Endocrinology Flashcards
Hormone axis phisiology
See notes
Hyperthyroidism
High thyroid hormone (T3/4)
Primary - thyroid gland pathology
Secondary - thyroid gland stimulated by excessive TSH in circulation - pathology in hypothalamus / pituitary
Hyperthyroidism causes
Graves
- TSH receptor ABs bind to TSH receptors in thyroid
Toxic multinodular goitre
- nodules develop + produce TH
Solitary toxic nodule
- usually benign adenoma
Thyroiditis
- inflammation - often initial hyperthyroid, then hypo
- DeQuervain’s - transient inflammation of thyroid after viral infection
- Hashimoto’s
- Post-partum
- Drug-induced - amiodarone, iodine, lithium
Secondary
- TSH-secreting pituitary adenomas
- TH-resistance syndrome
- hCG-secreting tumour
- Gestational thyrotoxicosis
Hyperthyroidism Px
- anxiety, irritable, sweaty, heat intolerance, tachy, palpitations, wt loss, fatigue, insomnia, diarrhoea, sexual dysfunction, brisk reflexes, AF, high output HF in elderly
- palmar erythema, lid lag, stare, lid retraction, thin hair, onycholysis, ?nodules
- oligomenorrhoea +/- infertility
Graves
- diffuse goitre
- Graves ophthalmopathy - exophthalmos, ophthalmoplegia
- pretibial myxoedema
- thyroid acropachy
Hyperthyroidism Ix
- TFTs - high T3/4, TSH low (high in 2ndary)
- Thyroid ABs - TSHR-Ab, TPO-Ab, TgAb
- CRP / ESR - thyroiditis
- baseline FBC, U/E
- US thyroid - if lump
- thyroid isotope scan
Hyperthyroidism Mx
- propranolol
- oral carbimazole, start high, titrate down, block-replace (add levo)
- propylthiouracil
- radioactive iodine
- subtotal / total thyroidectomy
Thyrotoxic crisis
- rapid T4 increase / release
- eg stress, infection, surgery, stopping anti-thyroid drugs
Px
- high temp, tachy, restless, delirium, coma, death
Mx
- IV fluids, corticosteroids, BBs, carbimazole / propylthiouracil
- potassium iodide (Lugol’s iodine)
Hypothyroidism
Low TH - T3/4
Primary - thyroid gland disease - T3/4 low, TSH high
Secondary - disease of hypothalamus / pituitary - T3/4 low, TSH low
Hypothyroidism causes
- Hashimoto’s - autoimmune inflammation, anti-TPO / anti-Tg ABs - IDDM, Addisons, pernicious anaemia associations (goitre then atrophy)
- Post-partum
- iatrogenic
- drug - carbimazole / PTU, lithium (goitre), amiodarone
- iodine deficiency
- congenital / infiltration
- secondary - tumour, surgery, radio, Sheehan’s, trauma
- Riedel’s - dense fibrous tissue (hard fixed painless goitre)
Hypothyroidism Px
- wt gain, fatigue, cold intolerance
- dry skin, coarse hair, hair loss
- fluid retention - non-pitting oedema, pleural effusions, ascites
- menorrhagia, oligomenorrhoea
- goitre
- decreased deep tendon reflexes, carpal tunnel syndrome, bradycardia, ataxia, hoarse voice, low mood
Hypothyroidism Ix
- TFTs
- thyroid ABs - anti-TPO, anti-Tg
- FBC - anaemia
Hypothyroidism Mx
- levothyroxine
Myxoedema coma
- severe hypothyroidism
Px
- confusion, coma, hypothermia, hypoglycaemia, hyponatraemia
Mx
- T3/4 replacement (T3 causes arrhythmias)
- IV glucose
- hydrocortisone if needed
- fluids / supportive care
Cushing’s syndrome
excess cortisol
Cushing’s causes
ACTH dependent (high)
- Cushing’s disease - ACTH-secreting pituitary adenoma + bl adrenal hyperplasia
- Ectopic ACTH - sg SCLC - paraneoplastic
ACTH independent (low)
- Exogenous steroids
- adrenal adenoma
Cushing’s Px
- round moon face, central obesity, proximal limb muscle wasting
- abdo striae, buffalo hump, hirsutism, acne, bruising, poor skin healing, osteoporosis
- hyperpigmentation - with high ACTH
- metabolic - HTN, T2DM, lipids,
- mental health - anxiety, depression, insomnia, psychosis rarely
Pseudo-cushing’s
- mimics cushings
- often from alcohol excess
- false positive on dex suppression test / 24hr urinary free cortisol
- insulin stress test to differentiate
Cushing’s Ix
- Bloods - hypokalaemic metabolic alkalosis, impaired glucose tolerance
Dexamethasone suppression test
- high 9am cortisol after dex administration
- low dose test - high cortisol -> Cushing’s syndrome
- high dose test -> high cortisol - adrenal adenoma / ectopic ACTH
- ACTH levels
- 24hr urinary free cortisol
- midnight + waking salivary cortisol
- CT / MRI adrenals / pituitary / TAP
Cushing’s Mx
- stop steroids
- Cushing’s - transsphenoidal resection of adenoma
- Adrenal adenoma - adrenalectomy
- adrenal carcinoma - surgery / radio / mitotane
- ectopic ACTH - surgery / metyrapone / ketoconazole
Nelson’s syndrome
- increased skin pigmentation from high ACTH from enlarging pituitary tumour - after adrenalectomy - removes -ve feedback
Hyperaldosteronism
excess aldosterone
Primary
- excess aldosterone independent of RAAS, renin low
Secondary
- high renin levels -> high aldosterone
Hyperaldosteronism causes
Primary
- Adrenal adenoma - Conn’s syndrome
- bl adrenocortical hyperplasia (more common)
Secondary
- reduced renal perfusion - eg RAS, HTN, diuretics, CCF, liver cirrhosis, ascites
Hyperaldosteronism Px
- asym
- HTN, headaches, flushing
- metabolic alkalosis - H secretion
- hypokalaemia - weakness, cramps, paraesthesia, polyuria, polydipsia, constipation, arrhythmias
Hyperaldosteronism Ix
- U/E - low K, high Na
- Aldosterone to renin ratio - high aldosterone, low renin in primary- first line
- ECG
- CT / MRI adrenals
- renal artery imaging - eg doppler, angiography
- adrenal vein sampling - which adrenal gland is producing more aldosterone
Hyperaldosteronism Mx
- oral spironolactone for bilateral adrenocortical hyperplasia
- laparoscopic adrenalectomy for adrenal adenoma
Adrenal insufficiency (AI)
Primary - low cortisol + aldosterone from adrenal cortex impairment
Secondary - low cortisol from low ACTH - pituitary / hypothalamus damage
Tertiary - lack of CRH from hypothalamus - suppression of HPA axis from exogenous steroids
AI causes
Primary
- worldwide - TB
- UK - Addison’s disease - autoimmune destruction
- mets, trauma
Secondary
- long-term steroid use
- hypothalamic / pituitary disease - tumour, trauma, surgery, sheehans…
AI Px
- tanned, toned, tired, tearful
- fatigue, muscle weakness, cramps, dizziness, fainting, thirst, wt loss, abdo pain, N+V, depression, reduced libido, vitiligo, bronze hyperpigmentation, postural hypotension
AI Ix
- bloods - low Na, high K, low glucose, high Ca, dehydration (raised urea / creatinine)
- short synacthen test - failure of cortisol to rise after synacthen
- ACTH levels
- adrenal ABs - adrenal cortex ABs, 21-hydroxylase ABs
- CT / MRI adrenals
- MRI pituitary
AI Mx
- hydrocortisone (double when ill)
- fludrocortisone
- steroid card, ID tag, IM hydrocortisone
Adrenal crisis
- acute severe adrenal insufficiency - eg infection, trauma
Px
- low GCS, hypotension, low BMs, low Na, high K
Mx
- IM/IV hydrocortisone, IV fluids, IV dextrose
Acromegaly
- excess GH - stimulates skeletal / soft tissue growth
- pituitary adenoma
- other tumours - lung / pancreas - paraneoplastic
Acromegaly Px
- headache, bitemporal hemianopia
- frontal bossing
- coarse, sweaty skin
- large nose, ears
- macroglossia
- widely spaced teeth
- large hands, feet - acral enlargement
- large jaw - prognathism
- acroparaesthesia
- decreased libido
- fatigue
- also - hypertrophic heart, HTN, T2DM, CTS, arthritis, colorectal cancer, OSA, galactorrhoea, amenorrhoea
Acromegaly Ix
- IGF-1 - raised
- OGTT - high GH after glucose
- MRI pituitary
- test visual fields, acuity
- ECG, ECHO
Acromegaly Mx
- transsphenoidal resection of adenoma
- IM octreotide
- SC pegvisomant
- Bromocriptine
T1DM
Autoimmune destruction of beta cells in pancreas leading to lack of insulin production
T1DM Px
- asym
- DKA
- polyuria
- polydipsia
- wt loss- asym
- DKA
- polyuria
- polydipsia
- wt loss
T1DM Ix
- cap BMs
- urine dip - glucose, ketones
Serum blood glucose
- fasting >7, IGT 6.1-6.9
- random >11.1, IGT 7.8-11
- if asym - meet criteria on 2 separate occasions
HbA1c (not helpful in T1DM)
- >6.5% (48) - rpt if asym
- IGT (42-48)
OGTT
- >11.1 2hrs after 75g glucose - diagnostic
- consider c-peptide, auto-ABs
T1DM Mx
- monitor HbA1c every 3-6mo
- self-monitor BMs - before every meal / bed - 5-7 on waking, 4-7 before meals
S/C insulin
- basal-bolus regime
- insulin pumps
- pancreas transplant
- FreeStyle libre
- closed loop system
T1DM sick day rules
- Don’t stop insulin
- Check BMs more frequently
- Consider checking ketones
- Maintain normal meal pattern if possible - carb drinks if necessary
- Drink plenty fluids
T1DM Cx
- insulin - hypos, lipohypertrophy, wt gain
Macrovascular
- atherosclerosis, stroke, IHD, PVD
Microvascular
- diabetic retinopathy, nephropathy, neuropathy, infections
Acute
- DKA, HHS, hypos
VRIII / sliding scale
- to control BMs
- actrapid infusion in one arm
- infusion 5% dextrose + KCl in other arm
- stop OHAs, short acting insulins, pre-mixed insulins
- continue long-acting insulins
Indications
- no oral intake
- vomiting
- NBM
- severe illness, eg sepsis
more details in notes….
Prescribing insulin
Who needs
- T1DM
- DKA
- OHAs not enough
Calculating TDD
- total no units over 24hrs on VRIII
- 0.5units/kg/24hrs
- start on small dose - 6-8 units long-acting / mixed, 4-6 units short acting with meals
How to split
- long acting only - extra boost
- mixed BD insulin - eg T2DM
- basal-bolus - eg T1DM
T2DM
increased insulin resistance and decreased production, leading to persistent hyperglycaemia
RFs
- non-modifiable - older age, Black / South Asian, FHx
- modifiable - obesity, sedentary lifestyle, high sugar diet
T2DM Px
- asym
- fatigue
- polyuria, polydipsia
- wt loss
- opportunistic infections - eg oral thrush
- slow wound healing
- acanthosis nigricans
T2DM Ix
- cap BM, urine dip
Serum blood glucose
- fasting >7, IGT 6.1-6.9
- random >11.1, IGT 7.8-11
- if asym - meet criteria on 2 separate occasions
HbA1c
- >6.5% (48) - rpt if asym
- IGT 42-48)
- measure every 3-6mo, aim for 48 in new dx, or 52 if on 1+ med that might cause hypoglycaemia (eg sulfonylurea)
OGTT
- >11.1 2hrs after 75g glucose - diagnostic
- bloods, FBC, U/E, LFTs etc
T2DM Mx overall
- diet (eg low glycaemic index), exercise, wt loss
- HTN - ramipril (if black - ARB)
- atorvastatin 20mg if QRISK >10%, 80mg if pre-existing disease
- oral hypoglycaemic agents
- insulin
OHAs
1st - metformin, add SGLT-2 if CVD / QRISK
2nd - add sulfonylurea / pioglitazone / DPP4 inhibitor / SGLT-2 inhibitor
3rd - triple therapy metformin + 2 second line drugs / insulin therapy / switch one drug to GLP-1 mimetic
…see notes for more details…
T2DM Mx 1st line
- metformin - titrate up slowly, modified release if GI sx
- if CVD / HF / QRISK>10% - add SGLT-2 inhibitor (add at any point if these develop)
if metformin CI’d
- SGLT-2 (if CVD/HF/QRISK)
- or DPP4/pioglitazone/sulfonylurea
T2DM Mx 2nd line
- add 2nd drug if HbA1c rises to 58
- continue metformin
- add sulfonylurea / pioglitazone / DPP4 / SGLT-2 (criteria)
T2DM Mx 3rd line
Triple therapy
- Metformin + DPP4 + sulfonylurea
- Metformin + pioglitazone + sulfonylurea
- Metformin + pioglitazone/sulfonylurea/DPP4 + SGLT-2 (if criteria met)
Insulin therapy
- consider if HbA1c>58 after >3mo dual oral therapy - humulin 1, continue metformin
T2DM further mx
If triple therapy fails and BMI>35, or if BMI<35 and insulin not suitable:
- Switch one drug to GLP-1 mimetic - only continue if reduction of >11 (1%) in HbA1c and weight loss >3% in 6mo
- Only add to insulin under specialist care
T2DM sick day rules
- Some OHAs may be stopped, restart once feeling better
- Metformin - stop if risk of dehydration
- Sulfonylureas - increase hypo risk
- SGLT-2 - check ketones
- GLP-1 - stop if dehydrated
- Monitor BMs more
DVLA DM
Group 1
- insulin - can drive if has hypo awareness, <1 bad hypo in last 12mo, no visual impairment
- tablets - no need to notify DVLA
- diet controlled - no need to notify
Group 2 must meet
- no severe hypos <12mo
- control of condition, monitoring etc
- understand hypo risks
- no cx of DM
DM ramadam
- Try to eat meal with long-acting carbs prior to sunrise (Suhoor)
- Use BM monitor
- If taking metformin - 1/3 dose before sunrise, 2/3 after sunset (Iftar)
- Switch OD sulfonylureas to after sunset
- If taking BD gliclazide - take larger proportion of dose after sunset
- No adjustments for pioglitazone
Diabetic neuropathy
- Glove + stocking sensory loss
- If painful - neuropathic pain meds, pain clinic
Also GI autonomic neuropathy
- Gastroparesis - erratic blood control, bloating, vomiting, Mx with metoclopramide, domperidone, erythromycin
- Chronic diarrhoea
- GORD
Diabetic foot disease
- from neuropathy / PAD
- loss of sensation, absent foot pulses, reduced ABPI
- calluses, ulcers, Charcot’s arthropathy, cellulitis, osteomyelitis,
- screen annually - palpate pulses, 10g monofilament
Biguanides - metformin
- reduce gluconeogenesis, increase insulin sensitivity
S/Es
- D+V
- lactic acidosis
When to stop
- not E+D
- AKI
- raised lactate
- before IV contrast
SGLT-2 inhibitors - cana/empa/dapa-gliflozin
- inhibit glucose resorption, increase urinary glucose loss
S/Es
- genital candidiasis, Fournier’s gangrene, UTIs
- increased UO, freq
- wt loss, DKA / EKA (stop on admission to hospital)
Thiazolidinediones / glitazones - pioglitazone, rosiglitazone
- increase insulin sensitivity, decrease liver glucose production
S/Es
- wt gain, fluid retention, HF, liver impairment
- bladder Ca risk
- fracture risk
Sulfonylureas - gliclazide, glimepiride
- stimulate insulin secretion from pancreas
S/Es
- wt gain
- hypos
- hyponatremia
Meglitanides work the same
DPP4 inhibitors - sita/lina/saxa-gliptin
- enhance incretin effect (increased insulin response to oral glucose) - increase insulin, lower glucagon
S/Es
- nausea, headaches
- pancreatitis
GLP-1 agonists - exanatide, liraglutide
- injectable S/C - increase incretin effect
S/Es
- nausea, GI sx, reduced appetite
- pancreatitis, AKI, wt loss
DKA
- diabetic emergency of high ketones, high BMs, acidosis
- lack of insulin, no glucose uptake, body starved, converts lipids into ketones - dissolve into blood, dehydration from this (also vomiting, glucose secretion in kidneys)
- eg first px of T1DM, missing insulin dose, stress (surgery / infection)
DKA Px
- pear drop breath
- Kussmaul’s respiration
- reduced LOC
- vomiting
- abdo pain
- dehydration - dry mucous membranes, slow CRT, tachycardia, hypotension
DKA Ix
- bloods - BMs, ketones, VBG, FBC, U/E, CRP, LFTs, ?cultures, lab BM
- Dx - BM>11, ketones>3, pH<7.3
- urine dip ketones
- look for infection source, eg CXR
DKA Mx
- Fluids - IV 0.9% NaCl
- insulin infusion - actrapid 0.1units/kg/hr
- glucose - 10% dextrose 125ml/hr once BM<14
- Potassium - 40mmol/L KCl if 3.5-5.5
- infection - tx cause
- chart fluid balance
- ketones, pH, bicarb - monitoring
DKA Cx
- cerebral oedema
- pulmonary oedema
- cardiac arrhythmias, hypokalaemia
- ARDS, AKI etc
HHS
- hyperglycaemia, hyperosmolality, no ketosis
- results in osmotic diuresis, severe dehydration, electrolyte deficiencies
- potential causes - illness, dementia, sedative drugs, MI, surgery
HHS Px
- sx onset over days
- dehydration
- polyuria, polydipsia
- lethargy
- N+V
- altered consciousness
- focal neurology
- hyperviscous blood -> MI, stroke, peripheral arterial thrombosis
HHS Ix
Bloods
- FBC, U/E, glucose, VBG, CRP, cultures etc
- high osmolarity >320 (2xNa + glucose + urea)
- high glucose >33
- no ketones, low K/Mg, hypo/hypernatraemia, normal anion gap, pH >7.3
- ix cause, eg CXR
Dx criteria
- Serum osmolarity >320
- Serum glucose >33
- Profound dehydration (elevated urea:creatinine ratio)
- No ketoacidosis
HHS Mx
- 0.9% NaCl - 0.5-1l/hr
- correct electrolytes
- insulin - give if BM stops falling with fluids
- LMWH for VTE prophylaxis
Hypoglycaemia
BM <4
Hypoglycaemia causes
EXogenous drugs - insulin, OHAs, alcohol, quinine, quinolones
Pituitary insufficiency - no GH/cortisol
Liver failure - no glycogen stores
Adrenal failure - no cortisol
Insulinomas / immune hypoglycaemia
Non-pancreatic neoplasms
Hypoglycaemia Px
Adrenergic
- sweating, palpitations, tremor, anxiety/irritable, hunger, feel cold
Neuroglycopenic
- confusion, dizziness, tingling, blurred vision, slurred speech, headache, N+V, seizure, coma
- fatigue, weakness
Hypoglycaemia Ix
- CBG
- ix for cause…
Insulin vs C-peptide level
Hypoglycaemia Mx
- conscious, orientated - oral glucose
- conscious, confused, IV access - 100mls 20% / 200mls 10% glucose
- conscious, confused, no IV access - 1mg IM glucagon
- unconscious / fitting - as above
- give long-acting carb on recovery
- review meds etc
Hyperglycaemia
- high BMs
Causes
- decompensated / undiagnosed DM
- stress - acute illness
- Cushing’s, pheochromocytoma, acromegaly, hyperthyroidism
- meds - eg steroids, BBs
Hyperglycaemia Px
- weakness, headache, blurred vision, polyuria, polydipsia, palpitations, N+V, abdo pain, drowsiness, seizure, coma
Hyperglycaemia Ix
- CBG, VBG, bloods, HbA1c
Hyperglycaemia Mx
- Novarapid if need to bring down BM
- diabetic team review
- meds review
- tx cause
Hyperparathyroidism
high PTH - raises blood Ca by
- resorbing Ca from bones
- reabsorbing Ca in kidneys
- absorb Ca in intestines - by increasing vit D activity
Primary hyperparathyroidism
- excess PTH production from parathyroid tumour -> hypercalcaemia
- mostly solitary adenoma, also hyperplasia, multiple adenoma, carcinoma
Primary hyperparathyroidism Px
- asym
- bones, stones, moans, groans
- short QT
- HTN, MEN1/2 associations
Primary hyperparathyroidism Ix
- ECG - short QT
- Bloods - high PTH, high Ca, low phosph, raised ALP
- technetium-MIBI subtraction scan
- XR - pepperpot skills, osteitis fibrosa cystica
Primary hyperparathyroidism Mx
- total parathyroidectomy - risk of low Ca / recurrent laryngeal nerve injury
- calcimimetic (cinacalcet)
- bisphosphonate - alendronate
Secondary hyperparathyroidism
- high PTH in response to low Ca
causes
- vit D deficiency - eg dietary, Crohn’s
- CKD - lack of Ca resorption
Secondary hyperparathyroidism Px
- Sx of CKD / vit D deficiency
Secondary hyperparathyroidism Ix
- Bloods - low/normal Ca, high PTH, low vit D
Secondary hyperparathyroidism Mx
- Tx cause - vit D replacement, renal transplant
- maybe cinacalcet
Tertiary hyperparathyroidism
- after long period of secondary, hyperplasia of PTH glands -> autonomously produce high PTH
Px
- as primary
Ix
- bloods - high PTH, high Ca
Mx
- total / subtotal parathyroidectomy
- cinacalcet
Hypoparathyroidism
Low PTH, leading to low Ca
Primary hypoparathyroidism
Low PTH due to PT gland failure
Causes
- DiGeorge syndrome
- Autoimmune cause
- Lack of PT gland at birth
- Genetic mutations
Secondary hypoparathyroidism
- low PTH after damage
Causes
- Parathyroidectomy / thyroidectomy (most common)
- Radiation
- Hypomagnesaemia - Mg required for PTH secretion
Pseudohypoparathyroidism
- End-organ resistance to PTH - failure of target cell response
Pseudopseudohypoparathyroidism
- Same phenotypic defects as pseudo- without abnormalities of Ca metabolism
Hypoparathyroidism Px
Hypocalcaemia - SPASMODIC
- Spasms - Trousseau’s
- Perioral paraesthesia
- Anxious, irritable, irrational
- Seizures
- Muscle tone increase in smooth muscle - wheeze
- Orientation impaired and confused
- Dermatitis
- Impetigo herpetiformis - reduced Ca and pustules in pregnancy
- Chvostek’s sign, cataracts, cardiomyopathy (long QT)
may see papilloedema
Cutaneous signs
- dry scaly puffy skin, brittle nails, coarse hair
Pseudo / pseudopseudo
- short stature, short 4/5th metacarpals, subcut calcification, intellectual impairment
Hypoparathyroidism Ix
- bloods - low serum Ca, PTH low (high in pseudo), ALP, phops, U/E, parathyroid ABs
- ECG
Pseudo
- measure urinary cAMP and phosph after PTH infusion - no increase in pseudo, increase in others
Hypoparathyroidism blood results
Hypo - normal appearance, low PTH, low Ca, high phosph
Pseudo - skeletal defects, high PTH, low Ca, high phosph
Pseudopseudo - skeletal defects, normal PTH, normal Ca, normal phosph
Hypoparathyroidism Mx
- IV calcium if severely low
- Ca supplements
- calcitriol - active vit D
SIADH
- excess ADH secretion -> increased water reabsorption from CDs, dilutes plasma, hyponatraemia
SIADH causes
- SCLC, pancreas, prostate ca
- stroke, SAH, SDH, meningitis, encephalitis, abscess
- TB, pneumonia, HIV
- sulfonylureas, SSRIs, TCAs, carbamazepine
- PEEP, porphyrias, post-op, endurance sport
SIADH Px
- hyponatraemia sx
- asym
- headache, fatigue, muscle aches, cramps, confusion, seizures, low GCS
Primary polydipsia (a DDx of SIADH)
- excessive water consumption, no cause
- euvolaemic hyponatraemia, but low urine Na/osmolality also
SIADH Ix
- euvolaemic
- FBC, U/E - low Na, low serum osmolality
- urine studies - high Na, high osmolality >100
- Ix for cause - CXR, CT TAP, short synacthen test, TFTs, serum cortisol
SIADH Mx
- hypertonic saline if neuro sx
- hyponatraemia tx
- Tx cause, eg meds, infection
- fluid restriction
- tolvaptan - vasopressin receptor antagonist
- demeclocycline - reduces CD response to ADH
- correct Na slowly
Diabetes insipidus (DI)
- hyposecretion / insensitivity to ADH - impaired water reabsorption - pass large volumes of dilute urine
Cranial DI - reduced ADH secretion from post pit
Nephrogenic DI - impaired response of kidney to ADH
DI causes
Cranial DI
- idiopathic, head injury, pituitary surgery, Wolfram’s syndrome, HHC, tumours, genetics
Nephrogenic DI
- meds (lithium), genetics, high Ca, low K, PKD, demeclocycline, sickle cell, CKD
DI Px
- polyuria
- polydipsia, chronic thirst
- nocturia
- infants - irritable, failure to thrive, crying, fever, anorexia
- dehydration
- postural hypotension
DI Ix
- urine collection - >3L/24hrs
- high/normal serum osmolality
- low urine osmolality
water deprivation test
- 8hr fluid restrict -> low urine osmolality
- administer desmopressin -> high urine osmolality in cranial DI, low in nephrogenic
- MRI head
DI Mx
Cranial DI
- oral desmopressin
Nephrogenic DI
- tx cause
- low salt / protein diet
- thiazide diuretics
- NSAIDs - ibuprofen
Pheochromocytoma
- catecholamine secreting tumour of adrenal glands
- secrete adrenaline in bursts -> intermittent sx
- more common in MEN II, NFT1, von-Hippel-Lindau
- 10% bl, 10% cancerous, 10% outside adrenal gland
- 30-40% genetic
Pheochromocytoma Px
- periodic sx
- anxiety, sweating, headache, tremor, palpitations, HTN, tachycardia
Pheochromocytoma Ix
- plasma free metanephrines
- 24hr urine catecholamines
- CT / MRI
- genetic testing
Pheochromocytoma Mx
- alpha blockers - phenoxybenzamine, doxazosin
- BBs
- partial adrenalectomy
Thyroid cancer
- cancer of thyroid gland
- papillary, follicular, anaplastic, lymphoma, medullary cell
RFs
- radiation exposure
- hx of goitre, nodule, thyroiditis, FHx, female, Asian
Thyroid cancer Px
- thyroid nodule
- hard / irregular thyroid
- cervical lymphadenopathy
- mets to lungs, brain, hepatic, bone
- hoarse voice
Thyroid cancer Ix
- fine needle aspiration biopsy / cytology
- Bloods - TFTs
- US thyroid
- thyroglobulin
Thyroid cancer Mx
- papillary / follicular - total thyroidectomy / radioactive iodine
- anaplastic / lymphomas - external radiotherapy
- medullary - thyroidectomy, lymph node removal
- levothyroxine - keep TSH reduced
- chemotherapy
Carcinoid tumour
- neuroendocrine malignancies - produce serotonin, bradykinin, histamine, prostaglandins, others….
- neuroendocrine tumour - neoplasm of NE cells
Carcinoid syndrome - GI carcinoid tumour metastasises to liver
Carcinoid tumour Px
- asym
- pain, wt loss, mass, vague R abdo discomfort
- CCF, face/neck flushing, appendicitis, obstruction
- RUQ pain
- diarrhoea, hypotension
- Cushing’s
Carcinoid tumour DDx
GI stromal tumour (GIST)
Carcinoid tumour Ix
- Liver USS
- 24hr urinary HIAA - raised (serotonin metabolite)
- ECHO
- CXR / CT / MRI
Carcinoid tumour Mx
- octreotide
- surgical resection
- antihistamines - cyproheptadine
Carcinoid crisis
- tumour outgrows blood supply / handled too much in surgery - mediators flow out
- vasodilation, hypotension, tachycardia, bronchoconstriction, hyperglycaemia
Mx
- high dose octreotide
Prolactinoma
- benign tumour of pituitary gland that secretes prolactin
Pituitary adenomas classified by:
- size - micro<1cm, macroadenoma >1cm
- hormonal status - secretory/functioning, non-secretory/functioning
Prolactinoma patho
- leads to hyperprolactinaemia
- women - raised prolactin, inhibits FSH/LH -> menstrual dysfunction, galactorrhoea
- men - raised prolactin, secondary hypogonadism, reduced libido, erectile dysfunction
- prolactin release inhibited by dopamine
Hyperprolactinaemia causes
- prolactinoma
- pregnancy
- acromegaly
- PCOS
- non-functioning pituitary tumour - compresses pituitary stalk
- meds - antidopaminergics, antidepressants, metoclopramide, domperidone, haloperidol
- head injury
- primary hypothyroidism
Prolactinoma Px
- headache
- bitemporal hemianopia
Women
- irregular menstruation, infertility, galactorrhoea, osteoporosis
Men
- impotence, loss of libido, galactorrhoea
Prolactinoma Ix
- pituitary blood profile - inc GH, prolactin, ACTH, FSH, LH, TFTs
- visual fields testing
- MRI head
Prolactinoma Mx
- dopamine agonist - cabergoline, bromocriptine
- transsphenoidal pituitary resection
Hyperkalaemia
- high serum K
Classification
- Mild - 5.5-5.9
- Moderate - 6.0-6.4
- Severe - >6.5
Hyperkalaemia causes
Renal
- AKI, CKD, Addison’s,
- drugs - spironolactone, ACEi, ARBs, NSAIDs, ciclosporin, heparin
Increased circulation of K
- exogenous - foods, blood transfusion
- endogenous - rhabdo, crush, burns, tumour lysis syndrome
IC->EC
- DKA, metabolic acidosis
- digoxin toxicity, BBs, sux, theophylline
Pseudo
- haemolysed sample
Hyperkalaemia Px
- asym
- Palpitations
- Chest pain
- Dizzy
- Muscle weakness
- Stiffness
- Fatigue
Hyperkalaemia Ix
- VBG, U/E, FBC, LFTs, BMs
- serum cortisol / aldosterone if adrenal insufficiency suspected
ECG
- tall tented T waves
- flattened P waves
- PR prolongation
- broad QRS
- sine wave pattern
- then VF
Hyperkalaemia Mx
- ABCDE
- remove cause
- calcium gluconate / chloride (if >6.5 / ECG changes)
- insulin + dextrose - 10-20 units in 500mls of 10% glucose
- salbutamol
- furosemide, calcium resonium (GI binder), sodium bicarb, dialysis
Hypokalaemia
serum K<3.5
Hypokalaemia causes
- not enough K in fluids
- GI losses - D+V, malabsorption, laxatives, high output stoma, poor oral intake / inadequate feed
- Renal losses - genetic syndromes, Conn’s, Cushing’s, renal tubular acidosis, furosemide, thiazides
- Intracellular shift - alkalosis, insulin, adrenaline, salbutamol
Hypokalaemia Px
- asym
- Muscle weakness
- Hypotonia
- Hyporeflexia
- Tetany
- Constipation
- Palpitations
- Light-headed
Hypokalaemia Ix
- U/E
ECG
- small / inverted T waves
- Long PR
- prominent U waves
- ST depression
- long QT, Torsades de Pointes
Hypokalaemia Mx
- tx cause
Mild >3.1
- oral sando-K
Severe <3.1
- IV KCl - no quicker than 10mmol/hr
- lower - ITU discussion
Hypercalcaemia
- normal serum Ca 2.1-2.6
Classification
- mild 2.65-3 - asym
- moderate - 3.01-3.40 - asym/sx
- severe >3.40 - arrhythmias, coma
Hypercalcaemia causes
High/normal PTH
- hyperparathyroidism
Low PTH
- malignancy - SCLC, bone mets, myeloma, ectopic
- sarcoidosis, TB
- Drugs - Ca/vit D, antacids, thiazides, lithium, theophylline
- rhabdo
- adrenal insufficiency, thyrotoxicosis, phaeo
Hypercalcaemia Px
Bones
- bone pain, fractures, osteopenia, osteomalacia, osteoporosis
Stones
- renal / biliary stones
Groans
- abdo pain, pancreatitis, malaise, nausea, constipation, polydipsia, dehydration, confusion
Moans
- depression, anxiety, cognitive dysfunction, insomnia, coma
- sx of malignancy etc
Hypercalcaemia Ix
- hydration
- Bloods - bone profile, vit D, ALP, U/E
- ECG - short QT, brady, 1st HB
- CXR, isotope bone scan, CT / MRI
- serum ACE (sarcoidosis)
Hypercalcaemia Mx
- 0.9% NaCl 4-6l/24hrs
- IV bisphosphonates - zolendronate
- dialysis
- cinacalcet, denosumab, calcitonin, prednisolone
Hypocalcaemia
Ca <2.1
Hypocalcaemia causes
- total thyroidectomy / parathyroidectomy / hypoparathyroid
- vit D deficiency
- CKD
- low Mg (PPIs)
- pancreatitis
- rhabdo, tumour lysis syndrome
- Loop diuretics, steroids, gent, phosphates, theophylline
- massive transfusion
Hypocalcaemia Px
SPASMODIC
- Spasms - Trousseau’s
- Perioral paraesthesia
- Anxious, irritable, irrational
- Seizures
- Muscle tone increase in smooth muscle - wheeze
- Orientation impaired and confused
- Dermatitis
- Impetigo herpetiformis - reduced Ca and pustules in pregnancy
- Chvostek’s sign, cataracts, cardiomyopathy (long QT)
may see papilloedema
Hypocalcaemia Ix
- Bloods - bone profile, U/E, Mg, vit D, PTH, amylase, CK
- ECG - prolonged QT
Hypocalcaemia Mx
Mild >1.9
- oral sandocal / adcal
- vit D - colecalciferol
- IV Mg if low
- may need calcitriol in para/thyroidectomy
Severe <1.9 / sx
- cardiac monitor
- calcium gluconate bolus / infusion
- tx cause
- ?endo referral
Hypophosphataemia
low serum phosph <0.8 (normal 0.8-1.5)
Hypophosphataemia causes
- redistribution into cells - resp alkalosis, insulin, adrenaline
- increased urinary excretion - acidosis, DKA, hyperparathyroid
- decreased intestinal absorption - antacids, vit D deficiency, D+V, malabsorption
- refeeding syndrome
- chronic alcohol
- acute liver failure
Hypophosphataemia Px
- Asymptomatic
- Myopathy, rhabdomyolysis, weakness
- Resp failure
- Arrhythmias, cardiomyopathy
- Irritable, confused, hallucinations, lethargy, seizure, coma
- Rickets / osteomalacia if chronic
Hypophosphataemia Ix
- bloods - bone profile, Ca, phosph, U/E
Hypophosphataemia Mx
- oral phosphate sandoz
- IV phosphates polyfusor / sodium glycerophosphate
Hypomagnesaemia
- low serum Mg (normal 0.7-1.05)
Hypomagnesaemia causes
- refeeding syndrome
- D+V, high output stoma
- alcoholism
- hypercalcaemia
- SIADH, DKA, aldosteronism
- renal losses
- post-parathyroidectomy
- drugs - diuretics, gent, PPIs
Hypomagnesaemia Px
- asym
- irritable, lethargy
- N+V
- confusion, depression, psychosis
- tremors, cramps, tetany, weakness, seizures
Hypomagnesaemia Ix
- ECG - PR prolongation, ST depression, altered T waves, ventricular arrhythmias, eg VF
- Bloods - U/E, Ca, Mg
- urinary Mg
Hypomagnesaemia Mx
0.4-0.7
- oral Mg salts
<0.4 / tetany, arrhythmias, seizures
- IV Mg
Hypernatraemia
- serum Na >145
Hypernatraemia causes
Hypovolaemic hypernatraemia - salt + water lost, but more water
- D+V, sweating, burns, loop diuretics, osmotic diuresis
Normovolaemic hypernatraemia - loss of purely water
- impaired thirst / water intake -> dehydration - dementia, decreased access to water
- diabetes insipidus
Hypervolaemic hypernatraemia - rare, iatrogenic
- hypertonic saline
- hypertonic dialysis
- hyperaldosteronism
Hypernatraemia Px
- Thirst, lethargy, weakness, nausea, loss of appetite
- Severe - myoclonic jerks, intracranial haemorrhage, coma, death
Hypernatraemia Ix
- assess fluid status
- bloods - U/E, glucose, Mg, Ca
- urine / serum osmolalities
Hypernatraemia Mx
- tx cause
- oral fluids
- 0.9% NaCl (unless hypervolaemic)
- correct <0.5mmol/L/hr (cerebral oedema risk)
Hyponatraemia
- low serum Na <135
Severity
- Mild – 130-134
- Moderate – 120-129
- Severe – <120
Hyponatraemia causes
Hypovolaemic hyponatraemia - loss of Na and water
- diuretics, Addisonian crisis, D+V, MDMA, pancreatitis
- exercise induced hyponatraemia (EAH)
Euvolaemic hyponatraemia - volume expansion, no oedema
- SIADH
- hypothyroidism
- beer potomania
- adrenal insufficiency
Hypervolaemic hyponatraemia - Na and water increase, more water
- HF, liver failure, nephrotic syndrome, excessive water consumption
Also classified by urine osmolality / Na conc - see notes
False hyponatraemia
- lab results show low Na, but no hypotonicity
- eg glucose - draws water into blood - appears like Na low
Hyponatraemia Px
- asym
early
- Headache
- Lethargy
- N+V
- Dizziness
- Confusion
- Muscle cramps
late
- seizures
- coma
- cardio-respiratory arrest
Hyponatraemia Ix
- fluid status
- U/E
- serum / urine osmolality
- urinary sodium
- if fluid overloaded - BNP, LFTs, urine dip, protein:creatinine ratio
- TFTs, 9am cortisol
Hyponatraemia Mx
Severe sx, Na <120
- HDU / ITU
- hypertonic saline - 3% NaCl
Hypovolaemic
- 0.9% NaCl
Euvolaemic
- fluid restrict 500-1000ml/d
- tolvaptan / demeclocycline
Hypervolaemic
- fluid restrict 500-1000ml/d
- furosemide / tolvaptan
Osmotic demyelination syndrome
- from rapid over-correction of hyponatraemia
- astrocyte/oligodendrocyte apoptosis -> demyelination
Px
- irreversible sx
- dysarthria, dysphagia, paralysis, seizures, confusion
- coma - locked-in-syndrome
Mx
- avoid - Na levels raised by 8mmol/L/24hrs
Bartter’s syndrome
- autosomal recessive disease of severe hypokalaemia
- defective NKCC2 transporter - like lots of furosemide
Px
- childhood - failure to thrive
- polyuria, polydipsia
- hypokalaemia
- normotension
- weakness
Insulinoma
- NE tumour derived from pancreatic Islets of Langerhans cells
Px
- hypoglycaemia - early morning, just after meal
- rapid weight gain
Ix
- high insulin, raised proinsulin:insulin ratio
- high c-peptide
- supervised prolonged fasting
- CT pancreas
Mx
- surgery
- diazoxide / somatostatin
Liddle’s syndrome
- autosomal dominant - disordered Na channels in distal tubules -> increased Na reabsorption
- HTN, hypokalaemic alkalosis
Mx
amiloride / triamterene
Maturity-Onset Diabetes of the Young (MODY)
- monogenic diabetes, autosomal dominant inheritance
- impaired insulin secretion
Px
- mild, non-ketotic hyperglycaemia
Ix
- genetic testing
Mx
- Sulfonylurea / insulin / nothing depending on type
Multiple endocrine neoplasia
- overgrowth / tumour of endocrine glands - benign / malignant - autosomal dominant
MEN-1
- parathyroid, pituitary, pancreas, adrenal, thyroid
- commonly px with hypercalcaemia
MEN-2a
- medullary thyroid cancer, parathyroid, phaeo
MEN-2b
- medullary thyroid cancer, phaeo, marfanoid body habitus, neuromas
Gynaecomastia
- abnormal breast tissue in males - increase in oestrogen:androgen ratio
Causes
- Physiological: normal in puberty
- Syndromes with androgen deficiency: Kallman’s, Klinefelter’s
- Testicular failure: e.g. mumps
- Liver disease
- Testicular cancer e.g. seminoma secreting hCG
- Ectopic tumour secretion
- Hyperthyroidism
- Haemodialysis
- Drugs - spironolactone, cimetidine, digoxin, cannabis, finasteride, GnRH agonists, oestrogens, anabolic steroids
Obesity
BMI = kg/m^2
Mx
- diet, exercise
- oristat, liraglutide
- surgical
Sick euthyroid syndrome
- low TSH, T3, T4 in pt who has non-thyroidal illness, but are actually euthyroid
- reverses on recovery from systemic illness
Subclinical hyperthyroidism
- normal T3/4, TSH low
- may lead to AF / osteoporosis, dementia
Causes
- multinodular goitre
- excessive thyroxine
Mx
- TSH normalises alone
- low dose anti-thyroid 6mo - induce remission
Subclinical hypothyroidism
- TSH raised, T3/4 normal
- tends to be asym
Mx
- levothyroxine
Thyroid eye disease
- affects 25-50% pts with graves
- autoimmune response, retro-orbital inflammation, collagen deposition in muscles
Thyroid eye disease Px
- May be eu/hypo/hyperthyroid
- Exophthalmos
- Conjunctival oedema
- Optic disc swelling
- Ophthalmoplegia
- Eyelid retraction
- Inability to close eyelids -> sore, dry eyes
Thyroid eye disease Mx
- stop smoking
- topical lubricants
- steroids
- radiotherapy
- surgery
Urgent ophthal review if
- Unexplained deterioration in vision
- Change in colour vision
- Hx of eye popping out – globe subluxation
- Corneal opacity
- Cornea visible when eyelids closed
- Disc swelling
Thyroid eye disease Cx
Exposure keratopathy
- FB sensation, pain, photophobia
- corneal scarring / ulcer
Optic neuropathy
- enlarged extraocular muscles compress optic nerve
Strabismus / diplopia
- fibrosis / enlargement of extraocular muscles
Pregnancy - thyroid problems
Hyperthyroid
- PTU
Hypothyroid
- thyroxine - titrate to TFTs (may need to increase)
Subacute thyroiditis (De Quervain’s thyroiditis)?
Subacute thyroiditis thought to occur following viral infection typically presents with hyperthyroidism
Typically 4 phases:
Phase 1- lasts 3-6 weeks- hyperthyroidism, painful goitre, raised ESR
Phase 2- 1-3 weeks- euthyroid
Phase 3- weeks-months- hypothyroidism
Phase 4- Thyroid structure and function back to normal
Investigations- thyroid scintigraphy- globaly reduced uptake of iodine-131
Management-
Usually self limiting
Thyroid pain may respond to aspirin or other NSAIDs
More severe cases- steroids particularly if hypothyroidism