Endocrinology

Question 1

what are thiazolidinediones?

Answer 1

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.

e.g. pioglitazone

Question 2

Adverse effects of Thiazolidinediones?

Answer 2

Adverse effects
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)

Question 3

What is Bartter’s syndrome?

Answer 3

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.

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

Question 4

Features of Bartter’s syndrome?

Answer 4

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

Question 5

Pregnant ladies with hypothyroid - how much do they need their hypothyroid treatment increasing by?

Answer 5

thyroxine is safe during pregnancy
serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
breastfeeding is safe whilst on thyroxine

Question 6

what may untreated severe hyponatraemia lead to?

Answer 6

cerebral oedema

Question 7

what is considered acute or chronic hyponatraemia?

Answer 7

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

Question 8

symptoms of hyponatraemia?

Answer 8

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

Question 9

How is hypovolaemic hyponatraemia managed?

Answer 9

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

Question 10

what is the management of euvolemic and hypervolemic hyponatreamia?

Answer 10

If a euvolemic cause is suspected
fluid restrict to 500-1000 mL/day
consider medications:
demeclocycline
vaptans (see below)

If a hypervolemic cause is suspected
fluid restrict to 500-1000 mL/day
consider loop diuretics
consider vaptans

Question 11

management of acute hyponatraemia?

Answer 11

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.

Question 12

complications of hyponatraemia treatment?

Answer 12

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’

Question 13

Physiological response to hypoglycaemia ?

Answer 13

hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system

Question 14

causes of hypoglycaemia?

Answer 14

Causes
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion
nesidioblastosis - beta cell hyperplasia

Question 15

Investigations for acromegaly?

Answer 15

1st line - serum IGF-1 levels
The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.

Serum IGF-1 may also be used to monitor disease

Oral glucose tolerance test
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly

A pituitary MRI may demonstrate a pituitary tumour

Question 16

What is Gitelman’s syndrome?

Answer 16

Gitelman’s syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.

Question 17

what are the features of Gitelman’s syndrome?

Answer 17

Features
normotension
hypokalaemia
hypocalciuria
hypomagnesaemia
metabolic alkalosis

Question 18

what causes thyroid eye disease?

Answer 18

Thyroid eye disease affects between 25-50% of patients with Graves’ disease.

Pathophysiology
it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation
the inflammation results in glycosaminoglycan and collagen deposition in the muscles

Question 19

how do you prevent thyroid eye disease?

Answer 19

smoking is the most important modifiable risk factor for the development of thyroid eye disease
radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves’ disease around 15% developed, or had worsening of, eye disease. Prednisolone may help reduce the risk

Question 20

what are the features of thyroid eye disease?

Answer 20

the patient may be eu-, hypo- or hyperthyroid at the time of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy

Question 21

What is the management of thyroid eye disease?

Answer 21

smoking cessation
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery

Question 22

complications of thyroid eye disease?

Answer 22

exposure keratopathy - due to eyelid retraction and proptosis - cornea becomes excessively exposed, disrupting the normal tear film → dryness, irritation, and corneal ulceration
symptoms include foreign body sensation, pain, and photophobia

Optic neuropathy - ccurs when enlarged extraocular muscles compress the optic nerve at the apex of the orbit → a reduction in visual acuity, colour vision deficits, and visual field defect

Strabismus and diplopia - fibrosis and enlargement of the extraocular muscles can result in restrictive strabismus → misalignment of the eyes → double vision (diplopia)
this not only affects visual function but can also significantly impair the quality of life.

Question 23

diagnostic thresholds for gestational diabetes?

Answer 23

fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L

Question 24

Management of gestational diabetes?

Answer 24

if the fasting plasma glucose level is < 7 mmol/l a trial of diet and exercise should be offered
if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
if glucose targets are still not met insulin should be added to diet/exercise/metformin
gestational diabetes is treated with short-acting, not long-acting, insulin
if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment

Question 25

what may be used to treat galactorrhea?

Answer 25

Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea.

Question 26

causes of raised prolactin?

Answer 26

prolactinoma pregnancy oestrogens physiological: stress, exercise, sleep acromegaly: 1/3 of patients polycystic ovarian syndrome primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)

Question 27

what drugs can cause raised prolactin?

Answer 27

metoclopramide, domperidone phenothiazines haloperidol very rare: SSRIs, opioids

Question 28

what are the antibodies in graves disease?

Answer 28

IgG antibodies to the thyroid-stimulating hormone (TSH) receptor IgG Anti-thyroid peroxidase antibodies

Question 29

what do non-functioning pituitary adenomas result in?

Answer 29

Non-functioning pituitary adenomas can result in panhypopituitarism due to infiltration of the normal pituitary tissue. Compression of the pituitary stalk can result in hyperprolactinaemia due to decreased transport of dopamine from the hypothalamus to the pituitary. Dopamine acts to suppress prolactin release

Question 30

what is the mechanism of action of orlistat?

Answer 30

orlistat acts as a pancreatic lipase inhibitor. Orlistat works by binding reversibly to pancreatic lipase in the gastrointestinal tract, preventing the breakdown of dietary triglycerides into absorbable free fatty acids and monoglycerides. This results in approximately 30% of ingested fat passing through the gut unabsorbed, thereby reducing caloric intake and promoting weight loss.

Question 31

when should orlistat be prescribed?

Answer 31

It should only be prescribed as part of an overall plan for managing obesity in adults who have: BMI of 28 kg/m^2 or more with associated risk factors, or BMI of 30 kg/m^2 or more continued weight loss e.g. 5% at 3 months orlistat is normally used for < 1 year

Question 32

how do sulfonylureas work?

Answer 32

They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.

Question 33

adverse effects of sulfonylureas?

Answer 33

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 should be avoided in breast feeding and pregnancy

Question 34

management of Hirsutism and acne in PCOS?

Answer 34

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

Question 35

key points of levothyroxine therapy?

Answer 35

start on 25mcg if over 50 other patients should be started on 50-100 following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks goal is normalisation of TSH level iron, calcium carbonate absorption of levothyroxine reduced, give at least 4 hours apart .

Question 36

side effects of thyroxine therapy ?

Answer 36

hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation

Question 37

what are the features of insulinoma?

Answer 37

of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc rapid weight gain may be seen high insulin, raised proinsulin:insulin ratio high C-peptide

Question 38

Diagnosis of insulinoma?

Answer 38

supervised, prolonged fasting (up to 72 hours) CT pancreas Whilst supervised fasting is normally the investigation of choice if this option is not given then insulin + C-peptide levels during an acute hypoglycaemic episode are useful.

Question 39

what is primary hyperparathyroidism?

Answer 39

Primary hyperparathyroidism is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible. Causes of primary hyperparathyroidism 85%: solitary adenoma 10%: hyperplasia 4%: multiple adenoma 1%: carcinoma

Question 40

what are the features of primary hyperparathyroidism?

Answer 40

80% of patients are asymptomatic polydipsia, polyuria depression anorexia, nausea, constipation peptic ulceration pancreatitis bone pain/fracture renal stones hypertension

Question 41

Investigations for primary hyperparathyroidism?

Answer 41

bloods raised calcium, low phosphate PTH may be raised or (inappropriately, given the raised calcium) normal technetium-MIBI subtraction scan x-ray findings pepperpot skull osteitis fibrosa cystica

Question 42

what is the treatment for primary hyperparathyroidism?

Answer 42

the definitive management is total parathyroidectomy conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage patients not suitable for surgery may be treated with cinacalcet, a calcimimetic a calcimimetic 'mimics' the action of calcium on tissues by allosteric activation of the calcium-sensing receptor

Question 43

what is the management of myxoedemic coma?

Answer 43

Myxoedemic coma is treated with thyroxine and hydrocortisone

Question 44

what is hungry bone syndrome?

Answer 44

Hungry bone syndrome is an uncommon entity but can occur after parathyroidectomy if the hyperparathyroidism has been long-standing. The mechanism is thought to be thus: high pre-operative levels of parathyroid hormone provide a constant stimulus for osteoclast activity creating the hypercalcaemic state by de-mineralizing the bones. This process can result in x-ray changes very similar to metastatic lytic lesions if left untreated. Upon removal of the parathyroid adenoma the hormone levels fall rapidly (they have a very short half-life) and the osteoclast activity is subsequently diminished and the bones rapidly begin re-mineralisation - 'hungry bone syndrome'. This process can be uncomfortable and also result in systemic hypocalcaemia.

Question 45

What is Addison's disease?

Answer 45

Autoimmune destruction of the adrenal glands is the most common cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison's disease and results in reduced cortisol and aldosterone being produced.

Question 46

features of Addison's disease?

Answer 46

lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-craving' Hyperpigmentation (especially in palmar creases) vitiligo loss of pubic hair in women hypotension hypoglycaemia hyponatraemia and hyperkalaemia may be seen crisis: collapse, shock, pyrexia

Question 47

Why do you get hyperpigmentation in Addison's disease?

Answer 47

ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is cleaved to produce ACTH, other melanocyte-stimulating hormones (MSH) are also produced. These MSHs have the effect of stimulating melanocytes in the skin to produce more melanin, the pigment responsible for skin colour primary Addison's is associated with hyperpigmentation whereas secondary adrenal insufficiency is not

Question 48

Causes of hypoadrenalism?

Answer 48

Primary causes tuberculosis metastases (e.g. bronchial carcinoma) meningococcal septicaemia (Waterhouse-Friderichsen syndrome) HIV antiphospholipid syndrome Secondary causes pituitary disorders (e.g. tumours, irradiation, infiltration) Exogenous glucocorticoid therapy

Question 49

What is Liddle's syndrome?

Answer 49

Liddle's syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium. Treatment is with either amiloride or triamterene

Question 50

How is Familial hypercholesterolaemia inherited?

Answer 50

Familial hypercholesterolaemia (FH) is an autosomal dominant FH is caused by mutations in the gene which encodes the LDL-receptor protein.

Question 51

How is familial hypercholesterolaemia managed?

Answer 51

Clinical diagnosis is now based on the Simon Broome criteria: in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus: for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels

Question 52

Diagnosis of diabetes?

Answer 52

If the patient is symptomatic: fasting glucose greater than or equal to 7.0 mmol/l random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test) If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions. When HbA1c is used for the diagnosis of diabetes: a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes) in patients without symptoms, the test must be repeated to confirm the diagnosis it should be remembered that misleading HbA1c results can be caused by increased red cell turnover (see below)

Question 53

In what conditions can HbA1c not be use for diagnosis?

Answer 53

haemoglobinopathies haemolytic anaemia untreated iron deficiency anaemia suspected gestational diabetes children HIV chronic kidney disease people taking medication that may cause hyperglycaemia (for example corticosteroids)

Question 54

How does alcohol lead to hypoglycaemia?

Answer 54

causes exaggerated insulin secretion mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion

Question 55

causes of hypoglycaemia?

Answer 55

insulinoma - increased ratio of proinsulin to insulin self-administration of insulin/sulphonylureas liver failure Addison's disease alcohol nesidioblastosis - beta cell hyperplasia

Question 56

physiological response to hypoglycaemia?

Answer 56

hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system

Question 57

Features of hypoglycaemia?

Answer 57

blood glucose levels and the severity of symptoms are not always correlated, especially in patients with diabetes. blood glucose concentrations <3.3 mmol/L cause autonomic symptoms due to the release of glucagon and adrenaline (average frequency in brackets): Sweating Shaking Hunger Anxiety Nausea blood glucose concentrations below <2.8 mmol/L cause neuroglycopenic symptoms due to inadequate glucose supply to the brain: Weakness Vision changes Confusion Dizziness Severe and uncommon features of hypoglycaemia include: Convulsion Coma

Question 58

Complications of HRT?

Answer 58

increased risk of breast cancer increased by the addition of a progestogen in the Women's Health Initiative (WHI) study there was a relative risk of 1.26 at 5 years of developing breast cancer the increased risk relates to the duration of use the risk of breast cancer begins to decline when HRT is stopped and by 5 years it reaches the same level as in women who have never taken HRT increased risk of endometrial cancer oestrogen by itself should not be given as HRT to women with a womb reduced by the addition of a progestogen but not eliminated completely the BNF states that the additional risk is eliminated if a progestogen is given continuously increased risk of venous thromboembolism increased by the addition of a progestogen transdermal HRT does not appear to increase the risk of VTE NICE state women requesting HRT who are at high risk for VTE should be referred to haematology before starting any treatment (even transdermal) increased risk of stroke increased risk of ischaemic heart disease if taken more than 10 years after menopause

Question 59

What is androgen insensitivity syndrome?

Answer 59

Androgen insensitivity syndrome is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome

Question 60

Features of androgen insesntivity syndrome?

Answer 60

'primary amenorrhoea' little or no axillary and pubic hair undescended testes causing groin swellings breast development may occur as a result of the conversion of testosterone to oestradiol

Question 61

Diagnosis and management of androgen insenstivity syndrome?

Answer 61

Diagnosis buccal smear or chromosomal analysis to reveal 46XY genotype after puberty, testosterone concentrations are in the high-normal to slightly elevated reference range for postpubertal boys Management counselling - raise the child as female bilateral orchidectomy (increased risk of testicular cancer due to undescended testes) oestrogen therapy

Question 62

What is Kallmann's syndrome?

Answer 62

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

Question 63

Features of Kallmann's syndrome?

Answer 63

'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

Question 64

Management of Kallmann's syndrome

Answer 64

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

Question 65

Pathophysiology of Osmotic demyelination syndrome?

Answer 65

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 ## Footnote 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'

Question 66

What is Primary hyperparathyroidism?

Answer 66

Primary hyperparathyroidism is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible. Causes of primary hyperparathyroidism 85%: solitary adenoma 10%: hyperplasia 4%: multiple adenoma 1%: carcinoma

Question 67

Investigations in primary hyperparathyroidism?

Answer 67

bloods raised calcium, low phosphate PTH may be raised or (inappropriately, given the raised calcium) normal technetium-MIBI subtraction scan x-ray findings pepperpot skull osteitis fibrosa cystica

Question 68

Treatment for primary hyperparathyroidism?

Answer 68

the definitive management is total parathyroidectomy conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage patients not suitable for surgery may be treated with cinacalcet, a calcimimetic a calcimimetic 'mimics' the action of calcium on tissues by allosteric activation of the calcium-sensing receptor

Question 69

Mechanism of action on sulfonylureas?

Answer 69

They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.

Question 70

Adverse effects of sulfonylureas?

Answer 70

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.

Question 71

What are the threee main types of multiple endocrine neoplasia?

Answer 71

Question 72

What oncogener is associated with medullary thyroid cancer?

Answer 72

Medullary thyroid cancer is associated with the RET oncogene

Question 73

what are dynamic pituitary function tests?

Answer 73

A dynamic pituitary function test is used to assess patients with suspected primary pituitary dysfunction Insulin, TRH and LHRH are given to the patient following which the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals. Prolactin levels are also sometimes measured *dopamine antagonist tests using metoclopramide may also be used in the investigation of hyperprolactinaemia. A normal response is at least a twofold rise in prolactin. A blunted prolactin response suggests a prolactinoma

Question 74

A normal dynamic pituitary function test has the following characteristics:

Answer 74

GH level rises > 20mu/l cortisol level rises > 550 mmol/l TSH level rises by > 2 mu/l from baseline level LH and FSH should double

Question 75

primary, secondary and tertiary hyperparathyroidism?

Answer 75

Primary hyperparathyroidism PTH over-secretion usually from a parathyroid adenoma both PTH and calcium are elevated surgery to remove the adenoma is the most effective treatment conservative measures such as bisphosphonates can be used Secondary hyperparathyroidism occurs in chronic kidney disease typically can be secondary to vitamin D deficiency PTH released due to low calcium, high phosphate and lack of vitamin D activation by diseased kidneys PTH level high with calcium levels being low or normal medical management primarily: phosphate binders, calcium and vitamin D supplementation Tertiary hyperparathyroidism autonomous hypersecretion of PTH due to hypertrophied parathyroid glands occurs after a period of long standing secondary hyperparathyroidism treatment involves parathyroidectomy

Question 76

What may cause Pseudohperkalaemia?

Answer 76

haemolysis during venipuncture (excessive vacuum of blood drawing, prolonged tourniquet use or too fine a needle gauge) delay in the processing of the blood specimen abnormally high numbers of platelets, leukocytes, or erythrocytes (such as myeloproliferative disorders) familial causes

Question 77

What is Pseudohyperkalaemia?

Answer 77

Pseudohyperkalaemia is a rise in serum potassium that occurs due to excessive leakage of potassium from cells, during or after blood is taken. It is a laboratory artefact and does not represent the true serum potassium concentration. The majority of potassium is intracellular and thus leakage from cells can significantly impact serum levels. In this case the potassium is released as the large numbers of platelets aggregate and degranulate.

Question 78

Hashimoto vs Graves disease?

Answer 78

** Anti-TPO with features of Hyperthyroid (Low TSH, High T3/T4) --> Grave’s Disease ** Anti-TPO with features of Hypothyroid (High TSH, Low T3/T4) --> Hashimoto Thyroiditis

Question 79

How do Sulfonylureas act?

Answer 79

Sulfonylureas - bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells They work via mimicking the role of ATP on potassium-ATP channels from the outside. They act to block these channels causing membrane depolarisation and thus opening of voltage-gated calcium channels. This process results in the stimulation of insulin release.

Question 80

Management of acromegaly?

Answer 80

Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients. If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated: somatostatin analogue directly inhibits the release of growth hormone for example octreotide effective in 50-70% of patients pegvisomant GH receptor antagonist - prevents dimerization of the GH receptor once daily s/c administration very effective - decreases IGF-1 levels in 90% of patients to normal doesn't reduce tumour volume therefore surgery still needed if mass effect dopamine agonists for example bromocriptine the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues effective only in a minority of patients

Question 81

What treatment may be used as an adjunct to surgery in acromegaly?

Answer 81

octreotide, a somatostatin analogue which is often used as an adjunct to surgery resulting in reduced growth hormone levels and reduction in tumour size

Question 82

Features of hypoclacaemia?

Answer 82

As extracellular calcium concentrations are important for muscle and nerve function many of the features seen in hypocalcaemia seen a result of neuromuscular excitability Features tetany: muscle twitching, cramping and spasm perioral paraesthesia if chronic: depression, cataracts ECG: prolonged QT interval

Question 83

What two clinical signs are seen in hypocalcaemia and what percentage of people are they seen in?

Answer 83

Trousseau's sign carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic wrist flexion and fingers are drawn together seen in around 95% of patients with hypocalcaemia and around 1% of normocalcaemic people Chvostek's sign tapping over parotid causes facial muscles to twitch seen in around 70% of patients with hypocalcaemia and around 10% of normocalcaemic people

Question 84

Causes of Hypokalaemia with acidosis, with alkalosis, with HTN without HTN?

Answer 84

Hypokalemia with alkalosis= CCTV=> cushing's, Conn's, thiazide n loop, vomiting Hypokalemia with acidosis=DRAP=> Diarrhea, RTA, Acetazolamide, Partially rx dka Hypokalemia with Hypertension= CCL11=> Cushing's, Con's, Liddle's,11-beta hydroxylase deficiency Hypokalemia without Hypertension: DR BiL Gates=> Diuretics, RTA 1 n 2, Barterr's, giteLman's and GI loss

Question 85

what is 11-beta hydroxylase deficiency?

Answer 85

a form of congenital adrenal hyperplasia (CAH) characterised by impaired cortisol synthesis and accumulation of 11-deoxycorticosterone (DOC), which has mineralocorticoid activity. The excess DOC leads to sodium retention, volume expansion, and hypertension. Additionally, the condition causes hypokalaemia due to increased potassium excretion driven by the mineralocorticoid excess.

Question 86

Management of hyperthyroidism in pregnancy?

Answer 86

Propylthiouracil is used in the first trimester of pregnancy in place of carbimazole, as the latter drug may be associated with an increased risk of congenital abnormalities. At the beginning of the second trimester, the woman should be switched back to carbimazole, as propylthiouracil has been associated with a small risk of severe hepatic injury.

Question 87

What is sick euthyroid syndrome?

Answer 87

In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3). Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.

Question 88

Causes of sick euthyroid?

Answer 88

Causes of sick euthyroid include: myocardial infarctions, starvation, burns, trauma, surgery, malignancy, diabetic ketoacidosis, any organ failure and inflammatory conditions.

Question 89

Pathophysiology of SIADH?

Answer 89

Pathophysiology SIADH involves an excessive release of antidiuretic hormone (ADH), also known as vasopressin, which leads to water retention, volume expansion, and dilutional hyponatraemia ADH is produced by the hypothalamus and stored in the posterior pituitary gland. Its primary function is to regulate the body's water balance It does this by increasing water reabsorption in the collecting ducts of the kidneys, thereby decreasing the volume of urine produced In SIADH, there is an inappropriate and continuous release of ADH that is not inhibited by normal physiological mechanisms, such as adequate or excess body fluid levels As a result, the kidneys reabsorb more water, leading to decreased urine output, and expansion of extracellular fluid volume. Importantly, this increase in body fluid volume does not lead to the expected signs of fluid overload, such as oedema or hypertension, because the excess fluid is uniformly distributed throughout all body fluid compartments. However, as water is retained in the body, the concentration of electrolytes in the blood, particularly sodium, becomes diluted, leading to hyponatraemia.

Question 90

Causes of SIADH

Answer 90

Question 91

Investigations for SIADH?

Answer 91

Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality. Urine sodium concentration: Urine sodium concentration is typically high (>40 mmol/L) due to the action of ADH on the renal tubules.

Question 92

management of SIADH?

Answer 92

correction must be done slowly to avoid precipitating central pontine myelinolysis fluid restriction demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH ADH (vasopressin) receptor antagonists have been developed

Question 93

What thyroid disorder is associated with MALT lymphoma?

Answer 93

Hashimoto's

Question 94

What is subclincial hyperthyroidism?

Answer 94

Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as: normal serum free thyroxine and triiodothyronine levels with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)

Question 95

Causes of Subclinical hyperthyroidism?

Answer 95

multinodular goitre, particularly in elderly females excessive thyroxine may give a similar biochemical picture

Question 96

why is it important to recognise subclinical hyperthyroidism?

Answer 96

The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and increase the likelihood of dementia

Question 97

Management of subclinical hyperthyroidism?

Answer 97

TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission

Question 98

Which type of renal tubular acidosis will cause renal stones?

Answer 98

Distal renal tubular acidosis can cause calcium phosphate renal stones and is linked to Sjogrens syndrome ## Footnote Type 1 RTA (distal) inability to generate acid urine (secrete H+) in distal tubule causes hypokalaemia complications include nephrocalcinosis and renal stones causes include idiopathic, rheumatoid arthritis, SLE, Sjogren's, amphotericin B toxicity, analgesic nephropathy

Question 99

What happens to the hormones in the follicular phase?

Answer 99

A rise in FSH results in the development of follicles which in turn secrete oestradiol When the egg has matured, it secretes enough oestradiol to trigger the acute release of LH. This in turn leads to ovulation

Question 99

What are the phases of the menstrual cycle?

Answer 99

Question 100

What happens to the hormones in the luteal phase?

Answer 100

Progesterone secreted by corpus luteum rises through the luteal phase. If fertilisation does not occur the corpus luteum will degenerate and progesterone levels fall Oestradiol levels also rise again during the luteal phase

Question 101

What may happen when paient recieve radioiodine treatment for Graves disease?

Answer 101

Radioiodine treatment may lead to the development / worsening of thyroid eye disease in up to 15% of patients with Grave's disease

Question 102

treatment for diabetic peripheral neuropathy?

Answer 102

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

Question 103

Management of Gastroparesis secondary to diabatic autonomic neuropathy?

Answer 103

management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Question 104

what is the first hormone secreted in response to hypogkycaemia?

Answer 104

Glucagon is the first hormone secreted in response to hypoglycaemia Glucagon promotes gluconeogenesis in an attempt to raise blood glucose levels.

Question 105

What are the different types of thyroid cancer?

Answer 105

Papillary Follicular Medullary Anaplastic Lymphoma

Question 106

What is Phaeochromocytoma?

Answer 106

Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome Basics bilateral in 10% malignant in 10% extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)

Question 107

Features of Phaeochromocytoma?

Answer 107

Features are typically episodic hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety

Question 108

Tests for phaeochromocytoma?

Answer 108

24 hr urinary collection of metanephrines (sensitivity 97%*) this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)

Question 109

Managment of phaeochromocytoma ?

Answer 109

Surgery is the definitive management. The patient must first however be stabilized with medical management: alpha-blocker (e.g. phenoxybenzamine), given before a beta-blocker (e.g. propranolol)

Question 110

what karyotype is associated with Klinefelter's syndrome?

Answer 110

karyotype 47, XXY

Question 111

Features of Klinefelter's syndrome?

Answer 111

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 Diagnosis is by karyotype (chromosomal analysis).

Question 112

causes of raised prolactin?

Answer 112

Causes of raised prolactin - the p's pregnancy prolactinoma physiological polycystic ovarian syndrome primary hypothyroidism phenothiazines, metoclopramide, domperidone ## Footnote Causes of raised prolactin prolactinoma pregnancy oestrogens physiological: stress, exercise, sleep acromegaly: 1/3 of patients polycystic ovarian syndrome primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release) Drug causes of raised prolactin metoclopramide, domperidone phenothiazines haloperidol very rare: SSRIs, opioids

Question 113

what is the target fasting glucose for gestational diabetes?

Answer 113

The target for fasting blood glucose in gestational diabetes is <5.3 mmol/L. The target for blood glucose two hours after an oral glucose tolerance test is <6.4 mmol/L.

Question 114

what is the most common cause of ectopic ACTH production

Answer 114

small cell lung cancer