Endocrine - Level 2 Flashcards

1
Q

Definition of T1DM?

A

o Absolute insulin deficiency causing persistent hyperglycaemia
o Most common is immune for 1A
o Some slower progression form occur later in life (LADA)

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2
Q

Pathology of T1DM?

A

o Islet cell antibodies lead to insulitis and destruction of B cells in Islet of Langerhans causing insulin deficiency

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3
Q

Epidemiology of T1DM?

A
  • Peak age is puberty but can be any age
  • Usually lean
  • Associated with autoimmune diseases of thyroid, blood, etc
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4
Q

Aetiology of T1DM?

A

o HLA-DR3/4

o Family history of Type 1

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5
Q

Environmental triggers of T1DM?

A

o Autoantibodies appear early (Glutamic acid decarboxylase)
o Diet
o Coxsackie virus

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6
Q

Acute symptoms of T1DM?

A
  • Young people with 2-6 week history of thirst, polyuria, weight loss
  • Ketoacidosis
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7
Q

Subacute symptoms of T1DM?

A
  • Over month/years (type 2 commonly)

- Thirst, polyuria, weight loss, fatigue, visual blurring, infections

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8
Q

Diagnosis of T1DM?

A

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

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9
Q

Management if T1DM diagnosed?

A
  • If type 1 diagnosed – refer same-day to diabetes specialist team
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10
Q

Initial care of newly diagnosed T1DM?

A
  • 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
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11
Q

Drug treatment in T1DM?

A

Insulin

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12
Q

Advice on self-monitoring in insulin management of T1DM?

Targets?

When to give real time glucose monitoring?

When is sensor pump therapy given?

A

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

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13
Q

Insulin regimens in T1DM?

A

 Offer Basal-bolus regimen 1st line
 Continuous insulin SC infusion (pump)
 2x day pre-mixed 70:30

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14
Q

Basal-bolus regimen in T1DM?

A

 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)

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15
Q

Continuous insulin SC infusion in T1DM?

A

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)
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16
Q

Pre-mixed insulin in T1DM?

A

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

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17
Q

Adjunctive treatments if insulin not achieving adequate glycaemic control in T1DM?

A

 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

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18
Q

Sick day rules in T1DM?

A

 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

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19
Q

Management of T1DM in hospital?

A

 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

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20
Q

Accessories needed in insulin therapy of T1DM?

A

 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

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21
Q

Other drug management given in T1DM?

A
  • 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
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22
Q

When to refer to nephrologist in T1DM?

A
  • To nephrologist if eGFR <30
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23
Q

Follow ups in T1DM?

A
  • 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
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24
Q

How to screen for retinopathy in T1DM?

A

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)

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25
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
26
How to screen for nephropathy in T1DM?
 Nephropathy (EMU for ACR, eGFR check) | • Start ACEi if confirmed nephropathy and T1DM
27
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
28
Complications of T1DM?
o Macrovascular  Atherosclerosis – stroke, MI, PVD o Microvascular  Affects all small vessels – particularly in retina and nerve sheath
29
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
30
Nephropathy complications in T1DM?
o Damages by glomerular disease – thickening of basement membrane and glomerulosclerosis – microalbuminuria and decreased eGFR
31
Neuropathy complications in T1DM?
o Symmetrical sensory polyneuropathy o Acute painful neuropathy o Mononeuritis
32
Diabetic foot complications in T1DM?
o Ulcers due to neuropathy and vascular disease
33
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
34
Other complications in T1DM?
- Infection – especially UTI and skin | - Gastroparesis
35
Definition of T2DM?
- Type 2 diabetes defined as persistent hyperglycaemia (RPG >11) caused by deficient insulin secretion and resistance to action of insulin
36
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
37
Epidemiology of T2DM?
- 2-4x more common in Asians, Africans | - One of most common chronic diseases in UK, prevalence increasing
38
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)
39
Symptoms of T2DM?
- Subacute with complications – infections, etc - Polydipsia, polyuria, weight loss and fatigue - Can be asymptomatic
40
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
41
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
42
What to do if risk assessment shows low or intermediate risk score in T2DM?
lifestyle and reassess in at least next 5 years
43
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
44
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
45
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
46
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
47
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
48
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
49
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
50
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
51
Drug treatment in T2DM - when metformin not appropriate - 1st line?
• DPP-4 inhibitor OR pioglitazone OR sulfonylurea
52
Drug treatment in T2DM - when metformin not appropriate - 1st intensification?
* DPP-4 inhibitor + pioglitazone OR * DPP-4 inhibitor + sulfonylurea OR * Pioglitazone + sulfonylurea
53
Drug treatment in T2DM - when metformin not appropriate - 2nd intensification?
• Consider insulin-based treatment
54
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
55
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
56
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) ```
57
Names of gliptins?
- DPP-4 inhibitor | - Sitagliptin, vildagliptin, saxagliptin, linagliptin
58
names of thiazolidinediones?
- Stimulates nuclear receptor PPAR-Gamma - Can cause fluid retention, anaemia - Pioglitazone, rosiglitazone
59
Names of flozins, SE?
- SGLT2 inhibitor | - Common SE UTIs, joints pains, fungal infection
60
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
61
Prognosis of T2DM?
- Optimal management, usually patients live normal life but may have complications - Reduced life expectancy by average of 10 years
62
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 ```
63
Management of low risk diabetic foot disease?
annual foot assessments, emphasise foot care importance
64
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)
65
Assessment in foot protection services?
* Assess feet * Advice, skin and nail care * Biomechanical status of feet, specialist footwear provision * Vascular status
66
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)
67
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
68
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
69
Definiton of Charcot's arthropathy?
 Deformed foot  Rocker bottom foot  Collapsed medial arch
70
Investigations of Charcot's arthropathy?
 Weight-bearing X-ray of foot and ankle |  MRI if X-ray normal but still suspected
71
Management of Charcot's arthropathy?
 Non-removable/Removable offloading device |  Monitor with foot-skin temperature difference and X-rays until resolves
72
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
73
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
74
Investigations of diabetic foot ulcer?
 Document size, depth and position of ulcer |  Use SINBAD (Site, ischaemia, neuropathy, bacterial infection, area and depth) to classify
75
Management of diabetic foot ulcer?
 Offloading (plantar, forefoot and midfoot)  Control infection/ischaemia  Wound debridement & dressing • UrgoStart dressings
76
Description of Graves' disease?
- Excess circulating thyroid hormones produced by overactive thyroid gland
77
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
78
Epidemiology of Graves' disease?
- 10x more common in women
79
Risk factors of Graves' disease?
``` o Women 10x o FHx of thyroid disease o Smoking o Low iodine intake o T1DM ```
80
Causes of primary hyperthyroidism?
 Graves’ Disease  Toxic Multinodular Goitre  Toxic thyroid adenoma  Drugs
81
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
82
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)
83
Definition of toxic thyroid adenoma?
• Nodule produces enough hormone to supress TSH from pituitary and contralateral thyroid lobe
84
What drugs cause hyperthyroidism?
• Iodine (amiodarone, IV contrast), lithium, IFN-alpha
85
Causes of secondary hyperthyroidism?
 High hCG (gestational, multiple pregnancy, choriocarcinoma, hydatidiform mole)  Pituitary adenoma
86
What causes thyrotoxicosis without hyperthyroidism?
 Drugs – levothyroxine, amiodarone, corticosteroids |  Thyroiditis (release of thyroid hormones into circulation due to inflammation of follicles)
87
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
88
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
89
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 ```
90
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
91
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
92
Blood tests to perform in hyperthyroidism?
TFTs (TSH, T3/4)
93
What to do if TSH within normal range in hyperthyroidism?
further investigations not usually needed
94
What to do if TSH low (but over 0.1) in hyperthyroidism?
recheck along with FT4 &FT3 after 1-2 months
95
What to do if TSH <0.1 in hyperthyroidism?
check FT4 and FT3
96
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
97
Investigations to perform if thyroiditis suspected?
CRP/ESR
98
Management of overt hyperthyroidism?
Refer overt hyperthyroidism to endocrinology Whilst awaiting specialist assessment:  Beta-blockers (propranolol) to control tremor and tachycardia
99
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
100
Specialist management in hyperthyroidism - drug treatment?
* Radioiodine | * Carbimazole (or propylthiouracil)
101
Management with radioiodine in hyperthyroidism?
o First line in toxic nodular goitre & Grave’s disease | o For 18 months
102
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
103
Surgical management in hyperthyroidism?
• Total or near-total thyroidectomy | o Second-line in multiple nodules
104
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
105
Management of Graves' orbitopathy?
o Admit immediately – if suspected optic neuropathy, corneal opacity or Hx of globe subluxation o Refer to ophthalmology
106
General advice given in hyperthyroidism/Graves' disease?
 Smoking cessation  Artificial tears to lubricate eyes  Avoid damage to eyes  Elevate head of bed
107
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
108
Follow up in hyperthyroidism - after radioactive iodine treatment?
 Every 6 weeks – TFTs
109
Follow up in hyperthyroidism - after surgery?
 TSH and FT4 at 2 and 6 months, then TSH annually
110
Follow up in hyperthyroidism - if in remission?
 TFTs annually
111
Follow up in hyperthyroidism - if untreated subclinical hyperthyroidism?
 Check TFTs every 6-12 months
112
Prognosis of hyperthyroidism?
 Remission in up to 30% without treatment in Grave’s |  Risk of relapse if anti-thyroid drug stopped
113
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
114
Symptoms of thyrotoxic storm?
tachycardia, fever, AF, HF, fever, diarrhoea, vomiting, dehydration, delirium, coma
115
Tests in thyrotoxic storm?
 Tests – TFTs, technetium uptake if possible
116
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
117
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 ```
118
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
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Causes of Primary adrenal insufficiency?
```  Addison's Disease (80%)  TB  Adrenal metastases/haemorrhage  Amyloidosis/haemachromatosis  Infection – histoplasmosis, cryptococcosis, CMV, HIV  CAH  Adrenalectomy ```
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Causes of Secondary adrenal insufficiency?
 Exogenous steroids  Antipsychotic medication  Tumours secreting steroids  Trauma, radiotherapy, surgery, neoplasm to hypothalamus
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Associated diseases with adrenal insufficiency?
o Hypothyroidism | o T1DM
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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
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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
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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)
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Secondary care tests performed in Addison's disease - autoantibodies?
 Adrenal cortex autoantibodies |  21-hydroxylase antibodies
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Secondary care tests performed in Addison's disease - imaging?
 CXR/AXR |  CT scan if TB, infection, haemorrhage or neoplastic disease suspected
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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
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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
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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
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Management of Addison's disease - Exercise rules?
``` o Strenuous (marathon) – up to double dose o Normal exercise – 5-10g hydrocortisone before activity ```
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Management of Addison's disease - follow up?
 Primary and secondary care shared  Annual • Weight, BP, U&Es • TFTs, glucose, HbA1c, FBC, VitB12, coeliac
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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
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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 ```
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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
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Prognosis of Addison's Disease?
o If untreated – fatal | o Require lifelong treatment
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Description of hypothyroidism?
- Impaired production of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3)
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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
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Epidemiology of hypothyroidism?
- Prevalence 1-2% - Women 10x - Secondary hypothyroidism is rare - Congenital hypothyroidism is screened for in Guthrie test
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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
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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)
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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 ```
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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 ```
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Symptoms specifically in secondary hypothyroidism?
also with headache, diplopia, pituitary hormone symptoms
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Symptoms in postpartum hypothyroidism?
usually 3-8 months PP and lasts 6 months
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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) ```
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Bloods tested if primary hypothyroidism suspected?
 FBC – anaemia  HbA1c – T1DM  Lipids  Thyroid peroxidase antibodies (TPOAb)
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Imaging if goitre present with hypothyroidism?
USS
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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
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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)
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Management of overt hypothyroidism - referral to endocrine?
 Suspected subacute thyroiditis, goitre, nodule, endocrine disease, female and planning pregnancy, CVD, drug-induced
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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
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Management of overt hypothyroidism - follow up?
o Once stable, TSH every 4-6 monthly and then annually | o Check lipids if elevated initially
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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’
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Follow up of subclinical hypothyroidism?
* Annually if symptoms, thyroid surgery, raised Ab levels | * Every 2-3 years if no features of disease
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Management of secondary hypothyroidism?
o Refer urgently to endocrinologist
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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
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Symptoms of myxoedema coma?
o Symptoms: hypothyroid, hypothermia, hyporeflexia, low glucose, bradycardic, coma, seizures, psychotic (myxoedema madness) o Signs: goitre, cyanosis, low BP, HF
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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 ```
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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
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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 ```
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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
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Definition of hyperparathyroidism?
excessive of PTH, leads to raised serum Ca and low phosphate
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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
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Epidemiology of hyperparathyroidism?
- 3rd most common endocrine disorder | - Primary hyperparathyroidism – common in women 50-60 years old
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Causes of primary hyperparathyroidism?
 Single parathyroid adenoma 80% (may be due to MEN1, 2a)  Hyperplasia of all glands 20%  Parathyroid carcinoma <1%
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Causes of secondary hyperparathyroidism?
 CKD – hyperplastic after long-term stimulation due to chronic hypocalcaemia  Low vitamin D intake  Malabsorption
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Causes of tertiary hyperparathyroidism?
 Prolonged secondary hyperparathyroidism • Glands become autonomous, producing excessive PTH even after corrected hypocalcaemia  CKD most common cause
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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 ```
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Signs of primary hyperparathyroidism?
 Hypertension, shortened QT interval  Peptic ulcers (duodenal 7x)  Depressed
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Symptoms of secondary hyperparathyroidism?
o CKD o Oesteomalacia, fracture risk, myopathy o Bone pain
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Symptoms of tertiary hyperparathyroidism?
o Hypercalcaemia symptoms so similar to primary
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What incidental findings indicate primary hyperparathyroidism?
 Hypercalcaemia |  Hypophosphataemia
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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 ```
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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
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Investigations once diagnosis confirmed of primary hyperparathyroidism?
 U&Es  DEXA scan of lumbar spine, distal radius and hip  US of renal tract
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Bloods in secondary hyperparathyroidism?
 Low-normal calcium  Raised PTH  Phosphate (high in CKD, low in Vitamin D deficiency)
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Bloods in tertiary hyperparathyroidism?
 Raised Ca  Raised PTH  Phosphate often raised
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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
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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
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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
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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
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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
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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
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Management of tertiary hyperparathyroidism ?
o Cinacalcet | o Total or subtotal parathyroidectomy
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Management of tertiary hyperparathyroidism ?
o Cinacalcet | o Total or subtotal parathyroidectomy
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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
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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
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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
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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 ```
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Symptoms of hypercalcaemia?
Bones, stones and psychiatric moans ```  Early • Lethargy • Malaise • Anorexia • Polyuria • Thirst • Nausea & vomiting • Constipation • Bone pain  Late • Confusion • Drowsiness • Fits • Coma ```
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Signs of hypercalcaemia?
``` o Hyporeflexia o Weight loss o Bradycardia o Short QT interval, wide T wave, Prolonged PR o BBB ```
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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
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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
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Definition of hyperlipidaemia?
- Raised serum levels of one or more of total cholesterol, LDLs or triglycerides
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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
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Inherited causes of hyperlipidaemia?
 Familial dyslipidaemia, hypercholesterolaemia, combined hyperlipidaemia  Apoprotein disorders
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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 ```
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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
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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
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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
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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
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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