Endocrinology_Medicine Flashcards
(48 cards)
1
Q
Hyponatremia - Sx? Ix & Approach? What happens if you correct Na too fast?
A
Sx: confusion, altered GCS, headaches, seizures, encephalopathic
Ix: fluid status, U&E, paired osmolalities (urine, serum)
Fluid status:
- HYPOvolaemic (dehydrated) - WASTING (diarrhoea/vomiting, diuretics) –> IV fluids
- EUvolaemic (normal) - ENDOCRINE (SIADH, hypothyroidism, Addison’s) –> fluid restrict + Tx underlying cause
- HYPERvolaemic (fluid overload) - FAILURE (liver, renal, heart) –> fluid restrict + Tx underlying cause
Urine Na:
- <20 mmol/L –> hypovolaemia (increased Na reabsorption in kidneys –> increasing H20 retention –> reducing urine Na)
- >20 mmol/L –> SIADH (BUT if on diuretics, urine Na can’t be interpreted) –> fluid restrict
Na corrected too fast (>10) = osmotic demyelination syndrome (central pontine myelinolysis) –> pseudo-bulbar palsy, paraparesis, locked-in syndrome
2
Q
Potassium homeostasis - areas involved? Hypo/hyper? Appearance on ECG? Hyper Tx?
A
Areas involved:
- Dietary intake
- Absorption in GI tract
- Adrenals & kidneys - regulate serum K concentration
HYPOkalaemia:
- Poor dietary intake, vomiting/diarrhoea
- Diuretics - loop/thiazide (block channels causing K reabsorption)
- Hyperadrenalism (Conn’s, bilateral adrenal hyperplasia, Cushing’s)
- Conn’s/BAH - excess aldosterone - NOTE: Aldosterone promotes reabsorption Na, excretion K
- Cushing’s = excess cortisol –> off-target effect on mineralocorticoid receptors –> mimics aldosterone
HYPERkalaemia:
- false = HAEMOLYSIS –> repeat sample
- Kidney failure e.g. on dialysis (kidneys = main route to remove K)
- Anti-HTN/diuretics
- ACEi/ARB - reduce kidney hyperfiltration, mainly a risk if CKD
- K+-sparing diuretics e.g. spironolactone/amiloride
- Addison’s disease (failure - can’t produce enough cortisol/aldosterone)
- NOTE: appearance on ECG = tented T-waves, broad QRS, prolonged PR interval
Hyperkalaemia Tx:
- Protect heart - IV 10-30ml 10% Ca Gluconate (repeat /15m, x5 MAX)
-
Reduce K+:
- 1st line - 10U Actrapid (insulin > drive K into cells) AND 100mL 20% glucose (to prevent hypo)
- 2nd line - 5mg Salbutamol NEB (b-agonist)
- Ix cause: drug chart, U&E (kidney funct), short SynACTHen test (Addison’s)
3
Q
Calcium homeostasis?
Hyper Sx? Ix & causes? Mx?
Hypo Causes? Sx? Ix? Mx?
A
Hormone production:
-
Parathyroid gland - PTH –> INCREASE Ca:
- Bone resorption
- GI absorption
- Kidney - decreased excretion, increases 1alpha-hydroxylation (vitD activation)
- Vit D3 aka cholecalciferol (UV)/ergocalciferol (diet)
- In Liver –> 25-OH(D) aka calcidiol
- In Kidney + 1alpha-hydroxylase –> 1,25-OH2(D) aka Calcitriol (activated vitD) –> INCREASE Ca
- GI absorption
- Kidney - decreased excretion
HYPERcalcemia
-
Sx:
- Stones - urinary tract calculi
- Bones - fractures
- (Abdo) moans - dyspepsia
- Thrones - polyuria, constipation
- (Psych) overtones - depression, psychosis
- Ix - check PTH:
- Low - hypercalcemia of malignancy (PTH axis is functioning normally) - bone mets, PTHrP (released by lung SCC), myeloma (CRAB)
- Normal/high - primary hyperparathyroidism (as if serum Ca high, PTH should be low) - adenoma, hyperplasia, MEN 1&2
- Other:
- Fluid status, ECG (short QT), protein electrophoresis, 24hr urinary Ca (familial hypocalciuric hypercalcemia)
- Bloods - bone profile (Ca, PO4), U&E
- Imaging: CXR
- Mx:
- IMMEDIATE = aggressive IV 0.9% fluid resus (4-6L over 24krs), repeat Ca
- Tx underlying cause:
- Parathyroid adenoma - minimally invasive surgery (subtotal/total parathyroidectomy)
- Malig - Zalendronate/Pamidronate (inhibit osteoclast activity), slow infusion
- Other:
- If bone mets –> bisphosphonates
- If renal failure –> Cinacalcet (reduce PTH)
- Recheck serum Ca @day 2 –> 4
HYPOcalcaemia
- Causes:
- Hypoparathyroidism (PO4 high, PTH low)
- Pseudohypoparathyroidism (PO4 high, PTH high) = PTH resistance
- CKD (high PO4, PTH high, ALP high)
- Vit D def (rickets/osteomalacia, low/normal PO4, high PTH, high ALP)
- Hypomagnesaemia (low/normal PO4, low/normal PTH, normal ALP)
- Presentation:
- Peri-oral numbness, digital paraesthesia, dermatitis
- +ve Trousseau’s (BP cuff 20 over SBP for 3mins –> salt bae hand), Chovstek signs (tap over the masseter muscle in the inferior pre-auricular area)
- Laryngospasm (wheeze, dysphagia, muscle cramps)
- Confusion, seizures, prolonged QT
- Ix: serum Ca, PO4, Mg, PTH, U&E, Vit D
- Mx: PO/IV replacement of Ca
4
Q
If a patient has metformin & CKD when to stop metformin?
A
eGFR <30
5
Q
If on insulin - what to do about driving?
A
Inform DVLA, must be able to record CBG every 2hrs
6
Q
Tired, thirsty and irritable, wees alot (very pale) - Dx?
What is there Serum Sodium lvl?
A
Diabetes insipidus
Ix: hypernatraemia
7
Q
Large hands + jaw + bitemporal hemianopia - Dx?
A
Acromegaly (anterior pituitary macroadenoma)
8
Q
Young female, resistant HTN, hypokalaemia - Dx?
A
Conn’s syndrome (hyperaldosteronism)
9
Q
Headache, sweating, tachy, HTN - Dx?
A
Phaeochromocytoma
10
Q
Hyperparathyroidism sub-categories?
A
- Primary - PTH secretion from primary parathyroid tumour/ectopic secretion from another tumour (high Ca, high PTH)
- Secondary - PT hyperplasia to maintain control of hypocalcemia, normally from CKD (low Ca, high PTH, normal -ve feedback)
- CKD –> bone profile, parathyroid hormone lvl every 3-6 months
- Tertiary - prolonged secondary, becomes irrepressible by serum Ca lvls. Mostly kidney transplant patients (high Ca, very high PTH)
11
Q
Hoarse voice post-thyroidectomy - why?
A
Recurrent laryngeal nerve injury
12
Q
Low Ca, high PO4, high PTH, short fingers
A
Pseudohypoparathyroidism (similar features to secondary hyperparathyroidism - consider if CKD or vit D deficiency does not explain the presentation)
13
Q
Facial twitching when tapping anterior to the tragus - sign?
A
Chvostek sign (hypocalcaemia)
14
Q
Diabetes: presentation? RFs? types? criteria for Dx? Mx? Complications?
A
Presentation: polyuria, polydipsia, dehydration
- Ketosis - malaise, vomiting
- FHx, other endo disorders
- If known DM:
- Previous DM control (hyp/hyper)
- Micro/macrovascular complications
- Diabetic eye disease (Dx & Tx)
RFs: overweight, FHx (DM), PMHx (GDM), PCOS, HTN, dyslipidemia, CVD
Criteria for Dx (repeat test needed for Dx):
- Fasting plasma glucose of ≥7.0 (normal ≤6)
- OGTT (BM 2hours after 75g glucose-load)/ Sx + random plasma glucose of ≥11.1mmol/l (normal <7.8)
- HbA1c ≥48mmol/mol (≥6.5%) - not for young/T1DM, acutely ill, haem disease, preg, iatrogenic
T1DM Mx: exogenous insulin to avoid DKA & long-term complications
- Diet - lower fat, higher carbs = counting carbs (adjust insulin around diet rather than limiting eating)
- Diabetic specialist nurse - EDUCATE:
- Self-adjust dose - DAFNE course for T1DM (D for DM)
- Fingerprick glucose
- Calorie intake & carb counting
- Phone support
- Don’t stop insulin during acute illness, maintain calorie intake
- Insulin regimens:
- 1st line - Basal-bolus regimen
- Basal (background) - BD insulin detemir (or Levemir/Lantus/Tresiba) as basal insulin
- Bolus (before meals) - analogue rapid-acting insulin e.g. insulin Lispro (Humalog)/Aspart (Novorapid)/Neutral (Actrapid)
- Other:
- BD biphasic (premixed insulin, hypos common) e.g. Novomix, Humulin M3, Humalog Mix
- OD before bed long-acting (for T2DM)
- NOTE: intermediate-acting insulin e.g. Humulin I, Insulatard
- 1st line - Basal-bolus regimen
T2DM Mx:
- 1st line - Lifestyle changes - DESMOND course for T2DM (D for DM), dietician input, self-BM monitoring (individual HbA1c target <6.5)
- HbA1c targets:
- No hypoglycaemics - 48mmol/mol
- Hypoglycaemics - 53mmol/mol
- Escalate Tx - 58mmol/mol
- HbA1c targets:
- Medication:
- 2nd - Metformin (SEs: diarrhoea, LA - avoid if eGFR <30)
- 3rd - ADD Sulphonylurea e.g. Gliclazide (SEs: hypoglycaemia, weight gain)
- 4th - ADD other DM med:
-
Pioglitazone (SEs: hypoglycaemia, weight gain, oedema, fractures in elderly)
- C/I in HF, bladder cancer
-
SGLT-2 inhibitor e.g. Empagliflozin (SEs: Hypoglycaemia, weight loss, UTI)
- Not recommended in impaired renal funct
- DPP-4 inhibitor e.g. Linagliptin (APPROVED FOR USE IN CKD, weight neutral)
-
GLP-1 analogues e.g. Exenatide/Liraglutide (SE: weight loss - useful if BMI >35; vomiting)
- Not recommended in impaired renal funct
-
Pioglitazone (SEs: hypoglycaemia, weight gain, oedema, fractures in elderly)
- 5th - If on triple therapy & not providing control –> commence insulin
- CVD risk Mx - anti-HTN, anti-lipid, QRISK-3 score
- Diabetic nephropathy Mx:
- Monitor albumin-creatinine ratio (ACR)
- Consider ACEi/ARB early
- Diabetic neuropathy Mx:
- Annual Sx review (erectile dysfunction, autonomic neuropathy - orthostatic hypotension, gastroparesis, bladder emptying difficulties)
- Annual foot screen + specialist foot Mx, monitor for diabetic foot/ulcers ± amputation
- Diabetic retinopathy: retinal screen annually (age ≥12yrs)
- Background: need to tighten control
- Venodilation, microaneurysms (dots), hard exudates (lipid deposits)
- Tx: tighten glycaemic control, refer if near macula
- Pre-proliferative (mild) - soft exudates (cotton wool spots e.g. infarcts)
- Proliferative - neovascularization (+ floaters, reduced acuity)
- Tx: pan-retinal photocoagulation
- Diabetic maculopathy - hard exudates, oedema (+ blurred vision, reduced acuity)
- Tx: intravitreal triamcinolone acetonide decreases macula oedema
- NOTE: Pre-diabetic –> refer to diabetes prevention programme (DPP)
- Background: need to tighten control
Diabetes complications:
- Microvascular:
- Eye - diabetic retinopathy (± cataracts, glaucoma)
- Kidney - diabetic nephropathy
- Neuropathy - damage to PNS –> diabetic neuropathy (peripheral neuropathy - glove & stockings distribution) –> diabetic ulcers/gangrene
- Macrovascular:
- Brain - stroke/TIA/cog impairment
- Heart - coronary heart disease
- Extremities - PVD, diabetic ulcers/gangrene
15
Q
Acromegaly cause? presentation? Ix? Mx? Complications?
A
Cause: macroadenoma in anterior pituitary
Presentation: coarse facial features
- Skin (acanthosis nigricans - thick & dark in creases), sweating, carpal tunnel syndrome (bilateral)
- Arthropathy, sleep apnoea, reduced sexual functioning, visual field defects (bitemporal hemianopia)
- Assoc: DM, HTN, MEN type 1 (15%)
Ix:
- Bedside: CN VI palsy, urine dip (glucose), ECG (cardiomyopathy)
- Bloods: elevated IGF-1, GH lvl during OGTT (not suppressed in acromegaly)
- Imaging: MRI brain (macroadenoma), sleep studies, colonoscopy (screening), visual field testing (driving)
Mx:
- Transsphenoidal hypophysectomy (curative)
- Medical: somatostatin analogue (octreotide)
- External pituitary radiotherapy (long-term 5-10yrs)
Complications:
- General: HTN, DM, carpal tunnel syndrome, sleep apnoea, colorectal cancer, LVH/cardiomyopathy/IHD
- Anterior pituitary hypofunction: hypogonadism
- Local compressive: bitemporal hemianopia
16
Q
Perioperative DM Mx?
A
Variable insulin infusion for 30-60 mins after starting SC insulin to avoid iatrogenic DKA
18
Q
SGLT2 inhibitors (dapagliflozin) S/E?
A
Increased yeast/UTIs, hypoglycaemia, weight loss
19
Q
Pioglitazone S/E? C/Is?
A
hypoglycaemia, weight gain, fluid retention (oedema), assoc with bladder cancer, osteoporosis (elderly - fractures)
C/Is: HF, bladder cancer
20
Q
Sulphonylureas (oral) or insulin (sc) S/E?
A
Weight gain & hypoglycaemia
21
Q
Diabetic patient having surgery:
- What to do if high HbA1c?
- What to do if long surgical period (missing 2 meals)?
- What to do if short surgical period if taking insulin/other diabetic meds?
- What to do the day before admission and day after surgery?
A
If poorly controlled DM (HbA1c ≥69) or long starvation period (≥2 missed meals) –> variable rate insulin infusion + IV maintenance fluids (5% glucose in 0.45% saline)
If on insulin:
- If using variable rate insulin infusion - stop all insulin until eating/drinking normally and has been 30mins since first post-op insulin dose
- Basal (background insulin) always maintained to prevent ketosis - dose reduced by 20% to avoid hypoglycaemia
- Bolus (before meals) avoided:
- If AM surgery - omit morning & lunch dose
- If PM surgery - omit lunch dose
If on diabetic medications:
- Stop ALL if variable-rate insulin infusion used - apart from GLP-1, which can be maintained
- Insulin & sulphonylureas (glipizide) - dose must be reduced as they lower BM –> hypoglycaemia
- AM surgery - omit morning dose
- PM surgery - omit morning and afternoon dose
- Metformin, GLP-1 analogues (liraglutide), DPP-IV inhibitors (linagliptin), SGLT2 inhibitors (dapagliflozin) - rarely cause hypoglycaemia while fasting (only reduced if other concerns)
- SGLT2 inhibitors - omit morning dose if AM/PM surgery
NOTE: take all as normal day before admission, take as normal day after surgery
22
Q
Hyperosmolar Hyperglycaemic State
- What does insulin do? Pathophysiology of HHS?
- HHS criteria? HHS Mx? HHS Mx Targets?
A
Insulin:
- High level of insulin –> reduces serum BM (pushes into surrounding tissues & hepatic glucose store)
- Low level of insulin –> switches off ketone production
Pathophysiology:
- HHS = complication of T2DM
- In HHS have enough insulin to switch of ketone production but not enough to reduce BM lvls
- High glucose - osmotically active –> polyuria –> dehydration
HHS criteria:
- Hypovolaemia
- Glucose >30mmol/L
- NO ketonaemia
- Serum osmolality >320mOsmol/kg
Mx: REHYDRATE = IV 0.9% NaCl (3-6L by 12hrs, deficit 110-220mL/kg)
- Targets:
- Reduce Na by less than 10mmol/L/day (otherwise risk osmotic demyelination syndrome)
- Reduce BM by over 5mmol/L/hr
- NOTE: if targets not met by 0.9% saline –> 0.45% instead
- If fluid alone are not enough –> 0.05 units/kg/hr fixed-rate insulin infusion
23
Q
SIADH - pathophysiology? criteria? causes?
A
Criteria:
- True hyponatraemia
- High urine osmolality
- Clinically euvolemic
- Dx of exclusion (9am cortisol + TFTs must be normal)
Causes:
- Malig (small cell lung cancer, breast cancer)
- CNS disorders (encephalitis, abscess)
- Chest disease (pneumonia, TB)
- Drugs (opiates, SSRIs, carbamazepine)
24
Q
Hypernatremia - breakdown into different causes? Mx?
A
Causes:
-
Hypovolaemia (H20 loss > Na loss) - most common
- GI loss: D&V
- Skin loss: excessive sweating, burns
- Renal loss: diabetes insipidus (DI), osmotic diuresis (glucose/mannitol), loop diuretics, kidney disease
- Euovolaemia - Resp (tachypnoea), skin (sweating, fever), renal (DI)
- Hypervolaemia
- Mineralocorticoid excess – Conn’s syndrome
- Inappropriate saline
Causes thirst –> most people self-correct UNLESS: failure to ingest water (Elderly/dementia, fasting (e.g., for surgery), excess loss)
Mx: SLOW Hartmann’s (rapid correction –> cerebral oedema)
25
Q
Calcium, PTH, Vit D, ALP levels in hyperparathyroidism & relevant differentials
A
26
Diabetes insipidus - Sx? Types? Ix? Tx?
**Sx:** hypernatremia (lethargy, thirst, irritable, confusion, coma, fits), polyuria, urine plasma osmolality \<2 (very dilute)
**Types:**
* Central (lack of ADH prod in hypothalamus) – pituitary surgery, irradiation, trauma, infarction
* Nephrogenic (resistance to ADH effects) – hypercalcaemia, hypokalaemia, meds (lithium)
**Ix:** rule out DDx (BM, review drugs, K/Ca lvls)
* U&E, Ca, BM, serum & urine osmolarities
* Dx: 2-step fluid deprivation test = give **desmopressin (DDAVP):**
* Normal/primary polydipsia --\> urine concentrates on fluid deprivation (\>600)
* Cranial DI - giving desmopressin allows ADH prod --\> urine conc
* Nephrogenic DI: urine never concentrates
* NOTE: DI excluded if urine to plasma (U: P) osmolarity ratio \>2:1
* _Cranial MRI_ - if suspect cranial DI
NOTE: Fluid deprivation test process:
* Baseline urine osmolality
* Fluid deprivation for 8hrs, take urine osmolality
* Give desmopressin, wait 8hrs, take urine osmolality
Tx:
* Nephrogenic DI --\> fluids (+ monitor UO) + **thiazide diuretics** (hydrochlorothiazide - weird/does not make sense)
* Central DI --\> fluids + **desmopressin**
27
Hypokalaemia - causes? features? Ix? Mx?
**Causes:**
* **GI loss** (D&V)
* **Redistribution into cells:** insulin (refeeding syndrome (KPMg), insulinoma), b-agonist (salbutamol), metabolic alkalosis (pump out H, pump in K)
* **Renal loss:**
* _Alkalosis:_ Conn’s, loop diuretics/Barter’s syndrome, thiazide diuretics/Gitelman syndrome (diuretics --\> K not reabsorbed)
* _Renal tubular acidosis:_ T1 (reduced H+ excretion), T2 (reduced bicarbonate reabsorption), T4 (aldosterone def/resistance – **_hyper_**kalaemia)
**Clinical features**: muscle weakness, cardiac arrhythmia, polyuria/dipsia (nephrogenic DI)
**Ix:** ECG, cardiac monitor (risk of VF/arrhythmia), aldosterone: renin ratio
**Mx:**
* Mild: **SandoK** (2 tablets TDS for 3 days, monitoring)
* Severe: **IV KCl** (\<10mM/hr)
* Treat cause, correct Mg
28
Hyperkalaemia - causes? Ix? Mx?
**Causes:**
* _Spurious sample_
* **Excessive intake:** oral, parenteral, stored blood transfusion
* **Transcellular mov** (ICF\>ECF):
* Acidosis, insulin shortage (DKA - high glucose, high ketones, metabolic acidosis)
* Tissue damage/catabolic state (rhabdomyolysis) – CK very high
* **Decreased excretion:**
* AKI (oliguric phase)/CKD (late)
* Drugs (spironolactone – K-sparing diuretic, ACEi/ARB/NSAID)
* Addison’s (mineralocorticoid def)
**Ix:**
* Repeat sample (VBG to also look for acidosis)
* CK, Creatinine & Urea
* AM Cortisol/Short synACTHen test
* **_ECG_**
* Loss of p-waves, tall, tented T-waves, broad QRS (+ bradycardia)
* If severe & untreated --\> ECG forms ‘sine wave’
**Mx** (if \>5.5 w/ ECG changes OR \>6.5):
* **IV 10mls 10% calcium gluconate** (cardioprotective, doesn’t lower K)
* If on Digoxin – IV Ca causes arrhythmias – cardiac monitoring
* **IV 10ml 20% dextrose + 10 units short-acting insulin** e.g., Actrapid (insulin drives K into cells, dextrose prevents hypo)
* **Neb salbutamol** adjunct + treat cause
29
Thyroid disease - types? presentations? causes? Mx? What is a thyroid storm?
**Hypothyroidism:**
* Causes:
* _Primary:_
* **Hashimoto's thyroiditis** - most common hypothyroidism
* Goitre, AI disease (vitiligo, pernicious anaemia, T1DM, Addison's)
* Elderly females
* May be initial ‘Hashitoxicosis’
* +++ Autoantibody titres
* _Antithyroid peroxidase (TPO) & antithyroglobulin (TG)_
* **Atrophic AI thyroiditis**
* No goitre, anti-TPO/TSH
* Iodine def, meds (carbimazole, lithium), thyroid surgery
* _Secondary:_ pituitary gland fails to produce TSH
* Tumour, vascular (Sheehan syndrome), radiation, inf
* Ix:
* Bedside: ECG (pericardial effusion, ischaemia)
* Bloods: FBC, U&E, TFTs, Lipids, Prolactin, Anti-TPO/TG
* Imaging: CXR (effusions, HF)
* Mx: thyroid replacement therapy (levothyroxine)
* Monitor with serum TSH, careful with dose in elderly (prone to IHD)
* Myxoedema coma - A-E & active warming, T3 slow IV, hydrocortisone IV
* Associated complications:
* Cardiac - HF
* Serous effusions (pleural, peritoneal, pericardial, joint)
* Neuro - carpal tunnel, proximal myopathy, cerebellar dysfunction, myxedema coma
* Systemic - dyslipidemia, anaemia
**Hyperthyroidism:**
* Presentation:
* Weight loss, increased appetite
* Heat intolerance, tremor, sweating, palpitations
* Mood (anxious, irritable)
* Bowel habit (diarrhoea), menses (oligomenorrhoea)
* Goitre
* Eye Sx (watering, gritty, red)
* Other AI disease (vitiligo)
* Signs:
* Lid lag (eyes)
* Palmar erythema
* Brisk reflexes
* Sinus tachy/AF
* Ix: TSH low, T3/4 high, TPO (may be raised), anti-TSHr ab (in Graves), technetium 99m uptake scan (diffuse/reduced)
* Causes:
* High-uptake:
* **Graves’ disease**: MOST COMMON, autoantibodies ++ (_anti-TSH-R ab_),
* Eye signs: proptosis --\> exophthalmos, diplopia, visual loss
* Peripheral signs: pretibial myxoedema, thyroid acropatchy, onycholysis, bruit over thyroid
* **Toxic multinodular goitre aka Plummer's disease:** hot nodules, _painless_
* Toxic adenoma: 5%, single ‘hot nodule’ on isotope scan (1 area of uptake)
* Low-uptake:
* **Subacute De Quervains (viral) thyroiditis**: self-limiting post-viral painful goiter. Initially hyperthyroid, then hypothyroid
* Tx: NSAIDs
* Postpartum thyroiditis (like De Quervain’s but postpartum)
* Mx:
* Conservative: lifestyle changes, corneal lubricants
* **Medical:**
* Sx relief – _B-blockers_
* Antithyroid meds - _Carbimazole_ (or propylthiouracil)
* SEs: rashes, agranulocytosis - monitor
* _Radioiodine:_
* acts slowly, effective, best Tx for toxic multinodular goitre
* Risk of permanent hypothyroidism (10%)
* CI in preg/lactating women
* **Surgical:** _subtotal thyroidectomy_ (in large goitre/relapse)
* Monitoring with TFTs annually
* **Thyroid storm:** acute state of shock, pyrexia, confusion, vomiting
* HDU/ITU support
* _Propylthiouracil_ 600mg --\> 200mg QDS
* Stable iodine (Lugol's iodine) ≥1hr later
* Propranolol, dexamethasone & IV fluids
30
Thyroid neoplasia types?
**Papillary** (\>60%)
* 30-40yrs,
* Psammoma bodies on histology
* Very good prognosis
* Surgery +/- radioiodine, thyroxine (to ↓TSH)
**Follicular** (35%)
* Middle age, well-differentiated but spreads early
* Surgery + RI + thyroxine
**Medullary (5%)**
* Originates in parafollicular “C” cells – linked to MEN2
* Produce _calcitonin_ (monitoring levels is useful to detect recurrence)
**Lymphoma (5%)**
* MALT origin
* RFs: chronic Hashimotos (lots of lymphocytes that proliferate)
* Good prognosis
**Anaplastic**
* Rare, elderly, poor response to all treatments
31
Multiple endocrine neoplasia (MEN) - what are these?
Group of 3 inherited disorders (AD) --\> predisposition to endocrine cancers
* MEN1 (**3Ps**): **P**ituitary, **P**ancreatic (e.g., insulinoma), **P**arathyroid (hyperparathyroidism)
* MEN2a (**2Ps, 1M**): **P**arathyroid, **P**haeochromocytoma, **M**edullary thyroid
* MEN2b (**1P, 2Ms**): **P**haeochromocytoma, **M**edullary thyroid, **M**ucocutaneous neuromas (& Marfanoid)
32
Adrenal disease breakdown? Causes? Presentations? Ix? Mx?
**Cushing's** #HighCortisol
* Causes:
* ACTH-dependent:
* **_Pituitary_ tumour** (85%) = “Cushing’s disease”
* _Ectopic_ ACTH-prod tumour (5%) - SCLC/carcinoid tumour
* ACTH-independent:
* _Adrenal_ tumour (10%)
* _Iatrogenic_ steroid use
* Presentation:
* Thin skin, easy bruising, proximal myopathy, obesity (moon face, buffalo hump), other (hirsutism, acne)
* Exam: vertical abdo striae
* HTN, DM, osteoporosis (back/bone pain)
* Ix:
* Exclude pseudo-Cushing's - depression, alcohol excess, chr inf (no muscle weakness)
* Confirm Dx: **low-dose dex suppression test** - fail to suppress cortisol in all
* Overnight dexamethasone suppression test (1g @11pm) OR
* 48hr low-dose 0.5mg/6h PO dexamethasone supression test OR
* 24-hr urinary free cortisol (test x3 as low sensitivity)
* **Plasma ACTH measured**:
* High - _CRH test_ identifies if pituitary or ectopic
* Could also do bilateral inferior petrosal sinus sampling --\> if no mass --\> CT contrast CAP for ectopic
* Low - adrenal tumour --\> _CT/MRI adrenal glands_ --\> if nothing --\> adrenal vein sampling
* Mx: treat underlying disease e.g. _withhold steroids_ or surgical removal of the lesion
* Cushing's disease (pituitary tumour) --\> **trans-sphenoidal hypophysectomy** (complications - DI, hypopituitarism)
* 2nd - _pituitary radiotherapy_ (also used if still high cortisol post-surgery) --\> progressive anterior pituitary failure
* Metyrapone & ketoconazole - sometimes before/after surgery
* 3rd - laparoscopic bilateral adrenalectomy in refractory (but require lifelong glucocorticoid/mineralocorticoid replacement + risk of Nelson's syndrome (increased skin pigment from high ACTH
**Hypoadrenalism**
* Causes:
* AI: **Addison's disease** (\>70%)
* Malig: **mets** (lung, breast. kidney)
* Inf: **TB** (\>10%), HIV (CMV adrenalitis), Fungal
* Infiltration: granulomatous disease, hemochromatosis, amyloidosis
* Iatrogenic: ketoconazole, rifampicin, phenytoin, bilateral adrenalectomy
* Congenital: congenital adrenal hyperplasia (late-onset)
* Presentation:
* Anorexia/weight loss, fatigue/weakness, postural dizziness, reduced libido, sweating
* N&V, diarrhoea, salt craving
* Signs: hyperpigmentation in skin creases/lip/mouth, vitiligo, sparse axillary/pubic hair
* Ix:
* Bedside - postural hypotension, IGRA (TB inf)
* Bloods - FBC, **U&E** (↑ K+, ↓ Na+), **low glucose**, serum Ca, AI/auto-ab screen, plasma renin & aldosterone, **short snACTHen 250mcg IM test** (not Addison's if 30min cortisol _rises \>550nmol/L_
* Imaging: CXR (past TB), adrenal CT (for TB/mets)
* Mx:
* Addisonina crisis: Tx underlying cause, ICU input & alert bracelet
* Ppt factors: inf, trauma, surgery, missed steroid doses
* Ix: _Cortisol, ACTH_, U&E
* Mx: **IV hydrocortisone + IV fluids ± fludrocortisone (if primary adrenal lesion)**
* Monitor BM ± IV dextrose
* Bloods, urine, sputum culture ± abx
* Chronic: hydrocortisone + fludrocortisone (Na homeostasis), _education_ (compliance, increase steroid dose if ppt factors, follow-up
**Hyperaldosteronism** (incl. Conn's)
* Primary (HTN, ↑ Na+ ↓ K+):
* **Conn's -** aldosterone-secreting adrenal adenoma
* _Bilateral adrenal hyperplasia_
* Secondary - decreased renal perfusion (high renin --\> Na reabsorption --\> HTN) - RAS, HF, liver failure
* Ix: **aldosterone-renin ratio** (ARR), CT/MRI adrenals, adrenal vein sampling
* Conn's is very high (high aldosterone, low renin) VS BAH has both high (high aldosterone, high renin)
* Mx: spironolactone, unilateral adrenalectomy (for Conn's)
****_PH_**aeochromocytoma** #HighCatecholamines
* Cause: adrenal medulla tumour --\>↑ catecholamines (adrenaline/NA)
* Presentation: episodic headache, sweating, tachycardia, hypertension, arrhythmias, death if untreated
* 10% exta-adrenal, 10% bilateral, 10% malignant
* Ix: ECG (LVF, increased ST seg, VT), **24hr urinary metanephrines**, abdo CT/MRI
* Mx: specialist endo centre - alpha blockade = **_PH_**enoxybenzamine then beta-blockade --\> then surgery when BP controlled (after 4-6wks)
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Mx of obesity?
* Conservative measures
* Medical (none proven to provide sustainable weight loss)
* Orlistat (gut lipase inhibitor, SEs: profound flatus, diarrhoea)
* Surgical – bariatric surgery (BMI \>40 OR \>35 w/ comorbidity assoc w/ obesity)
* Needs extensive screening + commitment to long-term follow-up
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Hyperprolactinaemia - causes? presentation? Ix? Mx
Causes:
* Prolactinoma (macroprolactinoma \>6000)
* Adenoma (non-funct pituitary adenoma 1000-5000, from compression & DA lvls)
* DA antagonist (metoclopramide, anti-psychotics, methyldopa)
* Hypothyroidism (increased TRH stimulates prolactin prod)
* Physiological (pregnancy, breastfeeding)
Presentation: irreg periods, decreased libido, galactorrhoea
* Bilateral hemianopia
Ix:
* Bedside - pregnancy test, visual fields assessment
* Bloods - serum prolactin, TFTs, U&E
* Imaging - pituitary MRI
Mx:
* Asymptomatic pre-menopausal/post-menopausal with microadenoma - observation
* Symptomatic pre-menopausal/macroadenoma post-menopausal/male:
* **Dopamine agonist** (Cabergoline/Bromocriptine), 2nd line - COCP (not if want pregnancy)
* Trans-sphenoidal surgery (if visual Sx/pressure effects refractory to medical Tx)
* Follow-up: monitor prolactin, check visual fields
35
DDx for tiredness & lethargy? Ix?
DDx:
* Anaemia - PUD, altered bowel habit? occult blood loss?
* Thyroid disease - thyroiditis?
* DM - polyuria, polydipsia, weight loss
* Adrenal insufficiency
* Primary hyperparathyroidism - constipation, urinary stones, abdo pain, depression
* Hypopituitarism
* Anxiety & depression - sleep disturbances, poor appetite, recent stress
Ix:
* FBC, U&E, LFTs, CRP, bone profile, HbA1c, TFTs, haematinics
* CXR
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DDx for weight loss?
DDx:
* Thyrotoxicosis - heat intolerance, palpitations, SoB, mood (irritable/anxious), bowel habit, menses, goitre, exophthalmos, recent pregnancy
* GI-related conditions (IBD, upper GI pathology, coeliac disease, chr pancreatitis) - dysphagia, vomiting, regurgitation, abdo pain, altered bowel habit
* Eating disorders (Anorexia nervosa) - reduced eating, compulsive exercise
* Systemic conditions (malignancy) - FLAWS
Ix:
* FBC, U&E, CRP, LFTs, fasting BM, bone profile, TFTs, anti-TTG, IgA levels, haematinics
* CXR
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What are the causes of goitre?
Diffuse: Graves' disease, Hashimoto's thyroiditis, De Quervain's thyroiditis
Nodular: Multinodular goitre, adenoma, carcinoma
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Addison's + T1DM - Dx?
Schmidt's syndrome
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What is subclinical hypothyroidism?
High TSH but normal T4
Common in treated hyperT4/elderly
40
Causes of secondary HTN? Stages? Ix?
Secondary HTN:
* Renal - CKD, RAS
* Endo - Conn's, Phaeo, Cushing's (thin skin, proximal myopathy, obesity), Primary hyperparathyroidism, acromegaly
* Drugs - CS, OCP
Stages:
* 1 - 140/90
* 2 - 160/100
* 3 - 180/120
* Accelerated - 180/120 + retinal haemorrhages ± papilloedema
Ix:
* Bedside: urine dip, PCR, ECG, fundoscopy, QRISK score
* Bloods: FBC, U&E, BM, HBA1c, lipids, if young - renin-aldosterone ratio, plasma free metanephrines (phaeo)
* Imaging: CXR (LVH, pul oedema), USS KUB, renal MR angiography (RAS)
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Causes of hypokalaemia?
GI - diarrhoea, laxatives
Endo - Conn's, Cushing's syndrome, Refeeding syndrome
Drugs - thiazides, loop diuretics, insulin, PPI, steroids, gentamicin
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Correcting hyperglycaemia in DM:
* How much does 1 unit of rapid-acting insulin reduce BM by?
* How much to adjust insulin dose by at one time?
* Target insulin dose?
ASK PATIENT - rule of thumb is 100/total daily dose (TDD)
* E.g. TDS Actrapid 7 units + 18U lantus = 39U TDD --\> 100/39 = 2.5
* Generally it is roughly 3mmol/L
10%
Target glucose: 4-10 (aim for 7-8)
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DPP-4 e.g. linagliptin - massive benefit in T2DM?
Approved for use in CKD
44
Why use GLP-1 analogue e.g. exenatide/liraglutide for T2DM? Other SE? How is it given?
Induces weight loss (good for BMI \>35, \>30 + comorb)
Vomiting
SC inj
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Diabetic Ketoacidosis (DKA)
* Normal glucose transport & during starvation?
* The problem in insulin deficiency (diabetes)? How does this relate to Sx of DKA?
* Ix? Dx criteria? Mx? Monitoring Tx & hourly targets?
**Normal glucose transport:** diet --\> blood --insulin--\> hepatic glucose store --GH, Cortisol, Adrenaline, Glucagon--\> blood
* During starvating - GH, Cortisol, Adrenaline, Glucagon make sure there is enough glucose in the blood BUT liver also produces ketones
* Ketones can cross BBB providing an alternative source of fuel for the brain when low glucose
* Pancreatic beta cells --\> insulin prod --\> reduces glucose (high glucose has--\> feedback on pancreatic beta cells --\> produce more insulin)
* High insulin (associated with high glucose) --\> -ve feedback on ketone prod
**In insulin deficiency** - high glucose but unable to produce insulin + no -ve feedback on ketone prod --\> _high glucose, high ketones_
* High glucose - osmotically active (moves along concentration gradient into urine --\> pulling more water with it) --\> POLYURIA --\> DEHYDRATION
* High ketones - acidic (metabolic acidosis) --\> enzyme dysfunction --\> COMA & DEATH
DKA Ix:
* Bedside - urine dip, ECG, continuous cardiac monitoring
* Bloods - VBG, FBC, U&E, BC, BM
* Imaging - possibly CXR
DKA Dx:
* BM: ≥11mmol/L
* Ketones: ≥3mmol/L (serum) OR ≥2+ (urine)
* Acidaemia: pH \<7.3 OR Bicarb \<15mmol (ketoacidosis)
DKA Mx: A-E assessment
* **IV FLUIDS** (rehydrate)
* Bolus --\> 1L over 1hr --\> 2hr --\> 3hr --\> 4hr
* Add _40mmol KCL_ to fluids after bolus
* **0.1 U/kg/hr fixed-rate INSULIN** **infusion** (reduce ketones)
* If BM \<14 --\> start _125ml/hr 10% dextrose_
* Insulin infusion continues until ketones normalise (not BM)
* NOTE: follow local trust guidelines for DKA Tx as varies slightly between trusts
Monitor - BM, ketones, VBG (K conc)
* Hourly targets:
* Fall in BM ≥3
* Fall in ketones ≥0.5
* Rise in HCO3 ≥3
* Continue until: blood ketones \<0.6, pH \>7.3, HCO3 \>18
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Young patient, being Tx for DKA with reduced GCS, severe acidosis, relative bradycardia - what is going on?
Cerebral oedema
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Case:
* A 52yrs male presents with hypercalcaemia (bones, stones, moans, thrones, overtones)
* Bloods - corrected Ca high, PO4 low, ALP high, PTH normal
Dx?
Dx: _primary hyperparathyroidism_
* In normal parathyroid with working -ve feedback --\> PTH low due to high Ca (so here must be abnormal)
* In tertiary - PTH very high, commonly in end-stage CKD on dialysis
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What do I need to check with Ca level?
**Albumin** to obtain the _corrected Ca level_ as Ca in serum is bound to albumin so if hypo/hyperalbuminaemia then total Ca conc may not reflect free ionised Ca
52
Osteomalacia vs osteoporosis - Ca, PO4, ALP, PTH?
Osteoporosis - everything normal as this is a problem of bone density
Osteomalacia - caused by vit D deficiency so low/normal Ca, high PTH, low/normal PTH --\> soft bones
