Endocrinology Flashcards
What is the definition of diabetes mellitus?
Disorder of carbohydrate metabolism characterised by hyperglycaemia due to relative insulin deficiency, resistance or both
What range should normal blood glucose be in?
3.5-8.0 mmol/L
What measurements need to be detected in bloods for a person to be diagnosed with diabetes?
Random plasma glucose > 11 mmol/L
Fasting plasma glucose > 7 mmol/L
HbA1c of 48 mmol/mol
2 hour postprandial > 11.1 mmol/L
What is the difference between type 1 and type 2 diabetes?
Type 1 is insulin deficiency, autoimmune
Type 2 is insulin resistance/relative insulin deficiency
What are the epidemiological differences between type 1 and type 2 diabetes?
Type 1
- Often presents in childhood, peak incidence at puberty
- Increasing prevalence
- Increased prevalence of those of Northern European ancestry
Type 2
- Common in all populations with affluent lifestyle
- Increasing incidence (ageing population, increasing obesity)
- Presents in adulthood > 40
- More prevalence in South Asia, African nad Caribbean ancestry
Other than type 1 and type 2, name 3 other types of diabetes
Maturity onset diabetes of youth, pancreatic diabetes, endocrine diabetes, malnutrition related diabetes, drug induced
Give 5 risk factors for developing type 1 diabetes
Northern European ancestry (particularly Finnish), family history, having another autoimmune condition, diet, enteroviruses, vitamin D deficiency, recreational drug use, alcohol, steroids
Give 5 risk factors for developing type 2 diabetes
Genetics, male, increasing age, obesity, lack of exercise, Asian, high calorie intake
What is the pathophysiology of type 1 diabetes?
- Autoimmune destruction of beta cells leads to insulin deficiency
- Chronic insulitis ensues
- Continued breakdown of liver gylcogen, unrestrained lipolysis and skeletal muscle breakdown, increased in hepatic glucose output and suppression peripheral glucose uptake
- Increased urinary glucose losses as renal threshold exceeded
- Perceived stress leading to increased cortisol and adrenaline
- Catabolic state leading to increasing levels of ketones (lack of glucose and fat breakdown) and muscle loss
What is the pathophysiology of type 2 diabetes?
- Insulin resistance post-receptor and progressive failure of insulin secretion
- Impaired insulin action leading to reduced muscle and fat uptake after eating
- Failure to suppress lipolysis and high circulating FFAs - depositing in islets of Langherhan’s leading to further impairment of insulin secretion
- Increased glucose levels in blood leads to damage - prevents NO release from endothelial cells so vessel lumen remains small = increased BP
- Hyperglycaemia and lipid excess toxic to beta cells = loss of beta cells
What occurs during diabetic ketoacidosis?
State of uncontrolled catabolism
- Rise in ketones
- Glucose and ketones excreted in urine leads to osmotic diuresis and falling circulatory blood volume
- Ketones acidic so lower blood pH, impairs Hb ability to bind to O2
- Reduced glucose = increased FFA oxidation = increased acteyl-CoA production = increased ketones exceeding ability of peripheral tissues to oxidise them
- Vicious circle of dehydration, hyperglycaemia and increasing acidosis eventually leading to circulatory collapse and death
What are the symptoms of ketoacidosis?
Polyuria and polydipsia Nausea and vomiting Weight loss Weakness Abdominal pain Drowsiness/confusion Hyperventilation as respiratory compensation Fruity breath
What are the risk factors for developing ketoacidosis?
Stopping insulin Infection Surgery MI Pancreatitis Undiagnosed diabetes
What occurs when someone develops hyperosmolar hyperglycaemic state?
- Endogenous insulin levels reduced but still sufficient to inhibit hepatic ketogenesis but insufficient to inhibit hepatic glucose production
- Severe dehydration, decreased level of consciousness, hyperglycaemia, hyperosmolality, no ketones in blood/urine, coma, bicarbonate not lowered
- Treat with insulin
- Fluid replacement and restore lost electrolytes
- Low molecular weight heparin
- Risk of cerebral oedema
What are the risk factors of developing hyperosmolar hyperglycaemic state?
Infection, consumption of glucose rich foods, concurrent medication eg thiazide diuretics or steroids
How might someone with type 1 diabetes present?
Lean, polydipsia, polyuria Weight loss and fatigue Ketosis Nocturia, ketonuria, glycosuria Dehydration Decreased appetite Blurred vision Hunger High levels of islet autoantibodies Short history of severe symptoms
How might someone with type 2 diabetes present?
Overweight in abdominal area Polydipsia, polyuria Ketosis Older Gradual onset Often able to control by diet, exercise and oral medication
How is diabetes diagnosed?
Random plasma glucose/fasting plasma glucose/2 hours postprandial/HbA1c
If symptomatic require only 1 abnormal
If asymptomatic require 2 abnormal
Microalbuninuria - kidney disease?
FBC, U&Es, fasting blood for cholesterol and triglycerides
Blood pH
Give 3 differential diagnoses of diabetes
Pancreatitis, trauma/pancreatectomy, neoplasia of pancreas, acromegaly, Cushing’s, Addison’s
How is type 1 diabetes treated?
Insulin - basal/bolus Educate to self-control doses Phone for support Modify diet and avoid binge drinking Make sure to change injection sites
How is type 2 diabetes treated?
Weight loss and exercise Statins BP control 1st drug - metformin Dual therapy of metformin with DDP4 inhibitor/ploglitazone/sulphonylurea/SGLT-2i
Give 5 complications of diabetes
Hypoglycaemia
Microvascular - retinopathy, nephropathy, neuropathy
Macrovascular - strokes, renovascular disease, limb ischaemia, heart disease, erectile dysfunction, hypertension
Staphylococcal skin infections
DKA
What is impaired glucose tolerance?
Abnormal 2 hours post-prandial
BUT glucose level not high enough to be diabetic
Insulin resistance
What is impaired fasting glucose?
Abnormal fasting glucose
BUT glucose level not high enough to be diabetic
Insulin resistance
What is diabetic nephropathy?
Glomerular damage due to diabetes
Main cause of end stage renal disease
Major risk factor for CVD
What are the risk factors for diabetic nephropathy?
Poor BP control
Poor glycaemic control
What occurs during diabetic nephropathy?
Progressive decline in renal function Prevents kidney filtration Glomerulus changes Increase of glomerular injury Filtration of proteins = proteinuria
What is the presentation of diabetic nephropathy?
Progressive decline in kidney function, proteinuria
How is diabetic nephropathy diagnosed and treated?
Diagnosis - kidney function test, amount of albumin in urine
Treatment - BP control, glycaemic control
Proteinuria control and cholesterol control
What is diabetic neuropathy?
Irreversible nerve damage due to hyperglycaemia
Occurs in 1 in 5 patients with diabetes
Can lead to foot ulceration
What are the risk factors for diabetic neuropathy?
Poor glycaemic control, hypertension, smoking, HbA1c changes, duration of diabetes, BMI, trigylcerides, high total cholesterol
How does diabetic neuropathy present?
Pain - burning, pins and needles, worse at night
Autonomic - diarrhoea, incontinence, constipation, erectile dysfunction
Insensitivity - foot ulceration, infection, amputation, falls
Glove and stocking
No significant motor deficit
How is diabetic neuropathy diagnosed and treated?
Diagnosis - 10gm monofilament, neurotips, tuning fork, ankle reflexes
Treatment - good glycaemic control, tricyclic antidepressants/SSRIs, anticonvulsants, opioids, IV lignocaine, capsaicin
Transcutaneous nerve stimulation/acupuncture
Psychological interventions
What is diabetic retinopathy?
Damage to blood vessels of light sensitive tissue in eye causing blindness
What are the risk factors for diabetic retinopathy?
Poor glycaemic control, long durational diabetes, hypertension, insulin treatment, pregnancy, higher HbA1c
What occurs in diabetic retinopathy?
- Blood vessel leakage
- Occlusion
- Pericyte loss and smooth muscle cell loss
- Micro-aneurysms adjacent to or upstream of capillary non-perfusion
- Thickened basement membrane
- Loss of junctional contact between endothelial cells
- Glial cells grow down capillaries
- Ischaemia/occlusion
How is diabetic retinopathy diagnosed and treated?
Diagnosis - eye screening once per year for early detection
Treatment - laser therapy to stabilise changes (doesn’t improve sight)
What are the risks of laser eye treatment?
Difficulty with night vision Loss of peripheral vision Tunnel vision Temporary drop in acuity Vitreous haemorrhage
How does metformin (biguandie) work?
- Reduces gluconeogenesis in liver
- Increases glucose uptake and ultilisation in skeletal muscle (increased insulin sensitivity)
What are the side effects of metformin?
Hypoglycaemia GI disturbances (anorexia, diarrhoea, nausea) - weight loss Lactic acidosis in renal disease, hepatic disease and HF
What is the action of sulphonyl-ureas? And give some examples
Stimulate B cells to secrete insulin
Glicalazide
Glipizide
What are contraindications of sulphonyl-ureas?
Pregnancy and breastfeeding as can cross placenta and enter breast milk causing hypoglycaemia in newborns
What are the side effects of sulphonyl-ureas?
Hypoglycaemia Weight gain (stimulate appetite)
What is the action of DPP4 inhibitors? And give an example
Inhibit DPP4, increasing effect of incretins that stimulate insulin secretion
Incretins - group of hormones released after eating and augment secretion of insulin
Don’t cause weight gain/loss
Sitagliptin
What is the action of gliazones? And give an example
Enhance uptake of fatty acids and glucose
Pioglitazone
What are the side effects of gliazones?
Fluid retention (increases Na+ reabsorption) - may worsen HF Weight gain (fluid retention and fat gain)
How does hypoglycaemia develop?
Too much insulin/oral hypoglycaemic agents leading to insufficient glucose to brain
What are the signs and symptoms of hypoglycaemia?
Odd behaviour (aggression)
Sweating (fight/flight)
Raised pulse
Seizures
How is hypoglycaemia diagnosed and treated?
Blood glucose level
Glucose (food/IV infusion)
Glucagon
What is the definition of Graves’ disease?
Hyperthyroidism
Excessive stimulation of TSH receptor which stimulates thyroid to produce more hormone and grow larger (goitre)
AKA - thyrotoxicosis - excess thyroid hormones in blood
What are the causes of thyrotoxicosis?
Overproduction of thyroid hormone
Leakage of preformed hormone from thyroid (destroyed follicular cells by infection/autoimmune)
Ingestion of excess hormone
Epidemiology of hyperthyroidism?
2-5% of women with have at some time
20-40 mainly
2 diseases account for majority of causes
2/3 cases Graves’
Name 3 other conditions that can cause hyperthyroidism
Toxic multi-nodular goitre
Toxic adenoma
Ectopic thyroid tissue
Exogenous (iodine/T4 excess)
Name 5 risk factors for developing Graves’
Female, family history, E coli/gram-negative bacterial infections (contain TSH binding sites), smoking, stress, high iodine levels, autoimmune disease
What is the pathogenesis of Graves’?
- Serum IgG antibodies called TSH receptor stimulating antibodies bind to TSH receptors in thyroid
- Stimulates production of T3/4 behaving like TSH
- Excess secretion of thyroid hormones and hyperplasia of thyroid follicular cells (diffuse goitre)
- Similar auto-antigen can result in retro-orbital inflammation - Graves’ opthalmopathy
Give 5 general symptoms and signs of hyperthyroidism
Symptoms - palpitations, diarrhoea, weight loss, oliomenorrhea/infertility, heat intolerance, tremor, behavioural change, hyperkinesis, muscle wasting, anxiety, sweats, Signs - diffuse goitre, lid lag and stare, atrial fibrillation, tachycardia, thin hair, onycholysis
Give 2 symptoms specific to Graves’
Graves’ ophthalmopathy - eye discomfort, grittiness, increased tear production, photophobia, diplopia, protruding eye
Thyroid acropachy - clubbing, finger and toe swelling
How is hyperthyroidism diagnosed?
How is Graves’ diagnosed?
Give a differential diagnosis
TFTs - TSH suppressed (only in primary), T3/4 raised
TPO and thyroglobulin antibodies present
Ultrasound thyroid
Graves’ - TSH receptor stimulating antibodies
Differential - mild cases of anxiety
How is hyperthroidism treated?
Beta-blockers
Anti-thyroid drugs - propylthiouracil/oral carbimazole
Radioactive iodine
Surgery - thyroidectomy
What is hypothyroidism?
What is myxoedema?
Underactivity of thyroid gland
Under production of thyroid hormone
What is the difference between primary and secondary hypothyroidism?
Primary - reduced T4 and T3
Secondary - reduced TSH from anterior pituitary - hypopituitarism
Give some examples of causes of primary hypothyroidism
Primary atrophic hypothyroidism, Hashimoto’s thyroiditis, iodine deficiency, post-thyroidectomy/radioiodine/antithyroid drugs, lithium/amiodarone
Give 5 epidemiology facts about hypothyroidism
Endemic in iron deficient areas
More common in women
Incidence increases with age
Associated with other autoimmune diseases
Associated with Turner’s and Down’s syndrome, cystic fibrosis, primary billiary cirrhosis and ovarian hyper-stimulation
How does goitre form?
The pituitary gland will detect low thyroid levels so it produces more TSH which will stimulate TSH receptors on thyroid resulting in thyroid enlargement
What is autoimmune hypothyroidism?
Antithyroid antibodies lead to lymphoid infiltration of gland and eventually atrophy and fibrosis
No goitre
What is Hashimoto’s thyroiditis?
Form of autoimmune hypothyroisism
Produces atrophic changes with regeneration resulting in goitre formation due to lymphocytic and plasma cell infiltration
Normally feels firm and rubbery
Thyroid peroxidase present in high titres
Levothyroixine - may shrink goitre
What is post-partum thyroiditis?
Observed after pregnancy
Modifications in immune system necessary in pregnancy and histologically lymphocyte thyroiditis
Can proceed to permanent hypothyrodism
What is iatrogenic thyroiditis?
From thyroidectomy or radioactive iodine treatment
What drugs may induce thyroiditis?
Carbimazole, lithium, amiodarone (can also cause hyper), interferon
What is iodine deficiency thyroiditis?
Lack of iodine in diet
Euthyroid or hypothyroid depending on severity
Borderline hypothyroidism leading to TSH stimulation and thyroid enlargement in face of continuing iodine deficiency
What are the symptoms of hypothyroidism?
Hoarse voice, goitre, constipation, cold intolerant, weight gain, menorrhagia, myalgia, weakness, tired, low mood, dementia, oedema
What are the signs of hypothyroidism?
BRADYCARDIC
Bradycardia, Reflexes relax slowly, Ataxia, Dry/thin hair/skin, Yawning, Cold hands, Ascites, Round, puffy face, Defeated demeanour, Immobile, Congestive heart failure
How is hypothyroidism diagnosed?
What is a differential diagnosis of hypothyroidism?
TFTs - serum TSH high (increases to make thyroid work again), TSH inappropriately low for low T3/4 (secondary)
Serum free T4 low
Thyroid antibodies
Blood tests
- Anaemia
- Raised serum aspartate transferase levels
- Increased serum creatine kinase
- Hypercholesterolaemia
- Hyponatraemia due to increased ADH and impaired free water clearance
Differential - ageing
How is hypothyroidism treated?
Hormone replacement
Monitoring
- Primary - dose titrated until TSH normalises
- Secondary - TSH always low, T4 monitored
What are the complications of hypothyroidism?
Myxoedema coma
Severe hypothyroidism - confusion, coma
Hypothermia, cardiac failure, hypoventilation, hypoglycaemia, hyponatraemia
Medical emergency - IV/oral T3 and glucose infusion, gradual rewarming
What is Cushing’s disease?
Chronic, excessive and inappropriately elevated levels of circulating plasma cortisol resulting from inappropriate ACTH secretion from pituitary due to a tumour
Most common cause oral steroids
What other things could cause high levels of cortisol?
Cushing’s syndrome, ectopic ACTH production, ACTH treatment for asthma, adrenal adenoma
What is the pathophysiology of high levels of cortisol?
Excess cortisol resulting from either excess ACTH or by ingesting excess glucocorticoids or from neoplasms in adrenals that stimulate zone reticularis to release more cortisol
What are the symptoms of Cushing’s?
CUSHING
Cataracts, Ulcers, Skin (striae), HTN, hyperglycaemia, Infections increase, Necrosis, Glucosuria
Aesthetic things
Central obesity, plethoric complexion - ruddy, swollen, moon face, mood change - depression, lethargy, irritability, psychosis, acne, buffalo hump, hirsutism
How is Cushing’s diagnosed?
Careful drug history
Random plasma cortisol
Overnight dexamethasone suppression test - should send negative feedback to pituitary and hypothalamus leading to decreased ACTH and reduced cortisol
Urine free cortisol over 24 hours
If no suppression - 48 hour dexamethasone suppression test
CT/MRI for tumour
Distinguish pituitary cause from ectopic ACTH production
If cortisol responds to CRH - Cushing’s
What is a differential diagnosis of Cushing’s?
Pseudo-Cushing’s syndrome - alcohol excess, resolves after 1-3 weeks of alcohol abstinence
What is the treatment of high cortisol?
Stop steroids
Cushing’s - surgical selective removal of adenoma, bilateral adrenalectomy, radiotherapy
Adrenal adenoma/carcinoma - adrenalectomy
Ectopic ACTH - surgery, drugs to inhibit cortisone sythesis
What is the difference between Cushing’s syndrome and Cushing’s disease?
Syndrome - excess cortisol, loss of hypothalamix pituitary axis feedback, loss of circadian rhythm
Disease - all that caused by pituitary adenoma
What is acromegaly?
What is gigantism?
Excess GH production in adults
Excess production in children before fusion of epiphyses of long bones
What is the epidemiology of acromegaly?
Rare - 3 per million/year
Equal prevalence between women and men
Incidence highest in middle age 40+
What are the risk factors and causes of acromegaly?
Risk factors - MEN-1
Aetiology - benign pituitary GH-producing adenoma, hyperplasia
What is the pathophysiology of acromegaly?
GH - pulsatile release
Stimulated by GHRH, ghrelin
Inhibited by somatostatin, high glucose
Exerts effects via IGF-1 or directly on tissues to induce metabolic changes
Increased secretion due to pituitary tumour or ectopic carcinoid tumour
Stimulates skeletal and soft tissue growth giving rise to giant-like symptoms
Local expansion of tumour can lead to compression of surrounding structures resulting in headaches and visual field loss
How does acromegaly present? - Symptoms
Headaches, excessive sweating, visual deterioration, snoring, wonky bite, increased weight, decreased libido, amenorrhea, arthralgia and backache, acroparaesthesia
How does acromegaly present? - Signs
Skin darkening, coarsening of face with wide nose, rings tight, deep voice, large tongue, increased size of hands and feet, puffy lips, eyelids and skin, obstructive sleep apnoea
What co-morbidites accompany acromegaly?
Impaired glucose tolerance, DM, sleep apnea, hypertension, LV hypertrophy, cardiomyopathy, arrhythmia, IHD, stroke, colon cancer, arthritis
How is acromegaly diagnosed?
High glucose, calcium and phosphate
Plasma GH levels - should be undetectable (but remember pulsatile secretion)
Glucose Tolerance Test - diagnostic if no suppression of glucose
IGF-1 - raised and doesn’t fluctuate so diagnostic
Visual field exam
MRI scan pituitary
ECHO for cardiomyopathy
Old photos - changes
Serum prolactin raised
How is acromegaly treated?
Trans-sphenoidal surgery - remove tumour and correct tumour suppression Somatostatin analogues GH receptor antagonists Dopamine agonist Radiotherapy Stereotactic radiotherapy Gamma knife, LINAC or proton beam
What is Conn’s syndrome?
Excess production of aldosterone independent of renin-angiotensin-aldosterone system
Results in increased sodium and water retention (increased BP) and decreased renin release
Primary hyperaldosteronism
Rare
What are the causes of Conn’s?
Adrenal adenoma that secretes aldosterone
Hyperaldosteronism - bilateral adrenocortical hyperplasia
What are the risk factors of Conn’s?
Hypertension
- Under 35 with no FH
- Malignant hypertension
- Hypokalaemia before diuretic therapy
- Resistant to conventional antihypertensives
- Unusual symptoms
How does Conn’s syndrome present?
Often asymptomatic
Hypertension - can be associated with renal, cardiac and retinal damage if severe
Hypokalaemia - weakness/cramps, paraesthesia, polyuria, polydipsia, constipation
How is Conn’s diagnosed?
Hypokalaemic ECG - flat T waves, ST depression, long QT
Serum hypokalaemia
Plama aldosterone:renin ratio - raised (decreased renin)
Increased plasma aldosterone levels not suppressed with 0.9% saline infusion or fludrocortisone administration
CT and MRI adrenals
U&E
What is a differential diagnosis for Conn’s?
Secondary hyperaldosteronism - excess renin stimulating aldosterone release
Caused by reduced renal perfusion due to
- Renal artery stenosis, accelerated hypertension, diuretics, congestive heart failure, hepatic failure
How is Conn’s treated?
Laproscopic adrenalectomy, aldosterone antagonist - oral spironolactone for 4 weeks pre-op to control BP and K+
What is Addison’s disease?
Primary hypoaldrenalism (can also be caused by TB)
Destruction of entire adrenal cortex resultin in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and sex steroid deficiency
Very rare 0.8 per 100,000
Can be fatal
More common in women
What is secondary hypoadrenalism?
Issue with pituitary glands leading to lack of release of products from adrenal glands
What are risk factors for Addison’s disease?
Autoimmune adrenalitis - destruction of adrenal cortex by adrenal autoantibodies
TB, adrenal metastases, long term steroid use (prevents ACTH release via negative feedback), opportunistic infections in HIV, adrenal haemorrhage/infarction
What are the risk factors in secondary hypoadrenalism?
Long term steroid therapy leading to suppression of pituitary-adrenal axis
Decreased ACTH production from hypothalamic-pituitary disease
How does Addison’s disease present?
Hyperpigmentation (increased CRH and ACTH)
Lethargy, depression, anorexia, weight loss, vitiligo, nausea and vomiting, diarrhoea, constipation, abdominal pain, impotence/amenorrhoea, postural hypotension, lean build, dizzy, dehydration
Tanned, Tired, Toned, Tearful
How is Addison’s diagnosed?
Bloods - hyponatraemia and hyperkalaemia (aldosterone), hypoglycaemia (cortisol), hypoaldosteronism, low cortisol, uraemia, hypercalcaemia, eosinophilia (lack of anti-inflammatory effects from cortisol), anaemia
Short ACTH stimulation test - cortisol will remain low
21-hydroxylase adrenal antibodies
9am ACTH levels
AXR/CXR
How is Addison’s treated?
IV hydrocortisone (cortisol replacement), IV 0.9% saline, glucose infusion if hypoglycaemia, replace steroids with daily 3x to mimic rhythm Fludrocortisone to replace aldosterone Adrenal crisis - IV hydrocortisone immediately and fluids
What are the symptoms of adrenal crisis?
Nausea, vomiting, abdominal pain, muscle cramps, confusion
Shock
How is secondary hypoadrenalism diagnosed and treated?
Diagnosis - ACTH levels low and mineralocorticoid production intact
Treatment - wean off steroids slowly and adrenals will recover
Oral hydrocortisone
What is diabetes insipidus?
Passage of large volumes (> 3L/day) of dilute urine due to impaired water reabsorption in kidney either due to reduced ADH secretion from posterior pituitary (cranial DI) and impaired response of kidney to ADH (nephrogenic DI)
What is the epidemiology of DI?
2-5% women at some time
Mainly between 20-40
What are the differences in causes between cranial DI and nephrogenic DI?
Cranial - pituitary tumour, head trauma
Nephrogenic - drug induced
What is the main risk factor for developing DI?
Family history
Why do patients with DI become dehydrated?
Reduced ADH secretion or impaired response to ADH resulting in significant water losses resultin g in dilute urine
How does DI present?
Polyuria - 15L in 24 hours
Polydipsia
Hypernatraemia due to water loss in excess of Na loss
Dehydration - impaired consciousness
What are the symptoms of hypernatraemia?
Lethargy, thirst, weakness, irritability, confusion, coma, fits
How is DI diagnosed?
Urine volume measured
Blood glucose to exclude DM
Water deprivation test - determine whether kidneys continue to produce dilute urine despite dehydration, measure serum and urine osmolality, urine vol and body weight hourly for 8 hours during fasting and w/o fluids
Cranial DI - MRI of head and test anterior pituitary
Desmopressin (ADH analogues) to differentiate
What differential diagnoses could be made other than DI?
DM - osmotic diuresis secondary to glycosuria
Hypokalaemia
Hypercalcaemia
How is cranial DI treated?
Treat cause - synthetic analogue of ADH - desmopressin
How is nephrogenic DI treated?
Treat cause - usually renal disease
Thiazide diuretics (bendroflumethiazide)
NSAIDs - lower urine volume and plasma Na+ giving prostaglandin synthase
What is SiADH?
Syndrome of inappropriate seretion of ADH
Continuous secretion of ADH despite plasma being very dilute leading to retention of water and excess blood volume and thus hyponatraemia
What is the epidemiology of SiADH?
2-5% of women at some time
20-40 years
What are the possible causes of SiADH?
Tumours CNS - meningitis, head trauma Pulmonary lesions Metabolic causes Drugs
What is the pathophysiology of SiADH?
Excess release of ADH results in increased insertion of aquaporin 2 channels in apical membrane of collecting duct
Excess water retention which will dilute blood plasma resulting in hyponatraemia as Na+ conc will decrease
What are the symptoms of SiADH?
Same as hyponatraemia Anorexia/nausea and malaise Weakness and aches Reduction in GCS and confusion with drowsiness Fits and coma Concentrated urine
How is SiADH diagnosed?
Low serum Na+ Euvolaemia - normal blood volume High urine Na+ > 30 mmol/L Low plasma osmolality High urine osmolality Normal renal, adrenal and thyroid function
How is SiADH treated?
Treat underlying cause where possible
Restrict fluid intake to 500-1000ml daily to increase Na conc
Hypertonic saline - prevents brain swelling
Oral demeclocycline daily - induces nephrogenic DI (inhibits ADH)
Vasoprssin antagonist - oral tolvaptan
Salt and loop diuretic - oral furosemide
What are the measurements that denote hyponatraemia?
Serum Na < 135 mmol/l
Biochemical severe - serum Na < 125 mmol/l
Normal serum Na 137-144mmol
What are the moderate (125-129 mmol/l) symptoms of hyponatraemia?
Headache Irritability Nausea/vomiting Mental slowing Unstable gait/falls Confusion.delerium Disorientation
What are the severe (<125 mmol/l) symptoms of hyponatraemia?
Stupor/coma
Convulsions
Respiratory arrest
What is the difference between acute and chronic hyponatraemia?
Acute - within 48 hours, rapid correction safer and may be necessary, may occur after subarachnoid haemorrhage
Chronic - CNS adapts, correction must be slow < 8mmol/24 hours
How do you investigate hyponatraemia?
Plasma osmolality low High urine osmolality Plasma glucose Urine sodium Urine dip test for proteins TSH Cortisol Consider alcohol TFTs Assessment of underlying causes Review drugs
What is hyperkalaemia?
Serum K+ > 5.5 mmol/L
Serum K+ > 6.5 mmol/L = medical emergency
What causes hyperkalaemia?
Decreased excretion - AKI or oligouric renal failure (v small amount of urine produced), drugs (ACEi, potassium sparing diuretics, NSAIDs), Addison’s disease (adrenal insufficiency, low aldosterone)
Redistribution - intracellular to extracellular - DKA, metabolic acidosis, tissue necrosis or lysis
Increased load - potassium chloride, transfusion of stored blood
What happens during hyperkalaemia?
When K+ levels rise, reduces difference in electrical potential between cardiac myocytes and outside cells meaning threshold for action potential significanly decreased resulting in increased abnormal action potentional = abnormal heart rhythms = ventricular fibrillation and cardiac arrest
What are the symptoms of hyperkalaemia?
Asymptomatic until high enough to cause cardiac arrest
Fast, irregular pulse, chest pain, weakness, light headedness
Muscle weakness and fatigue (over contraction)
Associated with metabolic acidosis
Kussmaul’s respiration
What is could cause a false positive in hyperkalaemia?
Haemolysis from venepuncture or K+ release from abnormal RBCs in blood disorders
Contamination with K+ EDTA anticoagulant in FBC bottles
Thrombocythaemia - K+ leaks out of platelets during clotting
How is hyperkalaemia diagnosed?
Serum K+
Progressive ECG abnormalities - tall, tented T waves, small P waves, wide QRS complexes
How is hyperkalaemia treated?
Non-urgent
- Treat underlying cause
- Review medications
- Dietary K+ restriction
- Polystyrene sulfonate resin binds to K+ in gut reducing absorption
Urgent
- Stabilise cardiac membrane - IV 10 ml 10% calcium gluconate reducing excitability of cardiomyocytes
- Drive K+ into cells - insulin (glucose uptake brings K+ with it) with glucose to avoid hypoglycaemia
- IV or nebulised salbutamol (increases B2 pumping of K+ into cell)
What is hypokalaemia?
Serum K+ < 3.5 mmol/L
Serum K+ < 2.5 mmol/L - medical emergency
What causes hypokalaemia?
Increased excretion - thiazide diuretics, loop diuretics, increased aldosterone secretion (Conn’s), liver/heart failure
Exogenous mineralocorticoids
Renal disease
Reduced dietary intake
Redistribution to cells - beta-agonists
GI losses - vomiting, severe diarrhoea, laxative abuse
How does hypokalaemia present?
Muscle weakness Cramps Hypotonia Hyporeflexia Tetany - spasms Palpitations Light headedness -arrhythmias Constipation
How is hypokalaemia diagnosed?
Serum K+
ECG - small/inverted T waves, prominent U waves, long PR interval, depressed ST segments
How is hypokalaemia treated?
Treat underlying cause
Acute can resolve on own - remove initiated factor
Mild
- K+ supplements
- If on thiazide diuretics move to K+ sparing diuretics
Severe
- IV K+ cautiously, no more than 20mmol/h
What happens in hyponatraemia?
Low Na+ causes water conc gradient out of cell
Increased leakage of ICF causes hyperpolarisation of myocyte membrane decreasing myocye excitiability
What is the action of parathyroid hormone?
Increased bone resorption by osteoclasts
Increased intestinal calcium reabsorption
Activates 1,25-dihydroxyVD in kidney
Increased calcium reabsorption and phosphate excretion in kidney
What are the causes of hyperparathyrodism?
80% solitary adenoma
20% parathyroid hyperplasia
Rare - parathyroid cancer
Secondary to hypocalcaemia - chronic kidney disease, VD deficiency, GI disease
How does hyperparathyroidism present?
Hypercalcaemia - weak, tired, depressed, thirsty, renal stones
Bone resorption - pain, fractures, osteoporosis
Hypertension
What investigations need to be done in hyperparathyroidism?
Bloods
- Primary: increased PTH, increase Ca, decreased phosph
- Secondary: increased PTH, decreased Ca, increased phosph
- Tertiary: increased everything
Increased 24 hour urinary calcium excretion
DEXA bone scan - osteoporosis
How do you treat hyperparathyroidism?
Fluids
Surgically treat underlying cause
Bisphosphonates
What are the causes of hypoparathyroidism?
Autoimmune destruction of PT glands Congenital Surgical removal (secondary) Mg deficiency VD deficiency
What are the symptoms of hypoparathyroidism?
Same as hypocalcaemia SPASM Spasms Peripheral paraesthesia Anxious Seizures Muscle tone increases
How do you treat hypoparathyroidism?
Ca supplements
Calcitriol
Synthetic PTH
What is pseudohypoparathyroidism?
Decreased response to PTH
Blood shows low Ca, high PTH
Treat as normal hypoparathyroid
What is hypercalcaemia?
When serum calcium is above normal
10.5-12 mg/dL
What can cause hypercalcaemia?
Occurs more in elderly women Primary hyperparathyroidism Secondary hyperparathyroidism Tertiary hyperparathyroidism Malignancies Thiazide diuretics Vitamin D analogues Lithium administration
How does primary hyperparathyroidism cause hypercalcaemia?
Excess PTH secretion and production and so hypercalcaemia
How does secondary hyperparathyroidism cause hypercalcaemia?
Physiological compensatory hypertrophy of all parathyroids resulting in excess PTH due to hypocalaemia that occurs in CKD and vitamin D deficiency
Due to diet/GI disease
How does tertiary hyperparathyroidism cause hypercalcaemia?
Occurs after many years of hyperparathyroidism that occurs from CKD or vit D deficiency
Causes glands to act autonomously having undergone hyperplastic or adenomatous change resulting in excess PTH secretion unlimited by feedback control
Most often seen in chronic renal failure
Treating disease so calcium high
How does malignant hpyerparathyroidism cause hypercalcaemia?
PT-related protein produced by some squamous cell lung cancer, breast and renal carcinomas (myeloma and non-Hodgkin’s lymphoma)
- Mimic PTH resulting in hypercalcaemia
- PTH low as PT-related protein not detected
Bone infiltration resulting in calcium mobilisation in multiple myeloma and secondary bone metastases
Production of osteoclastic factors by tumours
Excessive calcium intake
How does hypercalcaemia present?
BONES - pain, fractures, osteopenia/osteomalacia/osteoporosis
STONES - excess calcium, renal colic from renal calculi, biliary stones
GROANS - abdominal pain, malaise, nausea, constipation, polydipsia, calcium deposition in renal tubules, dehydration, confusion, risk of cardiac arrest
MOANS - depression, anxiety, cognitive dysfunction, insomnia, coma
How is primary hyperparathyroidism diagnosed?
High PTH
High calcium
Low phosphate
How is secondary hyperparathyroidism diagnosed?
High PTH
Low calcium
High phosphate
How is tertiary hyperparathyroidism diagnosed?
High PTH
High calcium
High phosphate
How is malignant hyperparathyroidism diagnosed?
Low/undetectable PTH from PT-like protein resulting in hypercalcaemia Low albumin Increased alkaline phosphatase (severe hyperparathyroidism) Protein electrophoresis for myeloma Renal function test TSH to exclude hyperthyroidism X-ray Ultrasound PT ultrasound Radioisotope scanning CT/MRI DXA bone scan ECG - tented T, short QT
How is hypercalcaemia caused by hyperparathyroidism treated?
Treat underlying cause - with surgery
Acute severe hypercalcaemia medical emergency
- Rehydrate with IV 0.9% saline to prevent stones
- Bisphosphonates after rehydration
- Serum U&Es after 48 hours
- Glucocorticoid steroids
Chemotherapy
How do you find the cause of the hypercalcaemia?
Corrected calcium levels mild increase in hyperparathyroidism and PTH high
Corrected calcium levels severe increase in cancer and PTH low
What is hypocalcaemia?
Deficiency of serum calcium
Less than 2.1 mmol/l
When is hypocalcaemia seen?
Hypoparathyroidism
Spans all ages
Common in hospitalised patients and common on ITU wards
What can cause hypocalcaemia?
Primary hypoparathyroidism (high phosph) Secondary hypoparathyroidism Tertiary hypoparathyroidism Pseudohypoparathyroidism Pseudopseudohypoparathyroisim Secondary to increased serum phosphate levels Vitamin D deficiency (low phosph) Reduced PTH function Acute pancreatitis (low phosph) Osteomalacia (low phosph) CKD (high phosph)
How does vitamin D deficiency cause hypocalcaemia?
Results in less calcium absorption
Due to reduced UV exposure, malabsorption, anti-epileptic drugs
How does CKD cause hypocalcaemia?
Inadequate production of active vitamin D and renal phosphate retention
Results in micro-precipitation of phosphate in tissues
How does reduced PTH function cause hypocalcaemia?
Low PTH due to parathyroid gland failure
Primary hypoparathyroidism
Calcium low and phosphate high
Primary hypoparathyroidism
What can cause hypoparathyroidism?
After parathyroidectomy or thyroidectomy surgery
Radiation
Hypomagnesaemia - required for PTH secretion
How does pseudohypoparathyroidism cause hypocalcaemia?
Syndrome of end-organ resistance to PTH due to a mutation in Gs alpha-protein
Low calcium, high PTH
How does hypocalcaemia present?
Parasthesia - pins and needles
Muscle spasms
Basal ganglia calcification
Cataracts
ECG abnormalities
Undermineralised bone with pseudofractures
Increased excitability of muscles and nerves
Papilloedema
SPASMODIC
Spasms, Peripheral paraesthesia, Anxious, irritable, irrational, Seizures, Muscle tone increases in smooth muscles (wheeze), Orientation impaired and confusion, Dermatitis, Impetigo herpetiformis, Chvostek’s sign, Cataract, Cardiomyopahty
What is Chvostek’s sign?
Tap over facial nerve and look for spasms of facial muscles
What is Trousseau’s sign?
Inflate BP cuff to 20mmHg above systolic for 5 mins
Hand will start to form into spasm
How is hypocalcaemia diagnosed?
Chvostek's sign Trousseau's sign Serum urine and creatinine and eGFR for renal disease PTH levels in serum PT antibodies Vitamin D Magnesium X-ray metacarpals (pseudohypoparathyroidism) ECG - long QT
What could a differential diagnosis of hypocalcaemia be?
Hypoalbuminaemia - low total serum calcium but not ionised calcium, work out corrected calcium
Alkalosis
Potassium and magnesium deficiency
Hyperventilation
How do you work out corrected calcium?
Total serum calcium + 0.02 (40-serum albumin)
How is hypocalcaemia treated?
Calcitonin - decreases plasma calcium and phosphate
Bisphosphonates - reduce osteoclast activity
Acute - hospital admission, IV calcium gluconate over 30 mins with ECG
Vit D deficiency - oral cholecalciferol or adcal, ineffective in hypoparathyroidism as PTH needed to convert vit D3 - 1,25 dihydroxyvitamin D
Hypoparathyroidism - calcium supplements, calcitriol
What is hyperprolactaemia?
Increased secretion of prolactin
Commonest hormonal disturbance of the pituitary
More common in women
Presents earlier in women with menstrual disturbance and later in men with erectile dysfunction
Give 4 potential causes of hyperprolactaemia?
Prolactimona - tumour of pituitary resulting in excess prolactin release
Pituitary stalk damage - results in less dopamine so there is no inhibition of prolactin
Drugs - most common, metoclopramide or ecstasy
Physiological - pregnancy, breast feeding, stress
What is the pathophysiology of hyperprolactaemia?
Prolactin secreted by anterior pituitary
Inhibited by dopamine from the hypothalamus
Raised prolactin leads to lactation and inhibition of gonadotropin releasing hormone resulting in reduced LH/FSH and thus reduced testosterone and oestrogen
How does hyperprolactaemia present?
Amenorrhoea/oligomenorrhoea
Infertility
Galatorrhoea - spontaneous flow of milk from breasts in both males and females
Low libido
Low testosterone in men
Erectile dysfunction and reduced facial hair in men
Local effect of tumour - headache, visual defects
CSF leak
How is hyperprolactaemia diagnosed?
Measure basal prolactin level - will be very high
How is hyperprolactaemia treated?
Medical approaches are more efficent that surgical
Dopamine agonists - massive tumour shrinkage, macroadenoma shrinkage = sight saving
Microadenoma usually responds to small doses just once/twice a week
What is a non-functioning pituitary adenoma?
Benign growth in the pituitary gland that doesn’t produce excess hormones in blood and isn’t cancerous
15% of all pituitary adenomas
How does a non-functioning pituitary adenoma present?
Tumour mass effects Hormone excess Hormone deficiency Local mass effects - Visual field defects - Cranial nerve palsy and temporal lobe epilepsy - Headaches - CSF rhinorrhoea
How is a non-functioning pituitary adenoma diagnosed?
Hormonal tests - test the different axes
Tumour mass effects and abnormal hormonal tests - MRI
Test normal pituiart function - may have borderline deficiecny of one or all, circadian rhythms
How do you test the pituitary-thyroid axis?
Primary hypothyroid - raised TSH, low Ft4
Hypopituitary - low Ft4 with normal/low TSH
Graves disease (toxic) - suppresses TSH, high Ft4
TSHoma (rare) - High Ft4, normal/high TSH
Hormone resistance - high Ft4 with normal/high TSH
How do you test the gonadal axis in men?
Primary hypogonadism - low T, raised LH/FSH
Hypopituitary - low T, normal/low LH/FSH
Anabolic use - low T and suppressed LH
Measure 0900 fasted T and LH/FSH in pituitary disease
How do you test the gonadal axis in women?
Before puberty - oestradiol low/undetectable, low LH and FSH (FSH slightly higher then LH)
Puberty - pulsatile LH increases and oestradiol increases
Post-menarche - monthly menstrual cycle with LH/FSH, mid-cycle surge LH/FSH and levels oestradiol increase throughout cycle
Primary ovarian failure (menopause) - high LH/FSH (FSH > LH), low oestradiol
Hypopituitary - olio or amenorrhoea with low oestradiol and normal/low FSH/LH
How do you test the HPA axis?
Circadian rhythm
Measure 0900h cortisol and synacthen
Primary AI - low cortisol, high ACTH, poor response to synacthen
Hypopituitarism - low cortisol, low/normal ACTH, poor response to synacthen
How do you test the GH/IGF1 axis?
GH secreted in pulses with greatest pulses at night and low/undetectable levels between pulses GH levels fall with age, low in obesity Measure IGF-1 and GH stimulation test - Insulin stress test - Glucagon test
How do you measure prolactin levels?
Under negative control of dopamine Stress hormone Measure prolactin or cannulated prolactin (3 samples over an hour to exclude stress of venepuncture) May be raised due to - Stress - Drugs - antipsychotics - Stalk pressure - Prolactinoma
How do you test hormonal axis using dynamic testing?
Dexamethasone suppression test - Cushing’s
Oral glucose GH suppression test - Acromegaly
CRH stimulation - Cushing’s
TRH stimulation - TSHoma
GnRH stimulation - gonadotrophin deficiency
Insulin-induced hypoglycaemia - GH/ACTH deficiency
Glucagon test - GH deficiency
Useful for further evaluation to test pituitary reserve/pituitary hyperfunction
How is non-functioning pituitary adenoma treated?
Hormone replacement therapies
Surgery - if sight threatening
Radiotherapy
Medications
What is precocious puberty?
Early puberty
Considered early puberty at ages 8 in girls and 9 in boys
What is the epidemiology of precocious puberty?
Incidence of 1 in 5,000 to 10,000
90% patients female
Females tend to be idiopathic and otherwise healthy
Males - high chance it’s a brain tumour
How is precocious puberty classified?
True precocious puberty - starts at pituitary, activation of hypothalamus activating GnRH system begins puberty, activation of HPG axis
- Stimulated LH:FSH ratio > 1
Precocious puberty - secreting tumours in gonads, brain, liver, retroperitoneum, mediastinum
- Stimulated LH:FSH ration < 1
- Not activation of HPG axis - could even be suppressed as hormones being produced by gonads will shut doesn HPG axis
What are the causes of true precocious puberty?
GnRH dependent Idiopathic in girls Boys - consider brain tumour CNS tumours CNS disorders - developmental abnormalities, encephalitis, brain abcess, hydrocephalus Secondary central precocious puberty Psychosocial
What are the causes of precocious pseudo-puberty?
Increased androgen secretion - congenital adrenal hyperplasia, virilising neoplasm, Leydig cell adenoma
Gonadotrophin secreting tumours - chorioepitheliomas, germinoma, hepatoma
Ovarian cyst
Oestrogen secreting neoplasm
Hypothyroidism
Iatrogenic or exogenous sex hormones
How is precocious pseudo-puberty diagnosed?
Differential diagnosis True - Stimulation pubertal range - Stimulated LH:FSH ratio > 1 Precocious - Stimulated pre-pubertal range or suppression - Stimulated LH:FSH ratio < 1
How is precocious puberty treated?
GnRH super-agonist the suppress pulsatility of GnRH secretion
Improves final height
Lowers risk of sexual abuse in children
Name an example of a biguanide
Metformin
What are biguanides used for?
To treat DMT2 as first choice medication for control of blood glucose, alone or in combination with other hypoglycaemics such as sulphonyl ureas or insulin
How do biguanides work?
Lower blood glucose by increasing response to insulin
Suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption
DOESN’T cause hypoglycaemia as does not stimulate pancreas
Reduces weight gain and can induce weight loss, which can prevent worsening of insulin resistance
What are the main adverse effects of biguanides?
GI disturbance - may contribute to weight loss
Lactic acidosis can occur in intercurrent lines such as renal or hepatic impairment or cardiac failure
Contraindicated in severe renal impairment and should be withheld in AKI and severe tissue hypoxia, used with care in hepatic impairment and alcohol intoxication
Can interact with IV contrast media so withheld before these investigations
Use with caution with other drugs that may impact renal function eg ACEI diuretics or NSAIDs
Prednisolone, thiazide and loop diuretics elevate blood glucose and may reduce efficacy of metformin
Name an example of a sulphonylurea
Gliclazide
What are sulphonylureas used for?
DMT2 as single agent to control blood glucose and reduce complications where metformin contraindicated/not tolerated
Can be used in combination with metformin and other hypoglycaemics in uncontrolled glucose levels
How do sulphonylureas work?
Lower blood glucose by stimulating pancreatic insulin secretion
Block ATP dependent K+ channels in pancreatic beta cell membranes, causing depolarisation of cell membrane and opening of voltage gates Ca2+ channels, stimulating insulin secretion
Only effective in patients with residual pancreatic function
What are the main adverse effects of sulphonylureas?
GI disturbance occurs infrequently, more serious hypoglycaemia especially when used with other hypoglycaemic medication
Rare hypersensitivity reactions and cause hepatic toxicity, rash and fever and haematological abnormalities
Use with care in hepatic and renal impairment and in people at increased risk of hypoglycaemia
Efficacy reduced by prednisolone, thiazide and loop diuretics which increase glucose
Name an example of a glitazone
Pioglitazone
What are glitazones used for?
DMT2, alone if metformin contraindicated or in combination with metformin/sulphonylurea when glucose levels uncontrolled
How do glitazones work?
Activate peroxisome proliferator-activated receptors which bind FFAs and induce genes that enhance insulin action in skeletal muscle, adipose tissue and liver
Increases peripheral glucose uptake and utilisation and reduces hepatic gluconeogenesis
Increases storage of fatty acids in adipocytes, decreasing amount present in circulation
Less risk of hypoglycaemia as does not stimulate pancreas
What are the main adverse effects of glitazones?
Increased fracture risk, peripheral oedema, anaemia and mild weight gain
Increased risk of bladder cancer
Lower risk of hypoglycaemia than other agents but risk increased in combination
Contraindicated in HF, DMT1 and diabetic ketoacidosis
Used with care in hepatic impairment
What are the different types of insulin?
Insulin aspart Insulin glargine Biphasic insulin Soluble insulin Isophane insulin
What is insulin used for?
Insulin replacement in people with DMT1 and control of blood glucose in those with DMT2 where oral hypoglycaemic treatment inadequate or poorly tolerated
IV in diabetic emergencies such as diabetic ketoacidosis and hyperglycaemic hyperosmolar state
How does insulin work?
Stimulates glucose uptake from circulation into tissue and increases use of glucose as energy source Stimulates glycogen, lipid and protein synthesis and inhibits gluconeogenesis and ketogenesis Rapid acting (insulin aspart), short acting (soluble insulin), intermediate acting (isophane insulin) and long acting (insulin glargine) Biphasic insulin contains mixture of rapid and intermediate acting
What are the main adverse effects of insulin treatment
Hypoglycaemia which can cause lipohypertrophy if administed by injection in same site
Care in renal impairment as increased risk of hypoglycaemia
Combinations with other hypoglycaemic agents increases risk of hypoglycaemia and use with corticosteroids increases the dose required to have to same effects
Name an example of a thyroid replacement hormone
Levothyroxine
What are thyroid replacement hormones used in?
Primary hypothyroidism and hypothyroidism secondary to hypopituitarism
How do thyroid replacement hormones work?
Regulate metabolism and growth preventing effects of hypothyroidism
Thyroixine (T4) converted to active triiodothyronine T3 in target tissues
Levothyroxine synthetic T4
What are the main adverse effects of thyroid replacement hormones?
Hyperthyroidism symptoms - GI disturbance, cardiac arrhythmias, neurological tremors
Increased HR and metabolism and precipitate cardiac ischaemia so used with care in CAD
Corticosteroid therapy must be initiated alongside levothyroixineif patient has hypopituitarism to avoid Addisonian crisis
GI absorption reduced
by antacid, Ca2+ and iron
Increased dose required with cytochrome 450 inducers such as carbamazepine
Increase insulin or other hypoglycaemic requirements in diabetes and enhance effects of warfarin
Name an example of an antithyroid drug
Carbimazole
What are antithyroid drugs used in?
Graves’ disease as long term treatment
Taken before thyroid surgery to lower hormone levels
How do anti-thyroid drugs work?
Prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, reduces production of thyroid hormones T3 and 4
Relief of clinical symptoms slow as large store of preformed T3 and 4 must be depleted before and effect seen - can be months
What are the main adverse effects of anti-thyroid drugs?
Rashes and pruritus common, treated with anti-histamines, more rarely and severely can be bone marrow suppression and resultig neutropenia and agranulocytosis
Care in patients with past or current blood disease or liver impairment
CYP450 enzyme inhibitor so drugs metabolism by this eg warfarin may become toxic if does not lowered
Name an example of a growth hormone receptor antagonist
Pegvisomant
What are growth hormone receptor antagonists used for?
Treatment of acromegaly if pituitary tumour cannot be controlled with surgery or irradiation
Administered as a powder solution injection
How do growth hormone receptor antagonists work?
Block action of growth hormone at the growth hormone receptor to reduce the production of IGF-1
What are the main adverse effects of growth hormone receptor antagonists?
Reactions at injection site GI disturbance Hypoglycaemia, chest pain, hepatitis Increased GH levels - reduces feedback Use with care in diabetics and patient with malignant tumours or liver impairment
Name an example of a vasopressin antagonist
Tolvaptan
What are vasopressin antagonists used for?
Treatment of euvolaemic (SIADH) and hypervolaemic hyponatraemia
How does vasopressin antagonists work?
Inhibit vasopressin-2 receptor so increases fluid excretion Causes aquaresis (exretion of H2O with NO electrolyte loss) leading to increases Na+ in hyponatraemia
What are the main adverse effects of vasopressin antagonists?
GI disturbance, headache, increased thirst, insomina
Hypersensitivity reactions
Contraindicated in hypovolaemic hyponatraemia and severe renal impairment
Can interact with statins and cause serious muscle problems
Side effects increased with macrolides
Can cause enhanced effects of benzodiazepines and digoxin when used together
What do statins do?
HMG-CoA reductase inhibitors
Enzyme responsible for cholesterol biosynthesis
Name 3 examples of statins
Atorvastatin
Lovastatin
Simvastatin
Fluvastatin
Name an example of a vasopressin analogue
Desmopressin
What are vasopressin analogues used for?
Treatment of cranial diabetes insipidus
Also used to distinguish cranial and nephrohenic diabetes insipidus
How do vasopressin analogues work?
Replace endogenous vasopressin that is missing in cranial diabetes insipidus
Works on renal collecting duct by binding to V2 receptors, which signal aquaporin 2 to be inserted into the collecting duct apical membrane and thus increase water reabsorption from the usrine
What are the main adverse effects of vasopressin analogues?
Headaches, facial flushing, nausea, seizures
Hyponatraemia
Contraindicated in moderate to severe renal impairment and patients with hyponatraemia
Use with tricyclic antidepressants, SSRIs, NSAIDs, opioid analgesics should be monitored carefully as may increase risk of water intoxication with hyponatraemia
Name an examples of an adrenal corticosteroid inhibitor
Metyrapone
What are adrenal corticosteroid inhibitors used for?
Diagnosis of adrenal insufficiency
Control cortisol hypersecretion in Cushing’s
How to adrenal corticosteroid inhibitors work?
Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11 beta-hydroxide enzymes
Enzyme normally stimulates adrenocorticotrophic hormone secretion and increases plasma 1–deoxycortisol level that is metabolised to cortisol - inhibiting enzyme leads to a reduction in cortisol
What are the main adverse effects of adrenal corticosteroid inhibitors?
GI disturbance, headache, dizziness and drowsiness
Hirsutism can occur because of excess androgen precursors created
Contraindicated in adrenal cortical insufficiency and patients taking corticosteroids
Use in care in patients on paracetamol as liver damage can be increased, and insulin or other hypoglycaemics as side effects may be increased
Corticosteroid, oestrogen and phenytoin can reduced effectiveness
Name 3 examples of synthetic corticosteroids
Bethamethasone
Prednisone
Prednisolone
Methyprednisolone
What are steroids used for?
Decreasing inflammation and reducing activity of immune system
Treat a variety of inflammatory diseases
What are the main adverse effects of steroids?
Acne Easy bruising High BP Increased appetite, weight gain Hirsutism Insomnia Osteoporosis Stomach irritation/bleeding Restlessness Lower resistance to infection Swollen, puffy face Water retention Worsening of diabetes
