endocrinology Flashcards

Question

what is adrenal insufficiency ?

Answer 1

where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.

Answer 2

aka addisons diseases refers to the specific condition where the adrenal glands have been damaged resulting in a reduction in the secretion of cortisol and aldosterone most common cause is autoimmune but can also be caused by TB infection and metastatic carcinoma in the adrenal glands

Answer 3

Secondary Adrenal Insufficiency is a result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland. This can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy. There is also a condition called Sheehan’s syndrome where massive blood loss during childbirth leads to pituitary gland necrosis.

Answer 4

Tertiary Adrenal Insufficiency is the result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus. When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.

Answer 5

low aldosterone leads to hyperkalaemia, hyonatraemia, hypovolaemia and metabolic acidosis - causing patients to crave salty foods, nausea, vomiting, fatigue, dizziness, cramps low cortisol - leads to low blood glucose during times of stress - makes patients weak tired and disorientated low androgens leads to loss of armpit and pubic hair and reduced libido but only in woman because men have the testis which also produce androgens hypotension - particularly postural hypotension Hyprerpigmentation to the skin because ACTH stimulated melanocytes to produce melanin

Answer 6

because the adrenal cortex has a high functional reserve meaning that a small amount of functional tissue can secrete enough hormones to meet the needs of the body it is only when around 90% of the tissue is destroyed will symptoms present

Answer 7

U&E - hyponatraemia - hyperkalaemia hypoglycaemia ABG - metabolic acidosis ACTH stimulation test - give synthetic ACTH and measure cortisol and aldosterone levels 30 to 60 mins after administration ACTH. In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol. In secondary adrenal failure the ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH. test for adrenal autoantibodies CT/MRI of adrenal MRI pituitary

Answer 8

replacement steroids titrated to signs, symptoms and electrolytes - hydrocortisone is a glucocorticoid used to replace cortisol - Fludrocortisone is a mineralocorticoid hormone and is used to replace aldosterone doses are doubled during acute illness until they have recovered

Answer 9

aka addison ian crisis acute presentation of severe addisons - where the absence of steroid hormones leads to a life threatening presentation

Answer 10

sudden pain in back abdomen or legs severe vomiting and diarrhoea which leads to dehydration low BP which leads to loss of consciousness

Answer 11

major stress injury/trauma surgery infection/sepsis adrenal haemorrhage e.g. waterhouse friderichsen syndrome - sudden rise in BP causes blood vessels in adrenal cortex to rupture - fills up adrenal cortex with blood and leads to tissue ischaemia and adrenal gland failure - fulminant meningococcemia

Answer 12

Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment. Hydrocortisone 100mg IM or IV stat then 100mg every 6 hours until patient is stable - no fludrocortisone is required because high cortisol exerts a weak mineralocorticoid action IV fluid resuscitation correct hypoglycaemia careful monitoring of electrolytes and fluid balance

Answer 13

Diabetes insipidus is a lack of antidiuretic hormone (ADH) or a lack of response to ADH. This prevents the kidneys from being able to concentrate the urine leading to polyuria (excessive amounts of urine) and polydipsia (excessive thirst).

Answer 14

Nephrogenic diabetes insipidus - where the collecting ducts of the kidneys do not respond to ADH cranial diabetes Insupidus is when the hypothalamus does not produce enough ADH for the pituitary gland to secrete

Answer 15

Drugs, particularly lithium used in bipolar affective disorder Mutations in the AVPR2 gene on the X chromosome that codes for the ADH receptor Intrinsic kidney disease Electrolyte disturbance (hypokalaemia and hypercalcaemia)

Answer 16

``` can be idiopathic Brain tumours - craniopharygngiomas Head injury Brain malformations Brain infections (meningitis, encephalitis and tuberculosis) Brain surgery or radiotherapy haemochromatosis ``` DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)

Answer 17

``` Polyuria (excessive urine production) Polydipsia (excessive thirst) Dehydration Postural hypotension Hypernatraemia ```

Answer 18

high plasma osmolality, low urine osmolality a urine osmolality of >700 mOsm/kg excludes diabetes insipidus water deprivation test

Answer 19

Initially the patient should avoid taking in any fluids for 8 hours. This is referred to as fluid deprivation. Then, urine osmolality is measured and synthetic ADH (desmopressin) is administered. 8 hours later urine osmolality is measured again. In cranial diabetes insipidus the patient lacks ADH. The kidneys are still capable of responding to ADH. Therefore initially the urine osmolality remains low as it continues to be diluted by excessive water secretion in the kidneys. Then when synthetic ADH is given the kidneys respond by reabsorbing water and concentrating the urine so the urine osmolality will be high. In nephrogenic diabetes insipidus the patient is unable to respond to ADH. They are diluting their urine with the excessive water secretion by the kidneys. Therefore the urine osmolality will be low initially and remain low even after the synthetic ADH is given. In primary polydipsia the 8 hours of water deprivation will cause the urine osmolality to be high even before the synthetic ADH is given. A high urine osmolality after 8 hours of water deprivation indicates no diabetes insipidus. - Primary polydipsia is when the patient has a normally functioning ADH system but they are drinking excessive quantities of water leading to excessive urine production. They don’t have diabetes insipidus.

Answer 20

nephrogenic diabetes insipidus: thiazides, low salt/protein diet (Desmopressin can be used in high doses but with careful monitoring) central diabetes insipidus can be treated with desmopressin

Answer 21

Anti-diurectic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland. It is also known as “vasopressin”. ADH stimulates water reabsorption from the collecting ducts in the kidneys. SIADH is a condition where there is inappropriately large amounts of ADH. This may be the result of the posterior pituitary secreting too much ADH or the ADH may be coming from somewhere else, for example a small cell lung cancer. The excessive ADH results in excessive water reabsorption in the collecting ducts. This water dilutes the sodium in the blood so you end up with a low sodium concentration (hyponatraemia). The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”. The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.

Answer 22

symptoms are similar to those of dehydration - headaches, nausea, muscle cramps and tremors as sodium continues to decrease it can cause cerebral oedema leading to confusion, mood swings, hallucinations, seizures and coma

Answer 23

malignancy - small cell lung cancer, also pancreas an prostate neurological - stoke, SAH, SDH, meningitis/encephalitis/anscess Infections - TB, pneumonia Drugs - sulfonylureas, SSRIs, tricyclics, carbamazepine, vincristine, cyclophosphamide head injury post operative from major surgery

Answer 24

Negative short synacthen test to exclude adrenal insufficiency No history of diuretic use No diarrhoea, vomiting, burns, fistula or excessive sweating No excessive water intake No chronic kidney disease or acute kidney injury

Answer 25

In a way, SIADH is a diagnosis of exclusion as we do not have a reliable test to directly measure ADH activity. Clinical examination will show euvolaemia. U+Es will show a hyponatraemia. Urine sodium and osmolality will be high.

Answer 26

the aim is to establish and treat the cause of SIADH it is essential to correct the sodium slowly to prevent central pontine myelinolysis - aim for a change in sodium of less than 10mmol/l er 24 hours. fluid restriction - restrict fluid intake to 500mls - 1 litre. Tolvaptan - vaptans are ADH receptor blockers - they are very powerful and can cause rapid increase in sodium - therefore they are usually initiated by specialist endocrinologist and require close monitoring Demeclocycline is a tetracycline antibiotic that inhibits ADH. It was used prior to the development of vaptans and is now rarely used for this purpose.

Answer 27

also known as osmotic demyelination syndrome. It is a complication of long term severe hyponatraemia being treated to quickly As blood sodium level falls water will move by osmosis across the blood-brain barrier into the cells of the brain from the area of low concentration of solutes (the blood) to the area of high concentration of solutes (the brain). This causes the brain to swell. The brain adapts to this by reducing the solutes in the brain cells so that water is balanced across the blood-brain barrier and the brain does not become oedematous. This adaptation takes a few days. Therefore, if the hyponatraemia has been present and severe for a long time the brain cells will also have a low osmolality. This is not a problem until the blood sodium levels rapidly rise. When this happens water will rapidly shift out of the brain cells and into the blood. This causes two phases of symptoms: First phase: this is due to the electrolyte imbalance and the patient presents as encephalopathic and confused. They may have a headache or nausea and vomiting. These symptoms often resolve prior to the onset of the second phase. Second phase: this is due to the demyelination of the neurones, particularly in the pons. This occurs a few days after the rapid correction of sodium. This may present as spastic quadriparesis, pseudobulbar palsy and cognitive and behavioural changes. There is a significant risk of death. Prevention is essential as treatment is only supportive once CPM occurs. A proportion of patients make a clinical improvement but most are left with some neurological deficit.

Answer 28

There are four parathyroid glands situated in four corners of the thyroid gland. The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to hypocalcaemia (low blood calcium).

Answer 29

Increasing osteoclast activity in bones (reabsorbing calcium from bones) Increasing calcium absorption from the gut Increasing calcium absorption from the kidneys Increasing vitamin D activity Vitamin D acts to increase calcium absorption from the intestines. Parathyroid hormone acts on vitamin D to convert it into active forms. So vitamin D and parathyroid hormone act together to raise blood calcium levels.

Answer 30

Primary hyperparathyroidism is caused by uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands. This leads hypercalcaemia: an abnormally high level of calcium in the blood. This is treated by surgically removing the tumour.

Answer 31

This is where insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones. This causes hypocalcaemia: a low level of calcium in the blood. The parathyroid glands reacts to the low serum calcium by excreting more parathyroid hormone. Over time the total number of cells in the parathyroid glands increase as they respond to the increased need to produce parathyroid hormone. This is called hyperplasia. The glands become more bulky. The serum calcium level will be low or normal but the parathyroid hormone will be high. This is treated by correcting the vitamin D deficiency or performing a renal transplant to treat renal failure.

Answer 32

This happen when secondary hyperparathyroidism continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of parathyroid hormone increases dramatically. Then when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. This high level of parathyroid hormone in the absence of the previous pathology leads to high absorption of calcium in the intestines, kidneys and bones and causes hypercalcaemia. This is treated by surgically removing part of the parathyroid tissue to return the parathyroid hormone to an appropriate level.

Answer 33

PTH (Elevated) Ca2+ (Elevated) Phosphate (Low) Urine calcium : creatinine clearance ratio > 0.01 May be asymptomatic if mild "bones, stones, abdominal groans and psychic moans' Recurrent abdominal pain (pancreatitis, renal colic) Changes to emotional or cognitive state

Answer 34

PTH (Elevated) Ca2+ (Low or normal) Phosphate (Elevated) Vitamin D levels (Low) May have few symptoms Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications

Answer 35

``` Ca2+ (Normal or high) PTH (Elevated) Phosphate levels (Decreased or Normal) Vitamin D (Normal or decreased) Alkaline phosphatase (Elevated) ``` Metastatic calcification Bone pain and / or fracture Nephrolithiasis Pancreatitis

Answer 36

It is important to consider the rare but relatively benign condition of benign familial hypocalciuric hypercalcaemia, caused by an autosomal dominant genetic disorder. Diagnosis is usually made by genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01-distinguished from primary hyperparathyroidism).

Answer 37

80%: solitary adenoma 15%: hyperplasia 4%: multiple adenoma 1%: carcinoma

Answer 38

``` Primary hypoparathyroidism decrease PTH secretion e.g. secondary to thyroid surgery* low calcium, high phosphate treated with alfacalcidol ```

Answer 39

The main symptoms of hypoparathyroidism are secondary to hypocalcaemia: tetany: muscle twitching, cramping and spasm perioral paraesthesia Trousseau's sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic Chvostek's sign: tapping over parotid causes facial muscles to twitch if chronic: depression, cataracts ECG: prolonged QT interval

Answer 40

target cells being insensitive to PTH due to abnormality in a G protein associated with low IQ, short stature, shortened 4th and 5th metacarpals low calcium, high phosphate, high PTH diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.

Answer 41

4.4-6.1 mmol/l

Answer 42

it causes cells in the body to absorb glucose from the blood and use it as a fuel and it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen

Answer 43

Ketogenesis occurs when there is insufficient glucose supply and glycogens stores are exhausted, such as in prolonged fasting. The liver takes fatty acids and converts them to ketones. Ketones are water soluble fatty acids that can be used as fuel. They can cross the blood brain barrier and be used by the brain as fuel. Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on very low carbohydrate, high fat diets. Ketones levels can be measured in the urine by “dip-stick” and in the blood using a ketone meter. People in ketosis have a characteristic acetone smell to their breath. Ketone acids (ketones) are buffered in normal patients so the blood does not become acidotic. When underlying pathology (i.e. type 1 diabetes) causes extreme hyperglycaemic ketosis this results in a metabolic acidosis that is life threatening. This is called diabetic ketoacidosis.

Answer 44

the cells in the body have no fuel and think that they are starving so they initiate the process of ketogenesis so they have a usable fuel. Over time the patiet gets higher and higher glucose and ketone levels. Initially the kidneys produce bicarbonate to counteract the ketone acids i the blood and maintin normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become more acidic.

Answer 45

ketoacidosis, dehydration and potassium imbalance

Answer 46

Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia.

Answer 47

Insulin normally drives potassium into cells. Without insulin potassium is not added to and stored in cells. Serum potassium can be high or normal as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts patients can develop severe hypokalaemia (low serum potassium) very quickly and this can lead to fatal arrhythmias.

Answer 48

- polyuria - polydipsia - nausea and vomiting - acetone smell to their breath - dehydration and subsequent hypotension - altered consciousness - they may have symptoms of and underlying trigger (i.e. sepsis)

Answer 49

Hyperglycaemia (i.e. blood glucose > 11 mmol/l) Ketosis (i.e. blood ketones > 3 mmol/l) Acidosis (i.e. pH < 7.3)

Answer 50

The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones. FIG PICK F – Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours) I – Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour) G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l) P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required I – Infection – Treat underlying triggers such as infection C – Chart fluid balance K – Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable) **Remember as a general rule potassium should not be infused at a rate of more than 10 mmol per hour.

Answer 51

Hypoglycaaemia - tremor, sweating, irritability, dizziness and pallor, more severe hypoglycaemia will lead to reduced consciousnness, coma and death if left untreated. treating hypos - give rapid acting glucose e.g. lucozade and a slower acting carb such as biscuits and toast for when rapid acting glucose is used up for severe hypos give IV detrose and IM glucagon Hyperglycaema - they may need their insulin dose to be increased

Answer 52

chronic exposure to hyperglycaemia causes damage to the endothelial cells of blood vessles - this leads to leaky, malfunctioing vessels that are unable to regenerate. High levels of sugar in the blood also causes supression of the immune system and provides optimal eniviroment for infectious organisms to thrive Macrovascular complications - coronary artery disease, peripheral ischaemia - diabetic foot, strokes, hypertension Microvascular complications - peripheral neuropathy, retinopathy, kidney disease particularly glomerulosclerosis Infection related complications UTI, pneumonia, skin and soft tissue infections particularly in the feet, fungal infections particularly oral and vagial candidiasis.

Answer 53

HbA1c - glycated haemoglobin - average glucose over the last 3 months capilary blood glucose

Answer 54

it may be triggered by certain viruses such as the coxsackie B virus and enterovirus

Answer 55

``` some people will present in DKA the remaining of the patients present with the classic triad of symptoms of hyperglycaemia: - polyuria - polydipsia - weight loss ```

Answer 56

when a new diagnosis is established the following bloods should be taken to exclude other associated pathology and get a baseling of the patients health: - baseline bloods including FBC, renal profile and glucose - blood cultures if there is a fever -HbA1c - TFT and TPO to test for associated autoimmune thyroid disease antie TTG antibodies to test for associated coeliac disease - insulin antibodies, anti GAD antibodies and islet cell antibodies to test for antibodies associated with the destruction of the pancreas and the development of type one diabetes

Answer 57

lipodystrophy

Answer 58

inslin regimes are initiated by a specialist in diabtes - patients are usally initiated on a basal bolus regime the basal part refers to an injection of a long acting insulin such as lantus - typically in the evening - this gives a constant background insulin throughout the day The bolus part refers to an injection of a short acting insulin such as actrapid usually three times a day before meals - this is also injected according to the number of carbohyrdrates consumed every time the patient has a snack

Answer 59

they are small devices that continuously infuse insulin at different rates to control blood sugar levels not everybody qualifies to have these on the NHS - local criteria may vary

Answer 60

a finger prick bedside glucose monitor a one off blood glucose - fasted or non fasted HbA1c glucose tolerance test

Answer 61

fasting glucose greater than or equal to 7.0mmol/l random glucose greater than or equal to 11.1 mmol/l WHO also states that a HbA1c greater or equal to 6.5% is diagnostic of DM for the above if the patient is asymptomatic the test must be repeated to confirm the diagnosis

Answer 62

HbA1c 42-47 mmol/mol (6-6.4%) | fasting glucose 6.1-6.9 mmol/l

Answer 63

``` insulin metformin sufonylureas (glicazide and glimepiride) thiazolidinediones (pioglitazone) DPP-4 inhibitors (-gliptins) - vildagliptin, sitagliptin SGLT-2 inhibitors GLP-1 agonists (-tides) - exenatide ```

Answer 64

hypoglycaemia weight gain Lipodystrophy

Answer 65

increases insulin sensitivity and decreases hepatic gluconeogenesis SE: GI upset Lactic acidosis - common in exams but in real life not that common can not be used in patients with an eGFR less than 30

Answer 66

they stmulate the pacreatic beta cells to secrete insulin the main side effects are hyppoglycaemia weight gain hyponatraemia

Answer 67

they activate the PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid utake side effects weight gain and fluid retention

Answer 68

increase the incretin levels which inhibit glucagon secretion they do not cause weight gain side effects - generally well tolerated but increase the risk of pancreatitits

Answer 69

inhibits reabsorption of glucose in the kidney SE: UTI

Answer 70

they increase insulin secretion and inhibit glucagon secretion - they are good becasue the result in weight loss SE: nausea and vomiting pancreatitis

Answer 71

the following conditions can cause increased red cell turnover which can cause misleading HbA1c results - haemoglobinopathies - haemolytic anaemia - untreated iron deficiency anaemia - suspected gestational diabetes - children - HIV - CKD - people taking medication whcih may cause hyperglycaemia e.g. corticosteroids

Answer 72

you should aim for HbA1c of 48mmol/mol (6.5%) but should only add a second drug if the HbA1c rises to 58mmol/mol (7.5%)

Answer 73

encourage high fibre, low glycaemic index sources of carbs include low-fat diary products and oily fish control the intake of foods containing saturated fats and trans fatty acids limited substitution of sucrose-containing foods for other carbs is allowable, but care should be taken to avoid excess energy intake