53mmol/mol)
Sulfonylurea or pioglitazone
Still not 58/7.5%
Metformin + sulfonylurea + pioglitazone
Metformin + sulfonylurea + gliptin
Start insulin
Insulin
Metformin Class Pharmacology Contraindications SE
Biguanide
Increases insulin sensitivity (GLUT 4), decreases gluconeogenesis
CKD, eGFR < 30
GI upset: nausea, anorexia, diarrhoea - 20% intolerable
Sulfonylurea Class Pharmacology CI SE
Oral hypoglycaemics
Increase panc insulin secretion
Pregnancy
*Hypo, weight gain
Piaglitazone Class Pharmacology CI SE
Oral hypoglycaemics
Increases insulin sensitivity
Heart failure and osteoporosis
Weight gain, fluid retention and osteoporosis
Insulin regimes (4)
Once-daily - Long or int at bedtime - only suitable T2DM
Twice-daily - Pre breakfast/evening meal
Basal-bolus - Long or int at bedtime with rapid/short to cover meals
Continuous subcut or insulin pump- If very poor control
Sickness and Diabetes
Stress response to illness -> increased cortisol
Cortisol increases blood sugars and decreases insulin
If oral meds - Seek help if glucose >13mmol/l
If insulin meds - Seek help if signs of DKA (Kussmaul, vomiting, drowsy/confused, can’t eat)
DKA
Causes
Presentation (7)
Reduced insulin levels caused by - missed insulin, infection, intoxication, ischaemia, infarction
Abdominal pain + vomiting Polyuria, polydipsia, dehydration Kussmaul respiration (deep hyperventilation to correct acidosis) Acetone breath (pear drop) (Fat -> Ketones)
DKA Ix (4)
Plasma glucose: high >11 or known DM
Plasma ketones: high >3mmol/l
ABG: metabolic acidosis pH < 7.3
Urine dip: ketones (++) and glucose
DKA management
ABCDE sats etc… + catheterise
Volume depletion: IV NaCl (1L/hour or maintenance)
*switch to 5% dex when glucose <12
Hyperglycaemia: IV insulin - will drop the potassium…
*Fixed rate IV infusion: 0.1U/kg/hr add glucose when drops
Hypokalaemia (as a result of fluids and insulin): K+in fluids
>5.5 = nil
3.5-5.5 = 40mmol/L infusion solution
<3.5 = senior review
Acidaemia: IV bicarbonate
Hyperosmolar hyperglycaemic state
What
Causes
Mechanisms
Often very high blood glucose >40 + v.high serum osmolality. (DKA equivalent for type II DM)
Infection, MI, dehydration, inability to take normal meds, thiazides + loop, poor control
Hyperglycaemia -> osmotic diuresis -> hyperosmolarity leading to fluid shift of water into intravascular compartment -> severe dehydration
No ketosis as enough insulin to suppress ketogenesis
Hypovolaemia
Marked hyperglycaemia (>30) without hyperketonaemia or acidosis
Osmolality > 320 mosmol/kg (concentration of blood)
N.b. osmolality = /kg, osmolarity = /L
Extreme dehydration + altered mental state ± seizures ± delirium
HHS Ix (6)
Urinalysis: glycosuria +++. Ketonuria + Capillary glucose > 30 Serum osmolarity > 320mmol/L U+E -> AKI ABG -> normal Blood cultures -> rule out sepsis
HHS management
Treat cause
Safely normalise osmolality - replace fluid and electrolytes
Normalise blood glucose
ABCDE
IV access, ECG, SaO2, BP
Calculate osmolality frequently (2Na + gluc + urea)
-IV 0.9% NaCl -> aim for fall of Na by 10mmol/24 hours, glucose 5mmol/hr
-Aim for 3-6 litres +ve by 12 hours
IV insulin (0.05U/kg/hr) if glucose no longer falling
Rapid correction of Na
Cerebral oedema, central pontine myelinosis
Metabolic syndrome
Cluster of common abnormalities including insulin resistance, impaired glucose tol, reduced HDL, elevated triglycerides and HTN
BMI classification
≤18.5 underweight 18.5-24.9 optimal 25-29.9 overweight 30-34.9 obese I 35-39.9 obese II ≥40 obese III - weight is imminent threat
Other causes of obesity
Drugs: Glitazone, sulfonylurea, antipsychotics , antidepressants: tricyclics and mirtazapine, lithium, progesterone only contraception, BB, corticosteroids
Conditions: Hypothyroid, PCOS, Cushing’s, hypogonadism
NICE recommended calorie decrease for weight loss
600kcal
Gynaecomastia
Physiology
Causes
Oestrogens stimulate, androgens inhibit therefore ratio is important
Conditions raising oestrogen
Conditions dropping testosterone/androgen resistance
Conditions causing increased conversion of androgens to oestrogen - aromatase (in increased adiposity)
Path (low test) - androgen resistance, Klinefelter’s, viral orchitis (mumps), renal disease
High oestrogen - Neoplasms secreting HCG (e.g. seminoma), RCC, adrenal tumour (oestrogen), *liver disease - increased prod androstenedione and aromatisation to oestrogen), obesity, hyperthyroid.
Drugs
Drugs causing gyneacomastia (4)
Digoxin - oestrogen like effect (enhanced with liver failure)
Increase prolactin - antipsychotics, TCA, metoclopramide
Spironolactone - inhibit testosterone synthesis
Anabolic steroids - androgens cause high oestrogens
T3 & T4
Which active
Where activated
T3
80% @ liver, 20% @ thyroid
Hypothyroid
Most common cause
Associations
Other causes (3)
Hashimoto’s thyroiditis
AI disease: T1DM, Addison’s, pernicious anaemia: 5x in women
Iatrogenic: surgery or radioiodine treatment
Drugs: lithium, amiodarone (*iodine rich may become hypo or hyper)
Iodine deficiency most common in developing world
Hypothyroid symptoms (8)
Tired + lethargic Intolerant to cold Slow intellectual: poor memory and difficulty concentrating Constipation Weight gain + decreased appetite Deep hoarse voice Menorrhagia Reduced libido, depression
Signs of hypothyroid (7)
Dry coarse skin/hair Puffy face/hands/feet (myxoedema) Bradycardia Goitre Delayed tendon reflex Carpal tunnel Serous cavity effusions: pericarditis/pleural effusions
Myxoedema
Features (6)
Severe cases
Treatment
Due to build up of mucopolysaccharide in tissues.
Expressionless face with peri-orbital fullness
Pale cool skin with rough - doughy texture
Enlarged heart
Megacolon
Cerebellar ataxia
Psychosis + encephalopathy -> myxoedema coma
Severe cases - Hypo features + seizures + hypothermia + decreased consciousness + hypoventilation + hypoglygaemia/natremia
IV levothyroxine + IV hydrocortisone (after blood cortisone) + resp support
Management of hypothyroid
Levothyroxine (T4) for life
Initial dose: 50-100 mcg, step up by 25-50 depending on TFT every 3-4 weeks
Annual TFT when stable
Hyperthyroid
Main cause
Other causes
Grave’s disease (assoc thyroid eye disease) - 75%
Toxic multinodular goitre - more common in >60 from high iodine (amiodarone or derbyshire)
Toxic nodule/adenoma
Drugs: amiodarone
Exogenous thyroid hormone excess: treatment
Ectopic thyroid tissue: metastatic follicular carcinoma or ovarian teratoma
TSH secreting pituitary adenoma (secondary)
Symptoms and Signs of hyperthyroid (5 each)
Weight loss and increased appetite Irritable + weak Sweating, tremor Diarrhoea Mental illness: anxiety to psychosis Heat intolerant Loss of libido Oligomenorrhoea
Sweaty/warm palms Fine tremor Tachycardia ± AF Hair thinning Goitre *Proximal myopathy (wasting and weakness) Gynaecomastia Brisk reflexes Urticaria/pruritus + thyroid acropachy + pretibial myxoedema
Graves disease
Antibody
Pathophysiology
Thyroid eye disease features (10)
Anti-TSH receptor (Abs may react with orbital antigens)
AAb stimulate TSH receptor leading to excess secretion of thyroid hormones and hyperplasia of follicular cells -> diffuse goitre
Lid lag, lid retraction, ophthalmoplegia, exophthalmos, gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema
Nb. Worsened by radio-iodine + smoking
Management of Hyperthyroid
Beta-blockers - propanolol
Lubricating eye drops
Antithyroid drugs
-Carbimazole: start 10-20mg/day titrate based on TFT (monthly)
-Propylthiouracil - causes liver fail: reserve for pregnancy and thyroid storm
Radioactive iodine (CI at pregnancy/breast feeding)
Relapsed Grave’s or toxic nodular (worsens eye disease in Grave’s)
Surgery
Warning with antithyroid drugs
myelosuppression - agranulocytosis + neutropenia sepsis
Usually presents as a sore throat
Thyroid storm
Happens in
Features
Cause
Grave’s or TMNG
Hyperpyrexia > 41 CVS: HR > 140, hypotension, AF, CHF GI: Nausea, jaundice, vomiting, diarrhoea, abdominal pain NEURO: Confusion, agitation, delirium Infection
Resus: O2, IV fluids, NG tube if vomiting
- Oral carbimazole or propylthiouracil
- @4 hours - Lugol’s solution - aqueous iodine to block TH
IV propanolol
IV hydrocortisone (treats possible relative adrenal insufficiency)
PTH physiology
Released in response to low ionised Ca
Actions
-To bone: increase osteoclastic activity - release Ca and PO4
-To kidney: 25-OH-D to 1,25-OH2-D (1-alpha hydroxylase) - increases Ca absorption gut
Increases reabs Ca, decreases reabs PO4 (increases PO4 in urine, decreases Ca)
-Net effect - increased Ca, decreased PO4
Calcitonin
Produced by para-follicular (medullary) C cells of thyroid inhibits osteoclast activity - reduces Ca and PO4
Primary hyperparathyroid
Who
Cause
Presentation
Occur in postmenopausal women
85% are solitary adenoma
10% are 4 gland hypertrophy
80% are asymptomatic and diagnosis when hyperCa found
Excess Ca absorption from bone: osteopenia and osteoporosis if extreme
Excessive renal Ca excretion: calculi
Mild symptoms of hypercalcaemia: fatigue, weakness, muscle pain
*Bones, stones, abdominal moans, thrones, psychic overtones
