ENDOCRINE Flashcards
(399 cards)
1
Q
PARATHYROID PHYSIOLOGY
Give 5 parathyroid hormone actions
A
- Increase Ca2+ reabsorption
- Decrease phosphate reabsorption
- Increase 1 alpha-hydroxylation of 25-OH vit D
- Increase bone remodelling (bone resorption >bone formation)
- Increase Ca2+ absorption because of increase 1,25(OH)2D (no direct effect)
2
Q
PARATHYROID PHYSIOLOGY
When serum calcium levels are low, what are PTH levels?
A
PTH levels are high
3
Q
PARATHYROID PHYSIOLOGY
When serum calcium levels are high, what are PTH levels?
A
PTH levels are low
4
Q
HYPERPARATHYROIDISM
What is hyperparathyroidism?
A
excessive PTH resulting in changes to blood calcium levels
5
Q
HYPERPARATHYROIDISM
what are the clinical features of hyperparathyroidism?
A
SYMPTOMS
- BONES – excess bone resorption caused by PTH Pain, fractures, osteopenia, osteomalacia, osteoporosis
- STONES – due to excess Ca. Renal colic from renal calculi and biliary stones
- (abdominal) GROANS – abdominal pain, malaise, nausea, constipation, polydipsia, polyuria, dehydration, confusion, risk of cardiac arrest
- (psychic) MOANS – depression, anxiety, cognitive dysfunction, insomnia, coma
SIGNS
hypercalcaemia
6
Q
HYPERPARATHYROIDISM
What is the pathophysiology of primary hyperparathyroidism
A
- parathyroid adenoma results in excessive PTH, causing symptoms associated with hypercalcaemia
7
Q
HYPERPARATHYROIDISM
what is the the pathophysiology of secondary hyperparathyroidism
A
- Parathyroid gland hyperplasia occurs as a result of low calcium, resulting in more PTH
- almost always in a setting of chronic renal failure
8
Q
HYPERPARATHYROIDISM
what is the pathophysiology of tertiary hyperparathyroidism?
A
- Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder,
- hyperplasia of all 4 glands is usually the cause
9
Q
HYPERPARATHYROIDISM
What blood results would you see in the 3 types of hyperparathyroidism?
A
PRIMARY =
- PTH = high
- calcium = high
- phosphate = low
- alk phos = high
SECONDARY =
- PTH = high
- calcium = low
- phosphate = high
- alk phos = high
TERTIARY -
- PTH = high
- calcium = high
- phosphate = high
- alk phos = high
10
Q
HYPERPARATHYROIDISM
what are the investigations?
A
- PTH level
- bone profile
- renal function
- Sestamibi scan of parathyroid gland
to consider
- urinary calcium
- vitamin D
- DEXA scan
- CT KUB
11
Q
HYPERPARATHYROIDISM
Describe the treatment for hyperparathyroidism
A
PRIMARY
- parathyroidectomy
- calcimimetics (cinacalet)
- bisphosphonates
- HRT
SECONDARY
- vitamin D supplementation
- renal transplant
- calcium supplementation
- phosphate binding agent
TERTIARY
- parathyroidectomy
- cinacalet
12
Q
HYPERPARATHYROIDISM
How does a calcium mimetic work?
A
Increases sensitivity of parathyroid cells to calcium so less PTH secretion occurs
13
Q
HYPOPARATHYROIDISM
What is the affect of hypoparathyroidism on serum calcium levels?
A
Hypoparathyroidism –> hypocalcaemia
14
Q
HYPOPARATHYROIDISM
what are the clinical features of hypoparathyroidism?
A
SYMPTOMS:CATs go numb
- convulsions / seizures
- arrhythmias / anxious
- tetany / muscle spasms
- numbness
SIGNS:
- CHVOSTEK’S SIGN - tap over facial nerve and look for spasm of facial nerves
- TROUSSEAU’S SIGN - inflate BP cuff 20 mmHg above systolic for 5 mins = hand spasm - hypocalcaemia
15
Q
HYPOPARATHYROIDISM
what are the causes of hypoparathyroidism?
A
- iatrogenic (neck surgery)
- autoimmune (isolated autoimmune hypothyroidism)
- metabolic (hyper/hypomagnesaemia)
- congenital (DiGeorge syndrome)
16
Q
HYPOPARATHYROIDISM
what are the investigations?
A
PTH (raised)
Bone profile (hypocalcaemia + hyperphosphataemia)
magnesium
vitamin D
ECG
To consider:
- 24hr urinary calcium
- CT KUB
- genetic studies
17
Q
HYPOPARATHYROIDISM
What are blood results for someone with hypoparathyroidism?
A
Calcium = Low
PTH = Low
Phosphate = High
18
Q
HYPOPARATHYROIDISM
What is the treatment for hypoparathyroidism?
A
ACUTE
- IV 10% calcium gluconate
LONG TERM
- increased dietary calcium + vitamin D
- calcium supplements
- Vitamin D supplements
- thiazide diuretics
19
Q
HYPOPARATHYROIDISM
what are the complications?
A
- calcifications
- renal stones
- renal failure
- cataracts
- life-threatening hypocalcaemia
20
Q
HYPERCALCAEMIA
what are the causes of Hypercalcaemia?
A
Hyperparathyroidism
Malignancy
Sarcoidosis
Thyrotoxicosis
Drugs
21
Q
HYPERCALCAEMIA
What is the treatment for hypercalcaemia?
A
- Treat underlying cause
- increase circulation volume, increase excretion
.- Bisphosphonates, glucocorticoids, gallium, dialysis
22
Q
HYPERCALCAEMIA
Give 2 ECG changes that you might see in someone with hypercalcaemia
A
- Tall T waves
- Shortened QT interval
23
Q
HYPOCALCAEMIA
Name 3 causes of hypocalcaemia
A
Hypoparathyroidism
Vitamin D deficiency
Hyperventilation
Drugs
Malignancy
Toxic shock
24
Q
HYPOCALCAEMIA
what are the investigations for hypocalcaemia?
A
ECG - prolonged QT + ST
Calcium + phosphate levels
LFTs - ALP
PTH
Vitamin D
U&Es
25
HYPOCALCAEMIA
what is the treatment for hypocalcaemia?
10ml calcium gluconate/chloride 10% slow IV,
oral calcium and Vit D
26
HYPOCALCAEMIA
Give 2 ECG changes that you might see in hypocalcaemia?
1. Small T waves
2. Long QT interval
27
PARATHYROID PHYSIOLOGY
What does the parathyroid control?
Serum calcium levels
| A low serum calcium triggers the release of PTH and a high serum calcium triggers c-cells to release calcitonin
28
PARATHYROID PHYSIOLOGY
What hormone does the parathyroid secrete and what is its function?
PTH - secreted in response to low serum calcium
29
PARATHYROID PHYSIOLOGY
What is released by c-cells in the parathyroid in response to high serum calcium?
Calcitonin
30
PARATHYROID PHYSIOLOGY
What biochemical test might you want to do to establish the cause of hypercalcaemia?
PTH measurement
31
T1DM
What disease is described as being a 'disorder of carbohydrate metabolism characterised by hyperglycaemia'?
Diabetes mellitus
32
T1DM
what is T1DM?
Autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency.
33
T1DM
what is the pathophysiology of T1DM
- autoimmune destruction of beta cells in the Islets of Langerhans by autoantibodies cause insulin deficiency and continued breakdown of liver glycogen
- this causes hyperglycaemia and glycosuria
34
T1DM
Is T1DM characterised by a problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion - severe insulin deficiency
35
T1DM
what are the risk factors for developing T1DM?
- Northern European
- Family History:
- HLA DR3 or
- HLA-DR4
- enterovirus infection
- Other autoimmune diseases:
- Autoimmune thyroid
- Coeliac disease
- Addison’s disease
- Pernicious anaemia
36
T1DM
what are the clinical features of T1DM?
SYMPTOMS
- polyuria
- polydipsia
- weight loss
- lethargy
- recurrent infections
- evidence of complications e.g. blurred vision or paraesthesia
SIGNS
- BMI typically <25
- failure to thrive in children
- glove + stocking sensory loss
- reduced visual acuity
- diabetic retinopathy
- diabetic foot disease (reduced peripheral pulses, calluses, ulceration + charcot joint)
37
T1DM
Describe the epidemiology of T1DM
Onset younger (<30 years)
Usually lean
More Northern European ancestry
38
T1DM
what are the investigations?
- random blood glucose (>11mmol/L)
- fasting blood glucose (>7.0mmol/L)
- oral glucose tolerance test (OGTT) (>11mmol/L after 2hrs)
- HbA1c
- urine albumin:creatinine ratio + eGFR
to consider
- c-peptide (only in atypical presentations)
- autoantibodies (only in atypical presentations)
39
T1DM
What would a persons fasting plasma glucose be if they were diabetic?
Fasting plasma glucose >7 mmol/L
40
T1DM
What would a persons random plasma glucose be if they were diabetic?
Random plasma glucose >11 mmol/L
41
T1DM
What might someone's HbA1c be if they have diabetes?
>48 mmol/L>6.5%
42
T1DM
What happens to C-peptide in T1DM?
C-peptide reduces
43
T1DM
How do you treat T1DM?
Education
Glycaemic control through diet (low sugar, low fat, high starch)
Insulin SC (basal bolus regime = 1st line)
44
T1DM
Give 6 complications of Diabetes Mellitus
1. Diabetic ketoacidosis
2. Diabetic nephropathy
3. Diabetic retinopathy
4. Diabetic neuropathy
5. Hyperosmolar hyperglycaemic coma
6. Stroke, ischaemic heart disease, peripheral vascular disease
45
T1DM
Give 2 potential consequences of T1DM
1. Hyperglycaemia
| 2. Raised plasma ketones --> ketoacidosis
46
T1DM
what is the 1st line insulin regimen?
basal-bolus regimen
Basal = levemir (detemir) BD or Lantus (glargine) OD
Bolus = Humalog (lispro) or Novorapid (Aspart)
47
T1DM
what is a mixed insulin regime for T1DM?
given twice daily (may be used in those unable to tolerate multiple injections with basal-bolus)
EXAMPLES:
- novomix 30 (30% rapid, 70% intermediate)
- humalog mix25 (25% rapid, 75% intermediate)
- humalog mix50 (50% rapid, 50% intermediate)
- humulin M3 (30% short, 70% intermediate)
- insuman comb 15 (15% short, 85% intermediate)
48
T1DM
Give 4 potential complications of insulin therapy
1. Hyperglycaemia
2. Lipohypertrophy at injection site
3. Insulin resistance
4. Weight gain
5. Interference with life style
49
T1DM
What is the affect of cortisol on insulin and glucagon?
Inhibits insulin
| Activates glucagon
50
DIABETIC KETOACIDOSIS
Describe the pathophysiology of diabetic ketoacidosis
- net reduction in insulin + increase in other hormones (cortisol, glucagon, catecholamines + GH)
- this leads to reduced glucose entry into cells
- cells metabolise lipids as alternative energy source
- uncontrolled lipolysis leads to elevated free fatty acids + ketone bodies
- this leads to a state of ketoacidosis
51
DIABETIC KETOACIDOSIS
what is it?
A metabolic state in which there is a triad:
- hyperglycaemia
- acidosis
- ketonaemia
52
DIABETIC KETOACIDOSIS
Where does ketogenesis occur?
Liver
53
DIABETIC KETOACIDOSIS
what are the causes?
- infection
- inadequate insulin or non-adhederence to insulin therapy
- MI
- physiological stress (trauma or surgery)
- co-morbidities (hypothyroidism, pancreatitis)
- drugs (corticosteroids, diuretics, salbutamol)
54
DIABETIC KETOACIDOSIS
what are the clinical features of diabetic ketoacidosis?
SIGNS
- Breath smells of pear drops (ketones)
- Kussmaul’s breathing - deep, rapid breathing
- Tachycardia
- Hypotension
- Reduced tissue turgor
SYMPTOMS
- Nausea and vomiting
- polyuria + polydipsia
- Dehydration
- exacerbated by vomiting
- Weight loss
- lethargy + confusion
- Abdominal pain
55
DIABETIC KETOACIDOSIS
what are the investigations?
- urine dip (glycosuria + ketonuria)
- bedside ketone + capillary glucose
- ABG/VBG
- U&Es
- FBC + CRP
- infection screen
56
DIABETIC KETOACIDOSIS
what is the diagnostic criteria?
Glucose >11mmol/L
HCO3 < 15mmol/L and/or venous pH <7.30
Ketonaemia (>3mmol/L) or 2+ ketones on dipstick
57
DIABETIC KETOACIDOSIS
what is the management?
IV FLUIDS
- if SBP<90 500ml bolus of 0.9% NaCl over 15 mins + call for senior help
- if SBP>90 1L 0.9% NaCl over 1 hour, 1 litre 0.9% NaCl with kCl over 2hrs, 2hrs, 4hrs, 4hrs and then 6hrs
INSULIN
- fixed rate insulin infusion
- 0.1U/kg/hr
- once glucose <14mmol/L add 10% glucose + consider reducing insulin
- do not stop long acting insulin
POTASSIUM REPLACEMENT
- >5.5 in first 24hrs = no replacement required
- 3.5-5.5 in first 24hrs = 40mmol/L KCl
- <3.5 in first 24hrs = consider HDU/ITU
58
DIABETIC KETOACIDOSIS
what are the complications?
- venous thrromboembolism
- arrhythmias
- ARDS
- AKI
- cerebral oedema
- hypokalaemia
- gastric stasis
59
DIABETES MELLITUS
Give 3 microvascular compilation of DM
1. Diabetic retinopathy
2. Diabetic nephropathy
3. Diabetic peripheral neuropathy
60
DIABETES MELLITUS
Give 2 macrovascular complications fo DM
CV disease
| Stroke
61
DIABETES MELLITUS
What is the main risk factor for diabetic complications?
Poor glycemic control
62
T2DM
Give 3 endocrine diseases that can cause diabetes
1. Cushing's
2. Acromegaly
3. Phaeochromocytoma
63
T2DM
What class of drugs can cause diabetes?
Steroids
Thiazides
Anti-psychotics
64
T2DM
Is T2DM characterised by problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion and insulin resistance
65
T2DM
what is the aetiology of T2DM?
- Decreased insulin secretion and increased insulin resistance
- No immune disturbance
- No HLA disturbance but strong genetic link
- Polygenic
- Associated with obesity, lack of exercise, calorie and alcohol excess
66
T2DM
Describe the pathophysiology of T2DM
Insulin resistance leads to compensatory increase in insulin until beta cell exhaustion.
This causes a state of relative insulin deficiency + hyperglycaemia.
67
T2DM
Why is insulin secretion impaired in T2DM
Due to lipid deposition in the pancreatic islets
68
T2DM
what are the risk factors for T2DM?
- increasing with age (increasingly common in adolescents)
- Asian + African ethnicities
- Family history
- Obesity
- Gestational diabetes
- PCOS
- Drugs (corticosteroids, thiazides)
69
T2DM
What is the clinical presentation of T2DM?
SYMPTOMS
- weight loss
- polyuria
- polydipsia
- lethargy
- recurrent infections
- evidence of complications
SIGNS
- acanthosis nigricans
- glove + stocking sensory loss
- reduced visual acuity
- diabetic retinopathy
- diabetic foot disease (reduced peripheral pulses, calluses, ulceration, charcot joint)
70
T2DM
What happens to insulin resistance, insulin secretion and glucose levels in T2DM?
Insulin resistance increase Insulin secretion decreases Fasting and post-prandial glucose increase
71
T2DM
Why do you rarely see diabetic ketoacidosis in T2DM?
Insulin secretion is impaired but there are still low levels of plasma insulin
Low levels of insulin prevent muscle catabolism and ketogenesis
72
T2DM
By how much has the beta cell mass reduced in T2DM when diagnosis usually occurs?
50% of normal beta cell mass
73
T2DM
Describe the epidemiology of T2DM
Onset older (>30)
Usually overweight
More common in African/Asian populations
Males > Females
74
T2DM
what are the investigations?
- fasting blood glucose
- random blood glucose
- oral glucose tolerance test
- HbA1c
to consider
- fasting lipids
- U&Es
- urine albumin:creatinine ratio
75
T2DM
Describe the treatment pathway for T2DM
LIFESTYLE ADVICE
-
MEDICATIONS
1st line = metformin
if patient has HF offer metformin + SGLT2i (-gliflozin)
if HbA1c >58, commence dual therapy
1. DPP4i (linagliptin, sitagliptin)
2. Sulfonylurea (gliclazide)
3. Pioglitazone
4. SGLT2i (dapagliflozin, empagliflozin)
if HbA1c > 58 despite dual therapy, commence intermediate acting insulin or triple therapy
triple therapy = metformin + sulfonylurea + GLP-1 mimetic (liraglutide)
76
T2DM
How does metformin work in treating T2DM?
Increase insulin sensitivity and inhibits glucose production in the liver
77
T2DM
How does sulfonylurea work in treating T2DM?
Stimulates insulin release
block ATP dependent K+ channels in beta cells -> causes depolarisations and opening of voltage gated Ca2+ channels -> stimulates insulin secretion
78
T2DM
what are the side effects of Sulfonylurea?
Hypoglycaemia
weight gain
hyponatraemia
79
HYPOGLYCAEMIA
What is hypoglycaemia classified as?
Plasma glucose <3.9 mmol/L and if <3.0 mmol/L it is severe hypoglycaemia
80
HYPOGLYCAEMIA
what are the symptoms of hypoglycaemia?
AUTONOMIC FEATURES
- diaphoresis
- tachycardia
- tremor
- anxiety
- N+V
- generalised tingling
NEUROGLYCOPAENIC FEATURES
- agitation
- fatigue
- blurred vision
- seizure
- reduced GCS
81
HYPOGLYCAEMIA
Why does hypoglycaemia continuously get worse?
Glucagon is not produced so rely only on adrenaline and the threshold for adrenaline release gradually lowers after time
82
HYPOGLYCAEMIA
Give 6 consequences of hypoglycaemia
1. Seizures
2. Comas
3. Cognitive dysfunction
4. Fear
5. Decrease in qualitative life
6. Accidents
83
HYPOGLYCAEMIA
what are the investigations?
- blood glucose
to consider:
- c-peptide
- FBC, U&Es, LFTs, renal function, urinalysis
- thyroid function, cortisol, ACTH, synacthen test, LH/FSH, prolactin
84
HYPOGLYCAEMIA
Briefly describe the treatment of hypoglycaemia
CONSCIOUS + CAN SWALLOW:
- fast acting carbohydrate (glucose tablets, glucose 40% gels, glucose liquid, fruit juice), repeat blood glucose after 10-15 mins
- long acting carbohydrate once blood gluucose >4mmol/L (biscuit, bread)
- IM glucagon or IV glucose 10% if patient does not respond to fast acting carb
REDUCED CONSCIOUSNESS/EMERGENCY
- IM glucagon
- IV 10% glucose 150-200ml
- long acting carbohydrate, once blood glucose is >4mmol/L (biscuit, bread, milk or normal carb containing meal)
in malnourished/alcoholic patients, IV glucose should be given alonside thiamine to prevent wernicke's encephalopathy
85
HYPOGLYCAEMIA
Why are patient with diabetes at a particular risk of hypoglycaemia?
In Diabetes there are defects in the physiological defences to hypoglycaemia and there is reduced awareness
86
HYPOGLYCAEMIA
What does prevention of hypoglycaemia include?
Eduction
Correct choice of therapy
Adjusting glucose targets in those at high risk
Specialist support from a MDT
87
T2DM
Is insulin secretion or insulin resistance the driving force of hyperglycaemia in T2DM?
Hepatic insulin resistance is the driving force
88
HYPERGYLCAEMIA
Give a potential consequence of acute hyperglycaemia
Diabetic ketoacidosis and hyperosmolar coma
89
HYPERGYLCAEMIA
Give a potential consequence of chronic hyperglycaemia
Mirco/macrovascular tissue complications
90
Name 5 possible diseases of the pituitary
1. Benign pituitary adenoma
2. Craniopharygioma
3. Trauma
4. Apoplexy/Sheehans
5. Sarcoid/TB
91
Give 3 potential consequences of a pituitary tumour
1. Pressure on local structures - e.g. optic chasm = bilateral hemianopia
2. Pressure on normal pituitary (lack of function) - Hypopituitarism
3. Functioning tumours - e.g. Cushing's, acromegaly, prolactinoma
92
Describe the growth hormone secretion from the anterior pituitary
It is secreted in a pulsatile fashion and increases during deep sleep
93
ACROMEGALY
What is acromegaly?
Overgrowth of all organ systems due to excess growth hormone (GH) production in adults
94
ACROMEGALY
What is gigantism?
Excess GH production in children before fusion of the epiphyses of the long bones
95
ACROMEGALY
what are the clinical features of acromegaly?
SYMPTOMS:
visual disturbance
headaches
rings and shoes are tight
polyuria + polydipsia due to T2DM
tingling in hands
galactorrhoea
menstrual irregularity/erectile dysfunction
SIGNS:
hypertension,
bitemporal hemiopia
prominent jaw + supraorbital ridge
coarse facial appearance
Prognathism (protrusion of lower jaw)
Macroglossia (large tongue)
Spade-like hands
Sweaty palms + oily skin
96
ACROMEGALY
what is the pathophysiology of acromegaly?
GH exerts activity indirectly through IGF-1 or directly on tissue
Excessive IGF- levels mediate most of the skeletal and soft tissue growth like features of acromegaly
97
ACROMEGALY
What can cause acromegaly?
- A benign pituitary adenoma producing excess GH (MOST COMMON)
| - rarely due to hyperplasia
98
ACROMEGALY
Describe the epidemiology of acromegaly
Average age is 40 years
male = female
Reduces life expectancy by 10 years
99
ACROMEGALY
What complications are associated with acromegaly?
type 2 diabetes
sleep aponea
heart disease
arthritis
100
ACROMEGALY
What are the investigations for acromegaly?
1st line = IGF-1 (high)
2nd line = oral glucose tolerance test (gold standard)
3rd line = pituitary function tests
4th line = MRI
also investigate for complications
101
ACROMEGALY
What is the gold standard diagnostic test for acromegaly?
Oral glucose tolerance test - failure of glucose to suppress serum GH
102
ACROMEGALY
what is the management for acromegaly?
1st line = trans sphenoidal surgery
2nd line
- medical = CABERGOLINE (dopamine agonist), bromocriptine is alternative
- OCTEOTIDE (somatostatin analogue) used in moderate/severe disease
3rd line = PEGVISOMANT (GH receptor antagonist)
4th line = radiotherapy
103
ACROMEGALY
Give 3 potential complications of transsphenoidal surgical resection for the treatment of acromegaly
1. Hypopituitarism
2. Diabetes insidious
3. Haemorrhage
4. CNS injury
5. Meningitis
104
ACROMEGALY
What types of medical therapy can be used to treat acromegaly?
somatostatin analogue = octreotide
dopamine agonist = cabergoline
GH receptor antagonist = pegvisomant
105
ACROMEGALY
Give 3 advantages of using dopamine agonists in the treatment of acromegaly
1. No hypopituitarism
2. Oral administration
3. Rapid onset
106
ACROMEGALY
Give 2 disadvantages of dopamine agonists in the treatment of acromegaly
1. Can be ineffective
| 2. Risk of side effects
107
ACROMEGALY
Name a dopamine agonist that can be used as a treatment for acromegaly
Cabergoline
108
ACROMEGALY
Why can somatostatin analogues be used in the treatment of acromegaly?
They inhibit GH release
109
ACROMEGALY
Why can GH receptor antagonists be used in the treatment of acromegaly?
They suppresses IGF-1
110
PROLACTINOMA
What is prolactinoma?
Lactotroph cell tumour of the pituitary
| Prolactin secreting tumour
111
PROLACTINOMA
Name the 2 types of prolactinoma
1. Microprolactinoma = most common, >90%
| 2. Macroprolactinoma = >10mm
112
PROLACTINOMA
what are the causes of prolactinoma?
1. Pituitary adenoma
2. Anti-dopaminergic drugs
3. Head injury - compression of the pituitary stalk
113
PROLACTINOMA
what are the clinical features of prolactinoma
SYMPTOMS:
amenorrhea,
galactorrhoea,
gynaecomastia,
low libido,
erectile dysfunction
SIGNS:
low testosterone,
infertility
visual field defects
headache
114
PROLACTINOMA
Briefly describe the pathophysiology of Prolactinoma
Increased release of prolactin can cause galactorrhoea and can inhibit FSH and LH
Compression of the pituitary stalk
Prevents secretion of dopamine from hypothalamus - stops inhibition of prolactin
115
PROLACTINOMA
what are the investigations for prolactinoma?
Serum prolactin levels - HIGH
| CT head
116
PROLACTINOMA
What is the treatment for prolactinoma?
Dopamine agonists - cabergoline - inhibits prolactin release
| Occasionally transsphenoidal pituitary resection
117
CUSHINGS
What is Cushing's Syndrome?
Chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
118
CUSHINGS
What is Cushing's Disease?
When Cushing's syndrome is caused by a pituitary tumour so excess glucocorticoids due to inappropriate ACTH secretion
119
CUSHINGS
what is the clinical presentation of Cushing's disease?
SYMPTOMS
- bloating + weight gain
- mood change
- increased susceptibility to infection
- menstrual irregularity
- reduced libido
SIGNS
- hypertension
- moon face
- buffalo hump
- central adiposity
- violaceous striae
- muscle wasting + proximal myopathy
- ecchymoses + fragile skin
120
CUSHINGS
what are the causes of excess cortisol? And are they ACTH dependent or independent?
ACTH dependent (ACTH raised):
- Cushing’s disease
- Ectopic ACTH production
- ACTH treatment
ACTH independent (ACTH not raised)
- adrenal adenoma
- iatrogenic
121
CUSHINGS
What is a differential diagnosis of Cushing's syndrome?
Pseudo-Cushing's = excessive alcohol consumption can mimic the clinical and biochemical signs but resolved on alcohol recession
122
CUSHINGS
Describe the epidemiology of Cushing's syndrome
women > men
majority diagnosed 20-50y/o
most common cause is oral steroids
123
CUSHINGS
what are the risk factors?
- long term steroid use
- pituitary adenoma
- adrenal adenoma
- small cell lung cancer
- neuroendocrine tumours
124
CUSHINGS
what are the investigations for Cushing's syndrome?
CONFIRM HYPERCORTISOLISM
- 1st line = overnight dexamethasone suppression test (shows failure of cortisol suppression)
- 24hr urinary free cortisol (2 measurements required)
SOURCE LOCALISATION
- 9am ACTH (elevated = ACTH-dependant cause)
if positive then perform
- high dose dexamethasone suppression test
125
CUSHINGS
what are the results for high dose dexamethasone suppression test for cushings syndrome, disease and ectopic ACTH syndrome?
CUSHINGS SYNDROME
- cortisol = not suppressed
- ACTH = suppressed
CUSHINGS DISEASE
- cortisol = supressed
- ACTH = suppressed
ECTOPIC ACTH SYNDROME
- cortisol = not suppressed
- ACTH = not suppressed
126
CUSHINGS
What is the treatment for Cushing's syndrome?
ACTH-dependent
- cushings disease - 1st line = trans-sphenoidal resection
- ectopic ACTH source - treat underlying cause of cancer
ACTH-independent
- iatrogenic = review need for medication + try weaning
- adrenal tumour = tumour resection/adrenalectomy
127
CUSHINGS
What are some complications associated with Cushing's Syndrome?
cardiovascular disease
hypertension
diabetes mellitus
osteoporosis
128
PHYSIOLOGY
What is the circadian system?
Body clock that regulates your body
| Clear rhythm of cortisol production follows circadian rhythm
129
PHYSIOLOGY
When do cortisol levels peak?
At around 8:30 am
130
PHYSIOLOGY
What's the primary cue that synchronises an organism's biological rhythms?
Light
131
ADDISONS DISEASE
What is adrenal insufficiency?
Adrenocortical insufficiency resulting in a reduction of mineralocorticoids, glucocorticoids and androgens
132
ADDISONS DISEASE
what is Addison's disease?
Primary adrenal insufficiency
Destruction of entire adrenal cortex resulting in mineralocorticoid (aldosterone), glucocorticoid and androgen deficiency
133
ADDISONS DISEASE
what are the causes of Addison's disease?
- autoimmune destruction (21-hydroxylase present in 60-90%) - most common in developed countries
- TB - most common in developing countries
- adrenal metastases- long term steroid use
134
ADDISONS DISEASE
what are the clinical features of Addison's disease?
SYMPTOMS
Lethargy + weakness
N+V
weight loss
'salt cravings'
collapse + shock (addisonian crisis)
SIGNS
Hyperpigmentation (particularly in palmar creases)
loss of pubic hair
hypotension + postural drop
135
ADDISONS DISEASE
What is the treatment for addisons disease?
Hormone replacement
ORAL HYDROCORTISONE - 20-30mg split into 3 doses (largest dose upon waking)
ORAL FLUDROCORTISONE - 50-200 micrograms OD
Patient education
- don't miss any doses
- wear medication alert bracelet/carry steroid card
- double dose of hydrocortisone if they develop intercurrent illness
136
ADDISONS DISEASE
What is the pathophysiology of Addison's disease?
Destruction of the adrenal cortex results in decreased production of the hormones
All steroids reduced
Reduced cortisol levels = increased CRH and ACTH production through feedback
137
ADDISONS DISEASE
What are the investigations for Addison's disease?
1st line = 8-9am cortisol (<100nmol/L = highly suggestive, 100-500nmol/L = refer for ACTH stimulation test)
Gold standard = ACTH stimulation test (short syntacthen test) - failure of rise in cortisol = addisions
Other tests
- 8am ACTH
- adrenal antibodies (anti-21-hydroxylase)
- U&Es (hyponatraemia + hyperkalaemia)
- aldosterone/renin ratio (decreased)
- CT adrenal (atrophied glands)
138
ADDISONS DISEASE
What investigations would you do to determine whether Adrenal insufficiency is primary or secondary?
Primary = adrenal antibodies, very long chain fatty acids, imaging and genetics
Secondary = any steroids?, imaging and genetics
139
ADDISONIAN CRISIS
what are the features of addisonian crisis?
SYMPTOMS
N+V
abdominal pain
trigger e.g. infection or MI
SIGNS
hypotension
hypovolaemic shock
reduced GCS
140
ADDISONIAN CRISIS
what are the causes?
- steroid withdrawal
- severe dehydration
- sepsis
- surgery
141
ADDISONIAN CRISIS
what are the investigations?
12 lead ECG = hyperkalaemic changes (flat P waves, short QT, broad QRS, ST depression + tented T waves)
VBG = metabolic acidosis, hyponatraemia, hyperkalaemia
FBC + CRP
TFTs
once crisis is under control, if patient has not already been investigated for Addisons they should now undergo these tests.
142
ADDISONIAN CRISIS
What is the management of adrenal crisis (addisonian crisis)?
ACUTE
- IV fluids - normal saline
- Corticosteroids = HYDROCORTISONE 100mg IV stat followed by 200mg over 24hrs. Oral replacement after 24 hrs with reduction to maintenance level over 3-4 days
- treat underlying cause
CHRONIC
- long term hydrocortisone + fludrocortisone
| Fluid resuscitation - saline (IV)
143
ADDISONS DISEASE
What would sodium and potassium levels be in someone with adrenal insufficiency?
Hyponatraemia = low sodium
Hyperkalaemia = high potassium
Lack of aldosterone and so less sodium reabsorbed and less potassium excreted
144
CUSHINGS
Why is it important to take a drug history when speaking to someone with potential Cushing's?
To exclude steroid use as a potential cause
145
GRAVES DISEASE
Briefly describe the mechanism of thyroid destruction
Cytotoxic (CD8+) T cell mediated thyroglobulin and Thyroid peroxidase (TPO) antibodies may cause secondary damage (alone have no effect)
Antibodies against the TSH receptor may block the effect of TSH (uncommon)
146
GRAVES DISEASE
What are the main 3 types of cells that cause thyroid destruction?
1. Cytotoxic T cells
2. Thyroglobulin
3. TPO antibodies
147
GRAVES DISEASE
Briefly describe the pathophysiology of Grave's disease
Specific serum IgG (TSH receptor stimulating antibodies) bind to TSH receptors in thyroid
Behave like TSH – stimulate T3 and T4 production
This results in excess secretion and hyperplasia of thyroid follicular cells – causing hyperthyroidism and graves ophthalmopathy
148
GRAVES DISEASE
what is the clinical presentation of Grave's opthlmopathy?
SYMPTOMS
Eye discomfort
Grittiness
increased tear production
Photophobia
Diplopia
reduced acuity
SIGNS
Exophthalmos – protruding eye
Proptosis – eye protrudes beyond orbit
Conjunctival oedema
Corneal ulceration
Ophthalmoplegia – paralysis of eye muscles
149
GRAVES DISEASE
what is the clinical presentation of grave's dermopathy?
Pretibial myxoedema – raised, purple red symmetrical skin lesions over anterolateral aspects of shin
Thyroid acropachy – clubbing, swollen fingers and periosteal bone formation
150
GRAVES DISEASE
what is the spectrum of orbital signs for graves eye disease?
NOSPECS
- No signs
- Only signs, no symptoms (lid lag or retraction only)
- Soft tissue involvement (swelling of soft tissue around eyes)
- Proptosis
- Extraocular muscle involvement (ophthalmoplegia, causes diplopia)
- corneal involvement
- sight loss (due to optic nerve involvement)
151
GRAVES DISEASE
what is the treatment for Grave's ophthalmology?
Conservative treatment – smoking cessation and sunglasses
Anti-thyroid medication e.g. carbimazole
IV METHYLPREDNISOLONE a
surgical decompression/eyelid surgery
152
GRAVES DISEASE
Name 5 risk factors for Graves disease
1. Female
2. Genetic association
3. E.coli
4. Smoking
5. Stress
6. High iodine intake
7. Autoimmune diseases
153
GRAVES DISEASE
Name 5 autoimmune diseases associated with thyroid autoimmunity
1. T1DM
2. Addison's disease
3. Pernicious anaemia
4. Vitiligo
5. Alopecia areata
6. Rheumatoid arthritis
154
GRAVES DISEASE
What would you see histological in someone with Graves disease?
Lymphocyte infiltration and thyroid follicle destruction
155
THYROID GOITRE
What is goitre?
Palpabel and visible thyroid enlargement
156
THYROID GOITRE
Why does goitre occur and when is is most commonly found?
Due to TSH receptor stimulation resulting in thyroid growth
| Seen in hypo and hyperthyroidism
157
THYROID GOITRE
Name 4 types of sporadic non toxic goitre
1. Diffuse --> physiological --> Graves
2. Multi nodular
3. Solitary nodule
4. Dominant nodule
158
HYPERTHYROIDISM
Define hyperthyroidism
Overactivity of the thyroid gland
159
HYPERTHYROIDISM
Define thyrotoxicosis
Excess of thyroid hormone in the blood (can be used interchangeably with hyperthyroidism)
160
HYPERTHYROIDISM
Name the 3 mechanisms of how hyperthyroidism may come about
1. Overproduction of thyroid hormone
2. Leakage of preformed hormone from the thyroid
3. Ingestion of excess thyroid hormone
161
HYPERTHYROIDISM
what are the causes of hyperthyroidism?
PRIMARY
- graves disease
- toxic multinodular goitre (iodine deficiency)
- toxic adenoma
- subclinical hyperthyroidism
- drugs (amiodarone)
SECONDARY
- pituitary adenoma
- ectopic tumour
- hypothalamic tumour
162
HYPERTHYROIDISM
Name 4 drugs which can induce hyperthyroidism
1. Iodine
2. Amiodarone
3. Lithium
4. Radioconstrast agents
163
HYPERTHYROIDISM
what are the clinical features of hyperthyroidism?
SYMPTOMS:
- weight loss
- heat intolerance and sweating
- palpitations
- menstrual irregularlity
SIGNS:
- postural tremor
- palmar erythema
- hyperreflexia
- goitre
- lid lag + retraction
164
HYPERTHYROIDISM
What investigations are done to diagnose hyperthyroidism?
TFTs:
primary = high T3 and T4, low TSH
secondary = high T3 and T4, high TSH
Antibodies:
Anti-TSH receptor = graves
165
HYPERTHYROIDISM
What are the thyroid function test results in primary hyperthyroidism?
high T4
high T3
low TSH
166
HYPERTHYROIDISM
What are the thyroid function rests in secondary hyperthyroidism?
high T4
high T3
high TSH
167
HYPERTHYROIDISM
What are the 4 main treatments for hyperthyroidism?
1. Beta blockers - PROPRANOLOL
2. Anti-thyroid drugs - CARBIMAZOLE
3. Radioiodine
4. Surgery - partial/total thyroidectomy
168
HYPERTHYROIDISM
Why are beta blockers used to treat hyperthyroidism?
For rapid control of symptoms
169
HYPERTHYROIDISM
Give examples of anti-thyroid drugs and why are they used?
- Carbimazole, methimazole, proplythiouracil (PTU) - (thionamides)
- Decreases synthesis of new thyroid hormone by targeting thyroid peroxidase
- PTU also inhibits conversion of T4 to T3
170
HYPERTHYROIDISM
Give 4 poor prognostic factors of those on anti-thyroid drugs
1. Severe biochemical hyperthyroidism
2. Large goitre
3. Male
4. Young age of disease onset
171
HYPERTHYROIDISM
Give 5 side effects of anti-thyroid drugs
1. Rash
2. Arthralgia
3. Hepatitis
4. Neuritis
5. Vasculitis
6. Agranulocytosis - very serious
172
HYPERTHYROIDISM
Why can radioiodine be used as a treatment for hyperthyroidism?
Emit beta particle that destroy thyroid follicle and therefore reducing the production of thyroid hormones
173
HYPERTHYROIDISM
Give 4 potential consequences of a partial thyroidectomy
1. Bleeding
2. Hypoglycaemia
3. Hypothyroidism
4. Recurrent laryngeal nerve palsy
174
HYPERTHYROIDISM
What is a complication of hyperthyroidism?
- Thyroid crisis/storm
- osteoporosis
- proximal myopathy
- thyrotoxic crisis
- iatrogenic (agranulocytosis from carbimazole, congenital malformations, foetal goitre)
175
HYPERTHYROIDISM
Briefly explain thyroid crisis/storm
Rapid deterioration of thyrotoxicosis
Hyperpyrexia, tachycardia and extreme restlessness Delirium --> coma --> death
176
HYPERTHYROIDISM
What is the treatment for a thyroid crisis?
symptomatic treatment e.g. paracetamol
treatment of precipitating event
beta blockers e.g. IV propranolol
anti-thyroid drugs - methimazole/propylthiouracil
lugols iodine
dexamethasone 4mg IV QDS to stop conversion of T4 to T3
177
HYPOTHYROIDISM
Define hypothyroidism
Under-activity of the thyroid gland
178
HYPOTHYROIDISM
Name the 3 types of hypothyroidism
1. Primary - absence/dysfunction of thyroid gland (problem with thyroid gland itself)
2. Secondary - reduced TSH from anterior pituitary (pituitary gland problem)
3. Tertiary - associated with treatment withdrawal
179
HYPOTHYROIDISM
Briefly describe the pathophysiology of primary hypothyroidism
Underactivity usually primary from disease of the thyroid but may be secondary due to hypothalamic-pituitary disease resulting in reduced TSH
180
HYPOTHYROIDISM
Briefly describe the pathophysiology of secondary hypothyroidism
Reduced release or production of TSH so reduced thyroid hormone release
181
HYPOTHYROIDISM
Briefly describe the pathophysiology of tertiary hypothyroidism
Thyroid gland overcompensates until it can reestablish correct concentration fo thyroid hormone
182
HYPOTHYROIDISM
what are the causes of primary hypothyroidism
- autoimmune thyroiditis (hashimotos thyroiditis)
- De Quervains thyroiditis (follows viral prodrome)
- post-partum thyroiditis
- iodine deficiency
- post-thyroidectomy or post-radioiodine
- drugs (amiodarone, lithium, anti-thyroid drugs e.g. carbimazole)
183
HYPOTHYROIDISM
Name 4 drugs that can cause hypothyroidism
1. Carbimazole (used to treat hyperthyroidism)
2. Amiodarone
3. Lithium
4. Iodine
184
HYPOTHYROIDISM
Name 3 causes of secondary hypothyroidism
- compression from a pituitary tumour
- hypothalamic tumours
- drugs (cocaine, steroids + dopamine)
185
HYPOTHYROIDISM
Why can amiodarone cause both hypo and hyperthyroidism?
Because it is iodine rich
186
HYPOTHYROIDISM
what are the clinical features of hypothyroidism?
SYMPTOMS
- weight gain
- cold intolerance
- lethargy
- dry skin
- constipation
- menorrhagia (followed by oligomenorrhoea + amenorrhoea)
SIGNS
- bradycardia
- goitre
- decreased deep tendon reflexes
- carpal tunnel
- hair loss
- loss of lateral aspect of eyebrows
- dry + cold skin
- coarse hair
- hoarse voice (unusual)
187
HYPOTHYROIDISM
What investigations are conducted to diagnose hypothyroidism?
- TFTs
- anti-TPO antibodies = if present suggests Hashimotos
- inflammatory markers = if raised suggests de Quervains
To consider
- USS
- fasting lipids
- serum glucose + HbA1c
- FBC + B12 levels
- coeliac serology
188
HYPOTHYROIDISM
What are the TFT results for primary hypothyroidism?
- High TSH
- low T4
189
HYPOTHYROIDISM
What are the TFT results for secondary hypothyroidism?
- normal/low TSH
- low T4
190
HYPOTHYROIDISM
Name 3 antibodies that may be present in the serum in someone with autoimmune thyroiditis
1. TPO (thyroid peroxidase)
2. Thyroglobulin
3. TSH receptor
191
HYPOTHYROIDISM
What is the treatment for primary hypothyroidism?
- LEVOTHYROXINE 50-100mg OD
- have lower starting dose (25mg OD) if >65 or history of IHD
- review dose every 8-12 weeks when dose is changed
192
HYPOTHYROIDISM
which drugs can interact with levothyroxine? what advice should you give?
- iron
- calcium carbonate
- should be given >4 hours apart from levothyroxine as they reduce it's absorption
193
HYPOTHYROIDISM
what are the side effects of levothyroxine?
- hyperthyroidism
- AF
- osteoporosis
- angina
194
HYPOTHYROIDISM
what are the complications of hypothyroidism?
- hypercholesterolaemia
- carpal tunnel
- peripheral neuropathy
- myoxedema coma
- thyroid lymphoma
195
HYPOTHYROIDISM
what is a myxoedema coma?
- severe form of hypothyroidism
- is life-threatening
196
HYPOTHYROIDISM
what are the clinical features of mxyoedema coma?
- deterioration in mental state
- confusion
- psychosis
- constipation
- bradycardia
- hypotension
- hypothermia
- myxoedematous face (puffiness, macroglossia, ptosis, periorbital oedema)
- hypoventilation
197
HYPOTHYROIDISM
what is the management for mxyoedema coma?
- ITU/HDU admission
- IV thyroid replacement (levothyroxine)
- antibiotics
- IV hydrocortisone (100mg)
198
HASHIMOTOS THYROIDITIS
What is Hashimoto's thyroiditis?
Hypothyroidism due to aggressive destruction of thyroid cells
199
HASHIMOTOS THYROIDITIS
Give 3 symptoms of Hashimoto's thyroiditis
1. Rapid formation of Goitre
2. Dyspnoea or dysphagia
3. General hypothyroidism symptoms
200
HASHIMOTOS THYROIDITIS
Name 3 triggers of Hashimoto's thyroiditis
1. Iodine
2. Infections
3. Smoking
4. Stress
201
HASHIMOTOS THYROIDITIS
What are the investigations for Hashimoto's thyroiditis?
TFTs - high TSH, low T3 and T4
high anti-TPO
202
HASHIMOTOS THYROIDITIS
What is the treatment for Hashimoto's thyroiditis?
Levothyroxine
203
HASHIMOTOS THYROIDITIS
what are the complications of Hashimoto's thyroiditis?
Hashimoto's encephalopathy
204
HYPERTHYROIDISM
What disease would you treat with Carbimazole?
Hyperthyroidism/Graves disease
205
HYPOTHYROIDISM
What disease would you treat with Levothyroxine?
Hypothyroidism
206
POSTERIOR PITUITARY
Name 3 disease associated with the posterior pituitary
1. Cranial diabetes insipidus - lack of ADH
2. Nephrogenic diabetes insipidus - resistance to action of ADH
3. Syndrome of antidiuretic hormone secretion - too much ADH release inappropriately
207
DIABETES INSIPIDUS
Define diabetes insipidus
Diabetes insipidus (DI) is an inability of the body to concentrate urine.
Passage of large volumes (>3L/day) of dilute urine due to impaired water reabsorption in the kidney due to hypo secretion or insensitivity to ADH
208
DIABETES INSIPIDUS
Name the 2 types of DI
1. Cranial (central) DI = reduced vasopressin (ADH) produced by hypothalamus and secreted by the posterior pituitary
2. Nephrogenic DI = impaired response of the kidney to ADH (kidneys are resistant to ADH)
209
DIABETES INSIPIDUS
what are the clinical features of DI?
SYMPTOM
- Polyuria + nocturia
- Polydipsia
- No glycosuria
- fatigue
SIGNS
Volume depletion
- Dry mucosa
- Sunken eyes
- Changes in skin turgidity
- Can lead to dehydration
Hypernatremia
- irritability
- hyper-reflexia
- confusion
- bitemporal hemianopia (when there is a craniopharyngioma)
210
DIABETES INSIPIDUS
what are the causes of cranial(central) DI?
CONGENITAL
- malformations of hypothalamus
- wolfram syndrome
ACQUIRED
- pituitary surgery
- tumours (craniopharyngiomas + metastasis, NOT pituitary adenomas)
- traumatic brain injury
- subarachnoid haemorrhage
- CNS infections (meningitis + encephalitis)
- pituitary stalk disease (sarcoidosis)
- drugs (phenytoin)
211
DIABETES INSIPIDUS
what are the causes of nephrogenic DI?
CONGENITAL
- mutations in vasopressin or aquaporin receptors
ACQUIRED
- drugs (lithium, gentamicin, cisplatin)
- renal disease (renal amyloid, obstructive uropathy)
- electrolyte disturbance (hypokalaemia, hypercalcaemia)
212
DIABETES INSIPIDUS
Give 3 possible differential diagnosis's of DI
1. DM
2. Hypokalaemia
3. Hypercalcaemia
213
DIABETES INSIPIDUS
what are the investigations for diabetes insipidus?
- Urine + serum osmolality = low urine osmolality + high serum osmolality
- U&Es = normal/raised Na
- serum glucose (to rule out DM)
- 24hr urine output (if <3L, DI is unlikely)
- Water deprivation test = low urine + high serum osmolality
- desmopressin suppression test = in cDI, urine volume decrease + osmolality increases, in nDI no response
To consider
- MRI pituitary
- anterior pituitary function tests
- genetic testing
214
DIABETES INSIPIDUS
how do you differentiate between cranial and nephrogenic DI?
DESMOPRESSIN SUPPRESSION TEST
- cranial DI = decreased urine volume + increased urine osmolality
- nephrogenic DI = no response
215
DIABETES INSIPIDUS
when is the desmopressin suppression test contraindicated?
- hypernatremia
- uncontrolled diabetes mellitus
- kidney insufficiency
- pregnancy
216
DIABETES INSIPIDUS
What are the test results for serum osmolality, urine osmolality + post desmopressin urine osmolality in cranial + nephrogenic DI?
CRANIAL
- high serum osmolality
- low urine osmolality
- high urine osmolality post desmopressin suppression
NEPHROGENIC
- high serum osmolality
- low urine osmolality
- no response post desmopressin suppression
217
DIABETES INSIPIDUS
What is the treatment for cranial DI?
- desmopressin
- manage fluid balance (water readily available in patients able to manage own fluids, IV fluids for those not able to)
- low sodium diet
218
DIABETES INSIPIDUS
What is the treatment for nephrogenic DI?
- manage fluid balance
- treat underlying cause
- sodium restriction
- thiazide diuretics (BENDROFLUMETHIAZIDE)
219
DIABETES INSIPIDUS
Do you have hyponatraemia or hypernatraemia in diabetes insipidus?
Hypernatraemia
220
POLYURIA
Give 4 causes of polyuria
1. Hypokalaemia
2. Hypercalcaemia
3. Hyperglycaemia
4. Diabetes insipidus
221
SIADH
What is SIADH?
Syndrome of inappropriate ADH secretion
- increased ADH released from posterior pituitary or ectopic source
- results in water retention + dilution of blood
- results in hyponatraemia
222
SIADH
what are the clinical features of SIADH?
MILD
- N+V
- headache
- lethargy
MODERATE
- weakness
- muscle aches
- confusion
- ataxia
SEVERE
- reduced consciousness
- seizures
- respiratory arrest
All patients are EUVOLAEMIC (no features of hyper/hypovolaemia)
223
SIADH
what are the causes of SIADH?
NEURO
- meningitis
- encephalitis
- intracranial haemorrhage
- stroke
MALIGNANCY
- small cell lung cancer
INFFECTION
- pneumonia
- TB
ENDOCRINE
- hypothyroidism
DRUGS
- SSRIs + TCAs
- PPIs
- Carbamazepine
- Cyclophosphamide
- Sulfonylureas
OTHER
- porphyria
- PEEP
224
SIADH
what are the investigations for SIADH?
- urine osmolality = inappropriately high in relation to serum osmolality
- urine sodium concentration = high
- ADH levels
- U and Es (low sodium normal potassium),
- fluid status
distinguish SIADH from salt & water depletion - test with 1-2L of
0.9% saline:
* Sodium depletion will respond
* SIADH will NOT RESPOND
225
SIADH
what are the diagnostic criteria?
- Low plasma osmolality <275mOsm/kg
- High urine osmolality >100mOsm/kg
- High urine sodium >30mmol/L
- Clinical euvolaemia
- Exclusion of glucocorticoid deficiency or hypothyroidism
226
SIADH
what is the pathophysiology of SIADH?
- Excess release of ADH will result in increased insertion of aquaporin 2 channels in apical membrane of collecting duct
- Excess water retention which dilutes blood plasma
- Result in hyponatremia as Na+ conc decreases
227
SIADH
Describe the treatment for SIADH
ACUTE (<48hrs)
- hypertonic 3% NaCl
CHRONIC (>48hrs)
- Na correction maximum 10mmol/L per day
- mild-moderate asymptomatic cases = fluid restriction (750-1000ml per day)
- severe or symptomatic = demeclocycline or tolvaptan
228
SIADH
How do you treat asymptomatic SIADH?
Fluid restriction
229
SIADH
How do you treat very symptomatic SIADH?
Give 3% saline (hypertonic)
demeclocycline or tolvaptan
230
SIADH
Would you expect a patient with SIADH to be hypovolaemic, euvolaemic or hypervolaemic?
Euvolaemic
231
SIADH
Would you associate SIADH with hyponatraemia or hypernatraemia?
Hyponatraemia - <135 mmol/L
232
SIADH
Would you associate SIADH with plasma hypo-osmolality or hyper-osmolality?
Plasma hypo-osmolality - <275 mOsmol/Kg
233
SIADH
Would you associate SIADH with a high to low urine osmolality?
High urine osmolality
234
HYPONATRAEMIA
Define hyponatraemia
<135 mmol/L
| Biochemically severe = serum sodium <125 mmol/L
235
POSTERIOR PITUITARY
What stimulates the posterior pituitary to release ADH?
Osmoreceptors in the hypothalamus detect raised plasma osmolality Posterior pituitary is signalled to release ADH
236
PITUITARY ADENOMA
Give 4 local effects a pituitary adenoma
1. Headaches
2. Visual field defects - bitemporal hemianopia
3. Cranial nerve palsy and temporal lobe epilepsy
4. CSF rhinorrhoea
237
PITUITARY DYSFUNCTION
What investigations are done when pituitary dysfunction is suspected?
Hormonal tests If hormonal tests are abnormal or tumour mass effect perform MRI pituitary
238
THYROID DISEASE
What do you test the thyroid axis for in pituitary disease?
Measure Free T4 and TSH
239
HYPOTHYROIDISM
What is the affect of primary hypothyroidism on TSH and T4 levels?
TSH highT4 low
240
THYROID DISEASE
What is the effect of secondary hypopituitarism on TSH and T4 levels?
TSH low
| T4 low
241
PROLACTINOMA
What can lead to elevated levels of prolactin?
1. Stress
2. Drugs
3. Pressure on pituitary stalk
4. Prolactinoma
242
PITUITARY
What is the best radiological evaluation for the pituitary?
MRI - better visualisation of soft tissue and vascular structures
243
DIABETES PHARMACOLOGY
In what class of drugs does metformin belong?
Biguanide
244
DIABETES PHARMACOLOGY
Give an example of a sulfonylurea
gliclazide
245
DIABETES PHARMACOLOGY
what are the side effects of sulfonylureas?
- weight gain
- hypoglycaemia
246
HYPOGLYCAEMIA
What are the physiological defences to hypoglycaemia?
Release of glucagon and adrenaline
247
HYPOGLYCAEMIA
What are the symptoms of hypoglycaemia?
Autonomic - sweating, tremor, palpitations
Neuroglycopenic - confusion, drowsiness, incoordination
Severe neuroglycopenic - convulsions, coma
248
HYPOGLYCAEMIA
Name 3 other types of diabetes other than T1DM, T2DM and DI
1. Maturity onset diabetes of the young (MODY)
2. Permanent neonatal diabetes
3. Maternal inherited diabetes and deafness
249
DIABETES MELLITUS
Name 3 exocrine causes of Diabetes
1. Inflammatory - actue/chronic pancreatitis
2. Hereditary haemochromatosis
3. Pancreatic neoplasia
4. Cystic fibrosis
250
DIABETES MELLITUS
Name 3 endocrine causes of Diabetes
1. Acromegaly
2. Cushing's syndrome
3. Peochromocytoma
251
PHEOCHROMOCYTOMA
What is Pheochromocytoma?
A rare catecholamine secreting tumour in the adrenal medulla (chromatin cells)
252
PHEOCHROMOCYTOMA
what are the different types of pheochromocytoma?
1. Familial type - more NAd
| 2. Sporadic - more Ad
253
PHEOCHROMOCYTOMA
what are the clinical features of pheochromocytoma?
SYMPTOMS
Headache
Profuse Sweating
Palpitations
Tremor
SIGNS
Hypertension
Postural hypotension
Tremor
hypertensive retinopathy
Pallor
254
PHEOCHROMOCYTOMA
What are the investigations for pheochromocytoma?
- Plasma metanephrines and normetanephrines
- 24 hour urinary total catecholamines
- CT – look for tumour
255
PHEOCHROMOCYTOMA
What is the treatment for pheochromocytoma?
Without HTN crisis:
1st Line = Alpha blockers (PHENOXYBENZAMINE)
Most patients will eventually get the tumour removed and then managed medically.
With HTN crisis:
1st Line = Antihypertensive agents (PHENTOLAMINE)
256
PHEOCHROMOCYTOMA
What is the major complication of surgery on a patient with a pheochromocytoma?
Can stoke out during surgery due to rapid effect of adrenaline on the BP
257
PHEOCHROMOCYTOMA
What is the major concern in someone with pheochromocytoma?
Dangerous cause of hypertension
258
PHEOCHROMOCYTOMA
What is the management of a phaeochromocytoma crisis?
Non-competitive alpha-blocker e.g. phenoxybenzamine
Excision of paraganglioma
Biochemistry: measure plasma and serum metanephrines
259
DIABETES MELLITUS
What are the 3 main sites where microvascular complications of Diabetes cause particular damage?
1. Retina = retinopathy
2. Glomerulus = nephropathy
3. Nerve sheath = neuropathy
260
DIABETES MELLITUS
How long after a young patient has been diagnosed do microvascular complications start to manifest?
10-20 years after diagnosis
261
DIABETIC NEPHROPATHY
What is the hallmark of diabetic nephropathy?
Development of proteinuria and progressive decline in renal function
262
DIABETIC NEPHROPATHY
What happens to the glomerular basement membrane in someone with diabetic nephropathy?
On microscopy there is thickening of the glomerular basement membrane
263
DIABETIC NEPHROPATHY
Give one way in which the presentation of diabetic nephropathy differs between T1 and T2DM
T1DM - microalbuminuria develops 5-10 years after diagnosis
| T2DM - microalbuminuria is often present at diagnosis
264
DIABETIC NEPHROPATHY
Give 2 risk factors for diabetic nephropathy
1. Poor blood pressure
| 2. Poor blood glucose control
265
DIABETIC NEPHROPATHY
Describe the treatment for diabetic nephropathy
1. Glycaemic and BP control
2. Angiotensin receptor blockers/ACE inhibitors - RAMIPRIL or CANDESARTAN
3. Proteinuria and cholesterol control
266
DIABETIC NEUROPATHY
what is the distribution of diabetic neuropathy?
Distal symmetrical neuropathy
267
DIABETIC NEUROPATHY
Give 5 risk factors for diabetic neuropathy
1. Poor glycaemic control
2. Hypertension
3. Smoking
4. High HbA1c
5. Overweight
6. Long duration DM
268
DIABETIC NEUROPATHY
Why do isolated mononeuropathies result from in diabetic neuropathy?
Occlusion of vasa nervorum - small arteries that provide blood supply to peripheral nerves
269
DIABETIC NEUROPATHY
Why do more diffuse neuropathies arise in diabetic neuropathy?
Accumulation of fructose and sorbitol which disrupts the structure and formation of the nerve
270
DIABETIC NEUROPATHY
Give 3 major clinical consequences of diabetic neuropathy
1. Pain
2. Autonomic neuropathy
3. Insensitivity
271
DIABETIC NEUROPATHY
Describe the pain associated with diabetic neuropathy
Burning
Paraethesia
Allodynia - triggering of pain from stimuli that doesn't usually cause pain
272
DIABETIC NEUROPATHY
What is autonomic neuropathy in relation to diabetic neuropathy?
Damage to the nerves that supply body structures that regulate function such as BP, HR, bowel/bladder emptying
273
DIABETIC NEUROPATHY
Give 5 signs of autonomic neuropathy in diabetic neuropathy
1. Hypotension
2. HR affected
3. Diarrhoea/constipation
4. Incontinence
5. Erectile dysfunction
6. Dry skin
274
DIABETIC NEUROPATHY
What are the consequences of insensitivity as a result of diabetic neuropathy?
Insensitivity --> foot ulceration --> infection --> amputation
275
DIABETIC NEUROPATHY
Describe the distribution of insensitivity as a result of diabetic neuropathy
Glove and sticking distribution - starts in the toes and moves proximally
276
DIABETIC NEUROPATHY
Describe the treatments for diabetic neuropathy
1. Improve glycaemic control
2. tricyclic antidepressants - AMITRIPTYLINE
3. Pain relief - PARACETAMOL and TRAMADOL
277
DIABETIC NEUROPATHY
Give 5 ways in which amputation can be prevented in someone with diabetic neuropathy
1. Screening for insensitivity
2. Education
3. MDT foot clinics
4. Pressure relieving footwear
5. Podiatry
6. Revascularisation and antibiotics
278
DIABETIC NEUROPATHY
What are the 4 main threats to skin and subcutaneous tissues in someone with diabetic neuropathy
1. Infections
2. Ischaemia
3. Abnormal pressure
4. Wound environments
279
DIABETIC NEUROPATHY
Would there be increased or decreased pulses in diabetic neuropathic foot?
Decreased foot pulses
280
DIABETES MELLITUS
what infections can poorly controlled diabetes lead to?
1. UTIs
2. Staphylococcal infection of skin
3. Mucocutaneous candidiasis
4. Pyelonephritis
5. TB
6. Pneumonia
7. rectal abscess
281
DIABETES PHARMACOLOGY
Why does the site of insulin injection need to be varied day to day?
Can cause lipohypertrophy if the same site is used everyday
282
PRIMARY HYPERALDOSTERONISM
what are the causes?
- bilateral idiopathic adrenal hyperplasia (most common)
- adrenal adenoma = Conn's syndrome
- unilateral hyperplasia
- familial hyperaldosteronism
- adrenal carcinoma
283
CONNS SYNDROME
What is Conn's syndrome?
Primary hyperaldosteronism caused by an adrenal adenoma
High aldosterone levels independent of RAAS activation - H20 and sodium retention and potassium excretion
284
CONNS SYNDROME
What are the clinical features of Conn's syndrome?
SYMPTOMS
- lethargy
- mood disturbance
- paraesthesia + muscle cramps
SIGNS
- refractory hypertension
- metabolic alkalosis
285
CONNS SYNDROME
A deficiency in which electrolyte causes the symptoms of Conn's syndrome?
HYPOKALAEMIA
causes:
1. Muscle weakness
2. Tiredness
3. Polyuria
286
CONNS SYNDROME
What hormone is raised in Conn's syndrome and what hormone is reduced? Where are these hormones synthesised?
1. Aldosterone is raised - synthesised in the zone glomerulosa
2. Renin is reduced - synthesised in the juxta-glomerular cells
287
CONNS SYNDROME
What investigations might you do in someone to confirm a diagnosis of Conn's syndrome?
1st line = aldosterone renin ratio (high aldosterone + low renin)
serum U&Es = hypokalaemia + hypernatraemia
high resolution CT abdomen
adrenal venous sampling
288
CONNS SYNDROME
Give 4 ECG changes you might see in someone with Conn's syndrome
HYPOKALAEMIC ECG
1. Increased amplitude and width of P waves
2. Flat T waves
3. ST depression
4. Prolonged QT interval
5. U waves
289
CONNS SYNDROME
What is the treatment for Conn's syndrome?
1st line
- laparoscopic adrenalectomy for unilateral
- spironolactone for bilateral
2nd line
- spironolactone if surgery is inappropriate in unilateral disease
290
HYPERKALAEMIA
What is hyperkalaemia?
Excess of potassium Serum K+ >5.5 mmol/L
| Serum K+ >6.5 mmol/L = medical emergency
291
HYPERKALAEMIA
what are the clinical features of hyperkalaemia?
SYMPTOMS
Fatigue
Palpitations
Muscle weakness
Muscle cramps
Paresthesia
SIGNS
Arrhythmias
Reduced power
Reduced reflexes
Signs of underlying cause
292
HYPERKALAEMIA
what are the causes of hyperkalaemia
IMPAIRED EXCRETION
- AKI and CKD
- drugs (spironolactone, ACEi, heparin)
- renal tubular acidosis (T4)
- Addisons disease
INCREASED INTAKE
- IV therapy
- increased dietary intake
- massive blood transfusion
SHIFT TO EXTRACELLULAR
- metabolic acidosis
- rhabdomyolysis
- DKA
- iatrogenic (digoxin, beta-antagonists)
293
HYPERKALAEMIA
what are the investigations?
12 lead ECG = flat P waves, short QT interval, broad QRS, ST changes + tented T waves
U&Es = high serum K+
Lithium-heparin sample
VBG - check for acidosis
294
HYPERKALAEMIA
What ECG changes might you see in someone with hyperkalaemia?
GO - absent/flat P waves
GO LONG - prolonged PR
GO TALL - Tall T waves
GO WIDE - Wide QRS
295
HYPERKALAEMIA
What is the treatment for hyperkalaemia?
CARDIAC MEMBRANE PROTECTION
- 10ml 10% IV calcium gluconate or calcium chloride given immediately
POTASSIUM REDUCTION
- insulin/dextrose infusion
- nebulised salbutamol
- potassium binders (sodium zirconium cyclosilicate or calcium resonium)
- sodium bicarbonate
- haemodialysis
296
HYPERKALAEMIA
What is a complication for someone with hyperkalaemia?
cardiac arrhythmias which can be life-threatening
297
HYPOKALAEMIA
What is hypokalaemia?
Deficiency in potassium
Serum K+ <3.5 mmol/L
Serum K+ <2.5 mmol/L = medical emergency
298
HYPOKALAEMIA
what are the clinical features of hypokalaemia?
SYMPTOMS:
- fatigue
- muscle weakness
- palpitations
- constipation (from diminished peristalsis)
SIGNS:
- hypotonia
- diminished deep tendon reflexes
299
HYPOKALAEMIA
Give 3 causes of hypokalaemia
- poor intake
- excessive loss (vomiting, diarrhoea, high-stoma output, dialysis)
- diuretic use (loop + thiazide)
- insulin or salbutamol use
- metabolic alkalosis
300
HYPOKALAEMIA
what are the investigations?
- serum U&Es
- serum magnesium (hypomagnesaemia)
- ECG
301
HYPOKALAEMIA
What ECG changes might you see in someone with hypokalaemia?
1. Increased amplitude and width of P waves
2. ST depression
3. Flat T waves
4. U waves
5. QT prolongation
302
HYPOKALAEMIA
What is the treatment for hypokalaemia?
POTASSIUM REPLACEMENT
- mild to moderate = oral supplements (Sando-K)
- severe = 20-40mmol IV KCl in 0.9% saline.
- the fastest rate of correction is 10mmol/hr so 1L bag with 40mmol KCl is run over 4hrs or more
TREAT UNDERLYING CAUSE
303
HYPOKALAEMIA
What are the complications of hypokalaemia?
- cardiac arrhythmias (VT/VF, long QT, torsades de pointes)
- respiratory weakness
- metabolic alkalosis
- hyperkalaemia (due to over-correction)
304
THYROID CANCER
Name 5 types of thyroid cancer
1. Papillary - thyroid epithelium
2. Follicular - thyroid epithelium
3. Anaplastic - thyroid epithelium
4. Lymphoma
5. Medullary - calcitonin C cells
305
THYROID CANCER
What types of thyroid cancers are usually asymptomatic thyroid nodule (usually hard and fixed)?
Papillary
Follicular
Anaplastic
306
THYROID CANCER
what is the clinical presentation of thyroid cancer?
- In 90% present as thyroid nodules
- Occasionally they present with cervical lymphadenopathy or with lung, cerebral, hepatic or bone mets.
- If thyroid gland increases in size, becomes hard and irregular in shape think cancer
- May experience dysphagia or hoarseness of voice if tumour presses on surrounding structures
307
THYROID CANCER
How does a medullary cancer of the thyroid present?
Diarrhoea
Flushing episodes
Itching
308
THYROID CANCER
Why is an anaplastic cancer of the thyroid one of the most aggressive cancers?
Cancer of the follicular cells of the thyroid but doesn't retain original cell features like iodine uptake or synthesis of thyroglobulin
309
THYROID CANCER
What hormone does a medullary cancer of the thyroid produce?
Calcitonin from C cells
310
THYROID CANCER
What is the most common form of thyroid cancer?
Papillary - 70%, young people, 3x more common in women
| Follicular - 20%
311
THYROID CANCER
What investigations can you do to confirm a thyroid cancer?
Fine needle aspiration
For a Medullary cancer - elevated serum calcitonin
Blood tests – check TFTs (TSH, T4, T3) – check if hyper or hypo thyroid
Ultrasound - benign/malignant
312
THYROID CANCER
What is the treatment for thyroid cancer?
- LEVOTHYROXINE T4 to keep TSH reduced as this is a growth factor for cancer Papillary and follicular
- total thyroidectomy
- ablative radioactive iodine Anaplastic and lymphoma
- external radiotherapy to provide relief
- largely palliative Medullary
- total thyroidectomy and prophylactic central lymph node dissection
313
DE QUERVAINS THYROIDITIS
what is de quervain's thyroiditis?
Transient hyperthyroidism sometimes results from acute inflammation of
the thyroid gland, probably due to viral infection
314
DE QUERVAINS THYROIDITIS
what is the clinical presentation of de quervain's thyroiditis?
Usually accompanied by fever, malaise and pain in the neck
315
DE QUERVAINS THYROIDITIS
what is the treatment for de quervain's thyroiditis?
Treat with aspirin and only give prednisolone for severely symptomatic
cases
316
DIABETES PHARMACOLOGY
what are the side effects of metformin?
GI upset
AKI
N+V
lactic acidosis
317
DIABETES PHARMACOLOGY
what is the mechanism of action for SGLT-2 inhibitors?
inhibits resorption of glucose in the kidney causing urinary glucose excretion
318
DIABETES PHARMACOLOGY
what are the side effects of SGLT-2 inhibitors?
UTI
319
DIABETES PHARMACOLOGY
what is the mechanism of action for pioglitazone?
PPAR gamma agoinsts reduce peripheral resistance
320
DIABETES PHARMACOLOGY
what are the side effects of pioglitazones?
Weight gain
Fluid retention
Hepatotoxicity
Bladder cancer
321
DIABETES PHARMACOLOGY
Give an example of DPP-4 inhibitors
linagliptin
sitagliptin
322
DIABETES PHARMACOLOGY
what is the mechanism of action for DPP-4 inhibitors?
prevent degradation of incretins _ promote insulin secretion
323
DIABETES PHARMACOLOGY
what are the side effects of DPP-4 inhibitors e.g. linagliptin?
pancreatitis
324
HYPOTHYROIDISM
what is the mechanism of action for levothyroxine?
synthetic T4
325
DKA
what is the diagnostic criteria for diabetic ketoacidosis?
glucose >11mmol/L
pH <7.3
bicarbonate <15mmol/L
ketones >3mmol/l or ketones in urine
326
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what is hyperosmolar hyperglycaemic state?
This is a life-threatening emergency characterised by marked hyperglycaemia,
hyperosmolality and mild or no ketosis
characteristic of uncontrolled type 2 diabetes
327
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what are the risk factors for hyperosmolar hyperglycaemic state?
- infection
- consumption of glucose rich fluids
- concurrent medication (thiazides or steroids)
- MI
- poor medication compliance
328
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what is the pathophysiology of hyperosmolar hyperglycaemic state?
hyperglycaemia drives osmotic diuresis, resulting in fluid + electrolyte loss (hyperosmolality + hypovolaemia)
due to presence of small amounts of circulating insulin, lipolysis does not occur so ketoacidosis is not seen
329
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what is the clinical presentation of hyperosmolar hyperglycaemic state?
SYMPTOMS
- generalised weakness + leg cramps
- confusion, lethargy, hallucinations + headache
- visual disturbance
- polyuria
- polydipsia
- N+V
- abdominal pain
SIGNS
- reduced GCS
- dehydration (tachycardia, hypotension, dry mucous membranes, reduced skin turgor)
- seizures
330
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what are the investigations for hyperosmolar hyperglycaemic state?
- urine dip = glycosuria
- bedside ketone + capillary glucose = hyperglycaemia without ketonaemia
- ABG/VBG = hyperglycaemia without metabolic ketoacidosis
- serum osmolality
- U&Es
- FBC + CRP
331
HYPEROSMOLAR HYPERGLYCAEMIC STATE
what is the treatment for hyperosmolar hyperglycaemic state?
FLUID REPLACEMENT
- IV 0.9% NaCl
- aim to replace 50% fluid loss in first 12 hrs
FIXED RATE INSULIN INFUSION
- do not use insulin initially due to risks of rapid correction
- IV insulin only used if there is ketonaemia or if blood glucose is not longer falling with IV fluids alone, otherwise do NOT start insulin
POTASSIUM REPLACEMENT
- if >5.5 in first 24hrs = no replacement required
- if 3.5-5.5 in first 24hrs = 20-40mmol/L KCl
- if <3.5 in first 24hrs = require senior review
ANTICOAGULATION
- LMWH unless contraindicated
-
332
HYPEROSMOLAR HYPERGLYCAEMIC STATE (HHS)
what are the complications?
- venous thromboembolism
- arrhythmias
- strokes
- seizures
- AKI
- iatrogenic (cerebral oedema)
333
HASHIMOTOS THYROIDITIS
what conditions is hashimotos thyroiditis associated with?
- other autoimmune conditions - coeliac disease, T1DM, vitiligo
- MALT lymphoma
334
HYPOTHYROIDISM
what are the side effects of levothyroxine?
- usually due to excessive doses
| - GI disturbance, cardiac arrhythmias and neurological tremors
335
HYPERTHYROIDISM
what is the mechanism of action for carbimazole?
prevents thyroid peroxidase from producing T3 and T4
336
ACROMEGALY
what is the mechanism of action for GH receptor antagonist's e.g. pegvisomant?
blocks action of GH at GH receptor -> reduces production of IGF-1
337
ACROMEGALY
what are the side effects of GH receptor antagonists e.g. pegvisomant?
- reactions at injection site
- GI disturbance
- hypoglycaemia
- chest pain
- hepatitis
338
PHARMACOLOGY
what is the mechanism of action for vasopressin antagonists e.g. tolvaptan?
- inhibits vasopressin-2 receptor -> increases fluid excretion
- causes aquaresis (excretion of H2O with no electrolyte loss) -> increased Na+
339
PHARMACOLOGY
what are the side effect of vasopressin antagonists e.g. tolvaptan?
- GI disturbance
- headache
- increased thirst
- insomnia
340
PHARMACOLOGY
what is the mechanism of action for vasopressin analogues e.g. desmopressin?
binds to V2 receptors -> aquaporin 2 inserted in collecting duct which increases water reabsorption
341
PHARMACOLOGY
what are the side effects of vasopressin analogies e.g. desmopressin?
- headache
- facial flushing
- nausea
- seizures
342
PHARMACOLOGY
what is the mechanism of action for metyrapone?
- blocks cortisol synthesis by irreversibly inhibiting steroid 11 beta-hydroxide enzyme
343
PHARMACOLOGY
what are the side effects of metyrapone?
- GI disturbance
- headache
- dizziness
- drowsiness
- hirsutism
344
ADRENAL INSUFFICIENCY
how would cortisol levels react to the synacthen test if there was secondary adrenal insufficiency?
short ACTH = no change
| long ACTH = increase
345
CARCINOID TUMOURS
what are they?
a type of neuroendocrine tumour
are typically slow growing and can potentially become malignant
can secrete serotonin
346
CARCINOID TUMOURS
what is the difference between carcinoid tumours and carcinoid syndrome?
carcinoid tumours = type of neuroendocrine tumour which can secrete serotonin
carcinoid syndrome = liver mets impair hepatic excretion of serotonin during 1st pass metabolism, resulting in increased serotoninergic symptons
347
CARCINOID TUMOURS
where is the most common site for carcinoid tumours?
appendix and small intestine
patients with GI carcinoid tumours will only experience symptoms if they have liver mets
348
CARCINOID TUMOURS
what are the clinical features?
SYMPTOMS
- abdominal pain
- diarrhoea
- flushing
- wheezing
- pulmonary stenosis
patients with GI carcinoid tumours will only experience symptoms if they have liver mets
349
CARCINOID TUMOURS
what are the investigations?
- urinary hormone levels = 5-HIAA
- plasma chromogranin A y
- CT or MRI
- tissue biopsy
350
CARCINOID TUMOURS
what is the management?
- somatostatin analogues = octreotide
- surgery
- cyproheptadine can help with diarrhoea
351
HYPOTHYROIDISM
what is the most common cause of hypothyroidism in the developing world and the developed world?
developing = iodine deficiency
developed = Hashimoto's thyroiditis
352
DIABETES MELLITUS
what is the levels of HbA1c in normal, pre-diabetes and diabetes?
```
normal = < 42
pre-diabetes = 42-47
diabetes = >48
```
353
CUSHINGS
what is the difference between cushing's syndrome and cushing's disease?
syndrome = elevated cortisol levels
disease = caused by ACTH secreting pituitary adenoma
354
CUSHINGS
what investigation can be used to differentiate between cushing's syndrome and cushing's disease?
dexamethasone suppression test
- overnight = cushing's syndrome (including disease) is confirmed when there is no suppression
- 48 hours = cushing's syndrome (not disease) = no suppression
355
THYROID DISEASE
which condition would cause TSH = low and T4 = high?
hyperthyroidism
thyrotoxicosis
graves
356
THYROID DISEASE
which condition would cause TSH = high T4 = normal?
subclinical hypothyroidism
| poor compliance with thyroxine
357
THYROID DISEASE
which condition would cause TSH = high T4 = low?
primary hypothyroidism
| hashimotos
358
THYROID DISEASE which condition would cause TSH = low T4 = low?
secondary hypothyroidism
359
HYPERKALAEMIA
what arrhythmia is a consequence of untreated hyperkalaemia?
ventricular tachycardia
- due to cell membranes becoming partially depolarised -> lower threshold potential so ventricles contract faster
360
HYPERNATRAEMIA
what is the classification of hypernatraemia?
>145mmol/L
361
HYPERNATRAEMIA
what are the causes?
six Ds
- diarrhoea
- dehydration
- diuresis (secondary to diuretic use)
- diabetes insipidus
- doctors (iatrogenic - over administration of IV hypertonic NaCl or steroid use)
- disease (renal)
362
HYPERNATRAEMIA
what are the risk factors?
- increasing age
- diabetes insipidus
- severe burns or trauma
363
HYPERNATRAEMIA
what are the clinical features?
- thirst
- confusion
- irritability
- weakness
- oliguria
- dry mucous membranes
- tachycardia
- reduced skin turgor
- weight loss
364
HYPERNATRAEMIA
what are the investigations?
- serum sodium
- blood glucose
- serum osmolality
- urine osmolality
To consider:
- water deprivation test
365
HYPERNATRAEMIA
what is the management?
- fluid replacement = IV 5% dextrose
- treat causes
- suspend medications
366
HYPERNATRAEMIA
what are the complications?
- cerebral oedema
- coma
- death
367
HYPONATRAEMIA
what is the definition of hyponatraemia?
<135mmol/L
368
HYPONATRAEMIA
what are the causes?
HYPOVOLAEMIC
- D+V
- sweat
- burns
- diuretics
- 3rd space
- addisons
EUVOLAEMIC
- SIADH
- hypothyroidism
HYPERVOLAEMIC
- HF
- renal failure
- liver failure
369
HYPONATRAEMIA
what are the clinical features
MILD
- N+V
- headache
- lethargy
MODERATE
- weakness
- muscle aches
- confusion
- ataxia
SEVERE
- reduced consciousness
- seizures
- respiratory arrest
370
HYPONATRAEMIA
what are the investigations?
- U&Es
- serum + urine osmolality
- TFTs
- early morning cortisol
To consider:
- lipids + protein electrophoresis
- CT imaging
371
HYPONATRAEMIA
what is the management?
ACUTE (<48hrs)
- mild/no symptoms = stop non-essential fluids + meds that can provoke hyponatraemia + treat cause
- moderate/severe symptoms = hypertonic 3% NaCl
CHRONIC (>48hrs)
- maximum increase 10mmol/L per day
- if hypovolaemic = 0.9% NaCl
- if hypervolaemic = fluid restriction
372
HYPONATRAEMIA
what are the complications?
- cerebral oedema
- central pontine myelinolysis
373
OBESITY
what is it?
accumulation of excess body fat resulting from a chronic imbalance between energy intake and expenditure.
374
OBESITY
what are the different classifications?
- overweight = BMI 25-29kg/m2
- obesity class 1 = 30-34.9kg/m2
- obesity class 2 = 35-39.9kg/m2
- obesity class 3 = >40kg/m2 (also known as severe or morbid obesity)
375
OBESITY
what are the risk factors?
- genetic predisposition
- unhealthy diet (excessed processed, calorie-dense, nutrient poor foods)
- sedentary lifestyle
- hypothyroidism
- cushings syndrome or corticosteroid use
- lower socioeconomic status
376
OBESITY
what are the clinical features?
SYMPTOMS
- dyspnoea
- joint pain
- snoring or sleep apnoea
SIGNS
- increased waist circumference
- elevated blood pressure
- acanthosis nigricans
377
OBESITY
what are the investigations?
- BMI calculation
to consider
- blood tests: FBC, LFTs, lipid profile, HbA1c, TFTs
- ECG
378
OBESITY
what is the management?
1st line - lifestyle modifications (dietary changes, increased physical activity + behavioural interventions)
2nd line -
- orlistat (considered if BMI>30 or >28 with co-morbidities + if lifestyle changes have not resulted in weight loss)
- bariatric surgery (gastric banding or bypass if BMI>40 or >35 with co-morbidities who have not responded to conservative measures)
- semaglutide (once weekly long acting subcut injection to increase insulin + suppress appetite)
379
OBESITY
what are the complications?
- HTN
- IHD
- heart failure
- T2DM
- dyslipidaemia
- obstructive sleep apnoea
- osteoarthritis, back pain
- depression, social isolation
- cancer risk
380
HYPERLIPIDAEMIA
what is it?
elevation of lipids in the blood
381
# *
HYPERLIPIDAEMIA
what are the different types?
Classified using Fredrickson classification
- Type I = hyperclylomicronaemia
- Type IIa = familial hypercholesterolaemia
- Type IIb = combined hyperlipidaemia
- Type III = dysbetalipoproteinaemia
- Type IV = hypertriglyceridaemia
- Type V = mixed hypertriglyceridaemia
382
HYPERLIPIDAEMIA
what are the risk factors?
- family history of hyperlipidaemia
- premature cardiovascular disease
- poor diet
- lack of exercise
- excessive alcohol intake
- obesity
- diabetes
- hypothyroidism
- nephrotic syndrome
- medications (BB, glucocorticoids, amiodarone + diuretics
383
HYPERLIPIDAEMIA
what are the clinical features?
SYMPTOMS
- often asymptomatic
SIGNS
- tendon xanthomata
- xanthelasma (yellow papules on and around the eyelids)
- corneal arcus
- lipaemia retinalis (lipid accumulation at the back of the eye)
384
HYPERLIPIDAEMIA
what are the investigations?
- fasting lipid profile
- cardiovascular risk assessment
to consider
- serum HbA1c
- TFTs
- genetic testing
- coronary angiography
385
HYPERLIPIDAEMIA
what is the management?
1st line
- lifestyle modifications (dietary changes, increased physical activity, weight loss + smoking cessation)
- statins (atorvastatin or simvastatin)
- fibrates
2nd line
- ezetimibe
- PCSK9 inhibitors (evolocumab)
386
HYPERCALCAEMIA OF MALIGNANCY
what is it?
serum calcium >2.6mmol/L
it is the most common life-threatening metabolic disorder in cancer patients
387
HYPERCALCAEMIA OF MALIGNANCY
what is the pathophysiology?
three main mechanisms:
- secretion of PTH-related protein (PTHrP) = most common
- osteolytic metastases
- secretion of 1,25-dihydroxyvitamin D (calcitriol)
388
HYPERCALCAEMIA OF MALIGNANCY
what types of cancer is PTHrP secretion associated with?
- renal cancer
- ovarian cancer
- endometrial cancer
- squamous cell carcinoma
389
HYPERCALCAEMIA OF MALIGNANCY
what is the mechanism of action of PTHrP?
stimulates osteoclastic resorption and inhibits osteoblast formation of the bone
this results in excessive calcium release from the skeleton
also acts on the kidneys to reduce calcium clearance, further increasing calcium levels in blood
390
HYPERCALCAEMIA OF MALIGNANCY
which types of cancer are associated with osteolytic metastases?
- breast cancer
- multiple myeloma
391
HYPERCALCAEMIA OF MALIGNANCY
what is the mechanism of action of osteolytic metastases?
local release of cytokine and chemokines results in increased osteoclast activity
the excessive calcium overwhelms the kidney's ability to clear it from the body
392
HYPERCALCAEMIA OF MALIGNANCY
what types of cancer are associated with calcitriol secretion?
lymphomas
393
HYPERCALCAEMIA OF MALIGNANCY
what is the mechanism of action for calcitriol secretion?
overexpression of 1-alpha hydroxylase (which converts 25-hydroxyvitamin D into calcitriol)
this leads to excessive calcitriol resulting in increased absorption of calcium and osteoclast activity
394
HYPERCALCAEMIA OF MALIGNANCY
what are the risk factors?
the type of cancer
- multiple myeloma
- breast cancer
- lung cancer (squamous)
- renal cancer
- thyroid cancer (squamous)
- lymphoma (all types)
medications
- thiazide diuretics
- lithium
- OTC supplements containing calcium or vitamin D
395
HYPERCALCAEMIA OF MALIGNANCY
what are the clinical features?
BONES, STONES, GROANS + psych MOANS
BONES
- bone pain
STONES
- renal stones
GROANS
- polyuria
- nausea + vomiting
- abdominal pain
- constipation
- anorexia
psych MOANS
- confusion
- fatigue
- anxiety
- depression
396
HYPERCALCAEMIA OF MALIGNANCY
what are the clinical features?
UNDERLYING CANCER
- lymphadenopathy
- hepatosplenomegaly
HYPERCALCAEMIA
- signs of dehydration (dry mucous membranes, sunken eyes, reduced skin turgor)
- hyporeflexia
- tongue fasciculations
- abdominal distention (due to constipation)
- bony tenderness
397
HYPERCALCAEMIA OF MALIGNANCY
what are the investigations?
- adjusted serum calcium (mild = <3, mod = 3-3.5, severe = >3.5)
- ECG = bradycardia, shortened QT, heart block
- U&Es
- PTH (suppressed when PTHrP raised)
- bone profile
- calcitriol
- vitamin D
- CXR
- CT scan
398
HYPERCALCAEMIA OF MALIGNANCY
what is the management?
SUPPORTIVE
- stop medications that contribute to hypercalcaemia (thiazides, calcium supplements, vitamin D supplements, lithium)
- stop medications that can worsen renal function (NSAIDs, ACEis)
- medications for associated symptoms
= laxatives for constipation
= anti-emetics for nausea
= analgesia for bone pain
REHYDRATION
- IV fluids (3 litres in first 24hrs)
BISPHOSPHONATES
- 1st line = IV zoledronic acid 4mg
- 2nd line = disodium pamidronate 30-90mg
- if hypercalcaemia lasts >7 days then further bisphosphonates may be considered or denosumab
399
HYPERCALCAEMIA OF MALIGNANCY
what are the complications?
- transient flu-like syndrome (due to bisphosphonate treatment)
- AKI
- acute pancreatitis
- cardiac arrhythmias
- seizures
- coma
it is a poor prognostic indicator with a mean survival of 2-3 months
