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Endocrinology Flashcards

1
Q

When might metformin be used in T1DM?

A

NICE recommend the use of metformin for patients with type 1 diabetes who are overweight with a BMI of 25kg/m² or over

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2
Q

What is the target HbA1c in T1DM

A

below 48mmol/mol
it should be checked every 3-6 months

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3
Q

what are sick day rules in diabetes?

A
  1. never stop insulin, continue taking insulin if they are not eating as usual they may just need to adjust the levels
  2. monitor CBGs more regularly
  3. stay hyrdrated and try to eat
  4. check ketones
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4
Q

What are the causes of hypocalcaemia?

A

vitamin D deficiency (osteomalacia)
chronic kidney disease
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
acute pancreatitis

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5
Q

How does hypoparathyroidism cause hypocalcaemia?

A

.PTH plays a crucial role in regulating blood calcium levels by increasing renal calcium reabsorption, promoting conversion of vitamin D into its active form which enhances intestinal absorption of calcium and mobilising calcium from bone. Therefore, deficiency of PTH leads to hypocalcaemia.

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6
Q

why does pseudohypoparathyroidism lead to hypocalcaemia?

A

This condition involves resistance to the action of PTH often due to genetic mutations affecting signalling pathways for PTH receptor. Despite normal or high levels of PTH, its effect on target organs is blunted leading to decreased release of calcium into the bloodstream resulting in hypocalcaemia.

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7
Q

why does acute pancreatitis lead to hypocalcaemia?

A

In acute pancreatitis, there can be saponification where released fatty acids bind with calcium ions forming insoluble soaps leading to fall in serum calcium levels. Moreover, inflammation associated with pancreatitis can lead to capillary leak syndrome causing loss of protein-bound calcium into extravascular space further contributing to hypocalcaemia.

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8
Q

How is hypocalcaemia managed?

A

severe hypocalcaemia (e.g. carpopedal spasm, tetany, seizures or prolonged QT interval) requires IV calcium replacement
the preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause

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9
Q

What is Bartter’s syndrome?

A

an inherited disorder (AR)
it causes severe hypokalaemia due to defective chloride absorbtion at the Na+K+2CL- cotransporter in the ascending loop of hence

It causes severe hypokalaemia

Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide

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10
Q

What can cause hypokalaemia with hypertension?

A

Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*

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11
Q

What can cause hypokalaemia without hypertension?

A

diuretics
GI loss (e.g. Diarrhoea, vomiting)
renal tubular acidosis (type 1 and 2**)
Bartter’s syndrome
Gitelman syndrome

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12
Q

What is first line treatment for patients with PCOS trying to conceive ?

A

Clomifene

however There is an ongoing debate as to whether metformin, clomifene or a combination should be used to stimulate ovulation

metformin is also used, either combined with clomifene or alone, particularly in patients who are obese

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13
Q

How can hirsutism and acne be managed in PCOS?

A

a COC pill may be used help manage hirsutism. Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
if doesn’t respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision

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14
Q

what are secondary causes of hyperlipideamia that cause predominantly hypertriglyceridaemia ?

A

diabetes mellitus (types 1 and 2)
obesity
alcohol
chronic renal failure
drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
liver disease

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15
Q

what are secondary causes of hyperlipideamia that cause predominantly hypercholesterolaemia ?

A

nephrotic syndrome
cholestasis
hypothyroidism

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16
Q

What is the mechanism of action of Sulfonyureas?

A

Sulfonyureas increase stimulation of insulin secretion by pancreatic B-cells and decrease hepatic clearance of insulin

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17
Q

What is the mechanism of action of SGLT-2 inhibitors?

A

e.g. dapagliflozin

Inhibits sodium-glucose co-transporter-2 in the proximal convoluted tubule of the nephron to stop glucose reabsorbtion, meaning it excrete in the urine

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18
Q

What is the mechanism of action of DPP-4 inhibitors?

A

sitagliptin, vildagliptin
Inhibits the principal enzyme that breaks down GLP-1 an incretin hormone that increases insulin secretion and suppresses glucagon secretion

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19
Q

What is the mechanism of action of metformin?

A

Reduces hepatic gluconeogenesis, increases peripheral glucose uptake and also reduces the absorption of carbohydrate in the gut

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20
Q

What is the mechanism of action of thiazolidinediones?

A

pioglitazone
upregulation of transcription of insulin responsive genes, leading to an increase in glucose transporters and insulin receptors at the surface of the cell

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21
Q

what are the adverse effects of sulfonylureas?

A

Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain

Rarer adverse effects
hyponatraemia secondary to syndrome of inappropriate ADH secretion
bone marrow suppression
hepatotoxicity (typically cholestatic)
peripheral neuropathy

Sulfonylureas should be avoided in breastfeeding and pregnancy.

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22
Q

Why does digoxin cause gynaecomastia?

A

Due to the similarity between the structure of digoxin and oestrogen, the drug is believed to act direct at oestrogen receptors, resulting in the hormone imbalance responsible for gynaecomastia.

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23
Q

What are causes of gynaecomastia?

A

Causes of gynaecomastia
physiological: normal in puberty
syndromes with androgen deficiency: Kallman’s, Klinefelter’s
testicular failure: e.g. mumps
liver disease
testicular cancer e.g. seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs: see below

Drug causes of gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids

Very rare drug causes of gynaecomastia
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa

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24
Q

What will cause hypokalaemia with alkalosis?

A

Hypokalaemia with alkalosis
vomiting
thiazide and loop diuretics
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)

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25
Q

What will cause hypokalaemia with acidosis?

A

Hypokalaemia with acidosis
diarrhoea
renal tubular acidosis
acetazolamide
partially treated diabetic ketoacidosis

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26
Q

why does acetazolamide cause hypokalaemia with acidosis?

A

Acetazolamide is a carbonic anhydrase inhibitor that is used to treat conditions such as glaucoma, altitude sickness and certain types of oedema. It works by reducing the reabsorption of bicarbonate in the proximal tubule of the kidney, leading to metabolic acidosis. The body compensates for this acidosis by increasing potassium excretion in an attempt to retain more hydrogen ions, which can result in hypokalaemia.

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27
Q

what are clinical features of Bartter’s syndrome?

A

short stature, polydipsia, polyuria, and nocturia

patients are typically normotensive in the setting of elevated renin and aldosterone.

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28
Q

How do you distinguish between Bartter’s syndrome and Gitelman’s ?

A

Hypercalciuria in Bartter’s

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29
Q

What is considered acute vs chronic hyponatraemia?

A

acute: develops over a period of < 48 hours
chronic: develops over a period > 48 hours

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30
Q

how is hyponatraemia classified on severity?

A

mild: 130-134 mmol/L
moderate: 120-129 mmol/L
severe: < 120 mmol/L

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31
Q

what are the symptoms of hyponatraemia?

A

patients with mild hyponatraemia may be symptomatic
early symptoms may include: headache, lethargy, nausea, vomiting, dizziness, confusion, and muscle cramps
late symptoms may include: seizures, coma, and respiratory arrest

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32
Q

what are the causes of hyponatraemia?

A

hypovolemic hyponatraemia/clinically dehydrated: diuretic stage of renal failure, diuretics, Addisonian crisis
euvolemic hyponatraemia: SIADH
hypervolaemic hyponatraemia: heart failure, liver failure, nephrotic syndrome

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33
Q

What are the initial steps before commencing treatment for hyponatraemia ?

A

exclude a spurious result (e.g. blood taken from a drip arm)
review medications that may cause hyponatraemia

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34
Q

How is acute hyponatraemia with severe symptoms managed?

A

Patients with acute, severe (<120 mmol/L) or symptomatic hyponatraemia require close monitoring, preferably in an HDU or above setting.

Hypertonic saline (typically 3% NaCl) is used to correct the sodium level more quickly than would be done in patients with chronic hyponatraemia.

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35
Q

How is hypovolemic hyponatraemia managed?

A

normal, i.e. isotonic, saline (0.9% NaCl)
this may sometimes be given as a trial
if the serum sodium rises this supports a diagnosis of hypovolemic hyponatraemia
if the serum sodium falls an alternative diagnosis such as SIADH is likely

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36
Q

How is euvolemic hyponatraemia managed?

A

fluid restrict to 500-1000 mL/day
consider medications:
demeclocycline
vaptans (see below)

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37
Q

how is hypervolemic hyponatraemia managed?

A

fluid restrict to 500-1000 mL/day
consider loop diuretics
consider vaptans

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38
Q

what are vaptans?

A

Vasopressin/ADH receptor antagonists (vaptans):
these act primarily on V2 receptors - antagonism of V2 receptors results in selective water diuresis, sparing the electrolytes
They should be avoided in patients who have hypovolemic hyponatremia
Vasopression/ADH receptor antagonists can stimulate the thirst receptors leading to the desire to drink free water. They can be hepatotoxic in patients with underlying liver disease.

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39
Q

what are the complications of hyponatraemia treatment?

A

Osmotic demyelination syndrome (central pontine myelinolysis)
can occur due to over-correction of severe hyponatremia
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’

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40
Q

What is Klinefelter’s syndrome and what are the features of it?

A

Klinefelter’s syndrome is associated with karyotype 47, XXY.

Features
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone

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41
Q

What would you see in the hormones of a patients with Klinefelter’s syndrome?

A

hypergonadotrophic hypogonadism, in which FSH and LH concentrations are elevated and serum testosterone concentrations are low. Gonadal dysgenesis secondary to Klinefelter’s syndrome impairs spermatogenesis, with semen analysis commonly showing azoospermia.

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42
Q

Why is thyroid storm?

A

Thyroid storm is a rare but life-threatening complication of thyrotoxicosis. It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic thyroxine excess does not usually result in thyroid storm.

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43
Q

What may precipitate a thyroid storm?

A

thyroid or non-thyroidal surgery
trauma
infection
acute iodine load e.g. CT contrast media

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44
Q

what are the clinical features of thyroid storm?

A

fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically

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45
Q

How do you manage a thyroid storm?

A

symptomatic treatment e.g. paracetamol

treatment of underlying precipitating event

beta-blockers: typically IV propranolol to counteract the peripheral effects of thyroid hormone

anti-thyroid drugs: e.g. methimazole or propylthiouracil and Lugol’s iodine to inhibit further function of thyroid hormone synthesis

dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3

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46
Q

what is subacute thyroiditis?

A

Subacute thyroiditis (also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism.

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47
Q

What are the features of subacute thyroiditis?

A

There are typically 4 phases;
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal

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48
Q

what are the investigations of subacute thyroiditis?

A

TFTs
thyroid scintigraphy: globally reduced uptake of iodine-131

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49
Q

How is subacute thyroiditis managed?

A

usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops

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50
Q

What is remnant hyperlipidaemia ?

A

rare cause of mixed hyperlipidaemia (raised cholesterol and triglyceride levels)
also known as Fredrickson type III hyperlipidaemia, broad-beta disease and dysbetalipoproteinaemia
associated with apo-e2 homozygosity
high incidence of ischaemic heart disease and peripheral vascular disease
thought to be caused by impaired removal of intermediate density lipoprotein from the circulation by the liver

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51
Q

what are the features of remnant hyperlipidaemia and how is it managed?

A

Features
yellow palmar creases
palmer xanthomas
tuberous xanthomas

Management
fibrates are first line treatment

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52
Q

What is multiple endocrine neoplasia?

A

Multiple endocrine neoplasia causes overgrowth or tumors on one or more endocrine glands.

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53
Q

what is MEN type I

A

3ps
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)

Also: adrenal and thyroid

MEN1 gene

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54
Q

how does MEN 1 most commonly present?

A

hypercalcaemia

55
Q

what is MEN type IIa?
what gene is likely to be affected?

A

medullary thyroid cancer (70%)
Parathyroid (60%)
Phaeochromocytoma

RET oncogene

56
Q

What is MEN type IIb , what gene is likely to be affected?

A

medullary thyroid cancer
pheochromocytoma
marfanoid body
habitus
neuromas

RET oncogene

57
Q

what is the pentagastrin test?

A

A pentagastrin stimulation test assesses the production of calcitonin by parafollicular C-cells in the thyroid gland. A positive result is suggestive of medullary thyroid cancer

58
Q

what cancer gene is commonly associated with papillary thyroid cancer?

A

BRAF

59
Q

What increases the risk of cervical cancer?

A

Human papillomavirus (HPV), particularly serotypes 16,18 & 33 is by far the most important factor in the development of cervical cancer. Other risk factors include:
smoking - two fold increase risk of developing cervical cancer than woman who do not
human immunodeficiency virus
early first intercourse, many sexual partners
high parity
lower socioeconomic status
combined oral contraceptive pill*

60
Q

when should statins be prescribed in T1DM and CKD?

A

Type 1 diabetes mellitus
NICE recommend that we ‘consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes’
atorvastatin 20 mg should be offered if type 1 diabetics who are:
older than 40 years, or
have had diabetes for more than 10 years or
have established nephropathy or
have other CVD risk factors

Chronic kidney disease (CKD)
atorvastatin 20mg should be offered to patients with CKD
increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and the eGFR > 30 ml/min. If the eGFR is < 30 ml/min a renal specialist should be consulted before increasing the dose

61
Q

what follow up is required when starting statins?

A

NICE recommend we follow up patients at 3 months
repeat a full lipid profile
if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient
NICE recommend we consider increasing the dose of atorvastatin up to 80mg

62
Q

what is the pathophysiology of DKA?

A

DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies

63
Q

what are the most common precipitating factors of DKA?

A

missed insulin doses and myocardial infarction.

64
Q

what are the clinical features of DKA?

A

abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell)

65
Q

what is the diagnostic criteria for DKA?

A

Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick

66
Q

How is DKA managed?

A

fluid replacement (isotonic saline)
Insulin - an IV infusion should be started at 0.1unit/kg/her
once blood glucose is < 14 mmol/l an infusion of 10% dextrose should be started at 125 mls/hr in addition to the 0.9% sodium chloride regime

Correct electrolyte disturbance
serum potassium is often high on admission despite total body potassium being low
this often falls quickly following treatment with insulin resulting in hypokalaemia
potassium may therefore need to be added to the replacement fluids
if the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required

Long acting insulin should be continues

67
Q

when is DKA resolved?

A

DKA resolution is defined as:
pH >7.3 and
blood ketones < 0.6 mmol/L and
bicarbonate > 15.0mmol/L

Further points
both the ketonaemia and acidosis should have been resolved within 24 hours. If this hasn’t happened the patient requires senior review from an endocrinologist
if the above criteria are met and the patient is eating and drinking switch to subcutaneous insulin
the patient should be reviewed by the diabetes specialist nurse prior to discharge

68
Q

what are the complications of DKA?

A

gastric stasis
thromboembolism
arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia
acute respiratory distress syndrome
acute kidney injury

68
Q

what is Liddle’s syndrome?

A

Liddle’s syndrome, also called Liddle syndrome, is a genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium, and normal to low levels of aldosterone

69
Q

If an obese type 2 diabetic taking metformin has poor diabetic control what is the most suitable second-line option?

A

a dipeptidyl peptidase-4 (DPP-4) (sitagliptin) inhibitor that works by inhibiting the breakdown of incretins in the gastrointestinal tract and therefore incretins can then stimulate insulin secretion. It is a good drug of choice for him given his severe obesity as it is associated with weight loss.

70
Q

what are the side effects of sulphonylureas?

A

e.g. gliclazide. Side effects include weight gain and hypoglycaemia.

71
Q

which SGLT-2 inhibitor can increase the risk of foot amputations?

A

canagliflozin

72
Q

what is glucagon like peptide 1?

A

GLP-1, a hormone released by the small intestine in response to an oral glucose load
In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM.

Increasing GLP-1 levels, either by the administration of an analogue (glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins)

73
Q

what is a Glucagon-like peptide-1 (GLP-1) mimetics and how does it work?

A

Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic.
These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. They are sometimes used in combination with insulin in T2DM to minimise weight gain.

Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.

Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day.

Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin.

74
Q

what are the causes of primary hyperaldosteronism?

A

bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases
adrenal adenoma: 20-30% of cases
unilateral hyperplasia
familial hyperaldosteronism
adrenal carcinoma

75
Q

what are the features of primary hyperaldosteronism?

A

hypertension
increasingly recognised but still underdiagnosed cause of hypertension

hypokalaemia
e.g. muscle weakness
this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients, and is more common with adrenal adenomas

metabolic alkalosis

76
Q

who should be screened for primary hyperaldosteronism ?

A

hypertension with hypokalemia
treatment-resistant hypertension

77
Q

what are the investigations for primary hyperaldosteronism?

A

plasma aldosterone/renin ratio is the first-line investigation
should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)

Following this a high res CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess

78
Q

hw do you manage primary hyperaldosteronism?

A

adrenal adenoma: surgery (laparoscopic adrenalectomy)
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone

79
Q

What is Kallmann’s syndrome?

A

Kallmann’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann’s syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.

80
Q

What are the feature of Kallmann’s syndrome?

A

delayed puberty’
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
patients are typically of normal or above-average height

Cleft lip/palate and visual/hearing defects are also seen in some patients

**The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.

81
Q

What is the management of Kallmann’s syndrome?

A

testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life

82
Q

what are meglitinides?
what are their mechanism of action and what are the adverse effects?

A

Meglitinides (e.g. repaglinide, nateglinide)
increase pancreatic insulin secretion in response to meal consumption

like sulfonylureas they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells

often used for patients with an erratic lifestyle
adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas)

83
Q

what is the frug group of metformin?

A

Biguanides

84
Q

what is pseudohypoparathyroidism?

A

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.

85
Q

what is Pseudopseudohypoparathyroidism

A

similar phenotype to pseudohypoparathyroidism but normal biochemistry

86
Q

what are symptoms of hypoparathyroidism?

A

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

87
Q

How Is primary hypoparathyroidism managed?

A

alfacalcidol

88
Q

How is urge incontinence managed?

A

bladder retraining (lasts for a minimum of 6 weeks, the idea is to gradually increase the intervals between voiding)
bladder stabilising drugs: antimuscarinics are first-line
NICE recommend oxybutynin (immediate release), tolterodine (immediate release) or darifenacin (once daily preparation)
Immediate release oxybutynin should, however, be avoided in ‘frail older women’
mirabegron (a beta-3 agonist) may be useful if there is concern about anticholinergic side-effects in frail elderly patients

89
Q

How is stress incontinence managed?

A

pelvic floor muscle training
NICE recommend at least 8 contractions performed 3 times per day for a minimum of 3 months
surgical procedures: e.g. retropubic mid-urethral tape procedures
duloxetine may be offered to women if they decline surgical procedures
a combined noradrenaline and serotonin reuptake inhibitor
mechanism of action: increased synaptic concentration of noradrenaline and serotonin within the pudendal nerve → increased stimulation of urethral striated muscles within the sphincter → enhanced

90
Q

when should amitriptyline be avoided?

A

In BPH due to risk of urinary retention

91
Q

what are the symptoms of diabetic peripheral neuropathy?

A

Diabetes typically leads to sensory loss and not motor loss. Sensory loss typically results in a ‘glove and stocking’ distribution, with the lower legs affected first due to the length of the sensory neurons supplying this area. Painful diabetic neuropathy is also a common problem in clinical practice.

92
Q

how is diabetic peripheral neuropathy managed?

A

first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinics may be useful in patients with resistant problems

93
Q

what are gastrointestinal autonomic neuropathy?

A

Gastroparesis
occurs secondary to autonomic neuropathy
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Chronic diarrhoea
often occurs at night

Gastro-oesophageal reflux disease
caused by decreased lower esophageal sphincter (LES) pressure

94
Q

what would bloods show in all types of renal tubular acidosis?

A

All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic metabolic acidosis (normal anion gap).

95
Q

What is Type 1 renal tubular acidosis (distal)?

A

inability to generate acid urine (secrete H+) in distal tubule
it causes hypokalaemia
complications include nephrocalcinosis and renal stones
causes include idiopathic, rheumatoid arthritis, SLE, Sjogren’s, amphotericin B toxicity, analgesic nephropathy

96
Q

What is type 2 renal tubular acidosis (proximal)

A

decreased HCO3- reabsorption in proximal tubule
it causes hypokalaemia
complications include osteomalacia
causes include idiopathic, as part of Fanconi syndrome, Wilson’s disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)

97
Q

What is type 3 renal tubular acidosis?

A

extremely rare
caused by carbonic anhydrase II deficiency
results in hypokalaemia

98
Q

What is type 4 renal tubular acidosis?

A

reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes

99
Q

What is lightwood Albright syndrome?

A

a neonatal form of RTA with a known genetic inheritance pattern. Affected children present early in life with complications and therefore would not present as an index case in adulthood

100
Q

What is Pendred’s syndrome?
what is the inheritance pattern and what is it characterised by?

A

autosomal recessive genetic disorder

characterised by bilateral sensorineural deafness, with mild hypothyroidism and a goitre.
The patients tend to present with progressive hearing loss and delay in academic progression. Often head trauma tends to make the sensorineural deafness worse, leading to patients having to avoid contact sports.

In Pendred syndrome there is a defect in the organification of iodine, leading to dyshormonogenesis. However thyroid symptoms in pendred syndrome are often mild and patients are often clinically euthyroid, presenting only with a goitre. Thyroid function tests are also often normal, requiring the perchlorate discharge test to aid diagnosis.

101
Q

How is Pendred’s syndrome investigated and managed?

A

The syndrome can be diagnosed via genetic testing (Pendred syndrome (PDS) gene, chromosome 7), audiometry and MRI imaging to look for characteristic one and a half turns in the cochlea, compared to the normal two and a half turns.

Treatment is with thyroid hormone replacement and cochlear implants.

102
Q

which T2DM medications are not associated with weight gain or hypoglycaemia?

A

gliptin class of medication (DPP-4 inhibitors)
they reduce the peripheral breakdown of incretins such as GLP-1

103
Q

what are the differentials for hypertension with low potassium?
What would be the first investigation

A

Conn’s, Cushing’s, renal artery stenosis and Liddle’s.

Quantifying the renin and angiotensin levels will help to distinguish the cause here, before going on to more specialised tests.

Cushing’s and Conn’s would be associated with a high aldosterone and a low renin, renal artery stenosis would be associated with a high renin and aldosterone, Liddle’s is associated with a low renin and aldosterone.

104
Q

What may cause increased levels of uric acid?

A

Increased levels of uric acid may be seen secondary to either increased cell turnover or reduced renal excretion of uric acid.

Increased synthesis
Lesch-Nyhan disease
myeloproliferative disorders
diet rich in purines
exercise
psoriasis
cytotoxics

Decreased excretion
drugs: low-dose aspirin, diuretics, pyrazinamide
pre-eclampsia
alcohol
renal failure
lead

105
Q

what is hyperuricaemia associated with ?

A

Hyperuricaemia may be associated with hyperlipidaemia and hypertension. It may also be seen in conjunction with the metabolic syndrome

106
Q

what would blood test show in Paget’s disease

A

Blood tests would usually only show an isolated, raised ALP. The calcium should be normal.

106
Q

What are the causes of hypercalcaemia?

A

Most common:
1. primary hyperparathyroidism (patients out of hospital)
2. malignancy (patients in hospital)

other causes
sarcoidosis, vitamin D intoxication, acromegaly , thyrotoxicosis, milk-alkali syndrome, drugs (thiazines, calcium containing antacids), dehydration

107
Q

Dietary advice for T2 DM?

A

encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage the use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%

108
Q

how often should HbA1c be checked?

A

3-6 months

109
Q

what is the second line therapy for T2DM?

A

metformin + DPP-4 inhibitor
metformin + pioglitazone
metformin + sulfonylurea
metformin + SGLT-2 inhibitor (if NICE criteria met)

110
Q

3rd line therapy for T2DM?

A

metformin + DPP-4 inhibitor + sulfonylurea
metformin + pioglitazone + sulfonylurea
metformin + (pioglitazone or sulfonylurea or DPP-4 inhibitor) + SGLT-2 if certain NICE criteria are met
insulin-based treatment

111
Q

Adverse effects of SGLT-2 inhibitors?

A

urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored

112
Q

what is the key physiological factor in metabolic syndrome?

A

Insulin resistance

113
Q

what factors are included in criteria for metabolic syndrome?

A

elevate waist circumference
elevated triglycerides
reduced HDL
raised BP
raised fasting plasma glucose
central obesity
microalbuminuria

Other associated features include:
raised uric acid levels
non-alcoholic fatty liver disease
polycystic ovarian syndrome

114
Q

What is Bartter’s syndrome?

A

Bartter’s syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn’s, Cushing’s and Liddle’s syndrome which are associated with hypertension).

Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide

115
Q

what are the features of Bartter’s syndrome?

A

usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness

116
Q

what is the mechanism of action of evolocumab ?

A

Evolocumab prevents PCSK9-mediated LDL receptor degradation. Evolocumab binds selectively to PCSK9 and prevents circulating PCSK9 from binding to the low-density lipoprotein receptor (LDLR) on the liver cell surface, thus preventing PCSK9-mediated LDLR degradation. Increasing liver LDLR levels results in associated reductions in serum LDL-cholesterol. Use of evolocumab is associated with a reduction in levels of free PCSK9 and this is taken as a measure of target engagement. it lowers LDL cholesterol by more than 50% in 85% of patients who are treated.

117
Q

How is Familial hypercholestrolaemia inherited?

A

AD

118
Q

what are the adverse effects of Thiazolidinediones?

A

weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)

119
Q

what kind of drug is pioglitazone?

A

Thiazolidinediones

Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.

120
Q

what skin manifestations are associated with hypothyroidism?

A

dry (anhydrosis), cold, yellowish skin
non-pitting oedema (e.g. hands, face)
dry, coarse scalp hair, loss of lateral aspect of eyebrows
eczema
xanthomata

121
Q

what skin conditions are associated with hyperthyroidism?

A

Skin manifestations of hyperthyroidism
pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
thyroid acropachy: clubbing
scalp hair thinning
increased sweating

122
Q

should pregnancy woman increase the dose of thyroxine ?

A

women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy

123
Q

what do the results of water deprivation test indicate?

A

Normal test –> starting plasma osm is normal, final urine osm is high and after desmopressine urine osm is high

PPsychogenic polydipsia - starting plasma osm is low, final urine osm is >400 and after desmopressine urine osm is >400

Cranial Diabetes insipidus - starting plasma osm is high, final urine osm is <300 and after desmopressine urine osm > 600

Nephrogenic diabetes insipidus - starting plasma osm is high, final urine osm is <300 and after desmopressine urine osm is <300

124
Q

what reduction in cholesterol is acceptable after starting statins?

A

NICE look for a 40% reduction in non-HDL cholesterol after 3 months.

125
Q

What type of thyroid cancer is associated with RET oncogene?

A

The RET oncogene encodes a receptor tyrosine kinase and is associated with MEN type 2.
Associated with medullary thyroid cancer

papillary thyroid cancer also appears to be associated with the RET oncogene

126
Q

what drugs reduce absorption of levothyroxine ?

A

iron, calcium carbonate
absorption of levothyroxine reduced, give at least 4 hours apart

127
Q

why may patients with uterine fibroids get polycythaemia ?

A

Uterine fibroids may rarely be associated with secondary polycythaemia due to autonomous production of erythropoietin

128
Q

what is a major complication of carbimazole?

A

agranulocytosis

129
Q

pathophysiology of t1DM

A

autoimmune disease
antibodies against beta cells of pancreas
HLA DR4 > HLA DR3
various antibodies such as islet-associated antigen (IAA) antibody and glutamic acid decarboxylase (GAD) antibody are detected in patients who later go on to develop type 1 DM - their prognostic significance is not yet clear

130
Q

what is the mechanism of action of mirabegron ?

A

Beta-3 receptor agonist

131
Q

what are the symptoms of gastrointestinal autonomic neuropathy ?
And how is it managed?

A

occurs secondary to autonomic neuropathy
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

manage with a pro-kinetic drug - e.e metoclopramide

132
Q

what is the target HbA1c

A

48mmol

if on agent which can cause hypoglycaemia - 53mmol/mol

MRCP (18 decks)

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