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Flashcards in Endocrinology Deck (100):
1

Pathophysiology of T1DM

autoimmune destruction of β-cells → absolute
insulin deficiency.

2

Pathophysiology of T2DM

insulin resistance and β-cell dysfunction → relative insulin deficiency

3

Presenting symptoms of diabetes mellitus

polyuria, polydipsia, ↓wt, lethargy

- T1DM - DKA

4

Diagnosis of DM

Symptoms and 1 abnormal result
Fasting ≥7mM
Random ≥11.1mM
HbA1c ≥ 6.5% (T2DM)

Or 2 results at different times

5

Secondary causes of DM

 Drugs: steroids, anti-HIV, atypical neuroletics, thiazides
 Pancreatic: CF, chronic pancreatitis, HH, pancreatic Ca
 Endo: Phaeo, Cushings, Acromegaly, T4
 Other: glycogen storage diseases

6

Define Metabolic Syndrome

Central obesity (↑ waist circumference) and two of:  ↑ Triglycerides
 ↓ HDL
 HTN
 Hyperglycaemia: DM, IGT, IFG

7

Lifestyle Modifications in DM

Diet - healthy, reduced refined CHO, avoid alcohol
Exercise
Lipids (T2 - >40 - statin)
ABP - <130/80
Aspirin >50y/o
Yearly/6m check up
- control, complications, competency, coping
Smoking cessation

8

Examination for DM complications

Macro
Pulses
 BP
 Cardiac auscultation
Micro
 Fundoscopy
 ACR + U+Es
 Sensory testing plus foot inspection

9

Medical management of T2DM

1) Metformin
2) + sulphonylura/Gliptin/ Pioglitazone
3) + another
4) + insulin

10

Metformin - action, SE and CI

↑ cells sensitivity to insulin
SE - diarrhoea, abdo pain, vitamin b12 deficiency, lactic acidosis
CI - GFR<30, tissue hypoxia (sepsis, MI)

11

Sulphonylureas - example action and SE

Gliclazide
↑ insulin release from β-cells

SE - weight gain, GI disturbances, ↑ risk hypoglycaemia

12

Pioglitazone - Action and SE

binding PPAR- γ- upregulates genes that affect glucose and lipid metabolism
SE - weight gain, oedema, liver dysfunction, effects on bone metabolism

13

Gliptins - example, action and SE

Sitagliptin - protect native GLP-1 from inactivation by DPP-4
SE - GI

14

Sodium – Glucose Co-transporter 2 inhibitors - example, action and SE

Dapagliflozin - Inhibit SGLT2 (PT) in kidney- decrease glucose reabsorption.

SE - weight loss, Low risk of hypoglycaemia, polyuria and lower UTIs/ Thrush/Urosepsis

15

Common Insulin Regimes

Twice daily pre-mixed
- Mixed intermediate and rapid acting insulin BD - before breakfast and dinner
- regular lifestyle: children, older pts.

Basal-Bolus Regime
- Bedtime long-acting + short acting before each meal
- allowing flexible lifestyle

16

Insulin requirements when ill

Insulin requirements usually ↑ (even if food intake ↓)
 Maintain calories (e.g. milk)
 Check BMs ≥4hrly and test for ketonuria
 ↑ insulin dose if glucose rising

17

SE of Insulin

 Hypoglycaemia
- At risk: EtOH binge, β-B (mask symptoms), elderly
 Lipohypertrophy
- Rotate injection site: abdomen, thighs
 Wt. gain in T2DM

18

Macrovascular DM complications and Rx

 MI: May be “silent” due to autonomic neuropathy
 PVD: claudication, foot ulcers
 CVA

Rx: Manage CV risk factors
 BP (aim <130/80)
 Smoking
 Lipids
 HBA1c <6%
- regular fundoscopy, foot check

19

Features of diabetic feet

ISCHAEMIA
 Critical toes
 Absent pulses (do ABPI)
 Ulcers: painful, punched-out, foot margins, pressure
points

NEUROPATHY
 Loss of protective sensation
 Deformity: Charcot’s joints, pes cavus, claw toes
 Injury or infection over pressure points
 Ulcers: painless, punched-out, metatarsal heads, calcaneum

20

Management of diabetic feet

Conservative
 Daily foot inspection (e.g. ̄c mirror)
 Comfortable / therapeutic shoes
 Regular chiropody (remove callus)

Medical
 Rx infection: benpen + fluclox ± metronidazole

Surgical
 Abscess or deep infection
 Spreading cellulitis
 Gangrene
 Suppurative arthritis

21

Pathophysiology of nephropathy in DM

Hyperglycaemia → nephron loss and glomerulosclerosis

22

Features of nephropathy in DM

 Microalbuminuria: urine albumin:Cr (ACR) ≥30mg/mM
 If present → ACEi / ARA
 Refer if UCR >70

23

Pathogenesis of retinopathy in DM

 Microvascular disease → retinal ischaemia → ↑VEGF
 ↑ VEGF → new vessel formation

24

Presentation of retinopathy of DM

 Retinopathy and maculopathy
 Cataracts
 Rubeosis iris: new vessels on iris → glaucoma
 CN palsies

25

Stages of Diabetic retinopathy

Background Retinopathy
 Dots: microaneurysms
 Blot haemorrhages
 Hard exudates: yellow lipid patches

Pre-proliferative Retinopathy
 Cotton-wool spots (retinal infarcts)
 Venous beading
 Haemorrhages

Proliferative Retinopathy
 New vessels
 Pre-retinal or vitreous haemorrhage

Maculopathy
 ↓ acuity may be only sign
 Hard exudates w/i one disc width of macula

26

Pathophysiology of neuropathy

 Metabolic: glycosylation, ROS, sorbitol accumulation
 Ischaemia: loss of vasa nervorum

27

Features of polyneuropathy in DM

 Glove and stocking: length-dependent ( feet 1st)
 Loss of all modalities
 Absent ankle jerks
 Numbness, tingling, pain (worse @ night)

28

Treatment of polyneuropathy of DM

 Paracetamol
 Amitriptyline, Gabapentin, SSRI
 Capsaicin cream
 Baclofen

29

Pathogenesis of DKA

Ketogenesis
 ↓ insulin → ↑ stress hormones and ↑ glucagon
 → ↓ glucose utilisation + ↑ fat β-oxidation
 ↑ fatty acids → ↑ ATP + generation of ketone bodies.

Dehydration
 ↓ insulin → ↓ glucose utilisation + ↑ gluconeogenesis → severe hyperglycaemia
 → osmotic diuresis → dehydration
 Also, ↑ ketones → vomiting

Acidosis
 Dehydration → renal perfusion
 Hyperkalaemia

30

Precipitants of DKA

 Infection / stress ± stopping insulin
 New T1DM

31

Presentation of DKA

 Abdo pain + vomiting
 Gradual drowsiness
 Sighing “Kussmaul” hyperventilation
 Dehydration
 Ketotic breath

32

Diagnosis of DKA

 Acidosis (↑AG): pH <7.3 (± HCO3 <15mM)
 Hyperglycaemia: ≥11.1mM (or known DM)
 Ketonaemia: ≥3mM (≥2+ on dipstix)

33

Investigations for DKA

 Urine: ketones and glucose, MCS
 Cap glucose and ketones
 VBG: acidosis + ↑K
 Bloods: U+E, FBC, glucose, cultures
 CXR: evidence of infection

34

Treatment of DKA

- Fluids
- Potassium replacement
- Insulin Infusion (actrapid)
+- catheter; NGT; LMWH; find and treat precipitating factors

35

Aims with DKA treatment

 ↓ ketones by ≥0.5mM/h or ↑HCO3 by ≥3mM/h
 ↓ plasma glucose by ≥3mM/h
 Maintain K in normal range
 Avoid hypoglycaemia

36

Resolution of DKA

 Ketones <0.3mM + venous pH>7.3 (HCO3 >18mM)
 Transfer to sliding scale if not eating
 Transfer to SC insulin when eating and drinking
 Pt Education

37

Hyperglycaemic Hyperosmolar State presentation

Usually T2DM, often new presentation
 Usually older
 Long hx (e.g. 1wk)
 Marked dehydration and glucose >35mM
 No acidosis (no ketogenesis)
 Osmolality >340mosmol/kg

38

Complications of HHS

Occlusive events are common: DVT, strok
- Give LMWH

39

Management of HHS

 Rehydrate ̄c 0.9% NS over 48h
- May need ~9L
 Wait 1h before starting insulin
- It may not be needed
- Start low to avoid rapid changes in osmolality
--> E.g. 1-3u/hr (to avoid cerebral oedema)
 Look for precipitant
- MI
- Infection
- Bowel infarct

40

Symptoms of hypoglycaemia

Autonomic: 2.5-3
 Sweating
 Anxiety
 Hunger
 Tremor
 Palpitations

Neuroglycopenic: <2.5
 Confusion
 Drowsiness
 Seizures
 Personality change
 Focal neurology (e.g. CN3)
 Coma (<2.2)

41

Causes of hypoglycaemia

 Usually insulin or sulfonylurea Rx in a known diabetic
 Exercise, missed meal, OD

 Exogenous drugs
 Pituitary insufficiency
 Liver failure
 Addison’s
 Islet cell tumours (insulinomas)
 Immune (insulin receptor Abs: Hodgkin’s)
 Non-pancreatic neoplasms: e.g. fibrosarcomas

42

Investigations of hypoglycaemia

 72h fast ̄c monitoring
 Symptom: Glucose, insulin, C-peptide, ketones

43

Management of hypoglycaemia

Alert and Orientated: Oral Carb
 Rapid acting: lucozade or 5-7 glucose tablets
- wait 15 min and check up to 3x
If corrected

Drowsy / confused but swallow intact: Buccal Carb
 Hypostop / Glucogel
 Consider IV access

Unconscious or Concerned re Swallow: IV dextrose
 2-% gluvose of 100ml/h for 15min

Deteriorating / refractory / insulin-induced / no access
 1mg glucagon IM/SC
 Won’t work in drunks + short duration of effect (20min)
 Insulin release may → rebound hypoglycaemia

Once CBG >4 --> Long acting: toast, sandwich
- refer for education

44

Thyrotoxicosis symptoms

 Diarrhoea
 ↑ appetite but ↓ wt.
 Sweats, heat intolerance
 Palpitations
 Tremor
 Irritability
 Oligomenorrhoea ± infertility

45

Thyrotoxicosis signs

Hands
 Fast / irregular pulse
 Warm, moist skin
 Fine tremor
 Palmer erythema
Face
 Thin hair
 Lid lag
 Lid retraction
Neck
 Goitre or nodules
Graves’ Specific
 Ophthalmopathy
 Exophthalmos
 Ophthalmoplegia: esp. up-gaze palsy
 Eye discomfort and grittiness
 Photophobia and ↓ acuity
 Chemosis
 Dermopathy: pre-tibial myxoedema
 Thyroid acropachy

46

Investigations for thyrotoxicosis

 ↓TSH, ↑T4/↑T3
 Abs: TSH receptor, TPO
 ↑Ca, ↑LFTs
 Isotope scan
 ↑ in Graves’
 ↓ in thyroiditis
 Ophthalmopathy: acuity, fields, movement

47

Management of thyrotoxicosis

Medical
 Symptomatic: β-B (e.g. propranolol 40mg/6h)
 Anti-thyroid: carbimazole (inhibits TPO)
 Titrate according to TFTs or block and replace  In Graves’ Rx for 12-18mo then withdraw
 ~50% relapse → surgery or radioiodine  SE: agranulocytosis

Radiological: Radio-iodine
 Most become hypothyroid
 CI: pregnancy, lactation

Surgical: Thyroidectomy
 Recurrent laryngeal N. damage → hoarseness  Hypoparathyroidism
 Hypothyroidism

48

Features of thyroid storm

 ↑temp
 Agitation, confusion, coma
 Tachycardia, AF
 Acute abdomen
 Heart failure

49

Precipitants of thyroid storm

 Recent thyroid surgery or radio-iodine
 Infection
 MI
 Trauma

50

Management of thryoid storm

1. Fluid resuscitation + NGT
2. Bloods: TFTs + cultures if infection suspected
3. Propranolol PO/IV (counteracts peripheral effects of t3/4)
4. Carbimazole
5. Hydrocortisone (I. thyroid hormone synthesis)
6. Rx cause
6. no change in 24h > thyroidectomy

51

Symptoms of hypothyroidism

 Lethargy
 Cold intolerance
 ↓ appetite but ↑wt.
 Constipation
 Menorrhagia
 ↓mood

52

Signs of hypothyroidism

 Cold hands
 Bradycardic
 Slow-relaxing reflexes
 Dry hair and skin
 Puffy face
 Goitre
 Myopathy, neuropathy
 Ascites
 Myxoedema
- eyes and dorsum of hand

53

Causes of hypothyroidism

Primary
 Atrophic thyroiditis (commonest UK)
 Hashimoto’s thyroiditis
 Subacute thyroiditis (e.g. post-partum)
 Post De Quervain’s thyroiditis
 Iodine deficiency (commonest worldwide)
 Drugs: carbimazole, amiodarone, lithium
 Congenital: thyroid agenesis

Post-surgical
 Thyroidectomy  Radioiodine

Secondary
 Hypopituitarism (v. rare )

54

Investigations for hypothyroidism

 ↑TSH, ↓T3/T4
 ↑MCV ± normochromic anaemia
 ↑ triglyceride + ↑ cholesterol
 Hyponatraemia (SIADH)
 ↑ CK if assoc. myopathy
 Abs: TPO, TSH

55

Management of hypothyroidism

 Levothyroxine
- Titrate to normalise TSH
- Enzyme inducers ↑ thyroxine metabolism
0 Clinical improvement takes ~2wks
 Check for other AI disease: e.g. Addison’s, PA

56

Features of hashimoto's thyroiditis

 TPO +ve
 Atrophy + regeneration → goitre
 May go through initial thyrotoxicosis phase
 May be euthyroid or hypothyoid

57

Features of myxoedema coma

 Looks hypothyroid
 Hypothermia
 Hypoglycaemia
 Heart failure: bradycardia and ↓BP
 Coma and seizures

58

Precipitants of myxoedema coma

 Radioiodine
 Thyroidectomy
 Pituitary surgery
 Infection, trauma, MI, stroke

59

Management of myxoedema coma

 Bloods: TFTs, FBC, U+E, glucose, cortisol
 Correct any hypoglycaemia
 T3/T4 IV slowly (may ppt. myocardial ischaemia)
 Hydrocortisone 100mg IV
 Rx hypothermia and heart failure

60

Complications of thyroid surgery

- haematoma
- laryngeal oedema
- recurrent laryneal nerve palsy
- hypoparathyroidism
- thyroid storm
- hypothyroidism

61

Features of cushing

Cataracts
Ulcers
Striae/ thin skin
Hypertension/ Hirsutidsm
Immunosuppresion/ INfection
Necrosis of femoral head
Glucose high
Osteoporosis, obesity
Impaired wound healing and bruising
Depression

- Moon face and thin limbs
- Proximal myopathy
- Acne
- hypokalaemia
Interscapular and supraclavicular fat pad

62

Causes of Cushing's

ACTH Independent causes
- Iatrogenic steroids
- Adrenal adenoma/ Ca
- Adrenal nodular hyperplasia

ACTH - dependent causes
- Cushing's disease
- Ectopic ATCH

63

Ix for Cushings

1) 24h urinary free cortisol x 3
2) Dexamethosone suppression test
- Suppression at high dose - cushing's disease (bilateral hyperplasia from ACTH secreting pituitary tumour)
> MRI pituitary
- No suppression - Adrenal cause/ Ectopic ACTH
> CT thorax/ adrenals

+- DEXA scan

64

Treatment for Cushing's

- Iatrogenic steroids --> stop meds
- Adrenal adenoma/ adrenal nodular hyperplasia --> adrenelectomy
- Ectopic ACTH - - tumour excision +- metyropone
- Cushing's disease - transphenoidal excision

65

What is Nelson's syndrome

Rapid enlargement of a pituitary adenoma following bilateral adrenelectomy for Cushing's

66

Physical effects of Cushing's disease

- Bitemporal hemianopia (compresses optic chiasm)
- hypopituitarism and hyperprrolactinaemia (compresses stalk and removes I)
- Headache and double vision (invades cavernous sinus)
--> opthalmoplegia, Chemosis, Proptosis, Horners, CN sensory loss

67

Features of Hyperaldosteronism

 Hypokalaemia: weakness, hypotonia, hyporeflexia, cramps
 Paraesthesia
 ↑BP

68

Causes of hyperaldosteronism

PRIMARY
 Bilateral adrenal hyperplasia (70%)
 Adrenocortical adenoma (30%): Conn’s syndrome

SECONDARY
 RAS
 Diuretics
 CCF
 Hepatic failure
 Nephrotic syndrome

69

Treatment of hyperaldosteronism

 Conn’s: laparoscopic adrenelectomy
 Hyperplasia: spironolactone, eplerenone or amiloride
Ix

70

Actions of Angiotensin 2

- ↑ADH (thirst centre and CD in kidney)
- ↑ sympathetic activity - ↑ NAdr
- ↑ Aldosteone
= ↑ Na + Cl reabsorption & H20+K excretion
- Arteriolar vasoconstriction - ↑ BP

71

Pathophysiology of Addison's Disease

Destruction of adrenal cortex → glucocorticoid and mineralocorticoid deficiency

72

Causes of Addison's

 Autoimmune destruction: 80% in the UK
 TB: commonest worldwide
 Metastasis: lung, breast, kidneys
 Haemorrhage: Waterhouse-Friedrichson
 Congenital: CAH

73

Clinical features of Addison's

 Wt. loss + anorexia
 n/v, abdo pain, diarrhoea/constipation
 Lethargy, depression
 Hyperpigmentation: buccal mucosa, palmer creases
 Postural hypotension → dizziness, faints
 Hypoglycaemia
 Vitiligo
 Addisonian crisis
 Sparse axillary and pubic hair

74

Symptoms of Addison's

Tired - fatigue and weakness
Tanned - hyperpigmentation
Tearful - apathy and depression
Thin - weight loss/ n&v&d/ anorexia
+- abdo pain

75

Investigations for Addison'

Bloods - ↓Na/↑K (as ↓ mineralocorticoid) ↓glucose (↓ cortisol); ↓Ca, (+- uraemia - dehydration)
 Anaemia

Differential
 Short synACTHen test
- Cortisol before and after tetracosactide (should stimulate adrenals to produce cortisol)
- Exclude Addison’s if ↑ cortisol; ↑ 9am ACTH (usually low)

Other
 21-hydroxylase Abs: +ve 80% AI
 Plasma renin and aldosterone
 CXR: evidence of TB
 AXR: adrenal calcification
 CT/MRI of adrenals

76

Treatment of Addison's

Replace
 Hydrocortisone
 Fludrocortisone
- emergency hydrocortisone injectino kit

Advice
 Don’t stop steroids suddenly
 ↑ steroids during intercurrent illness, injury
 Wear a medic-alert bracelet and steroid card

F/up
 Watch for AI disease e.g. pernicious anaemia
 yearly BP/ UE

77

Causes of secondary adrenal insufficiency

hypothalamo or pituitary failure

 Chronic steroid use → suppression of HPA axis
 Pituitary apoplexy / Sheehan’s
 Pituitary microadenoma

- No pigmentation as low ACTH

78

Presentation of an Addisonian Crisis

 Shocked: ↑HR, postural drop, oliguria, confused
 Hypoglycaemia

Usually known Addisonian or chronic steroid user

79

Precipitants of an Addisonian Crisis

 Infection
 Trauma
 Surgery
 Stopping long-term steroids

80

Management of an Addisonian Crisis

 Bloods: cortisol, ACTH, U+E, cultures
 ECG - ↑ K+
 Check CBG: glucose may be needed
 Hydrocortisone 100mg IV/IM 6hrly
- oral after 72h and ween off dose
 IV fluid bolus
 Septic screen
 Treat underlying cause

81

What is a pheochromocytoma

Catecholamine-producing tumours arising from sympathetic paraganglia

Usually found in adrenal medulla

Extra-adrenal phaeo’s found by aortic bifurcation

82

Presentation of a pheochromocytoma

Triad: episodic headache, sweating and tachycardia

 ↑BP, palpitations
 Headache, tremor, dizziness
 Anxiety
 d/v, abdo pain
 Heat intolerance, flushes

May have precipitant
 Straining, abdo palpation
 Exercise, stress
 β-B, IV contrast, TCAs, GA

83

Investigations for pheochromocytoma

 Plasma + 24h urine metadrenaline and normetadrenaline
 Also vanillylmandelic acid
 Abdo CT/MRI
 MIBG (mete-iodobenzylguanidine) scan

84

Management of pheo

Medical: Chemo or radiolabelled MIGB

Surgery: adrenelectomy
 α-blocker first, then β-blockade pre-op
 Avoids unopposed α-adrenergic stimulation  Phenoxybenzamine = α-blocker
 Monitor BP post-op for ↓↓BP

85

Hypertensive crisis features

Pallor
Pulsating headache Feeling of impending doom
↑↑BP
↑ ST and cardiogenic shock

86

Management of a hypertensive crisis

Phentolamine 2-5mg IV (α-blocker) or labetalol 50mg IV
 Repeat to safe BP (e.g. 110 diastolic)

87

Causes of raised prolactin

Pregnancy
Prolactinoma
Physiological
PCOS
Primary hypothyroidism
Pheothiazine/ metochlopramide

88

Symptoms of hyperprolactinaemia

 Amenorrhoea
 Infertility
 Galactorrhoea
 ↓ libido
 ED
 Mass effects from prolactinoma

89

Treatment of hyperprolactinaemia

prolactinoma (Prolactin 100,000 iU/L) --> treated medically (dopamine agonist e.g. bromocryptine)

Non-functioning adenoma (Prolactin 1,500 iU/L) --> treated surgically transphenotelectomy

90

Causes of Acromegaly

 Pituitary acidophil adenoma in 99%
 Hyperplasia from GHRH secreting carcinoid tumour

91

Symptoms of Acromegaly

 Acroparaesthesia
 Amenorrhoea, ↓libido
 Headache
 Snoring
 Sweating
 Arthralgia, back ache
 Carpal tunnel (50%)
 Change in shoe size

92

Signs of Acromegaly

Hands
 Spade-like
 Thenar wasting
 Boggy sweaty palms (if active)
 ↑ skin fold thickness
 Carpal tunnel: ↓ sensation + thenar wasting

Face
 Prominent supraorbital ridges
 Scalp folds: cutis verticis gyrata
 Coarse face, wide nose and big ears
 Prognathism/ Macrognathia
 Macroglossia
 Widely-spaced teeth
 Goitre
 Hirsutism

Other
 Puffy, oily, darkened skin skin
 Acanthosis Nigricans
 Tolling gait with bowed legs
 Proximal weakness + arthropathy
 Pituitary mass effects: bitemporal hemianopia

93

Investigations for Acromegaly

- GH response to OGTT (failure to suppress GH)
- MRI pituitary
- Plasma IGF1
Blood - TSH&T4, prolactin, FSH & LH, GH
- Visual fields and acuity

94

Treatment of acromegaly

1st line: trans-sphenoidal excision

2nd line: somatostatin analogues – octreotide

3rd line: GH antagonist – pegvisomant

4th line: radiotherapy

95

Effects of GH on the body

Direct
- carbohydrate metabolism - ↑ blood glucose
- Fat metabolism - ↑ breakdown and release

Indirect
--> LIVER --> IGF1
- ↑ cartilage formation & skeletal growth
- ↑ protein synthesis, cell growth & proliferation

96

Complications of Acromegaly

 Impaired glucose tolerance (40%)
 DM (15%)

 ↑BP
 LVH/ HF
Cardiomyopathy
 ↑ IHD and ↑ stroke

 ↑ risk of CRC

97

Symptoms of Diabetes Insipidus

 Polyuria
 Polydipsia
 Dehydration
 Hypernatraemia: lethargy, thirst, confusion, coma

98

Causes of DI

Cranial - inadequate ADH secretion
 Idiopathic: 50%
 Congenital: DIDMOAD / Wolfram Syndrome
 Tumours
 Trauma
 Vascular: haemorrhage (Sheehan’s syn.)
 Infection: meningoencephalitis
 Infiltration: sarcoidosis

Nephrogenic - failure of kidneys to respond to ADH
 Congenital
 Metabolic: ↓K, ↑Ca
 Drugs: Li, demecleocycline, vaptans
 Post-obstructive uropathy

99

Investigations for DI

Bloods: U+E, Ca, glucose
 Urine and plasma osmolality - Exclude DI if U:P osmolality >2
- Water deprivation test ̄c desmopressin trial

100

Management for DI

Cranial
 Find cause: MRI brain
 Desmopressin PO
Nephrogenic
 Treat cause +- bendroflumethiazide