endocrinology

Question 1

what is defined as an acute hyponatremia?

Answer 1

develops in less than 48 hours

Question 2

what is mild, moderate and severe hyponatremia?

Answer 2

mild- 130-135
moderate - 125-130
severe - <125

Question 3

what are the clinical symptoms of hyponatremia?

Answer 3

mild confusion
coma
if severe can develop pseudo bulbar palsy and spastic paraparesis

Question 4

what drugs can cause hyponatraemia?

Answer 4

Diuretics

• thiazide diuretics (indapamide, chlorothiazide)
• combination diuretics (amiloride/hydrochlorothiazide)
• loop diuretics - furosemide

ACE inhibitors - enalapril, ramipril

Anticonvulsants - carbamazepine

Hormonal analogues - desmopressin, oxytocin

Hypnotics - temazepam

Antidepressants

• SSRIS
• MAOI - moclobemide

ecstasy

Question 5

what is cushing’s syndrome?

Answer 5

cushng’s syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol in the blood.

Question 6

what is cushing’s disease?

Answer 6

cushing diseases refers specifically to the condition where a pituitary adenoma secretes excessive ACTH.

Cushing disease causes cushing syndrome

Question 7

what are the causes of Cushing disease?

Answer 7

NOTE: either endogenous or exogenous causes

ACTH dependant causes

• cushing’s disease,
• ectopic ACTH production e.. small cell lung cancer - also known as paraneoplastic cushings

ACTH independent causes

• iatrogenic - steroids
• adrenal adenomas
• adrenal carcinomas
• carney complex - syndrome including cardiac myxoma

Pseudo cushing’s - mimics cushing’s but is often due to alcohol excess or severe depression - causes false positive dexamethasone suppression test or 24 hour urinary free cortisol Insulin stress test may be used to differentiate.

Question 8

what are the features of cushing’s syndrome?

Answer 8

• muscle wasting and thin extremities
• easily bruising
• abdominal striae
• facial redness
• fractures - premature osteoporosis
• full moon shaped face, buffalo hump and central obesity
• hyperglycaemia leading to glucose intolerance or diabetes mellitus
• menstrual irregularities
• psychotic symptoms - mood changes
• poor wound healing
• increased vulnerability to infections

Question 9

what are the roles of cortisol in the body?

Answer 9

• part of the circadian rhythm - levels peak in the morning when we need to get up and drop off in the evening
• in stress cortisol increases gluconeogenesis, increases lipolysis and increased proteolysis
• cortisol maintains blood pressure by increasing sensitivity of peripheral blood vessels to catecholamine (epinephrine and norepinephrine) - which narrow the blood vessel lumen
• cortisol dampens inflammatory and immune response by decreasing the production and release of inflammatory mediators (prostaglandins and interleukins) and inhibits T-lymphocytes
• cortisol also has a rollin the brain

Question 10

what investigations do you perform for cushing syndrome?

Answer 10

• serum glucose
• late night salivary cortisol
• dexamethasone suppression test
• 24 hour urinary free cortisol
• ACTH plasma levels
• imagining - pituitary MRI, adrenal CT, CT of chest, abdomen and pelvis

Question 11

how does the dexamethasone test work?

Answer 11

This involves initially giving the patient the “low dose” test. If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.

To perform the test the patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am). The intention is the find out whether the dexamethasone suppresses their normal morning spike of cortisol.

Low Dose Dexamethasone Suppression Test (1mg dexamethasone) - A normal response is for the dexamethasone to suppress the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. The hypothalamus responds by reducing the CRH output. The pituitary response by reducing the ACTH output. The lower CRH and ACTH levels result in a low cortisol level. When the cortisol level is not suppressed, this is the abnormal result seen in Cushing’s Syndrome.

High Dose Dexamethasone Suppression Test (8mg dexamethasone)

The high dose dexamethasone suppression test is performed after an abnormal result on the low dose test.

In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.

Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisone is not suppressed however ACTH is suppressed due to negative feedback on the hypothalamus and pituitary gland.

Where there is ectopic ACTH (e.g. from a small cell lung cancer), neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland.

Question 12

how do you manage cushing’s disease?

Answer 12

first line is trans-sphenoidal removal of the pituitary adenoma

Question 13

how do you manage cushing syndrome

Answer 13

resection of the cause

Question 14

what is acromegaly?

Answer 14

it is the clinical manifestation of excessive growth hormone.

GH is produced by the anterior pituitary glad.

Question 15

what are the causes of acromegaly?

Answer 15

most common cause is unregulated growth hormone secretion by a pituitary adenoma - this adenoma can be microscopic or can be a significant sized tumour that causes compression of local structures

rarely it can also be secondary to a cancer such as lung or pancreatic cancer that secretes ectopic growth hormone releasing hormone or growth hormone

Question 16

what are the symptoms and signs of acromegaly?

Answer 16

if there is a space occupying lesion then they may develop teaches and visual field defects - bitemporal hemianopia

Overgrowth of tissues - prominent forehead and brow - frontal bossing, large nose, large tongue, large hands and feet, large protruding jaw - prognathism, arthritis from imbalanced growth of joint

GH can cause organ dysfunction - hypertrophic heart, hypertension, type 2 diabetes and colorectal cancer

they may also experience excessive sweating and oily skin - caused by sweat gland hypertrophy

Question 17

what investigations would you perform fo acromegaly?

Answer 17

Serum insulin like growth factor 1 (IGF-1) - will be elevated

The oral glucose tolerance test is recommended to confirm the diagnosis if the IGF-1 levels are raised. If there is a lack of suppression of GH during OGTT it can confirm the diagnosis of acromegaly

MRI brain for the pituitary tumour

Question 18

how do you manage acromegaly ?

Answer 18

trans-sphenoidal removal of the pituitary tumour

or surgical removal of cancer causing ectopic GH

There are medications that can be used to block GH

• Pegvisomant - GH antagonist give SC daily
• somatostatin analogues - block GH release
• dopamine agonists to block GH release - bromocriptine

Question 19

what is hyperaldosteronism?

Answer 19

when there is too much aldosterone produced in the zona glomerulosa in the adrenal gland

Question 20

what are the causes of hyperaldosteronism?

Answer 20

PRIMARY CAUSES:
where the adrenal glad itself is responsible for rise in aldosterone
- idiopathic hyperaldosteronism
- Conn’s syndrome - where an adenoma in the adrenal gland secretes too much aldosterone
- familial hyperaldosteronism - when the zona glomerulosa cells inappropriately make aldosterone in response to ACTH
- adrenal carcinoma

Secondary hyeraldosteronism - when the pathology lies outside the adrenal gland - there is excessive renin stimulating the adrenal glands to produce more aldosterone - causes of high renin are renal artery stenosis, renal artery obstruction, heart failure

Question 21

how does aldosterone act on the kidneys?

Answer 21

Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts

Question 22

what effects does hyeraldosteonism have on the body?

Answer 22

Lead to hypokalaemia (may present as muscle weakness, constipation and changes in heart rhythm)
leads to hypernatremia
leads to high blood volume and pressure
loss of hydrogen leads to a metabolic alkalosis

Question 23

what investigations would you perform for hyperaldosteronism?

Answer 23

renin/aldosterone ratio
High aldosterone and low renin indicates primary hyperaldosteronism
High aldosterone and high renin indicates secondary hyperaldosteronism

BP
Serum electrolytes
Blood gas analysis - alkalosis

CT/MRI to look for adrenal tumour
renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction

Question 24

how do you manage hyperaldosteonism?

Answer 24

treat underlying cause if possible : if they have adrenal adenoma - surgery
percutaneous renal artery angioplasty

if they have adrenocortical hyperplasia - give aldosterone antagonist - spironolactone or eplerenone or amiloride

Question 25

what is adrenal insufficiency ?

Answer 25

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

Question 26

what is primary adrenal insufficiency?

Answer 26

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

Question 27

what is secondary adrenal insufficiency?

Answer 27

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.

Question 28

what is tertiary adrenal insufficiency?

Answer 28

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.

Question 29

what are the symptoms and signs of adrenal insufficiency?

Answer 29

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

Question 30

why do patients usually present late on in the disease process in primary adrenal insufficiency?

Answer 30

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

Question 31

what investigations would you perform for adrenal insufficiency ?

Answer 31

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

Question 32

how do you treat adrenal insufficiency?

Answer 32

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

Question 33

what is adrenal crisis ?

Answer 33

aka addison ian crisis

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

Question 34

how does adrenal crisis present?

Answer 34

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

Question 35

what can trigger addison ian crisis?

Answer 35

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

Question 36

how do you manage adrenal crisis?

Answer 36

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

Question 37

what is diabetes insupidus?

Answer 37

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).

Question 38

how can diabetes insipidus be classified?

Answer 38

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

Question 39

what are the causes of Nephrogenic Diabetes Insipidus?

Answer 39

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)

Question 40

what are the causes of Cranial Diabetes Insipidus

Answer 40

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)

Question 41

what is the presentation of diabetes insipidus?

Answer 41

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

Question 42

what investigations would you perform for diabetes insipidus?

Answer 42

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

Question 43

what do the results of a water deprivation test show in diabetes insipidus?

Answer 43

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.

Question 44

how do you manage diabetes insipidus?

Answer 44

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

Question 45

what is SIADH?

Answer 45

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”.

Question 46

what are the symptoms of SIADH?

Answer 46

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

Question 47

what are the causes of SIADH?

Answer 47

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

Question 48

when you suspect SIADH what other causes of hyponatraemia should be excluded?

Answer 48

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

Question 49

how do you diagnose SIADH?

Answer 49

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.

Question 50

how do you manage SIADH?

Answer 50

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.

Question 51

what is central pontine myelinolysis?

Answer 51

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.

Question 52

where is parathyroid hormone secreted and what causes it to be excreted?

Answer 52

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).

Question 53

how does parathyroid hormone act to increase blood calcium levels?

Answer 53

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.

Question 54

what is primary hyperparathyroidism?

Answer 54

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.

Question 55

what is secondary hyperparathyroidism?

Answer 55

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.

Question 56

what is tertiary hyperparathyroidism?

Answer 56

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.

Question 57

what is the hormonal profile and clinical features in primary hyperarathyroidism?

Answer 57

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

Question 58

what is the hormonal profile and clinical features in secondary hyperarathyroidism?

Answer 58

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

Question 59

what is the hormonal profile and clinical features in tertiary hyperarathyroidism?

Answer 59

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

Question 60

what differential diagnosis should you consider for hyperparathyroidism?

Answer 60

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).

Question 61

what are the causes of primary hyerparathyroidism?

Answer 61

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

Question 62

what is hypoparathyroidism?

Answer 62

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

Question 63

what are the symptoms is hypoparathyroidism?

Answer 63

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

Question 64

what is pseudohypoparathyroidism?

Answer 64

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.

Question 65

what is the ideal blood glucose concetration?

Answer 65

4.4-6.1 mmol/l

Question 66

how does insulin reduce blood sugar?

Answer 66

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

Question 67

when is ketogenesis?

Answer 67

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.

Question 68

what happens in ketoacidosis?

Answer 68

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.

Question 69

whatt are the main problems if DKA?

Answer 69

ketoacidosis, dehydration and potassium imbalance

Question 70

what causes dehydration in DKA?

Answer 70

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.

Question 71

what causes potassium imbalance in DKA?

Answer 71

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.

Question 72

how does DKA present?

Answer 72

• 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)

Question 73

how do you diagnose DKA?

Answer 73

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

Question 74

how do you manage DKA?

Answer 74

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.

Question 75

what are the short term complications relate to insulinn and blood glucose management?

Answer 75

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

Question 76

what are the long term complications of diabetes?

Answer 76

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.

Question 77

how is diabetes moitered ?

Answer 77

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

capilary blood glucose

Question 78

what can trigger the onset diabetes?

Answer 78

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

Question 79

how does diabetes present?

Answer 79

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

Question 80

with a new diagnosis of diabetes what investigations h

Answer 80

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

Question 81

what can happen if insulin is injected in the same site repeatedly ?

Answer 81

lipodystrophy

Question 82

what are the basal bolus regimes?

Answer 82

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

Question 83

what are insulin pumps?

Answer 83

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

Question 84

what are the four main ways of checking blood glucose?

Answer 84

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

Question 85

what is the diagnostic criteria for diabetes?

Answer 85

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

Question 86

what is classified as pre diabetes?

Answer 86

HbA1c 42-47 mmol/mol (6-6.4%)

fasting glucose 6.1-6.9 mmol/l

Question 87

what are the main drugs used in the treatment of DM?

Answer 87

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

Question 88

what are the main side effects of insulin?

Answer 88

hypoglycaemia
weight gain
Lipodystrophy

Question 89

how does metformin work and what are the main side effects?

Answer 89

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

Question 90

what are the main side effects of sulfonylureas and how do they work??

Answer 90

they stmulate the pacreatic beta cells to secrete insulin

the main side effects are hyppoglycaemia
weight gain
hyponatraemia

Question 91

what are the main side effects of thiazolidinediones and how do they work??

Answer 91

they activate the PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid utake

side effects
weight gain and fluid retention

Question 92

what are the main side effects of gliptins and how do they work??

Answer 92

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

Question 93

what are the main side effects of SGLT-2 inhibotors (-gliflozins) and how do they work??

Answer 93

inhibits reabsorption of glucose in the kidney

SE:
UTI

Question 94

what are the main side effects of GLP-1 agonists (-tides) and how do they work??

Answer 94

they increase insulin secretion and inhibit glucagon secretion - they are good becasue the result in weight loss

SE:
nausea and vomiting
pancreatitis

Question 95

what conditions mean that HbA1c may not be used for diagnosis of diabetes?

Answer 95

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

Question 96

what is the aim for HbA1c for a patient who is on metformin?

Answer 96

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%)

Question 97

what dietary advice do you give to a type 2 diabetic?

Answer 97

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