1
Q
what is type 1 diabetes
A
an autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency
2
Q
what are risk factors for type 1 diabetes mellitus
A
family history
HLA - DR4-D8/DR3-DQ2
viral exposure
80-90% have insulin autoantibodies
3
Q
what are symptoms of type 1 diabetes mellitus
A
polyuria
polydipsia
weight loss
lethargy
blurred vision
exam may show: peripheral neuropathy, foot ulcers, lipodystrophy
4
Q
what key metabolic processes is insulin responsible for
A
increased glucose uptake into skeletal muscle and adipose tissue
promoting glycogen synthesis in the liver to store glucose
inhibition of lipolysis lowering serum free fatty acid levels
promoting protein synthesis
5
Q
what are differential diagnosis for suspected diabetes
A
psychogenic polydipsia
arginine vasopressin deficiency (central diabetes insipidus)
AVP resistance (Nephrogenic diabetes insipidus)
medication use - thiazide diuretics, glucocorticoids)
genetic conditions
6
Q
what bedside investigations can be done for type 1 diabetes
A
blood glucose levels
blood ketone level
urinalysis
fundoscopy
BMI
waist circumference
7
Q
what laboratory investigations can be done for type 1 diabetes mellitus
A
FBC
U&E
LFT
HbA1c
lipid profile
urinary albumin-to-creatinine
vitamin B12
TFT
insulin autoantibodies
C-peptide level: marker of endogenous insulin production
coeliac serology
8
Q
how is diabetes mellitus diagnosed
A
presence of hyperglycaemia symptoms and random blood glucose level >11.1mmol
in the absence of sx you need two abnormal blood glucose levels as defined by:
fasting glucose >7 mmol
blood glucose >11.1mmol/L two hours after 75g glucose in OGTT
9
Q
how is type 1 diabetes managed
A
- healthy dietary choices and exercise
- glucose monitoring
- insulin regimes: injection or pump
10
Q
when are continuous glucose monitors endorsed by NICE for those with type 1 diabetes
A
if they have type 1 diabetes and one of the following:
>1 episode of severe hypoglycaemia without obvious preventable cause
complete loss of hypoglycaemia awareness
frequent asymptomatic hypoglycaemia
extreme fear of hypoglycaemia
hyperglycaemia despite testing at least 10 times per day
pregnant women
11
Q
what is the first line insulin regime for diabetes
A
multiple daily injections which involves a basal bolus regimen
12
Q
what does an insulin pump do
A
it delivers a continuous subcutaneous insulin infusion of short acting insulin
- these systems can automatically adjust insulin delivery based on interstitial glucose levels to achieve tight control
13
Q
what are indications for continuous subcutaneous insulin infusion
A
disabling, unpredictable and repeated hypoglycaemia despite attempts to achieve targets with injections
HbA1c above target despite injection therapy and engagement with care
14
Q
what are disadvantages of continuous subcutaneous insulin infusion
A
risk of diabetic ketoacidosis if pump fails or is disconnected as there is no long acting insulin
constant attachment to a pump
infusion site problems - infection
complicated set up
cost of consumables related to pump
14
Q
what are advantages of continuous subcutaneous insulin infusion
A
fewer needle injections
convenient delivery with more flexibility
delayed bolus delivery, useful for gastroparesis or dealing with high-fat and/or high-protein meals
more reliable absorption
improved patient experience and satisfaction
15
Q
what is diabetic ketoacidosis
A
it is absolute insulin deficient state whereby uncontrolled hyperglycemia eventually results in the development of ketone bodies or ketone acid which dangerouly lower the pH of the blood
16
Q
what are symptoms of ketoacidosis
A
abdominal pain
nausea and vomiting
fruity smelling breath
deep rapid breathing
altered conscious state, including confusion and coma
17
Q
what are the diagnostic criteria for diabetic ketoacidosis
A
hyperglycaemia - blood glucose above 11mmol/L or known DM
ketonaemia - capillary or blood ketone above 3 mmol/L or significant ketonuria of 2+ or more
acidosis (bicarb less than 15mmol/L or venous pH of less than 7.3)
18
Q
what is a major precipitating factor for both DKA and HHS
A
infection
19
Q
what are the characteristic features of hyperosmolar hyperglycaemic state
A
marked hypovolaemia
marked hyperglycaemia (blood glucose of 30mmol/L or above)
hyperosmolality
20
Q
what are common signs and symptoms of HHS
A
dehydration due to polyuria and polydipsia
weakness
weight loss
tachycardia
dry mucous membranes
poor skin turgor
hypotension
acute cognitive impairment
shock
21
Q
what factors may precipitate DKA and HHS
A
infection
inadequate insulin and non adherence with insulin treatment
new onset of diabetes mellitus or other physiological stress
other medical conditions - hypothyroidism or pancreatitis
drugs - corticosteroids, diuretics, atypical antipsychotics, salbutamol
22
Q
how do you treat diabetic ketoacidosis if BP is under 90
A
if systolic BP <90mmhg give fluid bolus of 500mL saline over 10-15 minutes
if bp remains low repeat the bolus and get help
23
Q
how do you treat diabetic ketoacidosis if initial BP is over 90mmhg
A
- Give 1L saline over 60 minutes
- give ongoing fluid replacement with potassium chloride
- give 10% glucose in addition to normal saline if the blood glucose falls below 14mmol/L
24
what are microvascular complications of diabetes
diabetic retinopathy
diabetic nephropathy
diabetic neuropathy
25
what are the macrovascular complications of diabetes mellitus
coronary heart disease
cerebrovascular disease
peripheral vascular disease
26
what is hypogylcaemia defined as
a blood glucose level of equal to or less than 4.0mmol/l
27
what are precipitating causes of hypoglycaemia in type 1 diabetes
excessive insulin administration
exercise
alcohol
pregnancy
malabsorption
cortisol deficiency (addisons)
growth hormone deficiency
kidney disease
liver disease
28
what is type 2 diabetes mellitus
it is a common and complex metabolic disease characterised by insulin resistance and subsequent high blood glucose levels
29
what is the pathophysiology of type 2 diabetes
chronically high insulin levels from excess dietary sugar intake cause organs to develop resistance to the effects of insulin over time meaning more insulin is needed to lower glucose to the same degree. As the condition progresses the pancreas begins to tire and stops producing insulin
30
what are non modifiable risk factors for type 2 diabetes
age: over 40
sex: more common in men
Ethnicity: south asian, black african and black caribbean have higher risks
family history: first degree relatives with T2DM
30
what are modifiable risk factors for type 2 diabetes
obesity
alcohol excess
smoking
poor sleep and stress
31
what medical conditions increase the risk of type 2 diabetes
polycystic ovarian syndrome
gestational diabetes mellitus
mental health conditions
steroid induced diabetes
cushings
32
what are symptoms of type 2 diabetes
polyuria
polydipsia
unintentional weight loss
tired all the time
frequent or resistant infections
poor wound healing
blurred vision
33
what may be found on clinical examination in someone with type 2 diabetes
Raised BMI
raised waist circumference
acanthosis nigricans
diabetic retinopathy on fundoscopy
evidence of diabetic neuropathy and peripheral vascular disease on foot examination
evidence of renal replacement therapy (ateriovenous fistula/renal transplant scar)
34
what are normal capillary blood glucose ranges
pre meal = 4-5.9
2 hours post meal = less than 7.8
35
what might be seen on urine dipstick in someone with type 2 diabetes
urinary glucose
urinary ketones
urinary protein (diabetic nephropathy)
35
what is HbA1c a measure of
it is a measure of average blood glucose concentration (using glucose bound to haemoglobin) in the preceding 3 months
36
what is the urine albumin creatinine ratio
it is a urine sample which detects microalbuminuria and compares it with creatinine. In diabetic nephropathy a glomerular basement membrane damage allows small proteins like albumin to leak abnormally through the filtration system into the urine
37
how is type 2 diabetes diagnosed
HbA1c equal to or over 48mmol/mol
- if symptomatic 1 result is sufficient
- if asymptomatic then repeat in 2 weeks
38
what plasma venous glucose might indicate a diabetes diagnosis
fasting PVG - over 7 is T2DM, 6.1-6.9 indicates impaired fasting glucose
random PVG - over 11.1 is T2DM, 7.9-11 indicates impaired glucose tolerance
39
how is type 2 diabetes managed
weight loss
diet changes
exercise
reducing alcohol
stop smoking
improvement of sleep and stress
40
what is first line medication for type 2 diabetes
metformin
41
what is the mechanism of action of metformin
reduces insulin resistance of target cells
reduces liver gluconeogenesis
42
what are examples of SGLT-2 inhibitors
dapagliflozin
empagliflozin
43
44
what is the mechanism of SGLT-2 inhibitors
it reduces renal glucose reabsorption (inhibits sodium-glucose cotransporter 2) so more glucose is excreted in the urine to reduce hyperglycaemia
44
what is the benefit of SGLT-2 inhibitors
it has cardo/reno-protective effects
45
what are side effects of metformin
GI upset - changing to modified release can improve this
Do not use in renal failure (eGFR<45ml/min) or post MI due to the risk of lactic acidosis
46
what are side effects of SGLT-2 inhibitors
euglycemic diabetic ketoacidosis
UTI and genital thrush
should be paused in acute infection like metformin
47
what is an example of sulfonylureas
gliclazide
48
what is the mechanism of sulfonylureas
increase endogenous insulin secretion by stimulating pancreatic beta islet cells
causes rapid reduction in HbA1c and is useful if osmotic symptoms
49
what are side effects of sulfonylureas
hypoglycaemia
weight gain
abnormal LFTs
hyponatraemia (SIADH)
50
what are examples of DPP4 inhibitors
sitagliptin
linagliptin
51
what is the mechanism of DPP4 inhibitors
drugs which block dipeptidyl peptidase 4 which normally breaks down GLP-1 increasing the insulin release effect
52
what are side effects of DPP4 inhibitors
can cause pancreatitis
less effect in reducing HbA1C
- doesnt cause hypoglycaemia and weight neutral
53
what are examples of GLP-1 analogues
liraglutide
semaglutide
54
what is the mechanism of GLP-1 analogues
gut hormones like glucose like peptide to provoke insulin release post meal
major weight loss effect
55
what are side effects of GLP-1 analogues
significant weight loss
can cause pancreatitis
56
what are the HbA1C thresholds for
a. those on lifestyle or metformin alone
b. on more than one drug or any causing hypoglycaemia
c. intervention threshold for starting a 2nd drug if on metformin/3rd drug
a. =<48
b. =<53
c. =>58
57
when is insulin used in type 2 diabetes
if triple therapy fails or rapid control is required
58
what are the main risks of insulin
hypoglycaemia
weight gain
lipodystrophy
59
what is the target blood pressure for someone with type 2 diabetes
less than 140/90
(under 135/85 for home)
60
how is microalbuminaemia (CKD) managed in type 2 diabetes
>3 = should be on ACE/ARB regardless of BP
>30 = if on max ACE/ARB dose then add SGLT-2 inhibitor
>70 = stricter BP target of less than 130/80 in clinic
61
what should any patient with a QRISK of over 10 be offered
a statin - atorvastatin 20mg
62
if someone suffers a stroke/MI what statin should they be offered
high intensity statin - 80mg atorvastatin
63
what is on the diabetes annual review checklist
HbA1c and individualised target
lifestyle advice and education
BMI, BP, urine dip
U&E, lipids and QRISK
diabetic foot check
annual diabetic retinopathy screening
64
what regulations does the DVLA have for type 2 diabetes and driving
if it is managed with lifestyle alone or medications that dont cause hypoglycaemia the DVLA doesnt need informing.
Those on hypoglycaemic drugs, the DVLA needs to be informed and specific criteria need to be met to see if they can drive or not
65
in diabetic ketoacidosis how often do you need to measure potassium
need to measure urgently initially on venous gas, then again at 60 minutes, 2hrs and 2 hourly thereafter
66
what do you do if potassium is deranged
if potassium is under 3.5 get an immediate senior review as a bolus will need to be given
if its 3.5-5.5 then add 40mmol/L potassium to saline
if over 5.5 dont add potassium to fluid
67
what is resolution of diabetic ketoacidosis defined as
pH >7.3
and
bicarb >15
and
blood ketones <0.6mmol/L
68
what is Hyperosmolar hyperglycaemic state
this is non ketotic hyperglycaemic state, where there is profound hyperglycaemia (glucose >30), hyperosmolality and volume depletion in the absence of a significant ketoacidosis
69
what is the initial drug management for HHS
intravenous fluid replacement - 1 litre over 1 hours
followed by IV insulin - only start once fluid replacement is adequate and glucose concentrations have plateaued
70
what flow rate of IV fluid should be given to someone with DKA
give 500 mls over 15 minutes
71
what monitoring should happen for those with HHS
hourly blood glucose, Na, K, urea and calculated osmolality for first 6 hours then 2 hourly osmolality
continuous pulse oximetry
consider continuous cardiac monitoring
72
what are clinical features of hypoglycaemia
sweating
palpitations
tremor
hunger
confusion
drowsiness
behavioural change
speech change
incoordination
nausea
headache
73
what are risk factors for hypoglycaemia
insulin dependent diabetes
previous history of hypoglycaemic episodes or reduced hypoglycaemia awareness
impaired renal function
cognitive dysfunction/dementia
alcohol misuse
profound starvation
increased exercise
food malabsorption issues - coeliac, bariatric surgery, gastroenteritis
74
what is the normal reference range for fasting glucose
4-5.8mmol/L
75
what is the reference range for hypoglycaemia
plasma glucose less than 3.0mmol/L and blood glucose less than 4 should be treated if the patient is symptomatic
76
how do you manage hypoglycaemia in a conscious patient
if the patient is conscious: glucose gel by mouth, rpt cap.blood glucose after 10-15 mins and if patient still hypo give more gel a further 2-3 times. When fully alert give something with longer acting carbs such as toast
77
how do you manage hypoglycaemia in an unconscious patient
administer IV glucose (e.g 150 of 10%)
if the patient regains consciousness switch to oral glucose
if IV access isnt able to be established administer glucagon 1mg via the IM/subcut route
78
what is thyrotoxicosis
it is a clinical manifestation of excess thyroid hormone action and the tissue level due to high circulating thyroid hormone concentrations
79
what is the most common cause of hyperthyroidism
graves disease
80
what spinal level is the thyroid located at
c5-t1
81
what is the anatomy of the thyroid gland
it consists of a central isthmus and two lobes, sits anterior to the trachea with four parathyroid gland on the posterior surface
82
what is the physiology of the thyroid gland
thyroid hormones are produced by follicular cells in the thyroid gland, regulated by the hypothalamic-pituitary-thyroid axis.
THR is released from the hypothalamus, which stimulates TSH release from the pituitary. TSH causes production of thyroid hormones from the thyroid
83
where is the hypothalamus is TRH released from
the paraventricular nucleus
84
what cells in the pituitary release TSH
thyrotrophes
85
what is the main hormone that is released from the thyroid
T4 with smaller amounts of T3. T4 is then converted to T3 when it reaches the target tissues
86
what are the causes of thyrotoxicosis
graves disease
toxic multinodular goitre
iodine excess
iatrogenic
viral infection
postpartum thyroiditis
87
what is graves disease
it is an autoimmune condition mediated via anti-TSH receptor autoantibodies which bond to the thyroid and increase production of T4/3
88
what is toxic multinodular goitre
it is caused by the development of physiologically active nodules on the thyroid gland which are capable of secreting hormones
89
how does iodine excess cause thyrotoxicosis
because thyroid hormone production is dependent upon iodine so increased concentrations allow increased production of the hormones. It can occur following the use of contrast media for imaging modalities or via contamination of food
90
what are iatrogenic causes of thyrotoxicosis
amiodarone - increases iodine levels
levothyroxine
91
how can viral infections cause thyrotoxicosis
can cause a subacute De Quervains thyroiditis which can cause a transient rise in thyroid hormone production due to inflammation of the thyroid gland and subsequent excessive excretion of thyroid hormones into the circulation. presents with a painful lump in the neck
92
what is postpartum thyroiditis
occurs 2-6 months post birth where there is a transient acute phase of thyrotoxicosis followed by a period of hypothyroidism
93
what are symptoms of hyperthyroidism
recent unintended weight loss
increased appetite
diarrhoea
heat intolerance
over activity and restlessness
tremor
palpitations
irritability
muscle weakness
loss of libido
oligomenorrhoea
94
what are clinical features of hyperthyroidism
thin and brittle hair
warm and moist skin
irregular or fast heart rate
fine tremor
brisk reflexes
palmer erythema
lid lag and lid retraction
goitre
95
what are clinical features which are specific to graves disease
- thyroid eye disease: conjunctival injection, aching at back of eye, diplopia, gradual ptosis, lid retraction/lag, chemosis
- thyroid acropachy: clubbing or swelling of digits
- pretibial myxoedema: oedema of the pretibial portion of the leg
96
what investigations are done for suspected hyperthyroidism
thyroid function tests
presence of autoantibodies
imaging - doppler ultrasound
97
what is the management of hyperthyroidism
beta blockers
block and replace: carbimazole used to block and levothyroxine used to replace
radioiodine
thyroidectomy
98
what is a thyroid storm
it is a serious complication of thyrotoxicosis which involves excessive adrenergic activity secondary to thyrotoxicosis
99
what are the clinical features of a thyroid storm
palpitations
tachycardia
tremor
nausea and vomiting
abdominal pain
reduced level of consciousness
confusion/agitation
seizures
100
what cardiac complications can occur in thyrotoxicosis
atrial fibrillation
heart failure
angina
101
what is graves ophthalmology
symptoms involving the eyes in graves disease: has the potential to cause vision less
102
what is hypothyroidism
it is where there is insufficient thyroid hormone production and secretion by the thyroid gland to meet the bodies demand
103
what is primary hypothyroidism
it is where thyroid hormone underproduction is caused by the thyroid gland itself
104
what is secondary hypothyroidism
it is thyroid hormone underproduction caused by the structures/factors external to the thyroid gland
105
what is the most common cause of hypothyroidism in the western world
Hashimoto's disease
106
what is Hashimotos disease
it is autoimmune thyroiditis - anti-thyroid peroxidase antibodies attack the thyroid gland and impair the glands ability to make thyroid hormones
107
what population is hashimotos most common in
women aged 30-50
108
what are causes of hypothyroidism
Hashimotos
iodine deficiency
congenital hypothyroidism
pituitary tumours
De quervains thyroiditis
post-partum thyroiditis
iatrogenic
109
how does iodine deficiency cause hypothyroidism
iodine is a key component of thyroxine and triiodothyronine. therefore a deficiency leads to the underproduction of thyroid hormones
110
what is congenital hypothyroidism
this is a condition present from birth where the thyroid gland is underdeveloped of absent, resulting in thyroid hormone deficiency. Symptoms include reduced tone, poor growth and developmental delay
111
how do pituitary tumours cause hypothyroidism
if the pituitary gland is compressed or the blood flow is interrupted it can reduce the production of TSH. This can lead to secondary hypothyroidism
112
what is De Quervains thyroiditis
this is a transient inflammation of the thyroid gland causing three stages
1. thyrotoxicosis
2. hypothyroidism
3. euthyroidism
113
what is post partum thyroiditis
this is following the relative immunosuppressive state of pregnancy. The thyroid gland becomes inflamed causing a triphasic reaction
1. hyperthyroidism
2. hypothyroidism
3. euthyroidism
however the hypothyroid period may persist in 20-30% of cases
114
what medications can cause hypothyroidism
amiodarone
lithium
115
what are risk factors for developing hypothyroidism
family history
pregnancy in the last 6 months
autoimmune disease
previous thyroid surgery or treatment with radioactive iodine
radiation treatment to the head, neck and thorax
116
what are symptoms of hypothyroidism
weight gain
constipation
depression
brittle hair and nails
irregular or heavy periods
loss of libido
lethargy
cold intolerance
117
what clinical findings would there be in someone with hypothyroidism
dry skin
bradycardia
cold peripheries
stiff muscles
hair loss
Hertoghes sign
118
what is Hertoghe's sign
it is the loss of the outer third of the eyebrow and is a rare sign of hypothyroidism
119
what investigations would you do in someone suspected of having hypothyroidism
thyroid function tests
antibody testing
imaging
120
what is the management of hypothyroidism
hormone replacement therapy with levothyroxine
- life long
- thyroid function tests every three months to titrate medication
- following stable TSH level, they should be done annually
121
what are complications of hypothyroidism
myxoedema coma
cardiac complications
reproductive complications
122
what is myxoedema coma
this is a rare and potentially fatal complication of hypothyroidism presenting with altered mental state, hypothermia, bradycardia, hypoventilation
123
how do you treat myxoedema coma
rapidly under specialist endocrine input
- thyroid replacement therapy
- glucocorticoid therapy
- supportive measures
124
what cardiac complications can you get with hypothyroidism
heart disease - coronary artery disease, heart failure and atherosclerosis
due to elevated serum total and LDL cholesterol
125
what reproductive complications occur in hypothyroidism
sub-fertility and may increase the risk of miscarriage, still birth, pre eclampsia and post partum haemorrhage
126
what does the thyroid gland receive its arterial supply from
the superior and inferior thyroid arteries which are branches of the external carotid artery and thyrocervical trunk of the subclavian artery respectively
127
what is the venous drainage of the thyroid glands
the superior, middle and inferior thyroid veins.
the superior and middle rain into the internal jugular
the inferior drains into the brachiocephalic vein
128
what does the thyroid gland receive sympathetic innervation from
the sympathetic chain - vasomotor control
129
what is the most common type of thyroid cancer
papillary thyroid cancer
130
what are the characteristics of papillary thyroid cancer
it can commonly present as a neck node
it is associated with radiation exposure
it characteristically spreads via the lymphatics
131
what is the second most common type of thyroid cancer
follicular carcinoma
132
how does follicular carcinoma present
as thyroid swelling
haematogenous route of spread
133
what is medullary thyroid cancer
it is a cancer of the calcitonin cells associated with multiple endocrine neoplasia type 2A. these patients likely have a family history and may have other features of MEN2A such as hypertension secondary to pheochromocytoma
134
what is anaplastic thyroid carcinoma
it is an undifferentiated thyroid cancer. it is characterised by aggressive disease and metastasis at presentation. it has a poor prognosis and survival following diagnosis is usually limited to several months
135
what cancer subtype is associated with hashimotos thyroiditis
lymphoma in the thyroid gland
136
what are risk factors for thyroid cancer
female sex
obesity
benign thyroid disease - hashimotos, adenomas, goitre
radiation exposure
family history
SLE
137
what are symptoms of thyroid cancer
neck lump
horse voice
dysphagia
odynophagia
dyspnoea
stridor
138
what are general symptoms of thyroid cancer
weight loss, anorexia
lethargy, fatigue
diarrhoea
bone pain
pulsatile lesion
139
what might you find on clinical examination in someone with thyroid cancer
may have goitre or neck lump
general cachexia
stridor or hoarseness
140
when assessing thyroid nodules what features increase suspicion of malignancy
age under 20 or over 60
firmness of nodule
rapid growth
fixed to adjacent structures
vocal cord paralysis
regional lymphadenopathy
history of neck irradiation
family history of thyroid cancer
141
what are differential diagnosis of a neck lump
benign thyroid disease
thyroglossal cyst
lymphadenopathy secondary to another cancer or infection
142
what are differential diagnosis for hoarseness
laryngitis
laryngeal cancer
post operative complication
143
what are differential diagnosis for shortness of breath
chest infection
exacerbation of asthma or COPD
pleural effusion
pulmonary embolism
cardiac causes
144
what investigations would you do if you suspected thyroid cancer
ECG
urinalysis - catecholamines would indicate pheochromocytoma
thyroid function tests
thyroid autoantibodies
plasma calcitonin
genetic testing
ultrasound (+/- fine needle aspiration)
MRI/CT
145
what classification is used to grade fine needle aspiration cytology for thyroid cancer
Thy classification
146
what would the management be if there was suspicious cells on fine needle aspiration
benign - reassure, no further action
equivocal - rpt FNA or diagnostic hemithyroidectomy
suspicious - diagnostic hemithyroidectomy
malignant - managed according to tumour type and MDT outcome
147
what classification system does thyroid cancer use for staging
TNM
148
what are the different tumour stages in the TNM grading for thyroid cancer
T0 = no tumour
T1 = a: inside thyroid gland <1cm, b: inside thyroid gland 1-2cm
T2 = inside thyroid gland, 2-4cm
T3 = a: inside thyroid, >4cm, b: extra thyroid spread to strap muscles any size
T4 = a: soft tissue invasion, b = neck vessel invasion or spinal invasion
149
what are the different nodal stages in the TNM staging system for thyroid cancer
N0 = no spread
N1a = spread to pretracheal, paratracheal, prelaryngeal or superior mediastinal nodes
N1b = spread to cervical or retropharyngeal nodes
150
what is the two week wait criteria for patients suspected thyroid cancer
unexplained thyroid lump especially if they have red flag symptoms:
Unexplained hoarseness or voice changes
Associated lymphadenopathy
Sudden onset of an expanding painless thyroid mass
Any other red flags of malignancy
Compressive symptoms of dysphagia, or breathlessness
151
what is the primary treatment for thyroid cancer
surgery - diagnostic hemithyroidectomy and then often completion thyroidectomy +/- neck dissection
152
what other therapies might be used in the treatment of thyroid cancer
radioactive remnant ablation
if more advanced: chemotherapy, immunotherapy
if thyroid removed will need life long thyroxine replacement
153
what are complications relating to thyroid cancer
shortness of breath
hoarseness
upper airway obstruction
dysphagia
odynophagia
metastasis
death
154
what are the complications of the surgical management of thyroid cancer
bleeding: neck haemotoma
infection
recurrent laryngeal nerve damage
lifelong thyroid hormone replacement
calcium and vitamin D replacement
further procedures
155
what is cushings syndrome
it is a syndrome caused by prolonged exposure to elevated glucocorticoids, endogenous or exogenous
156
how is glucocorticoid production regulated by the hypothalamic-pituitary-adrenal axis
1. corticotropin-releasing hormone is secreted by the hypothalamus. this is caused by stress, time of day and serum cortisol levels
2. CRH stimulates increased production of adrenocorticotropic hormone (ACTH) from the pituitary
3. ACTH travels to the adrenals where it binds to receptors in the adrenal cortex
4. this causes the adrenal cortex to release cortisol
5. increased cortisol inhibits CRH and ACTH production
157
what is the function of cortisol
1. synthesis of glucose - gluconeogenesis
2. promotes breakdown of proteins
3. initial surge in cortisol triggers lipolysis, however chronically high levels promotes lipogenesis
4. inhibition of the production of several inflammatory cytokines and downregulation of the immune response
5. reduction in bone formation
6. in high concentrations exhibits a mineralocorticoid effect, increasing sodium and water retention
158
what are exogenous causes of cushings syndrome
exogenous glucocorticoid use - prednisolone, hydrocortisone
159
what are the two types of endogenous causes of cushings syndrome
1. corticotropin dependent
2. corticotropin independent
160
what is corticotropin dependent cushings
due to high levels of corticotropin hormone
80% are due to pituitary adenomas known as cushings disease
20% due to ectopic production of corticotropin such as small cell lung cancers
161
what is the most common cause of corticotropin independent cushings syndrome
adrenal adenomas
adrenal carcinomas
162
what are the symptoms of cushings syndrome
weakness
facial fullness
weight gain
low mood
decreased libido
polydipsia
polyuria
increased infection frequency
163
what are signs of cushings syndrome
truncal obesity
buffalo hump
supraclavicular fat pads
mood face
proximal muscle wasting
hypertension
oedema
headaches, visual field defects, galactorrhoea (cushings disease)
164
what lab investigations would you do for suspected cushings
full blood count
urea and electrolytes
24 hour urinary free cortisol
late night salivatory cortisol
165
how do you diagnose cushings syndrome
low dose dexamethasone suppression test
166
how does the low dose dexamethasone suppression test work
1mg of dexamethasone is administered at 11pm and serum cortisol is measured at 8am the following morning.
A normal result would be morning cortisol suppression. Failure to suppress cortisol may suggest cushings
167
what is the different ways to identify the causes of cushings syndrome
plasma ACTH
high dose dexamethasone test
inferior petrosal sinus sampling
168
how does plasma ACTH help determine cause of cushings
an elevated ACTH level along side a raised serum cortisol suggests a diagnosis of ACTH-dependent cushings syndrome
169
how does high dose dexamethasone testing help identify the underlying cause of cushings
give a very high dose of dexamethasone over 24 hours to differentiate between pituitary and ectopic ACTH production
a reduction of basal urinary free cortisol of greater than 90% suggests pituitary adenoma as ectopic ACTH causes less suppression
170
what is inferior petrosal sinus sampling
it is an invasive procedure in which ACTH levels are samples from veins that drain the pituitary gland
these levels are compared with peripheral levels to determine if a pituitary tumour is responsible for ACTH dependent cushings
171
what imaging can you do for suspected cushings
MRI pituitary
CT chest and abdomen - adrenal/ectopic tumours
172
what is the treatment for exogenous cushings syndrome
reviewing patients steroid treatments and reducing doses where possible
173
what is the management of endogenous cushings syndrome
definitive - resection of causative tumour
medical: ketoconazole, metyrapone and mitotane all inhibit glucocorticoid synthesis and secretion
174
what are complications of cushings syndrome
hypertension
diabetes
obesity
metabolic syndrome
osteoporosis
175
what is acromegaly
it is a condition caused by elevated levels of growth hormone over a prolonged period occuring post epiphyseal fusion
176
what are familial causes of acromegaly
multiple endocrine neoplasia type 1 (MEN-1)
McCune-Albright syndrome
carney complex
177
what is the most common cause of acromegaly
it is usually caused by growth hormone secreting pituitary adenoma.
178
what is the normal growth hormone pathway
growth hormone is produced by the pituitary gland and goes to the liver stimulating production of IGF-1. IGF-1 mediates the effects of growth hormone and has a negative feedback effect to inhibit GH be producing somatostatin
179
what is the role of growth hormone
muscle and bone growth
metabolism
IGF-1 production
180
what are the typical symptoms of acromegaly
headache
visual changes
change in appearance
weight gain
fatigue
snoring
joint pain
voice change
skin tags
amenorrhoea
galactorrhoea
erectile dysfunction
reduced libido
181
what are clinical findings in acromegaly
frontal bossing
macroglossia
prognathism (protruding lower jaw)
interdental separation
enlarged hands and feet
skin thickening
tight rings on fingers
signs of carpal tunnel
bitemporal hemianopia
galactorrhoea
hypertension
signs of heart failure
182
what investigations would you do for someone with suspected acromegaly
visual field examination
lab tests: IGF-1, bloods, calcium, phosphate, triglycerides
pituitary assessment (prolactin, cortisol, TFT, FSH/LH)
oral glucose tolerance test
MRI pituitary
183
what investigation is used to confirm the diagnosis of acromegaly
oral glucose tolerance test - glucose normally suppresses GH. In acromegaly GH will not be suppressed after a OGTT
184
how is acromegaly managed
surgical = removal of pituitary adenoma in transsphenoidal surgery
medical = somatostatin analogues (octreotide, lanreotide)
growth hormone receptor antagonists - pegvisomant
dopamine agonists - bromocriptine/cabergoline
radiotherapy
185
what are side effects of somatostatin analogues
gastrointestinal side effects are common - cramping, bloating, diarrhoea
gallstones
186
what are side effects of growth hormone receptor antagonists
abnormalities in liver function
187
what are side effects of dopamine agonists
nausea
fatigue
dizziness due to postural hypotension
nightmares
188
what needs monitoring long term in acromegaly
IGF-1
changes in signs and symptoms
pituitary hormone tests
MRI pituitary
Blood pressure
ECG and echo
Epworth sleepiness scale
OGTT
colonoscopy
189
what are complications of acromegaly
cardiovascular disease- Hypertension, congestive cardiac failure, stroke, coronary heart disease
diabetes mellitus
obstructive sleep apnoea
colorectal cancer
thyroid cancer
hypopituitarism
carpal tunnel
osteoarthritis
psychosocial impacts
190
what is hyperprolactinoma
it is elevates levels of prolactin in the blood
191
what are normal prolactin levels
<400mU/L in males
<500mU/L in females
192
what is the normal physiology of prolactin secretion
it is secreted in lactotrophs in the anterior pituitary gland. It is regulated by the hypothalamus via dopamine. TRH, serotonin and oestrogens can also stimulate prolactin release.
193
what is the primary function of prolactin
stimulate breast tissue proliferation during pregnancy and breast milk production post partum
194
what are physiological causes of high prolactin
stress
sexual intercourse
pregnancy
lactation
exercise
temporary and dont exceed twice the upper limit of normal
195
what are drug related causes of high prolactin
antipsychotics - risperidone, haloperidol
antidepressants - SSRI, MAO inhibitors, tricyclics
antiemetics - domperidone, metoclopramide
Verapamil
phenytoin
opioids
oestrogens
196
what are pathological causes of high prolactin
prolactinomas - tumours originating from pituitary (can be microprolactinomas or macroprolactinomas)
other masses of the pituitary gland can cause hyperprolactinaemia due to compression of the pituitary stalk
chronic kidney disease
cirrhosis
PCOS
hypothyroidism
sarcoidosis
197
what are typical symptoms of high prolactin
amenorrhoea
oligomenorrhoea
infertility
galactorrhoea
reduced libido
erectile dysfunction
headache
visual disturbance
other pituitary deficiencies or excess
198
what clinical findings will there be in hyperprolactinaemia
visual field defects - bitemporal hemianopia
cranial nerve palsies
gynaecomastia
galactorrhoea
clinical signs with dysfunction of other pituitary hormones
clinical signs of underlying systemic disorders
199
what investigations should be done for suspected hyperprolactinaemia
serum prolactin
pregnancy test
thyroid function tests
urea and electrolytes
pituitary function tests
MRI pituitary
200
what is the management of prolactinomas
dopamine agonists - cabergoline and bromocriptine
surgical management - transsphenoidal surgery
radiotherapy
201
how does dopamine management help treat prolactinomas
dopamine agonists bind to dopamine receptors and are effective inhibitors of prolactin secretion
202
what are complications of hyperprolactinaemia
hypogonadism secondary to it can lead to infertility, ED
osteoporosis
acute pituitary failure in prolactinoma due to haemorrhage or infection
203
what is carcinoid syndrome
it is a rare clinical condition caused by metastatic well differentiated neuroendocrine tumours, primarily originating in the midgut and associated with liver mets
204
what do carcinoid tumours secrete
biogenic amines - particularly serotonin
205
what are symptoms of carcinoid tumours/syndrome
flushing - triggered by stress, food, alcohol and diarrhoea
diarrhoea
wheezing
bronchospasm
systemic complications such as carcinoid heart disease - right sided valvular disease (tricuspid regurgitation, fatigue, cognitive impairment)
206
how is carcinoid syndrome diagnosed
biochemical markers - serum serotonin
imaging for tumour localisation and staging
echocardiogram
207
what is the management of carcinoid syndrome
somatostatin analogs (ocreotide and lanreotide): inhibits secretion of biogenic amines
radioligand therapy
surgical treatment
liver directed therapies
prevention and management of carcinoid crisis
208
what is a carcinoid crisis
potentially life threatening complication charactterised by severe haemodynamic instability flushing, bronchoconstriction and hypotension often triggered by surgery, anesthesia or tumour necrosis
209
what are complications of carcinoid disease/syndrome
carcinoid heart disease - fibrotic plaques
chronic diarrhoea
carcinoid crisis
210
what is Conns syndrome
primary aldosteronism - autonomous production of aldosterone by the adrenal cortex resulting in hypertension and occasionally hypokalaemia
211
what is the pathophysiology of conns syndrome
aldosterone is a steroid hormone produced by the adrenal gland by the cells of the zona glomerulosa in the adrenal cortex regulated by the renin-angiotensin-aldosterone system. Adrenal autonomous production of aldosterone causes fluid retention with increased sodium reabsorption and increased potassium secretion resulting in hypokalaemia
212
what is a typical history of primary aldosteronism
often asymptomatic
hypokalaemia - muscle weakness, fatigue, palpitations, cramps
hypertension - headache, blurred vision
213
what might be seen on clinical examination in conns syndrome
hypertension
hypertensive retinopathy on fundoscopy
displaced and/or forceful apex beat suggesting hypertensive cardiomyopathy
214
what investigations are done for conns syndrome
BP monitoring
ECG
urinalysis
urea and electrolytes
serum aldosterone-renin ratio
genetic testing
adrenal CT
seated saline suppression test
adrenal venous sampling
215
what is the seated saline suppression test
confirmatory test - baseline biochemistry and serum aldosterone and renin levels before administering a saline infusion and re-testing
a normal response is for aldosterone levels to decrease. In primary aldosteronism, aldosterone remains elevated
216
what is adrenal venous sampling
it is the gold standard for determining conns
involves sampling both adrenal veins and peripheral vein to measure aldosterone levels comparing these as a ratio. A higher ratio is more suggestive of unilateral aldosterone production with lower ratio being more suggestive of bilateral aldosterone production
217
what are the risks of adrenal venous sampling
bleeding
venous rupture
venous thrombosis
contrast allergy
damage to surrounding structures
218
what is the management of conns syndrome
medical: spironolactone and eplerenone which blocks aldosterone from binding to its receptor
surgery: surgical resection
219
what are complications of conns syndrome
increased cardiovascular mortality
atrial fibrillation
left ventricular hypertrophy
myocardial infarction
stroke
myocardial fibrosis
220
what is addisons disease
it is primary adrenal insufficiency - defective adrenal cortex which manifests as an impairment in the synthesis and release of glucocorticoids and mineralocorticoids
221
what are other causes of adrenal insufficiency
infections like TB and CMV
vascular issues like adrenal haemorrhage or VTE
short term steroid use
trauma
adrenal tumours
surgery, adrenalectomy
congenital adrenal hyperplasia
other drugs - ketoconazole, rifampicin, phenytoin
222
what is the pathophysiology of addisons disease
there is a lack of adrenal hormones due to the failure in the adrenal cortexs three layers (glomerulosa, fasciculata, reticularis).
in Addisons this decrease in steroid release will cause ACTH release
223
what are risk factors for addisons disease
female sex
other endocrine autoimmune disorders
presence of adrenocortical antibodies
thromboembolic or hypercoagulable states like sepsis
224
what is autoimmune polyglandular syndrome type II
this is defined by the combination of autoimmune adrenal insufficiency with either or both of autoimmune thyroid disease and type 1 autoimmune diabetes mellitus
225
what is a typical history for addisons disease
very vague signs and symptoms
- fatigue
- weakness: muscle, myalgia, arthralgia
- unintentional weight loss
- anorexia
- loss of libido
- loss of sexual function
- nausea and vomiting
- salt cravings
- dizziness
- abdominal pain
226
what are signs of addisons disease
mucosal and cutaneous hyperpigmentation
low BMI
orthostatic hypotension
tachycardia
loss of axillary and pubic hair
227
what is an addisonian crisis
acute severe presentation of addisons
- acute onset of severe weakness, syncope, severe abdominal pain, nausea and vomiting
- abdominal tenderness and guarding
228
what investigations should be done for addisons disease
blood glycose
ECG
VBG
bloods - FBC, U&E, morning cortisol, random cortisol
plasma ACTH
ACTH stimulation test
229
what investigations are done to confirm a diagnosis of Addisons
plasma ACTH: low serum cortisol with elevated plasma ACTH
ACTH stimulation test (synacthen test): give exogenous ACTH before measuring cortisol. If cortisol remains low it indicates the adrenal cortex is unresponsive
230
what other tests can you do to confirm addisons if needed
DHEA and DHEA-S: secreted by adrenal cortex. Low in addisons
Aldosterone and renin levels
231
what investigations can be done to determine aetiology after addisons is confirmed
autoimmune antibodies
Adrenal CT/MRI
232
what is the long term management of addisons
counselling patients - when to come to hospital, sick day plan, how to inject glucocorticoid for emergencies
Medications: oral hydrocortisone and fludrocortisone
at times of stress the glucocorticoid dose has to increase - double dose
233
what is the acute management of addisons disease/addisonian crisis
ACBDE
IV hydrocortisone
1L saline with further fluids over 24 hours
electrolyte and glucose monitoring
5% dextrose can be added in hypoglycaemia
234
what is the treatment of addisons during pregnancy
patients can still take hydrocortisone with extra monitoring
extra glucocorticoids given at start of labour as this also increases stress
235
what are complications of long term treatment of addisons
cushings syndrome secondary to exogenous steroids
hypertension
hypokalaemia
236
what is syndrome of inappropriate antidiuretic hormone secretion
a syndrome characterised by excessive secretion of antidiuretic hormone from the posterior pituitary gland or another source
237
what is the role of ADH
it controls water reabsorption via its affect on the kidney nephrons, causing retention of water (but not retention of the other solutes). By increasing water retention ADH assists in the dilution of the blood, decreasing the concentration of solutes such as sodium
238
what is the normal physiology of ADH
1. ADH is produced by the hypothalamus in response to increased serum osmolality
2. ADH is transported from the hypothalamus to the posterior pituitary gland
3. ADH is released into the circulation via the posterior pituitary
4. ADH binds to receptors in the distal convoluted tubule in the kidney
5. causes Aquaporin 2 to move to the membrane of the tubules and allow water reabsorption
239
what is the deranged physiology in SIADH
lack of effective feedback and continual ADH production independent of serum osmolality, leading to low serum sodium and high urinary sodium
240
what causes SIADH
primary brain injury
malignancy
drugs
infectious causes
hypothyroidism
241
what drugs can cause SIADH
carbamazepine
SSRI
amitriptyline
morphine
242
what is a typical history of SIADH
mild hyponatraemia: N+V, headache, anorexia, lethargy
Mod. hyponatraemia: muscle cramps, weakness, confusion, ataxia
sev. Hyponatraemia: drowsiness, seizures, coma
243
why might chronic hyponatraemic patients not show symptoms
due to cerebral adaption - brain adapts their metabolism to cope with abnormal sodium levels. This can only occur if the change in sodium is gradual
244
what are clinical signs of SIADH
decreased level of consciousness
cognitive impairment
focal or general seizures
brain stem herniation
hypervolaemia: pulmonary oedema, peripheral oedema, raised JVP and ascites
245
what would be seen in a fluid/hydration status assessment in someone with hyponatraemia
patients with SIADH are euvolemic or hypervolaemic
246
what lab investigations would you do for SIADH
urea and electrolytes
plasma osmolality
thyroid function tests
serum cortisol
247
what would be seen on urine tests of SIADH
there would be very concentrated urine
248
what imaging should be done in SIADH
chest x ray or chest CT to rule out causes of SIADH
- small cell lung cancer
- atypical pneumonia
249
what following features must be present for a diagnosis of SIADH to be established
hyponatraemia
low plasma osmolality
inappropriately elevates urine osmolality
urine sodium over 40mmol/L despite normal salt intake
euvolaemia
normal thyroid and adrenal function
250
what is the management of SIADH
fluid restriction - to increase serum sodium
assess hydration status
blood screening panel
treat underlying cause
251
what is diabetes insipidus
it is a disease characterized by the passage of large volumes of dilute urine (>3L in 24 hours)
252
what is neurogenic diabetes insipidus
it occurs as a result of decreased circulating levels of vasopressin (ADH). decreased ADH leads to increased urine production
253
what are causes of neurogenic diabetes
mutations in the vasopressin gene
idiopathic
tumours
trauma
infections (meningitis)
vascular (sheehans syndrome)
sarcoidosis
haemachromotosis
254
what is nephrogenic diabetes insipidus
where the kidneys fail to respond to ADH/ADH is unable to bind to receptors at the kidney level
255
what are causes of nephrogenic diabetes insipidus
mutations in the ADH receptor gene
mutations in the aquaporin 2 gene
metabolic - hypercalcaemia/hyperglycaema/hypokalaemia
drugs - lithium/demeclocycline
chronic renal disease
amyloidosis
post obstructive uropathy
256
what is dipsogenic diabetes insipidus
it is a result of hypothalamic disease or trauma. the hypothalamus is responsible for the thirst mechanism which is damaged in dipsogenic diabetes. As a result the patient is excessively thirsty and consumes large volumes of fluid
257
what is gestational diabetes insipidus
during pregnancy, the placenta produces vasopressinase which breaks down vasopressin
258
what is primary polydipsia
it is characterised by an individual consuming large amounts of fluid therefore producing very dilute urine. Mostly due to behavioural disorder
259
what are symptoms of diabetes insipidus
excessive urination (>3L/24hrs)
excessive thirst
nocturia
dehydration - headache, dizziness, dry mouth
260
what are signs of diabetes insipidus
hypotension
dilute urine
signs of dehydration (dry mucous membranes, prolonged capillary refill time)
261
what investigations would be done for diabetes insipidus
24 hour urine collection (over 3 litres)
blood tests: plasma glucose, U&E, urine specific gravity, simultaneous plasma and urine osmolality
fluid deprivation test
MRI brain
renal tract ultrasound
262
what will be seen in neurogenic diabetes after exogenous desmopressin is given?
urine osmolality will be low after fluid deprivation but will normalise after desmopressin is given
263
what will be seen in nephrogenic diabetes after exogenous desmopressin is given
urine osmolality will remain low regardless of desmopressin
264
what will be seen in primary polydipsia if exogenous desmopressin is given
urine osmolality will be high after fluid deprivation and after desmopressin
265
how do you manage neurogenic diabetes insipidus
replacement of synthetic ADH - desmopressin
can be given orally, intranasally or parenterally
patients require continuous monitoring as overdose leads to hyponatraemia - serum osmolality measured every 1-3 months
266
how is nephrogenic diabetes insipidus managed
if daily urine is less than 4 litres and the patient isnt severely dehydrated definitive therapy isnt always necessary
patients need access to drinking water - drink enough to satisfy thirst.
metabolic abnormalities should be corrected if present and any medications that could be causing issues should be stopped
high dose desmopressin
267
what is hyperparathyroidism
it is an excess of parathyroid hormone being secreted from the parathyroid glands of the neck
268
what is the normal pathophysiology of the parathyroid gland
regulation of serum calcium and phosphate levels via the secretion of PTH
the chief cells of the parathyroid gland are responsible for the synthesis and secretion of PTH as well as the sensing of changes in serum calcium levels via the calcium sensing receptor
269
how does PTH increase serum calcium in the body
Bone: promotes bone resorption and thus release of calcium into the blood
kidneys: stimulates calcium reabsorption in the distal convoluted tubule, inhibits phosphate reabsorption
small intestine: indirectly increases absorption of calcium by stimulating 1a hydroxylase, the enzyme that activates vitamin D in the kidneys
270
what is primary hyperparathyroidism
pathology of the glands - one or more of the parathyroid glands are over secreting PTH despite normal serum calcium which over time leads to hypercalacaemia
271
what is secondary hyperparathyroidism
disorder in calcium phosphate bone metabolism
in response to low serum calcium levels as a result of another condition commonly chronic kidney disease or vitamin D deficiency the parathyroid glands secrete PTH. This may/may not normalise serum calcium levels depending on the underlying condition
272
what is tertiary hyperparathyroidism
may occur following a prolonged period of secondary hyperparathyroidism. In response to chronic PTH secretion the glands may become hyperplastic and begin to secrete PTH autonomously
273
what blood tests results for calcium and phosphate do you get in:
a. primary hyperparathyroidism
b. secondary hyperparathyroidism
c. tertiary hyperparathyroidism
a. increased PTH, increased calcium
b. increased PTH, decreased calcium
c. increased PTH, increased calcium
274
what are risk factors for hyperparathyroidism
primary hyperparathyroidism is sporadic
post menopausal woman
previous radiation exposure to neck
lithium
secondary and tertiary hyperparathyroidism are associated with conditions affecting calcium metabolism such as chronic kidney disease
275
what is the clinical history of hyperparathyroidism
primary - often asymptomatically and picked up on blood tests
fatigue
polyuria and polydipsia
constipation
abdominal pain
vomiting
confusion
depression
bone pain
renal stones
276
whats an important diagnosis to rule out when you have hypercalcaemia
malignancy
277
what lab tests should you do to investigate hypercalcaemia
corrected calcium: in suspected primary hyperparathyroidism
serum PTH
vitamin D
U&E
24 hour urinary calcium excretion test
calcium: creatinine clearance ratio
278
what is the corrected calcium
it is the albumin - adjusted serum calcium
this is used because only 50% of serum calcium is in the free ionised form which is biologically active. 40% is bound to proteins such as albumin while 10% is bound to anions
279
what imaging can be done for suspected hyperparathyroidism
DEXA scan
ultrasound of renal tract
ultrasound of the neck
nuclear imaging
280
what is the management of hyperparathyroidism
acute severe hypercalcaemia = IV fluids, and IV bisphosphonate
medical: bisphosphonates, cinacalcet (calcium sensing receptor antagonist)
in secondary - treat underlying cause
tertiary - surgical intervention
281
what surgical management is done for hyperparathyroidism
parathyroidectomy
refer if:
- symptoms such as thirst, polyuria, constipation
- end organ disease
- corrected calcium level of 2.85 or higher
282
what are complications of parathyroidectomy
hypocalcaemia
hoarseness
cough
bleeding
infection
failure of surgery
283
what are complications of primary hyperparathyroidism
osteoporosis
renal impairment
calculi
pseudogout
pancreatitis
cardiovascular disease
284
what is hypoparathyroidism
endocrine disorder characterised by low serum calcium, raised serum phosphate and low, undetectable or inappropriately normal parathyroid hormone levels in the blood
285
what are acquired causes of hypoparathyroidism
neck surgery
infiltration of the parathyroid glands: haemochromotosis, wilsons, radiation
functional: hypermagnesaemia, hypomagnesaemia
transient: excess alcohol, burns, severe acute illness
286
what are congenital/genetic causes of hypoparathyroidism
DiGeorge syndrome - MC
autoimmune polyendocrine syndrome type 1 (APS-1)
hypoparathyroidism, deafness and renal (HDR) dysplasia genetic syndrome
some newborns might also have transient hypoparathyroidism in the neonatal period
287
what is pseudohypoparathyroidism
this is a rare inherited disorder with target organ resistance to PTH resulting in low serum calcium, high phosphate and high PTH
- patients with the commonest form (type 1a) have a characteristic pattern of skeletal abnormalities known as Albright's hereditary osteodystrophy
288
what are risk factors for hypoparathyroidism
recent anterior neck surgery
chronic alcohol excess
chronic malabsorption
proton pump inhibitors
frequent blood transfusions
hereditary haemochromotosis
wilsons disease
genetic syndromes
metastatic cancer
289
what is a typical history of someone with hypocalcaemia
paraesthesia
muscle pains and cramps
carpopedal spasm
stridor due to laryngospasm
tetany
seizures
290
what might be found on examination in someone with hypocalcaemia
chvosteks sign
trousseaus sign
dental abnormalities
dry skin
291
what is chvosteks sign
sign elicited by tapping on the facial nerve in front of the ear. Twitching of the corner of the mouth indicates a positive result
292
what is trousseaus sign
it is elicited by occluding the blood supple to the arm by inflation of a blood pressure cuff above the arterial pressure for three minutes. Carpopedal spasm is indicated in a positive result
293
what is a differential diagnosis for hypocalcaemia
hypomagnesaemia - serum calcium may be normal
hypoalbuminaemia
chronic kidney disease
vitamin D deficiency
pseudohypoparathyroidism
294
what investigations would you do in suspected hypocalcaemia
ECG: prolonged QT interval
serum PTH
corrected serum calcium
phosphate
vitamin D
U&E
magnesium
295
what imaging is done in hypocalcaemia
renal ultrasound
hand X ray
MRI brian
echo
296
what is acute management of hypocalcaemia
correcting the low calcium is a priority
- in severe (less than 1.9/symptomatic) then give 10-20mL of 10% calcium gluconate in 50-100mL of 5% glucose IV over 10 mins
oral replacement in mild
if there is hypomagnesaemia give IV magnesium sulphate
297
what is the chronic management of hypocalcaemia
medically managed:
active vit D analogue (calcitriol)
patients advised to have calcium rich diet
supplements
PTh replacement therapy in patients who arent adequately controlled by conventional therapy (symptomatic hypocalcemia, hyperphosphatemia, renal insufficiency, hypercalciuria, poor quality of life)
298
what are complications of hypoparathyroidism
cardiovascular complications - ECG abnormalities, QT prolongation
chronic kidney disease
renal calculi
cataracts
neuromuscular complications: seizures, tetany, muscle stiffness
neuropsychiatric complications: anxiety, depression, bipolar
infections
basal ganglia calcifications
299
what is phaeochromocytoma
it is a rare neuroendocrine tumour arising from the adrenal medulla. these tumours secrete excessive catecholamines such as adrenaline and noradrenaline
300
what cells do phaeochromocytomas arise from
chromaffin cells of the adrenal medulla
301
what genetic conditions are phaeochromocytomas associated with
associated in 40% of cases
- MEN2
- Von Hippel Lindau
- neurofibromatosis type 1
- familial paraganglioma phaeochromocytoma
302
where are most of the catecholamine secreting tumours located
in the abdomen: intra-adrenal
paragangliomas 85-90% (sympathetic/parasympathetic paraganglia) 10-15%
303
what are symptoms of phaeochromocytomas
triad: episodic headache, sweating and palpitations
tremor
generalised weakness
impending sense of doom
pallor
nausea
visual disturbance
visual blurring
polyuria
polydipsia
304
what might be found on clinical examination in phaeochromocytoma
hypertension
orthostatic hypotension
evidence of hypertensive retinopathy on fundoscopy
displaced and/or forceful apex beat suggestive of hypertensive cardiomyopathy
cafe-au-lait macules
axillary freckling
305
what are differential diagnosis for phaeochromocytoma
hyperthyroidism
anxiety
migraine disorder
primary hyperaldosteronism
cushings
renovascular disease
renal parenchymal disease
medications/substances: cocaine, methamphetamines, caffeine, decongestants
306
what investigations should you do for suspected phaeochromocytoma
ECG
blood glucose level
urinalysis
plasma free metanephrines
24 hours urine fractionated metanephrines
307
what imaging is done for suspected phaeochromocytoma
CT/MRI abdomen/pelvis
nuclear medicine imaging
echocardiogram
308
what is the management of phaeochromocytoma
medical; alpha blockers (phenoxybenzamine, doxazosin) first and then add in beta blockers once adequate alpha blockade has occurred
surgical: adrenalectomy
309
what medications may precipitate a hypertensive crisis in phaeochromocytoma
beta blockers without alpha blockade
glucagon
histamine
metoclopramide
high dose glucocorticoids
310
what are steps that need to take place before surgical management of phaeochromocytoma
pre-operative alpha blockade and adequate beta blockade
high sodium diet and well hydrated
IV 0.9% sodium chloride for volume expansion in the acute and peri-operative periods
311
what are patients at risk of post operatively in phaeochromocytoma
hypotension and hypoglycaemia
312
what are complications of phaeochromocytomas
due to uncontrolled hypertension
acute coronary syndrome
cardiomyopathy
arrhythmia
myocarditis
pulmonary oedema
acute respiratory distress syndrome renal infarction and/or failure
hypertensive retinopathy
hypertensive encephalopathy
stroke
seizures
pancreatitis
ischaemic enerocolitis
313
what three main mechanisms results in hypercalcaemia of malignancy
1. secretion of parathyroid hormone related protein
2. osteolytic metastasis
3. secretion of calcitriol
314
what is the most common cause of hypercalcaemia in malignancy
secretion of parathyroid hormone related protein
315
what is secretion of PTHrP mostly related to in malignancy
renal cancer
ovarian cancer
endometrial cancer
squamous cell carcinoma
316
what is the role of PTHrP
stimulates osteoclastic resorption and inhibits osteoblast formation of the bone resulting in excessive calcium release
317
what type of cancer does calcitriol mediated hypercalcaemia commonly occur in
lymphomas - overactivation of 1a hydroxylase which produces calcitriol leading to an excessive production
318
which cancers are associated with osteolytic metastasis
breast cancer and multiple myeloma
319
what is the main risk factor for hypercalcaemia of malignancy
type of cancer that the patient has:
multiple myeloma
breast cancer
lung cancer
renal cancer
thyroid cancer
lymphomas
320
what medications can worsen hypercalcaemia
thiazide diuretics
lithium
over the counter calcium/vitamin D supplements
321
what are clinical features of hypercalcaemia
confusion
nausea and vomiting
fatigue
thirst
polyuria
constipation
anorexia
bone pain
abdominal pain
renal colic
322
what clinical signs might you see in hypercalcaemia
signs of dehydration
hyporeflexia
tongue fasciculations
abdominal distension due to constipation
bony tenderness
323
what are the different levels of adjusted serum calcium (mild, moderate, severe hypercalcaemia)
anything over 2.6mmol/L indicated hypercalcaemia
mild = less than 3
moderate = 3-3.5
severe = over 3.5
324
what is the management of hypercalcaemia
supportive measures: laxatives, anti-emetics, analgesia
medications contributing stopped
rehydration (>3L in 24 hrs)
bisphosphonates - IV zoledronic acid
serum calcium monitored and if hypercalcaemia persists then further dose of bisphosphonate/denosumab after 7 days
325
what are complications of hypercalcaemia
transient flu like syndrome due to bisphosphonate treatment
AKI
acute pancreatitis
cardiac arrhythmias
seizures
coma
326
what dose of zoledronic acid is given in hypercalcaemia
4mg
- onset of effect is less than 4 days
- maximum effect 4-7 days
- durations: 4 weeks
327
what is hyperkalaemia
it is a plasma potassium of equal to or over 5.5 mmol/L
328
what is the classification of mild, moderate and severe high potassium
mild: 5.5-5.9
moderate: 6-6.4
severe: over 6.5
329
what are renal causes of hyperkalaemia
acute kidney injury
chronic kidney disease - dialysis, stage 4/5
hyperkalaemic renal tubular acidosis
330
what are iatrogenic causes of hyperkalaemia
ace inhibitors
angiotensin receptor blockers
potassium sparing diuretics
NSAIDs/COX2 inhibitors
digoxin
trimethoprim
beta blockers
nicorandil
heparin
ciclosporin
tacrolimus
renin inhibitors
potassium supplements
IV fluids containing potassium
331
why do trauma/burns cause hyperkalaemia
due to damaged cells releasing significant volumes of potassium
332
why does diabetic ketoacidosis cause hyperkalaemia
potassium shifts from the intracellular to extracellular space due to a lack of insulin
333
why does addisons disease cause hyperkalaemia
aldosterone promotes the excretion of potassium by the kidneys
due to lack of aldosterone in addisons it causes reduced renal excretion of potassium
334
what causes pseudohyperkalaemia
haemolysis (prolonged torniquet time, prolonged sample transport time, incorrect blood bottles)
blood samples being taken from limb receiving IV fluids containing potassium
leukocytosis and thrombocytosis
335
what are clinical signs that might indicate hyperkalaemia
bradycardia due to hyperkalaemia induced AV block
depressed or absent tendon reflexes
336
what investigations should be done in hyperkalaemia
serum potassium - U&E
12 lead ECG
blood gad
capillary blood glucose
FBC
serum cortisol
digoxin level
337
what ECG changes are seen in hyperkalaemia
tall tented T waves
prolonged PR interval
flattened P waves
wide QRS
sine wave pattern
arrhythmias
338
what is the initial management of hyperkalaemia
high potassium and ECG changes is an emergency and requires immediate treatment = 10mls 10% calcium chloride/30mls 10% calcium gluconate
339
after stabilising the heart muscle what is the further treatment of hyperkalaemia
stop any IV fluids containing potassium. Stop any medications/supplements which could be contributing
insulin-glucose infusion
salbutamol
potassium binders (sodium zirconium cyclosilicate)
correct underlying cause
haemodialysis
340
what is the insulin-glucose regime given in hyperkalaemia
10 units given in 25 grams of glucose over 15-30 minutes
341
what is the role of IV calcium in treating hyperkalaemia
it stabilises the myocardium - buys time
342
what is hypokalaemia
it is defined as a serum potassium under 3.5mmol/L.
severe hypokalaemia can be defined as a serum potassium of under 2.5mmol/L
343
what can happen clinically if potassium gets too low
destabilisation of the myocardium and arrhythmia
344
what are features of hypokalaemia on ECG
PR prolongation
widespread ST depression
T wave flattening
prominent U waves
345
what is the management of hypokalaemia
if potassium is above 3, the patient is asx and there is no ECG changed oral potassium replacement can be given (Sando-K)
if potassium is under 3 or ECG changes are present, IV potassium is indicated
recheck levels 4-6 hrs later
346
what other ion deficiency is often present in hypokalaemia
hypomagnesaemia - magnesium deficiency impairs potassium reabsorption in the renal tubules exacerbating potassium losses.
347
what is hyponatraemia
it is defined as a serum sodium level of under 135 mmol/L
348
why can acute hyponatraemia be life threatening
due to cerebral fluid shifts associated with the reduction in serum sodium.
349
as well as level of low sodium what is important to know about low sodium
the rate of change in sodium concentration
350
what symptoms is acute hyponatremia associated with
confusion
decreased GCS
seizures
351
how is hyponatremia managed
hypertonic saline administration
high level monitoring to prevent correcting hyponatraemia too rapidly - intracerebral fluid shift
if low sodium is more mild then ward based care is okay, perform a fluid status examination and consider treating based on cause
352
what is the first line investigation for low sodium
urine/serum osmolality (+ urine sodium)
353
what rate should sodium be corrected at
less than 0.5mmol/L per hour
less than 10mmol in 24 hours
354
what is hypernatremia
a sodium level of over 146mmol/L
severe hypernatremia is over 160
355
what is the most common cause of hypernatremia
dehydration - unreplaced skin or GI losses
356
what is the management of patient with mild/moderate hypernatremia
gentle rehydration with IV hypotonic fluids that dont contain sodium i.e 5% dextrose
357
what is the treatment of severe hypernatremia
medical emergency - ABCDE
patients may need hygh dependency bed for treatment (similar to moderate 5% dextrose)
358
what is hypocalcaemia
it is serum calcium under 2.2mmol/L
severe hypocalcaemia is under 1.9
359
what are symptoms of hypocalcaemia
mild: lethargy, weakness
severe: tetany, laryngospasm, bronchospasm, seizures
QT prolongation - can lead to torsades de pointes
360
what is the management of hypocalcaemia
ECG monitoring
mild - oral calcium replacement (calcium carbonate)
severe/ECG changes - IV calcium replacement (calcium gluconate)
361
what is hypercalcaemia
it is serum calcium over 2.6mmol/L
severe is over 3.5
362
what are symptoms of hypercalcaemia
pain, pancreatitis, constipation, confusion, hallucination, renal complications (bones, stones, abdominal groans, psychic moans)
363
what is seen on an ECG with hypercalcaemia
shortened QT interval which can progress to complete AV nodal block and cardiac arrest
364
what is the management of severe hypercalcaemia
aggressive IV fluid administration with normal saline
depending on severity IV bisphosphonate therapy will also be considered
365
what is the management of mild/moderate hypercalcaemia
IV fluids alone while waiting for further investigations as to the underlying cause
366
how might hypophosphataemia present
CNS features - delirium, seizures, coma
367
how do you manage low phosphate
mild/moderate - oral phosphate replacement
severe (less than 0.3mmol/L) then IV replacement is needed
368
what is hyperphosphatemia associated with
chronic kidney disease
369
what is the management of mild high phosphate
acute hyperphosphatemia without sx will generally self resolve within 6-12 hours if renal function is ok
IV saline can help
370
what can severe high phosphate present with
altered mental status
muscle weakness
muscle pain
sometimes seizures
often associated with severe hypocalcaemia
371
what is the treatment of severe hyperphosphataemia
urgent renal replacement therapy to normalise electrolytes
372
what are symptoms of low magnesium
mild weakness
confusion
tetany
arrhythmias
seizures
373
what is the treatment for low magnesium
mild - oral magnesium (magnesium aspartate 100mmol sachets BD)
severe - IV magnesium replacement
374
what are symptoms of high magnesium
asx if mild
nausea
flushing
vomiting
neurological impairment - drowsiness progressing to coma
respiratory depression
cardiac arrest
375
how do you treat hypermagnesaemia
remove any external magnesium sources
12 lead ECG to ensure QT is normal
IV calcium gluconate
renal replacement therapy if severe
376
what is the most common cause of end stage renal disease in the western world
diabetic nephropathy
377
what is the pathophysiology of diabetic nephropathy
poorly understood
* changes to haemodynamics of the glomerulus leads to increased glomerular capillary pressure
* non enzymatic glycosylation of the basement membrane causes BM thickening
378
what are histological changes in diabetic nephropathy
basement membrane thickening
capillary obliteration
mesangial widening
379
what screening is done for diabetic nephropathy
* all patients with diabetes should be screened annually using urinary albumin:creatinine ratio
* early morning specimen
380
what albumin:creatinine ratio indicates a clinically significant albuminuria
>3.0 mg/mmol
anything over 2.5 in men and 3.5 in women suggest abnormal excretion and should be confirmed with repeat testing
381
what is the management of diabetic nephropathy
tight glycaemic control to slow progression
BP control: aim for under 130/85 if ACR is over 3
ACE inhibitor or ARB
382
what is stage 1 diabetic nephropathy
hyperfiltration: increase in GFR
may be reversible
383
what is stage 2 diabetic nephropathy
silent or latent phase: most patients do not develop microalbuminuria for 10 years
GFR remains elevated
384
what is stage 3 diabetic nephropathy
incipient nephropathy
microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick negative)
385
what is stage 4 diabetic nephropathy
persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive)
hypertension is present in most patients
histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (Kimmelstiel-Wilson nodules)
386
what is stage 4 diabetic nephropathy
end-stage renal disease, GFR typically < 10ml/min
renal replacement therapy needed
387
what is diabetic neuropathy
sensory loss due to uncontrolled diabetes: typically in a glove and stocking distribution
388
where is normally affected first in diabetic neuropathy
lower legs due to the length of the sensory neurons supplying the area
389
what is the management of diabetic neuropathy
managed in the same way as other neuropathic pain
* first line: amitriptyline, duloxetine, gabapentin, pregabalin
* tramadol used as rescue therapy for exacerbations of neuropathic pain
* topical capsaicin may be used for localised neuropathic pain
390
what medication is given for primary prevention of hyperlipidaemia
atorvastatin 20mg daily
391
what medication is given for secondary prevention of hyperlipidaemia (known IHD or cerebrovascular disease or PAD)
atorvastatin 80mg
392
what should be measured when checking someone's lipid levels
need to check both the total cholesterol and HDL
also need a full lipid profile including triglycerides before starting a statin
393
when should familial hyperlipidaemia be investigated for according to NICE
the total cholesterol level greater than 7.5 mmol/L and/or
there is a personal or family history of premature coronary heart disease (an event before 60 years in an index person or first-degree relative [parents, siblings, children])
394
when should atorvastatin be offered to people with DM
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
395
when should atorvastatin be offered in kidney disease
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
396
what is the follow up for people on statins
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
397
how much exercise does NICE recommend per week to reduce the risk of cardiovascular disease
each week aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity or a mix of moderate and vigorous aerobic activity
do muscle-strengthening activities on 2 or more days a week that work all major muscle groups (legs, hips, back, abdomen, chest, shoulders and arms) in line with national guidance for the general population
398
what xanthoma are often seen in hyperlipidaemia
palmar xanthoma
eruptive xanthoma: on the extensor surfaces
tendon xanthoma
tuberous xanthoma
xanthelasma
399
what are xanthelasma
yellowish papules and plaques caused by localised accumulation of lipid deposits commonly seen on the eyelid
400
what is the management of xanthelasma
surgical excision
topical trichloroacetic acid
laser therapy
electrodesiccation
401
what is the mechanism of action of statins
Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis.
402
what are adverse effects of statins
myopathy
liver impairment
may increase the risk of intercerebral haemorrhage in patients who have perviously had a stroke
403
what are contraindications for taking statins
macrolides
pregnancy
404
what is the pathophysiology of thyroid eye disease
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
405
how can you prevent thyroid eye disease
stop smoking
prednisolone may help reduce the risk
406
what are features of thyroid eye disease
lid retraction (most common sign)
exophthalmos (most specific sign)
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close eyelids may lead to sore dry eyes
407
what is the management of thyroid eye disease
smoking cessation
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
408
what are complications of thyroid eye disease
exposure keratosis
optic neuropathy
strabismus and diplopia: fibrosis and enlargement of extraocular muscles can result in restrictive strabismus and misalignment of eyes
409
what monitoring should happen for patients with established thyroid eye disease
for patients with established thyroid eye disease the following signs/symptoms require urgent ophthalmology review:
unexplained deterioration in vision
awareness of change in intensity or quality of colour vision in one or both eyes
history of eye suddenly 'popping out' (globe subluxation)
obvious corneal opacity
cornea still visible when the eyelids are closed
disc swelling
410
what are causes of benign thyroid nodules
Multinodular goitre
Thyroid adenoma
Hashimoto's thyroiditis
Cysts (colloid, simple, or hemorrhagic)
411
what are malignant thyroid nodules
Papillary carcinoma (most common malignant cause)
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
412
what investigations should be done for thyroid nodules
thyroid function in all patients
ultrasound of the neck
413
what are red flags for malignancy in a thyroid nodule
rapid growth
hoarse voice or vocal cord palsy
compressive symptoms: dysphagia, dyspnoea
hard fixed nodule
associated lymphadenopathy
history of neck irradiation
family history of thyroid cancer
414
What does a suppressed TSH suggest in the context of a thyroid nodule?
A hyperfunctioning (“hot”) nodule → lower malignancy risk.
→ Proceed with radionuclide uptake scan.
415
which thyroid nodules require fine needle aspiration in the BTA guidelines
U3–U5 nodules (indeterminate → malignant) on ultrasound
Nodules ≥1 cm with suspicious features
Any nodule with compressive symptoms or high-risk history
416
what are suspicious ultrasound features of thyroid cancer
Irregular margins
Microcalcifications
Marked hypoechogenicity
Taller-than-wide shape
Extrathyroidal extension
417
what is the management of a benign thyroid nodule
reassurance
TSH normalisation
ultrasound surveillance
surgery if large or causing symptoms
418
what findings would make you suspect medullary thyroid cancer
raised calcitonin
family history of MEN2
419
how should a 'hot' nodule on radionucleotide scan be managed
Very low cancer risk → no FNA needed
Treat hyperthyroidism if present
(RAI, surgery, or antithyroid meds depending on symptoms)
420
when is surgery indicated for a thyroid nodule
Suspicious/malignant cytology
Large goitre causing compression
Cosmetic reasons (selected cases)
Patient preference
421
what factors increase the risk of thyroid nodules
Iodine deficiency
Radiation exposure (esp. childhood)
Hashimoto’s thyroiditis
Female sex
Increasing age
