KEY ENDOCRINE Flashcards
What does mitral stenosis cause?
Left atrial hypertrophy.
What does aortic stenosis cause?
Left ventricular hypertrophy.
What does mitral regurgitation cause?
Left atrial dilatation.
What does aortic regurgitation cause?
Left ventricular dilatation.
2 causes of mitral stenosis.
Rheumatic heart disease
Infective endocarditis
Murmur caused by mitral stenosis.
Mid-diastolic, low-pitched ‘rumbling’ murmur.
Effect of mitral stenosis on S1 sound.
Loud S1.
2 associations of mitral stenosis.
Malar flush (back pressure of blood in pulmonary system causes increased CO2 and vasodilation).
Atrial fibrillation (as left atrium struggles to push blood through the stenotic valve, causing strain + electrical disruption + fibrillation).
Murmur caused by mitral regurgitation.
Pan-systolic, high-pitched ‘whistling’ murmur.
Where does the mitral regurgitation murmur radiate to?
The axilla.
What additional heart sound can you hear in mitral regurgitation?
Third heart sound (S3).
3 causes of mitral regurgitation.
Idiopathic weakening of the valve with age.
IHD
Infective endocarditis
Rheumatic heart disease
Connective tissue disorders (EDS/ Marfan syndrome)
Murmur caused by aortic stenosis.
Ejection systolic, high-pitched murmur with a crescendo-decrescendo character.
Where does an aortic stenosis murmur radiate to?
The carotids.
Pulse characteristics of a patient with aortic stenosis.
Slow rising pulse + narrow pulse pressure
Common complaint with aortic stenosis
Exertional syncope due to difficulties maintaining blood flow to the brain
2 causes of aortic stenosis
Idiopathic age related calcification
Rheumatic heart disease
Murmur caused by aortic regurgitation
Early diastolic, soft murmur ± Austin flint murmur (early diastolic ‘rumbling’ murmur heard at the apex).
Pulse characteristic associated with aortic regurgitation.
Collapsing pulse.
2 causes of aortic regurgitation.
Idiopathic age related weakness.
Connective tissue disorders (EDS/ Marfan syndrome)
3 causes of Cushing’s syndrome.
Exogenous steroids.
Cushing’s disease (pituitary adenoma).
Adrenal adenoma (hormone secreting adrenal tumour).
Paraneoplastic Cushing’s
Most common cause of paraneoplastic Cushing’s?
Small cell lung cancer releasing ectopic ACTH.
Test of choice for diagnosing Cushing’s syndrome?
Dexamethasone suppression test.
Normal response for the low dose dexamethasone suppression test?
Suppression of cortisol release.
Abnormal result for low dose dexamethasone suppression test?
Non-suppressed morning cortisol measurement.
If a low dose dexamethasone suppression test is abnormal, what is the next test to be done?
What is the purpose of this test?
High dose dexamethasone suppression test to differentiate causes of Cushing’s syndrome.
High dose dexamethasone suppression test result in Cushing’s disease.
Cortisol suppressed by higher dose of dexamethasone as pituitary still shows some response to negative feedback.
High dose dexamethasone suppression test result in adrenal adenoma.
Cortisol is not supressed (as production is independent from pituitary).
ACTH is suppressed due to negative feedback on hypothalamus and pituitary.
High dose dexamethasone suppression test result in ectopic ACTH secretion.
Both cortisol and ACTH are not suppressed as production is independent of hypothalamus and pituitary.
Dose of dexamethasone used in:
1) Low dose suppression test.
2) High dose suppression test.
1) 1mg
2) 8mg
Describe the effects of the high dose dexamethasone suppression test on cortisol and ACTH in the following causes:
1) Pituitary adenoma
2) Adrenal adenoma
3) Ectopic ACTH
1) Cortisol suppressed + ACTH suppressed.
2) Cortisol not suppressed + ACTH suppressed.
3) Cortisol + ACTH both suppressed.
FBC results in Cushing’s syndrome.
Raised WCC
Raised electrolytes
Low potassium (if aldosterone also released from adrenal adenoma).
Cause of primary adrenal insufficiency.
Addison’s disease (autoimmune disease where adrenals are damaged)
What is secondary adrenal insufficiency?
Inadequate release of ACTH causing less cortisol to be released from adrenals.
Normally caused by loss of or damage to the pituitary gland.
What is Sheehan’s syndrome?
Where massive blood loss in childbirth leads to pituitary gland necrosis.
What is tertiary adrenal insufficiency?
Inadequate release of CRH.
Normally caused by long term use of exogenous steroids.
Signs of adrenal insufficiency.
Bronze hyperpigmentation of the skin + hypotension (normally postural hypotension).
Electrolyte abnormalities in adrenal insufficiency.
Hyponatraemia + hyperkalaemia
Investigation of choice for adrenal insufficiency?
Short synacthen test.
ACTH level in primary adrenal failure?
High.
Pituitary is producing loads of ACTH to try and stimulate adrenals + there is no negative feedback in the absence of cortisol.
ACTH level in secondary adrenal failure?
Low.
Adrenal glands are not releasing cortisol as they are not being stimulated by ACTH.
Which antibodies are present in 80% of autoimmune adrenal insufficiency patients?
Adrenal cortex antibodies + 21-hydroxylase antibodies.
Result of short synacthen test in primary adrenal insufficiency.
Cortisol does not increase (is not double the baseline).
When is ACTH measures in the short synacthen test?
Baseline, 30 minutes, 60 minutes.
Management of adrenal insufficiency.
Hydrocortisone to replace cortisol.
Fludrocortisone to replace aldosterone.
Sick day rules for adrenal insufficiency?
Double corticosteroid dose.
Presentation of Addisonian crisis.
Reduced consciousness Hypotension Hypoglycaemia Hyponatraemia Hyperkalaemia
Management of Addisonian crisis.
Intensive monitoring if very unwell IV hydrocortisone IV fluids Correct hypoglycaemia Monitor electrolytes and fluid balance
TSH level in hyperthyroidism?
Low
Only cause of hyperthyroidism where TSH is high?
Pituitary adenoma which secretes TSH.
TSH level in hypothyroidism?
High (as it is trying to stimulate more thyroid hormone release).
Cause of hypothyroidism where TSH is low?
Pituitary/ hypothalamic cause (secondary hypothyroidism).
T3 +T4 levels + TSH levels in hyperthyroidism?
T3+T4 elevated.
TSH low.
T3+T4 levels + TSH levels in hypothyroidism?
T3+T4 low
TSH high
TSH and T3/T4 levels in the following conditions:
1) Hyperthyroidism.
2) Primary hypothyroidism.
3) Secondary hypothyroidism.
1) TSH low, T4/T3 high
2) TSH high, T4/T3 low
3) TSH low, T3/T4 low
Antibodies present in Grave’s disease and Hashimoto’s thyroiditis?
Anti-TPO antibodies.
Antibodies present in Grave’s disease alone?
TSH receptor antibodies.
Special investigation for hyperthyroidism/ thyroid cancers?
Radioisotope scan
Diffuse high uptake on radioisotope scan is found in?
Grave’s disease.
Focal high uptake on radioisotope scan is found in?
Toxic multi nodular goitre and adenomas.
‘Cold’ areas on radioisotope scan can indicate?
Thyroid cancer.
What causes primary hyperthyroidism?
Thyroid pathology where the thyroid produces excessive T3/T4.
What causes secondary hyperthyroidism?
Pathology in the hypothalamus or pituitary causing the thyroid to produce excessive thyroid hormone due to overstimulation with TSH.
What is the most common cause of hyperthyroidism?
Grave’s disease.
Describe Grave’s disease pathophysiology.
TSH receptor antibodies > mimic true TSH > stimulate TSH receptors on thyroid > excess TSH production > excess T3/T4 production > negative feedback to hypothalamus and pituitary causes low TSH.
2 causes of hyperthyroidism aside from Grave’s disease.
Toxic multi nodular goitre.
Solitary toxic thyroid nodule.
De Quervain’s thyroiditis
Cause of exophthalmos.
Inflammation, swelling and hypertrophy of the tissue behind the eyeball, forcing the eyeball forward.
Cause of pre-tibial myoexema.
Reaction to TSH antibodies causes deposits of mucin under the skin which cause a discoloured, waxy and oedematous appearance to the skin.
Universal features of hyperthyroidism.
Anxiety and irritability Sweating and heat intolerance Tachycardia Weight loss Fatigue Frequent loose stools Sexual dysfunction
Diffuse goitre + bilateral exophthalmos + pre-tibial myxoedema = ?
Grave’s disease - these signs all caused by TSH receptor antibodies.
Goitre with firm nodules + >50 = ?
Toxic multi nodular goitre.
Second most common cause of hyperthyroidism?
Toxic multi nodular goitre;
Pathophys of toxic multi-nodular goitre?
Nodules develop on thyroid that act independently of normal feedback system + continuously produce excessive thyroid hormone.
Hyperthyroidism + single nodule (benign adenoma) = ?
Solitary toxic thyroid nodule.
Fever + neck pain + neck tenderness + dysphagia + hyperthyroidism features = ?
De Quervain’s thyroiditis.
Management of De Quervain’s thyroiditis?
Self-limiting condition
Symptomatic treatment = NSAIDs for pain and inflammation/ beta-blockers for hyperthyroidism symptomatic relief.
Signs and symptoms of thyroid storm?
Pyrexia + tachycardia + delirium.
1st line anti-thyroid drug for hyperthyroidism?
Carbimazole.
2 regimens that can be used with carbimazole after initial treatment?
1) Titration-block (titrate dose to maintain normal levels)
2) Block and replace (block all production and give levothyroxine).
2nd line anti-thyroid drug for hyperthyroidism?
Propylthiouracil.
How does radioactive iodine work?
Taken up by thyroid and emits radiation which destroys a proportion of thyroid cells.
Side effect of radio iodine treatment?
Can leave patient with hypothyroidism requiring levothyroxine replacement.
What are the rules for a patient using radio iodine?
1) Must not be pregnant + must not get pregnant within 6 months of use.
2) Must avoid close contact with children and pregnancy women for 3 weeks.
3) Limit contact with anyone for several days after receiving the dose.
1st line symptomatic control for hyperthyroidism?
Propranolol = non-selectively blocks beta receptors.
Definitive surgical treatment for hyperthyroidism?
Thyroidectomy or removal of toxic nodules.
Most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroiditis.
Cause of Hashimoto’s thyroiditis?
Autoimmune inflammation of thyroid gland.
Antibodies associated with Hashimoto’s thyroiditis?
anti-TPO antibodies and anti-thyroglobulin antibodies.
Most common cause of hypothyroidism in the developing world?
Iodine deficiency.
2 drugs which can cause hypothyroidism?
Lithium (inhibits production of thyroid hormones)
Amiodarone (interferes with thyroid hormone production and metabolism)
Cause of secondary hypothyroidism?
Most commonly hypopituitarism where pituitary fails to produce enough TSH.
General presentation of hypothyroidism?
Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Amenorrhoea/ menorrhagia Constipation
TSH and T3/T4 levels in primary hypothyroidism?
TSH high, T3/T4 low
TSH and T3/T4 levels in secondary hypothyroidism?
TSH low, T3/T4 low.
Site of pathology in primary hypothyroidism?
Thyroid gland
Site of pathology in secondary hypothyroidism?
Pituitary gland
1st line treatment for hypothyroidism?
Levothyroxine.
Monitoring required when starting levothyroxine?
Measure TSH levels monthly until stable.
What do you do if TSH level is too high in patients on levothyroxine?
Increase dose.
What do you do if TSH level is too low in patients on levothyroxine
Reduce dose.
What happens in hypopituitarism?
Decreased secretion of anterior pituitary hormones.
What order are anterior pituitary hormones affected in in hypopituitarism?
GH > FSH+LH > TSH > ACTH > Prolactin.
What is panhypopituitarism?
Deficiency in all anterior pituitary hormones.
What is Acromegaly?
Clinical manifestation of excessive growth hormone.
Most common cause of acromegaly?
pituitary adenoma.
Ophthalmological sign that can be seen in large pituitary adenomas?
Bitemporal hemianopia.
General signs and symptoms of acromegaly?
Prominent forehead and brown (frontal bossing)
Large nose
Large tongue (macroglossia)
Large hands and feet
Large protruding jaw (prognathism)
Arthritis from imbalanced growth of joints.
Management of pituitary adenoma?
Trans-sphenoidal removal.
3 classes of medications that can be used to block growth hormone?
1) Octreotide (somatostatin analogue - blocks GH release).
2) Bromocriptine (DA agonist - blocks GH release)
3) Pegvisomant (GH antagonist used 3rd line).
How does GH stimulate excessive bone and soft tissue growth?
Through IGF-1.
What causes gigantism?
Excess GH release before fusion of epiphyseal growth plates.
Types of organ dysfunction that can occur in acromegaly?
Hypertrophic heart
HTN
T2DM
Colorectal cancer
Blood results in acromegaly?
High IGF-1.
Method of diagnosis of acromegaly?
OGTT.
If lowest GH value during OGTT is >1, acromegaly is confirmed.
Where is parathyroid hormone produced?
Chief cells in the parathyroid glands.
Cause of PTH secretion?
Hypocalcaemia.
4 methods used by PTH to increase blood calcium levels.
Increasing osteoclast activity.
Increasing calcium absorption from the gut.
Increasing calcium absorption from the kidneys.
Increasing vitamin D activity.
What role does vitamin D do in increasing calcium levels?
Increases calcium absorption from intestines.
Effects of PTH on vitamin D?
Converts Vitamin D into it’s active form, causing further increased absorption of calcium from the intestines.
Cause of primary hyperparathyroidism?
Uncontrolled PTH production by a tumour.
Blood results in primary hyperparathyroidism?
High PTH
High Calcium
Cause of secondary hyperparathyroidism?
Insufficient vitamin D or CKD = low absorption of calcium from intestines, kidneys + bones.
Blood results in secondary hyperparathyroidism?
High PTH
Low/ normal calcium
Cause of tertiary hyperparathyroidism?
Persistent secondary hyperthyroidism causing hyperplasia of the parathyroid glands = increased baseline level of PTH secretion.
Blood results in tertiary hyperparathyroidism?
High PTH
High calcium
Most common type of thyroid cancer?
Papillary.
Thyroid cancer with best prognosis?
Papillary.
Thyroid cancer associated with MEN 2?
Medullary.
Thyroid cancer associated with Hashimoto’s thyroiditis?
Lymphoma.
Bloods associated with primary hyperaldosteronism?
Hypertension
Hypokalaemia
Hypernatraemia
1st line investigation for primary hyperaldosteronism?
Aldosterone/renin ratio
Drug that can cause gynaecomastia?
Metaclopramide.
Drug that can cause hypercalcaemia?
Bendroflumethiazide.
Dangerous side effect that can be caused by Carbimazole?
Agranulocytosis.
Define diabetes insipidus.
Lack of ADH or lack of response to ADH.
What is primary polydipsia?
When the patient has normally functioning ADH but is drinking excessive quantities of water = excessive urine production.
Brief pathophysiology in nephrogenic diabetes insipidus?
Collecting ducts in kidneys do not respond to ADH.
Causes of nephrogenic diabetes insipidus?
Drugs (lithium)
Mutations in AVPR2 gene that codes for ADH.
Intrinsic kidney disease.
Electrolyte disturbance (hypokalaemia/ hypercalcaemia)
Brief pathophysiology of cranial diabetes insipidus?
Hypothalamus does not produce any/ sufficient ADH.
Causes of cranial diabetes insipidus?
Idiopathic Brain tumours Head injury Brain malformations Brain infections Brain surgery/ radiotherapy
Clinical features of diabetes insipidus.
Polyuria Polydipsia Dehydration Postural hypotension Hypernatraemia
3 main investigations done in diabetes insipidus?
Urine osmolality
Serum osmolality
Water deprivation test (desmopressin stimulation test).
1st line investigation for diagnosing diabetes insipidus?
Water deprivation test (desmopressin stimulation test).
Describe the water deprivation test.
Fluid deprivation for 8 hours.
Measure urine osmolality.
Administer desmopressin (synthetic ADH).
Measure urine osmolality 8 hours later.
Results for the following in those with diabetes insipidus:
1) Urine osmolality
2) Serum osmolality
1) Low
2) High
Water deprivation test results in cranial diabetes insipidus?
Initial urine osmolality: low.
Urine osmolality after serum ADH: high.
Water deprivation test results in nephrogenic diabetes insipidus?
Initial urine osmolality: low.
Urine osmolality after serum ADH: low.
Water deprivation test results in primary polydipsia?
Initial urine osmolality: high.
Urine osmolality after serum ADH: high.
Diabetes insipidus management?
1) Treat underlying cause.
2) Desmopressin (higher doses required in nephrogenic DI).
