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?
What is the Gold standard for diagnosis of Hypothyroidism:
E.g What to order? When are autoantibodies used?
Gold standards of lab diagnosis
Hypothyroidism
- Order TFTs to diagnose hypothyroidism
- Thyroid autoantibodies are then used to confirm the diagnosis of autoimmune thyroiditis
- Thyroid peroxidase & antithyroglobulin elevated in 95% of AT
- A-TP sufficiently sensitive and specific to use alone for the diagnosis of AT
- A-TG has specificity issues - often elevated in other autoimmune conditions & seen in 10-15% of the general population
- Thyroid imaging NOT indicated unless suspicious abnormality being investigated
Pathway for diagnosis of hyperthyroidism: Note many causes for thyrotoxicosis: Read pathway
What blood tests are required? What blood tests are specific for Graves disease?
What role does imaging and in particular radioisotope scanning? What are the indications for this?
What are contraindications to the scan?
What does the result provide?
- TFTs
- Thyroid autoantibodies to diagnose autoimmune
- TSH-R Abs - used to establish diagnosis of Grave’s
- Grave’s can also have increased TPO
Imaging
- Radioisotope thyroid scan
- Iodine-123, technetium-99m
Indications
- Differentiate causes of hyperthyroidism
- Adenoma vs MNG vs Graves (indicated in hyperthyroidism)
- Assess function thyroid nodules
- Hot - treat as hyperthyroidism (not malignant)
- Cold - fine needle aspiration to assess diagnosis of ThCa
Contraindications
- Pregnancy
Results
COLD NODULE - BIOPSY
- Grave’s - diffuse increased uptake of isotope due to hyperactivity
- Toxic adenoma - adenoma takes up all of the isotope (appears as a round nodule) as hyperactive with normal thyroid suppressed
- Hashimoto’s/Thyroiditis - less taken up
- Multi-nodular - enlarged with patchy uptake
- Cold - low uptake –> fine needle aspirate as chance of malignancy
- Hot - increased uptake –> treat as hyperthyroidism
- Malignant - usually appear as cold nodules with almost no hot nodules (non-functional)
Thyroid radisotope scan: uptake patterns:
When is a thyroid USS indicated?
When is a CT required?
Thyroid USS
- ONLY REQUIRED FOR A MASS (GOITRE OR NODULE)
Indications
- Assess a goitre (if euthyroid or hypothyroid)
- Assess a nodule
- Facilitate FNA
CT
- Evaluate retrosternal goitre prior to surgery
Othe rinvestigations for hyperthyroidism in a work-up?
Hypothyroidism?
Management of thyroid nodule: Pathway
Investigations for thyroid nodule?
Thyroid nodules: Algorithm for management:
Management of hypothyroidism:
What needs to be explained to patient?
Monitoring and adjustmenet?
How much how levothyroxine be increased in pregnancy?
Approach to goitre, thyroid mass, neck mass/lump:
Differential diagnosis: Think: Midline, thyroid nodule, lateral
History? HPC? Pmhx? Social? Family hx?
Examination findings: For specific ddx? Diffuse enlargement? Nodular?
What investigations should be done? Bloods? Imaging?
When is USS FNA indicated?
What is the management dependant on? (Size) thus whens surgery indicated?
Management
- Depends on cause
- Small nodule <10mm
- Repeat USS in 6 months
Surgery
- Thyroidectomy
- Indications - mass effect, malignancy on FNA (or indeterminant), nodule with hyperthyroidism
Non-toxic goitre: Eitology:
Patho? Clinical features? Risks? Ix? Pathology?
Management?
Thryoid neoplasia: Overview: What are the major causes of solitary nodules?
How frequent are these malignant?
Thyroid adenoma: Features? Pathology? Clinical?
Investigations?
Management?
Thyroid carcinoma? Risk factors? List 4: 2 marks
Management: Specific: What are adjuncts? What is needed after initial management? Who do these patients need to be referred to?
What are the 4 major types of the thyroid malignancy?
What is the most common 2 in order?
What are features of papillary Ca? 4 ps
Follicular ca features?
What is a thyroglossal cyst? Epidemiology? Eitology? Clinical? Diagnosis? Management?
Hyperthyroidism:
Epidemiology? Primary: List 4 causes of hyperthyroidism? (2 marks)
Pathoegenesis:
Clinical features: List 6 examination features: (3 marks)
Investigations and expected findings in hyperthyroidism:
Bloods: 2 marks?
Imaging?
General management: Pharmacological agents list 2 and MOA
Definitive management? When is it indicated? 0.5 mark
Thyroidectomy indications over iodine? risks? List 4: 2 marks
Ongoing monitoring? follow up? 1 mark
Graves disease: What is it?
Eitology?
Epidemiology? Peak incidence
Pathogenesis? Exophthalmos? Pretibial myxoedema?
Clinical features: List: Features of grave ophthalamopathy: 2 marks Skin and mucle changes 1.5 marks?
What are the maon management option: List
Grave’s disease
Definition
- Autoimmune disorder characterised by TSH-R autoantibodies
Etiology
- Genetic - DR3, DR5 (strong genetic component)
- Environmental- viral trigger?
- Autoimmune - TSH-R Ab (TSI), TPO also used
Epidemiology
- Most common cause of hyperthyroidism in Australia
- Younger age than Hashimoto’s: 20-40 peak incidence
- F>M x7
Pathogenesis
- TSH receptor stimulating Ig produced by B cells –> increased production and release of TH
Exophthalmos
- TSI binds to receptors on fibroblasts in the orbit –> glycosaminoglycan deposition –> orbital edema –> displaces eyeball anteriorly
Pretibial myxoedema
- Non-pitting edema associated with Grave’s disease
- TSH-R antibodies stimulate TSH receptors on fibroblasts to increase cutaneous glycosaminoglycan production
Clinical features are of hyperthyroidism PLUS:
- Goitre with bruit & thrill
Grave’s ophthalmopathy (NO SPECS in order of usual changes)
- No signs
- Only signs - lid lag & retraction
- Soft tissue - peri-orbital edema
- Proptosis & exophthalmos
- Extraocular muscle paralysis (diplopia) - due to edema trapping muscles
- Corneal abrasions (unable to close eyes)
- Sight loss
Skin changes
- Pretibial myxoedema - scaly thickening of skin overlying shin + pigmented nodules
- Thyroid acropachy & onycholysis
Proximal myopathy
Pathology
- Gross - enlarged thyroid that is soft, smooth and red (hyperaemic)
What is subacute thyroidititis? What are the main subtypes?
What are the causes? Patho? Natural history?
Clinical features: List 4 2 marks
Investigations: List 3 most important 1.5 marks
Management: Supportive? Active?
What is subacute post-partum thyroiditis (painless subacute thyroiditis) Eitology? Epidemiology? Clinical features? IX? Management?
Toxic adenoma and toxic multinodular goitre:
What are they? What do they result in: Clinical features?
Investigations? 3 most important?
Management? List 3 points: 1.5 marks
Toxic adenoma & toxic multinodular goitre
Pathology
- Functional adenoma results in hypersecretion of T3 & T4
- May be single (adenoma) or multiple (MNG)
Clinical
- Goitre with nodules
- Presents in elderly - most commonly as new onset AF
- Hyperthyroidism of new onset
Ix
- TFTs
- USS thyroid
- Radionuclide thyroid scan - ↑uptake in nodule with suppression of rest of the gland
Rx
- B-blockers - symptoms
Medical
- Radioactive iodine is 1st line
- Antithyroid drugs rarely induce remission and must be continued lifelong if used
Surgery
- Compressive symptoms
What is a thyroid storm? How is it defined?
Eitology: Precipitated by trigger in hyperthyroid patient-
List 6 clinical features? 3 marks
List 3 complications: 1.5 marks
DDx?
Investigations? (think what you need to rule out)?
Management: Resus? Supportive? Active?
Invesitgation?
Management?
Hypothyroidism:
Epidemiology?
Eitology: Primary- list 4 causes? 2 marks
Clinical features: List 8 from examination: 4 marks: Think when examining:
Overview
Epidemiology
- F>M = 10:1
Etiology
Primary hypothyroidism (>90%)
- Autoimmune - Hashimoto’s thyroiditis (goitre type or atrophic type)
- Iatrogenic - radioactive iodine
- Drugs - antithyroid, amiodarone, lithium
- Post-partum thyroiditis
- Subacute thyroiditis - hypothyroid phase
- Neoplasia
- Congenital
- Iodine deficiency - no. 1 cause WW; rare in Australia
Secondary
- Pituitary hypothyroidism - ↓TSH
Tertiary
- Hypothalamic hypothyroidism - ↓TRH (rare)
Symptoms/signs
- Weight gain, insensitive to cold, hoarseness
- Depressive symptoms - flat affect, mental sluggishness, apathy
- Skin - dry hair, loss of outer 1/3 of eyebrow, myxoedema (mucopolysaccharide accumulation), diminished sweating
- GIT - constipation, enlargement of tongue
- Gyn - menorrhagia (hypothyroidism causes acquired vWD)
- CVS/Resp - bradycardia, pericardial effusion & pleural effusion
- Neurology - delayed relaxation of reflexes, carpal tunnel, paraesthesia
Diagnosis: TFTs? Thyroid antibodies? Other investigation? 2 marks
Management principles: Explaination: What are other considerations for pts with hypothyroidism? Follow up? How often should TSH be measured?
Diagnosis
TFTs
- ↓T3/T4; ↑TSH (primary)
- ↓T3/T4; ↓TSH (or not appropriately ↑)
- T3/T4; ↑TSH (subclinical)
Thyroid antibodies (Hashimoto’s)
- Anti-thyroid peroxidase (anti-TPO)
- Anti-thyroglobulin (anti-TG)
Other Ix
- FBC - normocytic or macrocytic anemia
- Lipids - hypercholesterolemia
Rx
- Levothyroxine 100microg PO once daily
- Start lower dose in elderly or heart disease (50) so to not precipitate CHF
Instructions
- Store in fridge - cool dry area
- Take with an empty stomach first thing in the morning
Other medications require dose adjusting
- Hypothyroid - reduced metabolism of drug –> once treated need to increase the dose of other medications
- Hyperthyroid - increased metabolism of drug –> opposite
- Only exception is warfarin which is the opposite as clotting factors are more affected - monitor INR very closely
- Often require specialist input
Follow-up
Follow up in 6 weeks then 3 months then yearly
- Re-check TSH & T4 (titrate to normal reference range) - takes 6 weeks to stabilise after a change; keep in ref range
- Check symptom resolution
- Check TSH annually after
- Titrate to ~2
Explanations for poor response to therapy
- Thyroid tissue diminishes with disease progression
- Poor compliance
- Malabsorption - at risk for Coeliac
- Storage problems
What is Hashimotos (chronic autoimmune thyroiditis)
Epidemiology:
Types? Eitology? Pathogenesis: read
Risk factors: List 3 1.5 marks
Clinical features: List 6 including few specific features:
Patho:
Management?
Hashimoto’s (chronic autoimmune thyroiditis)
- Epidemiology
Most common cause in Australia
- Elderly: 45-65 (although can occur in children)
- F>M = 10x
Types of autoimmune thyroiditis
- Goitre type - diffuse, rubbery goitre
- Atrophic type
Etiology
- Genetic
- Environmental - viral
- Autoimmune - Thyroid Peroxidase Ab (most important), anti-thyroglobulin
Pathogenesis
Above results in breakdown of self-tolerance causing 3 types of thyroid cellular damage
- CD8+ mediated cytotoxicity
- Th1 mediated injury (IFN-y release –> Activates MPs)
- B cell Ab dependent cytotoxicity - anti-thyroid Abs (anti-thyroglobulin, anti-thyroid peroxidase)
Risk factors
- Female
- Autoimmune history
- Family history
- Smoking
- Clinical features are hypothyroidism PLUS
- Goitre
- Firm/rubbery enlargement
- Non-pitting edema
Periorbital & pretibial
- Mucopolysaccharide accumulation in dermis non-pitting
Pathology
- Gross - firm, symmetrically enlarged (may atrophy), pale-grey thyroid
Microscopy
- Atrophic thyroid follicles
- Lymphocytic infiltration
- Lymphoid follicles
Rx
- Thyroxine as for hypothyroid
What is a myoxedema coma:
What are the clinical hallmarks: list 3 : 1.5 marks?
Vitals? 2 marks: U+Cs?
Ix?: +expected findings:
Management prciniples:List 4 general: 2 specific 3 marks
Thyroidectomy: Indications?
Hx? Management of thyroid cancer? Benefits? Risks- list 5 and explain: 5 marks:
Alternatives: Pros/Cons?
What do you need to explain Pre-operative, post-operative?
After thyroidectomy care- How long to stay in hospital? What to monitor for? Ongoing management? Long term? Specific management? (when can you work again? when can you excercise? and drive?
Outline a pre-surgical assessment for any surgery (Brief)
What is amiodarone? What can it do to the thyroid?
Whats the mechanisms by which it does this?
How do you treat amiodarone induce thyrotoxicosis?
What is diabetes insipidus? Define? What is characterized by?
GH excess: What is difference between gigantism and acromegaly?
What is first line test for GH excess?
What is the most specific test?
What is the treatment options: List 4
List 4 causes for hyperprolactinemia? 2 marks
Clinical features? list 4 - 2 marks
Investigations: List 3 important bloods and explain- 1.5 marks Imaging and why? 0.5 marks
Treatment: First line: list 2 agents - 1 mark
LH and FSH Pathologies:
What is hypogonadotropic hypogonadism?
What are 2 causes of it?
List 4 clinical features? 2 marks?
Treatment? 1 mark
What is Hypergonadotropic hypogonadism?
list 4 causes? Think congenital and acquried?
Clinical featutres? list 4 (same as above)
Treatment - 0.5 marks
What is diabetes insipidus?
How is the eitology classified? (central vs nephrogenic)
Clinical features? List 3 main - 1.5 marks
Investigations? - Plus expected findings - urinanaylsis findings -1 mark
Diagnosis- Initial ? And to differentiate cental vs nephrogenic? - 1 mark
Management - Central? Nephrogenic?
Diabetes insipidus
Overview
- ↓ADH or ADH action –> ↑diuresis –> dehydration & electrolyte imbalances
Etiology
Central (↓ADH from posterior pituitary)
- CNS - tumour, surgery, TBI, infection, CVA, hypoxic brain injury, Sheehan’s
- Idiopathic
Nephrogenic (↓ADH action on collecting ducts)
- Electrolytes - hypercalcaemia, hypokalaemia
- Drugs - alcohol, lithium, gentamicin, phenytoin, sulfonylureas, colchicine
- Renal disease - ATN, TIN, myeloma
Clinical
- Polyuria & polydipsia
- Dehydration
Ix
- UECs CMP - hypernatremia (requires inadequate compensatory water intake)
- Urinalysis - low FeNa+ even though hypernatremia
- Diagnosis
Water deprivation test - polyuria persists
Desmopressin test to distinguish central from nephrogenic
- Concentration of urine - Central
- No effect - Nephrogenic
Rx
- Central - desmopressin treatment
- Nephrogenic - salt restriction, thiazide diuretics (↑Na+ loss)
Treatment
- central DI: first line = desmopressin; second line = chlorpropamide, thiazides, NSAIDs, and
- carbamazepine
• nephrogenic DI: solute restriction, thiazide diuretics
What is SIADH? Patho?
Causes? List 4 catergories and 1 from each: 2 marks
Clinical features? 4 atleast - 2 marks
Investigations- 2 - 1 mark
Diagnosis: Definition: What do you have to compare? What are hallmarks for diagnosis - 2 marks?
Management: 1 mark
SIADH
Overview
↑ADH action –> ↑water reabsorption –> dilutionary hyponatremia + ↑urinary Na+ is inappropriately high for plasma osmolality
Causes
- CNS - trauma, infection, stroke, neurosurgery
- Pulmonary disease - pneumonia, TB, empyema, LuCa (SCC ectopic)
- Malignancy - leukemia, lymphoma, LuCa
- Drugs - anti-depressants (TCAs, SSRIs etc.), carbamazepine, omeprazole, vincristine, haloperidol, ACEi etc. (many)
Clinical
- Hyponatremia (cerebral edema) - headaches, N&V, cramps, confusion etc.
Ix
- UECs CMP
- Urinalysis
Diagnosis/DefinitionCompare urine and plasma osmolality
- Usually when plasma osmolality↓ –> ADH↓ –> urine osmolality falls
- In SIADH when plasma osmolality falls urine osmolality remains inappropriately high (concentrated)
Diagnosis
- Hyponatremia
- Urine Na+ >40
- Inappropriately concentrated urine with osmolality >100 mmol/L (concentrated)
- Corrects with water restriction
Rx
- Fluid restriction
- Vasopressin receptor antagonists
What is the normal function of the parathyroid gland?
What 3 factors regulate calcium homeostasis? 1.5 marks
PTH - what cells secrete PTH? What does PTH do to Calcium level? Phosphate?
How is and where does PTH act to increase calcium absorption?
What is the function of vitamin D? Where do you get it? whats it net effect?
What is calcitonin? what is it stimulated by? Whats its net effect?
What are common causes of hypercalciemia? less common?
What is hyperparathyroidism? (Primary vs secondary) 1 marks
List causes for each: 2 marks
Clinical features (Bones, stones, abdomina groans, psychotic moans) as per hypercalcaemia (List 2 from each) 4 marks
Investigations: Bloods: Most important- imaging?
Interpreting calcium + PTH in hyperparathyroidism:
Management- indications- List 4 - marks - Pre-op work up? 0.5 marks
Complications- specific - list 4 - 2 marks
What is hypoparathyroidism (rare)? Causes? What does it result in?
What is multiple endocrine neoplasia? What is its inheritance pattern?
MEN 1- Gene? Tumours PPPP? - list
MEN 2- Gene? (PTAG) - list
Investigaitons for both?
Management?
Anatomy and function of pituitary gland: refresher:
Where does it sit? What are important important relations to its location:
What are the two major parts of the pituitary (anterior+posterior)
What does the posterior secrete? What are there funtions- 2 marks
What does the anterior pituitary secrete- (FLAT GP) 3 marks what are there funtions
What control/role does the hypothalamus have on the pituitary gland?
Where are the adrenal glands located? What are the two portions of it?
What are the three major zones of the cortex- list (1.5 marks) - What does each release? 1.5 marks?
What does the medulla release? 1 mark
HPA axis: outline
What inhibits CRH and ACTH release
Overview: Basics to investigation endocrinie tests: read
Pituitary adenoma - most common functonial adenomas- list 3
What is the difference in pituitary microadenomas? Functionaly and how they present?
Macroadenoma? How are they more common in?
What is mass effect? What are symptoms of this? What is cushing triad? What else can occur clinically which is significant list 3 - 1.5 marks
What is the function of ACTH: list 2 major-
What are the functions of cortisol? list 4
What are androgens? What are adrenal androgens? What are there functions?
Outline different disorders of the adrenal cortex:
Endocrine cases:
50 yo with headache and bitemporial hemianopia by GP - DDX? exam? Ix? Diagnosis? Complications? Management?
60 yo weight gain, HTN, T2DM, purple violacious striae:
Ix? How do you interpret these (cushing disease)
49y/o faitgue, 2 months, N&V and weight loss 10kg-
What is this? Clinical features expected? Diagnosis? Education? What needs to be replaced lifelong?
What are causes of Hypertension (endocrine)
What is a phaeochromocytoma?
What causes hyperaldosteronism?
Cushings:
Weight gain - Outline DDx - 5 - 2.5 marks
What is the MOA of glucorticoids? 1.5 marks
List 8 adverse effects of long term steroids? 4 marks
Contraindications- 1 mark
What are the different types of “cushing”- disease?ectopic? Iatorgenic? +
Clinical features- list 8; 4 marks (CUSHINGOID)
Cushing’s
Weight gain DDx
- Lifestyle
- Fluid retention - CHF, renal failure, liver failure
- Endo - Cushing’s, hypothyroidism, PCOS
- Depression
- Drugs - anti-psychotics, anti-depressants
Use of therapeutic glucocorticoids (e.g. prednisone)
Use = anti-inflammatory & immunosuppression
MoA
- Binds to GC receptor
- Inhibits genetic transcription of pro-inflammatory genes
- Effect is anti-inflammatory and immunosuppressive
Adverse effects of long-term steroids
- Immunosuppression - infection
- Delayed wound healing
- Diabetes
- Osteoporosis
- Skin changes - atrophy, striae, poor wound healing
- Cataracts
- HTN & fluid retention - may exacerbate HF
- Hypokalaemia & hypernatremia
- Weight gain
- Mood disturbances and psychosis
- Adrenal insufficiency from rapid withdrawal - suppresses endogenous production
Contraindications
- Systemic fungal infections
- Hypersensitivity
Etiology Cushing’s
ACTH dependent (↑ACTH causing bilateral adrenal hyperplasia)
- Cushing’s disease - ACTH secreting pituitary adenoma
- Ectopic ACTH secreting tumour - lung SCC, carcinoid, pancreatic & others
ACTH independent (↓ACTH)
- Iatrogenic - most common
- Bilateral adrenal hyperplasia
- Primary adrenocortical tumours (uncommon) - adenoma, carcinoma
Clinical (CUSHINGOID)
- Cataracts
- Ulcers - delayed wound healing
- Skin - striae, bruising, thin
- HTN, hirsutism & acne
- Infection
- No muscle - proximal myopathy
- Glycosuria
- Obesity (truncal and moon face) & Osteoporosis
- Immunosuppression
- Diabetes
- psychosis
How is a diagnosis of Cushing disease made- Screening firs -0.5 marks
What is the next test done? How is this interpreted?
What further bloods shouldbe done? Results?
Radiology required? 4 important - think
Hyperaldosteronism:
Eitology: Primary vs secondary - List 3 causes of primary hyperaldosteronism-1.5 marks
Pathophysiology: Outline excess aldosteronism and what this leads to clinically and
Clinical features? Biochemical results? (Na, K, HCO3-)
Diagnosis: 2 tests- imaging- read
Management:
Adrenocortical insufficiency:
Eitology: Primary (addisons)
Clinical features: List 4 systems and signs/symptoms -4 marks
What investigations and findings?
Management:
Acute adrenal insufficiency:
Medical emergency: Eitology? What is the most common cause? (acutely) and Addisons? What is waterhouse-friderichsen syndrome?
What would you expect clinically in these patients?
Management: - resus+electolytes++++
Incidental adrenal mass: DDx-
Ix?
Management principles?
Adrenogenital syndrome: (aka 21-hydroxylase deficiency) - What is it?
Clinical features? List 3 1.5 marks
Phaeochromocytoma: What is it? Eitology? Which MEN syndrome is common with? Patho?
Clinical features?
Diagnostic test 0.5 marks
Management?
Hyperandrogenism:
What is it: Define:
Eitology: Think, Medication, ovarian, adrenal, pituatary
Clinical features: Females? Males?
Investigations: List 6 important: 3 marks
treatment:
