Passmedicine Flashcards
1
Q
Name 5 kinds of thyroid cancer
A
Papillary Follicular Medullary Anaplastic Lymphoma
2
Q
Which thyroid cancer is most common?
A
Papillary
3
Q
In which age group/gender is papillary thyroid cancer most common?
A
Young females
4
Q
Where does papillary thyroid cancer tend to metastasise to?
A
Cervical lymph nodes
5
Q
What can be used as a tumour marker in papillary thyroid cancer?
A
Thyroglobulin
6
Q
What do you see in light microscopy of papillary thyroid cancer cells?
A
Orphan Annie eyes
7
Q
What is the prognosis of papillary thyroid cancer?
A
Good
8
Q
In what age group does follicular cancer tend to occur?
A
> 50 year women
9
Q
Where does follicular thyroid cancer tend to metastasise to?
A
Lungs
Bone
10
Q
What can be used as a tumour marker in follicular thyroid cancer?
A
Thyroglobulin
11
Q
What is the prognosis of follicular thyroid cancer?
A
moderate
12
Q
What are the two ways in which a medullary thyroid cancer can arises?
A
Spontaneous or as part of MEN2
13
Q
From what cells does a medullary thyroid cancer arise?
A
Parafollicular cells (which make calcitonin hence this can be a tumour marker)
14
Q
Which group of individuals tend to get anaplastic thyroid cancer?
A
It is very rare! But mostly occurs in elderly patients
NB has really poor prognosis
15
Q
How might a lymphoma in the thyroid gland present?
A
Dysphagia
Stridor
16
Q
What conditions comprise MEN1?
A
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumours
17
Q
What conditions comprise MEN2A?
A
Parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma
18
Q
What conditions comprise MEN2B?
A
Mucosal neuroma, marfanoid appearance, medullary carcinoma, phaeochromocytoma
19
Q
With which condition is lymphoma of the thyroid gland associated?
A
Hashimoto’s thyroiditis
20
Q
How do you manage papillary/follicular cancer?
A
Total thyroidectomy
Radioiodine to kill residual cells
Yearly thyroglobulin levels to detect recurrent dx
21
Q
What lab results would you see in thyrotoxicosis?
A
TSH: low
Free T4: high
22
Q
What lab results would you see in primary hypothyroidism?
A
TSH: high
Free T4: low
23
Q
What lab results would you see in secondary hypothyroidism?
A
TSH: low
Free T4: low
24
Q
What must you give to individuals with secondary hypothyroidism before they get thyroxine?
A
Steroid replacement therapy
25
What lab results would you see in sick euthyroid syndrome?
TSH: low
Free T4: low
This is common in inpatients
26
What lab results would you see in subclinical hypothyroidism?
TSH: high
| Free T4: normal
27
What lab results would you see in poor compliance with thyroxine?
TSH: high
| Free T4: normal
28
What lab results would you see in steroid therapy?
TSH: low
| Free T4: normal
29
What are the lab results for primary hyperparathyroidism?
PTH elevated
Ca elevated
Phosphate low
Urine Ca:creatinine clearance ratio >0.01
30
What are the clinical features of primary hyperparathyroidism?
Asymptomatic if mild
Abdominal pain - pancreatitis, renal colic
Changes to emotional/cognitive state
31
What is the most common cause of primary hyperparathyroidism?
Solitary adenoma
Less common: multifocal disease or parathyroid carcinoma in <1%
32
What are the lab results in secondary hyperparathyroidism?
PTH: elevated
Ca: normal or low
Phosphate: elevated
Vit D: low
33
What causes secondary hyperparathyroidism?
Parathyroid gland hyperplasia as a result of low Ca, usually in setting of chronic renal failure
34
What are the clinical features of secondary hyperparathyroidism?
May have symptoms
| May eventually develop bone disease + soft tissue calcification
35
What are the lab results in tertiary hyperparathyroidism?
```
PTH elevated
Ca normal or high
Phosphate normal or low
Vit D normal or low
ALP elevated
```
36
What causes tertiary hyperparathyroidism?
Due to ongoing hyperplasia of the parathyroid glands after correction of renal disorder
37
What are the clinical features of tertiary hyperparathyroidism?
Metastatic calcification
Bone pain/fractures
Nephrolithiasis
Pancreatitis
38
How do you distinguish between primary hyperparathyroidism and benign familial hypocalcuric hypercalcaemia?
Diagnosis by genetic testing and urine calcium:creatinine clearance ratio <0.01
39
How is benign familial hypocalcuric hypercalcaemia inherited?
Autosomal dominant
40
What are the indications for surgery in primary hyperparathyroidism?
```
Elevated serum Ca >1mg/dL above normal
Hypercalciuria >400mg/day
Cr clearace <30% normal
Episode of lifethreatening hypercalcaemia
Nephrolithiasis
Age <50
Neuromuscular symptoms
Reduction in BMD of femoral neck, lumbar spine or distal radius <2.5SD below peak bone mass
```
41
How is secondary hyperparathyroidism usually managed?
Medical therapy
Surgery only if bone pain, persistent pruritus, soft tissue calcifications
42
How should you manage tertiary hyperparathyroidism?
Wait 12m after Tx as many cases resolve
May req. surgery (e.g. total parathyroidectomy + reimplantation of part of the gland)
43
What is the pathophysiology of DKA?
Uncontrolled lipolysis which results in excess of FFAs that are converted to ketone bodies
44
What are the most common precipitating factors of DKA?
Infection
Missed insulin doses
MI
45
What are the clinical features of DKA?
Abdominal pain
Polyuria, polydipsia, dehydration
Kussmaul respiration
Acetone smelling breath
46
What is Kussmaul respiration?
Deep hyperventilation in an attempt to blow of CO2 in a metabolic acidosis
47
What is the diagnostic criteria for DKA?
Glucose >11mmol or known DM
pH <7.3
Bicarb <15mmol/l
Ketones >3mmol/l or urine ketones ++ on dipstick
48
How do you manage DKA?
1. Fluid replacement with isotonic saline
2. Insulin: IV fixed rate 0.1units/kg/h
(once glucose <15mmol/l 5% dextrose infusion should be started)
3. Correct of hypokalaemia
CONTINUE LONG ACTING INSULIN, STOP SHORT ACTING INSULIN
49
What fluids should you use in DKA?
0.9% NaCl
| with 0.9% NaCl with K depending on K levels
50
In which patients is slower infusion recommended in DKA and why?
Young adults (18-25) as they are at greater risk of cerebral oedema
51
How much potassium replacement should be given in DKA if the potassium is over 5.5?
None
52
How much potassium replacement should be given in DKA if the potassium is 3.5-5.5?
40mmol/l
53
How much potassium replacement should be given in DKA if the potassium is less than 3.5?
Seek senior review as additional potassium must be given
54
What are complications that can occur due to DKA treatment?
Cerebral oedema, hypokalaemia, hypoglycaemia due to incorrect fluid therapy
55
What are complications of DKA?
```
Gastric stasis
TE
Arrhythmias due to hypokalaemia/hyperkalaemia
Acute respiratory distress syndrome
AKI
```
56
As children are particularly vulnerable to cerebral oedema in DKA what is usually required?
1:1 nursing to monitor neuro-obs, headache, irritability, visual disturbance, focal neurology
57
When will cerebral oedema usually present in DKA?
4-12h after starting treatment
58
What should you do if you suspect cerebral oedema in DKA?
CT head, senior review
59
What is the target HbA1c for a type 2 diabetic on just metformin/diet + lifestyle changes?
48mmol/mol
60
At what HbA1c should you add a second drug to metformin in a type 2 diabetic?
>58mmol/mol
61
What dietary advice should be given to type 2 diabetics?
```
High fibre, low glycaemic index sources of carbs
Low fat diary productions, oily fish
Low sat/trans fats
Avoid energy excess
Target weight loss if overweight 5-10%
```
62
How often should HbA1c be check in a type 2 diabetic?
3-6m until stable
| 6 monthly thereafter
63
What is the HbA1c target for someone on a drug that may cause hypoglycaemia?
53mmol/mol
64
What is the HbA1c target for someone who is already on 1 drug but HbA1c has risen to 58mmol/mol?
53mmol/mol
65
What is the first line drug for the management of T2DM?
Metformin
66
If HbA1c rises to 58mmol/mol on metformin what can you add?
SU
Gliptin
Pioglitazone
SGLT-2 inhibitor
67
If Hba1c rises to or remains above 58mmol/mol on double therapy, what should be offered?
→ metformin + gliptin + sulfonylurea
→ metformin + pioglitazone + sulfonylurea
→ metformin + sulfonylurea + SGLT-2 inhibitor
→ metformin + pioglitazone + SGLT-2 inhibitor
→ OR insulin therapy should be considered
68
If triple therapy if not effective or tolerated or CI then what drug therapy should you consider T2DM?
Metformin, SU, GLP1 mimetic (e.g. exenatide) if BMI 35+ if psychological/medical problems assoc. w. obesity or <35 whom insulin therapy would have significant occupational implications or if wt loss would benefit significant co-morbs (+ they reduce Hb1Ac by 11mmol/mol + lose 3% body wt in 6m)
69
If someone cannot tolerate metformin or it is CI what drugs can you offer them for treatment of T2DM?
SU, gliptin, pioglitazone
70
If someone cannot have metformin and is not able to keep HbA1c <58mmol/mol on single drug therapy what can you offer them?
Gliptin + pioglitazone
Gliptin + SU
Pioglitazone + SU
71
If HbA1c rises to or remains above 58mmol/mol on double therapy (without metformin) what should you consider?
Insulin therapy
72
What drugs should be continued when a T2DM starts taking insulin?
Metformin can be continued, review need for others
73
What insulin should T2DM be started on?
Human NPH insulin (isophane), intermediate acting
| Taken at bed time or twice daily according to need
74
What is the first line treatment of HTN in diabetics?
ACEi
75
What is the BP target for diabetics?
< 140/80 if no end organ damage
| < 130/80 if end organ damage
76
When should diabetics be given statins?
If 10 year CV risk >10%
77
What is the first line statin for primary prevention in diabetics?
Atorvastatin 20mg
78
What is the first line statin for secondary prevention (e.g. IHD, CV dx, PAD) in diabetics?
Atorvastatin 80mg
79
What can cause an Addisonian crisis?
Sepsis/surgery causing an acute exacerbation of insufficiency (e.g. Addisons, hypopituitism)
Adrenal haemorrhage
Steroid withdrawal
80
What is Water-house friderichsen syndrome?
Adrenal haemorrhage
81
How do you manage an Addisonian crisis?
Hydrocortisone 100mg IM/IV
1L normal saline infused over 30-60m w. dextrose if hypoglycaemic
Continue hydrocortisone 6hrly until patient stable
Oral replacement may begin after 24h and be reduced to maintenance over 3-4 days
82
What are the clinical features of an Addisonian crisis?
Low sodium, high potassium, low glucose
| Hx of steroid use may be there
83
What are clinical features of hypercalcaemia?
Fatigue, anorexia, thirst, constipation, general aches and pains
84
How do you diagnose T2DM?
Symptoms + fasting glucose of 7mmol/l+ or random glucose/OGTT 11.1mmol/l+
OR asymptomatic + high BG demonstrated on two different occasions
OR HbA1c 48mmol/mol+ (on 2 occasions or symptomatic + 1 reading)
85
In which conditions may HbA1c not be used for diagnosis?
```
Haemoglobinopathies
Haemolytic anaemia
Untreated iron deficiency anaemia
Suspected gestational diabetes
Children
HIV
CKD
People taking meds that may cause hyperglycaemia (e.g. steroids)
```
86
Define impaired fasting glucose
Fasting glucose 6.1-7mmol/l
87
Define impaired glucoses tolerance
Fasting glucose less than 7mmol/l and OGTT 2h value of 7.8mmol/l-11.1mmol/l
88
If someone has IFG what should they be offered?
Oral glucose tolerance test to rule out diabetes
89
What is a typical history of primary hyperparathyroidism?
Elderly female with an unquenchable thirst
90
What are the features of primary hyperparathyroidism?
Bones, stones, abdominal groans and psychic moans
```
Polydipsia, polyuria
Peptic ulceration, constipation, pancreatitis
Bone pain/fractures
Renal stones
Depression
HTN
```
91
What is primary hyperparathyroidism associated with?
HTN
| MEN 1 and 2
92
What investigations should you do in primary hyperparathyroidism?
Ca, phosphate, PTH
| Technectium MIBI substraction scan
93
What is the characteristic X-Ray finding in hyperparathyroidism?
Pepperpot skull
94
What is the definitive management of primary hyperparathyroidism?
Total parathyroidectomy
95
When can patients be offered conservative management of primary hyperparathyroidism?
If Ca <0.25mmol/L above upper limit and patient >50 AND no evidence of end organ damage
96
What drugs may be used for primary hyperparathyroidism in patients unsuitable for surgery?
Calcimemtics, e.g. cinacalcet
97
What findings may you see on hand-Xray of someone with primary hyperparathyroidism?
Generalised osteopenia
Erosion of terminal phalangeal tufts
Subperiosteal resorption of bone
98
How often should HbA1c be monitored in T1DM?
3-6mthly
99
What is the target HbA1c for adults with T1DM?
48mmol/mol (but take into account likelihood of complications, hx of hypos, occupation, comorbs etc.)
100
How often should T1DM monitor their BG?
At least 4 times a day - before each meal and before bed
101
When might more frequent monitoring of bloods be required in T1DM?
Frequency of hypos increases, during periods of illness, before, during and after sport, when planning pregnancy, during pregnancy, during breast feeding
102
What are the BG targets for type 1 diabetics?
5-7mmol/l on waking
| 4-7mmol/l before meals and at other times of the day
103
What is the treatment regimen of choice in T1DM?
Basal bolus regimens + twice daily detemir/once daily glargine/determir
Rapid acting insulin before meals
Consider adding metformin if BMI is 25+
104
What is Addison's disease?
Autoimmune destruction of the adrenal glands
105
What is the commonest cause of primary hypoadrenalism in the UK?
Addison's disease
106
Addison's disease results in a reduced level of which two hormones?
Cortisol
| Aldosterone
107
What are features of Addison's disease?
Lethargy, weakness, nausea, vomiting, wt loss, salt craving
Hyperpigmentation (esp. palmar creases), vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia
Hyponatraemia, hyperkalaemia
108
What are primary causes of hypoadrenalism?
```
TB
Mets
Meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
Antiphospholipid syndrome
```
Exogenous glucocorticoid therapy
109
What are secondary causes of hypoadrenalism?
Pituitary disorders, e.g. tumours, irradiation, infiltration
110
What electrolyte abnormalities are seen in Addison's disease?
Hyponatraemia
| Hyperkalaemia
111
What is the first line treatment of cerebral mets?
High dose dexamethasone to reduce cerebral oedema
112
For each of the following commonly used steroids comment on their glucocorticoid and mineralocorticoid activity
a. Fludrocortisone
d. Hydrocortisone
c. Prednisolone
d. Dexamethasone, Betamethasone
a. V. high mineralocorticoid
b. Bit of glucocorticoid, mostly mineralo
c. Mostly glucocorticoid
d. V. high glucocorticoid
113
What are SEs of glucocorticoids?
Endocrine - impaired glucose regulation, increased appetite/wt gain, hirsutism, hyperlipidaemia
Cushing's syndrome - moon face, buffalo hump, striae
MSK - osteoporosis, proximal myopathy, AVN of head of femur
Immunosupression - inc. risk of infections/reactivation of TB
Psychiatric - insomnia, mania, depression, psychosis
GI - peptic ulceration, acute pancreatitis
Ophthlamic - glaucoma, cataracts
Supression of growth in children
Intracranial HTN
Neutrophilia
114
What are SEs of mineralocorticoids?
Fluid retention
| HTN
115
What are some really important things to remember about people who are taking steroids long term?
Double doses during intercurrent illness
Gradually withdraw corticosteroids if pts have received >40mg pred daily for >1 week, received more than 3 weeks of treatment or recently received repeated courses
116
What are common adverse events with SUs?
Hypoglycaemic episodes
| Wt gain
117
What are rarer AEs seen with SUs?
SIADH
Bone marrow suppression
Cholestatic liver damage
Peripheral neuropathy
118
What is the mechanism of action of glicazide?
Releases vesicles of stored within the pancreas containing insulin + c-peptide
119
What can glicazide OD lead to?
Hyperinsulinaemia and raised c-peptide --> hypoglycaemia
120
What acid-base abnormality may be seen in cushing's syndrome?
Hypokalaemic metabolic alkalosis
121
Is impaired glucose tolerance seen in Cushing's?
Yes
122
Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically seen with very low levels of what electrolyte?
K
123
What test is used to differentiate between true Cushing's and pseudocushing's?
Insulin stress test
124
What two tests are most commonly used to confirm a diagnosis of Cushing's?
Overnight dexamethasone supression test (most sensitive)
| 24hr urinary free cortisol
125
What is the first line localisation test for cushing's?
9am and midnight plasma ACTH (and cortisol) levels
126
If on doing a 9am and midnight plasma ACTH (and cortisol) level you find ACTH is suppressed, what does this mean?
The cause is non-ACTH dependent and is likely something like an adrenal adenoma
127
What other tests may be used to localise the cause of cushing's syndrome?
Low and high dose dexamethasone suppression tests
128
If cortisol is not suppressed by a low dose dexamethasone test what does this mean?
Cushing's syndrome not due to primary causes, e.g. likely secondary to corticosteroid therapy
129
If cortisol is not suppressed by low dose but is suppressed by high dose dexamethasone then what does this mean?
Cushing's disease
130
If cortisol is not suppressed by low or high dose dexamethasone what does this mean?
Ectopic ACTH likely
131
How might you interpret the results of CRH stimulation to localise the cause of cushing's syndrome?
If pituitary source then cortisol rises
If ectopic/adrenal then no change in cortisol
132
What investigation may be required to distinguish between pituitary and ectopic ACTH secretion?
Petrosal sinus sampling of ACTH
133
How is the dexamethasone suppression test carried out?
Give dexamethasone at night (10pm) and measure cortisol level at 9am
134
What is the low dose dexamethasone test used for?
Confirm if they have a normal adrenal axis or to confirm they have cushing's syndrome
135
What is the high dose dexamethasone test used for?
To see what the cause of cushing's syndrome is
136
What does the dexamethasone do?
Acts on hypothalamus to suppress CRH
Acts on pituitary to suppress ACTH
--> reduced cortisol
(Normal response)
If you have high cortisol already - low dose dex (1mg) not going to do anything to pituitary/hypothalamus
Giving high dose dex (8mg) - big dose is enough to cause suppression of the pituitary even if there is an adenoma there
In ectopic ACTH production or adrenal adenoma, high dose dex does not cause suppression
137
What is acromegaly?
Condition where there is xs growth hormone secondary to a pituitary adenoma in 95% of cases
138
What are a minority of acromegaly cases caused by?
Ectopic GHRH or GH production by tumours, e.g. pancreatic
139
What are features of acromegaly?
Coarse facial appearance, spade like hands, increase in shoe size
Large tongue, prognathism, interdental spaces
Excessive sweating + oily skin (due to sweat gland hypertrophy)
Features of pituitary tumour (hypopituitism, headaches, bitemporal haemianopia)
Raised prolactin in 1/3rd cases --> galactorrhoea
140
What complications are associated with acromegaly?
HTN
DM
Cardiomyopathy
Colorectal cancer
141
What two conditions account for 90% of cases of hypercalcaemia?
Primary hyperparathyroidism
| Malignancy (e.g. due to bone mets, myeloma, PTHrP from squamous cell lung cancer)
142
What are other causes (apart from the big 2) of hypercalcaemia?
```
Sarcoidosis
Vit D intoxication
Acromegaly
Thyrotoxicosis
Milk-alkali syndrome
Drugs - thiazides, calcium containing antacids
Dehydration
Addison's
Paget's disease of the bone
```
143
What is the most common cause of thyrotoxicosis?
Grave's disase
144
In which group of people is Grave's disease typically seen?
Women aged 30-50 years old
145
What are features of Grave's disease?
Thyrotoxicosis
Eye signs (30% pts) - exophthalmos, ophthalmoplegia
Pretibial myxoedema
Thyroid acropachy (triad of digital clubbing, soft tissue swelling of hands + feet, periosteal new bone formation)
146
What autoantibodies are most commonly found in Grave's disease?
TSH receptor stimulating antibodies (90%)
| Anti-thyroid peroxidase antibodies (75%)
147
What mnemonic can be used to grade the severity of Grave's eye disease?
```
NOSEPCS -
No signs/symptoms
Only signs, e.g. upper lid retraction
Signs and symptoms (incl. soft tissue involvement)
Proptosis
Extra-ocular muscle involvement
Corneal involvement
Sight loss due to optic nerve involvement
```
148
What x-ray findings (of the hands) are associated with hyperparathyroidism?
Generalised osteopenia
Erosion of terminal phalyngeal tufts
Sub-periosteal resportion of bones
149
What are features of hypothyroidism?
```
Wt gain
Lethargy
Cold intolerance
Dry, cold, yellowish skin
Non-pitting oedema
Dry, coarse, scalp hair, loss of lateral aspect of eyes
Constipation
Menorrhagia
Decreased deep tendon reflexes
CTS
Hoarse voice
```
150
What are features of a myxoedemic coma?
Hypothermia
Hypotension
Bradycardia
Thin, brittle hair, peritorbital oedema, reduced reflexes
151
What is a myxoedemic coma?
Severe hypothyroidism leading to decreased mental status, hypothermia, and other symptoms related to slowing of function in multiple organ
152
How many types of MEN are there?
MEN I
MEN 2a
MEN 2b
153
What is MEN?
Inherited AD disorder
154
What are the neoplasias are found in MEN I?
3Ps -
Parathyroid - hyperparathyroidism due to parathyroid hyperplasia
Pituitary
Pancreas, e.g. insulinoma, gastrinoma
Also - adrenal + thyroid
155
What neoplasias are found in MEN IIa?
2Ps -
Parathyroid
Phaeochromocytoma
Medullary thyroid cancer
156
What neoplasias are found in MEN IIb?
```
1P -
Phaeochromocytoma
Medullary thyroid cancer
Marfanoid body habitus
Neuromas
```
157
MEN Ia is due to a mutation in which gene?
MEN1 gene
158
What is the most common presentation of MEN1?
Hypercalcaemia
159
MEN IIa is due to a mutation in which gene?
RET oncogene
160
MEN IIb is due to a mutation in which gene?
RET oncogene
161
How does subacute (De Quervain's) thyroiditis tend to present?
Hyperthyroidism
162
What does subacute (De Quervain's) thyroiditis tend to follow?
A viral infection
163
What are the classical 4 phases of subacute (De Quervain's) thyroiditis?
Phase 1 - 3-6w - hyperthyroidism, painful goitre, raised ESR
Phase 2 - 1-3w - euthryoid
Phase 3 - weeks-months - hypothyroidism
Phase 4 - thyroid structure + function returns to normal
164
What investigations can be done for suspected subacute (De Quervain's) thyroiditis and what will they show?
Thyroid scintigraphy (globally reduced uptake of iodine-131)
165
How is subacute (De Quervain's) thyroiditis managed?
Usually self-limiting + does not req. treatment
Thyroid pain may respond to aspirin/ other NSAIDs
In more severe cases steroids can be used (esp if hypothyroidism develops)
166
What is the mechanism of action of the SGLT-2 inhibitors?
Reversibly inhibit sodium-glucose co-transporter 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
167
What are e.g.s of SGLT-2 inhibitors?
Canagliflozin, dapagliflozin and empagliflozin
168
What are AEs of SGLT-2 inhibitors?
Urinary + genital infections (secondary to glycosuria)
Normoglycaemia ketoacidosis
Increased risk of lower limb amputation
169
What is a benefit of taking SGLT-2 inhibitors?
Often cause wt loss
170
What is the first line test for acromegaly?
Serum IGF-1 levels with serial GH measurements
OGTT recommended to confirm diagnosis if IGF-1 is raised
171
What parameter can be used to measure disease progression in acromegaly?
Serum IGF-1
172
What does the OGTT show in normal patient vs acromegalic patients?
Normal - GH supressed to <2mu/l with hyperglycaemia
In acromegaly - no suppression of GH
May also demonstrate impaired glucose tolerance which is associated with acromegaly
173
What investigation may you consider in confirmed acromegaly?
MRI pituitary to see pituitary tumour
174
What is a phaeochromocytoma?
Catecholamine secreting tumour
175
What conditions are phaeochromocytomas commonly associated with?
MEN II, neurofibromatosis, vHL syndrome
176
What is the rule of 10%s for phaeochromocytomas?
10% bilateral
10% malignant
10% extra-adrenal (most common site = organ of Zuckerkandl, adjacent to bifurcation of aorta)
177
What are features of phaeochromocytomas?
Episodic HTN, headaches, palpitations, sweating, anxiety
178
What test is used to diagnose phaeochromocytoma?
24hr urinary collection of METAnephrines
CT chest, abdo, pelvis would be done if this came back raised
179
What is the definitive management of phaeochromocytoma?
Surgery
180
What medications are given to stabilise patients with phaeochromocytomas?
Alpha blocker (e.g. phenoxybenzmine) given before a beta blocker e.g. propanolol
181
What HbA1c is indicative of prediabetes?
42-47mmol/mol
182
What is the management of prediabetes?
Encourage to increase physical activity, lose weight and improve diet
Consider metformin at 500mg and arrange repeat HbA1cs at regular intervals
183
What kind of neuropathy is diabetic neuropathy most commonly?
Sensory loss but not motor loss in peripheral neuropathy
Painful diabetic neuropathy a common issue
184
What is first line treatment of diabetic neuropathy (neuropathic pain)?
Amitriptyline, duloxetine, gabapentin or pregabalin
Tramadol as rescue therapy for exacerbations
Topical capsaicin for localised neuropathic pain
Pain management clinics for resistant problems
185
What conditions can result from GI autonomic diabetic neuropathy?
Gastroparesis
Chronic diarrhoea
GORD
186
What are features of gastroparesis?
Erratic blood glucose control
Bloating
Vomiting
187
What are management options for gastroparesis?
Metoclopramide, domperidone or erythromycin
188
What causes GORD in GI autonomic neuropathy?
Decreased LES pressure
189
What karotype is associated with Klinefelter's syndrome?
47 XXY
190
What are features of Klinefelter's syndrome?
Tall
Lack of secondary sexual characteristics
Small firm testes
Infertile
Gynaecomastia (inc. incidence of breast ca)
Elevated gonadotrophin levels but low testosterone
191
How is Klinefelter's syndrome diagnosed?
Karotyping
192
Who does hyperosmolar hyperglcyaemia state tend to occur in?
Elderly with T2DM
193
What is hyperosmolar hyperglcyaemia state?
Hyperglycaemia resulting in osmotic diuresis, severe dehydration + electrolyte deficiencies
194
What things may complicate hyperosmolar hyperglcyaemia state?
MI
Stroke
Peripheral arterial thrombosis
195
Over how long does hyperosmolar hyperglcyaemia state tend to come on?
Over many days, so dehydration + electrolyte disturbances often more pronounced than in DKA
196
What is the pathophysiology of hyperosmolar hyperglcyaemia state?
Hyperglycaemia --> osmotic diuresis + loss of Na and K --> hyperviscosity of blood
Despite this, pt may not look as dehydrated as they are as hypertonicity --> preservation of intravascular volume
197
What are clinical features of hyperosmolar hyperglcyaemia state?
Fatigue, lethargy, nausea, vomiting
Altered level of consciousness, headaches, papilloedema, weakness
Hyperviscosity
Dehydration, hypotension, tachcardia
198
What 3 criteria are useful in helping to distinguish HHS from DKA?
```
Hypovolaemia
Marked hyperglycaemia (>30mmol/L) without significant ketonaemia/acidosis
Significantly raised serum osmolarity (>320mosmol/kg)
```
199
What are the aims of management of HHS?
Normalise osmolality
Replace fluid + electrolyte losses
Normalise BG
200
What is the first line fluid used in HHS?
IV 0.9% sodium chloride solution
if serum osmolality not decreasing with this switch to 0.45% NaCl
201
Should insulin be used in the treatment of HHS?
NOOOOOOO - may cause CV collapse as water moves out of intravascular space --> decline in IV volume
Only start insulin if significant ketonaemia demonstrated as this may indicate mixed DKA/HHS picture
202
What are the two main factors responsible for diabetic foot disease?
Neuropathy - reduced protective sensation, Charcot's arthropathy, dry skin
Peripheral arterial disease (DM is a RF for macro and microvascular ischaemia)
203
How does diabetic foot disease present?
Neuropathy - loss of sensation
Ischaemia - absent foot pulse, reduced ABPI, intermittent claudication
Complications - calluses, ulceration, Charcot's arthropathy, cellulitis, OM, gangrene
204
How often should diabetic patients have their feet screened?
Yearly
205
How is screening for neuropathy in the feet done?
10g monofilament on various parts of sole of foot
206
What diabetics are at low risk of diabetic foot issues?
No risk factors except callus alone
207
What diabetics are at moderate risk of diabetic foot issues?
Deformity or neuropathy or non-critical limb ischaemia
208
What diabetics are at high risk of diabetic foot issues?
Prev ulceration/gangrene
On RRT
Neuropathy + non-critical limb ischaemia together or neuropathy + callus/deformity
Non-critical limb ischaemia + callus/deformity
209
All patients at moderate/high risk of diabetic foot problems should be followed up by who?
Local diabetic foot centre
210
What are treatment options for Grave's disease?
```
Antithyroid drugs
Block + replace regimens
Radioiodine treatment
Surgery
Propanolol for symptom control
```
211
What is the most commonly used anti-thyroid drug?
Carbimazole (started at 40mg and titrated upwards)
212
How long is a course of carbimazole usually continued for?
12-18 months
213
What does block + replace therapy for Grave's disease consist of?
Carbimazole started at 40mg, thyroxine added when patient is euthyroid
214
What is a major complication of carbimazole therapy?
Agranulocytosis
215
What are CIs to the use of radioiodine?
Pregnancy (avoid for 4-6 m after treatment)
Age <16
Thyroid eye disease (relative CI as may worsen condition)
216
Majority of patients will require what after radioiodine therapy for the treatment of Grave's disease?
Thyroxine
217
Where is PTH secreted from?
Chief cells in the parathyroid glands
218
What is the role of PTH?
Calcium homeostasis
219
How does calcium enter the body?
Intestines
220
How does calcium leave the body?
In urine + faeces
221
What is the main reservoir of calcium in the body?
In bone
222
What are the three forms that calcium exists as in the bone?
Free calcium
Bound to albumin
Complexed with anions
223
What form of calcium is physiologically active?
Only free calcium
224
What is PTH generated in response to?
Low calcium levels in the blood
225
Which two organ/tissues does the PTH mainly act on?
Bone
| Kidney
226
What is the effect of PTH on bone?
Increases osteoclastic activity (increased boen resportion --> Ca and phosp released into bloodstream)
227
What is the effect of PTH on the kidney?
Increases hydroxylation + activation of vitamin D in PCTs
| Increases calcium reabsorption from DCT + increase phosphate excretion
228
What kind of hormone is activated vitamin D?
Steroid hormone
229
What is the action of vitamin D?
Increases dietary calcium absorption from intestine by increasing expression of calcium-binding hormone
230
How are the levels of PTH regulated in the body?
Negative feedback loop
231
What is primary hyperparathyroidism?
A condition where the parathyroids are overactive (usually due to dysplasia/adenoma/malignancy)
232
What are the symptoms of primary hyperparathyroidism?
Hypercalcaemia (renal calculi, constipation, polyuria, ab pain, low mood)
233
What a common treatment of primary hyperparathyroidism?
Surgical removal of the glands
234
What is PTHrP?
A polypeptide which is similar in structure to PTH that is secreted from cancer cells causing hypercalcaemia
235
What is the only difference in the functional capabilities of PTHrP when compared to PTH?
It is unable to activate vitamin D
236
What cancer is PTHrP mostly associated with?
Squamous cell bronchial carcinoma
237
What is an adrenal adenoma causing primary aldosteronism known as?
Conn's syndrome
238
What are causes of primary hyperaldosteronism?
Conn's syndrome
Bilateral idiopathic adrenal hyperplasia
Adrenal carcinoma (rare)
239
What are features of primary hyperaldosteronism?
HTN
Hypokalaemia (e.g. muscle weakness)
Hypernatraemia
Alkalosis
240
What is the first line investigation for suspected primary hyperaldosteronism?
Plasma aldosterone/renin ratio
(Which should show high aldosterone levels alongside low renin levels - negative feedback due to Na retention from aldosterone)
241
After a plasma aldosterone/renin ratio what test should be done in suspected primary hyperaldosteronism?
High resolution CT + adrenal vein sampling to differentiate between unilateral + bilateral sources of aldosterone excess
242
What is the management of an adrenal adenoma?
Surgery
243
What is the management of bilateral adrenocortical hyperplasia?
Aldosterone antagonist, e.g. spirnolactone
244
What is the pathophysiology of thyroid eye disease?
Autoimmune response against an autoantigen (possibly the TSH receptor --> retro-orbital inflammation --> glycosaminoglycan + collagen deposition in muscles)
245
What is the most important modifiable risk factor for the development of thyroid eye disease?
Smoking
246
What may help reduce the risk that someone who has thyroid eye disease that undergoes radioiodine treatment will develop worsening eye disease?
Prednisolone
247
What are features of thyroid eye disease?
```
Exophthalmos
Conjunctival oedema
Optic disc swelling
Ophthalmoplegia
Inability to close eyelids --> sore, dry eyes (at risk of keratopathy)
```
248
What is involved in the management of thyroid eye disease?
Topical lubricants to prevent corneal inflammation
Steroids
Radiotherapy
surgery
249
For those with established thyroid eye disease, what signs/symptoms indicate need for urgent review by an ophthalmologist?
Unexplained deterioration in vision
Awareness of change in intensity/quality of colour vision in 1/both eyes
Hx of eye suddenly popping out (globe subluxation)
Obvious corneal opacity
Cornea still visible when eyelids close
Disc swelling
250
Why do patients with addison's disease sometimes get hyperpigmentation in skin creases, buccal mucosa + scars?
ACTH has the same precursor molecule as melanocyte stimulating hormone so overproduction of ACTH has the same SEs as raising MSH levels
251
What is the definitive investigation in Addison's disease?
ACTH stimulation test (short Synacthen test)
252
How is the short Synacthen test carried out?
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
253
What autoantibodies may be found in addison's disease?
Anti-21 hydroxylase
254
If a short Synacthen test is not available (e.g. in primary care) that investigation should you consider to help diagnose Addison's?
9am serum cortisol
>500nmol/l makes Addison's very unlikely
<100nmol/l is definitely abnormal
100-500nmol.l should prompt a ACTH stimulation test to be performed
255
What electrolyte abnormalities are seen in Addison's disease?
Hyperkalaemia
Hyponatraemia
Hypoglycaemia
Metabolic acidosis
256
Addison's disease leads to an insufficiency of what hormones?
All of those produced by the adrenal cortex (mineralocorticoids (e.g. aldosterone), glucocorticoids (e.g. cortisol), androgens)
257
What is the function of the mineralocorticoids?
Retention of sodium and water --> increased BP
258
What is the function corticosteroids?
```
Immunosupression, anti-inflammatory
Weight gain
Insulin resistance
Skin thinning
Increased osteoclastic activity in bones
Cortisol increases BP
```
259
What is the most common cause of Addison's disease?
Autoantibodies directed at adrenal cortical cells + 21-hydroxylase --> damage to adrenals --> reduced levels of adrenal hormones
260
To have a HGV license, what criteria must diabetics on insulin/other hypoglycaemics meet?
No severe hypo in last 12m
Pt has full hypoglycaemic awareness
Adequate control of condition w. regular BG monitoring
Driver demonstrates understanding of risks of hypos
No debarring complications of DM
261
What form do T1 diabetics have to fill out to get a group 2 (HGV) license?
VDIAB1I form
262
What are the rules for diabetics on insulin having a group 1 license?
Hypoglycaemic awareness
Not >1 episode of hypo req. assistance from another in the last 12m
No visual impairment
263
What is congenital adrenal hyperplasia?
Group of AR conditions affecting adrenal steroid biosynthesis
264
Abnormally high levels of what hormone are found in congenital adrenal hyperplasia? What is the consequence of this?
ACTH due to low cortisol levels
ACTH stimulates production of adrenal androgens that may virulize a female infant
265
What are the causes of congenital adrenal hyperplasia?
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency
17-hydroxylase deficiency
(good video on PM notes about this!)
266
What is the 21-hydroxylase enzyme responsible for?
Biosynthesis of aldosterone + cortisol
267
What is Hashimoto's thyroiditis?
Autoimmune disorder of the thyroid gland, typically associated with hypothyroidism
NB may be transient thyrotoxicosis in acute phase
268
What are the features of Hashimoto's thyroiditis?
Hypothyroidism
Firm, non-tender goitre
Anti-thyroid peroxidase and anti-thyroglobulin (Tg) antibodies
269
What things are associated with Hashimoto's thyroiditis?
Autoimmune conditions - coeliac, T1DM, vitiligo
| MALT lymphoma
270
Gastroparesis occurs in diabetics due to neuropathy of what nerve?
Vagus
271
What is the mechanism of action of thiazolidinediones?
Agonists to the PPAR-gamma receptor (a receptor thought to control adipocyte differentiate + function) + reduce peripheral insulin resistance
272
What AEs are associated with thiazolidinediones?
```
Wt gain
Liver impairment - monitor LFTs
Fluid retention
Increased fracture risk
Bladder cancer (pioglitazone)
```
273
When are the use of thiazolidinediones CI?
Heart failure (due to fluid retention)
274
What is DM?
Chronic condition characterised by abnormally raised levels of blood glucose
275
What is the main aim of treating DM?
Reducing incidence of macrovascular (IHD, stroke) + microvascular (eye, nerve, kidney damage) complications
276
What is type 1 DM?
Autoimmune disorder where the insulin producing beta cells of the islets of Langerhans are destroyed by the immune system --> absolute insulin deficiency --> raised BG
277
How do T1DM tend to present?
In DKA or very unwell
278
What is T2DM due to?
Relative deficiency of insulin due to excess of adipose tissue
279
Define prediabetes
Patients who don't meet the criteria for a formal diagnosis of T2DM but are likely to develop it over the next few years
280
What is maturity onset diabetes of the young?
Group of inherited genetic disorders affecting insulin production
Happens in younger patients and tends to cause symptoms similar to T2DM, i.e. asymptomatic hyperglycaemia with progression to DKA
281
What is latent autoimmune diabetes of adults?
Autoimmune related diabetes presenting in later life (often misdiagnosed)
282
What other things may cause diabetes?
Chronic pancreatitis
Haemachromatosis
Drugs may also impair BG levels, e.g. corticosteroids
283
What are the features of T1DM?
Wt loss
Polydipsia
Polyuria
May present with DKA
284
What are features of DKA?
Ab pain
Vomiting
Reduced conscious level
285
How does T2DM tend to present?
Often incidental finding
Polydipsia
Polyuria
286
What causes polydipsia/polyuria in diabetes?
Water being dragged out of the body due to osmotic effects of excess glucose being excreted in the urine
287
What are the four main ways to check blood glucose?
Finger prick with bedside glucose monitor
One off blood glucose (fasting/not fasting)
HbA1c
Glucose tolerance test
288
What does HbA1c measure?
Amount of glycosylated Hb + represents BG average over past 2-3 months
289
What does a glucose tolerance test involve?
Fasting glucose taken after which 75g glucose taken and BG measured 2 hours later
290
How is diabetes diagnosed?
If symptomatic
Fasting glucose >=7mmol/l
Random glucose/OGTT >=11.1
If asymptomatic above criteria demonstrated on two separate occasions
291
What HbA1c is diagnostic of diabetes?
6.5% (48mmol/mol)
292
In a patient without symptoms but an HbA1c >=48, what should be done?
Repeat to confirm diagnosis
293
What are SEs of insulin therapy?
Hypoglycaemia
Wt gain
Lipodystrophy
294
What is the mechanism of action of metformin?
Increases insulin sensitivity
| Decreases hepatic gluconeogenesis
295
What are common SEs of metformin?
GI upset
| Lactic acidosis
296
When is metformin CI?
eGFR <30ml/min
297
What is the mechanism of action of SUs?
Stimulate pancreatic beta cells to secrete insulin
298
What are SEs of SUs?
Hypoglycaemia
Wt gain
Hyponatraemia
299
Give two examples of SUs
Glicazide
| Glimepiride
300
What is the only available thiazolidinedione currently?
Pioglitazone
301
What is the mechanism of action of DPP-4 inhibitors (-gliptins)?
Increases incretin levels which inhibit glucagon secretion
302
What is an AE of DPP-4 inhibitors (-gliptins)?
Risk of pancreatitis
303
What is the mechanism of action of SGLT-2 inhibitors (-gliflozins)?
Inhibits resportion of glucose in the kidney
304
What are AEs of SGLT-2 inhibitors (-gliflozins)?
UTIs
305
What is a benefit of taking SGLT-2 inhibitors (-gliflozins)?
Generally cause wt loss
306
What is the mechanism of action of GLP-1 agonists (-tides)?
Incretin mimetics which inhibit glucagon secretion
307
What are SEs of GLP-1 agonists (-tides)?
Nausea, vomiting, pancreatitis
308
What is a benefit of GLP-1 agonists (-tides)?
Typically cause wt loss
309
What is the only T2 diabetic drug that needs to be taken s/c instead of orally?
GLP-1 agonists (-tides)
310
Define MODY
Onset of type 2 DM in someone <25
311
How is MODY inherited?
AD
312
How many types of MODY have been identified?
6
313
A defect in what gene causes MODY 3?
HNF-1 alpha gene
314
Having MODY 3 is associated with increased risk of what?
Hepatocellular carcinoma
315
A defect in what gene causes MODY 2?
Glucokinase gene
316
What is the most common type of MODY?
MODY 3
317
A defect in what gene causes MODY 5?
HNF-1 alpha gene
318
As well as diabetes what do those with MODY 5 commonly get?
Liver and renal cysts
319
How are those with MODY usually treated?
SUs
| Insulin not usually req.
320
What is glucagon-like peptide?
A hormone released by the small intestine in response to an oral glucose load
321
What is the incretin effect?
An oral glucose load results in a greater release of insulin that if the same load was given IV
322
What hormone largely mediates the incretin effect?
GLP-1 (known to be decreased in T2DM)
323
Give an e.g. of a GLP-1 mimetic
Exenatide
324
How is exenatide taken?
SC injection 60 minutes before morning and evening meals
325
What drugs can GLP-1 be taken with?
Metformin SUs
326
When should you consider adding exenatide to metformin and a SU?
BMI >35 in people of european descent
BMI <35 + insulin unacceptable due to occupation or wt loss would benefit co-morbs
Pts must have achieved 11mmol/mol reduction in HbA1c + 3% wt loss after 6 months to justify continuing treatment
327
How are DDP-4 inhibitors taken?
Orally
328
Give e.g.s of DDP-4 inhibitors
Vildagliptin, sitagliptin
329
When might you prescrbe a DDP-4 inhibitor?
If a thiazolidinedione would cause further wt gain or significant problems is CI or the person had a poor response to it
330
What is a rare neuropsychiatric complication of steroids?
Psychosis
331
What is toxic multinodular goitre?
A thyroid gland that contains a number of autologously functioning thyroid nodules causing hyperthyroidism
332
What does nuclear scintigraphy demonstrate in toxic multinodular goitre?
Patchy uptale
333
What is the treatment of choice for toxic multinodular goitre?
Radioiodine therapy
334
What is gynaecomastia?
Abnormal amount of breast tissue in males usually caused by an increase in oestrogen:androgen ratio
335
What are causes of gynaecomastia?
```
Physiological - in puberty
Syndromes with androgen deficiency, e.g. Kallman's, Klinefelter's
Testicular failure, e.g. mumps
Liver dsiease
Testicular cancer, e.g. seminoma secreting hCG
Ectopic tumour secretion
Hyperthyroidism
Haemodialysis
Drugs
```
336
What drugs can cause gynaecomastia?
```
Spirnolactone (most common)
Cimetidine
Digoxin
Cannabis
Finasteride
Gonadorelin analogues, e.g. Goserelin, buserelin
Oestrogen, anabolic steroids
```
337
What are causes of primary hypothyroidism?
```
Hashimoto's
De Quervian's
Riedel thyroiditis
After thyroidectomy/radioiodine treatment
Drugs, e.g. lithium, amiodarone, ATDs
Dietary iodine deficiency
```
338
What causes secondary hypothyroidism?
Pituitary failure
339
What conditions are associated with secondary hypothyroidism?
Down's
Turner's
Coeliac disease
340
What should you start the insulin infusion rate at in DKA?
0.1 unit/kg/hour
341
Why can hypomagnesaemia lead to hypocalcaemia?
Mg req for PTH secretion and action on target tissues so low mg --> patients being unresponsive to ca and vit D supplements
342
Where is mg stored in the body?
Half in bone
| Rest in muscle, soft tissue, extracellular fluid
343
What hormones affect renal handling of mg?
PTH, aldosterone
344
What are causes of hypoglycaemia?
```
Insulinoma
Self administration of insulin/SUs
Liver failure
Addison's
Alcohol
```
in children - nesidioblastosis (beta cell hyperplasia)
345
What is the physiological normal response to hypoglycaemia?
Hormonal --> decrease insulin secretion, increase glucagon secretion, GH and cortisol released later
Sympathoadrenal response --> increased catecholamine mediated + ACh mediated neurotransmission in peripheral ANS and CNS
346
How is hypoglycaemia in impaired GCS managed?
100ml 20% glucose IV stat or IM glucagon
347
What are causes of thyrotoxicosis?
```
Grave's disease
Toxic nodular goitre
Acute phase De Quervians
Acute phase post-partum thyroiditis
Acute phase hashimoto's
Amiodarone therapy
```
348
What is HbA1c dependent on?
RBC lifespan
| Average BG concentration
349
What things may cause HbA1c to be lower than expected (due to reduced RBC lifespan)?
Sickle cell anaemia
G6PD deficiency
Hereditary spherocytosis
350
What things may cause HbA1c to be higher than expected (due to increased RBC lifespan)?
Vit B12/folate deficiency
Fe deficient anaemia
Splenectomy
351
Patients with addison's disease are given ____ and ____ replacement
Mineralocorticoid and glucocorticoid
352
What is the typical drugs taken by someone with Addison's?
Hydrocortisone (20-30mg per day)
| Fludrocortisone
353
What is essential advice to give to a patient with Addison's about taking their medication?
Do not miss a dose of glucocorticoids!!
| In intercurrent illness double hydrocortisone dose, fludrocortisone remains at the same dose
354
In relation to treating hypothyroidism - the initial starting dose of levothyroxine should be lowered in which groups?
Elderly (>50)
Those with IHD
Those with severe hypothyroidism
355
What is the usual starting dose of levothyroxine?
50-100mcg od
356
Following a change in thyroxine dose, when should TFTs be measured?
8-12 weeks
357
What is the primary therapeutic goal when treating hypothyroidism?
Normalising the TSH level (0.5-2.5)
358
Does pregnancy impact what dose of thyroxine a women should be on?
Yes - increase (by 25-50mcg) during pregnancy due to increased demands of pregnancy
359
What are SEs of thyroxine therapy?
Hyperthyroidism due to overtreatment
Reduced BMD
Worsening of angina
AF
360
What DDIs with thyroxine are important to be aware of?
Iron, calcium carbonate - absorption of levothyroxine reduced so give at least 4h apart
361
What is sick euthyroid syndrome now referred to as?
Non-thyroidal illness
362
What do the TFTs look like in sick euthyroid syndrome?
Often said everything is low (TSH low, thyroxine low, T3 is low)
But in most cases TSH is normal
363
How is sick euthyroid syndrome managed?
Changes reversible upon recovery from systemic illness + so no Rx usually req.
364
What are the NICE recommended GH therapy indications?
Proven GH deficiency
Turner's syndrome
Prader-Willi syndrome
Chronic renal insufficiency before puberty
365
How is GH therapy administered?
Subcut
366
When should GH therapy be discontinued?
If there is poor response in the first year
367
What are AEs of GH therapy?
Headaches
Benign intracranial hypertension
Fluid retention
368
What is the initial management of hypercalcaemia?
Rehydration with normal saline (usually 3-4L/day)
| Then bisphosphonates can be used
369
What are other options for the management of hypercalcaemia (apart from bisphosphonates)?
Calcitonin (works quicker than bisphosphonates)
| Steroids in sarcoidosis
370
What are clinical features of hypercalcaemia?
```
Bones - bone pain
Stones - renal stones
Groans - ab pain, nausea, vomiting
Thrones - polyuria
Psychiatric undertones (confusion, cognitive dysfunction, depression, anxiety, insomnia, coma)
Corneal calcification
HTN
```
371
What is typically found on ECG in hypercalcaemia?
Shortened QT interval
372
What is the interaction between dopamine and prolactin?
Dopamine is the primary prolactin releasing inhibitory factor
373
What are features of hyperprolactinaemia in men?
Impotence
Loss of libido
Galactorrhoea
374
What are the features of hyperprolactinaemia in women?
Amenorrhoea
| Galactorrhoea
375
What are causes of raised prolactin?
```
Prolactinoma
Pregnancy
Oestrogen
Physiological - stress, exercise, sleep
Acromegaly
PCOS
Primary hypothyroidism (due to thyrotrophin releasing hormone stimulating prolactin release)
```
376
What are drug causes of raised prolactin?
Metoclopramide, domperidone
Phenothiazines
Haloperidol
SSRIs, opioids (rare)
377
What are ACTH dependent causes of Cushing's syndrome?
Cushing's disease (primary tumour secreting ACTH --> adrenal hyperplasia)
Ectopic ACTH production, e.g. small cell lung cancer
378
What are ACTH independent causes of Cushing's?
```
Steroids
Adrenal adenoma
Adrenal carcinoma
Carney complex (syndrome incl. cardiac myxoma)
Micronodular adrenal dysplasia
```
379
What is pseudocushing's?
A cushing's mimic (causes false +ve dexamethasone test or 24hr urinary free cortisol)
380
What is pseudocushing's often due to?
Alcohol excess or severe depression
381
What test can be used to distinguish between Cushing's and pseudocushing's?
Insulin stress test
382
It is estimated than 1 in how many adults in the UK have prediabetes?
7
383
How do you identify patients with prediabetes?
NICE recommend using a validated computer based risk assessment tool for all >40, people of South Asian and Chinese descent 25-39 or adults with conditions that predispose to diabetes
If at risk --> blood sample
Fasting glucose 6.1-6.9mmol/l or HbA1c of 42-47 indicates high risk
384
What HbA1c and fasting glucose is considered normal?
HbA1c 41 or less
| Fasting BG <=6
385
What is involved in the management of prediabetes?
Wt loss, increased exercise, change in diet
Yearly follow up with blood tests
Consider metformin in those who look as though they are progressing to having T2DM despite lifestyle changes
386
What are the two main types of IGR?
IFG - impaired fasting glucose - due to hepatic insulin resistance
IGT - impaired glucose tolerance - due to muscle insulin resistance
387
Define IFG
Fasting BG 6.0-6.9mmol/l
388
Define IGT
Fasting plasma glucose <7 and OGTT 2h value greater than 7.8 but less than 11.1
389
What test should be offered to those with IFG?
OGTT
390
What are treatments for galactorrhoea?
Dopamine agonists, e.g. bromocriptine
391
What is a pituitary adenoma?
Benign tumour of the pituitary gland
392
How are pituitary adeomas classified?
Size: <1cm microadenoma, >1cm macroadenoma
| Hormonal status: secretory/functioning vs non-secretory/functioning
393
What is the most common type of pituitary adenoma?
Prolactinomas
| then non-secreting adenomas, then GH secreting then ACTH secreting
394
How do pituitary adenomas cause symptoms?
Hormone excess, e.g. Cushing's dx --> xs ACTH, acromegaly --> xs GH, prolactinoma --> xs prolactin)
Depletion of hormone due to compression of normal functioning pituitary (non-functioning tumours often present with hypothyroidism)
Stretching of dura within/around pituitary fossa --> headaches
Compression of optic chiasm --> bitemporal hemianopia
395
What investigations should be done for a suspected pituitary adenoma?
Pituitary blood profile incl. GH, prolactin, ACTH, FH, LSH, TFTs
Formal visual field testing
MRI brain with contrast
396
What are differential diagnoses for pituitary adenoma?
```
Pituitary hyperplasia
Craniopharyngioma
Meningioma
Brain metastases
Lymphoma
Hypophysitis
Vascular malformation (e.g. aneurysm)
```
397
What does treatment of a pituitary adenoma involve?
Hormonal therapy
Surgery (e.g. transsphenoidal transnasal hypophysectomy), e.g. if progression in size
Radiotherapy
398
What is Nelson's syndrome?
Rapid enlargement of pituitary corticotroph adenoma that occurs following bilateral adrenalectomy for Cushing's syndrome (due to lack of negative feedback)
399
What key messages should be given to diabetics about sick day rules?
Increase monitoring of BG (4hrly or more)
Drink 3L+/day
Aware of DKA
Continue oral hypoglycaemics (as cortisol elevates BG even if they are not eating)
Do NOT stop insulin due to DKA risk
Stop metformin if becoming dehydrated due to risk of renal dysfunction
400
What is the first line treatment for acromegaly?
Trans-sphenoidal surgery
401
What drugs may be used in the management of acromegaly?
Dopamine agonists, e.g. bromocriptine
Somatostatin analogues, e.g. octreotide (may be used as adjunct to surgery; most effective)
Pegvisomant
402
How do somatostatin analogues work in the management of acromegaly?
Directly inhibit GH release
403
What is pegvisomant?
GH receptor agonist (prevents dimerization of GH receptor)
404
How is pegvisomant administered?
SC
405
What treatment is sometimes used for frailer patients with acromegaly? Or used in surgical/medical treatment has failed?
External irradiation
406
What is thyroid storm?
Rare, but lifethreatening complication of thyrotoxicosis
407
Who is thyroid storm more typically seen in?
Patients with established thyrotoxcisosi
408
What events may precipitate thyroid storm?
Thyroid/non-thyroidal surgery
Trauma
Infection
Acute iodine load, e.g. CT contrast media
409
What clinical features are associated with thyroid storm?
```
Fever >38.5C
Tachycardia
Confusion + agitation
NV
HTN
Heart failure
Abnormal LFTs, jaundice
```
410
How is thyroid storm managed?
Symptomatic treatment, e.g. paracetamol
Treat underlying precipitating event
Beta blockers - IV propanolol
ATDs, e.g. methimazole or prophylthiouracil
Lugol's iodine
Dexamethasone (blocks conversion of T4 to T3)
411
What is the action of insulin?
Causes cells in liver, skeletal muscles, fat tissue to absorb glucose fro the blood
412
How is insulin synthesised?
Pro-insulin is formed by rough ER in the beta cells
Pro insulin cleaved to form insulin + c peptide
Insulin stored in secretory granules + released in response to Ca
413
What are the functions of insulin?
```
Secreted in response to hyperglycaemia
Glucose utilisation + glycogen synthesis
Inhibits lipolysis
Reduces muscle protein loss
Increases cellular uptake of K (stimulates NaK ATPase)
```
414
What is Whipple's triad of features of an insulinoma?
Symptoms + signs of hypoglycaemia
Plasma glucose <2.5mmol/L
Reversibility of symptoms on administration of glucose
415
What test can be used to help identify an insulinoma?
Exogenous insulin injection checking c peptide levels before + after as c-peptide production does not fall on exogenous insulin injection in those with insulinoma
416
Where does a neuroblastoma arise from?
Neural crest tissue of adrenal medulla + sympathetic NS
417
What are features of a neuroblastoma?
```
Abdominal mass
Pallor, wt loss
Bone pain, limp
Hepatomegaly
Paraplegia
Proptosis
```
418
What investigation findings will you see in neuroblastoma?
Raised urinary vanillylmandelic acid (VMA) + homovanillic acid (HVA) levels
calcification on abdominal x-ray
Biopsy confirms
419
Why should all children with palpable abdominal masses or unexplained enlarged abdominal organs be referred very urgently to be assessed?
To ensure they do not have a Wilm's tumour or neuroblastoma
420
What are causes for hypoglycaemia in a non-diabetic patient?
```
EXPLAIN -
Exogenous drugs, e.g. alcohol, aspirin poisoning, pentamidine, quinine sulphate, ACE inhibitors
Pituitary insufficiency
Liver failure
Addison's disease
Islet cell tumours, e.g. insulinomas
Non-pancreatic neoplasms
```
421
What are common hypo symptoms?
```
Sweating
Anxiety
Hunger
Tremor
Palpitations
Dizziness
Confusion
Drowsiness
Visual disturbance
Seizures
```
422
Define hypoglycaemia
BG <3 (some say 4)
423
What are features of an addisonian crisis?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
424
How do SUs work?
Increase pancreatic insulin secretion by binding to ATP dependent K channel on the cell membrane of pancreatic beta cells
425
What are common AEs of SUs?
Hypos
| Wt gain
426
What are features of thyrotoxicosis?
```
Wt loss
Manic restlessness
Heat intolerance
Palpitations, tachycardia
Increased sweating
Pretibial myxoedema
Thyroid acropachy - clubbing
Diarrhoea
Oligomenorrhoea
Anxiety
Tremor
```
High output cardiac failure may develop in elderly patients, a reversible cardiomyopathy can rarely develop
427
What is pretibial myxoedema?
Erythematous, oedematous lesions above lateral malleoli
428
What is the significance of subclinical hypothyroidism?
Risk of progression to hypothyroidism
| Increased risk of presence of thyroid autoantibodies
429
How is subclinical hypothyroidism managed?
TSH between 4-10mU/L + free thyroine in normal range -->
<65 + symptomatic - trial levothyroxine, if no improvement stop it
In older people watch and wait
In asymptomatic patients - observe + repeat TFTs in 6 months
TSH >10mU/L + free thyroxine normal - start treatment with levothyroxine if <=70
Watch and wait in older people
430
What is the mechanism of action of carbimazole?
Blocks thyroid peroxidase from coupling + iodinating tyrosine residues on thyroglobulin --> reduced TH production
431
What AEs are associated with carbimazole?
Agranulocytosis (counsel re if develop sore throat/fever FBC must be done to check neutrophil count)
Crosses placenta, use in low doses during pregnancy
432
What is the step wise approach to treating obesity?
Conservative - diet, exercise
Medical
Surgical
433
What drug can be used in the management of obesity?
Orlistat
434
What is the mechanism of action of orlistat?
Pancreatic lipase inhibitor
435
What AEs are associated with orlistat?
Faecal urgency/incontinence + flatulence
436
Who should be prescribed orlistat?
BMI 28+ + associated RFs
BMI 30+
Continued wt loss, e.g. 5% at 3 months
437
How long is orlistat generally used for?
<1 year
438
Which hormones are increased during the stress response?
```
GH
Cortisol
Renin
ACTH
Aldosterone
Prolactin
ADH
Glucagon
```
439
Which hormones are decreased during the stress response?
Insulin
Testosterone
Oestrogen
440
What changes occur in the sympathetic nervous system during the stress response?
Increased catecholamine release --> tachycardia + HTN
441
What is the purpose of GH being increased after surgery?
Prevents muscle breakdown and promotes tissue repair
442
What BMI is considered underweight?
<18.49
443
What BMI is considered normal?
18.5-25
444
What BMI is considered overweight?
25-30
445
What BMI is considered obese class I?
30-35
446
What BMI is considered obese class II?
35-40
447
What BMI is considered obese class III?
>40
448
How many units does 1ml of insulin contain?
100
449
How is myxoedemic coma treated?
Thyroxine and hydrocortisone
450
What electrolyte disturbance is seen in hypoparathyroidism?
Low calcium, high phosphate
451
How is hypoparathyroidism treated?
Alfacalcidol
452
What is a common cause of hypoparathyroidism?
Thyroid surgery
453
What are symptoms of hypoparathyroidism?
```
(Hypocalcaemia)
Tetany - muscle twitching, cramping, spasm
Perioral paraesthesia
Trousseau's sign
Chvostek's sign
If chronic - depression, cataracts
```
454
What is a +ve Trosseau's sign?
Carpal spasm if the brachial artery occluded by inflating BP cuff and maintaining pressure above systolic
455
What is a +ve Chvostek's sign?
Tapping over parotids --> facial muscle twitching
456
What is pseudohypothyroidism?
Target cell insensitivity to PTH due to abnormality in G protein
457
What is pseudohypothyroidism associated with?
Low IQ, short stature, shortened 4th and 5th metacarpals
458
What calcium, phosphate and PTH levels is seen in pseudohypothyroidism?
Low calcium
High phosphate
High PTH
459
How is pseudohypothyroidism diagnosed?
Measuring urinary cAMP and phosphate levels following infusion of PTH
In hypoparathyroidism would cause increase in cAMP and phosphate
460
What is pseudopseudohypoparathyroidism?
Similar phenotype to pseudohypoparathyroidism but normal biochemistry
