Endocrine Flashcards
What is the pathophysiology of T1DM?
Condition where the pancreas stops being able to produce insulin due to destruction of the beta cells in the pancreas
What is the classical symptoms associated with hyperglycaemia?
Polyuria, polydipsia, weight loss
How does insulin work to decrease blood sugar?
- It causes cells to absorb glucose from the blood and use it as fuel
- It causes muscle and liver cells to absorb glucose from the blood and store it as glycogen (glycogenesis)
Why are ketones raised in a patient in DKA?
Ketones are made from fatty acids in the liver when there is insufficient glucose supply and glycogen stores are exhausted - occurs when all the glucose is stuck in the blood and unable to be used by the cells
What are the 3 features of DKA?
Ketoacidosis, dehydration and potassium imbalance
Why does potassium imbalance occur in DKA?
Normally insulin drives potassium into the cells, without insulin potassium is not added to and stored in cells
What can cause DKA to occur?
Infection, infarction, inflammation
What are the 3 diagnostic features of DKA?
Hyperglycaemia >11mol/L
Ketosis >3mmol/l or ++ on urine dipstick
Acidosis - pH <7.3
What is the initial step done in managing DKA?
Fluid resuscitation to correct dehydration and electrolyte disturbances - 0.9% saline 1L in first hour followed by 1 litre every 2 hours
Apart from fluid resuscitation what other steps are required in managing DKA?
Insulin - fixed rate insulin infusion + long acting SC insulin
Glucose - required when glucose <14mmol/L needs regular monitoring
Potassium - add potassium to IV fluids and monitor closely
Treat any underlying triggers such as infection
What are the complications of treating DKA?
Cerebral oedema (in children), hypoglycaemia, hypokalaemia, pulmonary oedema, VTE
What is the long term management of T1DM?
Insulin regimes - pumps, basal/bolus
What is a variable rate IV insulin infusion?
IV insulin of variable rate according to regular capillary glucose measurements (need finger pricks every hour)
Accompanied by infusion fluid usually 5% glucose with KCl
When is a variable rate insulin infusion used?
Patients with known diabetes unable to take oral food/medication, vomiting, T1DM and having surgery, severe illness and need to achieve good glycaemic control
When a patient is on a variable rate insulin infusion should you continue short acting and long acting insulin?
Stop short acting
Continue long acting
What is considered as hypoglycaemia?
Blood glucose <4mmol/L
At less than 2 they cannot maintain their airway
What symptoms are associated with hypo’s?
Hunger, tremor, sweating, irritability, dizziness, pallor, reduced GCS
What is the management for hypoglycaemia?
Rapid acting glucose
Oral if able to eat
IM glucagon if no access
IV dextrose 200ml of 10% over 10 minutes
What are the long term complications associated with hyperglycaemia?
Infections due to immune system dysfunction
CHD/stroke/hypertension
Peripheral ischaemia causing poor skin healing and diabetic foot ulcers
Peripheral neuropathy
Retinopathy
Diabetic nephropathy
What is the pathophysiology of T2DM?
Combination of insulin resistance and reduced insulin production caused by persistently high blood sugar levels
What is the presentation of someone with T2DM?
Tiredness, polyuria, polydipsia, opportunistic infections, visual blurring, slow wound healing, acanthosis nigricans
What is the HbA1c for someone with pre-diabetes?
42-47mmol/L
What are the glucose levels required for diagnosing diabetes?
HbA1c >48 mmol/L - need 2 samples to confirm or 1 sample with symptoms
Fasting glucose >7mmol/l
Random glucose >11mmol/l
OGTT >11mmol/L
What is the HbA1c target for someone with T2DM?
48mmol/l for new patients
53mmol/l for patients requiring more than one antidiabetic drug
What is the stepwise approach to managing T2DM?
- Lifestyle modifications
- Metformin
- SGLT-2 inhibitors if existing heart disease or high QRISK or
Sulfonylurea, pioglitazone, DPP4-inhibitor - Triple therapy or insulin
- Can also add GLP-1 agonist if BMI>35
What is the mechanism of action for metformin and what are the common side effects?
Increases insulin sensitivity and decreases glucose production by the liver
Side effects = GI symptoms (improved on modified release)
What is the mechanism of action for SGLT-2 inhibitors, some examples and the common side effects?
Blocks the action of protein that reabsorbs glucose from urine into blood –> excess glucose excreted in urine
Empagliflozin, dapagliflozin
Side effects = genital and urinary infections, increased urine output and frequency
What is the mechanism of action for pioglitazone and what are the common side effects?
Increases peripheral insulin sensitivity and decreases liver production of glucose
Side effects = increased risk of bladder cancer, weight gain, fluid retention
What is the mechanism of action for sulfonylureas, some examples and the common side effects?
Stimulate insulin release from the pancreas
Gliclazide
Side effects = hypoglycaemia, weight gain
What is the mechanism of action for DPP4-inhibitors, some examples and the common side effects?
Prevents the blocking of incretins which act to lower blood glucose
Sitagliptin and alogliptan
Side effects = headaches, low risk of acute pancreatitis, nausea
What is the mechanism of action for GLP-1 mimetics, some examples and the common side effects?
Imitate the action of incretins which act to lower blood glucose
Exenatide, liraglutide
Side effects = reduced appetitie, weight loss, GI symptoms, AKI, pancreatitis
How is peripheral neuropathy managed in diabetes?
Amitriptyline or duloxetine
What medications can be used to help CKD in those with diabetes?
ACE inhibitors if ACR above 3
SGLT-2 inhibitors if ACR above 30
How is diabetic gastroparesis managed?
Metoclopramide or domperidone
What is the management for hyperosmolar hyperglycaemic state?
0.9% saline 3-6L over 12 hours (the glucose will follow the water into the cells)
Only give insulin if refractory hyperglycaemia following adequate rehydration
How is hyperosmolar hyperglycaemic state diagnosed?
Hypovolaemia, hyperosmolality (concentrated blood), high sugar levels, absence of ketones
What is the first line antihypertensive for patients with T2DM (irrespective of age)?
ACE inhibitors/ARB
What is the difference between primary and secondary hyperthyroidism?
Primary = thyroid pathology
Secondary = pathology in the hypothalamus or pituitary gland
What is subclinical hyperthyroidsim?
When thyroid hormone levels are normal but TSH is supressed
What are the causes of hyperthyroidism?
Graves disease, thyroiditis (hyper followed by hypo), solitary toxic thyroid nodule, toxic multi nodular goitre
What are the antibodies associated with Graves disease?
TSH receptor antibodies
What are the risk factors for hyperthyroidism?
Female, 20-40, smoking, high iodine intake, stress, other autoimmune conditions
What symptoms are associated with hyperthyroidism?
Anxiety, sweating, heat intolerance, tachycardia, palpitations, weight loss, fatigue, weakness, diarrhoea, sexual dysfunction, oligomenorrhoea, fine tremor
What is a complication of hyperthyroidism?
Thyroid storm - may require fluid resuscitation, anti-arrhythmic medication and beta blockers
What features are specific to Grave’s disease?
Diffuse goitre
Pretibial myxoedema
Finger clubbing and hand swelling
Eye disease - exophthalmos, eyelid retraction and periorbital oedema
What are the TFTs of someone with hyperthyroidism?
Serum TSH will be low, T3/T4 levels will be high
What medications can be used to treat hyperthyroidism?
1st line = carbimazole (block and replace regime)
2nd line = propylthiouracil (1st line in 1st trimester of pregnancy)
Radioactive iodine
Beta blockers are used to control symptoms - propranolol is 1st line
Surgery to remove thyroid is also possible
What is the difference between primary and secondary hypothyroidism?
Primary = thyroid produces inadequate thyroid hormone
Secondary = pituitary behaves abnormally and produces inadequate TSH resulting in under stimulation of the thyroid gland and insufficient thyroid hormone
What are the causes of primary hypothyroidism?
Hashimotos thyroiditis = most common (associated with anti-TPO antibodies)
Atrophic hypothyroidism
Iodine deficiency
Lithium or amiodarone use
Post-partum thyroiditis
What symptoms are associated with hypothyroidism?
Weight gain, fatigue, dry skin, coarse hair and hair loss, fluid retention, heavy or irregular periods, constipation, cold intolerance, bradycardia, poor appetite, poor libido, depression
What are the TFT results in someone with hypothyroidism?
TSH high, T4 low
What is subclinical hypothyroidism?
When TSH is high but T4 levels remain normal
What is the treatment for hypothyroidism?
Oral levothyroxine - lifelong
What complication can arise due to hypothyroidism?
Myxoedema coma - hypothermia, coma and seizures
What is the most common type of thyroid cancer?
Papillary tumours which are relatively benign
Which thyroid cancer types have the worst prognosis?
Medullary and anapaestic
What is medullary thyroid cancer associated with?
Multiple endocrine neoplasia
What treatment options are available for thyroid cancer?
Thyroidectomy, radioiodine, radiotherapy
What is the difference between Cushing’s disease and Cushing’s syndrome
Syndrome = high levels of glucocorticoids in the body (cortisol)
Disease = due to pituitary adenoma secreting excessive ACTH –> high cortisol
What are the features of Cushing’s?
Round face, central obesity, abdominal striae, buffalo hump, proximal limb muscle wasting, easy bruising and poor skin healing, acne, amenorrhoea, hyperpigmentation of skin (disease only), osteoporosis
What are the causes of cushing’s?
Pituitary adenoma - disease
Adrenal adenoma
Paraneoplastic syndrome (SCLC is most common)
Exogenous steroids
Adrenal carcinoma
What test is used to diagnose Cushing’s
Dexamethasone suppression test
The high dose dexamethasone suppression test differentiates between the causes of Cushing’s disease - what are the results in pituitary adenoma and adrenal adenoma/ectopic ACTH
Pituitary adenoma the high dose suppresses high cortisol and ACTH
In adrenal adenoma or ectopic ACTH there is no suppression of cortisol after the high dose of dexamethasone
What is the treatment for Cushing’s syndrome?
Remove underlying cause
Trans-sphenoidal surgery for removal of pituitary adenoma
Surgical removal of adrenal tumour or tumour producing ectopic ACTH
What is Nelson’s syndrome?
Occurs after bilateral adrenalectomy for Cushing’s
There is hyperpigmentation due to very high levels of ACTH
What are the causes of primary hyperaldosteronism?
Bilateral adrenal hyperplasia
Adrenal adenoma (Conn’s)
Familial hyperaldosteronism
What is secondary hyperaldosteronism and what are the causes?
Excessive renin secretion –> excessive aldosterone
Causes = disproportionately lower BP in kidneys:
Renal artery stenosis
Heart failure
Liver cirrhosis and ascites
What is the screening test used for hyperaldosteronism?
Aldosterone:renin ratio
High aldosterone and low renin = primary
High aldosterone and high renin = secondary
What is the management for hyperaldosteronism?
Aldosterone antagonists = eplerenone, spironolactone
If due to renal artery stenosis - percutaenous renal artery angioplasty
Surgical removal of adrenal adenoma
What is acromegaly?
Result of excessive growth hormone after fusion of the growth plates
What are the causes of acromegaly?
Pituitary adenoma = most common
Ectopic GH being secreted from tumour such as SCLC
What are the common presenting features of acromegaly?
Headaches, bitemporal hemianopia, prominent forehead and brow, coarse/sweaty skin, large nose/tongue/hands/feet, large protruding jaw, increased interdental spacing, hypertrophic heart, carpal tunnel
What is the first line investigation for acromegaly?
Insulin-like growth factor 1 blood test
OGTT - done to confirm diagnosis
What is the treatment for acromegaly?
Trans-sphenoidal surgery to remove the pituitary adenoma = 1st line
Pegvisomant - GH receptor antagonist
Octreotide - somatostatin analogues (1st line medication)
Bromocriptine - dopamine agonists
What are the causes of hyperkalaemia?
AKI, CKD, rhabdomyolysis, adrenal insufficiency, tumour lysis syndrome, aldosterone antagonists, ACE inhibitors, NSAIDs, beta blockers
What ECG signs are associated with hyperkalaemia?
Tall tented T waves, flattened or absence of P waves, broad complex QRS
When does a patient with hyperkalaemia not require urgent treatment?
Potassium <6mmol/l and stable renal function, no ECG changes
What treatment is given in acute hyperkalaemia? (in what order?)
- Calcium gluconate - stabilises the cardiac muscle cells and reduced risk of arrhythmias
- Insulin and dextrose - drives glucose into the cells and takes potassium with it (10% IV over 2 minutes)
- Nebulised salbutamol - temporarily drives potassium into cells
- Calcium resonium - lowers total body potassium
Dialysis may be required in severe or persistent cases
What hormones are not produced in adrenal insufficiency?
Cortisol and aldosterone
What is Addison’s disease?
Damage to the adrenal glands causing reduced cortisol and aldosterone (primary)
What is secondary adrenal insufficiency and what are the causes?
Inadequate ACTH and lack of stimulation of the adrenal glands leading to low cortisol and aldosterone
Caused by damage or loss of the pituitary gland
What is the presentation of adrenal insufficiency?
Fatigue, muscle weakness, dizziness and fainting, thirst, weight loss, abdominal pain, depression, reduced libido, bronze hyperpigmentation in skin creases (primary only due to raised ACTH)
What are the key biochemical findings in adrenal insufficiency?
Hyponatraemia, hyperkalaemia, raised creatinine and urea
What is the diagnostic test for adrenal insufficiency?
Short synacthen test
Cortisol levels should at least double following dose of synthetic ACTH, does not happen in adrenal insufficiency
What is the management for adrenal insufficiency?
Hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) lifelong
How does adrenal crisis present?
Reduced consciousness, hypotension, hypoglycaemia, hyponatraemia and hyperkalaemia
What is the management of adrenal crisis?
ABCDE
IM/IV hydrocortisone (do not need fludrocortisone)
IV fluids
Correct hypoglycaemia
Careful monitoring of electrolytes and fluid balance
What is the pathophysiology of diabetes insipidus?
Lack of ADH (cranial) or lack of response to ADH (nephrogenic)
ADH stimulates water reabsorption from the collecting ducts in the kidneys
What are the causes of nephrogenic diabetes insipidus?
Lithium, genetic, hypercalcaemia, hypokalaemia, kidney diseases
What are the causes of cranial diabetes insipidus?
Brain tumours, brain injury, brain surgery, brain infection, genetic mutations
What are the symptoms of diabetes insipidus?
Polyuria, polydipsia, dehydration, postural hypotension
What is the diagnostic test for diabetes insipidus and what are the results for each type?
Water deprivation test - water deprivation for 8 hours, then low dose ADH
In primary polydipsia - urine osmolality will be high after water deprivation
In cranial DI - initially urine osmolality is low as it continues to be diluted by excessive water but after ADH is given the urine osmolality is high
In nephrogenic DI - patient is unable to respond to ADH and urine osmolality will be low both times
What is the management for diabetes insipidus?
Underlying cause should be treated
Desmopressin can be used in cranial diabetes insipidus
For nephrogenic - ensuring plenty of water, high dose desmopressin, thiazide diuretics, NSAIDs
What is the pathophysiology of SIADH?
Increased release of ADH from the posterior pituitary which increases water reabsorption from the urine diluting the blood and leading to hyponatraemia
What are the causes of SIADH?
Increased secretion from posterior pituitary or ectopic ADH
Post operative, lung infection, brain pathologies, SSRIs, carbamazepine, HIV, SCLC
What symptoms are associated with SIADH?
Headache, fatigue, muscle aches and cramps, confusion, severe hyponatraemia
How is SIADH treated?
Fluid restriction, treat any underlying cause, tolvaptan can be used, sodium is corrected slowly to prevent osmotic demyelination (no more than 10mmol/l in 24 hours)
What are the causes of hypokalaemia?
Vomiting, diarrhoea, thiazide and loop diuretics, cushing’s, conn’s, magnesium deficiency
What ECG changes are associated with hypokalaemia?
U waves, small or absent T waves, prolonged PR interval, ST depression
What is the management for hypokalameia?
Fluids replacement with potassium, may need cardiac monitoring
What is primary hypoparathyroidism and how is it managed?
Including whether calcium, phosphate and PTH are high/low/normal
Decrease in PTH secretion e.g. secondary to thyroid surgery
Low calcium, high phosphate, low PTH
Manage with alfacalcidol
What symptoms are associated with hypocalcaemia?
Muscle twitching, cramping and spasm, perioral paraesthesia, Trosseau’s sign, Chvostek’s sign
What is pseudohypoparathyroidism?
Including whether calcium, phosphate and PTH are high/normal/low
Target cells being insensitive to PTH
Low calcium, high phosphate, high PTH
How does PTH increase blood calcium levels?
Increasing osteoclast activity in the bones, increasing calcium reabsorption in the kidneys, increasing vitamin D activity resulting in increased calcium absorption in the intestines
What are the symptoms associated with hypercalcaemia?
Kidney stones, painful bones, abdominal groans (constipation, N+V), psychiatric moans (fatigue, depression)
What is primary hyperparathyroidism and how is it managed?
Caused by uncontrolled PTH production by a tumour of the parathyroid glands –> hypercalcaemia
Remove tumour surgically
What is secondary hyperparathyroidism and how is it managed?
Insufficient vitamin or CKD –> reduced calcium absorption from the kidneys/intestines and bones
Hypocalcaemia so more PTH excreted
Low calcium, high PTH
Treatment = correct underlying vitamin D deficiency
What is a pheochromocytoma?
Tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline
What genetic conditions are associated with neuroendocrine tumours?
Multiple endocrine neoplasia type 2, neurofibromatosis type 1, Von Hippel-Lindau disease
What investigations of done for pheochromocytoma?
Plasma free metanephrines and 24 hour urine catecholamines
What is the treatment of pheochromocytoma?
Alpha blockers, beta blockers and surgical removal of tumour
What is the first line treatment for prolactinoma?
1st line = dopamine agonists e.g. cabergoline
2nd line = trans-sphenoidal surgery
Other than diabetes and diabetes insipidus what can cause polyuria and polydipsia?
Hypercalcaemia
How does Conn’s syndrome present?
Hypertension and hypokalaemia
