Endocrine Flashcards
What defines prediabetes?
HbA1c 42-47mmol/mol
fasting glucose 6.1-6.9
What HbAlc defines diabetes?
> 48mmol/mol (6.5%)
What blood glucose defines diabetes?
fasting glucose >= 7.0 mmol/l
random glucose >= 11.1 mmol/l
HbA1c >48mmol/mol
What are some complications of diabetes?
lipohypertrophy vascular disease nephropathy neuropathy retinopathy
How can patients with diabetes reduce complications of diabetic neuropathy
foot check with mirror comfortable shoes no barefoot walking chiropody treat fungal infections
What is the advice from the DVLA for patients who take insulin?
need to inform the DVLA!!!
check blood glucose before driving and every two hours whilst driving
have snack in <5mmol/l
do not drive if <4mmol/l or sx of hypoglycaemia
What does HbA1c show?
level of glycated Hb
reflects average plasma glucose over the previous 2 to 3 months and provides a good indicator of glycaemic control.
How often should the HbA1c be monitored in diabetes?
every 3 to 6 months
in type 2, when stable and medications stable, can be every 6 months
How can cardiovascular risk be reduced in diabetes?
ACEi
statin
aspirin
How are patients monitored for diabetic nephropathy?1
yearly urine protein test (Albustix) and serum creatinine
if -ve for protein, test for microalbuminuria
If a diabetic patient is discovered to have proteinuria or micoalbuminuria, what is the appropriate management?
ACEi or Angiotensin II receptor antagonist
What can be used to treat painful diabetic neuropathy?
duloxetine
pregabalin
How often should patients with IDDM monitor their blood glucose?
at least four times a day
on waking, before each meal, before going to bed
What is a multiple daily injection basal-bolus insulin regimen
One or more separate daily injections of intermediate-acting insulin or long-acting insulin analogue as the basal insulin
plus multiple bolus injections of short-acting insulin before meals.
This regimen offers flexibility to tailor insulin therapy with the carbohydrate load of each meal.
What is a mixed insulin regimen?
One, two, or three insulin injections per day of short-acting insulin mixed with intermediate-acting insulin.
Who can a Continuous subcutaneous insulin infusion (insulin pump) be offered to?
adults who suffer disabling hypoglycaemia,
adults who have high HbA1c concentrations (69 mmol/mol [8.5 %] or above) with multiple daily injection therapy (including, if appropriate, the use of long-acting insulin analogues) despite a high level of care
What can persistent poor glucose control in insulin therapy be due to?
poor adherece
injection technique,
injection site problems,
blood-glucose monitoring skills,
lifestyle issues (including diet, exercise and alcohol intake),
psychological issues,
organic causes such as renal disease, thyroid disorders, coeliac disease, Addison’s disease or gastroparesis.
What can increase a diabetic’s insuln requirement?
Infection,
stress,
accidental or surgical trauma
What can decrease a diabetic’s insuln requirement?
physical activity,
intercurrent illness,
reduced food intake,
impaired renal function,
What are the warning signs of hypoglycaemia?
sweating, anxiety, hunger, tremor, palpitations, dizziness
confusion, drowsiness, visual problems, seizures, coma
What are the daily blood glucose targets when self testing for IDDM?
5-7 mmol/l on waking and
4-7 mmol/l before meals at other times of the day
How does metformin work?
increased insulin sensitivity
decreases liver gluconeogenesis
What are the important side effects if metformin?
GI upset
lactic acidosis
How do sulfonylureas work?
Stimulate pancreatic beta cells to secrete insulin
binding to and antagonising the β-cells K+-ATP channel activity,
increases K+ concentration within the cell
depolarisation.
increases Ca2+ ion entry into the cell
insulin release from β-cells.
What are the important side effects if sulfonylureas?
weight gain
hypoglycaemia
hyponatraemia
How do thiazolidinediones work?
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
What are the important side effects if thiazolidinediones?
weight gain
fluid retention
How do DPP-4 inhibitors (-gliptins) work?
Increases incretin levels which inhibit glucagon secretion
What are the important side effects if gliptins?
increased risk pancreatitis
How do SGLT-2 inhibitors (-gliflozins) work?
inhibits reabsorption of glucose in the kidney
What are the important side effects if SGLT-2 inhibitors?
urinary infections
increased risk DKA
How do GLP-1 agonists work?
Incretin mimetic which inhibits glucagon secretion and increases insulin secretion from pancreas
What are the important side effects if GLP-1 agonists?
Nausea and vomiting
Pancreatitis
How are GLP-1 agonists taken?
SC
What is the target HbA1c for type 2 diabetes?
<48mmol (6.5%)
If on drug associated with hypoglycaemia, aim for <53mmol/mol (7%)
If on two or more hypoglycaemic agents, aim for <53 (7%)
If a patient is being treated with oral hypoglycaemic, at what point would you consider adding another agent?
HbA1c >58 (7.5%)
How is hypoglycaemic treatment intensified?
metformin
\+ sulfonylurea thiazolidinedione DDP-4 inhibitor SGLT-2 inhibitor
then + 2 of them
consider insulin
When can GLP-1 agonists be prescribed?
If triple therapy with metformin hydrochloride and two other oral drugs is tried and is not effective, not tolerated or contra-indicated,
prescribed as part of a triple combination regimen with metformin hydrochloride and a sulfonylurea.
When is metformin contraindicated?
lactic acidosis
high risk of lactic acidosis: chronic cardiac failure
What is the first line treatment for NIDDM if metformin is contraindicated?
DDP4 inhibitor
Pioglitazone
a sulfonylurea (glibenclamide, gliclazide, glimepiride, glipizide, or tolbutamide).
What medications can trigger DKA?
steroids, thiazides sodium-glucose co-transporter 2 (SGLT2) inhibitors alpha blockers beta blockers
What are the key investigation findings in DKA?
hyperglycaemia >11
ketonaemia >3
acidosis <7.3
What are the key investigations in suspected DKA?
bedside: urine dipstick, ECG
bloods: FBC, U+E, glucose, ABG, troponin I, amylase
micro: blood cultures
Imaging: CXR, AXR
What is the immediate management of DKA?
fluid resuscitation
insulin - 50 units actrapid at 0.1unit/kg/hr
K+ replacement?
check pH, biarb, glucose and K+ hourly
What is HONK?
hyperosmolar non-ketotic coma
What are the key results defining HONK/HHS?
hypovolaemia
hyperglycaemia
low ketones <3mmol
high osmolarity >320mosmol/kg
What causes HONK/HHS?
develops in T2DM as a result of a combination of:
illness,
dehydration
an inability to take normal diabetes medication
What causes there to be hyperosmolarity and dehydration in HONK/HHS?
Hyperglycaemia causes an osmotic diuresis
due to glucose accumulating in the tubules of the kidney, reducing reabsorption of water in the kidneys, increasing urine output.
hyperosmolarity of the blood leads to an osmotic shift of water into the intravascular compartment,
resulting in severe intracellular dehydration
Why is there no ketosis in HONK/HHS
basal insulin is sufficient to prevent ketosis, but not enough to reduce blood glucose
What is the initial management in HONK/HHS?
A to E
IV fluids - 0.9% sodium chloride
insulin infusion
potassium replacement
What are the key investigations in HONK/HHS?
Bedside: ECG, urinalysis
Bloods: Glucose U and Es, HCO3-, amylase, ABG, calculate serum osmolarity
Micro: blood cultures
Imaging: CXR
What are the risks during pregnancy for a diabetic woman?
miscarriage pre-eclampsia premature labour worsening of diabetic retinopathy/nephropathy spontaneous abortion polyhydraminos
Wat are the risks to the fetus during pregnancy of a diabetic woman?
macrosomia congenital heart defects/neurological defects late intrauterine death stillbirth Erb's palsy
How can diabetic women decrease their risk of complications during pregnancy?
no unplanned pregnancies
good glycaemic control for 12 weeks at least before conception
good control during pregnancy - careful to avoid hypos
folic acid for 12weeks prior and up until 12 weeks fetal age
ne[hropathy and retinopathy screening
What are the key finding on fundoscopy in diabetic retinopathy??
micoaneurysms haemorrhages hard exudates neovascularisation cotton wool spots
What are hard exudates seen in fundoscopy?
lipoprotein infiltrates due to leakage from blood vessels
What are cotton wool spots seen in fundoscopy?
build up of axonal debris due to poor aconal metabolism
What causes diabetic retinopathy?
microvascular occlusion leading to retinal ischaemia
What are the stages of diabetic retinopathy?
background
pre-proliferative
proliferative
What are the changes seen in background diabetic retinopathy on fundoscopy?
hard exudates
microaneuyrsms
haemorrhages
What are the changes seen in pre-proliferative diabetic retinopathy on fundoscopy?
cotton wool spots
haemorrhage
venous bleeding
What are the changes seen in proliferative diabetic retinopathy on fundoscopy?
neovascularisation
How can diabetic retinopathy be prevented?
good glycaemic control
blood pressure control
lipid control
smoking cessation
State Wagner’s grading of diabetic foot ulcers
Grade 1: Superficial diabetic ulcer
Grade 2: Involves ligament, tendon, joint capsule or fascia, No abscess or osteomyelitis
Grade 3: Deep ulcer with abscess or osteomyelitis
Grade 4: Gangrene to portion of forefoot
Grade 5: Extensive gangrene of foot
What are the causes of primary hypothyroidism?
hashimoto's iodine deficiency primary atrophic hypothyroidism drug induced iatrogenic - radiotherapy or surgery
What drugs can cause hypothyroidism
carbimazole
amiodarone
lithium
iodine
What are the causes of secondary hypothyroidism?
hypopituitarism
hypothalmic disorders
State some key examination findings in hypothyroidism
delayed relaxation of reflexes
hair loss
congestive heart failure
carpal tunnel syndrome
What problems can hypothyroidism cause in pregnancy
eclampsia anaemia premature birth low birth weight still birth post partum haemorrhage
How should a patient with hypothyroidism be investigated?
Bedside: ECG
Bloods: TSH, FT4, FBC, HbA1c (assoc T1DM), serum lipids, TPO Ab
Imaging: USS neck if goitre
What test results indicate primary hypothyroidism?
TSH >10mU/l
low FT4
What test results indicate subclinical hypothyroidism?
raised TSH
normal FT4
What test results indicate secondary hypothyroidism?
low/normal TSH
low FT4
When can TFT results be misleading?
pregancy after tx for hyperthyroidism after starting levothyroxine poor compliance with levothyroxine drugs - dopamine, glucocorticoids, amiodarone
What is the differential diagnosis in hypothyroidism?
sick euthyroid diabetes coeliac hypopituitarism anaemia chronic liver disease fibromyaligia dementia
What do patients on carbimazole need to be checked for
Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat.
A white blood cell count should be performed if there is any clinical evidence of infection.
Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.
What is a key side effect of carbimazole
agranulocytosis
bone marrow supression
What is a common side of effect of carbimazole?
How can this be treated?
rash/pruritis
antihistamines
do not need to stop treatment
Can carbimazole be used during pregnancy?
yes at lowest possible dose that prevents hyperthyroidism
What monitoring is carried out in carbimazole therapy?
before: FBC, LFT
at first: TFTs every 4-6wks until stable
During: TFTs every 3m,
What is the cut off for a normal urine ACR in diabetes?
> 3 = microalbuminuria
Describe the actions of PTH
increased bone resorption
increased calcium reabsorption in kidneys
increased hydroxylation of vitamin D
leads to increased Ca2+ and lowphosphate
What can cause hypocalcaemia
hypoparathyroidism - surgical - autoimmune Decreased vitamin D - liver or kidney failure - reduced intake - lack of sunlight Phosphate retention - kidney disease Ca2+ deficiency - pancreatitis - rhabdomyolysis
What are the features of hypocalcaemia
tetany Chvostek's sign Trosseau's sign seizures perioral paresthesia
What are the features of hypocalcaemia on ECG
prolonged QT interval
What is Chvostek’s sign
tap on parotid - facial nerve
facial muscles twitch
+ve in hypocalcaemia
What is Trosseau’s sign
brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
carpal spasm - wrist flexion and fingers drawn together
+ve in hypocalcaemia
What are the key investigations in hypocalcaemia
Bedside: ECG
Bloods: Ca2+, phosphate, PTH, vit D, Mg2+
Describe the treatment of hypocalcaemia
emergency = intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
ECG monitoring
mild - oral calcium
chronic kidney disease - alfacalcidol
What can cause hypercalcaemia
primary hyperparathyroidism
malignancy
sarcoidosis vit D toxicity thiazides lithium Paget's disease + immobility thyrotoxicosis
Which cancers are most likely to cause hypercalcaemia due to bone metastasis
lung
breast
myeloma
Which cancers release PTHrP?
squamous lung cancer
gynae
GU
What are the symptoms of hypercalcaemia
bone pain constipation, N+V, calcium oxalate kidney stones dehydration slow/absent reflexes muscle weakness confusion, hallucinosis, coma
What are the signs of hypercalcaemia on ECG
bradycardia
short QT interval
What investigations should be carried out in hypercalcaemia
Bedside: ECG
Bloods: FBC, U+E (cancer), PTH, vit D, albumin, phosphate, alkaline phosphatase, LFTs
Imaging: CXR
What are the characteristic investigation findings in hypercalcaemia produced by malignancy
low PTH
raised alkaline phosphotase
Describe the treatment of hypercalcaemia
IV fluids - 0.9% sodium chloride
bisphosphonates eg
underlying cause
steroids if sarcoidosis
State the HPA axis for cortisol
CRH from hypothalamus
ACTH from anterior pituitary
cortisol from zona fasciculata of cortex of adrenal glands
What are the effects of cortisol?
rasied blood glucose
- gluconeogenesis
- lipolysis
- proteolysis
increased sensitivity to peripheral adrenaline
decreased inflammatroy response (T lymph)
What are the causes of cushing’s syndrome
ACTH dependent
- pituitary adenoma - increased ACTH
- ectopic ACTH - small cell lung, carcinoid
ACTH independent
- exogenous steroids
- adrenal adenoma
- adrenal carcinoma
What are the symptoms of Cushing’s disease
increased weight depression/psychosis proximal weakness amennorhea ED acne lots of infections
What are the signs of Cushing’s disease
central obbesity proximal wastage abdominal striae high blood pressure Moon face Supraclavicular fat pad easy bruising high BP high glucose
What investigations should be carried out in suspected Cushing’s disease
Bedside - 24hr urine cortisol
Bloods - 9am and midnight cortisol, plasma ACTH, FBC, U+E, glucose
Micro
Imaging: CAP CT if ectopic is suspected
Special Tests: 1mg overnight dexamethasone suppression test, high dose dexamethasone supression test, CRH test
Describe the low dose dexamethasone suppression test and the expected results
dexamethasone should suppress ACTH secretion
healthy patient: cortisol is supressed
Cushing’s syndrome: no change in cortisol levels
What can cause a false positive raised cortisol level?
pregnancy, anorexia, exercise, psychoses, alcohol and alcohol withdrawal. Strenuous exercise and illness raise cortisol secretion.
Describe the treatment of Cushing’s disease
pituitary adenoma - transspenoidal removal, radiotherapy
adrenal adenoma - adrenectomy, radiotherapy
ectopic - removal if possible!
What kind of acid/base problem does Cushing’s cause?
hypokalaemic metabolic alkalosis
Why does Cushing’s cause a hypokalaemic metabolic alkalosis
cortisol cross reacts with mineralocrticoids - aldosterone
leads to increased K+ excretion, increased sodium retention and increased H+ excretion
Describe the high dose dexamethasone suppression test and the expected results
should decrease ACTH and therefore cortisol levels
healthy: cortisol supressed
pituitary adenoma - supressed cortisol
ectopic - cortisol stays same
What is a phaeochromocytoma?
tumour of chromaffin cells of adrenal medulla
secretes catecholamines - adrenaline and noradrenaline
What is the 10% rule in phaeochromocytoma
10% familial
10% bilateral
10% malignant
10% extrarenal
What is an extrarenal phaeochromocytoma called?
paraganglionoma
What are the signs and symptoms of phaeochromocytoma?
EPISODIC palpitations anxiety sweating high HR
high BP
What investigation is crucial in phaeochromocytoma?
24hr urine metanephrines and VMA
plasma metanephrines
What is the treatment for phaeochromocytoma
presurgery:
alpha blockade - phenoxybenzylamine
beta blockade - propanolol
adrenalectomy
What are the causes of adrenal failure?
primary
Addison’s disease, TB, metastatic carcinoma
secondary
acute steroid withdrawal
physical stress whilst taking steroids
What are the symptoms and signs of Addison’s disease
fatigue weakness pigmentation weight loss reduced appetite N+V postural hypotension
Why does hyperpigmentation occur in Addison’s
increase in POMC in order to raise ACTH
also leads to raised melanocyte stimulating hormone
What investigations are important to do in suspected addison’s/
ECG, urinalysis
FBC, U+E, ABG, glucose, cortisol and ACTH levels
Synacthen test
What are the common investigation findings in addison’s
low sodium, high potassium, low blood pressure, metabolic acidosis
Why does metabolic acidosis occur in Addison’s
impaired H+ excretion due to laco of stimulation of H+ ATPase
What are the actions of aldosterone in the kidney
stimulate Na+/K+ATPase and H+ATPase in DCT
leads to increased sodium, decreased potassium and decreased H+
What are some truggers of an Addisonian crisis
infection
trauma
stopping steroids
surgery
What are teh expected results of the synacthen test in Addison’s
in teh test they give ACTH
normally expect to see rise in cortisol
in Addison’s there is little/no rise
What is the treatment for Addison’s disease (non-acute)
hydrocrotisone and fludrocortisone for life
What is the treatment for an Addisonian crisis
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable.
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
How should an intercurrent illness be managed in Addison’s
double hydrocortisone dose
What is the pathophysiology of Hashimoto’s
anti TPO Ab
lymphocytic and plasma cell infiltration
What are the symptoms of hypothyroidism
lethargy low mood cold intolerance weight gain constipation mennhoraggia myalgia cramps weakness
What are the diseases associated with hypothyroidism
diabetes
pernicious anaemia
Addison’s
Is there a goitre present in primary atrophic hypothyroidism or Hashimoto’s thyroiditis? Why?
PAH - no goitre due to diffuse lymphocytic infiltration and atrophy
HT - goitre due to lymphocytic and plasma cell infiltration
What are the causes of hyperthyroidism?
primary:
Graves
toxic mulitnodular goitre
toxic adenoma
post partum thyroiditis
levothyroxine excess
de Quervian’s
amiodarone
Describe the pathophysiology of Graves
IgG autoantibodies bind to TSH receptors, stimulating thyroid, stimulating thyroxine release and thyroid growth
Why is there eye disease in Grave’s
the autoantibodies react with the orbital autoantigens, leading to inflammation and swelling of orbital contents
What is de Querviann’s
post viral self limiting subacute thyroiditis causing hyperthyroidism
What are the symptoms of hyperthyroidism
irritability anxiety sweating palpitations weight loss increased appetite difficulty sleeping diarrhoea heat intolerance
What signs are seen in Grave’s disease but not other causes of hyperthyroidism
exophthalmos,
ophthalmoplegia
pretibial myxoedema
thyroid acropachy
What is thyroid acropachy
clubbing, painful finger and toe swelling, periosteal reaction in limbs
What is pretibial myxoedema
oedematous swellings above lateral malleolus)
What are the signs of hyperthyroidism
warm moist skin palmar erythema fine tremor fast pulse AF thin hair goitre thyroid nodules
What investigations should be carried out in hyperthyroidism
ECG
FBC, U+E, ESR, CRP, TFTs, thyroid autoantibodies
isotope scan (toxic multinodular/subacute)
visual fields and acuity
What is the treatment for hyperthyroidism
- carbimazole.
propanolol for control of symptoms - radioiodine treatment
- thyroidectomy
What is block-replace treatment of hyperthyroidism
give carbimazole and levothyroxine at same time. reduces risk of iatrogenic hypothyroidism
what are the risks of thyroidectomy
recurrent laryngeal nerve palsy - hoarse voice
hypoparathyroidim
hypothyroidism
Describe the titration method of treating hyperthyroidism
15–40 mg daily continue until the patient becomes euthyroid, usually after 4 to 8 weeks,
then reduced gradually to 5–15 mg daily
therapy usually given for 12 to 18 months.
What is a thyroid storm
hyperthyroid crisis with Fever, anxiety, agitation, confusion and tachycardia, and occasionally heart failure
What are the causes of hyperlipidaemia
primary:
common primary hyperlipidaemia
familial combined hyperlopidaemia
familial hypercholesterolaemia
secondary
due to diabetes, Cushing’s, hypothyroidism, CKD, chornic liver disease, steroids
What is the function of LDLs
transport cholesterol from liver/bowels to tissue
What is the function of chylomicrons
transport lipids form gut to liver after a meal
what is the function of VLDLs
transport lipids from liver to tissues
what is the function of HDLs
transport lipids from tissues to liver
How is cholesterol excreted from the body
bile salts
What are the blood lipid levels in familial hypercholesterolaemia
raised LDLs
What are the blood lipid levels in familial combined hyperlipidaemia
rasied LDLs and VLDLs
low HDLs
What are the blood lipid levels in common primary hypercholesterolaemia
raised LDLs
What are the blood lipid levels in secondary hyperlipidaemia
rasied LDLs
What are the signs of hyperlidiaemia
tendon xanthoma
xanthelasma
corneal arcus
Who is at greater risk of hyperlipidaemia
FH
corneal arcus <50y
xanthoma
xanthelasma
Who should you screen for hyperlipidaemia knowing they will be at increased risk of CVD
known CVD smoking diabetes CKD FH CVD <65y HTN obesity
Who should primary prevention of CVD with hyperlipidaemia be offered to?
those with a QRISK score >10% 10yr risk
those with diabetes (>40y, had for >10y, nephropathy, otehr CVD risk factors)
those with CKD
What drug is used for the primary prevention of CKD in hyperlipidaemia
20mg atrovastatin OD at night
Who should secondary prevention of CVD with hyperlipidaemia be offered to?
those with pre-existing IHD, PVD or cerbrovascular disease
What drug is used for the secondary prevention of CKD in hyperlipidaemia
80mg atorvastatin OD at night
What is the mechanism of action of statins
inhibition of HMG-CoA reductase, leading to decreased synthesis of cholesterol from HMG-CoA
leads to increased LDL receptor synthesis in liver
leads to increased LDL uptake, therefore less LDLs in blood
How should you follow up a newly prescribed statin
3 months later
full lipid profile
if the non HDl cholesterol has not decreased by >40%, increase the dose!
What are some lifestyle interventions used in hyperlidiaemia
cardioprotective diet
exercise
stop smoking
weight loss
Describe the characteristic blood results of primary hyperparathyroidism
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Describe the characteristic blood results of secondary hyperparathyroidism
low vit D
raised PTH
low calcium
raised phosphate
Describe the characteristic blood results of tertiary hyperparathyroidism
Ca2+ (Normal or high) PTH (Elevated) Phosphate levels (Decreased or Normal) Vitamin D (Normal or decreased) Alkaline phosphatase (Elevated)
State the pathophysiology of secondary hyperparathyroidism
background of chronic renal failure
vitamin D not able to be hydroxylated
low Ca2+
PTH stimulated to be released
Describe the characteristic blood results of primary hypoparathyroidism
low calcium, high phosphate
low PTH
What is the treatment of hypoparathyroidism
alfacalcidol
What are the causes of primary hypoparathyroidism
removal in thyroid surgery
DEscribe the pathophysiology of Paget’s disease
increased bone turnover
increased numbers of osteoblasts and osteoclasts
remodelling of bone, bone enlargement and deformity
What are the signs and symptoms of Paget’s disease
asymptomatic!
deep boring pain
bony deformity and enlargement
What are the most common sites for Paget’s to occur?
lumbar spine skull pelvis femur tibia
What are the complications of Paget’s disease
pathological fractures
OA
hypercalcaemia
nerve compression due to bony overgrowth
What are the signs of Paget’s disease on xray
localized bone enlargement
patchy cortical thickening
sclerosis, osteolysis and deformity
What are the typical blood test results in Paget’s disease
normal calcium and phosphate
ALP rasied
What is the treatment of Paget’s disease
analgesia
bisphosphonates eg alendronic acid
What is the bisphosphonates mechanism of action
adsorbed onto hydroxyapatite crystals in bone, slowing both their rate of growth and dissolution, and therefore reducing the rate of bone turnover.
DEscribe the pathophysiology of osteoporosis
low bone mass and structural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.
Why does osteoporosis occur in old age?
bone breakdown by osteoclasts increases and is not balanced by new bone formation by osteoblasts
Describe how bone mass changes with age
reached in the third decade and starts to decline in the fifth decade for men and women.
In women, this decline accelerates after the menopause for a period of between 5 and 10 years.
What are the risk factors for secondary osteoporosis
steroid use hyperthyroidism, hyperparathyroidism Alcohol and tobacco Thin <22 Testosterone low Early menopause Renal or liver failure Erosive/inflam bone disease Dietary calcium low
What are some causes of fragility fracture
osteoporosis Paget;s disease bone metastasis multiple myeloma osteomalacia
How should suspected osteoporosis be investigated?
calcium, phosphate, PTH, alk phos
calculate FRAX or QFracture score
What is the next step in management depending on the results of the FRAX score calculation
low risk - reassure
intermediate risk - do DEXA scan
high risk - start bisphosphonates
How is hte DEXA scan calculated
bone mineral density is compared to that of a young healthy adult
T score = number of standard deviations away from youthul average
What would the results of the DEXA scan be in osteoporosis
T score -2.5 or worse
What is the lifestyle advice for management of osteoporosis
stop smoking stop alcohol weight bearing exercise balance exercise - reduced risk of falls home-based fall prevention programme
How should a bisphosphonate be taken?
with whole glass of water
whilst upright - stay for 30mins
wait 30mins before eating or taking other drugs
What are the side effects of bisphosphonates
photosensetivity
GI upset
oesophageal ulcers
How long should bisphosphonates be taken for?
no evidence for further benefit on taking for more than 3YRS
What rare but important problems should patients be asked to look out for when taking bisphosphonates
osteonecrosis of jaw
osteonecrosis of external auditroy canal - ear pain, discharge from ear or an ear infection
oesophageal reactions
Which drugs are used in the treatment of osteoporosis
first line: alendronic acid
second line: risedronate or etidronate
vitamin D and calcium if deficient
What is osteomalacia
normal amount of bone, but loss of mineral content
excess uncalcified osteoid and cartilage
What is the difference between rickets and osteomalacia
both are the lack of mineral content in bone
rickets occurs during the process of bone growth
osteomalacia occurs after epiphyses have fused
What are the signs and symptoms of rickets
growth retardation
bow legs
hypotnonia
unwell!
What are the signs and symptoms of osteomalacia
bone pain and tenderness
fractures
proximal myopathy
What are the causes of osteomalcia
vitamin D deficinecy
renal osteodystrophy - lack of hydroxylation vit D
liver disease
What are the investigations carried out in osteomalacia
Calcium, PTH, phosphate, vit D, ALP
xray
bone biopsy
What are the typical xray findings in ostemalacia
loss of cortical bone
Looser’s zones = translucent bands
ragged Metaphyseal surfaces in ricket’s
What is the treatment for osteomalacia
dietary deficiency = vitamin D!
malabsorption or liver = vitamin D2
renal disease = alfacalcidol (1alpha hydroxylated vitamin D) or calcitriol (1,25-hydrocyvitamin d3)
State the metabolism of vitamin D
7-dehydrocholesterol made from production of cholesterol
converted to cholecalciferol (D3) in skin
hydroxylated in liver to 25-hydrocyvitamin d3
hydroxylated in kidney to 1,25-hydrocyvitamin d3
What are they typical blood results in osteomalacia
low serum calcium,
low serum phosphate,
raised ALP
raised PTH
What information shold be given to patients when prescribing metformin
take at the same time each day with a meal or snack
can cause GI upset but usually subsides within a few days
do not drink alcohol - increased risk of lactic acidosis
Let a doctor know straightaway if you are being sick or feel very unwell, or if you become unusually tired, or if you feel short of breath and your breathing becomes faster than normal. - lactic acidosis
Why is carbimazole not prescribed if a patient has severe liver impairment
metabolised in liver
Why is carbimazole not prescribed if a patient has had a sever blood disorder
risk fo agrannulocytosis adn bone marrow supression
What affect does carbimazole have on warfarin
carbimazole enhances the anticoagulant effect of warfarin because it is also a vit K antagonist
What is acromegaly due to?
anterior pituitary adenoma leading to increased GH release (can also be due to ectopic)
stimulates increased IGF-1 secretion which leads to hone and soft tissue growth
When can GH be raised
pregnancy
puberty
stress
sleep
what are the symptoms of acromegaly
paresthesia of the extremeties shoes adn rings no longer fitting back ache joint pain heacache, vidual pribs decreased libido amernorrhoea
What are the signs of acromegaly
spade hands large feet broad nose coarse facial features macroglossia sweaty skin acanthosis nigracans
What are the complications of acromegaly
impaired glucose tolerance HTN cardiomyopathy CVD increased risk colon cancer
What is the diagnostic test for acromegaly?
What are the expected results?
oral glucose tolerance test
check GH at intervals after glucose intake
normally, GH would be supressed by hyperglycaemia
in acromegaly, GH remains raised in hyperglycaemia
What investigations should be done in acromegaly
ECG, visual fileds and acuity
glucose, calcium, phosphate
MRI head - look for pituitary lesion
OGTT
what is teh treatmetn of acromegaly
- transphenoidal removal
- somatostatin analogues eg octreotide
- GH receptor antagonist - pegvisomant
