Clinical Flashcards
What is diabetes?
Elevation of blood glucose above a diagnostic threshold
what are the thresholds to diagnose someone with diabetes?
Fasting glucose= 7mmol/L or 126mg/dl 2hr plasma glucose= 11.1 mmol/L or 200mg/dl - “don’t eat after 10pm the previous night and only drink water”
HbA1c = 48 mmol/mole or 5.8% varies
just think above this value note if patient is asymptomatic then repeat test
what are the thresholds of someone with impaired glucose tolerance “pre-diabetes”?
Fasting glucose: 6.1-6.9 mmol/L
2hr plasma glucose: 7.8-11.0 mmol/L
HbA1c - 42-47 mmol/mole or 6-6.4%
what are the thresholds of someone with normal glucose tolerance?
Fasting glucose: >6mmol/L2hr
plasma glucose: >7.7 mmol/L
HbA1c: >41mmol/mole
What are the thresholds of Gestational diabetes?
Fasting glucose: 5.1 mmol/mole or 92mg/dl2hr
plasma glucose: 8.5 mmol/l
Give examples of disorders of insulin secretion.
- Type 1 diabetes
- Genetic disorders: MODY, NEONATAL diabetes, CF and Haemochromatosis
- Pancreatic disease Alcoholic and chronic pancreatitis, acute pancreatitis, Pancreatectomy and pancreatic cancer
- Type 2 diabetes
Give examples of disorders of insulin action.
pure disorders are rare and mostly genetic.
- Type 2 diabetes
- Donohue syndrome
- Familial partial lipodystrophy
- NAFLD
- Cushings syndrome
- Glucagonoma
- steroid induced
what is type 1 diabetes?
Autoimmune destruction of the pancreatic beta cells resulting in beta-cell deficiency
what is Type 2 diabetes?
disease which ranges from predominantly insulin resistance with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance patients do not have any other cause for diabetes ( i.e. it is a diagnosis of exclusion)
90% of patients who have diabetes have this form
what is the epidemiology of type 1 diabetes?
usually adolescent but can happen at any age
Genetics: associated with HLA D3 and D4 autoimmune diseases. HLA represent 50% familial risk of T1DM. if both parents have T1DM then child is 30% likely to have it
What are the the risk factors type 2 diabetes?
- Asians
- elderly
- men
- Most people get it over 40 but now becoming more common in teenagers
- Obesity
- Sedentary lifestyle
- calorie and alcohol excess
what are the causes of Diabetes mellitus?
T1: insulin deficiency from autoimmune destruction of insulin - secreting pancreatic beta cells
T2 - decrease in insulin secretion with/without increased insulin resistance
other causes: Drugs: steroids, anti HIV drug, new antipsychotics
Pancreas: Pancreatitis, surgery(removal of pancreas), trauma, pancreatic destruction (haemochromatosis,CF) and pancreatic cancer
Cushings disease, acromegaly, hyperthyroidsism and pregnancy
Define impaired glucose tolerance (IGT)?
IFG and IGT represent intermediate states of abnormal glucose regulation that exist between normal glucose homeostasis and diabetes
Fasting plasma glucose: <7mmol/L
2hour glucose >7.8mmol/L but <11.1 mmol/L
Define fasting glucose (IFG)?
Fasting plasma glucose >6.1mmol/L but <7mmol/L
what are the signs and symptoms of diabetes Mellitus?
1.General:
symptoms of hyperglycaemia: e.g.
polyuria (pees more) (osmotic symptom)
polyphagia (more hungry)
polydipsia (more thirsty) (osmotic symptom)
blurred vision
thrush
tiredness
signs of macrovascular and microvascular complications
- signs more common in T1:
Acetone breath
weight loss
Kussmaul breathing
nausea, vomiting
ketonuria
Enuresis (in children)
weight loss in Type 1
How do you diagnose Diabetes Mellitus?
Remember T2 is a diagnosis of exclusion
- Fasting glucose > or equal to 7mmol/l
- random glucose >11.1 mmol/L
- HbA1c: >48mmol/mol- more efficient in testing for T2
- Pancreatic Autoantibodies (T1 mainly) e.g. GAD 65, IAA ,IA2 and ZnT8 - can sometimes have negative but that is rare
- Ketones detected (T1 mainly)
- C-peptide levels - useful diagnosis for type 1 but should be done much later after diagnosis
Dr Iqbal Malik: to diagnose T1 all you need to do is random blood glucose >11.1 mmol with symptoms is enough
if with symptoms then fasting glucose >7mmol. if they dont have symptoms and you do fasting glucose then must do it twice
How do you manage Type 1 diabetes?
General: Education and lifestyle advice Bariatric surgery for some patients
Type 1:
- Educate to self adjust doses on the basis of exercise, fingerprick glucose and calorie count.
- DAFNE (dose adjusted for normal eating) programme. Use Basal bolus insulin via Multiple daily injections or continuous subcutaneous insulin infusion pump (CSII)
- GlucoGel if patient in coma
- Regular check HbA1c should be 48 to 58 mmol/mol
Pharmacological:
- Subcutaneous insulins: usually 100u/ml very rarely 500u/ml
rapid acting e.g. Humalog, Novorapid, Apidra. Inject at start of meal
short acting(soluble) e.g. Humulin S, Actrapid and Insuman
Rapid medium acting (isofane - NICE favourite) e.g. Insulatard, Humulin I, insuman Basal
Long acting e.g. Lanctus
Rapid acting analogue-intermediate mixture e.g. (novomix 30 = 30% short acting and 70% long acting), Humalog mix25 and Humalog mix50
short acting-intermediate mixture e.g. Humulin M3, Insuman comb 15,25,50
Alternatives:
- Can also use insulin pumps now instead of subcutaneous injections
- Flash glucose monitoring can be used instead of finger prick test
Surgery:
- Kidney-pancreas autotransplantion
- Pancreatic islet transplantation - usually reserved for patients with severe hypoglycaemia, severe and progressive long term complications despite maximal therapy.
four steps:
i. Pancreas donation and retireval
ii. islet culture
iii. Islet transplantation
iv. immunosuppression
if patient has acute illness and uses subcutaneous insulin dosing
- illness increases insulin requirement
- therefore maintain calorie intake
- check blood glucose and look for ketonuria
- admit if vomiting, dehydrated, ketotic or if they are a child or pregnant
What are the main complications of diabetes mellitus?
Macrovascular:
- IHD - MI four times more likely in DM and more likely to be silent
- Stroke
- Hypertension
Microvascular - caused by hyperglycaemia
- Retinopathy- any damage to the retina of the eyes, which may cause vision impairment
- Nephropathy
- Neuropathy
- erectile dysfunction
Psychological
- Depression
what is the pathophysiology of microvascular complication in Diabetes mellitus?
- Hyperglycaemia causes excess glucose goes through glycolysis
- Mitochondria cannot keep up with rate of excess glucose so other pathways are used. Diabetic patients are associated with mitochondrial impairment whether it be environmental or genetic.
- Polyoul pathway converts glucose to solbitol via aldose reductase. Solbitol due to its highly osmotic properties damages tissues which increases reactive oxygen species
- Pentose phopshate pathway uses up excess Glucose-6-phosphate in glycolysis causes excess NADPH and thus increase NADH oxidase which also increases reactive oxygen species
- Hexomsamine pathway converts Fructose 6 phosphate to produce UDP-glcNAC enzyme which results in inflammation
- Glyceral alderhyde 3 phosphate is converted to diacyl glycerol. This activates protein kinase C which leads to inflammation
- Glyceral alderhyde 3 phsophate can also be converted to methyl glyoxal. Along with excess glucose can form AGE products which bind to RAGE receptors leading to inflammation
Beside retinopathy what other eye complications can diabetes cause?
- Maculopathy - macular oedema
- Cataract-
- Glaucoma-increase in fluid pressure in the eye leading to optic nerve damage
- Acute hyperglycaemia - visual blurring but is reversible
What are the main types of diabetic retinopathy?
- Background (mild non proliferative) retinopathy - blood vessel leak leading to micro-aneurysms (dots), haemorrhages (blots) and hard exudates (lipid deposits)
- Pre proliferative retinopathy - signs include cotton wall spots (ischaemic areas) and Intra-retinal microvascular abnormalities (IRMA) as well as venous bleeding.
- Proliferative - fragile new vessels (neovascularitsation) form due to lack of oxygen in certain areas of the retina. These weak vessels mean there is a high risk of haemorrhage .
what is the pathophysiology of maculopathy?
Maculopathy (or macular oedema)
- Macular capillaries undergoes capillary endothelial change due high retinal blood flow from hyperglycaemia
- this causes vascular leakage fluid is rich in lipids. lipids are absorbed but leave exduates. Exudates close to the fovea (center of macula) can effect central vision
- local hypoxia and ischaemia occurs
- new vessels form - risk of detaching the retina if they bleed and fibrose
what are the clinical features of diabetic retinopathy?
- Blurry vision
- floaters
- sudden loss of vision
How do you diagnose Diabetic retinopathy?
Annual retinal screening is mandatory for diabetic patients
grading:
R0 - No disease - rescreen in 12 months
R1- Mild background diabetic retinopathy:
Microaneurysms, Flame exudates, >4 blot haemorrhages in one or both hemifields, and/or cotton wool blots - rescreen in 12 months
R2 - Moderate background diabetic retinopathy:
> 4 blot haemorrhages in one hemifield - rescreen in 6 months
R3 - pre proliferative diabetic retinopathy:
> 4 blots in both hemifields, IMRA and venous bleeding - refer
R4 - proliferative retinopathy:
NVD,NVE, vitreous haemorrhage, retinal detachment - refer
How do you manage Diabetic retinopathy?
1.Panretinal photocoagulation: removes peripheral retina which reduces oxygen requirements in the retina allowing for there to be less stress on the new vessels
Too much photocoagulation may reduce vision so much so you may not be able to drive
- vitrectomy: vitreous haemorrhage leads to profound loss of vision if the macula is obscured
How do you diagnose maculopathy?
Annual screening for diabetic patients via optic coherence tomography - assesses oedema
Grading:
MO: no macular findings - 12 months rescreening
M1: hard exudates within 1-2 disc diameters of fovea - 6 months rescreening
M2: blot haemorhage or hard exudate within 1 disc diameter of fovea - refer
How do you manage maculopathy?
- intravitreal anti vascular enothelial growth factor (VEGF)- stops drive for new blood vessels
- grid laser to macula reduces swelling
what is diabetic nephropathy?
a progressive kidney disease and most common cause of end stage renal failure
caused by damage to the capillaries in the kidneys’ glomeruli. It is characteriised by proteinuria and diffuse scarring of glomeruli
40% of patients require renal replacement
what are the main signs and symptoms of nephropathy?
First sign: Albuminuria
Later: Nodular Glomerulosclerosis and fibrosis with loss of renal function. Hypertension also develops.
Kimmelstiel-wilson nodules
How do you diagnose Diabetic nephropathy?
- ACR and PCR:
ACR in men >2.5
ACR in women >3.5
for PCR assume daily creatinine excretion is 10mmol, so ratio 100mg/mmol = 1g/day so to convert PCR to protein loss a day multiply by 10
when looking for microalbuminuria mainly use ACR however if patient has overt neropathy then look for proteinuria
Microalbuminuria - (ACR is 3-30 and PCR <50) repeat test. 2/3 tests positive then patient has microalbuminuria (dipstick NEGATIVE)
Proteinuria (overt neuropathy)- ACR >30 and PCR >50
(dipstick POSITIVE)
do random urines for ACR
why do you repeat microalbuminuria tests 3 times?
urine albumin excretion rate varies due to numerous factors
e.g. day vs night, different days, exercise, protein load, fluid load
Give examples of conditions which may give false positives for microalbuminuria?
Menstruation
Vaginal discharge
UTI
Pregnancy
Non diabetic renal disease
What other conditions should be checked if a patient has microalbuminuria?
- monitor serum creatine
- check for retinopathy
- investigate other causes for renal pathology
- check for peripheral vascular disease
- assess lipid profile
- check for IHD
How do you manage Diabetic nephropathy?
- Extensive diabetes control e.g. get HbA1c <53mmol/mol
Pharmacological
- ACE inhibitor or ARB. remember if dry cough occurs with ACE-i then use ARB. Regardless of blood pressure
- BP control to 130/80 (NICE guidelines) or 130/70 (SIGN)
- sodium restrictions to <2g/d
- patients with T2DM should be started of SGLT2i irrespective of HbA1c
How do ACE inhibitors work?
ii. what effect do they have on kidneys?
- juxtaglomerular apparatus makes renin in kidney
- Renin converts angiotensinogen to angiotensin 1
- Angiotensin-converting enzyme, or ACE converts angiotensin 1 to angiotensin 2 in the lungs
- angiotensin 2 is a vasoconstrictor. and is converted to aldosterone.
ACE i stops vasosconstriction and causes vasodilation
ii.kidneys:
dilation of renal arterioles
decrease filtration pressure
decrease proteinuria
DECREASES GFR
what other drug also acts on the renal arteriole constriction to cause dilation as ACE i/ ARBs?
SGLTi
what is diabetic neuropathy?
progressive damage to the peripheral nerves seen in some people with long-standing diabetes
different pathophysiology between type 1 and 2
what types of diabetic neuropathy are there?
- peripheral e.g. pain/loss of feeling in feets, hands (most common)
- Proximal: causes amyotrophy which is painful wasting of quadriceps and other pelvifemoral muscles. usually starts with weakness in the thighs, hips or buttocks - difficult to get out of chair
- Autonomic: e.g. postural bp drop, decrease in cerbrovascular autoregulation, heart rate , gastroparesis, erectile dysfunction, gustatory sweating and diarrhoea , vomiting
- Focal neuropathy: sudden weakness in one weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel syndrome, ulnar mononeuropathy, foot drop and bell palsy and cranial nerve palsy
what are the risk factors of diabetic neuropathy?
- increased length of diabetes (therefore more common in T1 than T2)
- poor glycaemic control
- high cholesterol
- smoking
- alcohol
- Genetics
- trauma
what are the signs and symptoms of neuropathy?
“glove and stocking distribution” of loss of sensation i.e. hands and legs. get it coz of gloves and stockings?
numbness
tingling
sharp pains or cramps
loss of balance
Hypersensitivity
Feet:
- absent ankle jerks
- neuropathic deformity - charcot foot
- claw toe
- loss of transverse arch
- neuropathic ulcers - lead to cellulitis, abscess and osteomyelitis
what occurs in diabetic feet?
combination of Neuropathy and ischaemia
Ischaemia
1. Charcot foot (joint)- refers to progressive degeneration of a weight bearing joint, presents as red hot swollen foot which is confused for DVT and cellulitis
- Proximal arterial occulsion
- distal gangreen
Neuropathy
4. Ulcer - painless punched out ulcer - in an area of thick callus with or without infection
- clawing toes
How do you diagnose neuropathy?
Annual screening of feet:
- Feel for pulses of feet (dorsalis pedis and posterior tibial)
- Feel sensation with a monofilament fibre
- check for deformities and breaks in the skin e.g. sign of infection and nail health
Assessment
Low risk:
Sensation unimpaired, foot pulses are present - annual screening by health cares
Moderate risk:
Sensation impaired and foot pulses absent but no skin callus or foot deformity but are unable to self care - annual assessment by podiatrist
High risk:
Sensation impaired and foot pulse absent AND have skin callus or deformity - annual assessment by podiatrist
put into high risk regardless of these symptoms if they had previous foot ulcer or amputation
Active risk:
Current foot ulcer, infection, critical ischaemia, gangrene or red swollen foot - urgent referral to specialist
how do you manage peripheral neuropathy?
regular check ups
bed rest and or therapeutic shoes
charcot joints: bed rest/ total contact cast until oedema and local warmth reduce along with bone repair
diabetic amyotrophy: usually self limiting
autonomic neuropathy:
diarrhoea - codeine phosphate
postural hypertension treated with fludrocortisone/ midodrine
Gastroparesis:
Improve glycaemic control.
Dietary - smaller meals
NSAIDs for abdominal pain or fentanyl and anti emitrics
promotility drugs e.g. metoclopramide, domperidone and erthromycin
Botox injections for spasms of pylorus
Gastric pacemakers
Sweat glands: topical glycopyrrolate, clonidine, botox
what is LADA?
latent autoimmune diabetes of adults is a form of type 1 DM, with slower progression of insulin dependence in later lifer
usually occurs in males aged 25-40
what does MODY stand for?
Maturity Onset Diabetes of the Young - common type of monogenic diabetes
what type of inheritence is Maturity Onset Diabetes of the Young (MODY)?
autosomal dominant inheritance
what is the age of onset of Maturity Onset Diabetes of the Young (MODY)?
usually before the age of 25
what are the 2 mutations causing Maturity Onset Diabetes of the Young (MODY) that give 2 distinct phenotypes?
mutation in transciption factor HNF - MODY 1
mutation in glucokinase - MODY 2
compare MODY glucokinase mutations to transcription factor mutations in terms of onset?
glucokinase mutations- onset at birth
transcription factor mutations- young adult onset
compare MODY glucokinase mutations to transcription factor mutations in terms of hyperglycaemia progression?
glucokinase mutations- stable hyperglycaemia
transcription factor mutation- progressive hyperglycaemia
compare MODY glucokinase mutations to transcription factor mutations in terms of treatment?
glucokinase mutations- diet treatment
transcription factor mutations- 1/3 diet, 1/3 oral hypoglycaemic agents, 1/3 insulin
compare MODY glucokinase mutations to transcription factor mutations in terms of complications?
glucokinase mutations- complications rare
transcription factor mutations- complications frequent
what is hypoglycaemia?
plasma glucose <4mmol/L
what are the signs and symptoms of hypoglycaemia?
can sometimes be asymptomatic
1.Autonomic:
sweating
anxiety
hunger
tremor
palpitations
dizziness
- Neuroglycopenic :
confusion
drowsiness
visual trouble
seizures
coma
personality change
What are the main causes for hypoglycaemia?
1.Diabetic:
Insulin or SU treatment - increased excercise or overdose
- NON- Diabetic - use EXPLAIN
EXogenous drugs e.g. insulin, oral hypoglycaemics, lots of alcohol in take with no food , ACE-i/ARBS, pentamidine
Pituitary insuffiency
Liver failure
Addison’s disease
Islet cell tumours ( insulinoma) and immune hypoglycaemia
Non-pancreatic neoplasms
What does whipples triad consist of?
ii. what does this triad indicate?
- Hypoglycaemia signs or symptoms
- decrease in plasma glucose when symptoms are detected
- Relief of symptoms when glucose level is raised
ii. insulinoma
what is Hyperinsulinemic hypoglycemia (HH)?
biochemically characterized by the unregulated secretion of insulin from the pancreatic β-cells in the presence of low blood glucose levels
what are the causes of HH?
- Insulinoma
- SUs
- Insulin injection
- Non-insluninoma pancreatogenous hypglycaemia syndrome
- Congenital - mutations in genes in insulin secretion e.g. ABCC8, KCNJ11 and GLUD 1
suggest causes of hypoglycaemia if there low insulin but no excess ketones?
Non pancreatic neoplasm
anti-insulin receptor antibodies
suggest causes of hypoglycaemia where there is low insulin but excess ketones?
alcohol
Pityutary insuffiency
Addison’s disease?
What is post prandial (reactive) hypoglycaemia?
also known as a sugar crash - is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes.
How do you manage Hypoglycaemia?
conscious and able to swallow: 15-20g of quick acting carbohydrate snack
Conscious and unable to swallow: glucose gel between teeth and gums
unconscious or not responding to treatment:
glucose IV (10% at 200mL/h if conscious or 10% at 200mL/15 mins)
or
Glucagon intramuscular injection 1mg
give long acting carbohydrate once blood glucose >4mmol/L
what is the insullin to carb ratio?
amount of rapid acting insulin needed to cover a specific amount of carbohydrate
what is the insulin sensitivity factor?
used to calculate the drop in glucose for each unit of insulin - also called a correction factor
what is the target blood glucose concentration for a type 1 diabetic pre-meal?
4-7mmol/l for children and adults
what is the target blood glucose concentration for a type 1 diabetic after a meal?
5-9 mmol/l for children and adults
what is the target blood glucose concentration for a type 2 diabetic pre-meal?
4-7 mmol/l
what is the target blood glucose concentration for a type 2 diabetic after a meal?
<8.5 mmol/l
what should the fasting glucose levels of a pregnant woman be?
<5.3 mmol/l
what should the target glucose concentration for a pregnant woman be for:
1 hour after meal
2 hour after meal
i. <7.8mmol/l
ii. <6.4mmol/l
How do you treat different types of MODY based on its genetic aeitiology?
- GCK MODY - no treatment or follow up required
- HNF1A MODY - can transition off insulin into low does SUs
- KCNJ11/ABCC8 NDM - can transition off insulin onto SUs
what is diabetic Ketoacidosis? (DKA)
disordered metabolic state that usually occurs in the context of an absolute (T1) or relative (T2) deficiency accompanied by an increase in the counter- regulatory hormones i.e glucagon, adrenaline, cortisol and growth hormone
More common in T1 but can happen in T2
what is the pathophysiology of DKA?
- Absolute or relative insulin deficiency occurs - switches metabolic balance in a catabolic direction
- Stress hormone activation
FIRST mechanism - fatty acids
- Stress hormones lead to increased lipolysis as glucose is not entering cells so requires fats
- more Free fatty acids goes to liver
- Increase ketogenesis in liver which forms ketone bodies - produces acetone as a byproduct
- Leads to metabolic acidosis as ketone bodies release hydrogen ions
Second mechanism - Amino acids
- Stress hormone activation can also use amino acids as a substrate for cells
- Muscle is degraded to release protein for gluconeogenesis
- Results in Hyperglycaemia
- Hyperglycaemia leads to glycosuria
- Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
- dehydration increases lactate production which in turn causes acidosis
Third mechanism - Glycogen
- Stress hormone activation can also promote glycogenolysis
- glycogen is converted into glucose
- Results in Hyperglycaemia
- Hyperglycaemia leads to glycosuria
- Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
- dehydration increases lactate production which in turn causes acidosis
How do you diagnose DKA?
commonly found in patients with known Diabetes however can be found before diagnosis of T1 diabetes
- Ketonaemia > 3mmol /L, or significant ketonuria (>2+ on standard urine stick)
blood ketones usually above 5
2.Blood glucose > 11.0 mmol /L or known DM
euglycaemic DKA - where glucose is not elevated. can occur as a rare complication of SGLT2 inhibitors for T2 patients.
3.Acidosis: Bicarbonate < 15 mmol /L or venous pH < 7.3
4.Potassium
Often raised to above 5.5 mmol/L
Beware a low normal reading
5.Creatinine: often raised
Sodium: often low or low N
Raised lactate is common. Normal range is 0.6 to 1.2 mmol/L
6.Amylase often raised
Rarely pancreatitis [i.e. non-surgical]
Origin can be salivary
7.White cell count
Median 25
Does not always equate to infection
if white cell doesnt fall after DKA management then assume infection
what are the complications of DKA?
Hypokalaemia- causes cardiac arrest
Aspiration Pneumonia - gas in stomach
ARDS
Co-morbidities
Cerebral oedema
what are the causes of DKA?
- Insulin deficiency - Type 1 mainly
- insulin demand - think of the 5 Is
- Infection: Pneumonia, UTIs and cellulitis
- Inflammation: Pancreatitis and cholecystitis
- Intoxication: Alcohol
- Infarction: Acute MI and stroke
- Iatrogenic: steroids and surgery
What are the signs and symptoms of DKA?
1.Osmotic related:
Polydipsia
polyuria
Dehydration
- Ketone body related
Flushed
Vomiting
Abdominal pain
tenderness
Breathless – Kussmaul’s respiration
NB. not all individuals can smell ketones on breath
3.Associated conditions
Underlying sepsis
Gastroenteritis
Large amount of fluid loss - sodium ,potassium and phosphate
How do you manage DKA?
- IV fluid resuscitation
1000ml NaCl 0.9% in first hour
2000ml NaCl by end of hour 2
3000ml NaCl by end of hour 4
- Monitor
Blood for U&E, pH, ketones and bicarbonate and level hour 2
Blood for U&E,pH, ketones and bicarbonate level hour 4
IV potassium replacement as it starts dropping
- Insulin
Give IV infusion
Continue patients long acting insulin at usage dosage and time even with infusion
premature end of treatment leads to recurrence
- Hypoglycaemia - AVOID
when glucose <14mmol/L start giving 10% glucose at 125ml/h along with the saline
MONITORS:
- Blood ketone testing
better as urine ketone gives an idea of levels 2-4 hours before and doesn’t improve straight away due to rate of mobilisation of ketones from fat tissue
Measures beta-hydroxbutyrate
<0.6mmol/L is good
> 3mmol/L significant ketosis
What is Hyperglycaemic Hyperosmolar state (HHS)
a complication mainly associated with Type 2 diabetes in which high blood sugar results in high osmolarity WITHOUT significant ketoacidosis
This is because these patients are still able to make insulin so the ketogenesis pathway is not involved
what is the pathophysiology of HHS?
- Relative insulin defiency causes cortisol and arenaline activation
- Stress hormone (cortisol, adrenaline) cause Gluconeogenesis and glycogenolysis
- Hyperglycaemia in HHS is much higher in comparison to DKA
- Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
- Dehydration causes hyperosmolarity
How do you diagnose HHS?
Diabetes may be known at presentation – often not
Often presents in Older patients. Young Afro-Caribbean
- Hypovolaemia – usually marked
- Marked hyperglycaemia > 30mmol/L
- No/mild ketonaemia <3 mmol/L
- Bicarbonate > 15 mmol /L or venous pH > 7.3
- Osmolality >320 mosmol/kg normal is 275- 295
- Higher glucose than in DKA – usually above 50 mmol/L
- Significant renal impairment
- Sodium often high normal or raised
High refined CHO intake pre-presentation
how do you calculate osmolarity?
2(Na + K) + glucose + urea
What is the main cause for HHS?
Relative insulin deficiency - Type 2 diabetes
How do you manage HHS?
- Measure or calculate osmolality frequently to monitor progress
- Assess severity of dehydration and use 0.9% saline for fluid replacement without insulin. This alone will lower blood glucose which reduce osmality
- Monitor and chart BG, osmolality and sodium every 1-2 hours
- start low dose IV insulin only if Ketonaemia >1mmol/L or ketonuria >2+ at presenetation or if BG falling at rate less than 5mmol/h
- asses for complications of therapy e.g. fluid overload and cerebral oedema
- start prophylactic anticoagulation with LMWH (fragmin)
- Patient with HHS are at high risk of foot ulceration - check feet daily and protect heels
- treat underlying precipitants e.g. sepsis
which type of lactic acidosis is associated with diabetes?
Type B- associated with metformin
How is lactate removed from the blood?
hepatic uptake and aerobic conversion to pyruvate then glucose
where does lactate orignate from?
red cells, skeletal muscle, brain and renal medulla - anaerobic respiation
what is the normal rate of lactate in blood?
0.6 to 1.2 mmol/L
what is the ion gap?
used to show whether your blood has an imbalance of electrolytes or too much or not enough acid
what is the normal ion gap?
10 to 18 mmol/L
how do you calculate the ion gap?
[Na+ + K+] – [HCO3- + Cl-]
what is usually associated with type A lactic acidosis?
tissue hypoxaemia
infarcted tissue, cardiogenic shock, hypovolaemic shock
what is usually associated with the type B lactic acidosis (diabetes one)
Mitochondrial defects
Cyanide toxicity
Beriberi (thiamine deficiency)
Drugs (metformin, salicylates, nucleoside reverse
transcriptase inhibitors)
Liver failure
Ethanol intoxication
what are the main clinical features of lactic acidosis?
hyperventilation
mental confusion
stupor/coma
how do you diagnose lactic acidosis?
Raised lactate
Reduced bicarbonate
- Raised anion gap [(Na+ + K+) – (HCO3 + Cl-)]
Other causes: dka, starvation, uraemia, alcohol, ethylene glycol, methanol, salicylate or paraldehyde poisoning. - Glucose variable – maybe [often] raised
- Absence of ketonaemia
- Raised phosphate
how do you manage lactic acidosis?
Fluids
Antibiotics
stop drugs which cause it e.g. metformin
what are the 2 classes of neonatal diabetes?
transient neonatal diabetes
permanent neonatal diabetes
when is permanent neonatal diabetes usually diagnosed?
0-6 weeks
What is Hypothyroidism?
Clinical effect of lack of thyroid hormone. Results from any disorder that results in insufficient secretion of the thyroid hormones from the gland.
Primary: due to disease affecting thyroid gland itself. Can occur with or without a goitre
Secondary: No thyroid gland pathology. Most likely problem with either hypothalamus or pituitary gland
How do you diagnose Hypothyroidism?
Thyroid function test:
testing with free T3/4 is better then total T3/4 as free forms of these hormones are less affected by TBG. As TBG levels are effected by different conditions (e.g. pregnancy causes increase in TBG whereas is decreased with nephrotic syndrome)
Primary
High TSH
Low Free T4/T3 - T4 would be normal if it was treated hypothyroidism, if there is thyroid resistance, or if it was subclinical hypothyroidism
Increase in PRL - mild
can get:
increase in MCV, CK and LDL cholesterol
Secondary:
Low TSH - due to hypothalamic or pituitary disease
Low Free T4/T3 (or normal)
Thyroid autoantibodies:
Anti TPO antibodies - found in 95%. useful especially for Hashitmoto’s thyroiditis
Anti thyroglobulin antibody - found in 60%
TSH receptor antibody - blocking type only found in 15%
What is Myxoedema?
severe hypothyroidism and is a medical emergency
what is pretibial myxoedmea?
not associated with hypothyroidism but Hyperthyroidism!
Rare clinical sign of Grave’s disease which is an autoimmune thyroid disease
What are the causes of Hypothyroidism?
Primary:
- Goitrous
i. Chronic lymphotic thyroiditis (Hasimoto’s thyroiditis)
ii Iodine defiency
iii. Drug induced e.g. lithium and amiodarone
iv. Maternally transmitted - if women are on antithyroid drugs it can cause neonatal hypothyroidism
v. Hereditary biosynthetic defects
2. Non-goitrous
i. Atrophic thyroiditis
ii. Post-ablative therapy - e.g. radioiodine, surgery
iii. Post- raditotherapy e.g. for lymphoma treatment
iv. congenital developmental defect
3. Self-limiting
i. withdrawal of antithyroid drugs
ii. subacute thyroiditis with transient hypothyroidism
iii. Post- partum thyroiditis
2. Secondary
Infiltrative
infection
Malignant
traumatic
congenital
what are the signs and symptoms of Hypothyroidism?
Loads of clinical features because almost all our cell nuclei have receptors showing a high affinity for T3. receptors are TRalpha 1, TR alpha 2 and TR beta 1
- Hair and skin
dry thin hair and skin
Dull, expressionless face
round puffy face
Pale cool skin
Hypercarotenaemia
- Dislikes cold more sensitive to it
- Cardiac
Bradycardic
Pericardial effusion
cardiac dilatation
- Metabolic
Hyperlipidaemia
Decreased appetite
weight gain
- GI
constipation
Megacolon and intestinal obstruction
Ascites - can have non pitting oedema in eye lids and feet
- Respiratory
Hoarse voice
Enlarged tongue
obstructive sleep apnoea
- CNS
Lethargic
mood/depression, psychosis
Decreased intellectual and motor activities
cramps
Peripheral neuropathy
carpal tunnel syndrome
cerebellar ataxia - signs: seems drunk
memory loss
weakness
- reproduction
Menorrhagia
Hyperprolactinaemia - increase TRH causes increase in in prolactin (PRL).
How do you manage Hypothyroidism?
General: restore metabolic rate to normal
Thyroxine treatment:
THYROXINE NEEDS TO BE TAKEN ON AN EMPTY STOMACH - therefore take before breakfast is best
Thyroxine half life is 7days so wait 4 weeks before checking if needs to adjust. Check TSH 2 months after any dose change
once stabilised TSH should be checked every 12-18months
Young patients: Levothyroxine (T4) 50-100 μg a day.
Elderly or IHD- start at 25-50 μg a day. adjust every 4 weeks according to TSH response
Secondary hypothyroidism:
TSH is unreliable - titrate dose of levothyroxine to the free T4 levels
DO NOT:
Take levothyroxine with PPI, iron tablet and calcium tablets. they affect its absorption
Pregnancy: increase dose by 25-50%
What are the sign and symptoms of myxodema coma?
Looks hypothyroid
often elderly women
Bradycardia
coma
seizures
Type 2 resp failure - hypoxia, respiratory acidosis and Hypercarbia
How do you diagnose Myxodema coma?
ECG: bradycardia, Low voltage complexes, varying degrees of heart block, T wave inversion and prolonged QT interval
Goitre
Cyanosis
can have co-existing adrenal failure in 10% of patients
How do you manage Myoxdema coma?
- Check blood for T3,T4, TSH, FBC and U&E. Close cardiac monitoring
- High flow O2 if cyanosed
- Passively rewarm if hypothermic e.g. blankets and fluid
- Rehydrate if needed but watch for cardiac dysfunction
- If infection is suspected give antibiotics
- Hydrocortisone for pituitary hypothyroidism and adrenal failure
- Give Levothyroxine
what diseases are associated with hypothyroidism?
Autoimmune:
- Type 1 dm
- Addison’s disease
- Genetic:
Down’s syndrome
Turner’s syndrome
cystic fibrosis
- others
primary biliary cholangitis (PBC)
What is the difference between hyperthyroidism and Thyrotoxicosis?
Hyperthyroidism - refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis
Thyrotoxicosis- clinical effect of excess thyroid hormone, usually from gland hyperfunction
What are the signs and symptoms of thyrotoxicosis?
Cardiac:
- Palpitations, pulse fast/irregular (AF)
- Cardiac failure - very rare
Sympathetic nervous:
- Tremor
- sweating - heat intolerance
CNS:
- Anxiety
- nervousness
- Irritability
- Sleep disturbance
GI:
- Diarrhoea
- Weight loss
- increase in apeptite
Hair and skin:
- thin hair
- palmar erythema
- rapid finger nail growth
Muscle weakness
Eyes:
- Lid lag
- Lid retraction
- Diplopia- double vision
what are the causes of thyrotoxicosis?
any condition associated with hyperthyroidism
Excessive thyroid stimulation:
- Grave’s disease - 2/3 of cases of hyperthyroidism, more common in 40-60yr old women. Caused by circulating IgG autoantibodies binding to and activating g-protein coupled thyrotropin receptors, which cause smooth thyroid enlargement and increased hormone production
- Hashitoxicosis - associated with hashimoto thyroiditis. Early in hashimoto, you get excess TSH which increases release of T3 and T4
- Thyrotropinoma
- Thyroid cancer - very rarely causes thyrotoxicosis
- Choriocarcinoma - trophoblast tumour secreting hCG
Thyroid nodules with autonomous function :
- Toxic solitary nodule
- Toxic multinodular goitre
Thyroiditis:
- Subacute thyroiditis (de Quervain’s) - temporary hypothyroidism after hyperthyroid phase. Associated with painful goitre, pyrexia and raised inflammatory markers. Give NSAIDs
- Post-Patrum thyroiditis
- Drug induced thyroiditis - amiodarone and lithium
Exogenous thyroid hormones:
- Over treatment with Levothyroxine
- Thyrotoxicosis factitia
Ectopic thyroid hormones
- Metastatic thyroid carcinoma
- Struma ovarii
what are the specific signs of Grave’s disease?
- Thyroid eye disease:
occurs in 20% of patients.
can be either unilateral or bilateral. It is mainly mild but can be severe and sight threatening
i. Ophthalmoplegia - paralysis or weakness of eye muscle
ii. Proptosis (exophthalmos) - eyes protrude beyond the orbit
iii. eye discomfort - grittiness
iv. corneal ulceration
v. diplopia - double vision
vi. loss of vision
2. Pretibial myxoedema - swellings above lateral malleoli
3. Thyroid acropachy - clubbing, painful fingers and toe swelling and periosteal reaction in limb bones
4. Thyroid bruit
only associated with large goitres
reflective of hypervascularity of thyroid
ausculate over the thyroid - not heard in other goitrous conditions
Goitre’s associated with Graves’ are smooth
What is thyroid eye disease mainly associated with?
Smoking
How do you diagnose Thyrotoxicosis?
TFTs:
Supressed TSH - due to pathological positive feedback
High Free T3/T4
Other:
High ESR
High Calcium ion level - hypercalcaemia. Grave’s is associated with osteoporosis
High LFTs (alkaline phosphatase is high)
Decrease in white cell count (leucopenia) - often mild and related to disease than treatment
Autoantibodies:
TSH receptor antibody (TRAb) - 70-100% people have it in grave’s
Anti TPO -70-80% in graves
Anti thyroglobulin - 30-50% in graves
Isotope scan to detect:
nodular disease: TRAb negative
subacute thyroiditis
what is a Hyperthyroid crisis (thyroid storm)?
It is severe hyperthyroidism
what are the signs and symptoms of a thyroid storm?
Agitation
confusion
coma
tachycardia and AF
Hyperthermia
Respiratory and caridc collapse
acute abdomen
thyroid bruit
exaggerated reflexes
Precipitants: hyperthyroid patients with acute infection, recent thyroid surgery or trauma
How do you manage a thyroid storm?
- IV access, fluids if dehydrated or NG tube if vomiting
- Take blood for TFTs and cultures (infections)
- Monitor BP if good cardiac output and if no contraindication give propanolol/ use diltiazem if beta blocker is contraindicated
- Digoxin may be needed to slow the heart. Ensure adequately beta blocked, give with cardiac monitoring
- Antithyroid drugs : carbimazole, after four hours give Lugols (aqueous iodine) solution
- Give hydrocortisone or dexamethasone to prevent peripheral conversion of T4 to T3
- Give antibiotics for infection
- Cool if hyperthermic
How do you manage Hyperthyroidism?
Beta blockers
- Beta blockers used for rapid control of symptoms - reduces activity of sympathetic nervous system e.g. propanolol
- Careful if they are asthmatic as it can cause bronchospasm
- Can use CBB instead e.g. diltiazem
Anti thyroid drugs - inhibits TPO thereby blocking thyroid hormone synthesis:
- Carbimazole
i. 1st line drug
ii. Once daily dosing
iii. lower rate of side effect than PTU
iv. risk of aplasia cutis in early pregnancy - Propylthiouracil (PTU)
i. 1st line only in trimester of pregnancy
ii. twice daily dosing
iii. Inhibits DIo1 (stops conversion of T4 to T3)
Graves disease:
two strategies:
Dose titration: e.g. carbimazole (12-18 months)
Block and replace: e.g. carbimazole and levothyroxine simultaneously (6 months)
RADIOIODINE
1st line IF Graves disease relapse or nodular thyroid disease
no increased risk of thyroid cancer
risk of hypothyroidism if the patient has grave’s disease
dont use if patient is pregnant
Thyroidectomy: usually total
Used if radioiodine is contraindicated
scar
Sugrical/anaesthetic risks:
recurrent laryngeal nerve palsy
Hypothyroidism
Hypoparathyroidism
What are the types of thyroiditis?
Hashimoto’s thyroiditis
De Quervain’s/ subacute - viral
Post partum
Drug-induced (amiodarone, lithium)
radiation induced thyroiditis
Acute suppurative thyroiditis (bacterial)
What is subclinical thyroid disease
ii. what are its readings?
Abnormal TSH with normal thyroid hormone levels
ii. Subclinical hypothyroidism:
TSH is high but normal level of free T4 and T3
treat if TSH >10 mu/L and positive thyroid autoantibodies. Also if patient previously had Grave’s disease
Always treat in pregnancy to maintain normal TSH
Subclinical hyperthyroidism:
Low TSH and normal level of free T4 and T3
associated with AF and osteoporosis
treat if TSH <0.1 mu/L or if they have co existing osteoporosis or AF
What is sick euthyroid syndrome?
non -thyroidal illness which causes TSH levels to be secreted due to severe illness
TSH will rise to normal when patient recovers from illness
what are the five types of thyroid cancer?
- Papillary - most common
- Follicular - second most common
- Medullary -
- Anaplastic - extremely invasive and difficult to treat
- Hurthle cell
What is differentiated thyroid cancer ? (DTC)
Refers to two types of thyroid cancer: papillary and follicular
Has histological appearance which is similar to normal thyroid cells
“differentiated” features means good prognosis
Best prognosis only second to non melanoma skin cancer.
How can you separate differentiated thyroid cancer from other forms of thyroid cancer?
they take up radioactive iodine
they secrete TSH - they are TSH driven
what is the incidence and prevalence of differentiated thyroid cancer?
1: 100,000 men
2: 100,000 in women
non existent in childhood
Females rates increase 15-40 but then plateau
Male rates increase steadily
what is the epidemiology of Differentiated thyroid cancer?
More common in women
Lower incidence with Afro carribeans
Risk factor :Radiation exposure
No association with diet, family history, smoking or other lifestyle factors
what are the clinical features of differentiated thyroid cancer?
Palpable nodules - move on swallowing
Hoarse voice - could lead to vocal cord palsy
swollen glands in the neck
pain in neck is uncommon
5% present with local or disseminated metastases
Papillary thyroid cancer:
have Psammoma bodies
Tends to spread via lymphatics
Haematogenous spreads to lungs, bone, liver and brain
Follicular carcinoma:
Tends to spread via haematogenous
Lymphatic spread and lymph node enlargement relatively rare
equal prognosis with Papillary cancer
How do you diagnose Differentiated thyroid cancer?
Ultrasound guided FNA of the lesion
Can involve excision of lymph node
No need for:
isotope thyroid scan
CT/MRI
How do you manage differentiated thyroid cancer?
- surgery treatment of choice:
thyroid lobectomy with isthmusectomy
Used for patients in AMES low risk group
For:
Papillary microcarcinoma (<1cm diameter)
Minimally invasive follicular carcinoma with capsurlar invasion only
subtotal thyroidectomy - safest option
Used for patients in AMES high risk group
for:
DTC with extra-thyroidal spread
Bilateral/multifocal DTC
DTC with distant metastases
DTC with nodal involvement
Total thyroidectomy - quiet difficult as thyroid is deep in the neck
used for patient in AMES high risk group
for:
DTC with extra-thyroidal spread
Bilateral/multifocal DTC
DTC with distant metastases
DTC with nodal involvement
- Whole body iodine scanning
Given Iodine 131 - 2-4 mCi given as a capsule
Used after patients who have undergone subtotal or total thyroidectomy
occurs 3-6 months post op
Make TSH levels elevated: Administer recombinant human TSH (rhTSH) means you dont need to stop T3/T4 medication. Injection twice a week. This makes the cancer cells “hungry” for iodine. This makes it easier to see them in scan
- Thyroid remnant ablation:
used if evidence of metastatic disease is found in whole body iodine scanning
Pre-treated with rhTSH as before
given a much HIGHER dosage of Iodine 131 (3.3 GBq)
Few side effects: Sialadenitis (inflammation of salivary glands) and sore throat. No link to causing tumours or effect infertility/ genetic abnormalities in foetus
- Follow up after TRA
80% of radioactive iodine is excreted in first 24 hours
patient maintained on T4 - causes TSH suppression. But must not have Free T4 at too high of a level
Use thyroglobulin as a tumour marker - if differentiated thyroid cancer recurs, thyroglobulin is made only by this type of cancer and healthy thyroid cells. Therefore it is very specific
High Thyroglobulin levels can only be used if TSH levels are low. TSH levels if raised is associated with high Tg therefore can lead to misdiagnosis
- Systemic Anti- cancer therapy
Patients with DTC refractory to radioactive iodine therapy use this
biological agents: types of Tyrosine kinase inhibitors
Lenavatinib
Sorafenib
How do you define Pituitary tumours?
Microadenomas <1cm
Macroadenomas >1cm - more aggresive
99.5% of pituitary tumours are benign
What are the main issues of non functioning adenomas?
They can grow too big:
Compresses optic chiasma
Compresses cranial nerves 3,4,6
They can squeeze out other hormone production:
Hypoadrenalism
Hypothyroidism
Hypogonadism
GH defiency
Can effect post pituitary gland too- vasopressin deficiency = Diabetes Insipidus
How do you manage a non functioning adenoma?
Transphenoidal surgery
Replace hormones
What are the cause for raised prolactin?
Physiological:
Breastfeeding
Pregnancy
Stress
Sleep
Pharmacological:
Dopamine antagonists e.g. metoclopramide
Antipsychotics e.g. Phenothiazines - mainly older antipsychotic drugs
Antidepressants e.g. TCA, SSRIs
oestrogens e.g. contraceptive pill
Cocaine
Pathological:
Hypothyroidism
Stalk lesions
Prolactinoma - prolactin secreting tumour
If the prolactin level is over 5000 mu/L what does this suggest?
prolactin secreting tumour
What are the signs and symptoms of Prolactinoma?
Female:
Early presentation
Galactorrhoea
30-80%
Menstrual irregularity
Amenorrhoea
Infertility
define what AMES low risk group is.
Younger patients ( men <40, women <50) with no evidence of metastases
Older patients with intrathyroidal papillary lesion or minimally invasive follicular lesion and primary tumour < 5cm and no distant metastases
Define what AMES high risk group is.
All patients with distant metastases
Extrathyroidal disease in patients with papillary cancer
Significant capsular invasion with follicular carcinoma
Primary tumour > 5cm in older patients
What is type 3 diabetes?
diabetes secondary to a disease/syndrome/drug/monogenic cause
what are the 3 main pancreatic causes of type 3 diabetes?
chronic/recurrent pancreatitis
haemochromatosis
cystic fibrosis
what are the 4 main endocrine causes of type 3 diabetes?
cushings syndrome
acromegaly
phaechromocytoma
glucagonoma
what are the 3 main drug-induced causes of type 3 diabetes?
glucocorticoids
diuretics
b-blockers
what are the 3 main genetic causes of type 3 diabetes?
CF
myotonic dystrophy
turner’s syndrome
will C-peptide be positive or negative in monogenic diabetes?
positive
what is type 4 diabetes?
gestational diabetes:
any degree of glucose intolerance arising or diagnosed during pregnancy
what are the main causes of Primary Hyperparathyroidism (PHPT)?
- Adenomas: (80%)
- Hyperplasia of all four parathyroid glands (20%)
- Carcinoma (0.5%) - parathyroid cancer
What are the signs and symptoms of Primary hyperparathyroidism?
Asymptomatic
- Hypertension
- Hypercalcaemia - weak, tired, depressed, thirsty, dehydrated-but-polyuric, renal stones, abdominal pain, pancreatitis and ulcers
- Bone resorption: Bone pain, fractures, and osteoporosis
How do you diagnose primary hyperparathyroidism?
1.Bloods:
Hypercalcaemia - incidental Ca ≥ 2.6 mmol/litre
Increase in PTH and Low PO43-
- Increased ALP from bone activity
- 24 hr urinary Ca2+
imaging:
Sesatimbi scan: osteitis fibrosa cystica - subperiosteal erosions, cysts or brown tumours of phalanges
Dexa for osteoporosis
How do you manage Primary hyperparathyroidism?
- Mild PHPT
increase fluid intake to prevent stones
avoid thiazides and High Ca2+/ Vit D intake
- Surgery:
Excision of adenoma or all parathyroid glands
this prevents peptic ulcers and fractures
Complications:
Hypoparathyroidism, recurrent laryngeal nerve damage (hoarse voice), hypocalcaemia
What are the indications of Primary hyperthyroidism?
- Hypercalcaemia
- Normal U&E
- High urine calcium
- Not on lithium or thiazide
- <50 years old
compare primary and secondary causes of hypothyroidism in terms of goitre (enlarged thyroid)?
primary gland failure- may have a goitre
secondary to TRH or TSH- no goitre
compare primary hyperthyroidism to pituitary disease causing secondary hyperthyroidism in terms of levels of T3/4 and TSH?
primary: low TSH, high T3/4
secondary: high TSH, high T3/4
compare primary hypothyroidism to pituitary disease causing secondary hypothyroidism in terms of levels of T3/4 and TSH?
primary: high TSH, low T3/4
secondary: low TSH, low T3/4
compare primary and secondary hypothyroidism in the use of TSH levels as an indicator for if thyroxine treatment is working?
primary: TSH is a good indicator- will be low when T4 treatment is successful
secondary: TSH is not a good indicator, will be low regardless of if the treatment is successful
(in this case montor T4 levels)
what is primary hyperparathyroidism?
overactive parathyroid glands: PTH is produced irrespective of calcium levels
what is secondary parathyroidism?
physiological high PTH in response to low calcium.
The release of PTH is appropriate
what is tertiary hyperparathyroidism?
parathyroid becomes autonomously overactive having undergone hyperplastic or adenomatous change this occurs after many years of secondary parathyroidism.
The release of PTH is inappropriate (i.e. too high)
what are the cause of Secondary and tertiary hyperparathyroidism?
Vitamin D deficiency
Chronic Kidney disease
How do you diagnose between Secondary and tertiary hyperparathyroidism?
Secondary:
Low Ca
High PTH
High PO4
Tertiary:
High Ca
Very high PTH
Low PO4
How do you manage Secondary and tertiary hyperparathyroidism?
Treat underlying cause
Renal disease: diet restriction, phosphate binders
Vitamin D
Cinacalcet if PTH >85pmol/L (secondary)
What is malignant Hyperparathyroidism?
Parathyroid related protein ( PTHrP) is produced by the following types of cancer:
- some squamous cell lung cancers
- breast and renal cell carcinomas
this mimics PTH resulting in increased Ca 2+
which MEN type are parathyroid neoplasms associated with?
both 1 and 2
what is primary hypoparathyroidism?
Low PTH secretion due to gland failure
What are the causes of primary hypoparathyroidism?
Autoimmune
Di george syndrome
Haemochromatosis/ wilsons
Iatrogenic: removal or accidental injury of parathyroid glands in surgery or radio ablation
What are the signs and symptoms of Primary hypoparathyroidism?
Hypocalcaemia: perioral numbness, cramps, carpopedal spasm, laryngospasm, seizures, wheeze and anxiety
How do you diagnose Primary hypoparathyroidism?
Bloods: Low ca, Low PTH and high PO4
How do you manage Primary hypoparathyroidism?
Treatment of underlying cause
calcium and vitamin D supplements
what is pseudohypoparathyroidism?
a genetic defect causing PTH resistance
what are the levels of PTH in pseudohypoparathyroidism?
high
What are the causes of secondary hypoparathyroidism?
Radiation
Surgery - thyroidectomy, parathyroidectomy
Hypomagnesaemia
what are the signs and symptoms of pseudohypoparathyroidism?
Short metacarpals ( 4th and 5th especially)
round face
short stature
calcified basal ganglia
Low IQ
obesity
How do you diagnose pseudohypoparathyroidism?
Low Ca2+
High PTH/PO4
High ALP
How do you manage Pseudohypoparathyroidism?
Calcium and vitamin D supplements
what is pseudo-pseudohypoparathyroidism?
a genetic defect causing PTH resistance
calcium is normal because PTH is high
compare calcium, phosphate and PTH levels in a patient with:
- Hypoparathyroidism
- pseudohypoparathyroidism
- pseudo-pseudohypoparathyroidism
Calcium Phosphate PTH
- Low high Low
- Low high High
- Normal Normal High
what is cushing’s syndrome?
the clinical state produced by chronic glucorticoid excess
What are the causes of cushing’s syndrome?
- Exogenous - prolonged use of oral steroid ( main cause)
- Endogenous:
i. ACTH-dependent (Increase in ACTH):
Cushing’s disease - bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma
Ectopic ACTH production - occurs especially in small cell lung cancer and carcinoid tumours
ii. ACTH-independent ( Decrease in ACTH due to -ve feedback):
Iatrogenic: Pharmacological doses of steroids
Adrenal adenoma/ cancer
Adrenal nodular hyperplasia
what are the signs and symptoms of cushings syndrome?
- Psychology
Euphoria - though sometimes depression or psychotic symptoms and emotional lability
increased appetite
- Head:
Benign intracranial hypertension
Cataracts
Moon face with red plethoric cheeks
- Body:
Hirsutism
Obesity
Osteoporosis
Increased abdominal fat
thin arms and legs - muscle wasting
osteoporosis
Poor wound healing
Easy bruising
thinning of skin
abdominal striae
- Legs
recurring Achilles tendon rupture
other:
Tendency to hyperglycaemia
negative nitrogen balance
infection-prone
Hypertension
Hyperglycaemia
How do you diagnose Cushing’s syndrome?
First line:
- Overnight 1mg dexamethasone suppression test (oral) - dexamethasone makes ACTH low which in turn makes Cortisol low if normal
If cortisol <50 nmol/L next morning then normal
if Cortisol >130 nmol/L next morning then abnormal
- 24hr urine free cortisol
If total <250 then normal
or
if cortisol/creatinine ratio <25 then normal
2nd line:
- 48 hr dexamethasone suppression test 0.5mg/6hr (oral) - diagnostic
measure at 0hr and 48hr
there is a failure to suppress cortisol
- Diurnal cortisol variation (midnight/8am)
Loss of diurnal variation suggests cushing’s
(cortisol lowest at midnight and highest in early morning)
Imaging:
CT/MRI head
CT CAP
others:
blood glucose : hyperglycaemia
How do you manage Cushing’s syndrome?
- Pharmacological:
Ketoconazole may have a direct effect on corticotropic tumour cells in patients with Cushing’s disease.
Metyrapone in controlling the symptoms of the disease
Adrenal enzyme inhibitors
- Cushing’s disease
selective removal of pituitary adenoma
- Adrenal adenoma or carcinoma
adrenalectomy. Radiotherapy and adrenolytic drugs follow if carcinoma - Ectopic ACTH: surgery if tumour is located and and hasn’t spread
- Iatrogenic:
stop medication
what is primary hyperaldosteronism?
excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high water retention and sodium levels. This independent of the functions of the RAAS system.
What are the causes of primary hyperaldosteronism?
- Conn’s syndrome - solitary aldosterone producing adenoma
- Bilateral adrenocortical hyperplasia (BAH)
other causes: adrenal carcinoma, glucorticoid-remediable aldosteronism
What are the signs and symptoms of Primary Hyperaldosteronism?
Often asymptomatic
Hypokalaemia
Polyuria
Polydipsia
headaches
weakness
cramps
parasthesia
muscle spasms
Hypertension- young onset and treatment resistant
How do you diagnose primary hyperaldosteronism?
Bloods:
U&Es
low Renin and high aldosterone levels
Sodium high
potassium low
Diagnostics
Plasma aldosterone: renin ratio >750
Saline suppression test - failure to suppress aldosterone production by 50% following consumption of water.
imaging:
CT abdomen - to identify adenoma
how do you manage primary hyperaldosteronism?
Conn’s syndrome:
- Medical management first: aldosterone antagonists - eg, spironolactone
- Surgery: Laparoscopic adrenalectomy
BAH:
treatment is medical with aldosterone antagonists:
Amiloride- potassium-sparing diuretic
Spironolactone - nonselective aldosterone antagonist
Eplerenone - relatively new selective aldosterone antagonist and therefore does not have the same troublesome side-effects as spironolactone.
GRA:
Dexamethasone for four weeks. if the patient is still hypertensive then use spironolactone
What is primary adrenal insufficiency (Addison’s disease)
destruction of the adrenal cortex leads to glucocorticoids and mineralocorticoids deficiency
What are the causes of primary adrenocortical insufficiency?
- TB - most common cause in the world
- Autoimmune - most common cause in UK
- Adrenal metastasis: Lung, breats, renal and lymphoma
- Opportunistic infection in HIV
- Waterhouse Friderichsens syndrome: bilateral adrenal haemorrhage due to sepsis
what are the signs and symptoms of primary adrenocortical insufficiency?
Anorexia
weight loss
fatigue/lethargy
dizziness
hypotension
abdominal pain
vomiting/ diarrhoea
hyperpigmentation of skin especially of palmar creases
myalgia and arthralgia
can have vitiligo and goitres
How do you diagnose primary adrenocortical insufficiency?
Blood:
Low sodium
high potassium
signs of hypoglycaemia
Very high ACTH levels - causes ksin pigmentation
Very high renin
low Aldosterone and low cortisol
- Short SYNACTHEN Test: diagnostic marker
Measure plasma cortisol before and 30 minutes after IV/IM ACTH injection
Normal results are:
baseline: > 250 nmol/L
30 min result post ACTH > 550 nmol/L
- Adrenal autoantibodies:
21-hydroxylase and 17 alpha hydroxylase
Imaging:
CXR
CT CAP
How do you manage primary adrenocortical insufficiency?
Pharmacological:
- cortisol replacement — hydrocortisone:
Glucocorticoid replacement should resemble the natural cycle of corticosteroid release
15–25 mg in divided doses
- Aldosterone replacement — fludrocortisone:
50–200 micrograms
careful monitoring of BP and K
Sick days:
they should double their usual dose of hydrocortisone until recovered.
if vomiting replace oral with IM
what is secondary adrenal insufficiency?
condition where there is a failure to produce adequate steroids as a result of ACTH deficiency
What are the causes of secondary adrenal insuffiency?
- Long term steroid therapy
- Pituitary disease
- Tumours - surgery and radiotherapy
what are the signs and symptoms of secondary adrenal insuffiency?
Same as primary except for:
No hyperpigmentation ( skin pale) due to no increase in ACTH
Aldosterone production intact - regulated with RAS
How do you diagnose secondary adrenal insufficiency?
Blood:
Low sodium
high potassium
signs of hypoglycaemia
Low Cortisol and normal aldosterone
- Short SYNACTHEN Test: diagnostic marker
Measure plasma cortisol before and 30 minutes after IV/IM ACTH injection
Normal results are:
baseline: > 250 nmol/L
30 min result post ACTH > 550 nmol/L
- Adrenal autoantibodies:
21-hydroxylase and 17 alpha hydroxylase
Imaging:
CXR
CT CAP
how do you manage secondary adrenal insufficiency?
Hydrocortisone replacement
What are the causes of an acute adrenal crisis (Addisonian crisis)?
Bilateral adrenal haemorrhage
Patient on long term steroids who suddenly doesn’t take them
Illness, trauma or surgery in those with primary adrenal failure
what are the signs and symptoms of an acute adrenal crisis?
Shock:
increased Heart rate
vasoconstriction
postural hypotension
oliguria
weak
confused
comatose
Hypoglycaemia
How do you diagnose acute adrenal crisis?
FBC
U&E
Glucose
Cortisol
ACTH
Lactase
cultures
How do you manage acute adrenal crisis?
ABCDE
Hydrocortisone 100mg IV
IV fluid bolus Resuscitation
monitor blood glucose: Glucose IV needed if hypoglycaemic
What are Phaeochromocytoma?
They are rare catecholamine-producing tumours of the adrenal medulla . They arise from sympathetic paraganglia cells (phaeochrome bodies) which are collections of chromaffin cells.
What is the 10% rule for phaeochromocytomas?
They roughly follows this rule
10% are malignant:
extra adrenal lesions (20-40%)
tend to be large and nectrotic
10% are extra-adrenal:
Called paraglangliomas
organs of zuckerkandl, carotid
10% are familial:
germline mutations
10% bilateral:
Up to 50% in familial cases
what are the signs and symptoms of phaeochromocytomas?
Classic triad:
Episodic headache
Sweating
tachycardia
Hypertension
CNS: Headache, visual disorder, dizziness, tremor, numbness, fits and encephalopathy
Psychological: anxiety, panic, hyperactivity, confusion; episodic psychosis
What are the associated conditions with phaeochromocytomas?
MEN2A - sipple syndrome
MEN2B
neurofibromatosis
von- Hippel Lindau syndrome
How do you diagnose phaeochromocytomas?
Detection of urinary excretion of catecholamines and metabolites
increased White cell count
MIBG scan - uses a chromaffin seeking isotope
How do you manage Phaeochromocytomas?
alpha blockage : phenoxybenzamine
then use
Beta blocker e.g. atenolol to avoid crisis from unopposed alpha adrenergic stimulation
what is hypopituitarism?
decrease in secretion of one type of pituitary hormones
Panhypopituitarism - deficiency of anterior hormones
it involves problems in the hypothalamus, the pituitary stalk or the pituitary gland itself
What are the causes of hypopituitarism?
Hypothalamus causes:
Kallman’s syndrome
tumour
inflammation
Infection ( TB and meningitis)
ischaemia
Pituitary stalk:
Trauma
surgery
mass lesion
meningioma
carotid artery aneurysm
Pituitary gland:
Tumour
irradiation
inflammation
autoimmune - may be triggered by pregnancy
infiltration: haemochromatosis , amyloid, sarcoid
Ischaemia: Sheehan syndrome, pituitary apoplexy
Sheehan syndrome: pan hypopituitarism due to pituitary ischaemia and necrosis following a post partum haemorrhage. commonly presents with failure to produce breast milk
Pituitary apoplexy: ischaemia due to bleeding of pituitary tumours
What are the signs and symptoms of hypopituitarism?
Lack of of GH: Central obesity, atherosclerosis, dry wrinkly skin, weakness, loss of balance, osteoporosis, hypoglycaemia
Absent TSH: hypothyroidism
Lack of corticotropin: adrenal insufficiency
Lack of GRH:
Women: amenorrhoea, decrease in fertility, decrease in libido, breast atrophy, dyspareunia
Men: erectile dysfunction, decrease in muscle bulk, decrease in libido, hypogonadism
lack of prolactin: absent lactation ( rare)
how do you diagnose hypopituitarism?
Basal testing:
LH, FSH, testosterone or oestradiol, TSH, T4, prolactin, IGF1
Dynamic tests:
short synacthen test : used for adrenal axis
Insulin tolerance test: used for adrenal and GH axes
both will rise in the presence of hypoglycaemia induced by giving insulin
How do you manage hypopituitarism?
Hydrocortisone for adrenal failure
thyroxine if hypothyroidism
Hypogonadism:
males: testosterone enanthate 250mg IM every three weeks
topical gels can also be used on the daily
females: transdermal oestradiol patches or contraceptive pill
Growth hormone deficiency:
somatotropin
what is Diabetes Insidpidus? (DI)
The passage of large volumes ( >3L/day) of dilute urine due to impaired water resorption by kidney
Either because of reduced ADH secretion from the posterior pituitary (central DI)
or
impaired response of the kidney to ADH ( nephrogenic DI)
what are the causes of DI?
Central DI:
- Idiopathic - most common
- Genetic - e.g. DIDMOAD
- Tumour - may present with DI and hypopituitarism
- Sarcoidosis
- Trauma to the pituitary stalk
Nephrogenic DI:
- Genetic
- Metabolic - Low potassium/ high calcium
- CKD
- Drugs - Lithium, demeclocycline
What are the signs and symptoms of DI?
Polyuria
Polydipsia
dehydration
How do you diagnose DI?
Gold test standard
Water deprivation tests: Tests the ability of kidneys to concentrate urine ( dilute urine in spite of dehydration) - must check calcium to exclude hypercalcaemia
osmolality >600 is normal
Can distinguish between the two types of DI via water deprivation test by giving desmopressin (ADH):
Cranial DI: will rise to >600 after desmopressin
Nephrogenic DI: will NOT rise >600 after desmopressin
How do you manage DI?
Cranial DI: Desmopressin
Nephrogenic:
Treat the cause
if it persists give Bendroflumethiazide - generate hyponatremia and drive water reabsorption
What is acromegaly?
abnormal growth of the hands, feet, and face, caused by overproduction of growth hormone by the pituitary gland.
What are the causes of acromegaly?
GH secreting pituitary tumours associated with MEN - 1
What are the signs and symptoms of acromegaly?
Symptoms:
Acroparaethesia (pins and needles)
amenorrhoea
decrease in libido
headache
increase in sweating
snoring
backache
signs:
Growth of hands, lower jaw, brow and tongue
coarsening face, wide nose
big supraorbital ridges
macroglossia
widely space teeth
puffy eyelids/ lips
skin darkening
goitre
obstructive sleep apnoea
signs of any pituitary mass
carpal tunnel syndrome
How do you diagnose Acromegaly?
high IGF1 levels - First line
bloods:
High glucose
High calcium and Phosphate
high GH - dont rely on random GH as secretion is pulsatile and during peaks acromegalic and normal levels overlap.
Tests:
Glucose tolerance tests: if OGTT is above 1mcg/L then acromegaly is confirmed
imaging:
MRI of pituitary
how do you manage acromegaly?
1st line: Trans-sphenoidal surgery is the treatment of choice
2nd line: pharmacology
carried out if surgery not possible or fails to correct growth hormone levels
Somatostatin analogues (somatostatin receptor ligands) are the first-choice medical treatments e.g. Octreotide and lanreotide
Side-effects are frequent and include abdominal discomfort and gallstones or gallbladder sludge
Dopamine agonists:
Bromocriptine, cabergoline and quinagolide are effective but are less effective than somatostatin analogues
Cabergoline is the most effective dopamine agonist
Pegvisomant (PEG):
This is a genetically modified analogue of human GH and a highly selective GH receptor antagonist which blocks the peripheral synthesis of IGF-1.
doesnt shrink tumour
Pregnancy
Medical therapy is withheld during pregnancy.
Short-acting octreotide may be used as needed when attempting to conceive.
What is Hyperprolactinaemia?
prolactin fasting levels of above 20 ng/ml in men and above 25 ng/ml in women at least 2 hours after waking up.
what are the causes of hyperprolactinaemia?
Drugs (most common):
metoclopramide
haloperidol
methyldopa
oestrogens
MDMA
antipsychotics
Physiological: pregnancy, breastfeeding, stress
Pathological:
Pituitary tumour (prolactinoma)
Stalk damage: pituitary adenoma, surgery, trauma
Hypothalamic disease: craniophayngioma
Hypothyroidism
chronic renal failure
What are the signs and symptoms of hyperprolactinaemia?
presents earlier in women than men
Females:
Amenorrhoea
infertility
galactorrhoea
decrease in libido
increase in weight
dry vagina
Male:
erectile dysfunction
reduced facial hair
galactorrhoea - less prominent in comparison to females
How do you diagnose hyperprolactinaemia?
Bloods: TFT, U&E, prolactin
pregnancy test if other causes are ruled out
imaging - MRI
How do you manage hyperprolactinaemia?
1st line - dopamine agonists e.g. bromocriptine or cabergoline
2nd - surgical excision of the tumour
What is a microprolactinoma?
A tumour <10mm on MRI
what is a macroprolactinoma?
a tumour >10mm on MRI
where are craniopharyngiomas found?
the pituitary and 3rd ventricle floor
a tumour of rathke’s pouch
what are the clinical features of craniopharyngioma’s?
most common intracranial tumour
Childhood growth failure
adults:
amenorrhoea
libido decrease
hypothalamic symptoms e.g. DI
How do you treat craniopharyngioma’s?
Surgery and post op radiation
imaging: CT/ MRI
what is the presentation of a thyroglossal cyst?
Lesion usually in the midline
moves upwards on protrusion of the tongue
not painful
what is osteoporosis?
progressive systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture
if trabecular bone is affected, crush fractures of vertebrae are common
if cortical bone is affected, long bone fractures are more likely
what are risk factors of osteoporosis?
- risk factors Reducing Bone material density include:
Endocrine disease including Diabetes mellitus,
Hyperthyroidism, and hyperparathyroidism.
Gastrointestinal conditions that cause malabsorption such as Crohn’s disease, Ulcerative colitis, Coeliac disease, and Pancreatitis - chronic.
Chronic kidney disease.
Chronic liver disease.
Chronic obstructive pulmonary disease.
untreated Menopause.
Immobility.
Body mass index of less than 18.5 kg/m²
- Risk factors which Do not reduce BMD include:
Age - risk increases with age and is at least partly independent of BMD.
Oral corticosteroids (dependent on the dose and duration of treatment).
Smoking.
Alcohol (3 or more units daily).
Previous fragility fracture (risk increases with increasing
number of fractures). Risk is highest for previous hip fractures and lowest for previous vertebral fractures.
rheumatoid arthritis, and other inflammatory arthropathies.
Parental history of hip fracture.
what are the signs and symptoms of osteoporosis?
asymptomatic until minimal trauma fractures occur
common fracture sites:
neck of femur
vertebral body
distal radius
humeral neck
domino fracture effect: one Vertebral Compression Fracture increases risk of another
how do you diagnose osteoporosis?
1.DEXA scan used to measure bone mass density:
T -score - the number of standard deviations the BMD is from the youthful average
T score > 0 -:Good BMD
T score 0 to -1 : normal BMD
T score -1 to -2.5: osteopenia. risk of later osteoporotic fracture
- 2.5 or worse: osteoporosis
2. Bloods:
Ca2+ : normal
Po43- : normal
ALP : normal
- For all other people with risk factors for osteoporosis, calculate the 10-year fragility fracture risk prior to arranging a DXA scan to measure BMD. e.g. FRAX or Q fracture
Who do you refer for DEXA scans?
patients over 50 years with low trauma fracture - often identified through fracture liaison service
Patients at increased risk of fracture based on risk factors - calculated with risk assessment tools e.g. FRAX or Q fracture >10% risk of fracture over 10 years
how do you manage Osteoporosis?
Lifestyle:
Fall prevention
avoidance of smoking and alcohol
Low impact weight-bearing exercise may increase BMD e.g. standing, one foot always on the floor
Diet: high in calcium and Vitamin D. Reference nutrition intake = 700mg calcium
Pharmacological:
- Bisphosphonates:
e. g. alendronate and risedronate.
prevent bone loss at all sites vulnerable to osteoporosis. reduce risk of hip and spine fractures . it prevents bone resorption
use in patients of T score <2.5
use zoledronic acid if intolerant to oral bisphosphonates or unable to comply with dosing regime
- calcium and vitamin D supplements: rarely used alone for prophylaxis. used to reduce risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake
- Denosumab - fully human monoclonal antibody to RANKL ( receptor activator of nuclear factor - kB ligand)
prevents activation of its receptor RANK which inhibits development and activity of osteoclasts which decreases bone resorption and increases bone density
sub cutaneous injection 6 monthly
adverse effects: cellulitis and eczema and hypocalcaemia
- Teriparatide
recombinant PTH
stimulates bone growth
consider for severe osteoporosis- especially in high risk of vertebral fracture
when to treat
= -2.5 - no steroids and with anti resorptive therapy
- 5mg prednisolone for three months)
- corticosteroids
directly - reduce osteoblast activity and lifespan
reduces calcium absorption
indirectly - inhibits gonadal and adrenal steroid production
what is the pathogenesis of osteoporosis?
caused by increase in bone turnover due to an imbalance in bone turnover
three is a shift towards increased resorption which reduces BMD and causes micro architectural changes
what is metabolic bone disease ?
e.g. osteomalacia and rickets
there is a normal amount of bone but its mineral content is low.
it is a reverse of osteoporosis
what is the difference between osteomalacia and rickets?
- rickets is the result of abnormal bone mineralisation occurring during the period of bone growth
- osteomalacia - is the result if it occurs after fusion of epiphyses
what are the causes of osteomalacia and rickets?
vitamin D deficiency - due to malabsorption, poor diet or lack of sunlight
Renal osteodystrophy - renal failure leads to 1,25 dihydroxy-cholecalciferol deficiency
vitamin D resistance
liver disease - due to reduce hydroxylation of vitamin D to 25 hydroxy-cholecalciferol deficiency e.g. cirrhosis
tumour induced osteomalacia
drugs: anticonvulsants
what are the signs and symptoms of osteomalacia and rickets?
1.Rickets:
growth retardation
hypotonia
apathy in infants
signs of hypocalcaemia
ii. when walking: knock kneed, bow legged and deformities of the metaphyseal-epiphyseal junction
2. osteomalacia
Bone pain and tenderness
fractures
proximal myopathy due to fall in PO43-
vitamin D deficiency
how do you diagnose osteomalacia and rickets?
hypocalcaemia with profile being particular to cause:
- Vitamin D deficiency:
fall in Po43-
fall in vitamin D
increase in ALP
increase in PTH
- Renal bone disease
increase in PO43-
increase in PTH
increase in ALP
may have high 25-OH Vitamin D
biopsy- shows incomplete mineralisation
x-ray:
osteomalacia - loss of cortical bone and looser’s zones ( partial fractures without displacement )
rickets- cupped, ragged metaphyseal surfaces are seen in rickets
how do you manage osteomalacia and rickets?
- Vitamin D deficiency - give Vitamin D e.g. calcium D3
- renal disease or vitamin D resistance - give alfacalcidol or calctirol and adjust dose to plasma ca2+. they both cause severe hypercalcaemia
what are the two forms of vitamin D -resistant rickets?
type 1 - low renal 1alpha hydroxy-lase activity
type 2 - end-organ resistance to 1,25 dihydroxy-vitamin D3
give calcitriol for both
due to FGF23 gene mutation - regukates phosphate levels
what is x linked hypophosphataemic rickets?
dominantly inherited due to PHEX gene mutation
plasma PO43- is low
ALP is high
phosphaturia occurs
treatment - oral phosphate and vitamin D supplements
what is pagets disease?
increased bone turnover associated with increased number of osteoblasts and osteoclasts with resultant remodelling, bone enlargement deformity and weakness
rare in the under-40s
what are the signs and symptoms of pagets disease?
primarily affects: long bones, pelvis, lumbar spine and skull - bone enlargement and deformity
asymptomatic in majority of cases
deep, boring pain
deafness
compression neuropathies e.g. nerve entrapment syndrome
headaches
large joint OA
complications: osteosarcoma
how do you diagnose paget disease?
imaging:
X-ray:
early - lytic lesions (mixed lytic and sclerotic appearance too)
late disease: cortical thickening, deformity
skull disease: cotton wool appearance
isoptope bone scan shows distribution of disease
Biochemistry:
ALP raised
ca2+ is normal
PO43- is normal
how do you manage Paget’s disease?
mild: analgesia e.g. NSAIDs
severe: bisphosphonates e.g. pamidronate
what is a goitre?
a thyroid lump normally found on the midline of the neck
normally rises on swallowing
what is a branchial cyst?
a lump in the neck which is smooth and round normally located on the anterior border of the upper third of the sternocleidomastoid muscle
presentation:
in young adults
painless and smooth swelling
surgical excision is management
what is an acute parotitis?
a recent swelling of the salivary glands
associated with painful pre-auricular swelling
What is MEN 1 defined as?
a group of inherited syndromes that are characterised by groups of tumours of the endocrine glands
MEN 1 is defined as tumours occurring with any two of the following:
parathyroid hyperplasia
Pituitary adenoma
pancreatic islet cell tumours
what is MEN 2 defined as?
MEN 1 is defined as tumours occurring with any two of the following:
medullary thyroid carcinoma
phaeochromocytoma
parathyroid tumour
what causes blue sclera in children?
ostegenesis imperfecta (brittle bone disease)
what are the four types of osteogenesis imperfecta?
Type 1 - mildest and most common form - multiple fractures, discoloured teeth, blue scerae, aortic root dilatation, aortic regurigitation Mitral valve prolapse
Type 2 - lethal form
Type 3 - severely progressive and deforming form
Type 4 - moderately progressive form
