Endocrinology Flashcards
pathology of T1DM
- autoimmune destruction of insulin producing beta cells in the islet of Langerhans
- insulin deficiency
- genetic and environmental triggers
pathology of T2DM
- low insulin secretions and peripheral insulin resistance
- genetic and mostly environmental (obesity, sedentary lifestyle stc)
what can cause secondary diabetes mellitus
- acromegaly = excessive GH, insulin resistance rises
- Cushing’s syndrome = increased insulin resistance
- Drug-induced diabetes = glucocorticoids increase insulin resistance
what is maturity onset diabetes of the young (MODY)
- single gene defect altering beta cell function
- good control on low dose insulin
- no ketosis
- parents affected with diabetes
- sensitive to sulphonyl urea
how does diabetes cause polyuria and thirst
- mobilisation of energy stores from muscles, fat and the liver
- hyperglycaemia
- in kidneys the glucose reabsorption mechanism becomes saturated so glucosuria
- glucose in renal tubules draws water in = osmotic diuresis
- raised plasma osmolality stimulates thirst centre
screening and diagnosis for DM
- fasting plasma gluctose >7mmol/L
- random plasma glucose >11mmol/L
- HbA1c 6.5% or 48mmol/mol
- neuropathy screening = sensation, vibration, ankle reflexes
consequences of untreated T1DM
- fat metabolisation = glycerol and free fatty acids
- FFA impair glucose uptake and are oxidised to for ketone bodies in the liver (acetone, beta-hydroxybutyrate)
- ketone bodies dissolve in the blood and release H+ causing acidosis
what are the symptoms of diabetic ketoacidosis
- polyuria
- polydipsia
- nausea and vomiting
- weight loss
- abdo pain
what are the signs of DKA
- hyperventilation (Kussmaul breathing to try remove CO2 to decrease blood acidity)
- dehydration
- fruity breath
- hypotension
- tachycardia
- coma
management of DKA
- Rehydration
- Insulin
- Replacement of electrolytes (K+)
- Treat underlying cause
complications of DM
- diabetic retinopathy
- diabetic nephropathy (end stage renal disease)
- peripheral vascular disease
- stroke
- CV disease
- diabetic peripheral neuropathy
diabetic neuropathy
-Pain – burning, paraesthesia
-Autonomic – orthostatic hypotension, constipation, ED
-Insensitivity – foot ulceration, Charcot foot, amputation
-Peripheral neuropathy – glove and stocking sensory loss
-Treatment: good glycaemic control, anticonvulsants, opioids.
-Consequences: diabetic foot ulceration can lead to
amputation.
diabetic retinopathy
- Micro-aneurysms: pericyte and smooth muscle loss
- Leakage: basement membrane thickening reduced junctional contact with endothelial cells
- Ischaemia: pericyte loss
- Treatment: laser therapy to stabilise changes
management of T1DM
- insulin treatment twice daily with meals
- DAFNE = dose adjustment for normal eating
management of T2DM
- first line = weight loss and exercise
- second line = meds for BP, blood glucose and lipids
> metformin = weight loss
> metformin and sulphonyl urea = weight gain and chance of hypo
> insulin
how does metformin work
- increases insulin sensitivity
how does sulphonyl urea work
- increase insulin release from beta cells
hyperglycaemic hyperosmolar state
- complication of T2DM (unwell patients) = hyperglycaemia result in high osmolarity without ketoacidosis
- dehydration and glucose>30mmol/L
- occlusive events = give LMWH prophylaxis
- rehydrate slowly of 48h then replace K+ when urine flows
what are the 3 mechanisms of hyperthyroidism
- overproduction
- leakage of preformed hormone
- ingestion of excess
causes of hyperthyroidism
- Grave’s disease
- toxic multinodular goitre
- toxic adenoma
- congenital
- thyroiditis
symptoms of hyperthyroidism
- weight loss, tachycardia, anxiety, heat intolerance, sweating, diarrhoea, menstrual disturbance
signs of hyperthyroidism
- Grave’s = diffuse goitre, thyroid eye disease, acropachy (swelling of hands/ clubbing)
- adenoma specific = solitary nodule
- multinodular goitre
investigations for hyperthyroidism
- TFT
- diagnosis of underlying cause
- clinical history
- thyroid antibodies
treatment of hyperthyroidism
- antithyroid drugs = thionamides (carbimazole)
- beta blockers (propranolol)
- radioiodine
- surgery (thyroidectomy)
pathology of Grave’s disease
- immune attack on TSH receptors on thyroid gland
- TSH receptor stimulating antibody (TRAb) activates receptor and causes high thyroid hormone levels
what will TFT show for Grave’s disease
- high T3/4
- low TSH
symptoms and signs of Grave’s
Anxiety and irritability A fine tremor of your hands or finger Heat sensitivity and sweating Weight loss goiter Bulging eyes – Graves’ ophthalmopathy Thick, red skin usually on the shins or tops of the feet - Graves’ dermopathy
what is Graves ophthalmopathy
- bulging eyes
- treat with corticosteroids/ orbital decompression surgery
what is Graves dermopathy
thick, red skin on shins or top of feet
management of Grave’s
- radioactive iodine therapy
- anti-thyroid meds = carbimazole
- beta blockers = propranolol
- thyroidectomy
what is primary hypothyroidism
- > 99%
- absence/dysfunction of thyroid gland
- most from Hashimoto’s thyroiditis (autoantibodies block TSH receptors)
- other causes = thyroidectomy or iodine deficiency
what is secondary hypothyroidism
- pituitary/hypothalamic dysfunction
- TSH deficiency
what is tertiary hypothyroidism
- withdrawal of thyroid suppressive therapy
signs of hypothyroidism
Weight gain Slowed speech and movements Dry skin Jaundice Pallor Coarse, brittle, straw-like hair Loss of scalp hair, axillary hair, pubic hair, or a combination Hoarseness Bradycardia Pericardial effusion
TFT results for primary hypothyroidism
- high TSH
- low T3/4
TFT results for secondary hypothyroidism
- inappropriately low TSH for low T3/4
management of hypothyroidism
- 100ug thyroid hormone (levothyroxine) - titre according to TSH
- monitor until correct titration
- T4 half life is long so check 6-8 weeks after dose adjustment
pathology of Hashimoto’s thyroiditis
- aggressive destruction of thyroid cells by cell and Ab mediated immune process
- Abs against thyroid peroxidase (TPO antibodies)
- Abs bind and block TSH receptors
- CD8+ cytotoxic t cells destroy thyroid follicular epithelial cells
- inflammation of thyroid gland
triggers of Hashimoto’s thyroiditis
- iodine
- infection
- smoking
management of Hashimoto’s disease
levothyroxine
resection of obstructive goitre
what are the 5 types of thyroid cancer
- papillary 60%
- follicular <25%
- medullary 5%
- lymphoma 5%
- anaplastic (rare)
what kind of thyroid cancer does radiation cause
papillary carcinomas
what kind of thyroid cancer does iodine deficiency cause
follicular carcinomas
clinical presentation of thyroid carcinomas
painless, palpable, solitary thyroid nodule
hard and fixed
rapid growth
investigations for thyroid carcinoma
- head and neck examination
- fine-needle aspiration biopsy
- indirect laryngoscopy
- serum calcitonin (high in medullary)
papillary thyroid carcinoma
- younger patients
- spread to lymph nodes and lungs
- treatment = total thyroidectomy, consider node excision/ radioiodine to ablate residual cells
- levothyroxine
follicular thyroid carcinoma
Middle age
Spreads early via blood (bone, lungs)
Treatment – total thyroidectomy + T4 suppression + radioiodine ablation
medullary thyroid carcinoma
Sporadic (scattered) or part of MEN syndrome (multiple endocrine neoplasia)
May produce calcitonin which can be used a cancer marker
Treatment – thyroidectomy + node clearance
lymphoma thyroid carcinoma
Female: male = 3:1
May present with stridor/ dysphagia
Do full staging pre-treatment (chemotherapy)
Assess histology for mucosa-associated lymphoid tissue (MALT)
anaplastic thyroid carcinoma
female, elderly
- poor response to treatment (excision and radiotherapy)
what is Cushing’s syndrome
chronic excess levels of corticosteroids (particularly cortisol) in the body due to hyperfunction of the adrenal gland (often due to the use of corticosteroid medication)
what is Cushing’s disease
a tumour on the pituitary gland that causes the gland to produce too much ACTH, leading to bilateral adrenal hyperplasia and high levels of cortisol production
symptoms of Cushing’s
Weight gain
Mood change – depression, lethargy, irritability
Proximal weakness
Gonadal dysfunction – irregular menstruation, erectile dysfunction
Acne
signs of Cushing’s
Central obesity - round face, supraclavicular fat distribution
Skin and muscle atrophy
Purple abdominal striae
Osteoporosis
investigations for Cushing’s
-Overnight dexamethasone suppression test
>1mg dexamethasone at midnight, the take serum cortisol at 8am
>Normally cortisol suppresses to <50nmol/L – NO suppression in Cushing’s syndrome
-If positive, test for plasma ACTH
If ACTH is undetectable, a tumour adenoma is likely
management of Cushing’s
- Iatrogenic – stop medications if possible
- Cushing’s disease – selective removal of pituitary adenoma
pathology of acromegaly
- excess GH stimulates growth of bone and soft tissue through secretion of insulin-like growth factor 1
- abnormal growth of hands, feet and face
symptoms of acromegaly
Acral enlargement (peripheries – hands and feet) Arthralgias (joint pain) Maxillofacial changes Excessive sweating Headache Backache Hypogonadal symptoms Acroparaesthesia (burning, tingling sensations in the extremities) Amenorrhoea (absence of menstruation) Decreased libido
signs of acromegaly
Growth of hands Coarsening face; wide nose Macroglossia (big tongue) Puffy lips, eyelids and skin Obstructive sleep apnoea Goitre
differential diagnoses for acromegaly
Marfan syndrome
Precocious puberty
Prolactinoma
Gigantism
investigations for acromegaly
-Acromegaly is excluded if; >GH <0.4 ng/ml and normal IGF-I -If either abnormal proceed to: >75mg glucose tolerance test (GTT) -Acromegaly excluded if: >IGF-I normal and GTT normal and GH <1 ng/ml
why can’t GH be relied on alone for diagnosing acromegaly
- GH secretions are pulsatile and increase during pregnancy, stress and sleep
management of acromegaly
- pituitary surgery (trans-sphenoidal)
- dopamine agonists (cabergoline)
- radiotherapy
what is Conn’s syndrome
- primary hyperaldosteronism
- disease of the adrenal glands involving excess production of aldosterone (independent of the renin-angiotensin system)
pathology of Conn’s syndrome
- excess aldosterone
- solitary aldosterone-producing adenoma (mutations in K+ channels)
- aldosterone causes transport of Na and K in distal renal tubule (increased reabsorption of Na and excretion of K)
symptoms of Conn’s syndrome
-Often asymptomatic
-Signs of hypokalaemia:
Weakness
Cramps
Paraesthesia
Polyuria (excessive urine production)
Polydipsia (excessive thirst)
signs of Conn’s syndrome
- hypertension
- low potassium
investigations for Conn’s syndrome
- investigate for supressed renin and increased aldosterone
- adrenal vein sampling
- U&E (K low or normal )
management of Conn’s syndrome
- Laparoscopic adrenalectomy
- Spironolactone (25-100)mg for 4 weeks pre-op controls BP and K+
what is secondary hyperaldosteronism
- excess aldosterone production due to high renin from decreased renin perfusion (renal artery stenosis, hypertension, diuretics etc)
pathology of adrenal insufficiency
- Autoimmune destruction of the entire adrenal cortex.
- reduction in ability to produce cortisol and/or aldosterone.
- Excess ACTH stimulates melanocytes, resulting in the pigmentation.
what is primary adrenal insufficiency (Addison’s disease)
Destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
what is secondary adrenal insufficiency
Hypopituitarism/ long-term steroid therapy leading to suppression of the pituitary-adrenal axis
symptoms of adrenal insufficiency
- Fatigue
- Weight loss
- Dizzy
- Faints
- Poor recovery from illness
- headache
- abdo pain
- diarrhoea/constipation
symptoms of adrenal crisis
Hypotension and cardiovascular collapse Fatigue Fever Hypoglycaemia Hyponatraemia and hyperkalaemia
signs of adrenal insufficiency
Pigmentation and pallor
Primary – Hyperpigmentation
Secondary – no pigmentation
Hypotension
investigations for adrenal insufficiency
- Short ACTH stimulation test – give ACTH, if cortisol remains low then it diagnoses AI.
- low Na, high K cue to decreased aldosterone
- history (TB, cancer, family history of autoimmunity, previous use of steroids)
management of AI
- Replace the aldosterone with fludrocortisone (for primary AI)
- Hydrocortisone 2/3 times daily to replace the cortisol
- Mineralocorticoids to correct postural hypertension
what is diabetes insipidus
- A rare metabolic disorder in which the patient produces large quantities of dilute urine and is constantly thirsty
pathology of diabetes insipidus
- deficiency of pituitary hormone vasopressin (AVP)/ADH
- body can’t concentrate urine and too much water is passed
cranial diabetes insipidus
- most common
- not enough AVP
- caused by damage to hypothalamus/ pituitary gland (after infection, surgery, brain tumour)
nephrogenic diabetes insipidus
- enough AVP but kidneys fail to respond
- caused by kidney damage or sometimes inherited
symptoms of DI
- Polydipsia (extreme thirst)
- Polyuria (excessive urine) – up to 20litres per day in severe cases
- Tiredness (having to pass urine at night)
- Irritability
- Difficulty concentrating
investigations for DI
- water deprivation test = no fluid for 8h = DI patients will still pass large amounts of dilute urine
- vasopressin test = inject small dose = urine production will stop in cranial DI but not nephrogenic
- MRI scan of head to look for damage
management of DI
- fluid intake increased
- desmopressin to replicate function of AVP in cranial
- thiazide diuretic for nephrogenic DI to reduce vol of urine
what is syndrome of inappropriate secretion of ADH
The hyponatraemia and hypo-osmolality resulting from inappropriate, continued secretion or action of the ADH/ vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion.
causes of syndrome of inappropriate secretion of ADH
Disordered hypothalamic -pituitary secretion or ectopic production of ADH.
- Malignancy – lung small-cell, pancreas, prostate, thymus, or lymphoma
- CNS disorders – meningoencephalitis, abscess, stroke, subarachnoid/ subdural haemorrhage
- Chest disease – TB. Pneumonia, abscess
- Drugs – opiates, cytotoxics
- Other – trauma, major abdominal surgery, symptomatic HIV
clinical chemistry of inappropriate secretion of ADH
- Decreased Na+ with decreased or normal urea and creatinine
- Decreased plasma osmolality
- Increased urine osmolality
- Increased urine Na+.
signs and symptoms of inappropriate secretion of ADH
- Nausea
- Irritability and headache with mild dilutional hyponatraemia
- Fits and coma with severe hyponatraemia
investigations for inappropriate secretion of ADH
- FBC = Na, K, Cl, bicarbonate
- hyponatraemia with hypo-osmolality (Na >20mmol/L in urine, osmolality >100mOsmol/kg)
management of inappropriate secretion of ADH
Treat the cause and restrict the fluid
Consider salt +/- loop diuretic if severe.
Vasopressin receptor antagonists - Vaptan
pathophysiology of PTH (parathyroid hormone)
- normally secreted in response to low ionized Ca2+ levels, by 4 parathyroid glands situated posterior to the thyroid.
- negative feedback via Ca2+ levels.
primary hyperparathyroidism
- caused by a solitary nodule or hyperplasia of all glands = additional secretive tissue
secondary hyperparathyroidism
- caused by decreased vit D intake or chronic renal failure
- gland becomes hyperplastic in response to chronic hypocalcaemia
- can present with skeletal or CV complications
tertiary hyperparathyroidism
- occurs after prolonged secondary hyperparathyroidism, causing glands to act autonomously after undergoing hyperplastic or adenomatous change
symptoms of hyperparathyroidism
- bones = osteoporosis
- stones = kidney stones
- psychic groans = confusion
- abdominal moans = constipation, acute pancreatitis
diagnosis of hyperparathyroidism
- Primary = Increased Ca2+ and PTH, Increased ALP – from bone resorption
- Secondary = Low serum calcium, Raised PTH
- Tertiary = Raised calcium, Raised PTH
management of hyperparathyroidism
- primary = removal of adenoma
- secondary = calcium correction and treat cause
- calcium mimetic
what is hypoparathyroidism
subnormal activity of the parathyroid glands, causing a fall in the blood concentration of calcium and muscular spasms
causes of hypoparathyroidism
genetics, autoimmune (polyglandular type 1), infiltration of the parathyroid glands by iron overload (haemochromatosis), parathyroidectomy
pathology of hypoparathyroidism
- no PTH to activate vit D so less intestinal and renal absorption of calcium and less calcium release from bones
symptoms of hypoparathyroidism
- increased excitability of muscles and nerves. - Numbness around the mouth/ extremities, cramps, tetany, convulsions.
- Chvostek and Trousseau signs
what is pseudohypoparathyroidism
- genetic defect that causes lack of response to PTH. - Treatment with calcium and vitamin D can reverse most of the features
- short stature, obesity, round faces, mild learning difficulties, short fourth metacarpals
what is pseudopseudohypoparathyroidism
symptoms of pseudohypoparathyroidism are present, but the patient’s response to parathyroid hormone is normal.
what is hypercalcaemia of malignancy
- Malignancies of the lung, oesophagus, skin, cervix, breast and kidney.
- tumour secretes parathyroid hormone-related protein which results in increased calcium levels.
symptoms of hypercalcaemia of malignancy
- bones, stones, groans and moans
- weight loss
- nausea
- polydipsia and polyuria
- dehydration
- seizure (short QT interval on ECG)
- coma
- many others
management
- aggressive rehydration
- bisphosphonates (zoledronic acid IV)
- control underlying malignancy
causes of hypocalcaemia
- HAVOC – hypoparathyroidism, acute pancreatitis, vit D deficiency, Osteomalacia, CKD
- respiratory alkalosis
clinical presentation of hypocalcaemia
SPASMODIC: spasms, paraesthesia, anxious/irritable, seizures, muscle tone increase, orientation impaired, dermatitis, impetigo herpetiformis, Chvostek’s sign/ cataracts/ cardiomyopathy.
- seizures = prolongation of QT interval (ST segment)
complications of hypocalcaemia
Dysphagia Wheezing; bronchospasm Syncope Congestive heart failure Angina
investigations for hypocalcaemia
- serum albumin (rule out albuminemia)
- Chvostek’s sign – tap over facial nerve and look for spasm
- Trousseau’s sign – compression of brachial artery causes carpopedal spasm (wrist and fingers flex)
- eGFR to look for CKD
- PTH and vit D levels
management of hypocalcaemia
- mild = calcium 5mmol/6hours with daily plasma Ca levels
- severe = 10ml of 10% calcium gluconate IV over 30 min
- treat cause (if resp alkalosis then correct it)
hyperkalaemia
- usually from failure of kidneys to secrete it
Mild: 5.5-6.0mEq/L
Moderate: 6.1-7.0mEq/L
Severe: ≥7.0mEq/L
causes of hyperkalaemia
- Renal impairment (retention of K in nephron)
- Rhabdomyolysis (muscle injury – death of muscle fibres that release their contents into the bloodstream)
- Metabolic acidosis
- Addison’s disease (primary adrenal insufficiency)
- Drugs interfering with potassium excretion e.g. ACEi
- Burns
clinical presentation of hyperkalaemia
- A fast, irregular pulse
- Chest pain
- Weakness
- Palpitations
- Light-headedness
- dyspnoea
- paraesthesia
- frank muscle paralysis
differential diagnoses for hyperkalaemia
Metabolic acidosis
Rhabdomyolysis
Acute tubular necrosis
investigations for hyperkalaemia
- plasma potassium >6.5 is an emergency
- bloods
- ECG ( tall tented T waves, small P waves, wide QRS complex and ventricular fibrillation)
- urine K, Na and osmolality
acute treatment of plasma potassium >6.5 mmol/L
- calcium gluconate = protects heart from ventricular fibrillation
- insulin and dextrose drives K into cells
- nebulised salbutamol
- calcium resonium
management of hyperkalaemia
- Polystyrene sulfonate resin, binds K+ in the gut, preventing absorption and bringing K+ levels down over a few days.
- If vomiting – 30g enema, followed by a 9 hour colonic irrigation
what is the main cause of hypokalaemia
- dehydration
- increase in aldosterone
pathology of hypokalaemia
- GI fluid loss -> less chloride -> increase in aldosterone -> decreased potassium reabsorption.
- Excessive loss of potassium through the kidneys in response to aldosterone or diuretic
causes of hypokalaemia
Diuretics - hyperaldosteronism Vomiting and diarrhoea Pyloric stenosis Intestinal fistula Cushing’s syndrome/ steroids/ ACTH Conn’s syndrome Alkalosis
clinical presentation of hypokalaemia
Muscle weakness Hypotonia Hyporeflexia Cramps Tetany (intermittent muscular spasms) Palpitations Light-headedness (arrhythmias) Constipation
investigations for hypokalaemia
- K <2.5mmol/L = urgent
- ECG = T wave inversion, prominent U wave
- Urine potassium, sodium and osmolality
management of hypokalaemia
- Mild (>2.5mmol/L) = Oral K+ supplement, Review after 3 days
- Severe (<2.5mmol/L) = IV potassium (no more than 20mmol/h and 40mmol/L), Do not give K+ if oliguric.
what are neuroendocrine tumours
Tumours that form from cells that release hormones into the blood in response to a signal from the nervous system
3 vital signs for neuroendocrine tumours
- Pressure on local structure e.g. optic nerves – bitemporal hemianopia
- Pressure on normal pituitary – hypopituitarism
- Functioning tumour – prolactinoma, acromegaly, Cushing’s disease
what is a prolactinoma
lactotroph cell tumour of the pituitary
sizes of prolactinomas
Microadenoma – tumour <1cm
Macroadenoma – tumour >1cm
Microprolactinoma – virtually always stays small
Macroprolactinoma – can be massive
clinical presentation of prolactinoma
- local effect of tumour
- effect of prolactin = menstrual irregularity/ amenorrhoea, Galactorrhoea, Infertility, Loss of libido, Low testosterone in men
diagnosis of prolactinoma
- US
- CT
- MRI
- PET
management of prolactinoma
dopamine agonists (cabergoline)
- remarkable shrinkage with macroadenoma
- microadenoma respond to small dose of cabergoline twice a week
what is a pheochromocytoma
Catecholamine (adrenaline) secreting tumour.
pathology of pheochromocytoma
tumours of the chromaffin cells of the medulla that produce catecholamine
clinical presentation of pheochromocytoma
Episodic Headaches Palpitations Sweating Tremor Anxiety and nausea Hypertension Tachycardia Pallor
investigations for pheochromocytoma
- 24 hour urine collection for urinary catecholamines and metabolites
- Plasma catecholamines
management of pheochromocytoma
-surgery preceded by alpha and beta blocker to stagger adrenaline loss
what is a carcinoid tumour
Neuroendocrine tumours that particularly affect the small bowel, large bowel or appendix
common sites for carcinoid tumours
appendix (45%), ileum (30%), rectum (20%), or elsewhere in GI tract
pathology of carcinoid tumours
- tumours of enterochromaffin cell origin
- secrete bioactive compounds if metastasise to liver (carcinoid syndrome)
what is carcinoid syndrome
collection of symptoms some people get when a neuroendocrine tumour (usually hepatic involvement) releases hormone such as serotonin into the blood stream
symptoms of carcinoid tumours
Bronchoconstriction
Diarrhoea
Skin flushing
carcinoid crisis
- when a tumour outgrows its blood supply, mediators flood out.
- Life-threatening vasodilation, hypotension, tachycardia, bronchoconstriction and hyperglycaemia occur.
- Treated with high dose octreotide (synthetic somatostatin)
investigations for carcinoid tumours
-Increased 24h urine 5-hydroxyindoleacetic acid (5HIAA)
CXR + chest/pelvis MRI/CT
Echocardiography (investigate carcinoid heart disease)
Liver ultrasound (metastases)
management of carcinoid tumours
- octreotide = blocks release of tumour mediators
- loperamide for diarrhoea
- tumour resection
