Learning objectives: Endocrinology Flashcards
What are the Learning Objectives for Endocrinology AH1
What is the Morbidity associated with diabetes:
Epidemiology of diabetes in Australia:
What is the definition of diabetes? (in relation to BSL) ? indeterminate?
Introduction
Morbidity
- Shortens lifespan by 15 years
- Leading cause of blindness, CKD and non-traumatic leg amputation
- Risk factor - stroke, MI
Epidemiology
- Most common lifestyle disease WW
- In Australia
- 6% of general population >18
- 13% of indigenous population
- Higher in lower SE class
- Nearly half of diabetics are estimated to be undiagnosed
- Increasing prevalence rapidly
- Increase lifestyle factors
- Growing rapidly in developing nations (greatest increase)
Definitions*
Finger-prick BGL - all that is required to diagnose T1DM
Diagnosis
- Random BGL ≥11.1 = DM
- Fasting BGL ≥7mmol/ = DM
- HbA1c ≥6.5%
- OGTT ≥11.1 at 2h
- Indeterminate
- Random BGL 7-11 = fasting test for DM
What is the classification of the different types of DM? What is secondary DM? What are causes of this?
What about Beta cell destruction? What conditions can cause this- thus leading to DM?
What is the normal blood sugar? What are the major actions of insulin: on liver, skeletal muscle, adipose tissue?
Insulin function?
What hormones oppose insulin (anti-insulin through their actions)
What occurs in a fasting state?
What occurs to insulin function in DM?
What is the function of incretins?
Eitology of T1DM?
Eitology of T2DM?
What are risk factors for T1DM?
What are risk factors for T2DM? (non-modifiable, modifiable)
Pathogenesis of T1DM?
Pathogenesis of T2DM? Describe pathogenesis of clinical features: Polyuria? Polydipsia? Weight loss? Weightloss/weakness?
Type 1 vs Type 2 diabetes mellitus:
Patho?
Age of onset?
Presentation?
Ketosis?
Fmhx? Pmhx?
Treatment?
Diagnosis?
Screening? How often?
Investigations?
General management measures?
Diabetes
à Syndrome of disordered glucose metabolism and inappropriate hyperglycaemia. Relative to absolute deficiency of insulin or insulin sensitivity or both.
Type 1 vs Type 2
- The distinction should be a clinical one, with suggestive investigation results. Eg type 1 should not be ruled out in a pt with clinical features but negative antibodies.
Type 1 Diabetes
Type 2 Diabetes
Pathophysiology
Insulin deficiency from autoimmune destruction of pancreatic B cells (islet cells). Believed to be triggered by environmental factors (eg viruses). 80% cell destruction before features of DM present.
Impaired insulin secretions, peripheral insulin resistance, excess hepatic glucose production. Starts as relative insulin deficiency then → B cell failure → +/- absolute insulin deficiency.
Age of onset
Typically adolescents, young adults
Can occur at any age
↑Incidence with age
Presentation
Acute
Polyuria, polydipsia
↓Weight
DKA
Often asymptomatic for a long period
Mild symptoms of fatigue
Associated with obesity and other CVD risk factors (dyslipidaemia, HTN)
Little/no ↓ weight
HONK
Ketosis
Often present, even when not in DKA
Rare
FHx / PMHx
Autoimmune disease
- Thyroid
- Coeliac
- Pernicious anaemia
- MG
Not often T1DM
FHx of T2DM common
PCOS
Gestational DM
Race - Asian, Aboriginal, Middle East
Treatment
Insulin
Lifestyle modifications
Antihyperglycaemic drugs
+/- Insulin
Diagnosis
- Symptoms PLUS one (any) result above the diagnostic BSL threshold
- If no symptoms, TWO abnormal results on two separate days
(Use OGTT to confirm uncertain results.)
Normal
Uncertain
Diabetes
Venous BSL
Fasting
≤6.0
6.1 - 6.9
≥7.0
Random
≤6.0
6.1 - 11.0
≥11.1
OGTT
2-hours
≤7.7
7.8 - 11.0
≥11.1
HbA1c
≥48 (6.5%)
Screening
Every 12-months screen high-risk groups for developing T2DM:
- Impaired glucose tolerance, impaired fasting glucose
- Hx of GDM
- PCOS
- Cardiovascular disease (AMI, angina, stroke)
- AUSDRISK tool (age, gender, ethnicity, FHx, BP, BSL, smoking, diet, physical activity, central adiposity)
Investigation
- Bloods: Anti-GAD (glutamic acid decarboxylase), ICA (islet cell antibodies), anti-insulin antibodies
- Lipid profile (T2DM)
General measures
Education and information of complications
- Self-monitoring BSLs
- Symptoms of hypoglycaemia
- Driving (while hypoglycaemic → loss of licence)
- Pregnancy counselling
Lifestyle modification
- Quit smoking
- Diet, exercise
- Reduce other CVD risk factors (start statin, BP, weight, etc)
Link in with allied health
- Dietician, podiatrist, optometrist
What are different variations of insulin?
How much should you adjust insulin dose in cases of hypos and hypers?
What is an insulin sliding scale?
Insulin
Target:
HbA1c = ≤ 53 (7%) BSL 4 - 7mmol before meals BSL 5 - 10mmol/L after meals
Types of insulin:
- Long-acting (glargine = Lantus®, detemir = Levemir®, isophane = Protophane ®)
- Short-acting (Acrapid®, Humulin®) given BEFORE meals
- Rapid-acting (Novorapid®, Humalog®, Apidra®) given WITH meals
- Pre-mixed insulins (70% long-acting, 30% short-acting)
Regimes:
Basal-Bolus
- Basal insulin = long-acting = 40% of daily insulin requirement OD
PLUS
- Bolus insulin = rapid-acting = 60% of daily insulin requirement divided into three doses
Mixed insulin
- Pre-mixed insulin BD
Insulin pump (continuous subcut insulin infusion)
- Need to be motivated, educated in insulin pump and diabetes, attend specialist centre.
- Pts need to monitor BSL frequently, count carbohydrates. Needle site needs changing every 3-days
- Complications incl abscesses at injection site, catheter blockages → DKA.
Adjustments:
Hypos (BSL <4mmol/L) → ↓total daily insulin dose by 20%.
Hypers (BSL >8mmol/L) and no hypos yesterday → ↑total daily insulin dose by 20%.
Sliding scale:
- Rapid-acting insulin given IV
- Good for T1DM peri-operative, fasting >6h, DKA/HONK, T2DM with poor peri-op BSLs
- Issues - hyperglycaemia, hypoglycaemia, iatrogenic DKA in T1DM
- Review if BSL <5 or >15 or 3x consecutive BSLs >10
What are the first line medical management for T2DM? What are their MOAs?
What is the definition of hypoglycemia?
T2DM
Minimising modifiable CVD risk factors is as important as glycaemic control.
- Metformin 500mg PO BD and increase dose up to 1g TDS max
o ↓Hepatic glucose production, does not cause weight gain
o GI intolerance, lactic acidosis (renal excretion)
- Add Sulphonylurea
o HYPOGLYCAEMIC (↑insulin secretion from the pancreas), can cause ↑weight
- Add DPP-4 inhibitor or GLP-1 agonist or Acarbose or SGLT-2 inhibitors
o DPP-4 inhibitors not associated with weight gain, may cause pancreatitis
o GLP-1 agonists are given SC, associated with ↓weight, may cause GI upset and pancreatitis
o Acarbose delays carbohydrate digestion and glucose absorption
o SGLT-2 inhibitors block glucose reabsorption in the kidney
- Add basal insulin or Thiazolidinedione if insulin is relative contraindicated (eg risk of hypos while driving a commercial vehicle)
What are the normal cell of endocrine pancreas?
What are microscopu changes that occur in T1DM & T2DM?
What are the changes seen in diabetic nephropathy? (AGE deposition) + late stage changes?
What are cardinal clinical features of T1DM and T2DM: Distiguish between:
What are other symptoms od DM? List 6?
What are symptoms of hyperglycemia?
What are complications of DM?
Acute complications?
Macrovascular?
Microvascular? Renal, eyes, peripheral, autonomic - Mechanisms by which this happens?
Immunosuppression?
How can you prevent DM? 3 marks?
Screening for T2DM? What is AUSDRISK? What is needed for this screening tool? How often and when should it be done?
Who are high risk patients that should be monitored regularly?
DDX for hyperglycemia?
How and when is diabetes diagnosed? E.g What are BSL required for diagnosis?
What is an OGTT? When is it required? explain:
What are additional required tests when newly diagnosed T1DM? (think autoimmunity)
How often should pre-diabetic be screened?
Management framework for T2DM:
Non-pharm- education, vaccination, diabetes educator, podiatrist (feet check)?
Lifestyle -SNAP?
Medical? Glycaemic control? CV and metabolic optimisation? Manage complications
Ongoing monitoring?
MDT? Who should be involved in patients care? list 6 allied health professionals:
Closing:
What should occur at 3-6 monthly reviews?
Outline a 12 monthly diabetic review: E.g what you need evaluate; hx, symptoms, review complication, exams, Ix, Rx
How often should Hba1c be done?
Who benefits from BSL self-monitoring? How? Targets? Benefits?
What are the CV targets for patient with DM?
Glucose lowering agents Algorithm:
Metformin+ ?
Dual therapy?
Third line?
Managing diabetic complications: Case Diabetic neuropathy:
Outline: Examination, Investigations?
Non-pharmacological management: Ulcers, lifestyle, educate, referrals?
Medical management? Neuropathic pain? optimise:
Closing?
Management of diabetic neuropathy (without ulcer)
Exam
- Diabetic foot
- Look for ulcers & PVD
IxInvestigate to exclude other common causes
- B12/folate
- TFTs (hypothyroidism)
- UECs (CKD)
Glucose control
- HbA1c
- Others - UECs, lipids, LFTs
- Urine - ACR
Non-pharmacological
- Ulcers - explain that this commonly leads to chronic ulcers which can become infected and lead to amputation –> need to monitor very closely
- Lifestyle - SNAP
- Check every day - self-check in the mirror for wounds daily
- Educate - this is caused by sub-optimal glucose control resulting in damage to nerves
Referrals for MDT team
- Podiatry assessment
- Chronic disease or wound care nurse - remove calluses; manage wound
- OT
- Dietician
- Ex phys
- Medical
Neuropathic painRx = amitriptyline
- TCAs are first line
- Pregabalin 2nd line
- Optimise diabetes
- Review medications
- Optimise CV risk
- Review medications
- Treat infection
- Augmentin for diabetic foot infection
Ongoing monitoring
- Exam - yearly foot exams, ophthalmology
- Ix - HbA1c every 3 months
Close
- Give information
- Refer - podiatrist, wound nurse, dietician, ex physiologist, ophthalmologist, OT
- Vascular surgeon - signs of PVD
Managing diabetic nephropathy:
- Strict BP and glucose control
- Ace inhibitor -> decreased ACEi –> decreased intra-glomerular pressure + dilation of efferent arteriole for better perfusion of tubules
- Glucose control - limits AGE deposition in BM and mesangium
Outline Assessment of diabetic patient: COMMON OSCE STATION
Hx: Think, symptoms, complications, medical, medication review,vaccines, obstetric, social
Diabetic examination: General, signs of insulin resistance, diabetic foot examination, CV exam including calculate CV risk, eye examination, urinanaylsis-proteinuria, glucose
Investigations to be reviewed (re done) + Findings?
Assessment of diabetic patient
Hx - assessment or review of known diabetic (COMMON OSCE)
- Sx hyperglycaemia - fatigue, polyuria, polydipsia, polyphagia, weight loss
- Sx hypoglycaemia - neuroglycopenic (hunger, altered LOC) & autonomic (sweating, tremor, pallor etc.)
- Complications - CV symptom review*, blurry vision*, sensory loss*, pins and needles*, erectile dysfunction, orthostatic changes*, diarrhoea, delayed wound healing, recurrent infections
- Medical - CV disease, HTN, haemochromatosis, pancreatic disease
- Medications - use of hyperglycaemic drugs, compliance with meds , side effects
- Vaccines - childhood, annual influenza recommended, pneumococcus recommended, tetanus boosters
- Obstetric - GDM
- Social - SNAP (review regularly), living arrangements
- Family Hx - diabetes, autoimmunity if T1DM suspected
Diabetic examination
- General - weight (F <80, M <92), BMI (aim <25), waist circumference
- Signs of insulin resistance - obesity, acanthosis nigricans, skin tags, hirsutism
- Diabetic foot examination
- CV exam including calculate CV risk
- Eye exam
- Repeat annually or refer to ophthalmologist
- Acuity, EOM, fundoscopy
- Urinalysis - proteinuria, glucose
Ix
Absolute CV risk
- Frequency depends on CV risk
- Include - BMI, waist circumference, BP
ECG
- Baseline monitoring for IHD
- Required for CV calculator (BUT DM automatically high risk)
HbA1c
- Every 3 months (max), aim for <7.0%
Urinalysis and ACR
- Proteinuria, ketones, glucose, leukocytes
- Ketones + need to do a UECs for HCO3
- Microalbuminuria: ACR ≥2.5 mg/mmol (men) or ≥3.5 mg/mmol (women)
- Proteinuria: ACR ≥25 mg/mmol (men) or ≥35 mg/mmol (women)
- Nephrotic syndrome: ACR > 30
- UECs & GFR - CKD
Fasting lipid screen
- Elevated TGs and low HDL-C characteristic
- Targets: LDL-C <2; HDL-C>1; total-C <4; TG<2
LFTs - NAFLD
What is HHS/HONK?
What are trigger for it?
Pathogenesis?
Clinical features? list - History (2 marks) Examination (4 marks) ?
Investigations and findings? bedside?(2 marks) Bloods (2 marks)? Imaging? (0.5 marks)
Management: Outline: DRSABCDE, rehydrate+correct electrolytes, specific, supportive, ongoing, complications?
Prognosis?
OSCE: Patient presents with Hyperglycemia: Exma, ketone breath+ dehydration:
Ix: Send as urgent: Urinanaylsis (dipstick, labs BSL, U+Ecs, VBG, FBC Ketones, Send hospital if worried (GP land)
Acute metabolic complications
Hyperosmolar Hyperglycaemic Syndrome (HHS/HONK)
Triggers
- Infection, infarction, insulin missed, iatrogenic (steroids), illness & surgery (CHF, stroke, renal failure, trauma etc.)
Pathogenesis
Hormone imbalance
- Relative insulin deficiency –> increased fat and protein breakdown
- Increased hyperglycaemic hormones - stress
Results in
- Increased hepatic glucose production
- Increased glucagon/adrenaline/cortisol
- Hyperglycaemic –> osmotic diuresis –> profound dehydration –> hypernatremia + loss of other electrolytes
Clinical features
Hx
- Gradual onset - T2 diabetic with a several week history of increased polyuria/weight loss/decreased fluid intake
- Dehydration - more severe than DKA due to gradual onset + impaired fluid intake in sick elderly patient
- Altered LOC - confusion, lethargy and coma
Exam
- General - confusion, altered LOC, delirium, seizures
- Vitals - hypotension, tachycardia, tachypnoea, febrile if infection
- Hands - perfusion, decreased skin turgor
- Eyes - sunken
- Mouth - dry mucosal membranes
- Neck - JVP (CHF may trigger)
- Chest
- Febrile - if infection
Ix
Bedside
- ECG - MI trigger
- Dipstick - glucose, ketonuria absent, UTI trigger
- BSL - severe hyperglycaemia (often >50)
- VBG - metabolic acidosis ABSENT (unless hypo-perfusing causing metabolic acidosis)
Bloods
- FBC - infection trigger
- CRP & culture - infection
- Serum ketones - normal, ketoacidosis suggests DKA
- UECs
- ↑urea & creatinine - pre-renal AKI
- ↓or ↑Na+ - hyponatremia early (hyperglycaemia draws water out) progresses to hypernatremia in severe dehydration
- ↓K+ - hypokalemia, total K+ depletion (less severe than DKA)
Imaging
- CXR - pneumonia
OSCE
- Patient comes in - check BSL and its +++
Exam
- Ketone breath + dehydration
Ix (send as urgent)
- Urine dipstick - ketones, glucose, protein
- Lab BSL
- UECs - looking for low HCO3, hypokalemia, hyponatremia
- VBG - normal or mildly acidotic
- FBC - underlying infective trigger
- Ketones
- Send hospital if worried
Vascular complications: Diabetic retinopathy:
What is it? What is its pathogenesis?
What are the features? 1) Non-proliferative 2) proliferative retinopathy
3) Cataracts in diabetics?
Management?
Features
Non-proliferative changes
- Microaneurysms (dots) & haemorrhages (blots)
- Retinal exudates - hard and soft
Proliferative retinopathy
- Neovascularisation
- Large haemorrhage with retinal detachment - new vessels more prone to rupture –> large retro-retinal haemorrhage –> may cause retinal detachment –> blindness
Cataracts in diabetics
- Polyol (sorbitol) accumulation in lens –> cataracts
Mx
- Eye exam annually
- Tight glucose control, HTN control, smoking cessation
Diabetic neuropathy: Peripheral neuropathy Mechanisms?
Clinical features: List 4: 2 marks
Painful diabetic neuropathy managament? Rx?
Autonomic neuropathy: CVS, GIT, GU, CNS (list disorder associated with each - 2 marks
Mononeuropathy multiplex? What is it?
Diabetic neuropathy (several types)
Peripheral neuropathy
Mechanisms
- AGE proteins –> interfere with nerve metabolism and conduction
- Microangiopathy –> ischemia
- Loss of sensory myelin –> symmetrical sensorimotor polyneuropathy (DSSP)
- Affects distal limbs first as they have longest nerve fibres with maximum myelin sheath –> damage to myelin hence affects more as required more for conduction
Clinical (symmetrical sensorimotor polyneuropathy)
- Progressive and irreversible
- Distal paraesthesias
- Sensory - vibration (earliest) & light touch loss in “glove and sock” distribution, decreased reflexes
- Motor (late stage) - wasting, weakness, CN palsies
- Neuropathic ulcers - decrease sensation causes ulceration at pressure points
- Painful diabetic neuropathy
- Rx - pregabalin
Autonomic neuropathy
- CVS - orthostatic hypotension
- GIT - dysphagia, alternating diarrhoea/constipation
- GU - urine retention & erectile dysfunction
- CN - diplopia, Bell’s palsy
Mononeuropathy multiplex
- Nerve infarcts or compression
Diabetic Nephropathy:
Early stage: Patho? Clinical?
Late stage: Pathology? Clinical?
Management?
Diabetic nephropathy
Pathology: early
- Early stage: Glomerular capillaries become thickened and leaky to proteins
- Deposition of AGE protein in BM –> protein leak
Clinical
- Asymptomatic proteinuria
- Nephrotic syndrome (severe)
Late stage Pathology
- Increased deposition of AGE in the mesangium causing expansion + fibrosis –> nodular/diffuse glomerulosclerosis
- NGS –> compression of capillaries –> decreased blood flow to glomerulus and tubules –> ischemia and decreased renal function
- Eventually results in diffuse glomerulosclerosis –> ESRF (low urine output end stage)
Clinical
- CKD
- ESRF - severe
Mx
- ACR/UECs /dipstick
- Mx - glycaemic control, BP control, ACEi
Neuropathic Ulcers:
Features? 1.5 makrs
Infectious complications in diabetes:
Immunosuppression pathology?
Skin complications: List 2 - 1 mark
Other types of DML
What is LADA?
What is Monogenic diabetes? (Maturity onset of youth)
Gestational DM? What is it ? Risk factors (3 marks)
Mechanism? Complications (higher rates of?)
Screening? How? Limits?
Gestational DM
Glucose intolerance beginning in pregnancy - usually around beginning of 3rd trimester
Risk factors
- Hx of GDM
- Advanced age
- FHx of diabetes
- Pre-pregnancy weight
- High gestational weight gain
- ATSI
Mechanism
- Increase in hormones - cortisol, GH, progesterone –> hyperglycemia + insulin resistance
- Normally compensated for by increased insulin
- In those with abnormal glucose tolerance or impaired B-cell reserve –> GDM
Complications (higher rates of)
- Pre-eclampsia
- Caesarean
- Maternal birth injury
- Post-partum haemorrhage
- Growth retardation of neonate
Screening
- All pregnant women at 26-28 weeks gestation by non-fasting glucose
- If >7.8 –> OGTT
Theme: Glucose lowering medications:
Class: Biguanides: MOA? Indications? Contraindications? Weight risk? Side effects?
Sulfonylureas? MOA? Indications? Contraindications? Weight risk? Side effects?
SGLT 2 inhibitors: MOA? Indications? Contraindications? Weight risk? Side effects?
DPP- 4 inhibitors: MOA? Indications? Contraindications? Weight risk? Side effects?
Thiazolidine-dione (Glitazones) MOA? Indications? Contraindications? Weight risk? Side effects?
Arcabose? MOA? Indications? Contraindications? Weight risk? Side effects?
Insulin basics:
Dose Basics (read)
Indications: T1DM, T2DM, Hyperglycemic emergencies? Hyperkalaemia?
Education for insulin? (management)
Insulin Formulations: read:
Starting insulin in T2DM - OSCE:
What to do with the oral drugs?
What are the 2 most common starting regimens?
Basal insulin at night: Explain:
Starting basal insulin: Read:
What is insulin instensification? (multiple daily basal bolus injections)
What are common side effects to insulin? Common? Rare and severe?
Thyroid anatomy and physiology:
Normal physiology of thyroid: Function? TH hormone synthesis? PTH and calcitonin?
Anatomy? Location: Arterial supply? Nerves?
Thyroid assessment:
ECG findings: Hyperthyroidism: 1.5 marks, Hypothyroidism: 1.5 marks:
What is sensitivity? 1.5 marks? What is specificty? 1.5 marks (SNOUT and SPIN)
Thyroid disease assessment:
Laboratory investigations: FBC? Lipids? Thyroglobulin? TFTS? WHat are most sensitive?
What are the expected results in:
Primary hypothyroidism?
Primary hyperthyroidism?
Subclinical hypo? Subclinical hyper?
What are the three most important thyroid autoantibodies? What are their indications? What do you expect in
Hashimotos? Graves?