1
Q
Definition of hypoglycaemia?
A
- Defined as blood glucose ≤4mmol/L
- In hospital, any blood sugar <4mmol/L should be treated promptly
- Can mimic any neurological presentation
2
Q
Prevalence of hypoglycaemia?
A
- 30% prevalence in T1DM
3
Q
Risk factors of hypoglycaemia?
A
o Strict glycaemic control o Impaired awareness of hypoglycaemia o Increased duration of diabetes o Alcohol o Injection into lipohypertrophic sites
4
Q
Causes - diabetic of hypoglycaemia?
A
Insulin or sulphonylurea with increased activity, missed meal, overdose
5
Q
Causes - non-diabetic of hypoglycaemia?
A
Exogenous drugs (insulin, sulphonylureas, alcohol, ACEi, BB)
Pituitary insufficiency
Liver Failure
Addison’s disease
Insulinoma
Non-pancreatic neoplasms (fibrosarcoma)
6
Q
Symptoms of hypoglycaemia?
A
- Rapid onset
- Preceded by odd behaviour
- Autonomic
o Sweating, tachycardia, anxiety, hunger, tremor, palpitations - Neuroglycopenic
o Confusion, drowsiness, visual trouble, seizures and coma
7
Q
Investigations of hypoglycaemia?
A
- BMG (if <3, take lab glucose)
- Bloods – glucose, LFTs, TFTs, HbA1c
8
Q
Diagnosis of hypoglycaemia - triad?
A
- Diagnosis (Whipple’s triad)
o Plasma hypoglycaemia
o Symptoms of low blood sugar
o Resolution with correction of hypoglycaemia
9
Q
Management of hypoglycaemia - conscious or mild hypoglycaemia?
A
10-20g of fast-acting oral carbohydrates (Lucozade, sugar lumps, GlucoGel, Dextrogel)
• Repeat BMG after 15 mins, repeat step up to 1-3 times if needed
After treatment, give longer-acting carbohydrate (sandwich, fruit, milk, biscuits or next meal)
10
Q
Management of hypoglycaemia - unconscious or severe hypoglycaemia?
A
If IV Access not available rapidly:
Glucagon 1mg, SC/IM (not suitable in alcohol, sulfonylureas or liver failure)
• If not effective in 10 minutes, give IV glucose
If IV access: IV glucose (e.g. 15g of 150ml 10% glucose over 15 minutes or 10g of Glucose 20% (50mls)) through large vein and large-gauge needle • Infusion can be given if prolonged
After treatment, give 20g longer-acting carbohydrate (sandwich, fruit, milk, biscuits or next meal)
11
Q
Management if prolonged hypoglycaemic coma?
A
o Usually >5 hours and caused by cerebral oedema
o IV mannitol and dexamethasone
o IV glucose
12
Q
When are ketones produced by body?
A
- Ketoacidosis is alternative metabolic pathway, normally used in starvation states
- Produces acetone as by-product
13
Q
Pathology of DKA?
A
o Excessive glucose, but due to lack of insulin, cannot be up taken into cells to be metabolised
o Causes osmotic diuresis, with Na and water loss
o Pushes body into starvation states where ketoacidosis is only mechanism of production – increased lipolysis
o Produces non-esterized fatty acids, oxidised in liver to ketones
14
Q
Risk factors of DKA?
A
o Infection
o Infarction
o Insufficient insulin
o Intercurrent illness
15
Q
Symptoms and signs of DKA?
A
o Dehydration – thirst, polydipsia, polyuria, decreased skin turgor, dry mouth, hypotension, tachycardia
o GI – nausea, vomiting, abdominal pain
o Hyperventilation – (resp compensation for metabolic acidosis) Deep rapid (Kussmaul breathing) and smell of acetone on breath
o Altered conscious state, focal neurological deficits
16
Q
When to get critical care review in DKA? PHOSSVGK
A
o Pregnant o Heart Failure o Oliguria or Anuria o Sat <92% on air o Systolic BP <90mmHg after 2L of fluid o Venous bicarbonate <5mmol/L or pH<7.1 o GCS<12 o K<3.5 on admission
17
Q
Essential investigations when DKA suspected?
A
o FBC, U&E, glucose
o VBG for bicarbonate, K, pH
o Depending on clinical suspicion – ECG/CXR/MSU/blood cultures/pregnancy test
18
Q
Diagnosis of DKA?
A
o Hyperglycaemia (>11mmol/L) o Ketonaemia (>3mmol/L or ++ or above on strip marking scale) o Acidaemia (pH<7.3 or plasma bicarbonate <18)
19
Q
Initial management of DKA?
A
o ABCDE approach
Secure airway if GCS low
2 large-bore cannulas
o If BP <90 – 500ml Bolus 0.9% saline (max 2L, then call critical care)
20
Q
Fluid management of DKA?
A
If BP>90mmHg or responds to 1st bolus:
1L 0.9% Saline in 1st hour, 1L over 2 hours, 1L over 2 hours, 1L over 4 hours, 1L over 4 hours, 1L over 6 hours
21
Q
Insulin management of DKA?
A
Insulin – fixed rate
IVI 50U actrarapid (soluable insulin) to 50mL 0.9% saline – 0.1u/kg/hr (1 unit/ml)
• Can increase to 1u/h
Continue long-acting insulin therapies
Call Diabetes specialist team
22
Q
Subsequent management of DKA - potassium replacement?
A
o Potassium Replacement (40mmol/L KCl added)
Don’t add K to 1st bag unless <3.5
Monitor UO hourly, infuse at 20mmol/hour
Check U&E hourly initially and replace as required
• >5.5 None
• 3.5-5.5mmol/L – 40mmol KCl/litre of IV fluid
• <3.5mmol/L – senior review (>40 may be necessary)
Continuous ECG monitoring
23
Q
Subsequent management of DKA - further management after potassium replacement?
A
o Catheter and NG tube (if drowsy)
o LMWH Anticoagulation
o When glucose <14mmol/L
10% glucose at 125mL/h to prevent hypoglycaemia alongside sodium chloride
24
Q
Monitoring in DKA?
A
o Vital signs hourly for 1st 4-6 hours and frequently thereafter
o Capillary glucose, ketones & VBG hourly
o U&Es every 6 hours
25
Targets of treatment in DKA?
o Blood glucose fall of >3mmol/L/hour until 14mmol/L (if not falling, increased insulin to 1U/hr)
o Venous bicarbonate rise >3mmol/L/hour until 15mmol/L
o Capillary ketones fall >0.5mmol/L/hour until <0.6mmol/L
26
Management after recovery in DKA?
o Transfer to SC insulin when patient well, able to eat and drink and venous pH >7.3 or blood ketones <0.6mmol/L
o Give SC fast-acting insulin and a meal and stop infusion
27
Complications in DKA?
```
o Cerebral oedema
Headache, agitation, fall in heart rate, increased blood pressure
o Aspiration pneumonia
o Hypokalaemia
o Hypomagnesaemia
o Hypophosphatemia
o VTE
```
28
Definition of impaired glucose tolerance?
FPG <7 and 75g OGTT 2h 7.8-11.0
29
Definition of impaired fasting glucose?
FPG 6.0-7.0
30
Definition of T1DM?
o Absolute insulin deficiency causing persistent hyperglycaemia
o Most common is immune for 1A
o Some slower progression form occur later in life (LADA)
31
Pathology of T1DM?
o Islet cell antibodies lead to insulitis and destruction of B cells in Islet of Langerhans causing insulin deficiency
32
Epidemiology of T1DM?
- Peak age is puberty but can be any age
- Usually lean
- Associated with autoimmune diseases of thyroid, blood, etc
33
Aetiology of T1DM?
o HLA-DR3/4
| o Family history of Type 1
34
Environmental triggers of T1DM?
o Autoantibodies appear early (Glutamic acid decarboxylase)
o Diet
o Coxsackie virus
35
Acute symptoms of T1DM?
- Young people with 2-6 week history of thirst, polyuria, weight loss
- Ketoacidosis
36
Subacute symptoms of T1DM?
- Over month/years (type 2 commonly)
| - Thirst, polyuria, weight loss, fatigue, visual blurring, infections
37
Diagnosis of T1DM?
Symptoms of hyperglycaemia
```
Fasting PG (8-hours) of ≥7mmol/L or random PG ≥11.1mmol/L
1 abnormal reading if symptomatic, 2 if asymptomatic
```
One or more of:
Ketosis, rapid weight loss, age <50, BMI <25, family history of autoimmune disease
38
Management if T1DM diagnosed?
- If type 1 diagnosed – refer same-day to diabetes specialist team
39
Initial care of newly diagnosed T1DM?
- Offer structured education programme – DAFNE programmed 6-12 post-diagnosis
- Teach self-monitoring of blood glucose
- Lifestyle changes – stop smoking, strict diet (low fat, sugar, high carbs), regular exercise and low alcohol intake
- Yearly influenza and pneumococcal vaccine
- Inform DVLA/insurance if having insulin
40
Drug treatment in T1DM?
Insulin
41
Advice on self-monitoring in insulin management of T1DM?
Targets?
When to give real time glucose monitoring?
When is sensor pump therapy given?
At least 4 times a day, before meals and before bed
• Encourage 10x/day if – poor control, hypo frequency increases, period of illness, around sport
Targets
• FPG 5-7 on waking, PG 4-7 before meals, PG 5-9 at least 90 mins after eating
Real time glucose monitoring used when patient has:
• >1 severe hypoglycaemia, loss of awareness of hypoglycaemia, frequent (>2/week) hypoglycaemias affecting ADLs, fear of hypoglycaemia, hyperglycaemia persistently (HbA1c >75)
• Can have multiple daily injection insulin or CSC insulin pump
Sensor-pump therapy given when:
• Episodes of hypoglycaemia despite continuous SC monitoring
42
Insulin regimens in T1DM?
Offer Basal-bolus regimen 1st line
Continuous insulin SC infusion (pump)
2x day pre-mixed 70:30
43
Basal-bolus regimen in T1DM?
Basal-bolus regimen 1st line
Long-acting insulin detemir BD 1st line
o Alternative: OD insulin glargine or insulin detemir
Offer rapid-acting insulin analogues before meals (Humalog/Novorapid)
Can adjust for meals and infections better
Need to test sugars more, at school inject (psychological)
44
Continuous insulin SC infusion in T1DM?
Continuous insulin SC infusion (pump)
* Recommended (children >12 and adults) if multiple daily injections result in disabling hypoglycaemia (repeated and unpredictable hypos that results in persistent anxiety about recurrence and effecting ADLs) OR HbA1c >69mmol/mol on MDI therapy
* Gives basal infusion and bolus when eat
* Needle changed every 2-3 days
* Cannot use in sports, swimming, baths (if disconnected – DKA)
45
Pre-mixed insulin in T1DM?
2x day pre-mixed 70:30
• Consider BD human mixed insulin if MDI basal-bolus regimen not possible
• Not suitable for kids’ normal daily activity
• Difficult to control/change insulin dosages
46
Adjunctive treatments if insulin not achieving adequate glycaemic control in T1DM?
Sotagliflozin/Dapagliflozin with insulin
• If BMI >27, when insulin does not provide adequate glycaemic control
• On >0.5u/kg/day of insulin
• Stop if not a sustained improvement (>3mmol/mol) of HbA1c in 6 months
47
Sick day rules in T1DM?
Increases insulin need
Monitor blood glucose more regularly (up to 10x/day)
Consider ketone monitoring
Keep hydrated
Seek medical attention if unable to keep fluids down
48
Management of T1DM in hospital?
Aim for 5-8mmol/litre during surgery or acute illness
IV insulin if – unable to eat or predicted to miss more than 1 meal or acute situation (major surgery, high-dose steroids, inotropes, sepsis) or circulatory compromise
Use SC insulin (including rapid acting insulin before meals) if eating – enable self-administration if willing
49
Accessories needed in insulin therapy of T1DM?
Insulin injection device
Needles
Blood glucose meter, test strips and lancets
Urine ketones
Blood ketones meter, test strips and lancets
Sharps bin
Glucagon oral gel/injection
50
Other drug management given in T1DM?
- Statin
o Atorvastatin 20mg
If >40, diabetes for >10 years, established nephropathy, CVD risk factors (obesity, hypertension)
- Antihypertensive (intervention if no risk >135/85, if albuminuria or 2 features of metabolic syndrome >130/80)
o ACEi
o Others: BB, low-dose thiazides, CCB
51
When to refer to nephrologist in T1DM?
- To nephrologist if eGFR <30
52
Follow ups in T1DM?
- Measure HbA1c every 3-6 months – target 48mmol/mol
- Annually
o HbA1c
o Height, weight, waist circumference, BMI
o Smoking status
o Assess erectile dysfunction (offer PDE-5i)
o Monitor for neuropathy
o Check injection sites
o Assess awareness of hypoglycaemia with Gold/Clarke score
53
How to screen for retinopathy in T1DM?
GP referral on diagnosis and annually
Emergency review by ophthalmologist if:
o Sudden loss of vision, rubeosis iridis, pre-retinal/vitreous haemorrhage, retinal detachment
Refer to ophthalmologist if:
o Maculopathy (exudates near fovea, macula)
o Pre-proliferative retinopathy (venous bleeding, reduplication, multiple round or blot haemorrhages)
54
How to screen for diabetic foot problems in T1DM?
Diabetic foot problems (foot checks annually, monthly-weekly if at risk)
• Assess neuropathy (10g monofilament), ischaemia, ulcers, callus, infection, deformity, ABPI
• If active diabetic foot problem – refer within 1 working day
55
How to screen for nephropathy in T1DM?
Nephropathy (EMU for ACR, eGFR check)
| • Start ACEi if confirmed nephropathy and T1DM
56
Prognosis of T1DM?
- Without insulin replacement – would die within days/weeks
- With insulin – live normal life and complication risk reduced by adherence to effective treatment
- Life expectancy is reduced by 10 years on average
57
Complications of T1DM?
o Macrovascular
Atherosclerosis – stroke, MI, PVD
o Microvascular
Affects all small vessels – particularly in retina and nerve sheath
58
Classes of diabetic eye disease in T1DM?
Diabetic retinopathy
1. Background – capillary microaneurysms, dot & blot haemorrhages, hard exudates
2. Pre-proliferative – soft "cotton wool" spots
3. Proliferative – New blood vessels, vitreous/retinal haemorrhages
4. Maculopathy – Bleeds/exudates encroach on macula causing decreased visual acuity
Cataracts
59
Nephropathy complications in T1DM?
o Damages by glomerular disease – thickening of basement membrane and glomerulosclerosis – microalbuminuria and decreased eGFR
60
Neuropathy complications in T1DM?
o Symmetrical sensory polyneuropathy
o Acute painful neuropathy
o Mononeuritis
61
Diabetic foot complications in T1DM?
o Ulcers due to neuropathy and vascular disease
62
Skin complications in T1DM?
o Lipohypertrophy
o Necrobiosis Lipoiditica – red plaques on skin
o Vitiligo – white patches
o Granuloma annulare – flesh coloured rings over extensor surface of fingers
63
Other complications in T1DM?
- Infection – especially UTI and skin
| - Gastroparesis
64
Definition of T2DM?
- Type 2 diabetes defined as persistent hyperglycaemia (RPG >11) caused by deficient insulin secretion and resistance to action of insulin
65
Pathology of T2DM?
o Partial insulin deficiency and insulin resistance
o Body unable to secrete enough insulin to meet demands, insulin less able to bind to receptors due to resistance
o Beta cell mass <50% - hyperglycaemia worsens disease and progression to impaired fasting glucose
66
Epidemiology of T2DM?
- 2-4x more common in Asians, Africans
| - One of most common chronic diseases in UK, prevalence increasing
67
Risk factors of T2DM?
- Older age
- FHx
- Hx of gestational diabetes
- Ethnicity – Asian, African
- Obesity
- Diet - High GI index food
- Hypertension/hyperlipidaemia
- Low birth weight
- Alcohol excess
- Drugs (steroids, statins, thiazide diuretic)
68
Symptoms of T2DM?
- Subacute with complications – infections, etc
- Polydipsia, polyuria, weight loss and fatigue
- Can be asymptomatic
69
What risk assessment is used in T2DM?
- Tool from Diabetes UK – gender, age, ethnicity, FHx, waist circumference, BMI, BP
- Gives risk score – low, intermediate, high
70
When is risk assessment offered in T2DM?
- Offer to:
o >40
o 25 and over in South Asian and Afro-Caribbean origin
o Adults with CVD, hypertension, stroke, obesity, PCOS, Hx of GDM
71
What to do if risk assessment shows low or intermediate risk score in T2DM?
lifestyle and reassess in at least next 5 years
72
What to do if risk assessment shows high risk score in T2DM?
HbA1c testing
o If FPG<5.5 or HbA1c <42 – reassess after 3 years
o If FPG 5.5-6.9 or HbA1c 42-47 – offer lifestyle advice, intensive lifestyle-change programme and reassess at least 1x per year
o If FPG>7.0 or HbA1c >48 – carry out second HbA1c and if confirmed – treat according to guidelines, if <48 offer lifestyle-change programme
73
HbA1c test - definitions and when to diagnose T2DM?
- Pre-diabetes 42mmol/mol-47mmol/mol
o Lifestyle advice only
- Diagnosed when ≥48mmol/mol (or fasting PG ≥7.0mmol/L):
o Asymptomatic – two abnormal readings
o Symptomatic – one abnormal reading
74
Initial management in T2DM?
- Structured group education programme – DESMOND programme
- Lifestyle modifications – stop smoking, lose weight, foot care, regular exercise, treat risk factors
o Low glycaemic index foods, low fatty foods, high fibre
o Over a week, at least 150 minutes of moderate intensity physical activity (such as brisk walking or cycling) in bouts of 10 minutes or more
o Sick day rules – see diabetic teams
75
Drug treatment in T2DM - aims?
o Aim for 48 - if managed by lifestyle or one drug not associated with hypoglycaemia
o Aim for 53 - if drug associated with hypoglycaemia
o If HbA1c ≥58 - reinforce lifestyle advice, intensify drug treatment
76
Drug treatment in T2DM - self-monitoring?
o Only offer if on insulin, evidence of hypoglycaemic episodes, OHA with risk of hypoglycaemia while driving or operating heavy machinery or pregnant
77
Drug treatment in T2DM - when metformin appropriate - 1st line?
SR Metformin, titrate dose over weeks - 500mg OD with breakfast for at least 1 week, then 500mg BD for at least 1 week, then 500mg TDS to maximum 2g/day
Monitor renal function
Before (do not start if eGFR <30), annually if normal renal function, biannually if renal impairment
Stop if eGFR<30, caution if <45
78
Drug treatment in T2DM - when metformin appropriate - 1st intensification?
• Metformin + DPP-4 inhibitor (gliptins)OR
• Metformin + Pioglitazone OR
o Do not use pioglitazone if HF, hepatic impairment, DKA, current or Hx of bladder cancer, uninvestigated macroscopic haematuria
• Metformin + Sullfonylurea
79
Drug treatment in T2DM - when metformin appropriate - 2nd intensification?
• Metformin + DPP-4 inhibitor + sulfonylurea OR
• Metformin + pioglitazone + sulfonylurea OR
• Starting insulin-based treatment OR
• Metformin + sulfonylurea + GLP-1 mimetic (liraglutide)
o If – BMI >35 and psychological or medical problem associated with obesity or BMI<35 where insulin would have significant occupational implications or weight loss would benefit
• Metformin + DPP-4 inhibitor + ertugliflozin
• Metformin + sulfonylurea/thiazolidinedione + empagflozin/canagliflozin
80
Drug treatment in T2DM - when metformin not appropriate - 1st line?
• DPP-4 inhibitor OR pioglitazone OR sulfonylurea
81
Drug treatment in T2DM - when metformin not appropriate - 1st intensification?
* DPP-4 inhibitor + pioglitazone OR
* DPP-4 inhibitor + sulfonylurea OR
* Pioglitazone + sulfonylurea
82
Drug treatment in T2DM - when metformin not appropriate - 2nd intensification?
• Consider insulin-based treatment
83
When insulin indicated in T2DM - what regimen is used?
Continue metformin
Regimens:
• Offer NPH (isophane) insulin OD/BD
• Consider both NPH and short-acting either separately or pre-mixed
• Consider insulin detemir/glargine as alternative to NPH
• If metformin not used – gliptin plus sulfonylurea/pioglitazone or together
84
Other drug management in T2DM?
- Statin
o If QRISK2 is ≥10% and <84 years, atorvastatin 20mg
- Antihypertensive
o Aim for <140/90
o Lifestyle advice for 2 months
o ACEi OD (ACEi + diuretic/CCB for Afro-Caribbean)
Add CCB
Add thiazide like diuretic
Alpha-blocker, Beta-blocker or spironolactone
85
Follow up in T2DM?
- Every review
o Measure height, weight, waist circumference, BMI
o Smoking status
o Assess neuropathy
- Every 6 months
o Measure HbA1c every 3-6 months until stable and then 6-monthly
o If BP stable on medication (1-2 months until stable)
```
- Yearly
o Retinopathy
o Diabetic foot problems (foot checks monthly-weekly if at risk)
o Nephropathy (EMU for ACR, eGFR check)
o CVD (lipids, BP)
```
86
Names of gliptins?
- DPP-4 inhibitor
| - Sitagliptin, vildagliptin, saxagliptin, linagliptin
87
names of thiazolidinediones?
- Stimulates nuclear receptor PPAR-Gamma
- Can cause fluid retention, anaemia
- Pioglitazone, rosiglitazone
88
Names of flozins, SE?
- SGLT2 inhibitor
| - Common SE UTIs, joints pains, fungal infection
89
Names of GLP-1 mimetics?
- Glucagon-like peptide 1 receptor agonists (GLP-1 receptor agonists)
- Liraglutide
- Used if insulin cannot be used or need weight loss
90
Prognosis of T2DM?
- Optimal management, usually patients live normal life but may have complications
- Reduced life expectancy by average of 10 years
91
How to assess diabetic foot infection in diabetes?
```
o Neuropathy (10g monofilament as part of sensory foot exam)
o Limb ischaemia (pulses, CRT)
o Ulcers
o Callus
o Infection
o Deformity
o Gangrene
o Charcot arthropathy
```
92
Management of low risk diabetic foot disease?
annual foot assessments, emphasise foot care importance
93
Management of moderate-to-high risk diabetic foot disease?
Refer to foot protection services
| Assess within 2-4 weeks (high) or 6-8 weeks (moderate)
94
Assessment in foot protection services?
* Assess feet
* Advice, skin and nail care
* Biomechanical status of feet, specialist footwear provision
* Vascular status
95
When to reassess diabetic foot problems?
* Annual – low risk
* 3-6 months – moderate risk
* 1-2 months – high risk (no immediate concern)
* 1-2 weeks – high risk (immediate concern)
96
When to refer diabetic foot problems to hospital?
Ulcer with fever or signs of sepsis
Ulcer with limb ischaemia
Deep-seated soft tissue or bone infection
Gangrene
97
Management of Charcot arthropathy?
o Suspect Charcot arthropathy if red, warm, swollen and deformed foot
Refer within 1 working day to MDT foot care service for triage
98
Definiton of Charcot's arthropathy?
Deformed foot
Rocker bottom foot
Collapsed medial arch
99
Investigations of Charcot's arthropathy?
Weight-bearing X-ray of foot and ankle
| MRI if X-ray normal but still suspected
100
Management of Charcot's arthropathy?
Non-removable/Removable offloading device
| Monitor with foot-skin temperature difference and X-rays until resolves
101
Investigations in diabetic foot infections?
Soft tissue or bone sample from base of debrided wound for microbiology
FBC/ESR/CRP/blood cultures
X-ray of foot
MRI
102
Management in diabetic foot infections?
Antibiotics
• Mild – Oral flucloxacillin 500mg-1g QDS for 7 days (clarithromycin/doxycycline/erythromycin)
• Moderate/Severe
1. IV flucloxacillin 1g QDS +/- Gentamicin +/- Metronidazole
2. IV Co-amoxiclav +/- Gentamicin
3. IV Co-trimoxazole +/- Gentamicin +/- Metronidazole
4. IV Ceftriaxone +/- Metronidazole
• Pseudomonas aeruginosa
1. Tazocin 4.5g TDS IV
• MRSA
1. Vancomycin/Teicoplanin/Linezolid
o Review after 48 hours and consider oral switch
103
Investigations of diabetic foot ulcer?
Document size, depth and position of ulcer
| Use SINBAD (Site, ischaemia, neuropathy, bacterial infection, area and depth) to classify
104
Management of diabetic foot ulcer?
Offloading (plantar, forefoot and midfoot)
Control infection/ischaemia
Wound debridement & dressing
• UrgoStart dressings
105
Description of Graves' disease?
- Excess circulating thyroid hormones produced by overactive thyroid gland
106
Types of hyperthyroidism?
o Primary – causes by abnormal thyroid gland
Overt – TSH is low and T3/T4 high
Subclinical – TSH low and T3/T4 normal
o Secondary – abnormal stimulation of thyroid gland
107
Epidemiology of Graves' disease?
- 10x more common in women
108
Risk factors of Graves' disease?
```
o Women 10x
o FHx of thyroid disease
o Smoking
o Low iodine intake
o T1DM
```
109
Causes of primary hyperthyroidism?
Graves’ Disease
Toxic Multinodular Goitre
Toxic thyroid adenoma
Drugs
110
Definition of Grave's disease?
* Most common cause, 75%
* Autoimmune disorder, antibodies that stimulate TSH leading to excessive secretion of thyroid hormones and hyperplasia of thyroid cells
* Causes toxic diffuse goitre
111
Definition of toxic multinodular goitre?
* Thyroid with >2 autonomously functioning thyroid nodules that secrete excess thyroid hormones (benign follicular adenomas)
* People >60, iodine deficient areas (Denmark)
112
Definition of toxic thyroid adenoma?
• Nodule produces enough hormone to supress TSH from pituitary and contralateral thyroid lobe
113
What drugs cause hyperthyroidism?
• Iodine (amiodarone, IV contrast), lithium, IFN-alpha
114
Causes of secondary hyperthyroidism?
High hCG (gestational, multiple pregnancy, choriocarcinoma, hydatidiform mole)
Pituitary adenoma
115
What causes thyrotoxicosis without hyperthyroidism?
Drugs – levothyroxine, amiodarone, corticosteroids
| Thyroiditis (release of thyroid hormones into circulation due to inflammation of follicles)
116
Types of thyroiditis?
• Postpartum
o Autoimmune, usually painless, occurs 2-6 months after delivery
o Thyrotoxicosis followed by hypothyroidism within 1 year of giving birth in previously euthyroid women
o Most becomes euthyroid within 12 months
• Acute
o Bacterial infection of thyroid gland via pyriform sinus connecting gland with oropharynx
• Subacute (De Quervain’s) thyroiditis
o Self-limiting, post-viral painful goitre, high temp, high ESR
o Rx NSAIDs
117
Symptoms of hyperthyroidism?
o Malaise, fever
o Thyroid pain
o Hyperactivity, insomnia, irritability, anxiety, palpitations
o Heat intolerance, sweating
o Increased appetite, weight loss, diarrhoea
o Infertility, oligomenorrhoea, amenorrhoea
o Reduced libido
118
Signs of hyperthyroidism?
```
o Agitation
o Fine tremor
o Moist skin
o Palmar erythema
o Sinus tachycardiac, AF
o Thin hair
o Goitre
o Muscle wasting
o Hyperreflexia
```
119
Features of goitres in Graves', toxic multinodular goitre, toxic adenoma, subacute de Quervains?
Grave’s – diffusely enlarged and pyramidal lobe palpable, may be bruit, soft and symmetrical
Nodules – toxic multinodular goitre
Unilateral non-tender – toxic adenoma
Tender, enlarged, firm, irregular gland – subacute de Quervain’s thyroiditis
120
Signs in Graves' disease?
o Eye disease – exomphalos, proptosis, ophthalmoplegia
o Pretibial myxoedema (swelling above lateral malleoli)
o Thyroid acropachy – clubbing, painful finger and toe swelling
121
Blood tests to perform in hyperthyroidism?
TFTs (TSH, T3/4)
122
What to do if TSH within normal range in hyperthyroidism?
further investigations not usually needed
123
What to do if TSH low (but over 0.1) in hyperthyroidism?
recheck along with FT4 &FT3 after 1-2 months
124
What to do if TSH <0.1 in hyperthyroidism?
check FT4 and FT3
125
Definitions of hyperthyroidism according to TSH and T3/4?
Low TSH and raised T3/4 = overt hyperthyroidism (Graves’, amiodarone)
Low TSH with thyroid pain = thyroiditis
Low TSH but normal T3/4 = subclinical hyperthyroidism
Low TSH on levothyroxine = over-treatment
High TSH & T3/4 = TSH-secreting pituitary adenoma
126
Investigations to perform if thyroiditis suspected?
CRP/ESR
127
Management of overt hyperthyroidism?
Refer overt hyperthyroidism to endocrinology
Whilst awaiting specialist assessment:
Beta-blockers (propranolol) to control tremor and tachycardia
128
Specialist management in hyperthyroidism - testing?
* Thyroid-stimulating hormone receptor antibodies (TSH-RAb) – Grave’s disease
* Radionucleotide thyroid uptake – diffuse in Grave’s, one or more hot nodule
129
Specialist management in hyperthyroidism - drug treatment?
* Radioiodine
| * Carbimazole (or propylthiouracil)
130
Management with radioiodine in hyperthyroidism?
o First line in toxic nodular goitre & Grave’s disease
| o For 18 months
131
Management with carbimazole (or propylthiouracil) in hyperthyroidism?
o After euthyroidism achieved:
Titration-block regime – carbimazole used and dose adjusted every 4-6 weeks, allow endogenous synthesis of thyroid hormone to continue
Block and replace regime – carbimazole used to block synthesis of thyroid hormone and levothyroxine added
o Both continued for 6-18 months
132
Surgical management in hyperthyroidism?
• Total or near-total thyroidectomy
| o Second-line in multiple nodules
133
Management of subclinical hyperthyroidism?
o Repeat TFTs in 3-6 months
o Refer to endocrinologist if persistent subclinical hyperthyroidism
Treatment given if TSH <0.1, >65, postmenopausal, or risk of osteoporosis/CVD
134
Management of Graves' orbitopathy?
o Admit immediately – if suspected optic neuropathy, corneal opacity or Hx of globe subluxation
o Refer to ophthalmology
135
General advice given in hyperthyroidism/Graves' disease?
Smoking cessation
Artificial tears to lubricate eyes
Avoid damage to eyes
Elevate head of bed
136
Follow up in hyperthyroidism - if on carbimazole/propylthiouracil?
Before – FBC, LFT
Every 6 weeks – TSH, FT4, FT3
Every 3 months – TSH
After stopping – TSH within 8 weeks, then every 3 months for a year then once a year
137
Follow up in hyperthyroidism - after radioactive iodine treatment?
Every 6 weeks – TFTs
138
Follow up in hyperthyroidism - after surgery?
TSH and FT4 at 2 and 6 months, then TSH annually
139
Follow up in hyperthyroidism - if in remission?
TFTs annually
140
Follow up in hyperthyroidism - if untreated subclinical hyperthyroidism?
Check TFTs every 6-12 months
141
Prognosis of hyperthyroidism?
Remission in up to 30% without treatment in Grave’s
| Risk of relapse if anti-thyroid drug stopped
142
Complications of Graves' disease - orbitopathy?
Autoimmune disorder in 90% of Graves disease
Eye irritation, photophobia, watering of eyes, swelling of eyes
Lid lag, troubled eyelid retraction
Double vision, low visual acuity
143
Symptoms of thyrotoxic storm?
tachycardia, fever, AF, HF, fever, diarrhoea, vomiting, dehydration, delirium, coma
144
Tests in thyrotoxic storm?
Tests – TFTs, technetium uptake if possible
145
Management of thyrotoxic storm?
* IV access, fluids if dehydrated and NG tube if vomiting
* Bloods – TFTs, cultures if infection, TRAbs
* Sedation (chlorpromazine)
* Propranolol 40mg/8h PO
* If CI: diltiazem
* High-dose digoxin to slow heart – ECG monitoring
* Carbimazole 15-25mg/6h PO
* Hydrocortisone IV or dexamethasone PO to prevent peripheral conversion of T4 into T3
* If infection – co-amoxiclav
146
Other complications in hyperthyroidism?
```
o AF
o Heart failure
o Reduced bone mineral density
o Anxiety/Depression
o In pregnancy – miscarriage, pre-eclampsia, prematurity, IUGR, low birthweight
```
147
Definition of adrenal insufficiency? Epidemiology?
- Destruction of cortex leads to primary adrenal insufficiency
o Reduces glucocorticoids (cortisol), mineralocorticoids (aldosterone) and adrenal androgens (dehydroepiandrosterone)
o Absence of cortisol leads to increased ACTH from pituitary gland
- Adrenal insufficiency can be caused by long-term corticosteroids or disorders of hypothalamus/pituitary but this is secondary:
o Pituitary ACTH insufficient and adrenal atrophy
- 1 in 20000
- Women 30-50
148
Causes of Primary adrenal insufficiency?
```
Addison's Disease (80%)
TB
Adrenal metastases/haemorrhage
Amyloidosis/haemachromatosis
Infection – histoplasmosis, cryptococcosis, CMV, HIV
CAH
Adrenalectomy
```
149
Causes of Secondary adrenal insufficiency?
Exogenous steroids
Antipsychotic medication
Tumours secreting steroids
Trauma, radiotherapy, surgery, neoplasm to hypothalamus
150
Associated diseases with adrenal insufficiency?
o Hypothyroidism
| o T1DM
151
Symptoms of Addison's disease?
```
o Lean
o Tanned (due to increase ACTH – sun-exposed areas, scars, palmar creases, mucous membranes)
```
o Fatigue, weight loss, anorexia, N&V, abdominal pain
o Muscle weakness, cramps, joint pains
o Postural dizziness (postural hypotension)
o Increased thirst/urination
o Craving soy sauce and liquorice
152
Primary care tests performed in Addison's disease? What are the findings?
```
Serum cortisol level
Specialist advice from endocrinologist before serum cortisol if people work shifts, on long-term corticosteroids, receiving oestrogen treatment
Obtain 8-9am
If <100 – admit
If 100-500 – refer to endocrinologist
```
o U&Es
Low Na and High K
153
Secondary care tests performed in Addison's disease - diagnostic 3?
1. ACTH Stimulation (Synacthen) test - Blood sample to check cortisol before and 30 minutes after 250mcg of tetracosactide (synthetic ACTH) IV or IM
* Normal – cortisol increase to >500-550nanomol/L after 30-60 minutes
* Adrenal insufficiency – cortisol does not increase adequately
2. ACTH levels (high in Addison’s, low in secondary adrenal insufficiency)
3. Plasma renin and aldosterone levels (renin high, aldosterone low)
154
Secondary care tests performed in Addison's disease - autoantibodies?
Adrenal cortex autoantibodies
| 21-hydroxylase antibodies
155
Secondary care tests performed in Addison's disease - imaging?
CXR/AXR
| CT scan if TB, infection, haemorrhage or neoplastic disease suspected
156
Management of Addison's disease - drug therapy?
o Steroid Replacement
Glucocorticoid replacement – hydrocortisone 15-30mg daily (10mg waking, 5mg lunch and 5mg in early evening)
Mineralocorticoid replacement – fludrocortisone 50-300mcg
o Androgen replacement
Dehydroepiandrosterone may be used in specialist care
157
Management of Addison's disease - general management?
Lifelong treatment
Do not stop abruptly
Steroid card and MedicAlert bracelet
Adjusting steroid medication
Recognise adrenal crisis and give IM hydrocortisone
If undergoing surgery, endoscopy or dental treatment
• Make team aware and cover glucocorticoid cover
158
Management of Addison's disease - illness rules?
o Double normal dose of hydrocortisone if fever/antibiotics
o If nausea – take 20mg hydrocortisone orally and sip ORS
o If vomited – IM hydrocortisone and seek advice
159
Management of Addison's disease - Exercise rules?
```
o Strenuous (marathon) – up to double dose
o Normal exercise – 5-10g hydrocortisone before activity
```
160
Management of Addison's disease - follow up?
Primary and secondary care shared
Annual
• Weight, BP, U&Es
• TFTs, glucose, HbA1c, FBC, VitB12, coeliac
161
Symptoms of adrenal crisis?
Symptoms: malaise, fatigue, N&V, abdominal pain, shock (tachycardia, postural hypotension, oliguria, weak, confused)
Precipitating factors – infection, trauma, surgery, missed medication
162
Initial management of adrenal crisis?
```
IM/IV hydrocortisone
• 100mg adults
• 50-100mg child >6 depending on size
• 50mg child 1-5
• 25mg child <1
Bloods – cortisol, ACTH, U&Es
IV fluid bolus
Monitor ECG, blood glucose
Blood, urine and sputum culture
Abx if infection suspected
```
163
Further management of adrenal crisis?
IV glucose if needed
IV fluids and correct electrolyte imbalance
Continue IV hydrocortisone 100mg/8h
Change to oral steroids after 72 hours if condition good
164
Prognosis of Addison's Disease?
o If untreated – fatal
| o Require lifelong treatment
165
Description of hypothyroidism?
- Impaired production of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3)
166
Types of hypothyroidism?
o Primary (95%) – thyroid gland unable to produce thyroid hormones:
Overt – High TSH and low T4
Subclinical – High TSH and normal T3/T4
o Secondary – insufficient production of TSH due to pituitary or hypothalamic disorder
167
Epidemiology of hypothyroidism?
- Prevalence 1-2%
- Women 10x
- Secondary hypothyroidism is rare
- Congenital hypothyroidism is screened for in Guthrie test
168
Causes of primary hypothyroidism?
o Iodine deficiency (MC worldwide cause)
o Autoimmune thyroiditis (atrophic/Hashimoto’s) – MC in UK
Atrophic – common, diffuse lymphocyte infiltrate of thyroid, atrophy and NO goitre
Hashimoto’s – goitre due to lymphocytic and plasma cell infiltration, women 60-70, high autoantibodies
o Post-ablative therapy or surgery
o Drugs – anti-thyroid drugs, iodine, amiodarone, lithium, thalidomide, rifampicin
o Transient thyroiditis (subacute, postpartum)
o Thyroid infiltrative disorders – amyloidosis, sarcoidosis, haemochromatosis, TB, scleroderma
o Congenital hypothyroidism – absence or thyroid, ectopic hypoplastic
169
Causes of secondary hypothyroidism?
o Pituitary dysfunction – tumours (pituitary adenoma), surgery, radiotherapy, infarction, Sheehan’s syndrome, infiltrative disorders
o Hypothalamic dysfunction – tumours (glioma), surgery, radiotherapy, infiltrative disorders, drugs (retinoids)
170
Symptoms of hypothyroidism?
```
o Tired/Lethargic
o Low mood
o Cold intolerance
o Weight gain
o Constipation
o Menorrhagia
o Dry skin, reduced body hair (eyebrows)
o Hoarse voice
o Myalgia, cramps, muscle weakness
```
171
Signs of hypothyroidism?
```
o Bradycardic
o Coarse dry skin/hair, hair loss
o Oedema, ascites and including around eyes
o Goitre
o Delayed relaxation of reflexes
o Paraesthesia – carpal tunnel syndrome
```
172
Symptoms specifically in secondary hypothyroidism?
also with headache, diplopia, pituitary hormone symptoms
173
Symptoms in postpartum hypothyroidism?
usually 3-8 months PP and lasts 6 months
174
Bloods taken in hypothyroidism? Interpretation of results?
TFTs
```
Overt = TSH high, T4 low
Subclinical = TSH high, T4 normal
• Measure again 3-6 months
Secondary = T4 low without raised TSH
Pregnancy = TSH high
• Measure thyroid peroxidase antibodies (TPOAb) and if negative, thyroglobulin antibodies (TgAb)
```
175
Bloods tested if primary hypothyroidism suspected?
FBC – anaemia
HbA1c – T1DM
Lipids
Thyroid peroxidase antibodies (TPOAb)
176
Imaging if goitre present with hypothyroidism?
USS
177
When to screen TFTs in people for hypothyroidism - if pregnant or planning?
>30, goitre, lives in iodine deficient area, FHx, symptoms, T1DM, Hx of neck radiotherapy, BMI>40
178
When to screen TFTs in people for hypothyroidism - if not pregnant?
Goitre, T1DM, T2DM, AF, Osteoporosis, Dyslipidaemia, hyperthyroidism surgery/radioiodine, Hx of neck radiotherapy, Down’s/Turners, subfertile, post-partum depression, drugs (lithium, amiodarone)
179
Management of overt hypothyroidism - referral to endocrine?
Suspected subacute thyroiditis, goitre, nodule, endocrine disease, female and planning pregnancy, CVD, drug-induced
180
Management of overt hypothyroidism - drug treatment?
Levothyroxine
• 50-100mcg OD, adjusted in steps of 25-50mcg
o Over 65 – 25-50mcg OD
• Review every 3-4 weeks and adjust dose
• Dose taken >30 minutes before breakfast or caffeinated drinks
181
Management of overt hypothyroidism - follow up?
o Once stable, TSH every 4-6 monthly and then annually
| o Check lipids if elevated initially
182
Management of subclinical hypothyroidism?
o Most do not need treatment but if so: levothyroxine
If TSH >10 – start if <70, if >70 watch and wait
If TSH 4-10 - <65 start, >65 ‘watch and wait’
183
Follow up of subclinical hypothyroidism?
* Annually if symptoms, thyroid surgery, raised Ab levels
| * Every 2-3 years if no features of disease
184
Management of secondary hypothyroidism?
o Refer urgently to endocrinologist
185
Management of postpartum hypothyroidism?
o If thyrotoxic pattern – refer to differentiate from Grave’s
o TFT every 2 months
If hypothyroid – if planning another pregnancy then treat, if not reassess in 2 months
o Annual TFTs
186
Symptoms of myxoedema coma?
o Symptoms: hypothyroid, hypothermia, hyporeflexia, low glucose, bradycardic, coma, seizures, psychotic (myxoedema madness)
o Signs: goitre, cyanosis, low BP, HF
187
Management of myxoedema coma?
```
ICU
Bloods – TFTs, FBC, U&Es, cultures, cortisol, glucose
ABG
High-flow O2 and ventilation if needed
T3 (liothyronine) IV slowly
Hydrocortisone 100mg/8h IV
Antibiotics
Warming (blankets, fluids)
Following initial management – levothyroxine PO
```
188
Prognosis of hypothyroidism?
o Good, most recover with levothyroxine for life
o Subclinical may revert spontaneously to euthyroid
o Postpartum usually resolves after 1 year
189
Complications of hypothyroidism?
```
o Impaired QoL
o Dyslipidaemia
o CHD/Stroke
o Heart failure
o Impaired fertility
o Pregnancy – miscarriage, pre-eclampsia, placental abruption, PPH, stillbirth, premature, LBW, congenital hypothyroidism
o Deafness, impaired cognitive function
o Myxoedema coma
Rare, presents with hypothermia, coma and seizures
Precipitant usually HF, sepsis, stroke
```
190
Describe calcium homeostasis - high levels and low levels?
o High calcium level leads to thyroid releasing (vitamin D3 – 1, 25-dihydroxy-vitamin D) calcitonin which:
Promotes osteoblasts deposit calcium in bone
Reduces absorption of calcium in kidneys
o Low blood calcium level leads to parathyroid releasing PTH which:
Promotes osteoclasts to release calcium from bones
Stimulates kidney to absorb calcium
Kidney converts 25-hydroxy Vitamin D to 1-25 dihydroxy Vitamin D to stimulate bowels to absorb calcium
191
Definition of hyperparathyroidism?
excessive of PTH, leads to raised serum Ca and low phosphate
192
Types of hyperparathyroidism?
o Primary – one or more parathyroid gland produces excess PTH
o Secondary – increased secretion of PTH in response to low calcium due to kidney, liver or bowel disease
o Tertiary – autonomous secretion of PTH, usually CKD
193
Epidemiology of hyperparathyroidism?
- 3rd most common endocrine disorder
| - Primary hyperparathyroidism – common in women 50-60 years old
194
Causes of primary hyperparathyroidism?
Single parathyroid adenoma 80% (may be due to MEN1, 2a)
Hyperplasia of all glands 20%
Parathyroid carcinoma <1%
195
Causes of secondary hyperparathyroidism?
CKD – hyperplastic after long-term stimulation due to chronic hypocalcaemia
Low vitamin D intake
Malabsorption
196
Causes of tertiary hyperparathyroidism?
Prolonged secondary hyperparathyroidism
• Glands become autonomous, producing excessive PTH even after corrected hypocalcaemia
CKD most common cause
197
Symptoms of hypercalcaemia?
```
o Lethargy
o Malaise
o Muscle weakness
o Anorexia
o Polyuria
o Thirst
o Nausea & vomiting
o Constipation
o Bone pain
```
```
o Confusion
o Memory problems
o Drowsiness
o Fits
o Coma
```
198
Signs of primary hyperparathyroidism?
Hypertension, shortened QT interval
Peptic ulcers (duodenal 7x)
Depressed
199
Symptoms of secondary hyperparathyroidism?
o CKD
o Oesteomalacia, fracture risk, myopathy
o Bone pain
200
Symptoms of tertiary hyperparathyroidism?
o Hypercalcaemia symptoms so similar to primary
201
What incidental findings indicate primary hyperparathyroidism?
Hypercalcaemia
| Hypophosphataemia
202
Diagnostic testing in primary care for primary hyperparathyroidism - when and results?
Albumin-adjusted serum Ca (total) – NOT IONISED CALCIUM
• When - Symptoms of hypercalcaemia, osteoporosis, renal stone, incidental elevated albumin-adjusted serum calcium >2.6mmol/L
• Results - Repeat if 1st measurement 2.6 or above or 2.5-2.6 with features of 1o hyperparathyroidism
```
Parathyroid Hormone (PTH)
• When - If calcium 2.6 or above on at least 2 separate occasions OR 2.5 or above on at least 2 separate occasions and 1o hyperparathyroidism suspected
• Results - Refer to endocrinologist if above midpoint of reference range and primary hyperparathyroidism suspected or below midpoint with Ca >2.6
```
203
Further testing performed in primary hyperparathyroidism?
Vitamin D
Urine calcium excretion
• To determine if familial hypocalciuric hypercalcaemia
• 24-hour urinary calcium, renal calcium:creatinine excretion ratio or calcium:creatinine clearance ratio
Skull XR
• Salt and pepper pot skull
204
Investigations once diagnosis confirmed of primary hyperparathyroidism?
U&Es
DEXA scan of lumbar spine, distal radius and hip
US of renal tract
205
Bloods in secondary hyperparathyroidism?
Low-normal calcium
Raised PTH
Phosphate (high in CKD, low in Vitamin D deficiency)
206
Bloods in tertiary hyperparathyroidism?
Raised Ca
Raised PTH
Phosphate often raised
207
Management of primary hyperparathyroidism - mild, asymptomatic disease?
o Mild, asymptomatic disease
Increase fluids
Avoid thiazides + high Ca diet
Check U&Es and calcium every 6 months
o Vitamin D supplements if deficient
208
Management of primary hyperparathyroidism - surgical management - when to refer, imaging before surgery?
Refer to surgeon if diagnosed and:
• Symptoms of hypercalcaemia
• End-organ disease (stones, fragility fractures, osteoporosis)
• Albumin-adjusted calcium 2.85 or above
Imaging before surgery (if needed):
• US
• Sestamibi scan
Type of surgery
• 4-gland exploration – if US doesn’t show single adenoma
• Focussed parathyroidectomy – if adenoma
209
Management of primary hyperparathyroidism - surgical management - follow up after surgery?
• Before surgery
o Albumin-adjusted serum calcium
o PTH
• 3-6 months after
o Albumin-adjusted serum calcium
210
Management of primary hyperparathyroidism - drug treatment?
Cinacalcet
• Increases sensitivity of parathyroid cells to Ca (lowers PTH)
• If surgery unsuccessful, unsuitable or declined and Ca is:
o 2.85 or above with symptoms of hypercalcaemia
o 3.0 or above with/without symptoms
• Continue until symptoms reduced and hypercalcaemia resolved
Bisphosphonates
• If increased risk of fractures
211
Monitoring of primary hyperparathyroidism?
Endocrinologist monitoring
If successful surgery:
• Albumin-adjusted serum calcium annually
• If osteoporosis - DEXA scan according to local guidelines
• If renal stones – US KUB according to local pathways
If no surgery or not successful:
• U&Es and albumin-adjusted serum calcium annually
• DEXA scan every 2-3 years
• US KUB if stone suspected
212
Management of secondary hyperparathyroidism ?
```
o Medical treatment
Treat vitamin D deficiency
Calcium supplementation
Phosphate restriction +/- binders
Cinacalcet if ESKD and SHPT refractory and not suitable for surgery
```
o Surgery
Parathyroidectomy if medical refractory
213
Management of tertiary hyperparathyroidism ?
o Cinacalcet
| o Total or subtotal parathyroidectomy
214
Management of tertiary hyperparathyroidism ?
o Cinacalcet
| o Total or subtotal parathyroidectomy
215
Definition of hypercalcaemia?
- Defined as a serum Ca concentration of 2.65 mmol/L or higher, on two occasions, following correction for the serum albumin concentration
216
Describe calcium homeostasis?
o High blood calcium level leads to thyroid releasing (vitamin D3 – 1, 25-dihydroxy-vitamin D) calcitonin which:
Promotes osteoblasts deposit calcium in bone
Reduces absorption of calcium in kidneys
o Low blood calcium level leads to parathyroid releasing PTH which:
Promotes osteoclasts to release calcium from bones
Stimulates kidney to absorb calcium
Kidney converts 25-hydroxy Vitamin D to 1-25 dihydroxy Vitamin D to stimulate bowels to absorb calcium
217
Pathophysiology of hypercalcaemia of malignancy?
o Transforming growth factor Alpha
Produced by tumours and powerful stimulator of bone resorption
o Parathyroid hormone (PTH) related peptides
Tumour-associated protein that mimics PTH, stimulates bone reabsorption and increases plasma calcium
218
Causes of hypercalcaemia?
```
o Primary Hyperparathyroidism
o Cancer
Squamous cell lung cancer
Breast cancer
Prostate cancer
Renal cell carcinoma
Multiple myeloma/lymphoma
Head and Neck cancers
o Drugs
Thiazide diuretics
Lithium
Vit A & D
o CKD
```
219
Symptoms of hypercalcaemia?
Bones, stones and psychiatric moans
```
Early
• Lethargy
• Malaise
• Anorexia
• Polyuria
• Thirst
• Nausea & vomiting
• Constipation
• Bone pain
Late
• Confusion
• Drowsiness
• Fits
• Coma
```
220
Signs of hypercalcaemia?
```
o Hyporeflexia
o Weight loss
o Bradycardia
o Short QT interval, wide T wave, Prolonged PR
o BBB
```
221
Investigations in known malignancy of hypercalcaemia?
```
o Bloods
Serum calcium corrected for albumin
• Mild – adjusted calcium 2.6-3.0mmol/L
• Moderate – adjusted calcium 3.01-3.4mmol/L
• Severe – adjusted calcium >3.4mmol/L
LFTs, FBC
```
o ECG
Shortened QT interval
Osborn wave
222
Management of severe hypercalcaemia?
Rehydration
0.9% saline 1L 4-hourly for 24 hours, then 6 hourly for 48-72 hours
Give K+
May need furosemide if at risk of fluid overload
```
IV Bisphosphonates (pamidronate or zoledronic acid)
Response seen in 70% around 6-11 days for 3-4 weeks
```
Salmon calcitonin SC/IM with oral prednisolone
Stop thiazides and vitamin D
223
Definition of hyperlipidaemia?
- Raised serum levels of one or more of total cholesterol, LDLs or triglycerides
224
Epidemiology of hyperlipidaemia?
- UK has highest serum cholesterol levels in world
- 2/3rds over 5.2mmol/L
- Heterozygous familial hypercholesterolaemia
o 1 in 500 people
225
Inherited causes of hyperlipidaemia?
Familial dyslipidaemia, hypercholesterolaemia, combined hyperlipidaemia
Apoprotein disorders
226
Secondary causes of hyperlipidaemia?
Medical – hypothyroidism, obstructive jaundice, Cushing’s syndrome, anorexia, diabetes, CKD
Drugs – thiazide diuretics, glucocorticoids, ciclosporin, ART, beta-blockers, COCP, atypical antipsychotics
Pregnancy
Obesity
Alcohol Abuse
227
Risk factors of hyperlipidaemia?
o Non-modifiable
Age, men, FHx, South Asian or sub-Saharan Africa
o Modifiable
Smoking, low HDL, high non-HDL, sedentary lifestyle, unhealthy diet, alcohol excess, overweight
Socio-economic status
o Co-morbidities
Hypertension, DM, CKD, AF, RA, SLE
228
What is the risk assessment performed in primary care for hyperlipidaemia?
o QRISK2 in primary care
For patients up to and including 84 years and patients with T2DM
• People aged 40-74 – offered an NHS health check every 5 years
• Repeat every 5 years
DO NOT USE WITH T1DM, eGFR<60, PRE-EXISTING CVD, FAMILIAL HYPERCHOLESTEROLAEMIA
229
How to take lipid measurement of hyperlipidaemia? When to refer?
Measure total and HDL cholesterol – before primary prevention of CVD, take at least 1 sample to measure full lipid profile
Consider familial hyperholesterolaemia if:
TChol >7.5 and FHx of premature coronary heart disease
Refer to specialist if:
Urgent if TG >20mmol/L, TChol >9.0mmol/L or non-HDL-C >7.5mmol/L
If TG 10-20 – repeat with fasting test within 2 weeks, refer is above 10
230
Management of hyperlipidaemia - primary prevention - lifestyle modifications?
Avoid exceeding alcohol limits and avoid binges
Total fats <30% total energy intake, cholesterol <300mg/day, reduce saturated fats, increase mono-unsaturated fats (olive oil, rapeseed oil), choose wholegrain food, reduce sugar, eat 5-a-day
150 minutes of moderate exercise per week
Stop smoking
Healthy body weight
231
Management of hyperlipidaemia - primary prevention - statin treatment - tests done before starting?
Smoking status, alcohol status, BP, BMI
Lipid profile, HbA1c, LFT (fine if <3x normal limit), U&E, TFTs
If generalise muscle pain – measure CK – if >5x limit of normal, re-measure after 7 days – if <5x then start statin at lower dose
Avoid grapefruit juice
232
Management of hyperlipidaemia - primary prevention - statin treatment?
Atorvastatin 20mg OD
• When to offer:
o QRISK2 >10% (<84 years, >84 decide clinically)
o Type 1 diabetic who: >40, diabetes for >10 years, established nephropathy, other CVD risk factors
o Type 2 DM – if QRISK2 >10%
o CKD – all patients
eGFR >30 (if under seek specialist)
Increase dose if <40% reduction in non-HDL cholesterol
o Familial hypercholesterolaemia
233
Management of hyperlipidaemia - secondary prevention - statin treatment - when to offer it and how much?
Atorvastatin 80mg OD
• When to offer:
o CVD (MI, angina, stroke, TIA, PAD) event
Atorvastatin 20mg OD
• Offer after CVD event in CKD
o eGFR >30 (if under seek specialist)
o Increase dose if <40% reduction in non-HDL cholesterol
234
Management if statin intolerance in hyperlipidaemia?
Aim to treat with maximum tolerated dose – any dose reduces CVD
Strategies:
• Stop and start again, reduce dose, change statin
235
Monitoring statin therapy in hyperlipidaemia?
o LFTs – baseline, 3 months of starting treatment and 12 months
o Lipid profile – baseline, 3 months
Aim for >40% reduction in non-HDL cholesterol
If not – consider adherence, diet and lifestyle and increasing dose
o Annual medication review
o If muscle pain or weakness on a statin:
Measure CK - if >5x limit of normal, re-measure after 7 days – if <5x then start statin
236
Definition of familial hypercholesterolaemia?
- Inherited autosomal dominant condition characterised by high cholesterol concentration in blood
o Can be heterozygous or homozygous
- Heterozygous is common – estimated between 1 in 250 and 1 in 500
237
Identifying people with familial hypercholesterolaemia?
o Suspect if TChol >7.5 +/- FHx of premature CHD
o If FHx of premature CHD – offer TChol
o In children with parent with FH – refer for DNA test
238
Assessment of people of familial hypercholesterolaemia?
```
o 2 LDL cholesterol measurements
Diagnosis if: adults >13, children >11
o Clinical signs – tendon xanthomas
o Exclude secondary causes:
Medical – hypothyroidism, obstructive jaundice, Cushing’s syndrome, anorexia, diabetes, CKD
Drugs – thiazide diuretics, glucocorticoids, ciclosporin, ART, beta-blockers, COCP, atypical antipsychotics
Pregnancy
Obesity
Alcohol Abuse
```
239
What is the Simon Broome criteria for familial hypercholesterolaemia?
Definite – Tchol >6.7 or LDL >4 in children, TChol >7.5 or LDL>4.9 in adults with tendon xanthomas and DNA mutation
Possible - – Tchol >6.7 or LDL >4 in children, TChol >7.5 or LDL>4.9 in adults with FHx of premature CHD
240
Management of familial hypercholesterolaemia - general advice?
o Adults with heterozygous
o Refer very high risk (established CHD, FHx of premature CHD, >2 CVD RF)
o Routine referral to cardiologist if FHx of CHD in early adulthood
Baseline ECG
241
Management of familial hypercholesterolaemia - lifestyle advice?
Avoid exceeding alcohol limits and avoid binges
Total fats <30% total energy intake, cholesterol <300mg/day, reduce saturated fats, increase mono-unsaturated fats (olive oil, rapeseed oil), choose wholegrain food, reduce sugar, eat 5-a-day
150 minutes of moderate exercise per week
Stop smoking
Healthy body weight
242
Management of familial hypercholesterolaemia - statin treatment?
Before
• Smoking status, alcohol status, BP, BMI
• Lipid profile, HbA1c, LFT (fine if <3x normal limit), U&E, TFTs
• If generalise muscle pain – measure CK – if >5x limit of normal, re-measure after 7 days – if <5x then start statin
• Avoid grapefruit juice
Primary Prevention
• Atorvastatin 20mg OD
o Aim for 50% reduction in LDLs
• If CI or statin therapy fails to achieve target – Ezetimibe 10mg OD or Simvastatin 80mg OD
243
Complications of familial hypercholesterolaemia?
o Without treatment – heterozygous FH leads to >50% risk of CHD in men by 50 and >30% in women
o If treated early – normal life expectancy
244
Physiology of PTH secretion?
o PTH secreted in response to low Ca2+ levels
| o By 4 parathyroid glands situated posterior to thyroid
245
Control of PTH secretion?
o Negative feedback via Ca2+ levels
246
Actions of PTH?
o Increased osteoclast activity releasing Ca and PO4 from bones
o Increased Ca and decreased PO4 resorption in kidney
o Active 1, 25-dihydroxy-vitamin D production is increased
247
OVerall effect of PTH?
Raise Ca, lower PO4
248
Definition of hypoparathyroidism? - Congenital and Acquired?
- Hypoparathyroidism = low Ca, high PO4 and low (or inappropriately normal) PTH
o Congenital = gland failure, low secretion of PTH
o Acquired = Radiation, surgery (thyroidectomy, parathyroidectomy), hypomagnesaemia (Mg required for PTH secretion)
249
Definition of pseudo-hypoparathyroidism?
- Pseudohypoparathyroidism = low Ca, high PO4 with high PTH (PTH resistance)
250
Causes of congenital hypoparathyroidism?
Autoimmune destruction of glands – autoimmune polyglandular syndrome
• Type 1 – mutation of auto immuneregulator gene on c21
o Features: Addison’s, chronic candiasis, hypoparathyroidism, hypogonadism, pernicious anaemia, vitiligo, alopecia
• Type 2
o Features: Addison’s, T1DM, coeliac disease, hypothyroidism, hypogonadism, pernicious anaemia, vitiligo, alopecia
DiGeorge Syndrome
• CATCH22
• Cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcaemia c22q11 deletion
Kenny-Caffey syndrome, Kearns-Sayre syndrome, Sanjad-Sakati syndrome, Defect in calcium-sensing receptor gene/PTH gene
251
Causes of acquired hypoparathyroidism?
Post-neck surgery (thyroid, parathyroid, laryngeal, oesophageal)
Accidental damage, removal
Radiation
Chemotherapy
Alcohol
Infiltration of parathyroid glands (iron, copper)
Magnesium deficiency
252
Symptoms of hypocalcaemia?
- Muscle, bone and abdominal pain
SPASMODIC
o Spasms (carpopedal spasms = Trousseau’s sign)
o Perioral paraesthesia (face, fingers, toes)
o Anxious, irritable, irrational
o Seizures (grand mal)
o Muscle tone increased in smooth muscle (colic, wheeze, dysphagia)
o Orientation impaired (confused)
o Dermatitis
o Impetigo herpetiformis
o Chvotek’s sign (corner of mouth twitches when facial nerve tapped over parotid), cataract, cardiomyopathy
253
Blood tests performed in hypoparathyroidism? ECG findings in hypocalcaemia?
```
- Bloods
o Bone profile – low Ca, high PO4, PTH
PTH – low in primary and secondary
PTH – high in pseudohypoparathyroidism
o Serum Mg (may be low)
o U&Es
o Vitamin D levels
o Others:
TFTs, ACTH, Fe, Copper
```
- ECG
o Prolonged QT interval
254
Other investigations to consider in hypoparathyroidism?
```
o 24-hour urine calcium – usually low
o Renal US
o Brain MRI
o Echocardiogram
Cardiac abnormalities (DiGeorge)
```
255
Emergency treatment in hypoparathyroidism?
o If hypocalcaemia severe (<1.88mmol)
IV calcium gluconate (90mg) then infusion
Continuous ECG monitoring
o IF hypomagnesaemia
IV Magnesium sulphate 1g QDS
256
Acute asymptomatic or chronic treatment in hypoparathyroidism?
o Calcium and vitamin D supplements
Oral calcium carbonate 500-1000mg BDS/TDS
Oral calcitriol (vitD) 0.25-1mcg BDS
If inadequate – PTH hormone 50mcg SC OD
Thiazide diuretic reduces urinary calcium
o Magnesium supplements (if low)
Magnesium oxide 400mg oral BDS
257
Monitoring in hypoparathyroidism?
o Regular - serum Ca, albumin, phosphate and U&Es
o Urine calcium
o Renal imaging
258
Dietary advice in hypoparathyroidism?
o Rich in calcium and vitamin D
259
Complications in hypoparathyroidism?
```
o Laryngospasm
o Muscle cramps, tetany, seizures
o QT prolongation – syncope, arrhythmias
o Renal stones
o Stunted growth, malformed teeth
```
260
How common is thyroid cancer?
- Most common endocrine malignancy
- 1% of all malignancies
- Women
261
Risk factors of thyroid cancer?
```
o Exposure to ionising radiation (especially papillary)
o History of thyroid goitre
o Thyroid nodule
o Thyroiditis
o FHx of thyroid cancer
o Females
o Asians
o Cowden’s syndrome
o FAP
```
262
Types of thyroid cancer?
```
o Papillary (60%)
o Follicular (25%)
o Medullary (5%)
o Anaplastic (5%)
o Lymphoma (5%)
o Hurthle Cell Carcinoma
```
263
Characteristics of papillary thyroid cancer?
Often younger patients 35-40
3x women
Spread – lymph nodes, lung (jugulo-diagastric node metastasis is called lateral aberrant thyroid)
264
Characteristics of follicular thyroid cancer?
Occur in middle age, 3x women
Well-differentiated
Spreads – early via blood (bone, lungs)
265
Characteristics of medullary thyroid cancer?
Parafollicular calcitonin-producing C cells of thyroid
Sporadic (80%) or part of MEN syndrome
May produce calcitonin
Do not concentrate iodine
266
Characteristics of anaplastic thyroid cancer?
From follicular cells but poor differentiation
Rare, elderly with poor response to treatment
Most aggressive cancer
267
Characteristics of lymphoma thyroid cancer?
Women more common
Mostly non-Hodgkins lymphoma
May present with dysphagia or stridor
268
Characteristics of Hurthle Cell carcinoma thyroid cancer?
Females
269
Symptoms of thyroid cancer?
- May be asymptomatic lump
- Thyroid nodule
o Hard, fixed, enlarging
o Non-tender on palpation
- Hoarseness with goitre
- Cervical lymphadenopathy
270
Investigations in thyroid cancer?
o Bloods - TFTs (mainly euthyroid), calcitonin for MTC
o US of thyroid gland - Hypoechogenicity, microcalcifications, irregular borders, solid
o Fine-needle aspiration cytology - Any thyroid nodule >1cm and <1cm if suspicious US
o 123I radionucleotide imaging
o CT/MRI to detect local/regional lymph node spread
271
Staging in thyroid cancer?
o 1
<45 – any T, any N and M0
>45 – T1, N0, M0
o 2
<45 – any T, any N, M1
>45 – T2, N0, M0
o 3
T3, N0, M0 or T1-3, N1, M0
o 4
T4, or any M1 tumours
272
Guidelines for referral of thyroid lump?
o Referral within 2 weeks to thyroid surgeon or endocrinologist if:
Unexplained thyroid lump
Unexplained voice changes with goitre
Cervical lymphadenopathy
Painless thyroid mass, rapidly increasing in size over weeks
o Non-urgent referral if:
Thyroid nodules and abnormal TFTs
Hx of sudden onset pain in lump
273
Specialist management of papillary, follicular and Hurthle Cell thyroid cancer?
Total thyroidectomy +/- node excision +/- radioiodine (131I) ablation
Levothyroxine (to supress TSH)
274
Specialist management of medullary Cell thyroid cancer?
Total Thyroidectomy + node clearance + Levothyroxine
| 2nd line - Vandetanib
275
Specialist management of lymphoma Cell thyroid cancer?
Chemoradiotherapy (CDVP + external beam radiotherapy)
276
Specialist management of anaplastic Cell thyroid cancer?
Total thyroidectomy/Palliative Excision + Chemoradiotherapy
Levothyroxine (suppress TSH)
277
Follow up of thyroid cancer?
o TFTs after 3 months
| o Annual – neck US, TFTs, CT scan
278
Complications of thyroid surgery?
laryngeal nerve palsy, hypoparathyroidism
279
Prognosis of thyroid cancer?
o 10-year survival 90% in differentiated cancers
| o 5-year survival in anaplastic is 5%
280
Definition of toxic multinodular goitre?
Plummer’s disease
o Multiple autonomously functioning nodules, resulting in hyperthyroidism
o Function independently to TSH and almost always benign
281
How common is multinodular goitre?
- Most common goitre in UK
| - Common in elderly
282
Risk factors for a multinodular goitre?
o Iodine deficiency
o >40
o Head and neck radiation
o Female
283
Symptoms of multinodular goitre?
```
- Thyroid lump – many nodules
o Often asymptomatic, may be seen by mirror or family
o Usually irregular
- Occasionally pain
- May have dysphagia, stridor
```
284
Symptoms if toxic multinodular goitre?
o Malaise, fever
o Thyroid pain
o Hyperactivity, insomnia, irritability, anxiety, palpitations
o Heat intolerance, sweating
o Increased appetite, weight loss, diarrhoea
o Infertility, oligomenorrhoea, amenorrhoea
o Reduced libido
285
Investigations in multinodular goitre?
- TFTs
o Euthyroid
o Hyperthyroid – toxic multinodular goitre
- Specialist investigations:
o USS of thyroid
o FNA cytology
o CT/MRI if cancer
286
Management of thyroid lumps in primary care - referral?
o Referral within 2 weeks to thyroid surgeon or endocrinologist if:
Unexplained thyroid lump
Unexplained voice changes with goitre
Cervical lymphadenopathy
Painless thyroid mass, rapidly increasing in size over weeks
o Non-urgent referral to thyroid surgeon or endocrinologist if:
Thyroid nodules and abnormal TFTs
Hx of sudden onset pain in lump
287
Management of toxic multinodular goitre?
Radioactive iodine
• Pre-treatment with thiamazole/propylthiouracil
Surgery
• 1st line if mass effect occurring
288
Definition of toxic nodule?
o Autonomously functioning nodules, resulting in hyperthyroidism
o Function independently to TSH and almost always benign
289
Types of toxic nodule?
o May be cystic, colloid, adenomatous, hyperplastic or cancerous
290
Causes of toxic nodule?
```
o Iodine deficiency (worldwide)
o Hashimoto’s thyroiditis and Grave’s disease (UK)
o Drugs – lithium, amiodarone
o Pregnancy
o Menopause
```
291
Symptoms of toxic nodule?
```
- Thyroid lump
o Asymptomatic mostly
- Pain
- Compression of trachea
- If toxic, signs of hyperthyroidism
o Malaise, fever
o Thyroid pain
o Hyperactivity, insomnia, irritability, anxiety, palpitations
o Heat intolerance, sweating
o Increased appetite, weight loss, diarrhoea
o Infertility, oligomenorrhoea, amenorrhoea
o Reduced libido
```
292
Investgiations of toxic nodule?
```
- TFTs
o Simple goitre – normal TFTs
o Toxic nodule – abnormal TFTs (TSH suppressed)
- Specialist tests:
o USS
o FNA cytology
o CT/MRI
```
293
Referral of people with thyroid lump in primary care?
- Referral within 2 weeks to thyroid surgeon or endocrinologist if:
o Unexplained thyroid lump
o Unexplained voice changes with goitre
o Cervical lymphadenopathy
o Painless thyroid mass, rapidly increasing in size over weeks
- Non-urgent referral to thyroid surgeon or endocrinologist if:
o Thyroid nodules and abnormal TFTs
o Hx of sudden onset pain in lump
294
Management of toxic nodule?
o Radioactive iodine (I-131)
Pre-treatment thiamazole
o 2nd line - Subtotal Thyroidectomy
1st line if mass effect
295
Definition of goitre?
- Enlargement of the thyroid gland
| - May be multi-nodular or single nodules
296
Types of goitre - diffuse smooth?
Grave’s disease
Hashimoto’s thyroiditis
Iodine deficiency
Lithium, amiodarone
297
Types of goitre - nodular goitre?
Multinodular
| Single nodule (cyst, adenoma, cancer)
298
Definition of de Quervain's thyroiditis?
Subacute granulomatous thyroiditis
Inflammation of thyroid
Triphasic course:
• Transient thyrotoxicosis, then hypothyroidism followed by euthyroidism
299
Aetiology of de Quervain's thyroiditis?
Viral – following URTI (influenza, adenovirus, mumps, coxsackie)
300
Pathology of de Quervain's thyroiditis?
Thyrotoxicosis due to follicular damage and release of preformed hormone
301
Symptoms and signs of de Quervain's thyroiditis?
o Symptoms
Thyroid pain, migratory, fever, palpitations, malaise, tremor, heat intolerance
o Signs
Enlarged, firm, painful thyroid
302
Investigations of de Quervain's thyroiditis?
TFTs – TSH low, T3/4 elevated
CRP/ESR – raised
US
Nuclear uptake low
303
Management of de Quervain's thyroiditis?
Thyrotoxicosis phase - self-limiting, BB and NSAIDs for symptom control, if severe then prednisolone
Hypothyroid – may need levothyroxine
304
Description of Hashimoto's thyroiditis?
Destruction of thyroid cells by lymphocytes and plasma cells – bind and block TSH receptor
Destructive thyroiditis with release of thyroid hormone and transient thyrotoxicosis, followed by hypothyroid phase – inadequate production and secretion of hormones
305
Epidemiology of Hashimoto's thyroiditis?
Women 20x
306
Aetiology of Hashimoto's thyroiditis?
HLA-DR3/5
307
Symptoms of Hashimoto's thyroiditis?
```
Enlarged thyroid, dyspnoea and dysphagia if large enough
Rarely, early – hyperthyroid symptoms
Hypothyroid more common
• Fatigue, constipation, dry skin and weight gain.
• Cold intolerance.
• Slowed movement and loss of energy.
• Decreased sweating.
• Mild nerve deafness.
• Peripheral neuropathy.
• Menstrual irregularities (typically menorrhagia).
• Depression, dementia and memory loss.
• Hair loss from an autoimmune process
```
308
Investigations of Hashimoto's thyroiditis?
TFTs – TSH raised
Anti-TPO and anti-Tg antibodies
Thyroid US
309
Management of Hashimoto's thyroiditis?
As hypothyroidism
• Life-long levothyroxine
Surgery for large, obstructive goitres
310
Definition of postpartum thyroiditis?
o Autoimmune disorder with hyperthyroidism followed by hypothyroidism within 1 year of delivery
311
Symptoms of postpartum thyroiditis?
Symptoms of hypothyroidism
| Painless, typically 2-6 months after delivery
312
Investigations of postpartum thyroiditis?
TFTs – high TSH, low T3/4 in hypothyroidism
| Anti-TPO and anti-Tg positive
313
Management of postpartum thyroiditis?
Refer to endocrinologist
Monitor hypothyroid phase every 4-6 weeks for 6 months, treat if symptomatic
• Levothyroxine for 6-12 months, withdraw over 4 weeks
Annual TFTs to screen for thyroid problems
314
Definition of Riedel's thyroiditis?
Very rare, sclerosing disease
Replacement of thyroid parenchyma with dense fibrous tissue, extends beyond thyroid capsule into surrounding structures of neck
Females 3x
315
Symptoms and signs of Riedel's thyroiditis?
Painless lump in neck, dyspnoea, stridor
Woody-hard, symmetrical fixed thyroid gland
Hypothyroidism usually
316
Management of Riedel's thyroiditis?
Surgery if pressure symptoms
317
What hormones are produced by anterior pituitary gland?
GH (growth in tissues, especially bones and muscles)
FSH (oestrogen secretion and follicular development, sperm production)/LH (production of oestrogen and testosterone)
PRL (breast milk production)
TSH (activates thyroid for metabolism)
ACTH (stimulates adrenal glands to produce cortisol and other hormones)
318
What hormones are produced by posterior pituitary gland?
Oxytocin (stimulate release of breast milk and contraction of uterus in labour)
ADH (conserve water and prevent dehydration)
319
Definition of hypopituitarism?
o Inability of pituitary gland to provide enough hormones
| o Usually chronic and lifelong
320
Definition of panhypopituitarism?
deficiency of all anterior hormones
321
Risk factors of hypopituitarism?
o Pituitary tumours/apoplexy/surgery
o Traumatic brain injury
o Hypothalamic disease
322
Causes of hypopituitarism - hypothalamic?
Kallman’s syndrome (congenital hypogonadotropic hypogonadism)
Tumour
Meningitis, encephalitis, TB
Stroke & SAH)
323
Causes of hypopituitarism - pituitary stalk?
Trauma
Surgery
Craniopharyngioma, meningioma, glioma
Carotid artery aneurysm
324
Causes of hypopituitarism - Pituitary?
Adenomas
Irradiation
Inflammation
Infiltration (haemochromatosis, amyloid, sarcoidosis, metastases)
Ischaemia (pituitary apoplexy, DIC, Sheehan’s syndrome)
325
Symptoms of GH deficiency in hypopituitarism?
```
Central obesity
Atherosclerosis
Dry, wrinkly skin
Low strength/balance/wellbeing/exercise ability
Low cardiac output/glucose
Osteoporosis
Children – failure to thrive
```
326
Symptoms of FSH/LH deficiency in hypopituitarism?
Males – erectile dysfunction, decreased libido/muscle bulk, hypogonadism (less hair, small testes, low ejaculate volume, low spermatogenesis)
Females – Oligo/Amernorrhoea, low fertility/libido, breast atrophy, osteoporosis, psyparenunia
327
Symptoms of TSH deficiency in hypopituitarism?
Hypothyroid picture
328
Symptoms of ACTH deficiency in hypopituitarism?
Adrenal insufficiency/Addison’s picture
• Acute – weakness, dizziness, N&V, fever, shock
• Chronic – fatigue, pallor, anorexia, weight loss
• Hypoglycaemia, hypotension, anaemia
NO INCREASED SKIN PIGMENTATION AS LOW ACTH
329
Symptoms of Prolactin deficiency in hypopituitarism?
Absent lactation
330
Symptoms of ADH deficiency in hypopituitarism?
(Diabetes Insipidus)
| Polyuria, polydipsia, hypernatraemia
331
Bloods performed in hypopituitarism?
o FBC
o U&Es
o TFTs
o Glucose
332
Hormone profile done in hypopituitarism?
o TFTs, prolactin, gonadotrophins, testosterone and cortisol
o Triple Stimulation of GnRH, TRH and insulin
Measure gonadotrophins, TSH, GH, glucose and cortisol
333
Other tests performed in hypopituitarism?
o Synacthen Test (ACTH administered and cortisol measured – low)
o Insulin Tolerance Test (adrenal and GH axis)
o Water deprivation test (for DI)
- Imaging
o MRI
334
Management of acute hypopituitarism?
o IV fluids
| o If apoplexy – IV hydrocortisone and surgical decompression
335
Management of chronic hypopituitarism?
o Treat underlying cause if possible
336
Management of ACTH deficiency in hypopituitarism?
Oral hydrocortisone
Carry steroid card, alert bracelet
Sick day dosing according to Addison’s rules
337
Management of TSH deficiency in hypopituitarism?
Levothyroxine after corrected ACTH (provoke adrenal crisis)
338
Management of Gonadotrophin (FSH/LH) deficiency in hypopituitarism?
Females
• Fertility not desired – oestrogens (with progesterone if uterus – prevent unopposed oestrogen) – patches or pill
• Fertility desired – Gonadotrophins
Males
• Fertility not desired – Testosterone gel, patches, buccal tablets
• Fertility desired – Gonadotrophins
339
Management of GH deficiency in hypopituitarism?
Recombinant somatropin
340
Management of ADH deficiency in hypopituitarism?
Desmopressin
341
Location of pituitary gland?
structure attached to base of brain behind the nose, protected by sphenoid bone
342
Classification of pituitary tumours?
o <1cm diameter – microadenoma
| o >1cm diameter – macroadenoma
343
Epidemiology of pituitary tumours?
- 10% of intracranial tumours
- Almost always benign adenomas – most common
- In children, prolactinoma most common
344
Types of pituitary tumours?
o Chromophobe – 70% - many non-secretory, some cause hypopituitarism, half produce prolactin, few produce ACTH, GH. Local pressure effect in 30%
o Acidophil – 15% - secrete GH or PRL
o Basophil – 15% - secrete ACTH
345
Classes of pituitary tumours?
```
o Non-functioning adenoma
o Prolactinoma
o GH-secreting
o ACTH-secreting
o TSH-secreting
o LH/FSH-secreting
```
346
Associations of pituitary tumours?
o MEN1 – endocrine cancer syndrome characterised by tumours in parathyroid gland, endocrine gastroenteropancreatic tract (gastrinoma, insulinoma) and anterior pituitary (prolactinomas)
347
Local effects of pituitary tumours?
o Headache
Retro-orbital or bitemporal
Worse on waking
If large, hydrocephalus
o Visual field defects
Bitemporal hemianopia (heteronymous) – compression of optic chiasm
Cranial nerve 3, 4 & 6 palsies
o Hypothalamic dysfunction of temperature, sleep, appetite, thirst
348
Hypopituitarism effects of pituitary tumours?
```
o Low LH/FSH
Infertility
Oligo/amenorrhoea
Decreased libido, muscle bulk
Erectile dysfunction
```
```
o Low GH
Central obesity
Atherosclerosis
Worse strength, balance, wellbeing, glucose
Impaired growth in children
```
o Low TSH
Hypothyroidism
o Low ACTH
Lean, tanned, tired, anorexia, dizzy, nausea, vomiting
349
Hormonal secretion symptoms of pituitary tumours?
o Acromegaly – GH
o Galactorrhoea – PRL
o Cushing’s - ACTH
o Thyrotoxicosis - TSH
350
Investigations to perform in pituitary tumours?
- Visual Fields
- Pituitary Function Tests
o Prolactin – PRL
o GH - IGF-1, insulin tolerance test
o ACTH - cortisol, Synacthen test
o LH/FSH, testosterone, estradiol
o TRH-stimulation test
- MRI with gadolinium
o Infra- and supra-stellar extension
o Vessel lateral to pituitary gland is internal carotid artery
351
Management of pituitary adenoma?
o Observation
If microadenoma & asymptomatic
Hormone replacement as necessary
o Surgery
Endoscopic transsphenoidal pituitary adenoma resection
Hormone replacement as needed
o Drugs
Bromocriptine (1st-line prolactin-secreting adenoma)
Somatostatin analogues (GH-secreting adenomas)
o Radiotherapy
Residual or recurrent adenomas
352
Prognosis of pituitary tumours?
o Remission in up to 90% of patients with microadenoma, 50% in macroadenoma
353
Compications of pituitary tumours?
o Pituitary Apoplexy – sudden-onset hypopituitarism caused by infarction of pituitary adenoma
Sx – Mass effect, collapse, acute onset headache, meningism, low GCS
Rx – urgent hydrocortisone, fluid balance and cabergoline (dopamine agonist if prolactinoma) +/- surgery
354
Adrenal gland made up of what two parts?
Cortex
| Medulla
355
Zones of cortex of adrenal gland and what hormones produced?
Zona Glomerulosa – secretes mineralocorticoids (aldosterone)
Zona Fasciculata – secretes glucocorticoids (cortisol)
Zona Reticularis – Secretes androgens
356
What hormones produced by medulla of adrenal gland?
Secretes catecholamines (adrenaline, noradrenaline, dopamine)
357
Definition of phaeochromocytoma?
o Catecholamine-producing tumours in adrenal medulla
| o Arise from sympathetic paraganglia cells (phaeochrome bodies), collections of chromaffin cells in the adrenal medulla
358
Rule of phaeochromocytoma?
```
10% malignant
10% extra-adrenal
10% bilateral
10% familial
• Hereditary cancer syndromes – thyroid, MEN-2a and 2b, neurofibromatosis, VHL syndrome
```
359
Where are phaeochromocytoma usually found?
- Usually found in adrenal medulla
| - Extra-adrenal tumours are rare - paragangliomas – aortic bifurcation (organs of Zuckerkandl)
360
Symptoms of phaeochromocytoma and what precipitates them?
- Symptoms precipitated by straining, exercise, stress, abdominal pressure, surgery or drugs (BB, IV contrast, TCAs)
- Triad:
o Episodic headache
o Sweating
o Tachycardia
361
Signs of phaeochromocytoma?
o Heart – hypertension, postural hypotension, tachycardia, palpitations, dyspnoea, faints, angina, MI
o CNS – Headache, visual disorder, dizzy, tremor, numbness, fits, Horner’s, CNS haemorrhage
o Psychological – anxiety, confusion
o Gut – D&V, abdominal pain
o Other – sweating, heat intolerance, pallor, pyrexia, backache
362
Investigations of phaeochromocytoma?
- BP
- Bloods
o FBC – Raised Hb, High WCC
o Glucose - raised
- 3 x 24-hour urines for metadrenalines, creatinine, total catecholamines, vanillylmandelic acid (VMA)
o Clonidine suppression test if borderline
363
Imaging of phaeochromocytoma?
o Abdominal CT
| o Meta-iodobenzylguanidine (MIBG)scan (look for extra-adrenal tumours)
364
Treatment of phaeochromocytoma?
o Surgical resection of tumour
Alpha-blockade 7-10 days pre-op (phenoxybenzamine)
B-blocker if heart disease or tachycardic (always after alpha blocker)
Consult anaesthetist
o Post-op
24h urine total catecholamines, VMA and metadrenalines 2 weeks post-op
Monitor BP
365
Emergency management of phaeochromocytoma?
o Get help
o ICU
o Short-acting Alpha blocker IV – phentolamine 2-5mg – repeat to maintain safe BP
o When BP controlled:
o Long-acting Alpha-blocker PO phenoxybenzamine 10mg/24h (can be increased)
Up dose until BP controlled and no postural hypotension
Alternative Alpha1 blocker is doxazocin
o B1-blocker given to control tachycardia or myocardial ischaemia
o Surgery
Elective 4-6 weeks after to allow full alpha-blockade and volume expansion
366
Definition of Cushing's syndrome?
- Prolonged exposure to elevated levels of endogenous/exogenous glucocorticoids
- Loss of normal feedback mechanisms of HPA axis and loss of circadian rhythm of cortisol
367
Causes of Cushing's syndrome - ACTH dependent?
Excessive ACTH from pituitary (Cushing’s disease)
• Bilateral adrenal hyperplasia – most common 80%
Ectopic ACTH-producing tumour
• Small cell lung cancer and carcinoid tumours
368
Causes of Cushing's syndrome - ACTH independent?
Adrenal adenoma
Adrenal carcinomas
Excess glucocorticoid administration
369
Symptoms of Cushing's syndrome?
o Weight gain
o Mood change (depression, lethargy, irritability, psychosis)
o Proximal weakness
o Gonadal dysfunction (irregular menses, hirsutism, erectile dysfunction)
o Acne
o Recurrent Achilles tendon rupture
370
Signs of Cushing's syndrome?
```
o Central obesity
o Plethoric, moon face
o Buffalo neck
o Supraclavicular fat distribution
o Skin and muscle atrophy
o Bruising
o Purple abdominal striae
o Osteoporosis
o Hypertension
o DM
o Infection prone
o Poor wound healing
```
371
Bloods in Cushing's syndrome?
Raised WCC
372
Confirmation of Cushing's syndrome?
24-hour urinary free cortisol
3 collections
Diagnosed if 2 or more collections measure cortisol excretion >3x upper normal limit
1mg overnight dexamethasone suppression test
Ingested at 11pm and serum cortisol measures at 8am
Late-night salivary cortisol
373
Determining cause of Cushing's syndrome?
o Plasma ACTH
If raised – high-dose dexamethasone suppression test (8mg)
• Inferior petrosal sinus sampling
Low plasma ACTH with high cortisol = ACTH-independent Cushing’s syndrome
High ACTH with high cortisol = ACTH-dependent Cushing’s syndrome
o MRI of pituitary
o Chest and abdomen CT
374
Management of Cushing's syndrome - iatrogenic?
o Stop steroids if possible
375
Management of Cushing's syndrome - Cushing's disease?
o Removal of pituitary adenoma
376
Management of Cushing's syndrome - Adrenal adenoma/carcinoma?
o Adrenalectomy (radiotherapy & adrenolytic if carcinoma)
377
Management of Cushing's syndrome - ectopic ACTH?
o Surgery if local tumour
| o Metyrapone, ketoconazole and fluconazole decreased cortisol secretion
378
Complications of Cushing's syndrome?
- Metabolic syndrome
- Hypertension
- DM
- Obesity
- Hyperlipidaemia
- Osteoporosis
- Coagulopathy
- Impaired immunity
379
Definition of congenital adrenal hyperplasia?
* Autosomal recessive disorders of cortisol biosynthesis
* Inadequate cortisol production leads to raised ACTH, adrenal hyperplasia and overproduction of androgenic precursors (particularly 17OH-progesterone) – leads to increased testosterone, decreased cortisol and aldosterone
380
Epidemiology of congenital adrenal hyperplasia?
- 1 in 5000 births and commoner in consanguineous marriages
381
Causes of congenital adrenal hyperplasia?
- 21-hydroxylase deficiency cause of about 95% of cases
- Characterised by cortisol deficiency, with or without aldosterone deficiency and androgen excess
- May be family history of neonatal death
382
Symptoms and signs of congenital adrenal hyperplasia?
- In infant females, virilisation of external genitalia, clitoral hypertrophy and fusion of labia
- In infant male, penis may be enlarged and scrotum small and hyperpigmented
- Other signs
• Male pattern bladness
• Infertility
• Irregular menses
• Short stature
• PCOS
• Precocious puberty
- Salt loss adrenal crisis
• Present 1-3 weeks old, vomiting, weight loss, hypotension and floppiness, circulatory collapse
383
Investigations of congenital adrenal hyperplasia?
- Biochemical screening can be performed
- Raised 17 alpha-hydroxyprogesterone in blood is diagnostic
- In salt losers:
• Low plasma sodium, high plasma potassium, metabolic acidosis and hypoglycaemia
- Pelvic USS to demonstrate uterus
- Corticotropin stimulation test
- Karyotyping
384
Management of congenital adrenal hyperplasia - medical and surgical?
- Multidisciplinary team assessment needed
- Birth registration must be delayed until sex is known
- Medical therapy
• Lifelong glucocorticoids (hydrocortisone) to supress ACTH levels
• Mineralocorticoids (fludrocortisone), saline, glucose if salt loss adrenal crisis
Double dose of steroids if ill or having surgery
• Monitoring of growth, skeletal maturity and 17 alpha-hydroxyprogesterone
- Surgery
• Reconstruction of clitoris and vaginoplasty
385
Definition of hyperaldosteronism?
- Excessive levels of aldosterone
| o Act at distal renal tubule, promoting sodium and water retention and excretion of potassium
386
Risk factors of hyperaldosteronism?
o FHx of PA or early hypertension
387
Types of hyperaldosteronism?
o Primary – excess production of aldosterone, independent of renin-angiotensin system, causing high Na, and water retention and low renin
o Secondary – High renin levels from low renal perfusion
388
Causes of primary hyperaldosteronism?
Adrenal Adenoma (Conn’s syndrome) – 80%
Bilateral Adrenal hyperplasia (BAH) – 15%
• Cells become hyperplastic, excessive secretion of aldosterone
Familial Hyperaldosteronism
Adrenal Carcinoma
Glucocorticoid remediable aldosteronism (GRA)
389
Causes of secondary hyperaldosteronism?
```
Renal artery stenosis
Accelerated hypertension
Diuretics
CCF
Hepatic failure
Nephrotic syndrome
Bartter’s syndrome
```
390
Symptoms of hyperaldosteronism?
```
o Often asymptomatic
o Hypokalaemia symptoms:
Muscle weakness
Hypotonia
Hyporeflexia
Cramps
Tetany
Palpitations
Light-headedness
Constipation
Polyuria, polydipsia
```
391
Signs of hyperaldosteronism?
o Hypertension
o Hypokalaemia
o Metabolic alkalosis
o Sodium normal or high end of normal
392
Investigations performed in hyperaldosteronism?
- BP
- Bloods (off diuretics for >4 weeks, off BB and CCB for 2 weeks, stop steroids, potassium, laxatvies)
- Urine
o 24-hour urinary aldosterone – raised in primary
393
Specific bloods done in hyperaldosteronism?
- Bloods (off diuretics for >4 weeks, off BB and CCB for 2 weeks, stop steroids, potassium, laxatvies)
o U&E – hypokalaemia, sodium (normal or high end of normal)
o Hormone Profiles (measure 9am lying and 12pm standing)
Renin activity
• If normal or high – excludes primary hyperaldosteronism - refer
• If low – aldosterone levels and refer to specialist
Aldosterone levels
On lying and standing
• If reduced aldosterone and cortisol on standing – Conn’s syndrome
• If increased aldosterone and reduced cortisol - BAH
394
Further tests done in hyperaldosteronism?
Fludrocortisone suppression test & Oral salt loading
ECG – arrhythmias
CT 1st line (MRI)
o Locate cause
Adrenal vein sampling
o If one side has higher aldosterone, adenoma likely and surgical excision indicated
Genetic Testing for GRA
395
Management of Conn's syndrome in hyperaldosteronism?
Aldosterone antagonists (spironolactone) 4 weeks before surgery
Surgery
• Adrenalectomy – laparoscopic
Post-op aldosterone antagonists if PA after surgery
396
Management of BAH in hyperaldosteronism?
Aldosterone antagonists (amiloride, spironolactone, eplerenone)
397
Management of GRA in hyperaldosteronism?
Dexamethasone 4-weeks
| If BP still high – spironolactone
398
Management of adrenal carcinoma in hyperaldosteronism?
Surgery
| Post-operative adrenolytics (Mitotane)
399
Complications of hyperaldosteronism?
o CVD and stroke as a result of hypertension
400
Definition of hypoaldosteronism??
- Decreased levels of aldosterone – produced by adrenals
401
Causes of hypoaldosteronism??
o Primary
Addison’s disease
Congenital adrenal hyperplasia
Aldosterone synthase deficiency
o Secondary
Secondary adrenal insufficiency
Disease of pituitary or hypothalamus
Steroids
402
Symptoms and signs of hypoaldosteronism??
- Hyperkalaemia
- Metabolic acidosis
- Hypotension
- Renal tubular acidosis
403
Investigations of hypoaldosteronism??
- Bloods
o U&E – hyperkalaemia
o Aldosterone
o Renin
- Interpretation
o Low aldosterone with high renin = primary hypoaldosteronism
o Low aldosterone and low renin = secondary hypoaldosteronism
404
Diagnostic investigations in hypoaldosteronism?
o Saline suppression test (Salt loading)
o Fludrocortisone suppression test
o CT scan
405
Management of hypoaldosteronism??
- Fludrocortisone +/- glucocorticoid replacement
406
Definition of hirsutism?
o Excess growth of terminal hair in androgen-dependent areas (faces, chest, linea alba, lower back, buttocks and anterior thighs)
Terminal hair = dark, thick and coarse
Vellus hair = soft, fine and unpigmented (NOT HIRSUTISM)
o Due to increased androgen production, increased sensitivity or both
407
How common is hirsutism?
- 5-15% of women of reproductive age
408
Causes of hirsutism?
o PCOS (70%)
o Idiopathic
o Congenital adrenal hyperplasia
o Ovarian or adrenal tumour (secreting androgens)
o Acromegaly
o Drugs – anabolic steroids, danazol, metoclopramide, methyldopa, sodium valproate
o Menopausal Women
409
Symptoms of hirsutism?
- Excess terminal hair in masculine pattern
- In androgen-secreting tumour/CAH - signs of virilisation (hair loss from scalp, voice deepen, increased muscle bulk, clitoromegaly)
410
Diagnosis of hirsutism?
o Excessive terminal hair in face, chest, linea alba, lower back, buttocks and anterior thighs
o Assess severity with hair growth and extent of impact on QoL
411
Assessment of underlying causes in hirsutism?
o PCOS – oligomenorrhoea/amenorrhoea, infertility, acne, hair loss on scalp, central obesity, acanthosis nigricans
o Androgen-secreting tumour – sudden onset, rapid progression, masses in abdomen/pelvis
o Cushing’s syndrome – facial weight gain/neck/torso, easy bruising, stretch marks, proximal muscle weakness
o Drugs
412
Further assessment in hirsutism - mild and no PCOS?
o No further investigations
413
Further assessment in hirsutism - moderate/severe hirsutism and no PCOS?
o Early morning plasma testosterone level (day 4-10 of cycle)
If >4 – referral
414
Further assessment in hirsutism - high risk of CAH?
o Early morning 17-hydroxyprogesterone levels
| If elevated - referral
415
What is hypertrichosis?
o Excessive hair growth in generalised pattern (not due to excess androgens)
o Can be congenital (Hurler’s syndrome, trisomy 18, fetal alcohol), hypothyroidism, porphyrias, anorexia, malnutrition, ciclosporin, phenytoin, hydrocortisone
416
When to refer within 2 weeks to endocrinologist in hirsutism?
Sudden onset, rapid progression, severe, signs of virilisation (hair loss from scalp, voice deepen, increased muscle bulk, clitoromegaly)
417
When to refer to endocrinologist?
Serum testosterone >4 (urgently if >6)
| 17-hydroxyprogesterone elevated
418
Management of hirsutism - general measures if no referral needed?
```
o Weight loss
o Hair reduction/removal (not on NHS)
Shaving
Waxing
Bleaching
Specialist clinic
• Electrolysis
• Laser photoepilation
```
419
Management of hirsutism - if mild?
reassure and advise no additional treatment
420
Management of hirsutism - if moderate/severe?
Facial hirsutism – Topical eflornithine
• If no benefit in 4 months – stop and refer to endocrinologist
• DO NOT PRESCRIBE IF PREGNANT, BREASTFEEDING or <19
All other women (pre-menopausal)
• Dianette (co-cyprindiol)
o Stop 3-4 months after hirsutism completely resolved
• Yasmin COCP
• If not worked after 6 months – refer to endocrinologist for specialist treatments
421
Management of hirsutism - Specialist treatments?
```
For hirsutism
• Anti-androgens (high-dose cyproterone acetate, spironolactone and flutamide)
• Finasteride
• Metformin, pioglitazone
• Goserelin, leuprorelin
```
For infertility – clomiphene
422
Description of hyperglycaemic hyperosmolar state (HHS)?
- Typically, those with Type 2 DM
- Develops over days/weeks and is more common in elderly
- Characterised by high glucose levels (>35mmol/L), high blood osmolarity (>340mosmol/kg) and lack of urinary ketones
- No switch to ketone metabolism as basal insulin secretion sufficient but insufficient to reduce blood glucose
423
Risk factors of hyperglycaemic hyperosmolar state (HHS)?
```
o Older
o Dementia
o Sedative drugs
o Heatwaves
o Immunocompromised
```
424
Causes of hyperglycaemic hyperosmolar state (HHS)?
```
o Infection
o Infarction
o Insufficient diabetic therapy
o Intercurrent illness
o Dehydration
o Drugs
Diuretics, Beta-blockers, CCB, Anti-psychotics, steroids, alcohol, cocaine, MDMA
```
425
Symptoms of hyperglycaemic hyperosmolar state (HHS)?
o Onset over days or weeks
o Dehydration – thirst, polydipsia, polyuria, decreased skin turgor, dry mouth, hypotension, tachycardia
o GI – nausea, vomiting, abdominal pain
o Hyperventilation – (resp compensation for metabolic acidosis) Deep rapid (Kussmaul breathing) and smell of acetone on breath
o Altered conscious state, focal neurological deficits
426
Diagnosis of hyperglycaemic hyperosmolar state (HHS)?
o Severe hyperglycaemia (>30mmol/L)
o Marked serum hyperosmolarity (>320mosmol/kg)
o WITHOUT Ketones (<3mmol/L)
427
Tests of hyperglycaemic hyperosmolar state (HHS)?
```
o Urinalysis – glycosuria
o BM - >30mmol/L
o Bloods – FBC, CRP, U&Es, blood glucose, osmolarity (>320mmol/L)
o ABG
o Blood cultures (if infection)
o CXR
o ECG
```
428
ABCDE approach in hyperglycaemic hyperosmolar state (HHS)?
o Secure airway if GCS low
o 2 large-bore cannulas
o High flow O2 if needed
429
Initial management of hyperglycaemic hyperosmolar state (HHS)?
LMWH prophylaxis
0.9% saline IVI over 48h, typically 8-15L for 70kg adult
Replace K+ when urine produced (Monitor UO hourly, add K when >30mL/h, check U&E hourly initially and replace as require, continuous ECG monitoring)
• 3.5-5.5mmol/L – 40mmol KCl/litre of IV fluid
• <3.5mmol/L – ICU/HDU help
```
Insulin IV (low dose – 0.05u/kg/hour)
If BG not falling by 5mmol/L/h with rehydration
```
Keep glucose at 10-15mmol/L to avoid cerebral oedema
Look for cause (MI, drugs, bowel infarct)
Consider NG tube and urinary catheter
Admission to ICU/HDY or acute medical admissions
430
Monitoring of hyperglycaemic hyperosmolar state (HHS)?
```
o At least hourly:
Capillary blood glucose
Vital signs
Fluid balance
Level of consciousness
ECG and K+
```
431
Complications of hyperglycaemic hyperosmolar state (HHS)?
```
o Ischaemia
o VTE
o ARDS
o DIC
o Cerebral Oedema
```
432
Description of diabetes insipidus?
- Passage of large volumes (>3L/day) of dilute urine due to impaired water reabsorption by kidney
- Due to reduced ADH secretion from posterior pituitary (cranial DI) or impaired response by kidney to ADH (nephrogenic DI)
433
Physiology of diabetes insipidus?
o ADH synthesised in hypothalamus and transported to posterior pituitary
o Released into circulation, governed by plasma osmolarity
o Failure causes inability to concentrate urine in distal renal tubules
434
Causes of cranial diabetes insipidus?
```
Idiopathic (<50%)
Congenital - DIDMOAD – diabetes insipidus, diabetes mellitus, optic atrophy and deafness (Wolfram’s syndrome)
Tumour - Craniopharyngoma, metastases, pituitary tumour
Trauma
Hypophysectomy
Autoimmune hypophysitis
Histiocyte sarcoidosis
Haemorrhage
Meningoencephalitis
```
435
Causes of nephrogenic diabetes insipidus?
```
Inherited
Metabolic
• Low potassium
• High calcium
Drugs
• Lithium
CKD
Post-obstructive uropathy
Pregnancy
```
436
Symptoms of diabetes insipidus?
o Polyuria
o Nocturia
o Polydipsia – uncontrollable and all-consuming
o Dehydration
o Symptoms of hypernatraemia -Lethargy, thirst, weakness, confusion, fits
437
Signs of diabetes insipidus?
o Dehydration
| o Enlarged bladder
438
Blood tests of diabetes insipidus?
o U&Es - Raised Na
o Glucose
o Ca
o Serum osmolarity - raised
439
Further test performed to confirm diabetes insipidus?
24-hour urine collection to measure urine volume
o Urine osmolarity – reduced
o Urine:plasma osmolarity ratio <2:1
440
Diagnostic test of diabetes insipidus?
8-hour Water Deprivation Test
| o Tests whether kidneys continue to produce dilute urine despite dehydration and localise the cause
441
Describe procedure of 8-hour water deprivation test in diabetes insipidus?
Free fluids until 07:30. Light breakfast at 06:30, no tea, no coffee, no smoking
Stage 1
• Fluid deprivation (0-8h), start at 08:00
• Empty bladder, then no drinks and only dry food
• Weigh hourly (if >3% then urgent serum osmolarity)
o If >300mOsmol/kg – proceed to stage 2
o If <300 – continue test
• Collect urine every 2h, measure volume and osmolarity
• Venous osmolarity every 4h
• Stop after 8h if urine >600 (normal)
Stage 2 (Differentiating cranial from nephrogenic)
• Proceed if urine still dilute (<600)
• Desmopressin 2ug IM – drink water if want
• Urine osmolarity for next 4h
442
Interpretation of diabetes insipidus 8-hour water deprivation test?
Cranial DI – urine os <300 & after desmopressin >800
Nephrogenic DI – urine os <300 & after desmopressin <300
Primary polydipsia – urine os >800 & after desmopressin >800
Normal – urine os >600 in stage 1 and U:P >2
443
Management of cranial DI?
o MRI head to find cause
o Desmopressin (synthetic analogue of ADH)
Watch out for hyponatraemia
o Test anterior pituitary function
444
Management of nephrogenic DI?
o Treat cause
| o If persistent – Bendroflumethiazide 5mg PO/24h & Desmopressin
445
Emergency management of diabetes insipidus?
o Urgent plasma U&E and serum & urine osmolarities
o Monitor urine output
o U&E BDS
o IVI to maintain fluid with urine output
o If hypernatraemia – 0.9% saline to reduce <12mmol/L per day
o Desmopressin 2ug IM
446
Physiology of sodium control?
- Sodium concentration maintained by ADH (vasopressin) secretion, RAAS system and renal handling of sodium
447
Definition of syndrome of inappropriate ADH secretion?
inappropriate ADH secretion from posterior pituitary or ectopic source despite low serum osmolarity
o Euvolaemic, hypotonic hyponatraemia
448
Causes of SIADH?
o Malignancy – lung small-cell, pancreas, prostate, thymus, lymphoma
o CNS Disorders – meningoencephalitis, abscess, stroke, SAH, SDH, head injury, GBS, SLE, vasculitis
o Chest – TB, pneumonia, abscess, aspergillosis, small-cell cancer
o Endocrine – hypothyroidism
o Drugs – thiazide diuretics, PPIs, opiates, SSRIs, psychotropics, cytotoxic
o Other – porphyria, major surgery, HIV
449
Symptoms and signs of SIADH?
- Anorexia, headache, nausea, vomiting, lethargy
- Personality change, muscle cramps, weakness,, confusion
- Drowsiness
- Euvolaemia
450
Bloods in SIADH?
o Hyponatraemia (Na <135mmol/L)
o Potassium normal
o TFTs – exclude hypothyroidism
451
Assessment of volume status in SIADH?
- Assess volume status, urine Na/osmolarity
o Concentrated Urine (Na>30mmol/L and osmolarity >100mosmol/kg)
o Low plasma osmolarity (<280mosmol/kg)
o In absence of hypovolaemia, oedema or diuretics
452
Test to find cause of SIADH?
o CT chest/abdomen/pelvis to exclude malignancy
453
Management of SIADH - mild?
```
Stop offending medications
Treat Cause
Fluid restriction
• Calculate Furst formule (urine Na + K/serum Na)
o <0.5 – 1L fluid restriction
o 0.5-1 – 0.5L fluid restriction
o >1.0 – do not fluid restrict
```
454
Management of SIADH - severe acute and chronic?
Specialist advice (demeclocycline/tolvaptan)
Acute
• IV hypertonic saline
• Fluid restriction
• Furosemide if fluid overload risk
```
Chronic
• IV hypertonic saline
• Tolvaptan
• Furosemide if fluid overload risk
• Demeclocycline
```
AKT Flashcards
flashcards
Decks in class (37)
# Cards
-
Last Minute . com146
-
DVLA Advice63
-
Statistics86
-
Organisation and Management152
-
Developmental Milestones44
-
School Exclusion Illnesses11
-
Immunisation Programme44
-
2-Week Cancer Pathways34
-
Questions I Got Wrong243
-
Learning Points from Questions96
-
Notifiable Diseases5
-
BP & Diabetes Targets9
-
CYP450 DRUGS5
-
DRUGS IN PREGNANCY AND BREASTFEEDING3
-
Haematology273
-
Cardiovascular516
-
Endocrine454
-
ENT313
-
Gastrointestinal 1402
-
Gastrointestinal 2513
-
Infectious Diseases335
-
MSK370
-
Neurology 1250
-
Neurology 2242
-
Ophthalmology & Skin353
-
Psychiatry345
-
Reproductive System 1232
-
Reproductive System 2280
-
Respiratory411
-
Urinary System368
-
Gynaecology357
-
Fertility72
-
Antenatal Obstetrics399
-
Postnatal Obstetrics75
-
Contraception Drugs212
-
General Paediatrics424
-
General Paediatrics 2530
