Endocrine and metabolic Flashcards
T1DM
- diagnosis
- management
Random blood glucose >11.1mmol/L
Management:
1st line - basal bolus regime:
1 long-acting insulin (e.g. Levemir) taken regular (bolus)
1 rapid-actinging insulin (e.g. novorapid, Humalog) taken before meals
T2DM
- diagnosis
- management
- what point is considered ‘pre-diabetes’
T2DM is diagnosed with an Hba1c >48 mmol/L and/or a fasting blood glucose >7 mmol/L. If the patient is asymptomatic, two separate abnormal test results are required.
Management:
* Hba1c >48 mmol/L despite lifestyle changes → metformin first-line
* HbA1c >58 mmol/L despite maximal dose metformin → dual therapy
* HbA1c >58 mmol/L despite dual therapy → triple therapy or insulin therapy + metformin
* First-line insulins in T2DM are intermediate acting (e.g., Humulin I).7.
Pre-diabetes is between 42-47mmol/mol
Diabetic peripheral neuropathy: management
1st line: amitrityline, duloxetine, gabapentin or pregablin
Rescue therapy: tramadol
Localised pain: topical capsaicin
Pain management clinics
Diabetes drug class and side-effects
Biguanides (metformin)
Sulfonylureas (gliclazide)
SGLT-2 inhibitors (dapagliflozin)
DPP-4 inhibitors (linagliptin, sitagliptin)
Thiazolidinediones (pioglitazone)
GLP-1 agonists (liraglutide, exenatide)
**Biguanides (metformin): ** Nausea and vomiting, abdominal pain, diarrhoea
Lactic acidosis
Sulfonylureas (gliclazide): Weight gain, hypoglycaemia
SGLT-2 inhibitors (dapagliflozin) UTIs, Fournier’s gangrene, DKA
DPP-4 inhibitors (linagliptin, sitagliptin):
Pancreatitis
**Thiazolidinediones (pioglitazone): **
Fluid retention, weight gain
Contraindicated in heart failure
Bladder cancer
GLP-1 agonists (liraglutide, exenatide):
Nausea and vomiting, reduced appetite
Pancreatitis
Addisons disease
- pathophysiology
- causes
- investigations
- management
Pathophysiology: caused by decreased production of the steroid hormones cortisol (glucocorticoid) and aldosterone (mineralocorticoid) by the adrenal gland.
Causes:
* Autoimmune (developed world)
* Tuberculosis (developing world)
* Haemorrhage (Waterhouse–Friderichsen syndrome)
Investigations:
* U&Es—Hyperkalaemia, hyponatraemia
* Blood glucose—Hypoglycaemia is common.
* Early morning cortisol is initial test.
* The short Synacthen test is the gold standard.
Management:
* Glucocorticoid—Hydrocortisone 2 × –3 × daily, with double dose during acute illness
* Mineralocorticoid—Fludrocortisone once daily
Hyperthyroidism:
TFTs for subclinical, primary and secondary
Mx
Subclinical: T4 ↔ TSH ↓
Primary: T4 ↑ TSH ↓
Secondary T4↑ TSH ↑ or ↔
TSH receptor antibodies (Graves’ disease)
Mx:
symptomatic - BBs e.g. propanolol
antithyroid:
1st line - carbimazole
2nd line - propylthiouracil
Radioiodine treatment for Graves and toxic multi nodular goitre
Surgical thyroidectomy
Hypothyroidism
- subtypes
- investigations
- Mx
Subtypes:
1. Hashimoto’s thyroiditis (autoimmune inflammation of the thyroid gland)
2. De Quervain’s thyroiditis (self-limiting post-viral infection, painful goitre, raised inflammatory markers)
3. Riedel’s thyroiditis (fibrosis causing hard non-tender goitre),
4. postpartum thyroiditis (autoimmune, initially thyrotoxicosis then hypothyroidism that normalises by 12 months)
5. iatrogenic post-thyroidectomy or radioiodine
6. drugs (e.g., lithium, amiodarone)
7. congenital hypothyroidism.
Investigations: \
* Antithyroid peroxidase (anti-TPO) antibodies—Hashimoto’s thyroiditis
* Inflammatory markers (raised in De Quervain’s thyroiditis)
Subclinical: T4 ↔ TSH ↑
Primary: T4 ↓ TSH↑
Secondary T4↓ TSH ↓ or ↔
Mx:
* Lifelong thyroxine (T4) replacement with levothyroxine, initially 1.6 mcg/kg once daily
* Check TSH levels every 3 months, then yearly once stable.
* Lower dose if over 65 years old or cardiovascular risk factors
Hyperparathyroidism
- pathophysiology
- classification
- presentation
- investigation
- management
Parathyroid hormone (PTH) is produced by the four parathyroid glands located on the posterior surface of the thyroid gland in response to low calcium levels.
* Primary hyperparathyroidism—Most common type and due to a parathyroid adenoma, hyperplasia
* Secondary hyperparathyroidism—Caused by renal impairment/vitamin D deficiency leading to low calcium levels & elevated PTH
*** Tertiary hyperparathyroidism **-longstanding secondary hyperparathyroidism leading to parathyroid hyperplasia
Sx - Usually asymptomatic. Possible symptoms include bone pain, abdominal pain, dehydration, polydipsia, polyuria, depression, anxiety, impaired concentration, poor sleep, fatigue, nausea, anorexia, and constipation.
Investigations
* PTH level
* Bone profile (calcium, phosphate)
* U&Es—Poor renal function may suggest secondary or tertiary hyperparathyroidism.
Management
* Primary
* Parathyroidectomy. If surgery is contraindicated, medical therapy with cinacalcet may be trialled to reduce calcium and PTH levels.
* Bisphosphonates or HRT to reduce fracture risk
* Secondary—Treat underlying cause with calcium supplements and phosphate-binding agents.
Hypoparathyroidism:
- causes
- presentation
- investigation
- management
Causes:
* Post-surgical (most common)
* Autoimmune
* DiGeorge syndrome
Presentation (asymptomatic or signs similar to hypocalcaemia)
* * * Myalgia, spasms, cramps
* * * Paraesthesia or numbness
* * * Memory impairment or slowed thinking
* * * Dry hair, brittle nails
* * * Chvostek’s sign—Tapping over facial nerve (CN VII) causes twitching of facial muscles.
* * * Trousseau’s sign—Carpopedal spasm when BP cuff is inflated above systolic BP
Investigations:
* Parathyroid hormone (PTH) is reduced.
* Bone profile (↓ calcium, ↑ phosphate)
* Magnesium and vitamin D may be low.
* ECG—Low calcium can cause prolonged QT interval.
* Pseudohypoparathyroidism refers to end-organ PTH resistance causing hypocalcaemia and hyperphosphataemia with elevated PTH level.
Management
* Correct hypocalcaemia
* Calcium and vitamin D sups
* Human recombinant PTH i
* Thiazide diuretics if hypercalciuria is present
MEN1 and MEN2
- associated tumours
MEN-1:
Pituitary adenoma
Primary hyperparathyroidism
Pancreatic neuroendocrine tumour (e.g., gastrinoma, insulinoma)
MEN-2A:
Medullary thyroid cancer
Phaeochromocytoma
Primary hyperparathyroidism
MEN-2B:
Medullary thyroid cancer
Phaeochromocytoma
Marfanoid body habitus
Mucosal neuromas
Cushing’s syndrome
- causes
- investigations
- management
Causes:
* Exogenous steroid use (most common)
* Pituitary adenoma (Cushing’s disease)
* Adrenal adenoma
* Small cell lung cancer (paraneoplastic)
Investigations:
Cushings syndrome e.g. adrenal adenoma : cortisol not surpressed, ACTH surpressed
Cushings disease (i.e. pituitary adenoma → ACTH secretion): cortisol & ACTH surpressed
**Ectopic **= both surpressed
Management (depend on underlying cause)
Cushing’s disease (pituitary adenoma)—Trans-sphenoidal resection
* Adrenal adenoma—Resection/adrenalectomy
* Ectopic ACTH—Treat underlying cancer.
Hyperaldosteronism (Conns syndrome)
- causes
- where is aldosterone produced?
- Sx
- investigations
- Mx
Aldosterone is a mineralocorticoid hormone produced in the zona glomerulosa of the adrenal cortex. It is released in response to angiotensin II as part of the renin–angiotensin–aldosterone system (RAAS).
Causes:
* Bilateral adrenal hyperplasia is most common.
* Adrenal adenoma (= Conn’s syndrome)
* Adrenal carcinoma (rare)
Features:
* HTN
* Hypokalaemia e.g muscle weakness
Investigations:
* Aldosterone/renin ratio would be increased.
* U&Es—Low K+, mildly elevated or normal Na2+
* Spironolactone and diuretics should be stopped 6 weeks before testing, as they will affect the measurements.
* CT adrenals
* Adrenal venous sampling (determines laterality and if any masses are functional)
Mx:
* Unilateral hyperplasia or adenoma—Laparoscopic adrenalectomy
* Bilateral hyperplasia—Aldosterone antagonist (e.g., spironolactone)
Diabetes Insipidus
- Cranial DI vs nephrogenic DI causes
- DI presentation
- investigations
- management
Cranial DI (most common) - neurosurgery, cranipharyngioma, head trauma, infection (meningitis)
Nephrogenic DI - drugs, lithium, electrolyte abnormalities, CKD, genetic
Presentation:
* Polydipsia (excess thirst)
* Polyuria (excess urine volume)
* Nocturia (waking at night to pass urine)
* Signs of fluid depletion (e.g., dry mucous membranes, reduced skin turgor, tachycardia)
Investigations:
* Serum osmolality will be raised.
* Urine osmolality is reduced.
* Water deprivation test:
Primary polydipsia
- after fluid dep: ↑
- after desmopressin: ↑
Cranial DI:
- after fluid dep: ↓
- after desmopressin: ↑
Nephrogenic DI:
- after fluid dep: ↓
- after desmopressin: ↓
Management:
* Encourage hydration and correct electrolytes.
* Cranial DI—Desmopressin (synthetic ADH)
* Nephrogenic DI—Thiazide diuretics
Phaeochromocytoma
- what is it?
- presentation
- investigation
- initial Mx
- definitive Mx
A rare catecholamine (adrenaline)-producing tumour of the chromaffin cells of the adrenal medulla.
Presentation:
* HTN
* Headaches
* Palpitations
* Sweating
* Anxiety
Investigation:
* 24-Hour urinary metanephrines and plasma free metanephrines.
* CT abdomen and pelvis to image the adrenals
Initial Mx: alpha blockers (e.g., phenoxybenzamine), then add beta blockers (e.g., propranolol). Starting a beta blocker before an alpha blocker may precipitate a hypertensive crisis
Definitive Mx: adrenalectomy
Hypopituitarism
- causes
- presentation
Causes:
* Pituitary adenoma (functional or non-functional)—Most common cause in adults
* Craniopharyngioma
* Pituitary surgery or radiotherapy, trauma
* Pituitary apoplexy (haemorrhage into or ischaemic infarction of an adenoma)—Consider if sudden severe headache
* Sheehan syndrome—Pituitary ischaemic necrosis secondary to a postpartum haemorrhage
Presentation: depends on the hormone which is deficient
- GH: short stature if during childhood; in adulthood, causes obesity
Prolactin: problems with lactation
FSH and LH: amenorrhoea, infertility, ↓ libido
ACTH: adrenal insufficiency (fatigue, postural hypotension)
TSH Secondary hypothyroidism (tiredness, cold, constipation)
Oxytocin: deficits in cognitive empathy
ADH/vasopressin: diabetes insipidus
Prolactinoma
- presentation
- investigation
- management
Sx:
* premenopausal women: secondary amenorrhoea or oligomenorrhoea, infertility, and galactorrhoea.
* men: loss of libido and erectile dysfunction.
* Visual field defect: Bitemporal hemianopia (loss of peripheral vision) due to optic chiasm compression by a large pituitary macroadenoma
Investigation:
* Serum prolactin level (raised)
* MRI pituitary
* Visual field testing (bitemporal hemianopia)
Management:
* Dopamine agonists (e.g., cabergoline) are first line and act to inhibit prolactin release.
* Combined oral contraceptive pill (COCP)
* Surgery (transsphenoidal resection) is indicated if medical management fails
* Radiotherapy (rarely used)
Metabolic acidosis
- causes
- anion gap calculation
- causes of raised anion gap
- causes of normal anion gap
Causes:
* Addition of acid (e.g., ketoacidosis, lactic acidosis, metformin)
* Decreased acid removal (e.g., renal failure, renal tubular acidosis types 1 and 4)
* Increased loss of bicarbonate, such as gastrointestinal losses (diarrhoea/stoma output, pancreatic) and renal tubular acidosis type 2
Anion gap calculation:
AG = (Na+ + Cl-) - (Cl- + HCO3-) (normal = 4-12mmol/L)
Cause of raised anion gap (MUDPILES):
* Metformin, methanol
* Uraemia
* Diabetic (or alcohol/starvation) ketoacidosis
* Paracetamol, propylene glycol, pyroglutamic acid
* Iron, isoniazid
* Lactic acidosis - most common cause by tissue hypoperfusion (sepsis), tissue hypoxia, renal failure
* Ethylene glycol
* Salicylates
Cause of normal anion gap: GI losses, renal losses
Metabolic alkalosis
- causes
- investigations
- management
Causes:
*GI H+ losses
* Renal H+ losses
* Intracellular H+ shift
* Alkali administration (IV bicarb)
Investigations: urinary chloride
* If <10 mmol/L, suggestive of volume depletion and gastrointestinal losses
* If >20 mmol/L, suggestive of mineralocorticoid excess, causing renal loss
Management:
* Treat underlying cause (e.g., give antiemetics, correct pyloric obstruction, cease diuretics)
* Crystalloid (e.g., 0.9% saline or Harmann’s solution) to replace water and Cl– losses
* Avoid hyperventilation
Respiratory acidosis - causes
Airway obstruction - foreign body, anaphylaxis
Parenchymal lung disease - COPD, asthma, ARDS
Impaired chest wall movement - obesity, pleural effusions, pneumothorax, trauma
Neuromuscular disorders
CNS depression - drugs (opiates, benzos)
Respiratory alkalosis
- causes
- Central—Head injury; stroke; anxiety, pain, or fear; drugs (e.g., salicylate overdose)
- Pulmonary (hypoxaemia without hypoventilation)—Pulmonary embolism, pulmonary oedema, pneumonia, mild/moderate asthma
- Iatrogenic—Hyperventilation of mechanically ventilated patients to cause cerebral vasoconstriction and reduce intracranial pressure
Hypernatraemia
- Causes
- Symptoms
- Investigations
- Management
- Complication
Causes:
- free water loss: vomiting, diarrhoea, burns, diabetes
- reduced free water intake: dementia
- excess Na+: iatrogenic, Cushings, Conns
Sx: symptoms of dehydration
Investigation:
* Urine osmolality < serum osmolality suggests diabetes insipidus.
* Urine osmolality > serum osmolality suggests other water loss (e.g., GI losses).
Mx:
* 0.9% saline to correct hypovolaemia (causes less marked fluid shifts in a hypertonic patient)
* When euvolaemic is correct, use 0.45% saline or 5% dextrose with regular electrolyte monitoring.
* Correct free water deficit over 48 hours:
* Free water deficit (L) = 0.6 × Weight (kg) × ([Current serum Na ÷ 140] – 1)
* Do not correct sodium faster than 1 mmol/hr.
Complications: cerebral oedema
Hyponatraemia
- Sx
- Clinical examination
- Investigations
- Management
Symptoms:
* Mild—Anorexia, nausea, malaise
* Moderate—Headaches, confusion, weakness
* Severe—Reduced GCS score, seizures
Clinical examination: Determine hydration status by examining mucous membranes, skin turgor, JVP, and peripheral oedema; monitor heart rate, blood pressure, and urine output.
Investigations:
Urinary Na+>20mmol/L
Sodium depletion, renal loss (patient often hypovolaemic)
* diuretics: thiazides, loop diuretics
* Addison’s disease
* diuretic stage of renal failure
Patient often euvolaemic
SIADH (urine osmolality > 500 mmol/kg)
hypothyroidism
Urinary Na+>20mmol/L
Sodium depletion, extra-renal loss
* diarrhoea, vomiting, sweating
* burns, adenoma of rectum
Water excess (patient often hypervolaemic and oedematous)
* secondary hyperaldosteronism: heart failure, liver cirrhosis
* nephrotic syndrome
* IV dextrose
* psychogenic polydipsia
SIADH
- diagnostic criteria
- causes
- treatment
Diagnostic criteria:
* Hyponatraemia (plasma sodium <135 mmol/L)
* Low plasma osmolality (<260 mOsm/kg)
* Clinical euvolaemia
* Concentrated urine (urine sodium >20 mmol/L and urine osmolality >100 mOsm/kg)
Causes:
* Respiratory—Pneumonia, abscess, tuberculosis, malignancy (especially non–small-cell lung cancer)
* Neurological—Stroke, subarachnoid or subdural haemorrhage, trauma, abscess, neurosurgery, meningoencephalitis, Guillain-Barré syndrome
* Malignancy—Lymphoma, lung, pancreatic and prostate tumours
* Medications—Selective serotonin re-uptake inhibitors, cytotoxics, opiates, chemotherapy agents, psychotropics
* Other—Major trauma, after major abdominal or thoracic surgery
Management:
1st line - hypertonic saline if severe Sx
2nd line - tolvaptan
Complication: central pontine myelinolysis
Hyperkalaemia
- causes
- ECG
- Investigations
- Mx
Causes:
- reduced excretion: AKI, Addisons, drugs (K+ sparing diuretics, ACEi, NSAIDs)
- cell injury - rhabdomyolysis, burns, tumour lysis
- extracellular shift: acidosis, insulin deficiency (DKA), drugs e.g. BBs, digoxin
ECG:
* Tall “tented” T waves
* Small or absent P wave
* Increased PR interval
* Widened QRS complex → sine-wave pattern
Investigations:
* Urgent VBG or ABG—Check potassium (severe, >7; moderate, >6; mild, >5.5), pH, and BGL.
* Urea and electrolyte panel including magnesium and calcium
* Full blood count
* Random cortisol
* Urinalysis and measure urine output
Mx:
* Stabilise cardiac membrane—10 mL 10% calcium gluconate (or chloride)
* Shift potassium → intracellular space—Insulin/dextrose infusion (10 units short-acting insulin in 50 mL 50% dextrose) and consider nebulised salbutamol
* Promote excretion of potassium—GI potassium binders (calcium resonium), IV fluids to increase renal perfusion
* Stop all nephrotoxics, optimise fluid status, treat potential underlying cause (e.g., steroids for Addison’s)
* Haemodialysis or haemofiltration if appropriate.
Hypokalaemia
- ECG features
- causes
- management
ECG features:
* Increased P-wave amplitude
* PR prolongation
* Widespread T-wave flattening/inversion
* U waves (most prominent V2–V3)
Causes:
* decreased intake - rare, EDs
* intracellular shift - increasing extracellular pH, increased beta-adrenergic activity (e.g., salbutamol), increased insulin availability (e.g., refeeding syndrome)
* increased losses - loop and thiazide diuretics, mineralocorticoid excess (e.g., Conn’s syndrome), vomiting, laxative abuse & skin losses (e.g., burns)
Mx:
* Urgent potassium replacement with continuous cardiac monitoring and regular monitoring of electrolytes and urine output
* Magnesium deficeincy can also cause hypokalaemia so correct magnesium first!!!
Hypercalcaemia
- Sx
- Causes
- Investigation
- Mx
Sx:
* Bones—Pain secondary to abnormal remodelling
* Moans—Abdominal pain, constipation, vomiting
* Stones—Dysuria, increased risk of renal calculi
* Groans—Confusion, agitation
Causes:
- parathyroid: 1 hyperparathyroidism
- non-parathyroid: malignancy, drugs (calcium, vitamin D, thiazides)
InvestigationsInvestigations: Formal calcium and phosphate levels, parathyroid hormone level, albumin, alkaline phosphatase (ALP)
5.
Interpretation:
* Albumin raised? Consider dehydration or cuffed specimen.
* Phosphate low? Likely hyperparathyroidism; check PTH.
* Phosphate high? Check alkaline phosphatase.
* ALP raised? Consider bony metastases or granulomatous disease.
* ALP normal? Consider myeloma (raised plasma protein), vitamin D excess.
Mx:
* Rehydration with IV 0.9% saline
* Bisphosphonates (e.g., pamidronate, zoledronic acid) to inhibit osteoclast activity; takes 2 to 3 days for effect
* Calcitonin—Inhibit osteoclast activity and increase urinary calcium excretion.
* Treat underlying cause (e.g., chemotherapy for malignancy, steroids for sarcoidosis).
Hypocalcaemia:
- clinical Sx
-Causes
- investigation
- acute/chronic Mx
Sx:
SPASM:
* Spasm of skeletal muscle
* Paraesthesia (perioral and peripheral)
* Anxiety/confusion
* Seizures if severe
* Muscle tone, including smooth muscle, causing wheeze, colic, dysphagia
also: trousseaus sign & chvosteks sign
Causes:
1. Low parathyroid hormone (PTH) (hypoparathyroid):
* Parathyroid destruction (e.g., following surgery/radiotherapy, autoimmune disease)
* Parathyroid agenesis (e.g., DiGeorge syndrome)
* Hypomagnesaemia causing decreased PTH secretion
- High PTH (secondary hyperparathyroidism):
* Vitamin D deficiency due to diet, malabsorption, liver disease
* PTH resistance (pseudohypoparathyroidism, hypomagnesaemia)
* Chronic renal disease - Other:
* Bisphosphonate use with untreated vitamin D deficiency
* Acute pancreatitis
* Rhabdomyolysis
* Tumour lysis
* Respiratory alkalosis (decreased ionised Ca2+)
Investigations: Urea and electrolytes, calcium, phosphate, magnesium, PTH, vitamin D; ECG (QT prolongation)
Mx:
Acute management:
* Give 10 mL 10% calcium gluconate IV.
* Monitor Ca2+ and repeat as necessary.
* Correct concurrent hypomagnesaemia and alkalosis.
Chronic management/prevention:
* Optimise dietary intake, supplementary oral calcium and vitamin D, consider alfacalcidol in chronic renal disease
Kallmans syndrome
- Sx
- Mx
Features
* ‘delayed puberty’
* hypogonadism, cryptorchidism
anosmia
* sex hormone levels are low
* LH, FSH levels are inappropriately low/normal
* patients are typically of normal or above-average height
Mx:
* testosterone
* gonadotrophin supps if need fertility
