Passmed Endocrinology Mushkies Flashcards
1
Q
What is the pathophysiology of DKA?
A
DKA is causes by uncontrolled lipolysis which results in an excess of free fatty acids that are ultimately converted into ketone bodies
2
Q
What are the 3 most common precipitating factors of DKA?
A
- Infection
- Missed insulin doses
- MI
3
Q
What are some features of DKA?
A
- Abdo pain
- Polyuria, polydipsia, dehydration
- Kussmaul respiration (deep hyperventilation)
- Acetone-smelling breath (pear-drops smell)
4
Q
What are the diagnostic criteria for DKA?
A
- Glucose >11mmol/l or known DM
- Ketones > 3mmol/l or ++ on dipstick
- pH < 7.3
4, Bicarb < 15mmol/l
5
Q
What is the management of DKA?
A
- 0.9% saline
- Insulin = 0.1 unit/kg/hour
- 5% dextrose once blood glucose < 15mmol/l
- Correction of hypokalaemia
- Long acting insulin continued, short acting insulin stopped
6
Q
How fluid depleted are most pts with DKA?
A
5-8 litres
7
Q
What is the JBDS fluid replacement regime for pts with DKA with SBP>90mmHg?
A
- 0.9% NaCL = 1000ml over 1st hour
- 0.9% NaCL + KCl = 1000ml over next 2hrs
- 0.9% NaCL = 1000ml over next 2hrs
- 0.9% NaCL = 1000ml over next 4hrs
- 0.9% NaCL = 1000ml over next 4hrs
- 0.9% NaCL = 1000ml over next 6 hours
8
Q
What is the JBDS potassium replacement guideline for pts in DKA?
A
Potassium level in 1st 24 hours
- > 5.5 = No K
- 3.5-5.5 = 40 mmol/L
- <3.5 = senior review as additional K needs to be given
9
Q
What are some complications of DKA and its management?
A
GVAAAI
- Gastric stasis
- VTE
- Arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
- ARDS
- AKI
- Iatrogenic due to incorrect fluid therapy = cerebral oedema, hypokalaemia, hypoglycaemia
10
Q
What are children/young adults particularly susceptible during fluid resus for DKA?
A
- Cerebral oedema, usually 4-12 hours after commencement of tx
- 1:1 nursing ut monitor neuro obs, headache, irritability, visual disturbance, focal neurology etc.
- Any suspicion of oedema –> CT head and senior review
11
Q
What does an ‘unrecordable’ blood glucose mean?
A
It is rather high
12
Q
For group 1 vehicles, when are diabetic pts on insulin allowed to drive?
A
- If they have hypoglycaemic awareness
- Not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months
- No relevant visual impairment
13
Q
What overdose could cause metabolic acidosis with a raised anion gap?
A
Aspirin
14
Q
What is the eponymous triad for an insulinoma?
A
Whipple’s triad
15
Q
What is Whipple’s triad of symptoms for an insulinoma?
A
- Hypoglycaemia with fasting or exercise
- Reversal of symptoms with glucose
- Recorded low BMs at the time of symptoms
16
Q
What is an insulinoma?
A
A neuroendocrine tumour deriving mainly from the pancreatic Islets of Langerhans cells
17
Q
What are some stats about insulinomas?
A
- Most common pancreatic endocrine tumour
- 10% malignant
- 10% multiple
- Of pts with multiple tumours, 50% have MEN1
18
Q
What are the features of MEN1?
A
3 Ps
- Pituitary adenoma
- Parathyroid hyperplasia
- Pancreatic tumour e.g. insulinoma, gastrinoma (recurrent peptic ulceration)
19
Q
How is an insulinoma diagnosed?
A
- Supervised, prolonged fasting (up to 72 hours)
2. CT pancreas
20
Q
What is the management for an insulinoma?
A
- Surgery
2. Diazoxide and somatostatin if pts are not candidates for surgery
21
Q
What are features of MEN2A?
A
- Parathyroid hyperplasia
- Medullary Thyroid Carcinoma
- Phaeochromocytoma
22
Q
What are features of MEN2B?
A
- Mucosal neuromas
- Marfanoid body habitus
- Medullary Thyroid Carcinoma
- Phaeochromocytoma
23
Q
What is the management of subclinical hypothyroidism in the elderly?
A
Watch and wait
24
Q
What are the TFT features of subclinical hypothyroidism?
A
- Raised TSH
- Normal T3 and T4
- No symptoms
25
What is the risk of progression to overt hypothyroidism from subclinical hypothyroidism?
2-5% per year
26
Pt <65 y/o with symptoms of hypothyroidism, high TSH, normal T3 and T4?
Trial of levothyroxine, if there is no sx improvement, stop
27
Mx of asymptomatic subclinical hypothyroidism <65 y/o?
Observe are repeat TFTs in 6m
28
TSH > 10 and normal T3 and T4 management?
Start tx even if asymptomatic
29
What is the management of myxoedema coma?
Levothyroxine and hydrocortisone
30
Why is hydrocotisone given for myxoedema coma?
To treat adrenal insufficiency, pts w/ myxoedema due to secondary hypothyroidism are at risk of hypopituitarism due to location of lesion, thus are treated as presumed adrenal insufficiency until it has been ruled out
31
How can you classify the features of hypothyroidism?
1. General = weight gain, lethargy, cold intolerance
2. Skin = dry, cold, non-pitting oedema, coarse hair, loss of lateral 1/3rd of eyebrow
3. GI = constipation
4. Gynae = HMB
5. Neuro = dereased deep tenon reflexes, carpa tunnel syndrome
6. Hoarse voice
32
What mutation accounts for 70% of MODY cases?
Hepatic Nuclear Factor 1 Alpha (HNF1A) mutation (MODY 3)
33
What is the optimal treatment for HNF1A-MODY?
Sulfonylureas
34
What is MODY?
The development of T2DM in pts <25y/o, typically inherited in an autosomal dominant fashion
35
How many different mutations are documented to cause MODY?
6
36
What malignancy is MODY 3 associated with?
HCC
37
How do you diagnose T2DM in a symptomatic pt?
1. Fasting glucose ≥ 7.0 mmol/l OR
2. Random glucose ≥ 11.1 mmol/l OR
3. Post OGTT glucose ≥ 11.1mmol/l
38
How do you diagnose T2DM in an asymptomatic pt?
Same as symptomatic, but must be demonstrated on 2 separate occasions
39
What is the HbA1c T2DM diagnostic threshold?
>48mmol/mol (6.5%)
40
What is pre-diabetes, in terms of both HbA1c and fasting glucose?
1. HbA1c 42-47 mmol/l (6.0-6.4%)
| 2. Fasting glucose 6.1-6.9 mmol/l
41
What is normal fasting glucose in terms of both HbA1c and fasting glucose?
1. HbA1c < 41mmol/mol (5.9%)
| 2. Fasting glucoe <6.0mmol/l
42
What is 48mmol/mol HbA1c in %?
6.5%
43
What is 41mmol/mol HbA1c in %?
5.9%
44
Does a HbAlc value of less than 48 mmol/mol (6.5%) exclude diabetes?
No, fasting samples are more sensitive
45
What can cause misleading HbA1c results?
Conditions that cause increased red cell turnover
1. Haemoglobinopathies
2. Haemolytic anaemia
3. Untreated IDA
4. Children
5. HIV
6. CKD
7. Steroids
46
What defines impaired fasting glucose?
6.1-6/9 mmol/l
47
What defines impaired glucose tolerance?
1. Fasting plasma glucose <7.0mmol/l
| 2. OGTT > 7.8 but less than 11.1 mmol/l
48
What should pts with IFG be offered?
An OGTT to rule out a diagnosis of diabetes
49
What is the first line investigation for Conn's syndrome?
Renin:aldosterone ratio
50
What are 3 causes of primary hyperaldosteronism?
1. Bilateral idiopathic adrenal hyperplasia (70%)
2. Conn's syndrome (adrenal adenoma)
3. Adrenal carcinoma
51
What are 4 features of primary hyperaldosteronism?
1. Hypertension
2. Hypokalaemia
3. Hypernatraemia
3. Alkalosis
52
What is the management of bilateral idiopathic adrenal hyperplasia?
Aldosterone antagonist e.g. spironolactone
53
What is the management of Conn's syndrome?
Surgery
54
What are the different types of thyroid cancers?
1. Papillary (65%)
2. Follicular (20%)
3. Medulllary (5%)
4. Anaplastic (1%)
5. Lymphoma
55
Where does papillary thyroid cancer commonly metastasise to?
Cervical lymph nodes
56
What is a tumour marker for papillary and follicular thyroid carcinoma?
Thyroglobulin
57
What do you see on light microscopy of papillar thyroid carcinoma?
Orphan Annie eyes
58
Where does follicular thyroid carcinoma commonly metastasise to?
Lung and bones
59
Where do MTCs originate from and as such what is the tumour marker?
Parafollicular Cells, that produce Calcitonin
60
What demographic does papillary thyroid cancer usually affect, and what is its prognosis?
Young females, excellent prognosis
61
What condition is thyroid lymphoma associated with?
Hashimoto's thyroiditis
62
What is the management of papillary and follicular thyroid cancer?
1. Total thyroidectomy
2. Followed by radioiodine (I-131) to kill residual cells
3. Yearly thyroglobulin levels to detect early recurrent disease
63
In what demographic is anaplastic thyroid carcinoma most common?
Elderly females
64
What steroid has minimal glucocorticoid activity, and very high mineralocorticoid activity?
Fludrocortisone
65
What steroid has high glucocorticoid activity, and high mineralocorticoid activity?
Hydrocortisone
66
What steroid has high glucocorticoid activity, and low mineralocorticoid activity?
Prednisolone
67
What steroids have very high glucocorticoid activity, and minimal mineralocorticoid activity?
1. Dexamethasone
| 2. Betamethasone
68
What are the s/es of
| mineralocorticoids?
Fluid retention and hypertension
69
What are the s/es glucocorticoids?
1. Endocrine = Cushings
2. MSK = osteoporosis, proximal myopathy, AVN femoral head
3. Immune = suppression
4. Psych = Insomnia, mania, depression, psychosis
5.
70
How does Kartagener's syndrome present?
Dextrocardia and a history of recurrent sinusitis/bronchitis
71
What is the karyotype of Klinefelters?
47XXY
72
What are some features of klinefelter's?
1. Taller than average
2, Lack of secondary sexual characteristics
3. Small, firm testes
4. Infertile
5. Gynaecomastia
6. Elevated gonadotrophin levels but low testosterone
73
What diabetes drug is c/i in HF?
Thiazolidinediones e.g. pioglitazone, as they cause fluid retention
74
What is the MOA of thiazolidinediones?
1. PPAR-y agonists in adipocytes to promote adipogenesis and fatty acid uptake
2. Reduce peripheral insulin resistance
75
What are some features of Hashimoto's thyroiditis?
1, Hypothyroidism
2. Firm, non-tender goitre
3. Anti-TPO Abs (also anti-Tg Abs)
76
How much more common is hashimoto's thyroiditis in women?
10x
77
High TSH, normal T4, on levothyroxine, whats going on?
Poor compliance with medication - started taking thyroxine properly just before test. This will correct the thyroxine level but the TSH takes longer to normalise
78
What is Nelson's syndrome?
Rapid enlargement of an ACTH producing adenoma that occurs after bilateral adrenelectomy for Cushings syndrome
79
What is the prevalence of pituitary adenomas?
10% all people
80
How can pituitary adenomas be classified?
1. Size (microadenoma <1cm, macroadenoma >1cm)
| 2. Hormonal status (functioning vs. non-functioning)
81
What is the most common pituitary adenoma?
Prolactinoma
82
How do pituitary adenomas cause symptoms?
1. Excess hormone production
2. Depletion of hormone due to compression of normal functioning gland
3. Headache due to stretching of dura within/around pituitary fossa
4. Bitemporal hemianopia due to compression of optic chiasm
83
What are the components of a pituitary blood profile?
1. GH
2. Prolactin
3. ACTH
4. LH
5. FSH
6. TFTs
84
What are some differentials of a pituitary adenoma?
1. Pituitary hyperplasia
2. Craniopharyngioma
3. Meningioma
4. Brain mets
5. Lymphoma
6. Hypophysitis
7. Vascular malformation e.g. aneurysm
85
What are the general management strategies for pituitary adenomas?
1. Hormonal therapy
2. Surgery (e.g. transsphenoidal transnasal hypophysectomy)
3. Radiotherapy
86
What are the TFT findings of sick euthyroid syndrome?
Everything is low (sometimes TSH is normal)
87
What 2 conditions account for 90% of cases of hypercalcaemia?
1. Primary hyperparathyroidism (commonest in non-hospitalised pts)
2. Malignancy (commonest in hospitalised pts)
88
What are some malignancies that cause hypercalcaemia?
1. Bone mets
2. Myeloma
3. PTHrP from squamous cell lung cancer
89
What are some 'other' causes of hypercalcaemia
1. Endo = Acromegaly, Thyrotoxicosis, Addison's, Vit D intoxication
2. Inflammation = sarcoidosis
3. Drugs = thiazides
4. Dehydration
5. Milk-alkali syndrome
90
How many phases are there in subacute thyroditis?
4 phases following viral infection
91
What are the phases of subacute thyroiditis?
1. 3-6 weeks = hyperthyoidism, painful goitre, raised ESR
2. 1-2 weeks = euthyroid
3. Wks-ms = hypothyroidism
4 . Thyroid structure and function returns to normal
92
What investigation can you do for subacute thyroiditis?
Thyroid scintigraphy --> globally reduced uptake of Iodine-131
93
What is the management of subacute thyroiditis?
1. Usually self limiting, no tx
2. Thyroid pain may respond to aspirin or NSAIDs
3. If hypothyroidism develops --> steroids
94
What are the causes of primary hypothyroidism?
1. AI (Hashimoto's, atrophic)
2. Iodine deficiency
3. Thyroiditis (post-viral, post-partum, Riedel's)
4. Iatrogenic (thyroidectomy, radioiodine, drugs)
95
What is the triad of presentation of phaeos?
1. Sweating
2. Headaches
3. Palpitations
96
What is the first line investigation for phaeos?
24hr Urinary metanephrines (97% sensitivity)
97
What are the 3 genetic associations of phaeos?
1. MEN II
2. vHL
3. NF
98
What is the rule of 10%s for phaeos?
1. 10% extra-adrenal
2. 10% bilateral
3. 10% familial
4. 10% children
5. 10% malignant
6. Discussed 10x more than it is actually seen
99
What is the most common extra-adrenal site for phaeos?
The organ of Zuckerkandl, adjacent to the bifurcation of the aorta
100
What is the management of phaeos?
1. Alpha blocker (e.g. phenoxybenzamine) THEN
2. Beta blocker (e.g. propranolol) THEN
3. Surgery
101
What are the causes of primary hyperparathyroidism?
1. Solitary adenoma (80%)
2. Hyperplasia (15%)
3. Multiple adenomas (4%)
4. Carcinoma (1%)
102
What are the features of primary hyperparathyroism
'Bones, stones, abdominal groans and psychic moans'
1. Bone pain/fracture
2. Renal stones, polydipsia, polyuria
3. Peptic ulceration/constipation/pancreatitis
4. Depression
5, HTN
103
What is a characteristic X ray finding of primary HPT?
Pepperpot skull
104
What scan can be done for primary HPT?
Technetium-MIBI subtraction scan
105
What is the management of primary HPT
1. Definitive = total parathyroidectomy
2. Conservative management if there is no evidence of end organ damage and and calcium levels arent too high
3. Calcimimetic agents e.g. cinacalcet in pts unsuitable for surgery
106
What are some causes of an Addisonian crisis?
1, Sepsis or surgery causing acute exacerbation of chronic insufficiency
2. Adrenal haemorrhage (Waterhouse-Friderichsen syndrome due to fulminant meningococcaemia)
3. Steroid withdrawal
107
What is the management of an Addisonian crisis?
1. Hydrocortisone 100mg IM/IV
2. 1L normal saline infused over 30-60mins or with dextrose if hypoglycaemic
3. Continue hydrocortisone 6 hrly until pt is stable (no fludrocortisone required as hydrocortisone exerts weak mineralocorticoid action)
108
What is the tx for painful diabetic neuropathy to relieve pain?
1. First line = Duloxetine, Amitryptiline, Gabapentin, Pregabalin
2. If 1st drug doesnt work try one of the others
3. Tramadol may be used as rescue therapy for acut exacerbations
4. Topical capsaicin for localised neuropathic pain e.g. post-herpetic neuralgia
5. Pain clinics
109
How can diabetes cause GI symptoms?
GI autonomic neuropathy
110
What are 3 forms of GI autonomic neuropathy?
1. Gastroparesis
2. Chronic diarrhoea (often at night)
3. GORD (caused by decreased lower oesophageal pressure)
111
What are the symptoms and management for gastroparesis due to GI autonomic neuropathy?
1. Sx = erratic blood glucose control, bloating and vomiting
| 2. Mx = metoclopramide, domperionde, erythromycin (prokinetic agents)
112
Thyrotoxicosis with tender goitre?
Subacute (De Quervain's) thyroiditis
113
What is the infusion rate of insulin during DKA?
0.1 unit/kg/hr
114
What is the most common cause of thyrotoxicosis?
Graves' disease
115
What are features seen in Graves that arent seen in other causes of thyrotoxicosis
1. Eye signs (30%) pts = exophthalmos, ophthalmoplegia
2. Pretibial myoxoedema
3. Thyroid acropachy
116
What Abs are seen in Graves disease?
1. TSH receptor stimulating Abs (90%)
| 2. Anti-thyroid peroxidase Abs (75%)
117
In whom does a hyperosmolar hyperglycaemic state commonly present?
In the elderly with T2DM
118
What has higher mortality, HHS or DKA?
HHS
119
What are some salient vascular complications of HHS?
1. MI
2. Stroke
3. Peripheral arterial thrombosis
120
How long does it take for DKA and HHS to onset?
1. DKA = hours
| 2. HHS = days
121
What is the pathophysiology of HHS?
1. Hyperglycaemia --> osmotic diuresis w/ associated loss of sodium and potassium
2. Severe volume depletion --> very high serum osmolality (typically >320 mosmol/kg) --> hyperviscosity of blood
122
What are some clinical features of HHS?
1. General - fatigue, lethargy, N&V
2. Neuro = altered consciousness, headaches, papilloedema, weakness
3. Haem = hyperviscosity --> MI, stroke, peripheral arterial thrombosis
4. CVS = dehydration, hypotension, tachycardia
123
How is HHS diagnosed?
1. Hypovolaemia
2. Marked hyperglycaemia (>30mmol/l) WITHOUT significant ketonaemia or acidosis
3. Markedly raised serum osmolality (>320 mosmol/kg)
124
What are the goals of management of HHS?
1. Normalise osmolality (gradually)
2. Replace fluid and e- loss
3. Normal blood glucose (gradually)
125
What are fluid losses in HHS estimated to be?
100-220ml/kg
126
What is the fluid replacement for HHS?
1. 0.9% Nal, rate of rehydration determined by clinical picture
2. 0.45% NaCl if serum osmolality is not declining with normal saline
127
What is the goal of fluid replacement in initial management of HHS?
Replace 50% loss in first 12 hours, remainder in next 12 hours, but use your clinical judgement
128
What should be carefully monitored during tx of HHS?
Serum osmolality, glucose and sodium. Should be plotted on a graph initially.
129
What are the ideal rates of fall of sodium and glucose during management of HHS?
1. Na = Should not exceed 10mmol/l in 24hrs
| 2. Glucose = 4-6mmol/hr, targeting a blood glucose b/w 10-15mmol/l
130
Should insulin usually be used for management of HHS, and explain?
1. NO
2. Fluid replacement alone with 0.9% sodium chloride solution will result in a gradual decline of blood glucose and osmolarity
3. Because most patients with HHS are insulin sensitive (e.g. it usually occurs in T2DM), administration of insulin can result in a rapid decline of serum glucose and thus osmolarity, and may precipitate CPM
131
Why are potassium levels not as concerning in HHS?
Pts with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced. K should be replaced or omitted as required during management
132
How many units of insulin are in 1ml of standard insulin?
100 units
133
How can you classify insulin?
1. By manufacturing process
| 2. By duration of action
134
What are the different manufactured forms of insulin
1. Porcine = from pig pancreas
2. Human sequence = enzyme modification of porcine or from recombinant DNA or yeast
3. Analogues
135
What are the different subtypes of insulin based on duration of action?
1. Rapid acting analogues
2. Short acting
3. Intermediate acting
4. Long acting analogues
5. Premixed preparations
136
What is the onset, peak and duration of rapid acting insulin?
```
O = 5 mins
P = 1 hour
D = 3-5 hours
```
137
What is the onset, peak and duration of short acting insulin?
```
O = 30 mins
P = 3 hours
D = 6-8 hours
```
138
What is the onset, peak and duration of intermediate acting insulin?
```
O = 2 hours
P = 5-8 hours
D = 12-18 hours
```
139
What is the onset, peak and duration of long acting insulin?
```
O = 1-2 hours
P = flat profile
D = up to 24 hours
```
140
What are some rapid acting insulin analogues?
1. Insulin aspart = NovoRapid
| 2. Insulin lispro = Humalog
141
What are some short acting insulins?
1. Actrapid (soluble)
| 2. Humulin (soluble)
142
What are some intermediate acting insulins?
Isophane insulin, often used in premixed formulation with long acting insulin
143
What are some long acting insulins?
1. Insulin detemir = Levemir = Od or BD
| 2. Insulin glargine = Lantus = OD
144
What is a premixed insulin preparation?
1. Combine intermediate acting insulin with with either:
2. Rapid acting insulin analogue OR
3. Soluble insulin
145
Why is it important to rotate insulin injection sites?
To prevent lipdystrophy
146
What menstrual problem is hyperthyrodism associated with?
Oligomenorrhoea or amenorrhoea
147
What menstrual problem is hypothyroidism associated with?
Menorrhagia
148
How can hypothyroidism be classified?
1. Primary = problem with gland itself
2. Secondary = disorder of pituitary gland or lesion pressing on it
3. Tertiary = disorder of hypothalamus
4. Congenital = problem with thyroid dysgenesis or dyshormonogenesis
149
What drugs can cause hypothyroidism?
Lithium and amiodarone
150
What is Riedel's thyroiditis?
Hypothyroidism caused by fibrous tissue replacing the normal thyroid parenchyma, causing a painless goitre
151
What is the most common cause of hypothyroidism in the developed world?
Hashimoto's thyroidits
152
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
153
What drug can cause both hypo and hyperthyroidism?
Amiodarone
154
What is a good way to classify the features of hypo/hyperthyroidism?
GGG CNS
1. General
2. GI
3. Gynae
4. Cardiac
5. Neuro
6. Skin
155
How can you classify the features of thyrotoxicosis?
1. General = Weight loss, restlessness, heat intolerance
2. GI = diarrhoea
3. Gynae = a/oligomenorrhoea
4. Cardio = palpitations
5. Neuro = anxiety, tremor
6. Skin = sweating, pretibial myxoedema, thyroid acropachy
156
What component of TFTs is used to guide treatment and why?
TSH, as it is the most sensitive marker of thyroid disease
157
What are some treatments for thyrotoxicosis?
1. Cause = carbimazole, radioiodine
| 2. Complications = propranolol
158
What is the MOA of carbimazole?
Blocks TPO from coupling and iodinating the tyrosine residues on thyroglobulin --> reduced thyroid hormone production
159
What is the most salient s/e of carbimazole?
Agranulocytosis
160
When should a second drug be added in T2DM?
If HbA1c is > 58mmol/l
161
What is the target HbA1c for pts being managed with lifestyle, diet and 1 drug not associated with hypoglycaemia?
48mmol/mol
162
What is the target HbA1c for pts on any drug associated with hypoglycaemia?
53mmol/mol
163
How often should HbA1c be checked in pts with diabetes?
Every 3-6 months until stable and then every 6 months
164
How does NICE split the diabetes treatment pathways?
Depending on if they can tolerate metformin or not
165
What is the pathway for treatment of a pt who can tolerate metformin?
1. Metformin --> HbA1c > 58mmol/mol -->
2. Metformin + sulfonylurea/pioglitazone/gliptin/SGLT2-inhibitor --> HbA1c > 58mmol/mol -->
3. Metformin + 2 others (triple therapy) --> not effective/tolerated/contraindicated AND BMI >35 -->
4. Metformin + sulfonylurea + GLP1 mimetic
5. Insulin
166
What is the pathway for treatment of a pt who can't tolerate metformin?
1. Sulfonylurea/gliptin/pioglitazone --> HbA1c>58mmol/mol
2. Combine 2 of them --> HbA1c>58mmol/mol
3. Insulin
167
What is HbA1c 58mmol/mol as a %?
7.5%
168
What is first line statin for those with QRISK score > 10%?
Atorvastatin 20mg OD (primary prevention dose)
169
What is the secondary prevention dose of statin?
Atorvastatin 80mg OD
170
Why does diabetic foot disease occur?
1. Neuropathy = loss of protective sensation, Charcot's arthropathy, dry skin
2. Peripheral arterial disease = micro and macrovascular ischaemia
171
What are some complications of diabetic foot disease?
1. Calluses
2. Ulcers
3. Charcot's arthropathy
4. Cellulitis
5. Osteomyelitis
6. gangrene
172
How does diabetic foot disease present?
1. Neuropathy
2. Ischaemia = absent foot pulses, reduced ABPI, intermittent claudication
3. Complications
173
How can you screen for diabetic foot disease?
1. Ischaemia = Dorsalis pedis and posterior tibial artery palpation
2. Neuropathy = 10g monofilament on various parts on sole of the foot
174
Does any vision change in thyroid eye disease require urgent review by a specialist?
Yes
175
What percentage of pts with Graves have thyroid eye disease?
25-50%
176
What is the pathophysiology of thyroid eye disease?
AI response against TSH receptor --> retro-orbital inflammation --> GAG and collagen in the muscles
177
What is the most important modifiable RF for the development of thyroid eye disease?
Smoking
178
What treatment may increase the inflammatory sx seen in thyroid eye disease?
Radioiodine tx
179
What are some features of thyroid eye disease?
1. Exophthalmos
2. Ophthalmoplegia
3. Conjunctival oedema
4. Optic disc swelling
5. Inability to close eyelids --> dry, sore eyes
180
What is the management of thyroid eye disease?
1. Topical lubricants to prevent corneal inflammation caused by exposure
2. Steroids
3. Radiotherapy
4. Surgery
181
What could cause eye suddenly popping out with thyroid eye disease?
Globe subluxation
182
Most common cause of Addisons in UK?
AI
183
Most common cause of Addisons worldwide?
TB
184
What is Addison's disease?
Primary adrenal insufficiency
185
What are some features of Addison's disease?
1. Lethargy, weakness, anorexia, N&V, weight loss
2. Salt craving
3. Hyponatraemia and hyperkalaemia
4. Hyperpigmentation, esp palmar creases
5. Vitiligo
6. Loss of pubic hair in women
7. Hypotension, hypoglycaemia
186
What are the causes of hypoadrenalism?
1. Primary = AI, TB, Malignancy, Waterhouse Friedrichsen, HIV, Antiphospholipid syndrome
2. Secondary = pituitary
3. Tertiary = hypothalamic
4. Exogenous glucocorticoid therapy
187
What are some causes of thyrotoxicosis?
1. Graves
2. TMN
3. Amiodarone
4. Acute phase of subacute thyroiditis
5. Acute phase of post-partum thyroiditis
6. Acute phase of Hashimoto's thyroiditis
188
What are examples of GLP-1 agonists?
Exenatide and Liraglutide
189
What is the MOA of GLP-1 agonists?
Increase insulin secretion and inhibits glucagon secretion
190
What is GLP1 physiologically?
A hormone released by he small intestine in response to an oral glucose load
191
How is exenatide given?
SC injection within 60 mins before the morning and evening meals
192
What are some examples of DPP4 inhibitors?
Sitagliptin, vildagliptin
193
What is the inheritance of CAH?
Autosomal recessive
194
What are the causes of CAH?
1. 21-hydroxylase deficiency (90%)
2. 11b-hydroxylase deficiency (5%)
3. 17-hydroxylase deficiency (very rare)
195
What is CAH?
A group of autosomal recessive disorders affecting adrenal steroid biosynthesis
196
What biochemical abnormalities are seen in CAH?
Hyponatraemia, hyperkalaemia
197
How much is life expectancy reduced with T1DM?
13 years
198
What is the HbA1c target in T1DM?
48mmol/mol (6.5%)
199
How often should blood glucose be self monitored in T1DM?
At least 4 times a day (before each meal and before bed)
200
What are the blood glucose targets in T1DM?
1. 5-7mmol/l on waking
| 2. 4-7mmol/l before meals at other times of the day
201
When should metformin be added in T1DM?
If BMI >= 25 kg/m2
202
What is the most common presentation of MEN1?
Hypercalcaemia
203
What mutation causes MEN2?
RET oncogene
204
What is the effect of insulin?
Causes cells in the liver, skeletal muscles and fat tissue to absorb glucose from the blood
1. In liver and skeletal muscles, glucose is stored as glycogen
2. In adipocytes it is stored as triglycerides
205
What is the structure of insulin?
A dimer of an A-chain and a B-chain, which are linked together by disulfide bonds
206
How is insulin synthesises?
Pro-insulin is formed by the rough endoplasmic reticulum in pancreatic beta cells --> pro-insulin is cleaved to form insulin and C-peptide --> insulin is stored in secretory granules and released in response to Ca2+
207
What are some effects of insulin?
1. Glucose utilisation and glycogen synthesis
2. Inhibits lipolysis
3. Reduces muscle protein loss
4. Increases cellular uptake of K via stimulation of Na/L ATPase pump
208
What inhibits release of prolactin?
Dopamine
209
What drug may be used to control galactorrhoea?
Bromocriptine (DA agonist)
210
What are some features of excess prolactin?
1. Men = impotence, loss of libido, galactorrhoea
| 2. Women = amenorrhoea, galactorrhoea
211
What are causes of a raised prolactin?
6 Ps, OA
1. Prolactinoma
2. Pregnancy
3. Physiological = stress/exercise/sleep
4. PCOS
5. Primary hypothyroidism (due to TRH stimulating prolactin release)
6. Phenothiazines, metocloPramide, domPeridone
7. Oestrogens
8. Acromegaly (1/3rd)
212
What are some drugs that cause a raised prolactin?
1. Metoclopramide, domperidone
2. Phenothiazines
3. Haloperidol
4. Very rare = SSRIs, opioids
213
What are the BP targets for T2DM?
1. No organ damage = <140/80
| 2. End-organ damage = <130/80
214
What is the MOA of SGLT2 inhibitors?
Increase urinary excretion of glucose by reducing glucose absorption in the PCT (additional 70g of glucose excreted per day), alongside some diuresis which may lower BP
215
What is an example of an SGLT2 inhibitor?
Empagliflozin
216
What are some s/es of empagliflozin?
1. Urinary and genital infection
2. Normoglycaemic ketoacidosis
3. Increased risk of lower limb amputation
217
What are 3 hormones that are reduced as part of a stress response?
1. Insulin
2. Testosterone
3. Oestrogen
218
What is the 1st line treatment for pts with a pituitary tumour causing acromegaly?
Trans-sphenoidal surgery
219
What can be used for treatment of acromegaly if surgery fails/tumour is unresectable?
Somatostatin analogues and Dopamine agonists
220
What is an example of a somatostatin analogue?
Octreotide
221
What is an example of a dopamine agonist?
Bromocriptin
222
What is a new medical therapy for management of acromegaly?
Pegvisomant, a GH receptor antagonist
223
What diabetic medication is associated with an increased risk of osteoporosis?
Thiazolidinediones
224
Biguanide example?
MEtformin
225
S/e of metformin?
1. GI upset
| 2. Lactic acidosis in those w/ renal failure
226
Sulfonylurea s/e?
Gliclazide
227
S/es of sulfonylureas?
1. Weight gain
| 2. Hypoglycaemia
228
What is the normal value for TSH?
0.5-5.5 mu/l
229
What is the normal value for free T4?
9-18 pmol/l
230
What is the management of Graves disease?
1. Ant-thyroid drugs e.g. Carbimazole
2. Block and replace regimes
3. Radioiodine
4. Surgery
5. Propranolol
231
What is the ATD titration for Graves?
1. Carbimazole started at 40mg and reduced gradually to maintain euthyroidism
2. Typically continued for 12-18ms
3. Fewer s/e than B&R regimes
232
What is the block and replace regime for Graves?
1. Carbimazole started at 40mg
2. Thyroxine added when pt is euthyroid
3. Tx typically lasts for 6-9 months
233
What are some c/i's to radioiodine tx?
1. Pregnancy
| 2. <16 y/o
234
What medication is useful for T2DM pts who are obese?
DPP4 inhibitors
235
What is an important differential for being 'drunk'?
Hypoglycaemia
236
What is the definition of hypoglycaemia?
Plasma glucose level of 3mmol/L or less
237
What are the most common causes of hypoglycaemia in a diabetic pt?
Insulin/sulfonylurea tx with an increase in activity or missed meal or non-accidental OD
238
What are some causes of hypoglycaemia in a non-diabetic pt?
```
ExPLAIN
1. Exogenous drugs
2 Pituitary insufficiency
3. Liver failure
4. Addison's
5. Islet cell tumours
6. Non-pancreatic neoplasms
```
239
What are some exogenous drugs that can cause hypoglycaemia in a non-diabetic pt?
1. Alcohol
2. Aspirin
3. Pentamidine
4. Quinine sulfate
5. ACEi
240
What is DM?
A chronic condition characterised by abnormally raised levels of glucose
241
What are the microvascular complications of DM?
1. Retinopathy
2. Nephropathy
3. Neuropathy
242
What are the macrovascular complications of DM?
1. IHD
2. Stroke
3. PVD
243
What is LADA?
1. Latent autoimmune diabetes of adults
| 2. T1DM diagnosed in later life
244
What are some medical causes of diabetes?
1. Chronic pancreatitis
| 2. Haemochromatosis
245
What is the MOA of insulin?
1. Increases insulin sensitivity
| 2. Decreases hepatic gluconeogenesis
246
In what pts can metformin not be used?
eGFR < 30ml/min
247
What is the MOA of sulfonylureas?
Stimulate pancreatic beta cells to release insulin
248
What are 3 s/es of sulfonylureas?
1. Hypoglycaemia
2. Hyponatraemia
3. Weight gain
249
Sulfonylurea example?
Gliclazide
250
Thiazolidinedione example?
Pioglitazone
251
What are 4 s/es of thiazolidinediones?
1. Weight gain
2. Fluid retention
3. Liver impairment (monitor LFTs)
4. Bladder cancer
252
What is the MOA of DPP4 inhibitors?
Increases incretin levels which inhibit glucagon secretion
253
What is the 1st line test for acromegaly?
Serum IGF-1 levels
254
What used to be the 1st line test for acromegaly?
OGTT with serial GH measurements (now used to confirm the diagnosis if IGF1 levels are raised)
255
OGTT results in normal person and acromegaly?
1. Normal = GH suppressed to <2 mu/L
| 2. Acromegaly = no suppression of GH
256
What causes acromegaly?
1. Pituitary adenoma (95%)
2. Ectopic GHRH
3. GH by tumour e.g. pancreatic
257
What are some features of acromegaly?
1. Face = coarse facial appearance, large tongue, prognathism, interdental spaces
2. Hands = spade like hands
3. Feet = increase in shoe size
4. Skin = excessive sweating and oily skin (sweat gland hypertrophy)
5. Tumour effects = hypopituitarism, headaches, bitemporal hemianopia, galactorrhoea
258
What proportion of acromegalic pts have a raised prolactin?
1/3rd
259
What percentage of pts with acromegaly have MEN1?
6%
260
What are 4 complications of acromegaly?
1. HTN
2. Diabetes
3. Cardiomyopathy
4. Colorectal cancer
261
What is Cushing's syndrome?
A collection of signs and symptoms due to prolonged exposure to cortisol
262
What is Cushing's disease?
A specific type of Cushings syndrome characterised by increased ACTH production because of a pituitary adenoma
263
How can you classify the causes of Cushing's syndrome?
1. ACTH dependent
2. ACTH independent
3. Pseudo-Cushing's
264
ACTH dependent causes of Cushing's?
1. Cushing's disease (80%)
| 2. Ectopic ACTH (10%) e.g. small cell lung cancer
265
ACTH independent causes of Cushing's?
1. Iatrogenic = steroids
2. Adrenal adenoma
3. Adrenal carcinoma
4. Carney complex
5. Micronodular adrenal dysplasia
266
What is Pseudo-Cushing's?
Condition that mimics Cushing's, often due to alcohol excess or severe depression
1. Causes false positive dexamethasone suppression test or 24hr urinary free cortisol
2. Insulin stress test may be used to differentiate
267
What are 3 conditions associated with secondary hypothyroidism?
1. Downs
2. Turners
3. Coeliac disease
268
Clubbing with hyperthyroidism?
Graves
269
What diabetic medication is associated with an increased risk of bladder cancer?
Thiazolidinediones
270
What should be done to long-term steroid dosage during intercurrent illness?
Doubled
271
In what pts should steroid withdrawal be done gradually?
1. Pts receiving >40mg prednisolone daily for >1wk
2. Received more than 3 weeks treatment
3. Recently received repeat courses
272
First line insulin regime in newly diagnosed adults with T1DM?
Basal bolus insulin regimen with twice daily insulin detemir
273
What is the effect of iron on TFTs?
Iron reduces the absorption of thyroxine --> raised TSH, low T4
274
What are 4 s/es of thyroxine therapy?
1. Hyperthyroidism
2. Reduced bone mineral density
3. Worsening of angina
4. AF
275
What are some interactions of thyroxine therapy?
Iron and calcium carbonate --> absorption of levothyroxine reduced --> give at least 4 hours apart
276
Levothyroxine starting dose?
50-100mcg OD
277
Levothyroxine starting dose in >50y/o OR IHD?
25mcg OD and dose slowly titrated
278
TSH aim during thyroxine therapy?
0.5-2.5 mU/l
279
Thyroxine dose during pregnancy?
Increase by at least 25-50mcg
280
What medication OD causes hyperinsulinaemia and high C peptide levels?
Gliclazide (it functions by releasing vesicles stored within the pancreas containing insulin and C-peptide)
281
What is the management of bilateral adrenocortical hyperplasia?
Spironolactone
282
Inheritance of MODY?
AD
283
MOA of orlistat?
Pancreatic and gastric lipase inhibitor to reduce digestion of fat
284
What is the management of obesity?
1. Conservative = diet and exercise
2. Medical = orlistat
3. Surgical
285
What is the criteria for orlistat prescription?
1. BMI > 28 w/ RFs
| 2. BMI > 30
286
How long is orlistat usually used for?
<1 year
287
Mx of a child with palpable abdo mass or unexplained enlarged abdo organ?
Refer very urgently (<48hr) for specialist assessment for neuroblastoma and Wilms' tumour
288
Most common location for neuroblastoma to arise?
Neural crest tissue of adrenal medulla
289
Diagnosis of neuroblastoma?
1. Raised vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
2. Calcification on AXR
3. Biopsy
290
Why was the rosiglitazone withdrawn in 2010?
Concerns about CVS s/e profile
291
How can the severity of Graves eye disease be rated?
NOSPECS
1. No signs/symptoms
2. Only signs e.g. upper lid retraction
3. Signs and symptoms
4. Proptosis
5. Extra-ocular muscle involvement
6. Corneal involvement
7. Sight loss due to optic nerve involvement
292
Trousseau's sign?
Carpal spasm on inflation of BP cuff to pressure above systolic, due to hypocalcaemia
293
Chvostek's sign?
Tapping over parotid (CN7) causes facial nerves to twitch due to hypocalcaemia
294
Froment's sign is a sign of?
Ulcer nerve palsy
295
Finkelstein's sign is a sign of?
De Quervain's tenosynovitis
296
Primary hypoparathyroidism management?
Alfacalcidol
297
Symptoms of hypoPT?
1. Tetany = muscle twitching, cramping, spsm
2. Perioral paraesthesia
3. Trousseau's sign
4. Chvostek's sign
5. ECG = prolonged QT
6. Chronic = depression, cataracts
298
What causes pseudohypoparathyroidism?
Target cells being insensitive to PTH due to abnormality in a G protein
299
3 associations of pseudohypoparathyroidism?
1. Low IQ
2. Short stature
3. Shortened 4th and 5th metacarpals?
300
Pseudohypoparathyroidism on bloods?
Low calcium, high phosphate, high PTH
301
Dx of Pseudohypoparathyroidism?
1. Measuring urinary cAMP and phosphate levels following an infusion of PTH
2. HPT = increase in cAMP and PO4
3. PseudoHPT = both low/only PO4 low
302
Dx of pseudopseudohypoparathyroidism?
Similar to pseudohypoparathyroidism but normal biochemistry
303
Addisons pt unwell?
Double the glucocorticoids
304
Mx of Addisons?
1. Hydro and fludrocortisone
2. MedicAlert bracelet
3. Double dose of hydro during illness
305
Why can steroids worsen diabetic control?
Due to their anti-insulin effects
306
What is gynaecomastia?
An abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio
307
Causes of gynaecomastia?
1. Physiological (puberty)
2. Drugs
3. Syndromes = Kallman's, Klinefelters
4. Liver disease
5. Testicular disease = mumps, seminoma secreting hCG
6. Hyperthyroidism
7. Haemodialysis
308
What drugs can cause gynaecomastia?
1. Spironolactone
2. Digoxin
3. Cannabis
4. Finasteride
5. GnRHa e.g. goserelin
6. Oestrogens
7. Anabolic steroids
8. Cimetidine
309
What is the most common drug cause of gynaecomastia?
Spironolactone
310
What percentage of Graves pts have eye disease?
30%
311
Signs of Cushings with normal dexamethasone suppression test?
Chronic alcohol abuse (Pseudo-Cushings)
312
ABG of Conn's syndrome?
Metabolic alkalosis with hypokalaemia
313
ABG of Cushing's?
Hypokalaemic metabolic alkalosis
314
Cushing's syndrome dx?
1. Overnight dexamethasone suppression test (most sensitive)
| 2. 24hr urinary free cortisol
315
Cushing's syndrome localisation test?
1. 9am and midnight plasma ACTH OR
| 2. Low and high dose dexamethasone suppression test
316
Cushings, suppressed 9am and midnight plasma ACTH?
Suppressed ACTH = adrenal adenoma (non-ACTH dependent cause)
317
Interpretation of low and high dose dexamethasone suppression tests for Cushings?
1. Not suppressed by low dose = Cushing's syndrome not due to primary causes, i.e. likely secondary to corticosteroid therapy
2. Suppressed only by high dose = Cushings disease
3. Not suppressed = Ectopic ACTH
318
Hormonal management of Turners?
GH
319
3 s/es of GH therapy?
1. Headache
2. Benign intracranial HTN
3. Fluid retention
320
GH indications?
1. Proven GH deficiency
2. Turners
3. Prader-Willi
4. Chronic renal insufficiency before puberty
321
Erratic blood glucose control, bloating, and vomiting?
Gastroparesis
322
How does gastroparesis occur?
Diabetic neuropathy of the vagus nerve causing abnormal gut movement
323
How can you distinguish b/w MODY and T1DM?
Measure C-peptide
324
What syndrome is acromegaly associated with?
MEN1
325
Severe hyperglycaemia, dehydration and AKI, mild/absent ketonuria?
HHS
326
What are the DM sick day rules?
1. Blood glucose monitoring 4hrly
2. 3L fluid intake/24hrs
3. Struggling to eat --> sugary drinks to maintain carb intake
4. Box of 'sick day supplies'
5. Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
327
2 causes of central scotoma?
1. Macular degeneration
| 2. Optic neuritis
328
Addisonian crisis hyper or hypotension?
Hypertension
329
Does a negative pituitary MRI rule out Cushing's disease?
No - adenoma often too small to be picked up on imaging
330
1st line mx of symptomatic cerebral metastases?
High dose dexamethasone to reduce cerebral oedema
331
How can you differentiate b/w DKA and HHS by looking at bloods?
HHS does NOT cause metabolic acidosis or hyperketonaemia
332
Thiazide effect on calcium?
Hypercalcaemia
333
When must levothyroxine be taken re food?
30 mins before food as absorption may be affected by food, caffeine, or other meds
334
What must be done if an incidentaloma is found, even if asymptomatic?
Lab investigation must be undertaken to determine if it is functional or non-functional
335
Postmenopausal woman with a fracture mx?
Bisphosphonates
336
Best test to diagnose Addisons?
Short Synacthen test
337
E- abnormalities in Addisons?
1. Hyperkalaemia
2. Hyponatraemia
3. Hypoglycaemia
4. Metabolic acidosis
338
What is a short synacthen test?
Plasma cortisol measured before and 30 mins after giving Synacthen 250ug IM
339
What adrenal autoantibody may be found in Addisons?
anti-21-hydroxylase
340
Hypoglycaemia w/ impaired GCS mx?
100ml 20% glucose IV stat
341
2 main physiological responses to hypoglycaemia?
1. Hormonal = decreased insulin, increased glucagon secretion, LATER GH and cortisol release
2. Sympathoadrenal = = increased catecholamine and acetylcholine neurotransmission in CNS and PNS
342
What is the treatment of choice for toxic multinodular goitre?
Radioiodine
343
Why can splenectomy give a falsely high HbA1c?
Due to the increased lifespan of RBCs
344
What 2 main factors determine HbA1c?
1. Average blood glucose conc.
| 2. RBC lifespan
345
3 conditions that cause lower than expected HbA1c?
1. Sickle cell
2. G6PDD
3. Hereditary spherocytosis
346
3 causes of higher than expected HbA1c levels?
1. Vit B12/folic acid deficiency
2. IDA
3. Splenectomy
347
Hypothermia, hyporeflexia, bradycardia, seizures?
Myxoedema coma
348
What is the first line treatment for prolactinomas?
DA agonists e.g. carbergoline, bromocriptine
349
What should every person treated with insulin also be given for emergencies?
A glucagon kit
350
Mx of conscious hypoglycaemia?
10-20g of short acting carbohydrate e.g. one glass of glucozade or non-diet drink, 3 or more glucose tablets, glucose gel
351
What is Zollinger-Ellison syndrome?
Rare condition caused by gastrin-secreting tumour found in either the islet cells of the pancreas or in the duodenal wall
352
Management of diabetic gastroparesis?
Metoclopramide, domperidone, erythromycin (all prokinetic agents)
353
What is the maximum dose of metformin?
1g BD
354
Most common cause of impaired hypoglycaemia awareness in a pt with long-standing type 1 diabetes?
Neuropathy of the autonomic nervous system
355
Acute management of DKA?
Fixed rate insulin 0.1mg/kg/hr, continue long acting insulin but stop short acting insulin
356
Mx of thyrotoxic storm?
1. IV propranolol (for tachy)
2. Propylthiouracil (anti-thyroid)
3. IV Dexamethasone (blocks T4 to T3 conversion, also treats any underlying adrenal insufficiency)
4. Underlying cause
357
Precipitating events of a thyroid storm?
1. Thyroidal/non-thyroidal surgery
2. Trauma
3. Infection
4. Acute iodine load e.g. CT contrast media
358
Clinical features of thyroid storm?
1. Fever > 38.5
2. Tachy
3. Confusion and agitation
4. N&V
5. HTN
6. HF
7. Abnormal LFTs/jaundice
359
Most common metabolic complication of cancer?
Hypercalcaemia
360
Why is dexamethasone used for brain tumours?
Anti-inflammatory effects of corticosteroids but minimal mineralocorticoid (fluid retention) effects
361
What is the 4th most abundant cation in the body?
Magnesium
362
How much Mg is in the body?
1000mmol
363
Pt with malabsorption and low calcium, why?
Malabsorption --> magnesium deficiency --> low calcium
364
Why does low Mg cause low Ca?
1. Mg is required for both PTH secretion and its action on target tissues
2. Mg and Ca interact at a cellular level also and as a result decreased magnesium will tend to affect the permeability of cellular membranes to calcium, resulting in hyperexcitability
365
Hypokalaemia, hypernatraemia, and HTN?
Primary hyperaldosteronism
366
What are the gliptins?
Dipeptidyl peptidase 4 (DPP4) inhibitors
