Endocrine and Metabolic Flashcards
Cushing’s syndrome
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Syndrome associated with chronic inappropriate elevations of free circulating cortisol
ACTH dependent
- Excess ACTH from pituitary adenoma (Cushing’s disease)
- Ectopic ACTH (small cell lung cancer)
ACTH independent
- Adrenal adenoma
- Adrenal carcinoma
Mostly females 20-40yrs old
RF
- Exogenous corticosteroid use (most common cause overall)
- Pituitary or adrenal adenoma
- Adrenal carcinoma
excess alcohol consumption can mimic cushings
CLINICAL FEATURES
- Thin, easily bruisable skin with ecchymoses
- Stretch marks (striae)
- Proximal myopathy (muscle weakness)
- Central adiposity
- Fatigue
- Hirsutism
- Acne
- Hyperpigmentation (if ACTH dependent)
- Lethargy & depression
- Osteopenia & osteoporosis
- Hypertension
- Hyperglycaemia
- Increased susceptibility to infection
KEY FEATURES
- Bruising and thin skin
- Myopathy
- Purple striae >1cm wide
- DM, HTN, osteoporosis at young age
INVESTIGATIONS
1st Low dose (1mg) overnight dexamethasone suppression test
- Morning cortisol >50 nanomol/L
- Patient is given 1 mg of dexamethasone at 11 pm and a plasma cortisol level is measured the following morning at 8am
- Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed, will still be raised
High dose dexamethasone suppression test: to disinguish between cushings disease and ectopic ACTH production.
Excess ACTH production from pituitary is inhibited by high dexamethasone dose however autonomous cortisol production from adrenals won’t be inhibited
so if Cushings Disease then ACTH will be supressed, if its is an ectopic ACTH then it wont be supressed
24 hour urinary free cortisol or late night salivary cortisol: elevated in cushings
Other:
Pregnancy Test
Bloods:
- hyperglycaemia (cushings leads to glucose intolerance and diabetes)
- hypokalaemia : usually K+ is very low in Ectopic ACTH production due to small cell lung cancer
- hypernatraemia
- metabolic alkalosis (due to increased H+ excretion and bicarbonate reabsorption)
MANAGEMENT
Drug induced Cushings: stop steroids or lower dose
Metyrapone or ketoconazole (inhibits cortisol synthesis)
osilodrostat, ketoconazole, levoketoconazole, metyrapone (pituitary or adrenal)
- Transsphenoidal pituitary adenomectomy (if pituitary tumour)
IF HAD TPA MUST BE ON HYDROCORTISONE X3 - Adrenalectomy (if adrenal adenoma or carcinoma)
IF HAD ADRENALECTOMY must be on: hydrocortisone x3 per day and fludrocortisone X1
PROGNOSIS
Untreated disease has a poor survival rate of 50% at 5 years. Patients may have decreased quality of life after treatment
COMPLICATIONS
- diabetes
- osteoporosis
- hypertension
- pre-disposition to infections
Addisons Disease
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Primary adrenal insufficiency → decreased production of adrenocortical hormones (reduced cortisol and aldosterone)
Main causes:
- Autoimmune (more developed countries)
- Tuberculosis (more common worldwide)
- May be caused by metastases
Other causes:
- Meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- HIV
- Antiphospholipid syndrome
Risk Factors:
- Female
- Presence of adrenocortical autoantibodies
- Adrenal haemorrhage
- Anticoagulant use
Addisonian crisis: A sudden worsening of symptoms and drop in cortisol levels
- Sudden withdrawal of steroids if patient on long-term steroid medication
- sepsis
- surgery
CLINICAL FEATURES
- Fatigue
- Abdominal pain
- Weight loss
- Hyperpigmentation: -ve feedback causes increased ACTH leading to increased POMC, leading to increased α-MSH
- Nausea and vomiting
- Hypotension
- Hypoglycaemia → may cause dizziness and falls
Addisonian Crisis: Severe hypovolaemia and hyponatraemia
INVESTIGATIONS
ACTH stimulation test (short synacthen test): synacthen should stimulate adrenal glands to secrete cortisol but will not happen in Addisons
Morning serum cortisol: do if first test is unavailable aka in GP. Take blood between 8-9am when cortisol peaks, if its low suspect addisons
Plasma ACTH (take at same time)
Bloods:
- seum electrolytes : check for hyponatraemia and hyperkalaemia (caused for aldosterone deficiency)
- ABG: metabolic acidosis with normal anion gap
- FBC: anaemia
- Glucose- hypoglycaemia
MANAGEMENT
Hydrocortisone given in 2 or 3 divided doses (glucocorticoid) + fludrocortisone (mineralocorticoid)
If patient is having an illness: hydrocortisone dose should be doubled but fludrocortisone stays same
Addisonian crisis:
- IV hydrocortisone sodium succinate
- Fluid resus- saline (saline with 5% dextrose is good to ensure dont worsen low sodium by doing too much with glucose dose)
- Glucose (if hypoglycaemia)
Phaemochromocytoma (NOT NEEDED)
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Tumour of adrenal medulla- irregular secretion of adrenaline and noradrenline
- hypertension (around 90% of cases, may be sustained)
- headaches
- palpitations
- sweating
- anxiety
24 hour urinary collection of metanephrines
Surgery but need medical management before
- Alpha blocker e.g. phenoxybenzamine
- Beta blocker e.g. propranolol
Alpha blocker before beta
Primary Hyperaldosteronism (NOT NEEDED)
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
- hypertension
- hypokalaemia → muscle weakness
- metabolic alkalosis
- Bilateral idiopathic adrenal hyperplasia- most common
- Adrenal adenoma (Conn’s syndrome)- 2nd most common
- Unilateral hyperplasia
- Familial hyperaldosteronism
- Adrenal carcinoma
1st Plasma aldosterone/renin ratio → high in this disease
High res CT abdo to differentiate between unilateral adenoma and bilateral hyperplasia
- If CT normal- Adrenal venous sampling (AVS) to distinguish between them
If renin is higher aka low aldosterone/renin ratio- Think renal artery stenosis
MANAGEMENT
adrenal adenoma: laparoscopic adrenalectomy
bilateral adrenocortical hyperplasia: aldosterone antagonist- spirinolactone
Diabetes Insipidus
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Condition in which kidneys are unable to concentrate urine due to inadequate secretion or sensitivity to ADH, resulting in the production of large quantities of dilute urine
ADH increases water reabsorption into blood in collecting duct via V2 receptors- so lack of sensitivity or low secretion results in lots of peeing
Two types:
1) Central/cranial: INSUFFICIENT/deficiency levels of ADH from posterior pituitary
- pituitary tumour/surgery
- traumatic brain injury
- infection (meningitis)
- sarcoidosis
- TB
- SAH
- hereditary haemochromatosis
2) Nephrogenic: resistance as defective ADH receptors in the distal tubules and collecting ducts
- lithium therapy
- inherited (AVP2 gene)
- electrolyte imbalances (hypercalcaemia or hypokalaemia)
- idiopathic
CLINICAL FEATURES
- Polyuria → with very dilute urine
- Nocturia → restless sleep, daytime sleepiness
- Polydipsia → excessive thirst
- Dehydration:
- tachycardia
- reduced tissue turgor
- dry mucous membranes
INVESTIGATIONS
Urine osmolality:
- Low urine osmolality
- High serum osmolality
To confirm do water deprivation test:
- if osmolality corrects itself: psychogenic polydipsia
- if osmolality doesnt correct itself: After 8 hours administer desmopressin
- Urine osmolality will rise in CDI
- Urine osmolality will remain low in NDI
Hypertonic saline stim test with copeptin measurement
baseline copeptin level >21.4 picomol/L is diagnostic of nephrogenic DI; after given hypertonic saline copeptin level >4.9 picomol/L differentiates central DI from primary polydipsia
MRI to look for brain/pituitary tumour
Urine Dip- exclude diaetes mellitus as a cause of polyuria
24 hour urine collection
Bloods:
Hypernatraemia: if sodium is low then psychogenic polydipsia
Hypokalaemia: on ECG will show as T wave inversion,QT prolongation, U waves. Associated with nephrogenic
Hypercalcaemia: nephrogenic
Normal blood glucose
TREATMENT
Hypernatramia correction: Oral of IV fluids to prevent dehydration. If correct too fast the predisposes to cerebral oedema
Central DI: Intranasal desmopressin
Nephrogenic DI: Discontinue cause if its a medication like lithium, thiazide diuretics (hydrochlorothiazide), sodium restriction
COMPLICATIONS
- hypernatraemia
- iatrogenic hyponatraemia (side effect of desmopressin)
What drug should not be given with thiazide diuretics and what symptoms occur
Digoxin
arrythmias, N+V, lethargy, anorexia, yellow-green vision, confusion, generally unwell
Diabetes Mellitus type 1
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
autoimmune response that triggers the destruction of insulin-producing beta cells in the pancreas leading to an absolute insulin deficiency (⇒ lipolysis and ketogenesis)
Usually in childhood, associated with HLA DR3/4 gene and see autoimmune diseases in FHx
CLINICAL FEATURES
- Polyuria
- Polydipsia
- Unexplained weight loss
- Fatigue
- Increased susceptibility to infection
- blurred vision, N&V, abdo pain, dehydrated, tachy
May get gastroparesis : bloating, voiting and erratic blood glucose control due to neuropathy of the vagus nerve
FEATURES SPECIFIC TO TYPE 1
DKA is 1st manifestation in 1/3 of cases
- Nausea and vomiting
- Abdo pain
- Kussmaul breathing → deep, rapid breathing
- Sweet smelling breath
INVESTIGATIONS:
Blood glucose: Fasting plasma glucose, random non-fasting plasma glucose, HbA1c, 2 hour OGTT
1) Finger prick
2) one-off blood glucose (fasting or non-fasting)
In diabetic this is 11.1mmol/L or over
If fasting:
Normal: below 5.5, prediabetes/impaired 5.6-6.9, diabetic 7 or over
3) HbA1c (average blood glucose over last 2-3 months)
Normal: Below 42 mmol/mol (Below 6.0%)
Prediabetes: 42 to 47 mmol/mol (6.0% to 6.4%)
Diabetes: 48 mmol/mol or over (6.5% or over)
- Sickle cell, G6PD deficiency, hereditary spherocytosis can all cause lower than expected because of reduced RBC lifespan.
4) 2 hour OGTT Oral glucose tolerance test: 75g glucose and measure after 2 hours
Normal= below 7.8, impared glucose tolerance/prediabetes is 7.8 to 11 (if also had impaired fasting glucose), diabetes is over 11
Diagnostic for symptomatic patients: Fasting glucose ≥7 mmol/L OR random glucose ≥11.1 mmol/L
Diagnostic for asymptomatic= same but repeat on two different days
C Peptide: decreased in Type 1
Urine Dip: Glucosuria, Ketone bodies (secific to type 1), Microalbuminuria (signs of nephropathy)
Anti-GAD antibodies, Islet cell antibodies (IA2 and IA2-beta), and the zinc transporter ZnT8. (specific to type 1)
MANAGEMENT
Basal-bolus insulin which is a combo of:
- Long acting (e.g. insulin glargine, detemir, degludec subcutaneous injection OD)
- Short acting (e.g. insulin lispro or aspart, glulisine before meals)
Usually when first diagnosed: basal bolus using insulin detemir twice daily, bolus using any of the short acting
Consider Metformin in patients with BMI over 25
COMPLICATIONS
- Microvascular
- Retinopathy
- Neuropathy (foot ulcers)
- Nephropathy
- Macrovascular
- MI/stroke/PVD
- Metabolic
- DKA
- HHS
- Hypoglycaemia
- eating disorders and depression
COMPLICATIONS OF TYPE 1
- DKA
- hypoglycaemia
- retinopathy
- diabetic kidney disease
- neuropathy (peripheral or autonomic)
- CVD
Diabetes Mellitus type 2
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
insulin resistance (decreased insulin sensitivity) and relative insulin deficiency (insulin production reduces over time)
Strong genetic component and association with obesity and a sedentary lifestyle
RF:
- Obesity
- Hypertension
- South Asian/Afro-Caribbean ethnicity
- Old age
- FHx
- Dyslipidaemia
- CVD
- Polycystic ovary syndrome
MODY (maturity onset diabetes of the young). MODY limits the body’s ability to produce insulin, is Autosomal dominant inheritance, usually a FHx of early onset diabetes.
Treatment for HNF1A MODY: Sulfonylureas e.g. gliclazide
CLINICAL FEATURES
- Polyuria
- Polydipsia
- Unexplained weight loss
- Fatigue
- Increased susceptibility to infection
May get gastroparesis : bloating, voiting and erratic blood glucose control due to neuropathy of the vagus nerve
FEATURES SPECIFIC TO TYPE2
- Many patients are asymptomatic
- Some may present with HHS (hyperosmolar hyperglycaemic state)- blood glucose very high >40mmol and severe dehydration and confusion
- Acanthosis nigricans (hyperpigmentation)
- UTI, candidal infection, skin infections, fatigue, blurred vision
INVESTIGATIONS:
Blood glucose: Fasting plasma glucose, random non-fasting plasma glucose, HbA1c, 2 hour OGTT
Finger prick
one-off blood glucose (fasting or non-fasting)
In diabetic this is 11.1mmol/L or over
If fasting:
Normal: below 5.5, prediabetes/impaired 5.6-6.9, diabetic 7 or over
HbA1c (average blood glucose over last 2-3 months)
Normal: Below 42 mmol/mol (Below 6.0%)
Prediabetes: 42 to 47 mmol/mol (6.0% to 6.4%)
Diabetes: 48 mmol/mol or over (6.5% or over)
- Sickle cell, G6PD deficiency, hereditary spherocytosis can all cause lower than expected because of reduced RBC lifespan.
Oral glucose tolerance test: 75g glucose and measure after 2 hours
Normal= below 7.8, impared glucose tolerance/prediabetes is 7.8 to 11 (if also had impaired fasting glucose), diabetes is over 11
Diagnostic for symptomatic patients: Fasting glucose ≥7 mmol/L OR random glucose ≥11.1 mmol/L
Diagnostic for asymptomatic= same but repeat on two different days
C Peptide: increased in Type 2
Urine Dip: Glucosuria, NO Ketone bodies, Microalbuminuria (signs of nephropathy)
TREATMENT
Lifestyle: diet, exercise, education with a HbA1c target
TARGETS: 48mmol/L if managed with lifestyle or one diabetic drug (step 1)
53mmol/L if on two or more diabeteic drugs or on a drug that can cause hypoglucaemia like sulfonylureas
Consider : BP, lipids, antiplatelets, add on therapies if have CKD
If QRISK over 10% also start atorvastatin 20mg oral, if have CVD/IHD/PAD then 80mg
If QRISK (for CVD) changed at any time to over 10% then add SGLT2 inhibitor
If have CVD/IHD/PAD also give antiplatelet- aspirin 75mg
BP management
- Step 1: ACEi or ARB (ARB preferred for black African patients)
- Step 2: Add CCB e.g. amlodipine or thiazide-like diuretic (TLD) e.g. indapamide
- Step 3: ACEi + CCB + TLD
- Step 4: Check K+ and if it’s <4.5 add spironolactone and if >4.5 add beta blocker
CKD- give ACEi, if already taking ACEi give SGLT2 + angiotensin 2 receptor antagonist, if already taking. If CKD stage 3/4 then finerenone
Glycaemic control:
Step 1: Metrofmin if HbA1c still over 48 despite lifestyle advice. If their eGFR is under 30 may cause accumulation due to renal impairment so can get lactic acidosis.
If high risk of CVD, established CVD or CHF then add SGLT-2
If metformin isnt tolerated due to GI issues try modified release before second line
If metformin contraindicated then move onto second line
Step 2 if HbA1c or not tolerating metformin add another drug:
- DPP4i’s (gliptins)
- Sulfonylureas (gliclazide + glimepiride)
- SGLT-2i’s (flozins)- use if CVD/heart failure risk
- Pioglitazone
Step 3: add another drug or try basal insulin, will need a Glucagon kit for treating hypoglycaemias
If triple therapy not effective switch one of the drugs for a GLP-1 mimetic if BMI over 35 or insulin would impact work
If admitted to hospital for ACS: stop meds and start IV dose adjusted insulin infusion with glucose monitoring
COMPLICATIONS
- diabetic kidney disease
- impaired vision
- amputation
- stroke
- infection
- CHF
- Obstructive Sleep apnoea
Drugs used in Diabetes, mode of action, side effect and what patients theyre contraindicated in
Metformin: increases insulin sensitivity and reduces hepatic gluconeogenesis.
SE: GI issues- Nausea or diarrhoea, weight NEUTRAL, lactic acidosis (therefore if have vomiting or diarrhoea, dehydrated, sepsis, CT with contrast, renal or heart failure, if the patient is frail or elderly must STOP
Sulfonylureas (gliclazide): stimulating the release of insulin from beta cells pancreas (act on ATP sensitive K+ channels). best 2nd choice in non obese
SE: if too much insulin secreted = hypoglycaemia, weight gain.
Dont give to severe renal impairment (CKD)
Overdose= hyperinsulinamia and hgigh C-peptide
dont give on morning of surgery because hypo
SGLT-2 inhibitors (flozins): inhibits SGLT co transporter 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. Best 2nd for obese patients.
Add SGLT-2 if CVD, high risk of CVD, CHF
SE: weight loss, UTIs, fournier’s gangrene, DKA if used with insulin.
Contraindicated if active foot disease (skin ulceration)
DPP4 inhibitors (gliptins): reduce peripheral breakdown of incretins like GLP-1
SE: weight neutral (may increase satiety so useful in obese patients)
Pioglitazone
Weight gain, Fluid retention (dont give in HF), liver dysfunction, fractures
dont give in bladder cancer
GLP1 agonist (exantide): increase insulin secretion and inhibit glucagon secretion
SE: weight loss
can continue GLP1 and DPP4 on the day of surgery
Diabetes Ketoacidosis
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Acute metabolic complication of diabetes that is potentially fatal and requires prompt medical attention
ONLY TYPE 1 as no insulin to suppress lipolysis leading to ketone formation and acidosis. May be the first presentation of T1DM
RF: infection (increases cortisol which is an antagonist of insulin so body needs more insulin), inadequate insulin therapy (non-compliance), undiagnosed T1DM, MI
T1DM SICK DAY RULE: continue normal insulin dose, check blood glucose more regularly, 3L of fluid over 24 hours, self monitor ketones regularly throughout the day
CLINICAL FEATURES
- Diabetic symptoms: Increased thirst (polydipsia), Polyuria, Weight loss, Tiredness
- Nausea and vomiting
- Severe abdo pain
- Dehydration
- Dry mucous membranes
- Decreased skin turgor
- Slow CRT (cap refill)
- Tachycardic
- Hypotensive
- Hyperventilation/ Kussmal breathing: Decrease in pH stimulates resp centre to try and correct acidosis by blowing off CO2
- Reduced consciousness
- Fruity breath
- Rapid onset- less than 24 hours
INVESTIGATIONS
Venous Blood gas: metabolic acidosis with raised anion gap, partial resp compensation by hyperventilating
Blood ketones: raised
Blood glucose: raised
U+E: low sodium, high potassium as no insulin
FBC- leukocytosis
Alcoholic ketoacidosis: normal or low glucose : give rehydration with IV saline and thiamine to prevent wernickes
MANAGEMENT
Rehydration : IV fluids (isotonic saline 10ml/kg, + potassium chloride repletion IF potassium low)
- Cerebral Oedema can happen if rehydrated too quickly, will get headaches, reduced consciousness, rise in BP, seizures
Reduce Ketones: fixed rate IV insulin 0.1 unit/kg/hr, do after fluids
- if glucose falls below 14mmol/lthen 10% dextrose
- continue long acting insulin but stop short acting insulin
If severe metabolic acidosis: IV bicarbonate
Signs that DKA has not resolved in 24 hours: ph under 7.3 (acidosis), ketones over 0.6mmol/L or 2+ on urine dip, bicarbonate lower than 15
- refer to senior endocrinologist
PROGNOSIS
close monitoring and correction of electrolytes leads to reduction in overall mortality
COMPLICATIONS
hypokalaemia and hypoglycaemia from excessive insulin therapy
Hypophosphataemia : continue with insulin therapy and give IV phosphate replacement therapy
Cerebral Oedema
Cardiac Arrythmias
Diabetic Eye Disease/ Retinopathy
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Two types:
- Non-proliferative (early stage, less severe)
- Proliferative (more advanced)
- Eventually occurs in some degree in all patients with DM
- Most common cause of visual impairment and blindness in patients aged 25-74
Progression:
Background retinopathy → pre-proliferative retinopathy → proliferative retinopathy (maculopathy)
CLINICAL FEATURES
- Asymptomatic until v late stages
- Visual impairment- progression to blindness
- Maculopathy- changes to macula
- Non-proliferative features
- Microaneurysms
- Blot haemorrhages
- Cotton wool spots
- Hard exudates
- Proliferative features
- Non-proliferative features usually present
- Retinal neovascularisation (lots of blood vessels in macula)
- Retinal detachment (see a yellow line)
- Vitreous Haemorrhage (thick haemorrhage)
Retinal detatchment causes sudden painless complete vision loss, starts peripherally and progresses centrally. Get flashers/floaters too
Vitreous haemorrhage : another cause of complete vision loss
- Bleeding into vitreous humour
- Sudden appearance of spots/floaters- blurred vision
- No flashing lights like in retinal detachment
INVESTIGATIONS
Fundoscopy:
Background retinopathy: microaneurysms, blot haemorrhages, hard exudates
Pre-proliferative: background and cotton wool spots
Proliferative: non-proliferative + neovascularisation (vessels on disk)
Maculopathy: hard exudates near macula (centre of the picture (the bright thing is optic disk))
Optical coherence tomography
MANAGEMENT
For all diabetics:
- Improve blood glucose
- Improve BP control
- Improve serum lipid control
- Regular review by ophthalmology
Background retinopathy: improve glycaemic control and observe regularly
Pre-proliferative: Pan-retinal laser photocoagulation
proliferative: Pan-retinal laser photocoagulation and intravitreal VEGF inhibitors
Maculopathy: VEGF inhibitors
PROGNOSIS
chronic, progressive disease. Visual loss may develop despite treatment
COMPLICATIONS
- Cataract
- Macular oedema
- Visual field loss
Diabetes Nephropathy
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
patient with long-standing diabetes (>10 years) with albuminuria and/or reduced estimated glomerular filtration rate (eGFR)
CKD most common cause
20-40% of patients with diabetes mellitus develop
Pathological changes:
- Mesangial expansion
- Glomerular basement membrane thickening
- Glomerulosclerosis
CLINICAL FEATURES
- Hypertension
- Oedema in advancing diabetic nephropathy
- Polyuria
- Lethargy
- Retinopathy (usually develops alongside): blot haemorrhages, microaneurysms, neovascularisation
INVESTIGATIONS
1st urinalysis: increased early morning ACR : urineary albumin of 30 to 300 mg/d or a random urine albumin-tocreatinine ratio (ACR) between 2 and 20 mg/mmol = microalbuminuria
Need urinalysis for urinary ACR annually]
Serum creatinine and eGFR: GFR raised in early disease amd reduced in late disease
Kidney Ultrasound: look for other cuases like stones or cysts or polynephritis
Kidney Biopsy is gold standard;
- Kimmelstiel-Wilson nodules
- Mesangial expansion
- GBM thickening
MANAGEMENT
1) Hypertension: ACEi or ARB ; 2nd line is CCB or thiazide like diuretic
2) Tight glycaemic control
3) Control dyslipidaemia: atorvastatin
4) Lifestyle: Dietary modification: reduce protein and salt intake
5) Lifestyle: Stop smoking
6) Lifestyle: exercise
PROGNOSIS
morbidity and mortality can be avoided or delayed with intensive treatment of hyperglycaemia, hypertension, and dyslipidaemia and with careful attention to diet and avoidance of nephrotoxic agents
COMPLICATIONS
- end stage renal disease
- hyperkalaemia
- cardiovascular events
- PVD
- anaemia
Diabetes Neuropathy
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Peripheral nerve dysfunction and/or autonomic nerve dysfunction in diabetes patients by blockage of vasa nervorum
Chronic hyperglycaemia → glycation of axon proteins → neuropathy
can lead to: Diabetic foot problems and ulceration (leading cause of diabetes related hospital admissions and non-traumatic amputation). Diabetic foot ulcers usually occur over pressure points like plantar surface of metatarsal head and plantar surface of hallux. Painless with normal ABPI, give cushioned shoes to reduce callous formation
RF:
- poorly controlled hyperglycaemia
- older age (>70yrs old)
- prolonged duration of diabetes (>10yrs)
- tall stature
- hypertension
- dyslipidaemia
CLINICAL FEATURES
Peripheral neuropathy:
- Peripheral pain- burning/sticking/aching- often worse at night
- Loss of peripheral sensation- glove and stocking distribution
- Peripheral dyaesthesia- burning sensation in feet
- Reduced/absent ankle reflexes
- Peripheral painless injuries occurring at pressure points
Mononeuropathy:
Sudden motor loss e.g. wrist drop, foot drop, 3rd nerve palsy (down and out eye)
Autonomic symptoms:
- Resting tachycardia
- Urinary frequency/urgency/nocturia/incontinence/hesitancy/weak stream/retention
- Erectile dysfunction
- Constipation
- Difficulty swallowing
- Postural hypotension
- Gastroparesis- give Metoclopramide (pro kinetic that improves gastric emptying)
autonomic NS neuropathy causes Impaired hypoglycaemia awareness
INVESTIGATIONS:
Sensation, use 10g monofilament, can also use tuning fork (decreased vibration sense) and pinprick
Bloods- fasting blood glucose and HbA1c
MANAGEMENT
If painless; optimise glucose control
If painful:
gabapentin or pregabalin and/or duloxetine (also with glucose control)
2nd line add or replace with amytriptyline
COMPLICATIONS
- foot wounds/ulcers (arterial, venous or neuropathic)
- wound infection/gangrene
- amputation
- silent MI
- depression
- death
PROGNOSIS
depends on how well diabetes is managed. Improvement in blood glucose control may slow the progression of neuropathy, but recovery may be very slow
What patients is amytriptyline contraindicated in
BPH as can cause urinary retention
Hypoglycaemia
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
blood glucose falls below the normal fasting glucose range, generally <3.3 mmol/L
Whipples Triad; (low glucose, symptoms, glucose makes better)
- low blood glucose concentration
- hypoglycaemic symptoms
- resolution of symptoms after raising blood glucose concentration to normal
Risk Factors:
Diabetic patients: fasting/missing meals, insulin or sulphonurea use
Drugs: Sulfonylureas and insulin, SGLT2, DPP4
Hormone Deficiency: Hypopituitarism, Adrenal insufficiency- Addisons
Other- liver failure, sepsis, Insulinoma (tumour in pancreas secretes insulin, if administer exogenous insulin C peptide doesnt fall aka keeps secreting insulin)
CLINICAL FEATURES
Increased sympathetic activity: sweating, anxiety, tachycardia, tremor, palpitations, pallor
Increased parasympathetic activity: hunger, nausea, vomiting, paraesthesia
Neuroglycopenic symptoms: confusion, seizures, agitation
INVESTIGATIONS
Bloods:
- glucose: less than 3.3 cause autonomic symptoms, less than 2.8 cause neuroglycopenic symptoms
- insulin: insuloma
- C peptide: if elevated suggests insulinoma, if low suggests exogenous insulin
- cortisol: adrenal insufficiency
Check blood glucose in any confusiond patient with neurological symptoms
MANAGEMENT
Supportive care to correct glucose:
if conscious and can swallow: oral glucose 15-20g (liquid, gel or tablet) and fast acting carbs (glucose tablet, sweets, juice)
if unconscious: IM Glucagon and IV Dextrose (20% glucose).
if impaired GCS: IV glucose
If insuloma: surgical excision
If IGF-II secreting tumour: surgical excision + chemo/radio
COMPLICATIONS
- Seizure
- Coma
Hyperosmolar Hyperglycaemic State
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Characterised by profound hyperglycaemia (>30), hyperosmolality (>320), and volume depletion (dehydration) in the absence of significant ketoacidosis.
Avoids ketoacidosis as small amounts of insulin being secreted by pancreas still
Affects: older people with T2DM, may be the inital presentation of T2DM
RF:
- Infection (most commonly pneumonia or UTI)
- Acute illness (MI, sepsis, stroke)
- Inadequate insulin therapy
- Non-adherence to diabetes medications
- Surgery
CLINICAL FEATURES
- Acute cognitive impairment (recorded via GCS) due to hypernatraemia
- Polyuria
- Polydipsia
- Weight loss
- Nausea and vomiting
- Dry mucous membranes and decreased skin turgor → dehydration signs
- More insidious onset (over days)
INVESTIGATIONS
Bloods
- Blood glucose- markedly raised (>30 mmol/L) without ketonaemia/acidosis
- Blood ketones- negative (distinguish DKA vs HHS)
- Serum osmolality significantly raised (>320) due to hypovolaemia → key parameter to monitor
VBG- slight acidosis
ECG- check for MI which can cause HHS
Overall findings: Severe Hyperglycaemia (>30) + Hypotension + Hyperosmolality (>320)
MANAGEMENT
Correct hypotension: Fluid resus (IV fluids)- isotonic saline solution (0.9% NaCl)
- excess NaCl can cause hyperchloraemic acidosis (use hartmanns if lots administered), excess infusion of any fluid can cause pulmonary oedema and cardiac failure
Correct electrolytes abnormalities: Add KCl (potassium) to saline solution infusion if serum potassium is under 5.5
After- correct glucose only if blood glucose stops falling while giving fluids
IV insulin (0.05 units/kg/hr) if not acidotic and blood ketones over three, 0.1 units/kg/hr if acidotic or high blood ketones
Dont give this first because the fast shift in glucose can cause cerebral oedema so get glucose down with fluids diluting it and then correct
If glucose falls below 14 then 5% -10% glucose at 125mL/h
Prophylaxis: VTE as high risk from dehydration so give LMWH
Continuous blood glucose monitoring for 24 hours, for first 6 hours sodium, potassium, urea and osmolality every hours, every 2 hours if decreasing by 3-8 mOsm/kg/hour
Continuous pulse oximetry
Cardiac monitoring
Monitor complications with GCS: cerebral oedema and central pontine myelinolysis (look for a deteriorating conscious level) as well as fluid overload.
PROGNOSIS
Mortality attributed to hyperosmolar hyperglycaemic state (HHS) ranges from 5% to 15%. This is mostly as a consequence of the older patient population that is affected by HHS, and their comorbid conditions
COMPLICATIONS
! insulin-related hypoglycaemia
! treatment-related hypokalaemia
- stroke
- MI
- PE
- DIC
- coma
Obesity
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Chronic adverse condition due to an excess amount of body fat
Defined as BMI ≥30kg/m², can be grouped into 3 classes
- Class 1 → 30-34.9 kg/m²
- Class 2 → 35-39.9 kg/m²
- Class 3 → ≥40 kg/m²
40% of adults and 20% of adolescents (12-19 years)
Causes:
Genetics
Behavioural: poor dietary habits, sedentary lifestyle, larger portion size
Environmental: low socioeconomic status
Hormonal: hypothyroidism, hypercortisolism, insulinoma
CLINICAL PRESENTATION
Large waist circumference
May see comorbidities:
- T2DM
- CVD
- Hypertension
- Hyperlipidaemia
- GORD
- OSA
- Gout
- Cancer
- Gallbladder disease
INVESTIGATIONS
BMI → (weight in kg) / (height in m)²
Not accurate in pregnancy or people with high muscle mass
MANAGEMENT
Class 1: Dietary changes + increase in physical activity
consider: Orlistat (pancreatic lipase inhibitor)
can consider Liraglutide IF BMI over 35 with a comorbidity, or prediabetic hyperglycaemia (e.g. HbA1c 42 - 47 mmol/mol), or high risk of CVD
Class 2 with comorbidity or class 3: Bariatric surgery → sleeve gastrectomy
COMPLICATIONS
- pst surgical N+V, atelectasis and pneumonia
- post-surgical DVT
- PE
- bleeding
- wound infection
- vitamin deficiency
- Peri-operative death
- ACS
- T2DM
- hypercholesterolaemia
- hypertension
- non-alcoholic fatty liver disease
- metabolic syndrome
- cancer
PROGNOSIS
Hyperlipidaemia
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Elevated blood lipid levels (Total cholesterol, LDL, triglycerides)
Elevated LDL and reduced HDL → promote atherosclerosis → increased risk of cardiovascular events
Causes:
- Obesity
- Diabetes
- Physical inactivity
- Hypothyroidism
- Nephrotic syndrome
- Alcohol
- Cholestatic liver disease
Familial Hypercholesterolaemia:
- Autosomal dominant inherited disorder
- Caused by a mutation in the gene coding the LDL receptor
- Causes early-onset hypercholesterolaemia and hyperlipidaemia, leading to cardiovascular disease in young patients
CLINICAL FEATURES
- FHx of early onset CHD
- CVD history
- saturated and trans-fatty acid consumption
- abdominal obesity
- Xanthomata → nodular lipid deposits in the skin and tendons
- Xanthelasma → yellow, flat plaques on upper eyelids
- Corneal Arcus → crescentic-shaped opacity at the periphery of the cornea
INVESTIGATIONS
Lipid profile- total cholesterol, HDL, LDL, triglycerides
Tests for secondary causes:
- HbA1c/fasting glucose
- TSH (if high might be hypothyroidism)
- LFTs
- Urinalysis
QRISK2 → screens for risk of cardiovascular disease
MANAGEMENT
If QRISK under 10% then lifestyle:
- Improve diet
- Physical activity
- Weight management
- Alcohol intake reduction
- Smoking cessation
If QRISK 10 or above: Atorvastatin 20mg (alternative simvastatin). Decreases cholesterol synthesis by inhibiting HMG-CoA reductase
If QRISK 10 or above with known IHD/cerebrovascular disease/PAD then Atrovastatin 80mg
- take statins last thing at night
- If serum transaminase concentrations rise to and persist at 3x the upper limit of reference range then stop statin
2nd line if cant have statin: Ezetimibe- cholesterol absorption inhibitor
3rd: PC-SK9 if tried voth and less than 50% reduction in LDL
If xanthelasma is affecting activities of daily living : Laser therapy or surgical excision
Who are statins contraindicated in and what medication can they not be combined with
Pregnant women
Erythromycin/clarithromycin (macrolides)
Can cause myopathy and increase likelihood of rhabdomyolysis
Hypercalcaemia of Malignancy
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Three types
1) Humoral hypercalcaemia of malignancy: turmour secretes PTHrP (PTH related peptide). Occurs in SCC, renal, ovarian, bladder and breast cancer
2) Local osteolytic hypercalcaemia: Bony metastases release factors locally to promote osteoclast function. Occurs in multiple myeloma and breast cancer
3) Calcitriol-mediated hypercalcaemia: autonomous production of calcitriol (1,25 dihydroxyvitamin D) due to 1-alpha-hydroxylase activity in tumour cells. Occurs in hodgkin lymphoma and non-hodgkin lymphoma
Risk Factors:
- non-metastatic malignancy (humoral hypercalcaemia)
- metastatic skeletal involvement (local osteolytic hypercalcaemia)
- lymphoma (calcitriol-mediated hypercalcaemia)
- Thiazides may also cause hypercalcaemia
CLINICAL FEATURES
- Polyuria
- Polydipsia
- Constipation
- Bone pain
- Low mood
- Confusion and fatigue
- Poor skin turgor or dry mucous membranes
- Loss of appetite
- Nausea
INVESTIGATIONS
Bloods:
- Calcium: elevated
- PTH: low (helps distinguish from hyperparathyroidism)
- PTHrP: high if humoral hypercalcaemia of malignancy
- Phosphorus: high in humerol
- ALP: high if bone metasteses, normal in multiple myeloma
- Calcitriol: elevated in vitamin d mediated hypercalcaemia
ECG- may show shortened QT interval indicative of hypercalcaemia
MANAGEMENT
IV saline (fluids) to reverse dehydration, IV bisphosphonates (or denosumab)- most effective for treating malignancy associated hypercalcaemia by blocking osteoclastic bone resorption.
If hypercalcaemia is improved with the initial infusion of bisphosphonate, but serum calcium levels begin to increase again, the bisphosphonate infusion may be repeated: in 7 days, and then every 3-4 weeks thereafter (zoledronic acid); every 2-3 weeks (pamidronate)
If established calcitriol issue then corticosteroids: prednisolone or hydrocortisone sodium succinate
avoid medications that can worsen hypercalcaemia (e.g., thiazide diuretics, calcitriol [(1,25-dihydroxyvitamin D)], calcium supplementation, antacids, lithium) and those that may worsen symptoms of hypercalcaemia (e.g., sedatives, hypnotics, analgesics, if possible)
Then treat underlying malignancy
COMPLICATIONS
- AKI
- Coma
- Acute pancreatitis
PROGNOSIS
Intravenous hydration and pharmacological therapy for malignancy-associated hypercalcaemia can provide transient restoration of normocalcaemia. Eradication of underlying malignancy is crucial for permanent reversal of hypercalcaemia
Pituitary Tumour
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Benign tumours that arise sporadically from the anterior pituitary gland
Classified by size and hormonal status
- Size: 10mm or less are microadenomas, over are macroadenomas
- Hormonal status: functional (secretes hormones: prolactinoma, acromegaly, cushings disease)or non functional
Causes:
Most sporadic
Multiple Enocrine Neoplasia Type 1 (MEN1): associated with pituitary tumour, parathryroid adenoma, pancreatic tumour/insulinoma. Signs of MEN1 are peptic ulceration, hypercalcaemia, galactorrhoea
CLINCIAL PRESENTATION
Non functioning pituitary tumour
-1) Headache
2) Bitemporal hemianopia : pressure on optic chiasm, If upper quadrant defect only then inferior chiasmal compression from pituitary tumour, if lower quadrant then superior chiasmal compression from craniopharyngioma
3) Panhypopituitarism: Tumour may compress other parts of the pituitary gland → non-functioning tumours typically present with generalised hypopituitarism
- Low ACTH → tiredness, postural hypotension, nausea
- Low FSH/LH → amenorrhoea, infertility, loss of libido, erectile dysfunction, small balls, gynaecomastia
- Low TSH → feeling cold, constipation, tired
Functional pituitary tumour:
Prolactinoma
- Women → amenorrhoea, infertility, galactorrhoea, osteoporosis
- Men → impotence, loss of libido, galactorrhoea
Cushing’s Disease (too much ACTH)
Acromegaly (too much GH)
- OSA
- Excess sweating
- Large tongue
- Increase in shoe and hand size
- Cardiomyopathy
rarely affects TSH levels
If macroadenoma:
- Headache
- Visual disturbances
- Symptoms of hypopituitarism- prolactinoma compresses pituitary stalk
Pituitary apoplexy : bleeding haemorrhage or infarction to pituitary
Acute onset of severe headache, associated with nausea, vomiting, meningismus, altered level of consciousness, ophthalmoplegia, hypotension in acute adrenal crisis.
INVESTIGATIONS
Bloods:
Pituitary Blood Profile: to determine if functioning or non functioning
- GH
- Prolactin
- ACTH
- FSH
- LH
- TFTs
Serum IGF-1 for acromegaly, then do OGTT with serial GH measurements: would lead to a paradoxical rise (no suppression) in GH following glucose load
Cant do serum GH as pulsatile
Serum prolactin + Visual field testing for prolactinoma
Brain MRI with gadolinium enhancement
TREATMENT
Pituitary apoplexy
- without effect : hydrocortisone or dexamethosone + levothyroixine
- with effect and altered consciousness: paraenteral hydrocortisone or dexamethosone + trans-sphenoidal surgery and hormone replacement after
Microadenoma: observe
Macroadenoma without affecting optic chiasm- observe
Macroadenoma affecting optic chiasm: trans-sphenoidal surgery and hormone replacement
Prolactinoma: bromocriptine or cabergoline (dopamine agonists)
2nd = surgery
Acromegaly = surgery
2nd octreotide (somatostatin analogue)
Hormone Replacements
Levothyroxine
Hydrocortisone
Testosterone or testosterone cipionate (IM), testosterone topical, testosterone transdermal
Somatotropin
Estradiol (if in tact uterus MUST have progesterone or medroxyprogesterone)
COMPLICATIONS
- hypopituitarism
- DI
- meningitis
- pituitary apoplexy
PROGNOSIS
Patients with clinically non-functional pituitary adenomas (CNFPAs) generally have a good prognosis
What is carcinoid syndrome and the clinical features, investigations and management
Due to neuroendocrine tumour secreting serotonin
- Flushing
- Diarrhoea
- SOB
- Abdo pain
- Cushing’s-like symptoms due to ACTH secretion
- Cardiac issues: tricuspid insufficiency (regurg) and pulmonary stenosis
Urinary 5-HIAA
Octreotide (somatostatin analogue)
Hypothyroidism
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Condition in which the thyroid gland is underactive, resulting in deficiency of the thyroid hormones T3 & T4.
Affects women more
Most common cause= iodine deficiency, in developed countries Hashimotos thyroiditis is most common
Hashimotos inc chance of MALT lymphoma (mucosa associated lymphoid tissue)
Subclinical hypothyroidism: May occur in intercurrent illness → high TSH with normal T3 and T4
Repeat TFTs in 3-6 months, if under 65 with hypothyroidism symptoms then trial levothyroxine, if over 65 observe and repeat in 6 months
Causes:
- Congenital-
- Thyroid dysplasia
- Thyroid aplasia
- Acquired
- Hashimoto’s thyroiditis (autoimmune)
- Postpartum thyroiditis
- De Quervain thyroiditis
- Iatrogenic (post-surgery)
- Lithium toxicity
- Secondary
- Pituitary disorders (e.g. pituitary adenoma) leading to TSH deficiency
CLINICAL FEATURES
- Decreased basal metabolic rate
- Slow cognition
- Apathy
- Dry skin
- Cold intolerance
- Decreased sympathetic activity
- Decreased sweating
- Constipation
- Bradycardia
- Fatigue
- Hair loss
- Weight gain (despite poor appetite)
- Depression
- Menorrhagia (heavy periods)
Hashimotos: firm and non-tender goitre
INVESTIGATIONS
TFTs:
- primary is high TSH and low T3/4
- secondary is low TSH, low T3/4
- pregnancy can cause normal TSH free T3+4 but high total T3+4 because of hgher concentrations of thyroid-binding globulins
Euthyroid sick syndrome: serum levels of thyroid hormones are low in patients who have nonthyroidal systemic illness aka low because theyre ill not thyroid issue: normal TSH, low t3+4 and acute illness
Antibody testing for autoimmune hypo: Anti-TPO in Hashimotos
Euvolaemic Hyponatramia
If suspect secondary aka pituitary: brain MRI
MANAGEMENT
Lifelong levothyroxine, adjust dose based on TFTs
- TSH annual check needed, if poor compliance see raised TSH and normal T4
- if pregnant: increase dose by 50% as early as 4-6 weeks in
- If overreplace thyroxine then high risk of osteoporosis
- Should take iron/calcium 4 hours apart from levothyroxine as can reduce absorption
- If amiodarone induced hypothyroidism continue amioradone and give levothyroxine
Myxoedema Coma: severe hypothyroidism causing impaired mental status, hypothermia, hypotension
- IV levothyroxine (T4) & liothyronine (T3)
- IV hydrocortisone
- oxygen
- rehydration
PROGNOSIS AND COMP
lifelong levothyroxine required. Myxoedema Coma has mortality rate of 80%
Thyroid Nodule
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Abnormal growths within the thyroid gland- nodules are usually non-functioning
Female, incidence increases with age
Benign nodules;
- Thyroid adenoma
- Thyroid cyst
- Non-toxic multinodular goitre
- Hashimoto’s thyroiditis
Malignant nodules:
Thyroid carcinoma
- Papillary carcinoma: 30-40 yr olds, mets to lymph nodes, thyroglobulin is a tumour marker, on light microscopy see orphan annie eyes- good prognosis
- Follicular carcinoma: 2nd most common 30-60yrs, more common if low iodine, more common in women, mets to lung and bones, thyroglobulin is a tumour marker
- Medullary carcinoma: cancer of parafollicular cells, secretes calcitonin, MEN-2 hereditary, MEN-2a (parathyroidhyperplasia and phaeochromocytoma)
RF:
- Radiation
- Family history
- Rapid enlargement/compression
- Lymphadenopathy
CLINICAL FEATURES
Asymptomatic
Single isolated nodules most likely to be malignant
If radiates to head or neck then suspect thyroid cancer
INVESTIGATIONS
TFTs: TSH
Ultrasonography to check for features of malignancy
If suspect malignancy: Fine needle aspiration biopsy
Radioiodine uptake scan:
Diffuse uptake through enlarged gland: Grave’s
Single hot/functioning nodule: Toxic adenoma
Multinodular Gland with single hot/functioning nodule, patchy uptake: toxic multinodular goitre
Diffuse uptake with single cold nodule: thyroid cancer
No uptake: De Quervain’s (viral) thyroiditis
MANAGEMENT
Thyroid surgery
- papillary and follicular carcinomas: total thyroidectomy and radioiodine after. Thyroixine for life with yearly thyroglobulin levels to detect recurrent disease
Hyperthyroidism: beta blockers and anti thyroid drugs (carbimazole)
Differentials of Neck lumps, causes and clinical presentations
Neck lumps
1) reactive lymphadenopathy: history of local infection or viral illness, tender lymph node
2) Lymphoma: rubbery, painless lymphadenopathy, weight loss, night sweats, fever, splenomegaly. Linked to Hashimotos thyroiditis
3) Thyroid swelling: Hypo/Hyper/Euthyroid symptoms, moves up when swallowing
4) Thyroglossal cyst: Mass that develops from tissues that remain after formation of thyroid gland during embryonic development. Less than 20yrs old, midline, moves up when protrude tongue, painful if infected
5) Pharyngeal pouch: When part of pharyngeal lining herniates through muscle of the pharyngeal wall. Older men, if large then midline mass not usually seen though, gurgles on palpitation, dysphagia, regurgitation, aspiration, chronic cough
6) Branchial cyst: Embryonic remnant. Oval, mobile, cystic mass, between SCM and pharynx, in early adulthood, has cholesterol crystals
7) Carotid aneurysm: pulsatile, lateral neck mass, doesnt move on swallowing
Hyperthyroidism
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Symptoms caused by the excessive circulation of thyroid hormones
Women affected more
Caused by conditions that lead to hyperthryoidism
- Graves’ : 20-30 yrs
- Toxic multinodular goitre
- toxic adenoma
- Amiodarone induced
CLINICAL FEATURES
weight loss, restlessness, heat intolerance
palpitations, tachycardia
increased sweating, pretibial myxoedema (graves’), onycholysis (nail seperated from nail bed)
diarrhoes, anxiety, tremor, oligomenorrhoea, amenorrhoea
Graves specific:
- exophthalmos
- pretibial myxoedema
- thyroid acropachy (clubbing of fingernails)
INVESTIGATIONS
TFT: High T3/T4 + Low TSH
Anti-TSH receptor antibody: Graves’
Thyroid ultrasound
Fine needle aspiration for neck
Radioactive iodine uptake:
- Graves= diffuse uptake in enlarged node
- Multinodular gland with single hot nodule: toxic multinodular goitre (need radioiodine therapy)
- Diffuse uptake with single cold nodule= thyroid cancer
- No uptake= de quervains viral thyroiditis. Initially are hyperthyroid and have painful tender goitre after a viral (flu-like) illness. Then become hypothyroid after. Is self limiting only need NSAIDs for pain
MANAGEMENT
Propanolol for cardiac/sympathetic symptoms
Anti-thyroid drugs:
- Carbimazole/Thiamazole for 12-18 months (inhibits TPO). 1st line for Graves’, cant give if pregnant. Can cause agranulocytosis so need urgent med attention if infection develops so can meaure FBC
- Propylthiouracil: if in pregnancy first tiremester or thyroid storm
- Potassium iodide
- Radioactive iodine ablation: destroys thyroid tissue, do if resistant to antithyroid drugs. Definitive treatment for Graves and toxic multinodular goitre. Pretreat with anti-thyroid drugs
- Total thyroidectomy
PROGNOSIS AND COMP
High output cardiac failure
What is thyroid storm/Thyrotoxicosis , the causes, presentation and treatment
Thyroid storm: acute exacerbation of hyperthyroidism that results in alife-threateninghypermetabolic state. Can be triggered by surgery, trauma and infection.
- Hyperpyrexia
- hypertension
- tachycardia
- jaundice
- confusion and agitation/syncope
- severe N&V
Management:
- IV propranolol
- IV digoxin
- Propylthiouracil (followed by Lugol’s iodine 6 hours later)
- Prednisolone/hydrocortisone
Hypothermia
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
core body temperature <35°C
- Mild (32-35°C)
- Moderate (28-32°C)
- Severe (<28°)
RF
- General anaesthetic use
- Older age
- Very young age
- Immobility
- Substance misuse
- Hypothyroidism
- Stroke
- Homelessness
- Parkinson’s disease
CLINICAL PRESENTATION
Mild: tachycardia, tachypnoea, vasoconstriction, shivering, hypertension, frostbite
Moderate: cardiac arrhythmias, hypotension, respiratory depression, bradycardia, reduced consciousness, may cease to shiver
Severe: coma, apnoea, arrhythmia, fixed and dilated pupils
INVESTIGATIONS
Core temperature measurement
12 lead ECG:
- J wave/Osborn wave
- Broad (prolonged) QRS complexes
Bloods: glucose, VBG (hypoventilation leads to respiratory acidosis), electrolytes, FBC, clotting screen
MANAGEMENT
Mild: passive external rewarming: remove wet clothing, cover with blankets in a warm room
Moderate: active external rewarming: warm blankets, radiant heat, forced warm air
Severe: IV administration of warmed crystalloid
Cardiac arrest:
3 shocks before patient rewarmed to 30 degrees. chest compressions should continue, dont give adrenaline or any more shocks until over 30
If over 30 then double intervals for adminostration of vasoactive drugs on a normothermic aka every 4 cycles instead of 2
COMPLICATIONS
- cardiac arrhythmias
- hypoglycaemia
- hyperkalaemia
- rhabdomyolysis
- GI disorders
Hyperthermia
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Core body temp >40°C
Heat Stroke: Life-threatening condition that presents with hyperthermia and CNS dysfunction
Three classes
1) Classic Heat Stroke: passive exposure to environmental heat
2) Exertional Heat Stroke: strenuous physical exercise
3) Heat exhaustion: no CNS dysfunction
RF:
- Older age
- Impaired cognition
- Medicines
- Lack of acclimatisation to hot environments
- Dehydration
CLINICAL FEATURES
- CNS dysfunction
- Altered level of consciousness
- Agitation
- Lethargy
- Seizures
- Irritability
- Anhidrosis- hot & dry skin
- Intense thirst
- Weakness
- Anxiety
- Dizziness
- Nausea and vomiting
- Syncope
INVESTIGATIONS
Core temperature measurement : Rectal temperature
Bloods: LFTs, renal, FBC, glucose, electrolytes, ABG
ECG
MANAGEMENT
Heat Stroke:
- Stabilisation (ABC and remove clothing)
- Rapid Active cooling:
whole body iced water immersion or wetted ice pacs in exertional heat stroke
Wetting and fanning skin or wetted ice packs in classic heat stroke
Heat exhaustion: oral isotonic fluids, consider active cooling
COMPLICATIONS
- ARDS
- Shock
- AKI
- DIC
- CVD
Hyperparathyroidism
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Abnormally high PTH levels in blood due to overactivity of the parathyroid glands
PTH increases serum calcium & decreases serum phosphate. Secretion is stimulated by decrease in serum calcium
Usually female over 50
Primary Hyperparathyroidism: Parathyroid gland adenoma (benign tumour). High calcium levels
Secondary Hyperparathyroidism
- CKD
- Malnutrition
- Vitamin D deficiency (reduced sunlight or nutritional deficiency)
Low calcium levels
Tertiary Hyperparathyroidism: Caused by persistent sHPT. Hyperplasia of parathyroid glands after correction of underlying renal disorder.
High calcium due to chronic increase in PTH
CLINICAL FEATURES
Primary : Painful bones, renal stones, abdo groans and psychic moans (hypercalcaemia symptoms)
- Polydipsia
- Polyuria
- Anorexia
- Nausea
- Constipation
- Bone pain (esp back pain)
- Renal stones
- Low mood
Secondary and Tertiary:
- Symptoms of underlying cause (i.e. renal failure)
- Bone pain
- Increased risk of fractures
INVESTIGATIONS
PTH, calcium, creatinine, urea
Primary vs tertiary: in primary PTH is raised and ALP is raised, in tertiary PTH is markedly raised
Secondary: low calium, low phosphate if vit D deficient, high phosphate if CKD
USS to look for parathyroid gland adenoma
X Ray:
- Pepperpot appearance
- osteopenia/erosion of bone
MANAGEMENT
Total parathyroidectomy
Use if cant have surgery
- Calcimimetics (Cinacalcet) which inhibits PTH release
- IV fluids to treat hypercalcaemia
Secondary: treat underlying cause
lack of sunlight -> get sun, take vit D, take calcium
Hypoparathyroidism
- aetiology: define, pathophysiology, risk factors
- clinical features
- investigations
- management
- prognosis + complication
Disorder caused by deficiency of PTH synthesis and secretion, leading to low serum calcium and elevated serum phosphate
Causes:
Postoperatively : thyroidectomy or parathyroidectomy
Autoimmune
Non-autoimmune: Wilson disease, haemochromacytosis
Congenital: DiGeorge syndrome
Pseudoparathyroidism: rare genetic condition resulting in failure of target organs to respond to normal levels of parathyroid hormone
- Short stature
- Short fingers
- Symptoms of hypocalcaemia
- Vitamin D deficiency
CLINICAL PRESENTATION
same as signs for hypocalcaemia or hypomagnasemia
- Tetany- Muscle twitching, cramping, spasm
- Paraesthesia, numbness, tingling
- Poor memory, slowed thinking
- Malnutrition, malabsorption, diarrhoea
- Arrhythmias- Prolonged QT interval
- Chvostek’s sign- Contraction of facial muscles when facial nerve is tapped in front of the ear
- Trousseau sign- painful clasping response of fingers and hands when blood pressure cuff is inflated above systolic blood pressure
ATs go numb (Convulsions, Arrhythmias, Tetany, Paraesthesia)
INVESTIGATIONS
Blood:
- Low PTH
- Low serum calcium (and normal ALP)
- High serum phosphate
- Normal serum albumin (low albumin gives falsely low serum calcium)
- Vitamin D
ECG: Isolated prolonged QT interval (predisposes to TDP), indicates severe life-threatening hypocalcaemia. Treat with Urgent IV calcium gluconate
MANAGEMENT
- IV or oral calcium
- Low dose calcitriol (form of Vit D)
If magnesium low: paraenteral magnesium
COMPLICATIONS
- cataract
- hypercalcaemia
- renal insufficiency
- renal stones
