Disease Summary - Endocrine and Diabetes

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What is gigantism?

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1

What is gigantism?

excess GH due to pituitary tumour before epiphyseal plates of long bones close

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2

What is acromegaly?

excess GH due to a pituitary tumour after epiphyseal plates have sealed

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3

Cause of acromegaly

pituitary gland producing too much growth hormone usually due to an adenoma in the pituitary gland

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4

Presentation of acromegaly

  • swollen hands and feet

  • tiredness and difficulty sleeping

  • sometime sleep apnoea

  • gradual changes in facial features - brow, lower jaw and nose getting larger

  • teeth becoming more widely spaced

  • numbness and weakness in your hands - carpal tunnel syndrome

  • children and teenagers abnormally tall

  • thick, coarse, oily skin

  • joint pain

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5

Investigations for acromegaly

  • blood tests - measure GH levels, insulin-like growth factor 1 (IGF-1) (elevated suggests acromegaly)

  • MRI scan of brain

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Management of acromegaly

  • surgery to remove tumour

  • monthly injections of octreotide, lanreotide or pasireotide

  • a daily pegvisomant injection

  • bromocriptine or cabergoline tablets

  • radiotherapy - stereotactic or conventional

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7

Complications of acromegaly

  • type 2 diabetes

  • hypertension

  • heart disease

  • cardiomyopathy

  • arthritis

  • bowel polyps

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What is 1º hypercortisolism / Cushing’s syndrome?

hypersecretion of cortisol due to a tumour in the adrenal cortex

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9

What is 2º hypercortisolism / Cushing’s disease

hypersecretion of cortisol due to a tumour in the pituitary gland

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10

Causes of Cushing’s Syndrome

  • tumour in the pituitary gland in the brain

  • tumour in one of the adrenal glands

  • body producing too much cortisol

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Presentation of Cushing’s Syndrome

  • increased fat on chest and tummy but slim arms and legs

  • a build-up of fat on the back of neck and shoulders, known as ‘buffalo hump’

  • red, puffy, rounded face

  • weight gain

  • skin that bruises easily

  • large purple stretch marks

  • weakness in upper arms and thighs

  • low libido and fertility problems

  • depression and mood swings

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Investigations of Cushing’s Syndrome

measure cortisol levels in urine, blood and saliva (high cortisol suggests Cushing’s)

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Management of Cushing’s Syndrome

  • reduce or stop steroids if they are the cause

  • surgery to remove tumour

  • radiotherapy

  • medicine to reduce the effect of cortisol (ketocanazole, mitotane, metyrapone), (mifepristone for people with type 2 diabetes)

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What causes hypotension in Addison’s Disease?

loss of permissive effect of cortisol on adenoreceptors and loss of ability to retain Na⁺ leading to hypovolaemia

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15

What is Addison’s Disease?

hyposecretion of all adrenal steroid hormones

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16

Causes of Addison’s Disease

  • autoimmune destruction of adrenal cortex resulting in disruption of the production of the steroid hormones aldosterone and cortisol

  • TB can also damage adrenal glands

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Presentation of Addison’s Disease

  • fatigue

  • muscle weakness

  • low mood

  • loss of appetite and unintentional weight loss

  • increased thirst

  • dizziness / fainting, cramps, exhaustion develop over time

  • darkened skin, lips or gums

  • hypotension

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18

Management of Addison’s Disease

medication to replace missing hormones - hydrocortisone (prednisolone and dexamethasone can also be used) to replace cortisol and fludrocortisone to replace aldosterone

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19

Investigations for Addison’s Disease

  • blood tests

    • sodium (low)

    • cortisol (low)

    • potassium (high)

    • ACTH (high)

    • aldosterone (low)

    • glucose (low)

    • adrenal antibodies (positive)

  • synacthen stimulation test - ACTH level high but cortisol and aldosterone low = Addison’s Disease

  • thyroid function test

  • CT / MRI

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20

Causes of hypercalcaemia

overactive parathyroid glands

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21

Presentation of hypercalcaemia

  • excessive thirst

  • frequent urination

  • nausea and vomiting

  • constipation

  • muscle weakness

  • fatigue

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Management of hypercalcaemia

IV isotonic saline, subcutaneous calcitonin and a bisphosphonate

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23

Complications of hypercalcaemia

  • osteoporosis

  • kidney stones

  • kidney failure

  • arrhythmia

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24

Causes of hyperprolactinaemia

  • pregnancy

  • lactation

  • stress

  • drugs

  • pituitary lesions

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25

What drugs can cause hyperprolactinaemia

  • dopamine antagonists

  • DA-depleting agents

  • oestrogens

  • some antidepressants

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26

Presentation of hyperprolactinaemia

  • milky nipple discharge

  • menstrual irregularities

  • erectile dysfunction

  • headaches

  • visual problems

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Investigations for hyperprolactinaemia

  • bloods - prolactin (high)

  • MRI

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Management of hyperprolactinaemia

  • surgery to remove tumour

  • medicine to lower prolactin levels - Bromocriptine, cabergoline

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29

What is hypopituitarism?

deficiency of one or more of the pituitary hormones

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30

Causes of hypopituitarism

  • head injuries

  • brain surgery

  • radiation treatment to head or neck

  • stroke or haemorrhage

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Presentation of GH deficiency hypopituitarism

  • fatigue

  • muscle weakness

  • changes in body fat composition

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Presentation of LH and FSH deficiency hypopituitarism

  • hot flashes

  • irregular or no periods

  • loss of pubic hair

  • an inability to produce milk for breast-feeding

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Presentation of TSH deficiency hypopituitarism

  • fatigue

  • weight gain

  • dry skin

  • constipation

  • sensitivity to cold or difficulty staying warm

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Presentation of ACTH deficiency hypopituitarism

  • severe fatigue

  • hypotension

  • frequent and prolonged infections

  • nausea and vomiting

  • abdominal pain

  • confusion

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Presentation of ADH deficiency hypopituitarism

  • eccessive urination

  • extreme thirst

  • electrolyte imbalances

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Management of hypopituitarism

  • hormone replacement therapy

  • surgery to remove pituitary adenoma

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Management of hypersecretion pituitary tumours

  • dopamine agents (prolactinoma)

  • somatostatin analogues (acromegaly)

  • GH receptor antagonist (acromegaly)

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Management of hyposecretion pituitary tumours

  • cortisol, T4, sex steroids, GH

  • desmopressin

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39

Adverse effects of somatostatin analogues

  • nausea, cramps, diarrhoea, flatulence

  • cholesterol gallstones

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40

Causes of hypothyroidism

  • immune system attaching the thyroid gland

  • thyroid cancer

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Presentation of hypothyroidism

  • fatigue / lethargy

  • cold intolerance

  • weight gain

  • weakness, arthralgia, myalgia

  • constipation

  • menstrual irregularities

  • depression, impaired concentration / memory

  • dry skin

  • reduced body and scalp hair

  • thyroid pain

  • oedema, including swelling of eyelids

  • hoarse voice

  • goitre

  • bradycardia and diastolic hypertension

  • paraesthesia

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Investigations for hypothyroidism

  • thyroid function test - measures TSH and free T4 (high TSH, low FT4 = hypothyroidism)

  • bloods - FBC, glucose or HbA1c

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Management of hypothyroidism

  • levothyroxine daily

  • regular blood tests until correct does of levothyroxine is reached

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What dosage of levothyroxine should adults <65 years be started on?

1.6 micrograms per kg daily

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What dosage of levothyroxine should adults >65 years or with pre-existing cardia disease be started on?

25 to 50 micrograms daily

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How should levothyroxine be taken?

  • first thing in the morning

  • with water

  • on an empty stomach

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47

Causes of hyperthyroidism

  • Graves’ disease

  • nodules on the thyroid

  • amiodarone

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Presentation of hyperthyroidism

  • nervousness, anxiety, irritability

  • mood swings

  • difficulty sleeping

  • persistent tiredness and weakness

  • sensitivity to heat

  • swelling in neck (goitre)

  • palpitations

  • light periods

  • bowel frequency

  • hyperreflexia

  • twitching or trembling

  • weight loss

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49

Investigations for hyperthyroidism

  • thyroid function blood test - measure TSH, T3 and T4 (low TSH and high FT3/FT4 = hyperthyroidism)

  • thyroid scan

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50

Management of hyperthyroidism

  • carbimazole / propylthiouracil to stop thyroid producing excess hormones

  • radioiodine treatment

  • surgery to remove some or all of thyroid

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51

Causes of thyroid cancer

  • thyroiditis

  • goitre

  • radiotherapy in childhood

  • obesity

  • familial adenomatous polyposis

  • acromegaly

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Presentation of thyroid cancer

  • a painless lump or swelling in the front of the neck

  • swollen glands in the neck

  • unexplained hoarseness that does not get better after a few weeks

  • a sore throat that does not get better

  • difficulty swallowing (dysphagia)

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53

Investigations for thyroid cancer

  • thyroid function test - rule in hyper/hypothyroidism instead of cancer

  • ultrasound

  • biopsy

  • CT / MRI

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Management of thyroid cancer

  • surgery - to remove all or part of the thyroid

  • radioactive iodine treatment

  • external radiotherapy

  • chemotherapy and targeted therapies

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55

Normal calcium level

between 2.1 mmol per litre and 2.6 mmol per litre

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56

Causes of hypocalcaemia

  • total thyroidectomy

  • parathyroidectomy

  • severe vitamin D deficiency

  • Mg²⁺ deficiency

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Presentation of hypocalcaemia

  • paraesthesia

  • tetany (neuromuscular irritability)

  • carpopedal spasm

  • muscle cramps

  • muscle twitching

  • seizures

  • prolonged QT interval

  • hypotension

  • heart failure

  • arrythmia

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Investigations for hypocalcaemia

  • ECG

  • serum calcium

  • albumin

  • phosphate

  • U&Es

  • vitamin D

  • magnesium

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Management of mild hypocalcaemia

  • oral calcium tablets

  • vitamin D if deficient

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Management of severe hypocalcaemia

  • IV calcium gluconate

  • treat underlying cause

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Growth disorders - indications for referral

  • extreme short or tall stature

  • height below target height

  • abnormal height velocity

  • history of chronic disease

  • obvious dysmorphic syndrome

  • early / late puberty

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Causes of short stature

  • undernutrition

  • chronic illness - JCA, IBD, coeliac

  • iatrogenic - steroids

  • psychological and social

  • hormonal - GHS, hypothyroidism

  • syndromes - Turner, P-W

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What is early puberty in boys?

<9 years

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What is delayed puberty in boys?

14 years

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What is early puberty in girls?

<8 years

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What is delayed puberty in girls?

13 years

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Causes of delayed puberty

  • gonadal dysgenesis

  • chronic diseases - Crohn’s, asthma

  • impaired HPG axis

  • bone age delay

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68

What is type I diabetes mellitus?

insulin-dependent diabetes - where your blood glucose level is to high because your body can’t make insulin

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Presentation of type I diabetes mellitus

short duration of:

  • thirst

  • peeing more frequently (polyuria)

  • nocturia

  • fatigue

  • weight loss

  • abdominal pain

  • blurred vision

on examination:

  • ketones on breath

  • dehydration

  • increased RR, tachycardia, hypotension

  • low grade infections, thrush

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Investigations for diabetes

  • diagnostic glucose levels - fasting ≥ 7.0mmol/l, random ≥ 11.1mmol/l

  • oral glucose tolerance test 2hrs after 75g CHO ≥ 11/1mol/l

  • HbA1c ≥ 48mmol/mol

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Management of type I diabetes mellitus

  • eat healthily

  • exercise regularly

  • regular blood tests

  • smoking cessation

  • reduce alcohol intake

  • regular insulin injections for rest of life

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72

What is type II diabetes?

non-insulin dependent diabetes - when the insulin your pancreas makes can’t work properly as the body’s cells do not react to insulin properly, or your pancreas can’t make enough insulin and so blood glucose levels keep rising

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73

Risk factors for type II diabetes mellitus

  • obesity

  • unhealthy diet

  • hypertension

  • long-term steroid use

  • age

  • ethnicity

  • family history

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Management of type II diabetes mellitus

  • eat healthily

  • exercise regularly

  • regular blood tests

  • smoking cessation

  • reduce alcohol intake

  • weight loss

  • metformin

  • gliclazide / glimepiride / alogliptin / pioglitazone

  • dapagliflozin / empaglifozin

  • exenatide or liraglutide injections

  • insulin

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75

Side effects of metformin

  • nausea and vomiting

  • diarrhoea

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Impaired fasting glucose level in intermediate hyperglycaemia

6.1 - 7mmol/l

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Impaired glucose tolerance 2hrs glucose test in intermediate hyperglycaemia

≥7.8 and <11mmol/l

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HbA1c in intermediate hyperglycaemia

42 - 47mmol/mol

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When can HbA1c not be used for diagnosing diabetes mellitus?

  • children and young people

  • pregnancy - correct or recent (<2months)

  • short duration diabetes symptoms

  • high risk of diabetes and acutely ill

  • patients taking medications that can cause rapid glucose risk (corticosteroids, antipsychotic drugs)

  • acute pancreatic damage / pancreatic surgery

  • renal failure

  • HIV infection

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Presentation of type II diabetes mellitus

  • thirst

  • peeing more frequently (polyuria)

  • nocturia

  • fatigue

  • weight loss

  • blurred vision

  • not ketotic

  • overweight

  • low grade infections, thrush

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81

Causes of autoimmune diseases

  • genetic factors

  • environmental factors

  • infections

  • drugs

  • UV radiation

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Management of autoimmune diseases

  • suppression of the damaging immune response

  • replacement of the function of the damaged organ

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83

What is cretinism?

hypothyroidism present in the new-born where there is physical growth and mental development impairment

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84

What is the most common cause of acquired hypothyroidism in adults?

Hashimoto thyroiditis

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85

What are autoimmune polyendocrine syndromes?

a diverse group of clinical conditions characterised by functional impairment of multiple endocrine glands due to loss of immune tolerance

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86

Examples of autoimmune polyendocrine syndromes

  • alopecia

  • vitiligo

  • coeliac disease

  • autoimmune gastritis with vitamin B12 deficiency

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Presentation of autoimmune polyendocrine syndrome type 1 (ASP-1)

  • at least two of three cardinal components during childhood:

    • chronic mucocutaneous candidiasis

    • hypoparathyroidism

    • primary adrenal insufficiency

  • other typical components:

    • enamel hypoplasia

    • enteropathy with chronic diarrhoea or constipation

    • primary ovarian insufficiency

  • less frequent components:

    • bilateral keratitis

    • periodic fever with rash

    • autoimmunity-induced hepatitis, pneumonitis, nephritis, exocrine pancreatitis, functional asplenia

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What is more common, autoimmune polyendocrine syndrome type 1 or 2?

type 2

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Presentation of autoimmune polyendorine syndrome type 2 (ASP-2)

  • at least two of:

    • type 1 diabetes

    • autoimmune thyroid disease

    • Addison’s disease

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90

Presentation of hyperglycaemia

  • tiredness

  • nausea

  • hyperactivity

  • irritability

  • blurred vision

  • increased breathing

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Presentation of hypoglycaemia

  • headache

  • hunger

  • sweating

  • confusion

  • shakes

  • irritability

  • anxiety

  • blurred vision

  • drowsiness

  • confusion

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What can chronic poor control of diabetes lead to in small blood vessel damage

  • visual impairment

  • renal dysfunction

  • foot ulcers

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What can chronic poor control of diabetes lead to in large blood vessel damage

  • stroke

  • myocardial infarction

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Why are laboratory tests used for in diabetes?

  • diagnosis

  • monitoring

  • prognosis

  • screening

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95

Co-morbidities associated with obesity

  • asthma

  • cancer

  • cardiovascular disease

  • dementia

  • depression

  • type 2 diabetes

  • fertility problems

  • gastro-oesophageal reflux disease

  • kidney disease

  • liver disease

  • osteoarthritis

  • acute pancreatitis

  • obstructive sleep apnoea syndrome

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Management of obesity tier system

  • Tier 1 - population-wide health improvement work

  • Tier 2 - primary care

  • Tier 3 - specialist weight management

  • Tier 4 - specialist surgical service

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97

Tier 1 management of obesity

population-wide health improvement work:

  • community interventions including active referral

  • walking groups

  • leisure club classes

  • cooking classes

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98

Tier 2 management of obesity

Primary care

  • NHS Health Weight programmes

  • lifestyle adviser

  • community dietetic

  • drug therapy if appropriate supported by local clinical guidance

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Tier 3 management of obesity

Specialist Weight Management

  • access to multi-disciplinary team e.g. dietetic led programme, psychological expertise, physiotherapy

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Tier 4 management of obesity

Specialist Surgical Service:

  • bariatric surgery

  • gastric bands

  • specialist follow up

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