endocrinology Flashcards
what are the causes of subclinical hypothyroidism
Chronic autoimmune disease (Hashimoto’s thyroiditis, atrophic thyroiditis)
Iatrogenic (due to treatment of hyperthyroidism with radioiodine, surgery, radiotherapy to neck)
Medications (e.g. lithium, amiodarone) Iodine deficiency (the commonest cause worldwide)
Infiltration of the thyroid (e.g. sarcoidosis, haemochromatosis)
what are the effects of therapy in subclinical hypothyroidism?
Prevention of progression to overt hypothyroidism
Improvement in total and LDL cholesterol
Improvement in symptoms, mood and cognition
what must you be aware of when treating hypothyroidism
The TSH should not fall below the normal range during treatment as this increases the risk of atrial fibrillation, osteoporosis and some neuropsychological symptoms
would you offer annual surveillance or thyroid testing at initial presentation for these at risk patients?
- AF
- T1DM
- T2DM
- downs/turners
- addisons
- postpartum depression
- osteoporosis
- on amiodarone/lithium
- history of postpartum thyroiditis
- subfertile
- hx of radio active iodine
- giotre
- previous neck radiation
- dyslipidaemia
- AF - initial
- T1DM - follow-up
- T2DM - initial
- downs/turners - follow-up
- addisons - follow-up
- postpartum depression -initial
- osteoporosis -initial
- on amiodarone/lithium -follow-up
- history of postpartum thyroiditis -follow-up
- subfertile -initial
- hx of radio active iodine - follow-up
- giotre - initial
- previous neck radiation - follow-up
- dyslipidaemia -initial
in women who are pregnant or planning pregnancy offer thyroid function testing at earliest opportunity if…
Goitre (also at 6 weeks postpartum/after miscarriage/termination)
Family history of thyroid disease; personal history of thyroid disease
History or thyroid lobectomy; history of other autoimmune disorders
Positive thyroid autoantibodies (also at 6 weeks postpartum/after miscarriage/termination)
History of postpartum thyroiditis
hyponatraemia what is acute classification clinical symps causes how to approach when bleeped mgmt worries with overcorrection
acute
<48hrs
classification
mild - 130-135 asymp, subtle changes in mental and physical function
mod - 125-130, non-specific symps (nausea + malaise)
severe - <125, progressive neurologic symps ranging from confusion to coma
clinical symps
diarrhoea/vomiting/polyuria - likely to be hypovolaemic
dizziness on standing - suggests postural hypotension
thirst
habitual drinking/alc (beer potomania)
recent surg or IV fluids cont.
resp symps - as can be assoc with pneumonia
stroke
any failures (cardiac/renal etc)
causes
ISOTONIC 280-295 - hyperproteinemia, hyperlipidaemia
HYPOTONIC <280:
- hypovolaemic -> dehydration, diarrhoea, vomiting, diuretics, ACEi, nephropathies, mineralcorticoid deficiencies
- euvolemic -> SIADH, post-op hyponat, hypothyroidism, psychogenic polydipsia, beer potomania, endurance exercise
- hypervolaemic - FAILURES - heart, liver, nephrotic, kidney
HYPERTONIC >295 - hyperglycaemia, mannitol, sorbitol, glycerol, maltose, radiocontrast agents
how to approach when bleeped
- EXAMINATION
- gen look + weight
- obs - pulse, BP, postural BP
- assessment of volume status + calc osmolality
- skin turgor and mucous membranes
- resp status
- cardio - JVP, pulm oedema
- full neuro - ?confusion/agitation/seizures/CVA
- review prev lab tests- sodium, cortisol, TFT, paired osmolalities
- ix to send now - U/E, FBC, LFT, Glc, TFT, 0900 cortisol, lipids, urine analysis, CXR, ?CT head, ECG
- ?SIADH - paired urine + plasma osmolality and urine sodium
mgmt
MILD CHRONIC - IV 0.9% nacl - repeat UE 12hrs then daily
MODERATE - stop drugs PPI/ACEi, liase with neuro/psych for carbamazepine/anti-dep, rx hypothyroid/ GC insuff, check for HF, liver failure, kidney failure
SEVERE - emergency, senior help, reduce brain oedema, avoid overcorrection/osmotic demyelination + HDU/ITU transfer, within 1hr 150ml hypertonic saline 3% over 20 min with close monitoring
NEVER INCREASE SODIUM QUICKLY
worries with overcorrection (central pontine myelinosis)
also happens in alcoholism, liver disease and malnutrition
- hyponatraemia can lower the seizure threshold
- neuro det 48-72 hrs
- variable
- confusion
- horizontal gaze paralysis
- spastic quadriplegia - increased tone, weakness, hyper-reflexia
- pseudobulbar palsy - demyelination
- c-sp and c-bul tracts in pons
basically it causes the brain tor shrink after it has been swollen from hyponatraemia
causes of pseudohyponatraemia
hyperglycaemia
SIADH def patho causes pres ix if euvolaemic types mgmt worries with management
def
Euvolaemic hypotonic hyponatremia with concentrated urine
hyponat <135mmol/L
patho
increased AVP release leads to impairment of free water excretion
AVP release mediated by osmotic pressure at hypothalamus
Decrease of osmolality by 1% rapidly suppresses AVP -> this is lost with below conditions
ADH works to stop you peeing to increase intravascular volume at collecting duct in kidney
causes
Pulmonary processes: pneumonia, lung cancer (esp small cell)
CNS disorders: infection, trauma, MS, haemorrhage, malignancy
Malignancy: lung, pancreas, prostate
Drugs: SSRIs, tricyclics, NSAIDs, SU, chemo drugs, rule out thiazide (most common hyponatraemia)
pres
Euvolaemic, confusion, nausea, irritability, nausea, vomiting
ix
assess volume and TFT, cortisol,
renal function - sodium <135 (wont be responsive to saline infusion)
request paired osmolalities - serum = <280 proportional to hyponatraemia, urine = >100Osm/kg - typically higher than plasma
spot urine na = hgih >30mmol/l
NORMAL renal + adrenal function
if euvolaemic - SIADH is diag of exclusion
subtypes
1-4
mgmt
Acute (<48) + severe (<125)
- IV hypertonic saline (3%) and check Na every 2 hours
- Aim to increase 1-2 per hour until neurological symptoms resolve
+ treat cause + furosemide if risk of fluid overload
Chronic + severe
- IV hypertonic saline
- Vasopressin receptor antagonist tolvaptan + cause + furosemide
- demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
Mild - mod (>125) + acute
- Treat cause + fluid restrict: 1-1.5l /day
Mild - mod + chronic
- Treat cause + vasopressin receptor antagonist
worries with management
central pontine myelinolysis
endocrine tests:
- what test for under secretion/deficiency
- over secretion/excess?
- acromeg
- cushings
- prolactinoma
- GH deficiency
under
- stimulation test
- eg short synacthen test
over secretion
- suppression test
- eg dexamethasone suppression test (cushings rule out)
acromeg - OGGT with GH profiles
cushings syndrome - Over Night Dexamethasone Suppression Test
prolactinoma - cannulated prolactin
Growth Hormone deficiency - Insulin Tolerance Test/glucagon
causes of adrenal insufficiency and aka + def
AAb
aka addisons, primary hypoaldosteronism
def Destruction of adrenal cortex and subsequent reduction in output of adrenal hormones: glucocorticoids (cortisol), and mineralocorticoids (aldosterone)
CAUSES primary - TB - addisons - autoimmune destruction - malignancy - infiltration - infection - vascular haemorrhage - infarction - iatrogenic - surgery
secondary
- pituitary/hypothalamic lesions
- exogenous steroids suppress axis
- CRH def
tertiary
- suppression from GC
- post treatment cushings disease
AAB - anti-21-hydroxylase -> causes loss of aldosterone and cortisol, but testosterone if fine
presentation of adrenal insufficiency
either acute (addinsonian crisis) or chronic
fatigue lack of energy weight loss tanned - due to increase of CRH and ACTH low BP postural dizziness hypotension (>20mmhg drop) hypovolaemic shock abso pain, tenderness, gaurding, vomiting fever confusion somnolence delirium coma cramps in back of legs primary - skin pigmentation, palmar creases, scars, oral mucosa secondary - pale skin, alabaster
adrenal insufficiency history key points
insidious onset - malig? check FH smoking - lung lesion and ACTH GI symps thyroid disease symps hypoglycaemia symps DH - inhalers, creams, steroid inject, alt meds reduced axillary/pubic hair
findings on examination in adrenal insufficiency
gen exam to rule out malig - breast, thyroid, colon
BP lying/standing
skin/hair - depp pig, fine wrinkles, pale skin of hypopituitarism, pallor of anaemia, myxoedema of hypothryoidism
body habitus and BMI - weight loss
muscle wasting
adrenal insuff ix
FBC
haematinics
U/E - low sodium, high potassium (due to low aldosterone, low ENaC and ROMK)
LFT
bone
glucose - low
0900 cortisol <350 probable insufficiency
random if unwell with paired ACTH - to diff primary (high)/secondary (low)
DIAGNOSTIC = Short Synacthen Test = take cortisol, give 250mcg synacthen IM, 30mins retake cortisol, if rises exclude addisons >500
TSH FT4
HBa1c
Aantibodies = anti 21-hydroxylase
lipids
renin and aldosterone - high r + low a = addisons
ABG - met acidosis
Bilateral CT adrenals
CXR
DEXA
vit D levels
adrenal insufficiency
mgmt and comps
screening
start treatment hydrocortisone
emergency immediate HC - 100mg IM, then 200mg infusion 24hrs
IV sline 1L over 1 hr followed by 4-6 L/24 hours
urgent endocrine input
maintenance dosing
counsel patient - sick day rules, provide emergency kit 100mg HC sodium succinate, medical emergency bracelet + steroid card, explain imp of not missing steroid doses
sick day rule 1 - double daily oral dose of glucocorticoids
sick day rule 2 - parenteral admin during prolonged vom or diarrhoea, prep colonoscopy, surgery
if not emergency = glucocorticoid replacement = hydrocortisone TDS highest dose at morning 15-30mg
mineralcorticoid = fludrocortisone 50-300mcg/day will correct postural hypotension and electrolyte balance
comps
over replacement = HTN, thin skin blah blah
screening
annual TFT, glucose + hba1c, coeliac
pituitary apoplexy
what is it
how to manage
Rapid enlargement due to bleed into tumour -> mass effect, CV collapse and acute hypopituitarism
emergency: ABCDE call senior valuate electrolytes, glucose, and pituitary hormones high dose corticosteroids
T1 diabetes what is it ix to differentiate from T2DM main comps assoc panc cells + their function insulin release + action when eat patho causes pres immediate comp ix diagnostic criteria ix for comp mgmt regimes + SE sick day rules
what is it
Autoimmune destruction of pancreatic beta cells in islet of langerhans leading to reduced insulin
ix to diff
C-peptide: low @ T1, high @ T2
released at the same time as insulin to distinguishes lack of insulin from resistance
main comps
Retinopathy, neuropathy, nephropathy, skin infection (low immunity), DKA, CVS risk, autonomic dysfunction
assoc
AI diseases
panc cells and their function
alpha - glucagon
beta - insulin
insulin release - Glucose -> beta cell. Enters via GLUT-2. Increases ATP. ATP closes K+ channels which depolarise cell. VgCa channels open Ca to cell. Insulin released.
insulin action - To peripheral muscle. Binds insulin receptor. Mobilises GLUT-4 to membrane. Glucose able to enter cell.
when eat -
Increase glucose -> increased insulin
Increase uptake liver (200g) and muscles (150g) as glycogen
Suppresses gluconeogenesis, lipolysis, proteolysis, ketogenesis
cause
Genetic predisposition and autoimmune process (insulin/islet cell autoantibodies)
Family history of other autoimmune conditions HLA DR3/4
pres
Polyuria, polydipsia (due to water being dragged out by glucose in urine), weight loss, lethargy, DKA problems… (dehydration, kussmauls breathing, abdo pain)
immediate comp
DKA
ix urine dip FPG RPG OGTT HbA1c - measures the amount of glycosylated haemoglobin and represents the average blood glucose over the past 2-3 months.
diagnostic criteria diabetes
1. symptoms + FPG >7 or RPG >11.1
2. asymp + 2x FPG or RPG
3. OGTT 75g glucose with 2hr glucose reading >11.1
4. HbA1c >48 or 6.5%
prediabetes
hba1c = 5.7-6.4%, FPG 5.6-7, OGTT 7.8-11.0
ix for comp
DKA - blood glucose, ketones, ABG
long-term = Urine dip for protein, BP for HTN, Fasting lipid for hyperlipidaemia
mgmt GEN 1. education 2. diet + exercise - low sug, low fat, high starchy carb 3. no smoking 4. maximal glucose control - test QDS, target 5-7 morning, 4-7 before meals MEDS insulin regimes: 1. twice daily - pre breaky/evening meal 2. basal-bolus - long or intermed at bedtime with rapid/short to cover meals 3. continuous subcut or insulin pump - if control very poor S/E - hypo (sweating, anxiety, blurred vision, confusion), lipodystrophy, weight gain NICE RECOMMENDS basal-bolus insulin regime: twice daily: - long acting eg detemir - rapid acting eg novorapid before meals ANNUAL REVIEW Educate + modifiable RFs Check BMI Check complications: hypos, DKA Assess CVS: BP, pulses, bruits Inspect injection sites - lipodystrophy Foot check - neuropathy and pulses Urine dip - protein, nitrites, ketones Check eyes - acuity and ophthalmoscopy -> refer opthalmology Ask erectile dysfunction Bloods: HbA1c every 3-6 months and home capillary monitoring results, random lipids
diabetic comps patho
NEUROPATHY -
Hyperglycaemia -> oxidative stress -> lipid peroxidation of myelin -> glove and stocking + loss of ankle jerks (loss of afferent arc of the tendon reflex)
mononeuropathy = single nerve trunk affected eg 3rd nerve palsy
mononeuropathy multiplex - more than one individual nerve trunk affected
diabetic fem neuropathy - sudden onset wasting and weakness of quads with loss of knee jerks
autonomic neuropathy
cerebrovascular disease
diabetic peripheral polyneuropathy - typically affects longest nerves first (length dependent neuropathy). loss of all modalities in glove + stocking. if small fibres affected presents as painful neuropathy. can cause tingling, numbness or ‘walking on cotton wool’.
causes: ABCDE
A - alcohol
B - B12 deficiency - as well as causing subacute combined degen of cord
C -CKD and carcinoma - para-neoplastic
D - diabetes + drugs eg nitrofurantoin, metronidazole, ethambutol, isoniazid
E - every vasculitis (RA, polyarteritis, sarcoid, scleroderma, wegener’s)
NEPHROPATHY
Hyperglycaemia -> mesangial expansion + thickening of glomerular BM
Narrowing of efferent renal artery -> increased pressure in glomerulus -> glomerular sclerosis + thickening BM -> increased gaps between podocytes (more permeable) = hyperfiltration
Proteinuria and loss of pericytes
Use photocoagulation
screen for microalbuminaemia - urinary albumin : creat ratio
ACE-i slows the progression of renal impairment
CVS RISK
MI/Stroke -> BP control + diet + smoking + statin -> QRISK
AUTONOMIC DYS
Erectile dysfunction, bladder retention, postural hypotension, tachycardia, diarrhoea
INFECTION
Hyperglycaemia -> reduced phagocytsis
Pneumococcal vaccine and annual influenza
sick day rules for diabetics + why
GEN 4 hourly monitoring be aware of DKA monitor ketones 3L fluids/24 hours cant eat? take sugary drinks
MEDS
continue metformin + insulin but with increased monitoring
if glucose goes above upper limit, increase insulin or seek help
WHY
Stress response to illness -> increased cortisol
Cortisol increases blood sugars and decreases insulin
diabetic foot RF for ulcers + PAD what is it pres synonym exam
RF
ulcers: PAD, peripheral neuropathy, callus
PAD: hypercholesterolaemia, HTN, smoking
what is it
neurovascular foot
secondary to:
Peripheral artery disease, neuropathy + charcot’s
Loss of protective sensation -> severe damage and disruption due to mechanical and vascular factors
large and small vessel injury
pres
Ulcers (neuropathic painless and punched out or arterial), loss of pulses
Bone and joint degeneration -> deformity, osteoporosis, fracture, acute inflammation
Hot, swollen foot after minor trauma
chronic:
- Rockerbottom sole, claw toes, loss of transverse arch
synonym
neuropathic joints
exam inspect heels palpate cap refill + pulses light touch - loss of sensation glove + stocking vibration ankle jerks
diabetes and ramadan
normally have type 2
they can be excused as they have a chronic condition
if choose to fast:
- try eat a long-acting carbohydrate before sunrise
- provide glucose monitor
- if taking metformin then split dose one-third before sunrise and two-thirds after sunset
- if on SU - take these after sunset if OD, if BD then larger proportion of dose taken after sunset
- no adjustment needed for pioglitazone
T2DM what is it ix to diff assoc who gets it RF pres ix mgmt
what is it
Hypersecretion of insulin by depleted beta cell mass. Increasing insulin resistance.
ix diff
c-peptide
assoc
metabolic syndrome
who
30+ obese, low physical activities
RFs obesity lack of activity PCOS metabolic synd fam hist south asian pre-diabetes
pres
Polyuria, polydipsia, lethargy, prolonged/frequent/recurrent infections (e.g. vaginal thrush)
ix
Urine dip, FPG, RPG, OGTT, HbA1c
as for T1DM
mgmt
gen stuff as T1DM
Lifestyle and diet - (6 weeks) + inform DVLA
Low GI, low dairy, control fats, limit sugar, aim 5-10% weight loss
MEDS
if can have metformin (aka are they FAT)
if >58 dual therapy:
+ gliptin or SU or pioglitazone
if still >58 with dual:
- Metformin + sulfonylurea + pioglitazone
- Metformin + sulfonylurea + gliptin
- Start insulin
if cant have metformin then start with one of others
diabetic eye problems which ones patho for retinopathy features ix classification mgmt emergency referral for
which probs
Cataracts, retinopathy, maculopathy, glaucoma
patho for retinopathy
Microvascular occlusion -> retinal ischaemia -> AV shunts + neovascularisation
Pericyte loss -> leakage -> haemorrhages or diffuse oedema
features
Painless, gradual reduction of central vision, sudden onset dark, painless floater
Microaneurysm - from physical weakness
Hard exudates - lipoproteins from leakage
Haemorrhages - rupture of weakened capillaries small dots, blots or flame (track along nerves in superficial retinal haemorrhages)
Cotton wool spots - build up of axonal debris
Neovascularisation
ix
slit lamp
classification
Background - one microaneurysm (dot haem), hard exudates, blot haemorrhages
Mod/maculopathy - microaneurysms, IR haem ± cotton wool spots, venous beading + IRMAs (intra-retinal micro vasular abnormalities)
Severe/pre-prolif - depends on number and quadrants, mainly same as above
Proliferative (non-high risk) new vessels on disc (or <1 diam) or NV everywhere
Proliferative/end-stage (high risk) large NVD or NVE
mgmt
Optimise glycaemic control
Blood pressure control
Lipid control
Laser photocoagulation: Or intravitreal steroids, Anti-VEGF
signs for referral - fall in correct visual acuity, single cotton wool spot, 3 blot haemorrhages, anything @ macula
emergency ref sudden LOV red eye retinal detachment new vessels
metformin type of oral hypoglycaemic MoA CI SE
type - Biguanide
MoA - Increases insulin sensitivity (GLUT 4), decreases gluconeogenesis
CI - CKD, eGFR < 30
SE - GI upset: nausea, anorexia, diarrhoea - 2e0% intolerabl
Gliptin
type
MoA
SE
type - DPP-4 inhibitors (DPP-4 destroys incretin)
MoA - Raised incretin -> produce more insulin when needed
SE - GI upset and flu-like symptoms
sulphonylurea type MoA CI SE
type - Oral hypoglycaemics
MoA - Increase panc insulin secretion
CI - Pregnancy
SE - Hypo, weight gain
Piaglitazone
MoA
SE
CI
MoA
Increases insulin sensitivity
SE
Weight gain, fluid retention and osteoporosis
CI
Heart failure and osteoporosis
DKA precipitants pres patho ix mgmt monitor
precipitants
Missed insulin, infection, intoxication, ischaemia, infarction
pres Abdominal pain + vomiting Polyuria, polydipsia, dehydration Kussmaul respiration (deep hyperventilation to correct acidosis) Acetone breath (pear drop)
patho
decreased insulin ->
1. increased protein catabolism -> hyperglycaemia, glycosuria, osmotic diuresis, K+ depletion (acidosis buffer) -> dehydration acidosis coma + death
2. decreased cell glucose uptake -> hyperglycaemia etc
3. increased lipolysis -> Increased plasma FFA to liver. Ketogenesis: ketonuria and ketonaemia (beta hydroxybutyrate and aceto- acetate) -> dehydration, acidosis, coma, death
ix Plasma glucose: high >11 or known DM Plasma ketones: high >3mmol/l ABG: metabolic acidosis pH < 7.3 Urine dip: ketones (++) and glucose
mgmt
ABCDE sats etc… + catheterise
Volume depletion: IV NaCl (1L stat, over 1hr, 2h, 4h, 8h)
*switch to 5% dex when glucose <12
Hyperglycaemia: IV insulin - will drop the potassium…
*Fixed rate IV infusion: 0.1U/kg/hr add glucose when drops
Hypokalaemia (as a result of fluids and insulin): K+in fluids
>5.5 = nil
3.5-5.5 = 40mmol/L infusion solution
<3.5 = senior review
Acidaemia: IV bicarbonate
if vomiting + decreased consciousness - gastric aspiration
MONITOR - electrolytes + ABG, fluid balance, glucose ECG hourly
hypoglycaemia
def
vital signs
neuro manifestations
def
FOUR IS THE FLOOR <4mmol/l
neuroglycopaenia <3mmol/l
vital signs THIS PATIENT LOOKS UNWELL normal RR/BP peripheral vasoconstriction (alpha 1) pale cold clammy sympth overdrive tachycardia (B1)
neurological mani
low GCS
seizure - tonic/clonic -> todds paralysis (hemi parasis post seizure)
brisk reflexes
bilateral upgoing plantars -> ddx pontine haemorrhage
in peripheral neuropathy which is more likely to be affected first motor or sensory, except when
sensory
except in acute segmental demyelination (GBS) where motor involvement is the main feature + hereditary sensory motor neuropathy eg charcot marie tooth disease
large fibre neuropathy
when
symps
eg b12 affecting large myelinated sensory nerves
neg symps - unsteady gait, walking on cotton wool as loss of discriminatory sensation
posi symps - pins and needles, band-like feeling around calf
small fibre neuropathy
when
symps
alcohol affecting small unmyelinated c fibres
neg symps - loss of pain and temp sensation
posi - painful dyasthesiae eg burning causalgia, hyperalgesia
mixed nerve fibre neuropathy
when
symps
diabetes
very variable - some have painful neuropathy others have no pain and profound loss of proprioception and unsteady gait
what sensation do large, medium and small nerve fibres carry
large - A alpha - proprioception
medium - A beta - touch
small - c fibre - pain/temp
testing for loss of protective sensation
screened using 10g monofilament over 3 toes, 3 points on ball of foot, 3 points near arch of heel
instruction should be ‘say yes when you feel it’
1-2 not felt = reduced sensation, ‘at risk’ foot
all not felt = absent sensation
charcot joint
what is it
patho
aspects of management
arthropathy is a progressive condition of the musculoskeletal system that is characterized by joint dislocations, pathologic fractures, and debilitating deformities
patho
1. loss of protective sensation = repeated microtrauma -> degen change, joint destruction, rubbery feel when moving MetoTarsoPharngeal joints, ulceration
- autonomic neuropathy = increased blood supply -> oedema, warmth, redness + increase in osteoclast activity = bone resorption
mgmt
vascular, infection control, pressure relief
hyperosmolar hyperglycaemic state who features precip patho criteria ix mgmt comp
who
T2DM + elderly
features
extreme dehydration (but may not look it as all the water in the intravascular space)
fatigue + n+v
altered mental state, headache +/- seizures +/- delirium
hyperviscosity = MI, stroke, peripheral arterial thrombosis
comes on over many days in comp to DKA which is hours
precip infection MI dehydration inability to take normla meds thiazides + loop poor control
mech
Hyperglycaemia -> osmotic diuresis = loss of na + k -> hyperosmolarity leading to fluid shift of water into intravascular compartment -> severe dehydration
No ketosis as enough insulin to suppress ketogenesis
criteria
1. Hypovolaemia
2. Marked hyperglycaemia (>30) without hyperketonaemia or acidosis
3. Osmolality > 320 mosmol/kg (concentration of blood)
Calc osmolarity = 2(Na + K) + gluc + urea
Plasma osmolality is a guide to intracellular osmolality -> if high will secrete ADH
ix Urinalysis: glycosuria +++. Ketonuria + Capillary glucose > 30 Serum osmolarity > 320mmol/L U+E -> AKI ABG -> normal Blood cultures -> rule out sepsis
mgmt
GRADUAL
Treat cause
Safely normalise osmolality - replace fluid and electrolytes
Normalise blood glucose
ABCDE
IV access, ECG, SaO2, BP
Calculate osmolality frequently (2Na + gluc + urea) and plot on graph
IV 0.9% NaCl -> aim for fall of Na by 10mmol/24 hours (if not switch to 0.45%), glucose 5mmol/hr
Aim for 3-6 litres +ve by 12 hours
IV insulin (0.05U/kg/hr) if glucose no longer falling + ketonuria + acidosis
RAPID DECLINE IS HARMFUL
Rising sodium is only a concern if the osmolality is NOT declining concurrently
comp
cerebral oedema
central pontine myelinosis
metabolic syndrome what is it criteria increased risk of.. causes assoc mgmt comps
Cluster of common abnormalities including insulin resistance, impaired glucose tol, reduced HDL, elevated triglycerides and HTN
criteria
- Truncal obesity: men ≥ 94cm, women ≥ 80cm or BMI > 30
- BP: Systolic ≥130 diastolic ≥ 85 or prev Dx HTN
- Reduced HDL: <1.03mmol/l (men), <1.29mmol/l (women)
- High triglycerides: ≥ 1.7mmol/l
- Fasting glucose ≥6.1mmol/l (prediabetes)
increased risk of atherosclerosis - CVD, diabetes
causes
obesity
assoc NAFLD PCOS CVD T2DM
mgmt
lifestyle - smoking, activity, diet
HTN control
lose weight
comps
hypercoag
obesity catagory BMI causes ix mgmt tactics mgmt comps
catagory - 25-29.9 overweight
30-34.9 obese I
35-39.9 obese II
≥40 obese III - weight is imminent threat
causes MED Glitazone, sulfonylurea Anticonvulsants Antidepressants: tricyclics and mirtazapine Lithium Progesterone only contraception BB Corticosteroids CONDITIONS hypothyroid, PCOS, cushing, hypogonadism GENE - KRS2 - severe insulin resistance and reduced metabolic rate
ix
hormone - sex + cortisol
TFT
mgmt tactics
prev, correction, population, individual
mgmt
motivational interviewing
Overweight: structured advice diet + ex, if comorbid consider drug post lifestyle
Obese I: structured advice diet + ex, if comorbid consider drug post lifestyle
Obese II: structured advice ± drug, consider referring for surgery
Obese III: structured advice ± drug, consider referring for surgery
DIET - NICE rec diet 600kcal deficit/low fat
Low calorie 800-1600 may be considered
Very low calorie < 800, for no more than 12 weeks
EXERCISE - increases BMR, 30 mins mod x5/week
MED - orlistat, 1 tablet 1 hour after each meal. lipase inhibitor, continue beyond 3M only if lose 5%, SE deficiency in DEAK, abdo discomfort, oily stool, CI cholestasis
SURG - bariatric:
1. Restrictive: gastric banding
2. Malabsorptive: biliopancreatic diversion
3. Both: roux en y gastric bypass (RYGB)
comp HTN CaCo T2DM MI angina ovarian cancer sroke
gynaecomastia def pathophys causes ix cancer risk for
def Enlargement of male breast tissue - disc of tissue under skin (true)
pathophys
Oestrogens stimulate, androgens inhibit therefore ratio is important
Conditions raising oestrogen
Conditions dropping testosterone/androgen resistance
Conditions causing increased conversion of androgens to oestrogen - aromatase (in increased adiposity
causes
1. Physiological @ 14 (unilateral + tender) - assoc delayed testosterone, aging - low testosterone
2. Path (low test) - androgen resistance, Klinefelter’s, viral orchitis (mumps), renal disease
3. Path (high oes) - neoplasms secreting HCG (e.g. seminoma) or ectopic BCG lung, RCC, adrenal tumour (oestrogen), CAH, *liver disease - increased prod androstenedione and aromatisation to oestrogen), obesity, hyperThyroid
4. Path (high PRL) - prolactinoma
5. *Medication (25%) - DISCO BOOBS lol:
Digoxin, isoniazid, spironolactone, cimetidine, oestrogen
ix
U/E, LFT, TFT
homrones -
Estradiol, testosterone, prolactin, bHCG, AFP, LH
LH high + test low = testicular failure
LH low + test low = increased oestrogens
LH high + test high = androgen resistance or neoplasm
imaging - USS, mammography if suspicious or unilateral + needle core biopsy
cancer risk BRCA1/2 klinfelters unilateral rapid fixed painful >5cm
thyroid axis
hypothal TRH pit - ant TSH thyroid follicle circ t3/4: free or bound -> liver conjugation/excretion, peripheral conversion of T4 to active T3 target tissue THRa or THRb receptors renal excretion
define: TRH TSH TSHa subunit where prod: T3 T4 T4->3 causes of : diffuse goitre nodular goitre painful goitre constituents of t4 func thyroid hormones
TRH Thyrotropin releasing hormone
TSH Thyroid stimulating hormone
T3 Tri-iodothyronine (active), 20% by thyroid T4 Thyroxine (inactive), 80% by thyroid T4->3 80% @ liver, 20% @ thyroid
diffuse goitre - physiological, graves, hasimotos
nodular goitre - multinodular, adenoma, carcinoma
painful goitre - de quervains
constituents of t4 - tyrosine or iodine
func thyroid hormones - control metabolic rate of tissues
hypothyroidism assoc causes may cause course types pres - symps/signs AI hypo + goitre + AAb + pres ix if untreated if asymmetrical if ?secondary mgmt comps with overmed
assoc
AI disease: T1DM, addisons, pernicious anaemia: 5x women
causes
Atrophic hypothyroidism (no goitre)
Subacute: De Quervain’s painful goitre and raised ESR
Riedel’s thyroiditis fibrous tissue replaces thyroid
Postpartum thyroiditis (2.5%) often transient
Iatrogenic: surgery or radioiodine treatment
Drugs: lithium, amiodarone (*iodine rich may become hypo or hyper)
Iodine deficiency most common in developing world
may cause transient thyrotoxicosis in acute
course
subclinical
types
primary - as above
secondary - isolated TSH disorders (Hypopituitary disorders: neoplasm, radiotherapy, infection
Hypothalamic disorders: neoplasm and trauma)
pres - BRADYCARDIC Bradycardia Reflex relax slowly Ataxia Dry thin skin/hair Yawning/drowsiness Cold hands and cold intolerant Acites and non-pitting oedema Round puffy face Double chin/obese/deafeted demeanor Immobile and ileus CHF SYMPS - deep hoarse voice, mennorhagia, weight gain, constiaption, tired, lethargy, slow intellect (poor mem and diff conc), reduced libido, depression SIGNS - Dry coarse skin/hair Puffy face/hands/feet (myxoedema) Bradycardia Delayed tendon reflex Carpal tunnel Serous cavity effusions: pericarditis/pleural effusions
AI hypo + goitre + AAb + pres
hashimotos (most common) or atrophic
GOITRE
1. In Hashimoto’s = painless, diffuse, varying size, rubbery, irregular surface may be normal or abnormal TF
2. In atrophic patients are overtly hypothyroid and have no goitre
AAb
Anti-TPO (anti-thyroid peroxidase), anti-Tg (antithyroglobulin) in 90-95%
pres - Viral infection -> local symptoms and tenderness with nodularity, starts thyrotoxic and then hypothyroid
ix
TFT: TSH, T3 and T4 -> (primary or secondary)
Primary: high TSH, low T3/T4, secondary: low TSH, low T3/T4
Thyroid Ab: antiTPO and antiTg
if untreated = high colesterol, trigylcerides, anaemia (normocytic/chromic)
if asymmetrical = neoplasm - USS
if ?secondary = pit imaging and visual field test, MRI
mgmt treat when symps or TSH >10 levothyroxine T4 for life 50-100mcg TFT every 3-4 weeks
risk of
osteoporosis and arrhythmia
myxoedema
what is it
pres, precip, mgmt
severe hypothyroidism
Myxoedema: mucopolysaccharides accumulate under skin and tissue: thickening of facial features
Ventilatory dysfunction and coma
pres
Expressionless face with peri-orbital fullness
Pale cool skin with rough - doughy texture + purple tinge
common places - face and hands ‘tight rings’ ‘bunch of banana hands’
Enlarged heart
Megacolon
Cerebellar ataxia
Psychosis + encephalopathy -> worry in myxoedema coma (elderly)
COMA - Hypo feats + seizures + hypothermia + decreased consciousness + hypoventilation
precip
infection
mgmt
IV levothyroxine + IV hydrocortisone (after blood cortisone) + resp support
sick euthyroid
what is it
mgmt
low thyroid hormones in a clinical euthyroid patient
mgmt
treat underlying cause
hyperthyroidism causes RF symps signs AI assoc ix mgmt warning with med
causes
Main = Grave’s disease (assoc thyroid eye disease) - 75%
Toxic multinodular goitre - more common in >60 from high iodine (amiodarone or derbyshire)
Toxic nodule/adenoma
Subacute/De Quervain’s (transient) - toxicosis + fever + pain in neck + local tenderness: TFT - hyperthyroid + raised ESR - Rx: aspirin and pred - self resolve
Drugs: amiodarone
Exogenous thyroid hormone excess: treatment
Ectopic thyroid tissue: metastatic follicular carcinoma or ovarian teratoma
TSH secreting pituitary adenoma (secondary)
RF
fam hist
high iodine
smoking esp thyroid eye
symp Weight loss and increased appetite Irritable + weak Sweating, tremor Diarrhoea Mental illness: anxiety to psychosis Heat intolerant Loss of libido Oligomenorrhoea
signs Sweaty/warm palms Fine tremor Tachycardia ± AF Hair thinning Goitre *Proximal myopathy (wasting and weakness) Gynaecomastia Brisk reflexes Urticaria/pruritus + thyroid acropachy + pretibial myxoedema
AI
graves
anti-TSH receptor abs react with orbital antigens
path - AAb stimulate TSH receptor leading to excess secretion of thyroid hormones and hyperplasia of follicular cells -> diffuse goitre
assoc - Thyroid eye disease: lid lag, lid retraction, ophthalmoplegia (upward gaze palsy), exophthalmos (aka proptosis best assessed from side), gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema
Worsened by radio-iodine + smoking
IX
TFT: TSH low, high T3/T4
Oligoclonal IgG AAb: anti-TSHR (99%) at Grave’s + anti thyroglobulin + anti TPO
Imaging:
USS ?cancer
Radioisotope uptake scan hot = overactivity, no uptake @ DeQuervain’s
ESR raised at DeQuervain’s
If orbital involvement: visual fields, CT/MRI head
mgmt
BB - propanolol
lubricating eye drops
antithyroid drugs - carbimazole 10-20mg/day titrated based on monthly TFT - can do BLOCK and REPLACE tactic with carbimazole + thyroxine or dose titration
Normally euthyroid at 4-8 weeks, then reduce carbimazole till lowest dose, remission at 18 months - stop drugs. 18 month F/U
propylthiouracil - causes liver fail: reserve for preg and thyroid storm
WARNING
stop drugs if Sore throat: anti-thyroid drugs can cause myelosuppression - agranulocytosis + neutropenia sepsis
OTHER MANAGEMENT PLANS
- Radioactive iodine (CI at pregnancy/breast feeding)
- Relapsed Grave’s or toxic nodular (worsens eye disease in Grave’s) - Surgery
Only when euthyroid
Subtotal thyroidectomy in 98% - comp = hypoparathyroidism + damage to recurrent laryngeal nerve
thyrotoxic storm who pres precip ix mgmt
who
graves or TMNG
pres Hyperpyrexia > 41 CVS: HR > 140, hypotension, AF, CHF GI: Nausea, jaundice, vomiting, diarrhoea, abdominal pain NEURO: Confusion, agitation, delirium
precip
infection
ix sepsis screen TFT ECG CXR ABG U/E, LFT
mgmt
treat infection
resus o2, IV fluids, NG tube if vom
antithyroid rx - oral carbimazole or propylthiouracil
@4 hours - lugol’s solution - aqueous iodine
IV propanolol
IV hydrocortisone
keep cool with tepid sponging NOT PARACETAMOL
thyroid cancer
types
pres
mgmt
TYPES
70% papillary carcinoma - young females - excellent prognosis, lymphatic spread
20% follicular carcinoma - middle age, haematogenous spread
anaplastic - 3% - elderly, v poor prog
lymphoma - 1%
medullary - 1% - rare, derived from parafollicular c cells, secretes calcitonin, assoc woth adrenal phaeochromocytoma + 1 HPT, mucosal neuromas
PRES
Thyroid nodules + CLNs
IX
radioiodine scan
USS
fine needle aspiration
MGMT
Total thyroidectomy
Radioiodine to kill residual cells
Yearly thyroglobulin to detect recurrence
when is PTH secreted? and its actions
in response to low calcium
actions
1. BONE: increase osteoclastic activity - release Ca and PO4
2. KIDNEY:
- 25-OH-D to 1,25-OH2-D (1-alpha hydroxylase) - increases Ca absorption gut
- Increases reabs Ca, decreases reabs PO4 (increases PO4 in urine, decreases Ca)
Net effect - increased Ca, decreased PO4
where is calcitonin produced
what it does
Produced by para-follicular (medullary) C cells of thyroid
inhibits osteoclast activity - reduces Ca and PO4
hyperparathyroid
types + PTH/Ca/phosphate/vit D levels with each
ddx
types
- Primary - solitary adenoma at PTH glands (85%) postmenopausal women - high PTH, Ca, low phosphate - probs asymp
- Secondary - as a result of low calcium - PT gland hyperplasia, *almost always associated with kidney, liver or bowel disease. High PTH, low Ca, high phosphate, low vitamin D (kidney)
- Tertiary - ongoing hyperplasia of PT glands after correction of underlying renal disorder CKD . i.e. after prolonged secondary hyperplasia of all 4 glands - High PTH, high Ca, high phosphate, normal vitamin D, high alk phos (DDx primary)
* Renal for 2 and 3
ddx
benign familial hypocalciuric hypercalcaemia - AD
primary hyperparathyroidism who what assoc pres ix mgmt comps
who
postmenopausal women
what
85% solitary adenoma
10% 4 gland hypertrophy
assoc
MEN 1/2
pres
80% asymp and diagnosed when hypercalc found
Excess Ca absorption from bone: osteopenia and osteoporosis if extreme = osteitis fibrosa cystica (salt + pepper pot skull + subperiosteal resorption phalanges)
Excessive renal Ca excretion: calculi
Mild symptoms of hypercalcaemia: fatigue, weakness, muscle pain
*Bones, stones, abdominal moans, thrones, psychic overtones
ix thiazide + lithium repeat plasma albumin adjusted calc - high check U/E measure PTH - high (which should trigger you to measure 25-OH-D, hydroxyvitamin D) phosphate levels - low DEXA - annual renal tract imaging USS XR - skull and hand
mgmt
mild hypercalc + kid stones - surveillance - check creat + ca 6m
vit D suppresses PTH
avoid dehydration, thiazide diuretics
MEDS = bisphos (alendronate), cinacalcet - reduces serum ca and PTH levels and raises PO4 (no affect on bone turnover)
CURATIVE = surgery: Single adenoma = excision, 4 gland hypertrophy = 3.5 gland subtotal parathyroidectomy
comps
osteoporosis and peptic ulcers
comps of a subtotal or total parathyroidectomy
acute early rare - bleeding, thryoid crisis (hyperthermia, fast AF, pulm oedema)
damage to local structures - hypoparathyroidism -> hypocalc (chvostek’s sign + trousseau’s sign), damaged recurrent laryngeal nerve
common - late hypothyroid, recurrent hyperthyroid
hungry bone syndrome - Ca and PO4 rapidly deposited in bone
which cancers metastasize to bone
breast bronchus thyroid kidney prostate
what is chvosteks sign
Chvostek sign is contraction of facial muscles provoked by lightly tapping over the facial nerve anterior to the ear as it crosses the zygomatic arch
what is trousseaus sign
Trousseau’s sign is carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes
lumps in neck ddx
midline
goitre
thyroglossal cyst
lateral lymph node solitary thyroid nodule vascular - aneurysm, carotid body tumour sebaceous cyst/lipoma cystic hygroma/branchial cyst salivary glands nerve: neurofibroma
graves triad
goitre
eye signs
thyrotoxicosis
most common cause of large goitre
multinodular
patients usually euthyroid - rarely go toxic
indications for surg - patient choice, cosmetic, compression of local structures, (change of voice/ stridor)
positive pemberton’s test = retrosternal goitre, patient raises arms and holds them above head, pembertons sign is if the patient goes pink due to temp SVC obstruction + stridor
ddx of goitre
simple - physiological, colloid or non-toxic - typically small and smooth, common
multinodular - usually euthyroid, gland large, firm, smooth, nodular - common
graves - smooth soft +/- bruit
hypo - NO GOITRE
hashimotos - firm, small/med size
secondary hyperparathyroid assoc patho pres ix mgmt comps
assoc
CKD or vit D deficient
patho
Hyperplastic PT glands in response to to long term stimulation by chronic hypocalcaemia
pres
CKD pres with predominant bone pain
If low vit D - osteomalacia and fracture
ix
High PTH, low Ca, PO4 high in renal disease, low in vitamin D deficiency
mgmt
Correct vitamin D deficiency
In CKD: Ca supp, correct vit D, phosphate binders, calcimimetics (only at end-stage kidney disease)
tertiary hyperparathyroid assoc patho pres ix mgmt comps
assoc
prolonged secondary, CKD
patho
glands become autonomous producing excess PTH even after cause of hypocalcaemia is corrected -> hypercalc
hyperplasia of all 4 glands
pres
symps of high ca
ix high PTH high ca decreased phos alk phos elevated
mgmt
cinacalet
total or subtotal parathyroidectomy
primary hyperparathyroidism surgery requirements
Elevated serum Calcium > 1mg/dL above normal
Hypercalciuria > 400mg/day
Creatinine clearance < 30% compared with normal
Episode of life threatening hypercalcaemia
Nephrolithiasis
Age < 50 years
Neuromuscular symptoms
Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)
hypoparathyroidism main prob types pres ix mgmt
main prob
LOW CALC
types
PRIMARY -
1. congenital (digeorge, defect in PTH gene, defect in calc sensing)
2. acquired - neck surg, neck irradiation, alc, iron dep (haemochromatosis, copper (wilsons), mag def or excess
SECONDARY - pseudohypoparathyroidism - defect in PTH action:
Rare metabolic disorders with characteristic morphology and end-organ resistance to PTH
morph = Low IQ, short stature, short 4th and 5th metacarpals
ix = Low Ca, high PO4, high PTH (but fail action), urinary cAMP + phosphate following infusion of PTH -> in hypopara = increase in cAMP and phos, in pseudo = none are increased
TERTIARY =
Pseudopseudohypoparathyroidism
Similar phenotype to above but normal biochemistry
pres
hypocalc features - tetany (muscle twitching, cramping and spasm), perioral paraesthesia, chronic - prolonged QT
trousseau + chvostek sign
ix Low Ca, high PO4, low PTH, normal alk phos (@ pseudohypoparathyroidism = low Ca, high PO4, high PTH) Serum Mg - low U+E - to exclude CKD 25-hydroxyvitamin D3 to exclude vitamin D deficiency as cause of hypocalcaemia Low 24 hr urine calcium Echo in DiGeorge ECG - prolonged QT (hypocalcaemia)
mgmt
if tetany = urgent IV calc
diet rich in ca and vit d
anterior pituitary
aka
what does it secrete?
Adenohypophysis
GH: stimulates liver to produce IGF-1 and counteracts insulin
Prolactin: promotes growth of mammary glands and reproductive organs
FSH: stimulates release of sex steroids
LH: stimulates release of sex steroids
ACTH: adrenocorticotropic hormone: stimulates adrenal cortex to release glucocorticoids and androgens
TSH
posterior pituitary
aka
what does it secrete
Neurohypophysis
Supraoptic nucleus - vasopressin
Paraventricular nucleus - oxytocin
pituitary tumour affects assoc types hormonally active types local affects hormonal deficiencies pres ix ddx mgmt big worry
affects - Excessive hormone, local effects, inadequate production by rest of gland
assoc
MEN-1 = parathyroid, endocrine gastric i.e. gastrinoma, insulinoma, and ant pit
types
benign adenoma = most common
prolactinoma -> GH -> ACTH -> TSH -> LH/FSH
hormonally active types
15% Eosinophilic/acidophile: GH/prolactin, prolactin normally small and intrasellar, GH may extend to suprasellar
15% Basophilic: ACTH - presents with Cushing’s, confined to sella turcica but may enlarge post adrenalectomy (Nelson’s syndrome)
70% Chromophobe: non-secretory i.e. incidentaloma (<1cm): often present with visual loss
local affects
cavernous sinus - CN3, 4, 5a, 5b, 6
optic chiasm
headaches - retroorbital, bilateral worse on waking from stretching of dura
visual field defect - bitemporal hemianopia
ocular nerve palsies - squint
hormonal deficiencies - Panhypopituitarism or varying degrees of loss of any problem
Order of hypopituitarism - LH, GH, TSH, ACTH, FSH
Pres = infertility/oligomenorrhoea, erectile dysfunction, loss of libido -> loss of muscle bulk and body hair
gen ix
Pituitary function tests - GH, prolactin, ACTH, FH, LSH, TFT
Visual fields
MRI with contrast
ddx
- Craniopharyngioma - from Rathke’s pouch, between pit and floor V3. Benign and cystic (grows down = lose bottom half vision) most common childhood IC neoplasm. Headache + visual field defects + hypopituitarism
- pit hyperplasia
- meningioma
- brain metastases
- lymphoma
- hypophysitis
- vascular malformation (e.g. aneurysm)
mgmt
Surgery: transsphenoidal transnasal hypophysectomy
SE: pituitary dysfunction -> adrenal insufficiency, DI, SIADH
Radiation: for recurrence
Drugs:
Prolactinoma - bromocriptine
GH - somatostatin analogues
Hormone replacement: *ensure steroids given before levothyroxine as thyroxine may precipitate adrenal crisis
big worry
pituitary apoplexy - rapid enlargement due to bleed into tumour -> mass effect, CV collapse and acute hypopituitarism
prolactinaemia def axis effects of prolactin causes assoc pres ix mgmt long term comp
def Hyperprolactinaemia = raised prolactin in blood. Physiologically high in pregnancy, puerperium and stress (oestrogen promotes PRL + stress - hypothalamus)
effects of prolactin
Women - inhibits GNRH -> reduced gonadotropin (FSH + LH) secretion -> menstrual dysfunction + galactorrhoea -> low oestrogen
Men - direct reversible response on hypothalamus -> secondary hypogonadism -> decreased libido and ED
causes
Prolactinoma - benign adenoma - micro, macro, craniopharyngioma
Hypothyroid -> raises TSH -> raises PRL
Other endocrine = Cushing’s syndrome
Antipsychotics -> block dopamine -> raise PRL
Dopamine receptor antag: domperidone, metoclopramide, neuroleptics
Dopamine depleting: methyldopa
Antidepressants: e.g. TCA, MAOI, SRI
Physiological - pregnancy, puerperium, stress, exercise
Head injury
assoc
MEN1 - parathyroid tumours, prolactinoma, pancreatic islet tumour
pres
Women: oligomenorrhoea, amenorrhoea, galactorrhoea, infertility, hirsutism
Men: slower pres, reduced libido, reduced beard growth, ED
Children: growth failure and delayed puberty
If macroprolactinoma
Headache, vis disturb, bitemporal hemianopia or upper temporal quadrantanopia
ix PRL: normal < 400, if mild el = 400-1000 - repeat before referral > 5000 = true prolactinoma TFT Exclude pregnancy Assess other pituitary function MRI pituitary
mgmt
Treat if effect of size, adverse effect hyperprolactinaemia
Rx: dopamine agonist
Cabergoline or bromocriptine -> reduce prolactin, allow oestrogen normalise
SE: sleepiness, hypotension, cardiac/retroperitoneal/pulmonary fibrosis - monitor
Use bromocriptine if fertility is goal (ergot deriv)
If ineffective: trans-sphenoidal surgery
long-term comp
Of hyperprolactinaemia = hypogonadism - osteoporosis, reduced fertility, ED
Sudden onset headache, visual symptoms = pituitary apoplexy (haemorrhage or infarction)
acromegaly axis main mediator acro vs giant types course assoc pres ix mgmt comps
axis
hypothalamus -> ant pit -> GH -> liver releases IGF1 and adipose tissue releases FFA which causes adrenal output
main mediator
IGF1
Acromegaly = overgrowth of all organ systems bones, joints and soft tissues by IGF1 Giantism = excess GH or IGF1 before closure of epiphyseal plates
types
macro + micro
causes
pituitary adenoma - 95%
ectopic GHRH or GH production of tumour eg panc
course
slow growth - insidious onset
assoc MEN1 T2DM prolactinoma colon cancer
pres
headaches
bitemp hemianopia
APPEARANCE -> large hands/feet, frontal bossing, thickened nose, coarsening facial features
MOUTH -> macroglossia, OSA, snoring, wide spaced teeth, large jaw
SKIN -> dark thick oily skin + sweating
ARTICULAR -> arthralgia, osteoarthritis, jaw pain
NERVE COMPRESSION -> bilateral carpal tunnel, acroparasthesia
VISCERAL -> cardio/hepatomeg
CARDIAC -> HTN, arrhythmia, LVH
T2DM
raised prolactin in 1/3 = galactorrhoea
ix GH - secretion is pulsatile and during peaks, this is inhibited by glucose - this is lost in acromeg serum IGF1 - raised OGTT - to confirm raised IGF1 (75g glucose load, Failure to suppress to < 0.4mcg/L) random GH >0.4mcg pit MRI prolactin blood glucose visual field test
mgmt
FIRST LINE - transsphenoidal surgery
SECOND LINE - SomatoStatin analogues - ocreotide (SE abdo cramps)
THIRD -
1. GH receptor antagonist - pegvisomant - very effective (but doesnt reduce tumour size so still mass effect)
2. dopamine agonist - cabergoline (safe at preg), bromocriptine - chronic use of ergot derivatives = fibrosis, good for mixed acro + high prolactin
comps
CARDIAC - LVH, arrhythmia - monitor with ECG, echo
HTN - serial BP monitoring
sleep apnoea
impaired glucose tolerance + diabetes
carpal tunnel
colon cancer increased risk - monitor every 3-5 yrs
main diseases wrong with adrenals
mnemonic to rememebr them
cushings
conns - hyperaldosteronism
addisons - adrenal insufficency
THE DEEPER YOU GET THE SWEETER YOU GET!!!
zona glomerulosa - mineralcorticoids - ALDOSTERONE
zona fasiculata - glucocorticoids - CORTISOL
zona reticularis - androgens - DHEA
effect of cortisol
when its active?
disease assoc
suppression of RIDGE reproduction immunity digestion growth energy (mobilisation of = elevated sugars - insulin ineffective)
diurnal variation - highest in morning, lowest at midnight
CUSHINGS
pit adenoma = bilateral adrenal hypertrophy
cushings def types most common pres ddx ix localisation ectopic pres triad patho of pigment mgmt comp
def Prolonged exposure to exogenous or endogenous glucocorticoids with clinical state of increased free cortisol and loss of negative feedback
types
ACTH independent = Adrenal adenoma/adrenal carcinoma/excess glucocorticoids
ACTH dependent = Excessive ACTH pit (Cushing’s disease), ectopic ACTH producing tumours (due to lung cancer, small cell)
most common
Excess exogenous glucocorticoids
ACTH dependent = next, Cushing’s disease = 80%, ectopic = 20%
ACTH independent: 60% = adrenal adenoma, 40% = adrenal adenocarcinoma
pres
BODY Truncal obesity, buffalo hump, weight gain, prox muscle wasting
FACE Facial fullness, moon face
Diabetes or impaired GT: polyuria, polydipsia
Hypertension
Osteoporosis
Infection prone and poor healing
MOOD change: depression, lethargy, irritable, psychosis
SKIN: atrophy, purple striae, easy bruising, hirsutism, acne, pigmentation, acne
If ACTH adenoma: headaches, visual problems, galactorrhoea
If hypopituitarism: amenorrhoea, loss of libido, ED
ddx
alcoholism
poorly controlled diabetes
ix
serum glucose - elevated
FIRST LINE - 1mg @ night DEXAMETHSONE SUPPRESSION TEST, measure 8am in morn- failure to suppress to <50mmol = +ve
can confirm with late night salivary cortisol
24hr urinary free cortisol - should be high in 2/3 samples
SECOND LINE - 48hr 2mg dex sup test - failure to suppress <50mmol
if ABG then would see hypokalaemic met alkalosis - especially ectopic ACTH secretion
localisation
plasma ACTH:
low = adrenal - CT
high = distinguish pit from ectopic (give IV CRH - if rise = pit = MRI pit, if no rise = ectopic = IV contrast CT chest (SCLC), abdo (carcinoid)
ectopic pres triad
pig, hypokal, wt loss
patho of pigment
ACTH structurally similar to MSH (melanocyte stimulating hormone) -> increases melanin
mgmt
CUSHINGS = transsphenoidal pit adenomectomy
surg fails? pit irradiation
last resort = bilateral adrenalectomy - monitor @6/12 months with ACTH + MRI
comp = nelsons syndrome = development of large ACTH secreting tumour: presents with pigmentation and VF defects.
if anything else remove via surg
comp adrenal insuff post surg CV disease - main cause of death - HTN, DM, dyslipidaemia metabolic syndrome impaired immunity osteoporosis
DAFNE
what is it
one week course in self management of diabetes
what to give to a patient when they are hypoglycaemic but:
- concious + able to swallow
- conscious + able swallow but no coop
- uncon has IV access
- uncon no iv access
- glucojuice/tabs
- glucogel
- 10% glucose giving set 50ml syringe
- glucagen
diabetic treatment review post hypoglycaemia
insulin never omitted in type 1 - though dose reduction may be needed
need for prolonged 10% glucose infusion over 24-48hrs after gliclazide induced hypo coma. omit further doses until diabetes team seen them if <3, if 3-3.9 reduce dose by 50%
short acting insulin types
affect
actrapid + humulin s
have peak effect about 2 hours after injection
lasts 6-8 hours
carbohydrate snacks normally required between meals and at bedtime so inject 20 mins before
rapid acting insulin
types
action
humalog
novorapid
peak = 1 hr after meal
lasts 3-5 hours
immediately before meal inject or upto 15 mins after
snacks not usually necessary between meals
medium or long acting insulin
administration
types
once or twice
bedtime/morn
dont need to be followed by food
medium - human (humulin I + insulatard)
long - genetically engineered (lantus + levemir) - usually once daily at night
insulin mixes
what are they
when given
types
provide basal + meal related insulin
when
They are usually given twice daily before breakfast and before tea, sometimes three times before meals.
In elderly, they may occasionally be given once before breakfast.
They are never given at bedtime
types
premixed - humulin M3 - 15-20 mins before a meal, NEVER at bedtime, bedtime snack necessary
biphasic analogue mixtures - humalog mix25 and novomix 30, 15 mins after meal, NEVER at bedtime
typical ways of giving insulin
multiple - basal bolus regime - long acting and quick for meals T1DM
twice daily
injections of insulin mixtures, often with metformin in type 2 diabetes
once daily
Of a medium or long-acting insulin at bedtime together with oral hypoglycaemic agents in type 2 diabetes
Occasionally elderly patients are managed with a single injection of a long-acting insulin or an insulin mixture in the morning
when giving insulin what must you make sure you use
AN INSULIN SYRINGE
- much smaller and if you use big syringe = fatal dose
important points of insulin infusion
the body can lack insulin within minutes if the infusion is interrupted or stopped
diabetic ketoacidosis can develop within a few hours if intravenous insulin is interrupted in type 1 diabetes
when discontinuing intravenous insulin the first dose of subcutaneous insulin should be given one hour before intravenous insulin is stopped (15 minutes before for Novorapid or Humalog)
intravenous insulin and glucose are usually stopped once patient is eating and drinking
what is pseudo cushings
how to differentiate
mimics cushings
due to alc excess or sev depression
will have a false posi dexmethasone suppression test or 24hr urinary free cortisol
insulin stress test to differentiate
addisonian crisis def precip biggest risk factor pres ix mgmt
def Acute deficiency of glucocorticoid cortisol and mineralocorticoid
precip
Major or minor infx, commonly vom/diarrhoea
Injury, surgery, pregnancy causing acute exac of chronic insuff
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
biggest RF
long term steroid therapy
pres malaise fatigue n+v low grade fever muscle crmaps confusion which can progress to: hypotension and hypovolaemic shock
ix
u+e - low sodium, high pot, creatinine raised,
blood glucose - hypoglycaemia
bloods for cortisol and ACTH
mgmt
IV/IM hydrocortisone (only as high dose = mineralcorticoid too) 100mg adult
rehydration - fluids IL n. saline over 30-60 mins
further hydrocortisone + glucose - 100mg in 5% over 24 hours
continuous cardiac and electrolyte monitoring - ECG, reg U+E
treatment of infection - IV abx
conns synonym action of aldosterone def when to consider other causes pres ix ddx rx comp
synonym
primary causes of primary hyperaldosteronism
aldosterone =
Insertion of ENaC and ROMK to luminal membrane of DCT
Leads to hypernatraemia, water retention and hypokalaemia
def excess production of aldosterone independent of RAAS system due to adrenal adenoma -> renin is suppressed
when to consider
HTN, hypokalaemia, or alk in someone not on diuretics
other causes
adrenal adenoma
bilateral adrenal hyperplasia
secondary - due to high renin from decreased renal perfusion in renal art stenosis
pres
oedema
HTN
hpokalaemia - weakness, cramps, parasthesia
met alk - secretion of H+ in exchange of K+ (more k+ in urine) in intercalated cells
polyuria - from reduced ability of the kidney to concentrate urine
ix
U+E - hypernat, hypokal
BP - high
aldosterone:renin ratio >800 (imaging req)
ECG for arrhythmia
CT/MRI for confirmation of adrenal adenoma
lyind and standing aldosterone: affected by posture
ddx
high ald, low renin = primary (conns, BAH, familial)
high ald/renin = renal art stenosis, diuretics, bartters, gitelmans
mgmt
conns - medical mgmt prior to surg:
- 4w spiro or eplerenone (aldosterone antag)
- lapro adrenalectomy (only if unilat)
surgery only considered if unilateral
BAH - aldosterone ant (spiro - also blocks test so may cause gynaecomastia, ED, menstrual prob)
eplerenone - doesnt cause gynaeco
ENaC inhibitor: Amiloride, a potassium-sparing diuretic, may be used if aldosterone antagonists are not tolerated - worse option tho - weak HTNive
comp
HTN may persist
renal tubular acidosis electrolyte finding type 1 type 2 type 3
HYPERCHLORAEMIAC METABOLIC ACIDOSIS
type 1 - distal inability to secrete H+ distally -> hypokalaemia, comp = renal stones
type 2 = proximal inability to resorb HCO3 -> hypokalaemia, comp = osteomalacia
type 3 - mixed - rare
type 4 - reduced aldosterone -> reduced proximal tubule ammonium excretion, causes = hypoaldosteronism
phaeochromocytoma def 10% rule main worry precip assoc classic quartet other pres course O/E ix mgmt
def Catecholamine producing adrenal tumour @ adrenal medulla. Secrete autonomously from SNS
10% rule
are bilateral, malignant, extra-adrenal (organ of zuckerkandl), familial (MEN2)
main worry
life threat HTN + arrhythmias
precip = anaesthesia, opiates, decongestants, drugs inhib reuptake catecholamines eg TCA, childbirth, xray contrast
mgmt - Phentolamine or IV nitroprusside
asoc
MEN (bilateral)
neurofibromatosis
von-hippel lindau
quartet
Episodic headache + sweating + palpitations + tremor
other pres
sense of doom
anxt
course
secrete constant or intermittent
O/E
Hypertension, postural hypotension, tremor, flushing, tachycardia
ix 24 hour urine catecholamines, metanephrines, Raised serum metanephrines Genetic testing Abdominal CT/MRI
mgmt
surgery = definitive
pre surg - alpha blocker - phenoxybenzamine for 7-10 days to allow expansion of blood volume
pre surg BB - post alpha - use propanolol
Monitor with 24 hour catecholamines + VMA 2 weeks after surgery
adrenergic receptor blockers
A1 - SM @ BV = reduces BP, SM contraction @ bladder neck = increased peeing
A2 - Inhibit insulin release @ pancreas = more insulin
B1 - Tachycardia + increased contractility -> decrease HR + CO
Increased renin release -> decreased renin
B2 - Bronchodilation -> bronchoconstriction
Carcinoid syndrome def common pres other clinical features whats released which tumours assoc ix localised disease
def tumour of enterochromaffin cell in liver
common pres
flushing
diarrhoea
other clin wheeze palps telangiectasia abdo pain hypotension
whats released = serotonin, other vasoactive peptides
which tumours
30% of gut
5% bronchial
assoc
MEN1
ix
serum chromogranin A/B
urinary 5ht
CT CAP - to find tumour, check liver mets
mgmt
localised disease - surgical resection - appear bright yellow
+ peri-opeative ocreotide infusion (to prevent carcinoid crisis - continue for 48 hours post)
MEN stands for inheritance types in all
stands for
multiple endocrine neoplasia
inheritance
all AD
type 1
cancers = parathyroid, pituitary, pancreas
common pres = hypercalc
type 2a
RET oncogene
cancers = parathyroid, phaechromocytoma, medullary thyroid
type 2b
RET oncogene
cancers = Phaeochromocytoma + neuromas + marfanoid body
in all
proph thyroidectomy
diabetes insipidus types def amounts ADH synth, action causes pres ix mgmt
types
nephrogenic or cranial
def passage of large amounts of dilute urine due to hyposecretion or resistance to ADH/vasopressin (same thing) and inability to concentrate urine
amounts
3l of <300mOsm/kg
ADH synth
Synthesised at supraoptic nucleus of hypothalamus and transported in vesicles to posterior pituitary
action
Binds V2 receptor and inserts aquaporin 2 to luminal membrane of DCT and CD
causes
lithium - nephro
CRANIAL
damage to hypothalamus
acquired = idiopathic, tumour (e.g. craniopharyngioma), intracranial surgery, head injury, granulomatous disease (sarcoid, TB, GPA), infection (men, enceph)
inherited = AD vasopressin gene, DIDMOAD (association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness aka Wolfram’s syndrome)
NEPHROGENIC
Acquired: hypokalaemia, CKD, lithium, RTA, hypercalcaemia
Inherited: X linked mut V2 ADH receptor gene, AR AQuaPorin2 gene
pres Marked polyuria > 3 litres Polydipsia and chronic thirst Nocturia Symptoms of hypernatraemia -> lethargy, weakness, confusion Distended bladder
ix
24 hour urine collection >3l
Urine osmolality <300mOsm/kg (2[Na+K] + urea + glucose)
Serum osmolality: normal or high (normal/high sodium, calcium, potassium)
Urine dip: -ve for glucose
*Water deprivation test with *desmopressin response - tests ability of kidneys to concentrate urine:
if cranial: dep <300, desmo >800
if nephrogenic: dep <300, desmo <300
psychogenic: dep >800, desmo >800
normal urine osmolality 500-800
MRI pituitary/hypothalamus
mgmt
cranial = desmopressin replacement, if overdose = hyponat
nephrogenic = drink adequate fluid in response to thirst, stop causative drugs, treat underlying hypok, hyperca
low sodium - either dietary or with thiazide + NSAID
if hyernat - oral/IV fluids with hypotonic eg 5% dex or 0.45% saline - aim reduce 1mmol/hr
thiazide - paradoxical effect: in this case they concentrate urine and decrease polyuria - slight hyponatraemia -> increased Na and water uptake
explain patho of cerebral oedema with rapid correction of hyponatraemia
Acute hyponatraemia: low serum osmolality, low sodium or high water in blood: water moves into brain (higher conc Na/K/Cl) = cerebral oedema
Chronic hyponatraemia: low serum osmolality - electrolytes (Na/K/Cl move out of brain as does water) to try and correct serum osmolality
If rapid correction, = rapid increase in serum osmolality and rapid movement of water out of brain - osmotic demyelination
symptoms for:
Na 130-135
Na 125-130
Na <125
130- 135 Headaches
125-130 Weakness + lethargy
<125 Agitation + coma
