Endocrinology Flashcards
Pathophysiology of T1DM
autoimmune destruction of β-cells → absolute
insulin deficiency.
Pathophysiology of T2DM
insulin resistance and β-cell dysfunction → relative insulin deficiency
Presenting symptoms of diabetes mellitus
polyuria, polydipsia, ↓wt, lethargy
- T1DM - DKA
Diagnosis of DM
Symptoms and 1 abnormal result
Fasting ≥7mM
Random ≥11.1mM
HbA1c ≥ 6.5% (T2DM)
Or 2 results at different times
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
Define Metabolic Syndrome
Central obesity (↑ waist circumference) and two of: ↑ Triglycerides
↓ HDL
HTN
Hyperglycaemia: DM, IGT, IFG
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
Examination for DM complications
Macro Pulses BP Cardiac auscultation Micro Fundoscopy ACR + U+Es Sensory testing plus foot inspection
Medical management of T2DM
1) Metformin
2) + sulphonylura/Gliptin/ Pioglitazone
3) + another
4) + insulin
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)
Sulphonylureas - example action and SE
Gliclazide
↑ insulin release from β-cells
SE - weight gain, GI disturbances, ↑ risk hypoglycaemia
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
Gliptins - example, action and SE
Sitagliptin - protect native GLP-1 from inactivation by DPP-4
SE - GI
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
Common Insulin Regimes
Biphasic - 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
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
if in hospital and NBM - variable rate insulin infusion (check capillary blood glucose every 1-2 hours)
- stop when eating and drinking and and long acting insulin
SE of Insulin
Hypoglycaemia
- At risk: EtOH binge, β-B (mask symptoms), elderly
Lipohypertrophy
- Rotate injection site: abdomen, thighs
Wt. gain in T2DM
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
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
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
Pathophysiology of nephropathy in DM
Hyperglycaemia → nephron loss and glomerulosclerosis
Features of nephropathy in DM
Microalbuminuria: urine albumin:Cr (ACR) ≥30mg/mM
If present → ACEi / ARA
Refer if UCR >70
Pathogenesis of retinopathy in DM
Microvascular disease → retinal ischaemia → ↑VEGF
↑ VEGF → new vessel formation
Presentation of retinopathy of DM
Retinopathy and maculopathy
Cataracts
Rubeosis iris: new vessels on iris → glaucoma
CN palsies
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
Pathophysiology of neuropathy
Metabolic: glycosylation, ROS, sorbitol accumulation
Ischaemia: loss of vasa nervorum
Features of polyneuropathy in DM
Glove and stocking: length-dependent ( feet 1st)
Loss of all modalities
Absent ankle jerks
Numbness, tingling, pain (worse @ night)
Treatment of polyneuropathy of DM
Paracetamol
Amitriptyline, Gabapentin, SSRI
Capsaicin cream
Baclofen
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
Precipitants of DKA
Infection / stress ± stopping insulin
New T1DM
Alcohol
Presentation of DKA
Abdo pain + vomiting Gradual drowsiness/ confusion Sighing “Kussmaul” hyperventilation Dehydration Ketotic breath
Diagnosis of DKA
Acidosis (↑AG): pH <7.3 (± HCO3 <15mM)
Hyperglycaemia: ≥11.1mM (or known DM)
Ketonaemia: ≥3mM (≥2+ on dipstix)
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
Treatment of DKA
- Fluids
- Potassium replacement (if <5.5)
- Insulin Infusion (actrapid) - 1 unit/kg/hr
+- catheter; NGT; LMWH; find and treat precipitating factors
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
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 and action plan
Hyperglycaemic Hyperosmolar State presentation
Usually T2DM, often new presentation Usually older Long hx (e.g. 1wk) Marked dehydration and glucose >30mM/L No acidosis (no ketogenesis) Osmolality >320mosmol/kg
Complications of HHS
Occlusive events are common: DVT, stroke, leg ischaemia
- Give LMWH
Management of HHS
Rehydrate --> 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
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)
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
Investigations of hypoglycaemia
72h fast ̄c monitoring
Symptom: Glucose, insulin, C-peptide, ketones
Management of hypoglycaemia
Conscious and able to help self –> Rapid acting: lucozade or 5-7 glucose tablets
Conscious but unable to help self –> Dextrogel
- wait 15 min and check; can repeat up to 3x
If corrected then give long acting snack (toast)
Unconscious (GET SENIOR HELP)and IV access –> 20% glucose 75ml in 15min (can repeat)
Unconscious and no Iv access –> IM 1g Glucagon
If responded long acting snack
After snack check CBG in 30-60 mins then refer for hypoglycaemic education. Monitor CBG for 24-48 hours.
Thyrotoxicosis symptoms
Diarrhoea ↑ appetite but ↓ wt. Sweats, heat intolerance Palpitations Tremor Irritability Oligomenorrhoea ± infertility
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
Investigations for thyrotoxicosis
↓TSH, ↑T4/↑T3 Abs: TSH receptor, TPO ↑Ca, ↑LFTs Isotope scan ↑ in Graves’ ↓ in thyroiditis Ophthalmopathy: acuity, fields, movement
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
Features of thyroid storm
↑temp Agitation, confusion, coma Tachycardia, AF Acute abdomen Heart failure
Precipitants of thyroid storm
Recent thyroid surgery or radio-iodine
Infection
MI
Trauma
Management of thryoid storm
- Fluid resuscitation + NGT
- Bloods: TFTs + cultures if infection suspected
- Propranolol PO/IV (counteracts peripheral effects of t3/4)
- Carbimazole
- Hydrocortisone (I. thyroid hormone synthesis)
- Rx cause (e.g. Abx)
- no change in 24h > thyroidectomy
Signs of hypothyroidism
Bradycardic Reflexes relax slowly Ataxia Dry hair and skin Yawning (lethargy) Cold hands Ascites and Myxoedema Round Puffy face Depression and mental slowing Intolerant to cold Appetite ↓; ↑wt
Other: Constipation Menorrhagia CTS Goitre Myopathy, neuropathy
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 )
Investigations for hypothyroidism
↑TSH, ↓T3/T4 ↑MCV ± normochromic anaemia ↑ triglyceride + ↑ cholesterol Hyponatraemia (SIADH) ↑ CK if assoc. myopathy Abs: TPO, TSH
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
Features of hashimoto’s thyroiditis
TPO +ve
Atrophy + regeneration → goitre
May go through initial thyrotoxicosis phase
May be euthyroid or hypothyoid
Features of myxoedema coma
Looks hypothyroid Hypothermia Hypoglycaemia Heart failure: bradycardia and ↓BP Coma and seizures
Precipitants of myxoedema coma
Radioiodine
Thyroidectomy
Pituitary surgery
Infection, trauma, MI, stroke
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
Complications of thyroid surgery
- haematoma
- laryngeal oedema
- recurrent laryneal nerve palsy
- hypoparathyroidism
- thyroid storm
- hypothyroidism
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
Causes of Cushing’s
ACTH Independent causes
- Iatrogenic steroids
- Adrenal adenoma/ Ca
- Adrenal nodular hyperplasia
ACTH - dependent causes
- Cushing’s disease
- Ectopic ATCH
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
Treatment for Cushing’s
- Iatrogenic steroids –> stop meds
- Adrenal adenoma/ adrenal nodular hyperplasia –> adrenelectomy
- Ectopic ACTH - - tumour excision +- metyropone
- Cushing’s disease - transphenoidal excision
What is Nelson’s syndrome
Rapid enlargement of a pituitary adenoma i fhave cushing disease following bilateral adrenelectomy
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
Features of Hyperaldosteronism
Hypokalaemia: weakness, hypotonia, hyporeflexia, cramps
Paraesthesia
↑BP
Causes of hyperaldosteronism
PRIMARY
Bilateral adrenal hyperplasia (70%)
Adrenocortical adenoma (30%): Conn’s syndrome
SECONDARY RAS Diuretics CCF Hepatic failure Nephrotic syndrome
Treatment of hyperaldosteronism
Conn’s: laparoscopic adrenelectomy
Hyperplasia: spironolactone, eplerenone or amiloride
Ix
Actions of Angiotensin 2
- ↑ADH (thirst centre and CD in kidney)
- ↑ sympathetic activity - ↑ NAdr
- ↑ Aldosteone
= ↑ Na + Cl reabsorption + H20+K excretion - Arteriolar vasoconstriction - ↑ BP
Pathophysiology of Addison’s Disease
Destruction of adrenal cortex → glucocorticoid and mineralocorticoid deficiency
Causes of Addison’s
Autoimmune destruction: 80% in the UK TB: commonest worldwide Metastasis: lung, breast, kidneys Haemorrhage: Waterhouse-Friedrichson Congenital: CAH
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 Dry mouth and reduced skin turgor Hypoglycaemia Vitiligo Addisonian crisis Sparse axillary and pubic hair
Symptoms of Addison’s
Tired - fatigue and weakness
Tanned - hyperpigmentation
Tearful - apathy and depression
Thin - weight loss/ n+v+d/ anorexia +/- abdo pain
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
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
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
Presentation of an Addisonian Crisis
Shocked: ↑HR, postural drop, oliguria, confused
Hypoglycaemia
Usually known Addisonian or chronic steroid user
Precipitants of an Addisonian Crisis
Infection
Trauma
Surgery
Stopping long-term steroids
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
What is a pheochromocytoma
Catecholamine-producing tumours arising from sympathetic paraganglia
Usually found in adrenal medulla
Extra-adrenal phaeo’s found by aortic bifurcation
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
Investigations for pheochromocytoma
Plasma + 24h urine metadrenaline and normetadrenaline
Also vanillylmandelic acid
Abdo CT/MRI
MIBG (mete-iodobenzylguanidine) scan
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 and 24hr urine 2 weeks post up
follow up is lifelong
Hypertensive crisis features
Pallor Pulsating headache Feeling of impending doom ↑↑BP ↑ ST and cardiogenic shock
Management of a hypertensive crisis
Phentolamine 2-5mg IV (α-blocker) or labetalol 50mg IV
- Repeat to safe BP (e.g. 110 diastolic)
Then α-blocker PO with elective surgery 4-6 weeks latere
Causes of raised prolactin
Pregnancy Prolactinoma Physiological PCOS Primary hypothyroidism Pheothiazine/ metochlopramide
Symptoms of hyperprolactinaemia
High PRL --> ↓ LH/FSH Amenorrhoea Infertility Galactorrhoea ↓ libido ED Mass effects from prolactinoma - headache; bitemporal hemianopia; CN 3,4,5,6 palsy; DI; CSF rhinorrhoea
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 (or if visual/ pressure symptoms)
Causes of Acromegaly
Pituitary acidophil adenoma in 99%
Hyperplasia from GHRH secreting carcinoid tumour
Symptoms of Acromegaly
Acroparaesthesia Amenorrhoea, ↓libido Headache Snoring Sweating Arthralgia, back ache Carpal tunnel (50%) Change in shoe size
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
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
Treatment of acromegaly
1st line: trans-sphenoidal excision
2nd line: re – octreotide
3rd line: GH antagonist – pegvisomant
4th line: radiotherapy
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
Complications of Acromegaly
Impaired glucose tolerance (40%)
DM (15%)
↑BP
LVH/ HF
Cardiomyopathy
↑ IHD and ↑ stroke
↑ risk of CRC
Symptoms of Diabetes Insipidus
Polyuria
Polydipsia
Dehydration
Hypernatraemia: lethargy, thirst, confusion, coma
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
Investigations for DI
Bloods: U+E, Ca, glucose
Urine and plasma osmolality - Exclude DI if U:P osmolality >2
- Water deprivation test +/- desmopressin trial
Management for DI
If mild (3-4L) - no treatment
Cranial- Find cause: MRI brain and Desmopressin PO (SE - hyponatraemia and worsen myocardial ischaemia)
Nephrogenic - Treat cause +- bendroflumethiazide
Causes of Hirsutism
- familial
- idiopathic
- increased androgens (PCOS; Cushings; Adrenal Ca; Steroids)
Causes of gynaecomastia
- Cirrhosis
- Hypogonadism
- Hyperthyroidism
- Hypopituitary
- oestrogen/ HCG - producing tumour
- Drugs - spiro/ oestrogen
Causes of erectile dysfunction
- smoking
- alcohol
- DM
- Endo - hypogonadism, hyperthyroidism
- Neuro - MS; autonomic neuropathy; cord lesion
- Pelvic surgery - bladder; prostate
- Peyronie’s disease