1
Q
Describe the pathogenesis of acromegaly
A
- MC cause excess GH from pituitary tumour
- GH stimulates release of IGF-1
- IGF-1 stimulates soft tissue and skeletal overgrowth
- can also be from lung/pancreatic tumour secreting GHRH or GH
2
Q
What is the relationship between IGF-1, somatostatin and GH?
A
- IGF-1 stimulates the release of somatostatin
- This inhibits GH production from the hypothalamus
3
Q
What are some signs of acromegaly?
A
- prominent forehead and brow
- large hands, nose, feet, tongue
- bitemporal hemianopia (pressure on optic chiasm) + headaches
- excess sweat + oily skin
- larger jaw + wide spaced teeth
4
Q
What are some conditions caused by acromegaly?
A
- arthritis due to bony overgrowth
- fatigue
- carpal tunnel syndrome
5
Q
What is the 1st line investigation for acromegaly?
A
- IGF-1
- levels increased correlating with increased levels of GH
6
Q
What is the 2nd line investigation for acromegaly?
A
- OGTT to confirm IGF-1
- normally GH inhibited by a rise in glucose, so should be undetectable
- GH release unsuppressed in acromegaly
- pituitary MRI may show tumour
7
Q
What diseases may develop resulting from acromegaly?
A
- diabetes
- htn and heart disease
- colorectal cancer
8
Q
What is the first line management of acromegaly?
A
- transsphenoidal surgery to remove pituitary adenoma
9
Q
What is the treatment for acromegaly if surgery isn’t appropriate?
A
- somatostatin analogues to block GH release
- GH receptor antagonists
- dopamine agonists which suppress GH
- radiotherapy last
10
Q
What is an example of a somatostatin analogue?
A
- octreotide
11
Q
What is an example of a GH receptor antagonist?
A
- pegvisomant
- decreases IGF-1 levels
- OD s/c
12
Q
What is Conn’s syndrome?
A
- primary hyperaldosteronism
- excess of aldosterone
- serum renin is low as it is suppressed by high bp
13
Q
What is the aetiology of primary hyperaldosteronism?
A
- Adrenal adenoma (only actual cause of Conn’s, others are hyperaldosteronism)
- bilateral adrenal hyperplasia
14
Q
What is secondary hyperaldosteronism and its aetiology?
A
- excessive renin stimulating adrenal glands to produce more aldosterone
- serum renin is high
- causes: renal artery stenosis/obstruction, HF
- due to lower BP in afferent arterioles in kidney than in rest of body
15
Q
How does Conn’s present?
A
- often asymptomatic
- hypertension (Conn’s + hyperaldosteronism are usually indistinguishable unless measuring renin + aldosterone)
- headaches
- hypokalaemia (excretion of K+)
- weakness, cramps, polyuria, polydipsia, thirst
16
Q
How is Conn’s investigated?
A
- high aldosterone, low renin = 1º
- high aldosterone, high renin = 2º
- CT/MRI to look for adrenal mass
- selective adrenal venous sampling (gold)
17
Q
How is Conn’s managed?
A
- aldosterone antagonists to control BP and low K+ e.g. Spironolactone
- adrenalectomy
- percutaneous renal artery angioplasty for 2º hyperaldosteronism
18
Q
What is the difference between Cushing’s syndrome and Cushing’s disease?
A
- syndrome: signs and symptoms which develop after prolonged, abnormal elevation of cortisol
- Cushing’s disease: a pituitary adenoma secretes excessive ACTH
- Cushing’s disease can cause Cushing’s syndrome but the syndrome isn’t always caused by the disease
19
Q
What is the presentation of Cushing’s?
A
- round moon face
- central obesity
- abdominal striae
- proximal limb muscle wasting
- fat pad on upper back
- hypertension
- hyperglycaemia
- depression
- insomnia
20
Q
What is the management of Cushing’s disease & syndrome?
A
- pituitary adenoma: transsphenoidal removal
- adrenal tumour/ectopic ACTH: surgical removal of tumour
- iatrogenic: stop steroids
21
Q
What is the aetiology (ACTH independent vs ACTH dependent - 2 for each) & epidemiology of Cushing’s?
A
- ACTH independent: iatrogenic e.g. steroids (MC) or adrenal adenoma
- ACTH dependent: Cushing’s disease (MC) or ectopic ACTH (small cell lung/neuroendocrine tumour)
- more likely in women
22
Q
What is the investigation of Cushing’s?
A
- 1st line: raised plasma cortisol
- CT/MRI for tumours
- Low dose dexamethasone test initially
23
Q
What may be seen on VBG in Cushing’s?
A
- hypokalaemic metabolic alkalosis
- (cortisol causes Na reabsorption and K+ and H+ excretion)
24
Q
What is high dose dexamethasone test?
A
- usually to differentiate pituitary and ectopic ACTH
- 8mg dexamethasone
- low cortisol: Cushing’s disease
- High cortisol, low ACTH: Adrenal Cushing’s
- High cortisol, high ACTH: ectopic ACTH
25
What is the low dose dexamethasone test?
- 1mg dex at night
- cortisol and ACTH are measured in the morning
- normal: dexamethasone suppresses cortisol release by -ve feedback on hypothalamus and pituitary
- hypothalamus reduces CRH, pituitary reduces ACTH
- Cushing's: cortisol not suppressed
26
What is nephrogenic diabetes insipidus and what are some causes?
- Collecting ducts don't respond to ADH
- lithium
- mutations in gene coding for ADH receptor
- electrolyte disturbance
27
What is cranial diabetes insipidus and what are some causes?
- hypothalamus doesn't produce ADH
- idiopathic
- brain tumour, infection, surgery, head injury
28
What is diabetes insipidus?
- lack of ADH (cranial) or lack of response to ADH (nephrogenic)
- prevents kidneys being able to concentrate urine > polyuria or polydipsia
29
How does diabetes insipidus present?
- polyuria
- polydipsia
- dehydration
- postural hypotension (BP drops on standing after sitting/lying down)
- hypernatraemia
- nocturia
30
How is diabetes insipidus managed?
- treat underlying cause
- cranial: desmopressin (synthetic ADH) but monitor Na (hyponatraemia risk)
- nephrogenic: thiazides + low salt/protein diet
31
How is diabetes insipidus investigated? Give osmolality values
- low urine osmolality <300
- high serum osmolality >395
- water deprivation test (gold standard)
32
What is the water deprivation test?
- patient avoids taking in fluids for 8hrs
- urine osmolality measured and desmopressin administered
- urine osmolality measured 8hrs later
- in CDI > urine osmolality: low > high
- in NDI > urine osmolality: low > low
33
What does a desmopressin test show? What does a higher urine osmolality suggest?
- differentiates cranial and nephrogenic DI
- inc urine osmolality suggests cranial DI
34
What are causes of hypokalaemia with alkalosis?
- vomiting
- thiazide and loop diuretics
- Cushing's
- Conn's
35
What are causes of hypokalaemia with acidosis?
- diarrhoea
- renal tubular acidosis
- acetazolamide
- DKA partially treated
36
How does hypokalaemia present?
- muscle weakness and hypotonia
37
What is seen on ECG in hypokalaemia?
- U waves
- small or absent T waves
- prolonged PR interval
- ST depression
- long QT
38
Hyperkalaemia decreases action potential threshold, what does this cause in the heart?
- Leads to easier depolarisation and abnormal heart rhythms
39
What are causes of hyperkalaemia?
- AKI
- drugs: spironolactone, ACEi, ARBs, ciclosporin, heparin
- Addison's
- rhabdomyolysis
- metabolic acidosis
40
How is hyperkalaemia diagnosed?
- high K+ on U&Es
- serum potassium >5.5mmol/L
- ECG: absent P wave, prolonged PR interval, tall T waves, widened QRS complex
41
How is hyperkalaemia classified?
- mild: 5.5-5.9
- moderate: 6.0-6.4
- severe: ≥6.5mmol/L
42
How is hyperkalaemia treated?
- urgent: calcium gluconate to stabilise the cardiac membrane
- shift K from ECF to ICF: insulin/dextrose infusion and nebulised salbutamol
43
What are options to remove potassium from the body?
- calcium resonium
- loop diuretics
- dialysis
44
What are differential diagnoses for hyperkalaemia?
- CKD, DKA, HHS
- uncommon: AKI, Addison's
45
What is diabetes mellitus?
A disorder of carbohydrate metabolism characterised by hyperglycaemia
46
What glucose levels define diabetes in a symptomatic patient?
- fasting glucose ≥7mmol/l
- random ≥11.1mmol/l
47
What glucose levels define diabetes in an asymptomatic patient?
- demonstrate on two separate occasions
- fasting ≥ 7 and random ≥ 11.1
- HbA1c ≥ 48mmol/mol (6.5%)
48
What glucose levels define pre diabetes?
- fasting 6.1-6.9 mmol/l
- HbA1c 42-47 mmol/mol
49
What can be a cause of misleading HbA1c results?
increased red cell turnover e.g. dialysis
50
In which conditions should HbA1c not be used for diagnosis of T2DM?
- haemolytic anaemia
- haemoglobinopathies
- CKD
- people taking meds causing hyperglycaemia e.g. corticosteroids
- HIV
51
Why are polyuria and glycosuria symptoms of diabetes?
- glucose draws water into the blood by osmotic diuresis
- kidneys reach max reabsorptive glucose capacity
- excessive levels of glucose and water being excreted
52
What is the definition of type 2 diabetes?
- progressive disorder
- characterised by increased insulin resistance and impaired insulin secretion
- due to genetic predisposition and environmental factors
53
What is the pathophysiology of type 2 diabetes?
- Repeated exposure to glucose and insulin > more insulin needed to produce response from cells for glucose uptake.
- β cells become fatigued and damaged > produce less insulin
- insulin resistance and pancreatic fatigue leads to chronic hyperglycaemia
54
What is the epidemiology of type 2 diabetes?
- Mainly found in Asians, men, elderly.
- Mostly in over 40s but prevalence increasing in teenagers
55
What is the aetiology of type 2 diabetes?
- age
- obesity
- family history
- genetics: determines whether or not you develop the disease, lifestyle factors determine when. genetic link stronger than in T1DM
56
What are the risk factors for type 2 diabetes?
- smoking
- obesity
- hypertension
- sedentary lifestyle
- age
- ethnicity
- FHx
57
What are the signs and symptoms of T2DM?
- polyuria
- polydypsia
- opportunistic infection
- slow healing
- lethargy
- glucose in urine (glycosuria)
- blurred vision
58
What is 1st line management for T2DM?
- dietary changes, higher in complex carbs, low in fat and sugar
- smoking cessation and dec alcohol
- inc exercise
- blood glucose and HbA1c monitoring
59
What are the target HbA1c levels for T2DM?
- lifestyle changes - 48mmol/mol
- lifestyle + metformin - 48
- drugs causing hypoglycaemia - 53
- HbA1c of 58 - 53
60
Why should metformin be slowly titrated?
- minimise GI upset
- trial modified release if standard not tolerated
61
When should SGLT-2 inhibitors be added to metformin?
- high CVD risk - QRISK >10%
- established CVD
- chronic heart failure
62
What drugs should be given in T2DM if metformin is contraindicated?
- SGLT-2 monotherapy if CVD, risk of CVD or CHF
- no risk of CVD: DPP-4 inhibitor/pioglitazone/sulfonylurea
63
What HbA1c threshold triggers further treatment with metformin?
- 58mmol/mol
64
What are dual therapy options for T2DM?
add to metformin:
- DPP-4 inibitor
- pioglitazone
- sulfonylurea
- SGLT-2 inhibitor
65
Under what circumstances can GLP-1 mimetics be started?
- BMI≥35 and psych/med problems associated with obesity
- BMI ≤35 would benefit from weight loss/insulin wouldn't work
- only continue if reduction of >11mmol/mol in HbA1c + >3% weight loss in 6 months
66
How should insulin be started in diabetes?
- continue metformin and review other drugs
- start with human insulin BD
67
What is the action of sulphonylureas?
- stimulate insulin release by binding to β cell receptors
- don't prevent failure of insulin secretion (beta cell fatigue) and can cause hypoglycaemia
68
What is the action of thiazolidinediones?
- activate genes concerned with glucose uptake, utilisation and lipid metabolism
- improve insulin sensitivity but need insulin for a therapeutic effect
- can inc weight, risk of heart failure and fractures
69
What is the action of metformin?
- inc peripheral insulin sensitivity, decreases liver production of glucose
- reduces insulin resistance by modifying the glucose metabolic pathways
- lowers blood glucose levels
70
How do GLP-1 mimetics work?
- inc insulin secretion and inhibit glucagon secretion
- e.g. exenatide or liraglutide
71
How do DPP-4 inhibitors work?
- increase incretin levels by decreasing peripheral breakdown
- do not cause weight gain
- e.g. sitagliptin
72
What are the macrovascular complications associated with diabetes?
- stroke
- CVD/MI
73
What are the microvascular complications associated with diabetes?
- diabetic retinopathy > visual loss
- nephropathy > end stage renal disease
- neuropathy > foot ulcers and amputation
74
How is screening managed for diabetic nephropathy?
- patients screened annually using urinary albumin:creatinine ratio
- ACR ≥ 3mg/mmol is significant
- ACR > 2.5mg/mmol in men or >3.5mg/mmol in women is significant and tests repeated
75
What is the management of diabetic nephropathy based on ACR?
- if ACR ≥3: aim for BP 130/80 and add ACEi or ARB
- if ACR <3: aim for BP 140/90
76
What is the distribution of diabetic neuropathy?
- glove and stocking sensory loss
- lower legs affected first
77
How is diabetic neuropathy managed?
- 1st line: amitriptyline, duloxetine, gabapentin or pregabalin
- tramadol rescue therapy for exacerbations
- topical capsaicin if localised
78
What GI symptoms can occur from diabetic neuropathy?
- gastroparesis: erratic BM control, bloating, vomiting - prokinetic to manage
- chronic diarrhoea
- GORD
79
What is the pathophysiology of T1DM?
- GLUT4 transporters require insulin to take up glucose from the blood and use it for fuel
- no insulin produced so glucose remains in blood
- cells think the body is being fasted so blood glucose levels keep rising causing hyperglycaemia
80
Pathophysiology of the cause of T1DM?
- insulin deficiency characterised by loss of β cells of islets of Langerhans
- due to autoimmune destruction
- may be triggered by viral infection
81
What are the risk factors for T1DM?
- genetic predisposition
- northern European
- HLA DR3 or HLA DR4 human leukocyte antigens
82
What are some signs and symptoms of T1DM?
- manifests in childhood and commonly presents with DKA
- polyuria
- polydypsia
- sudden unexplained weight loss
83
How can T1DM be investigated?
- urine dip for glucose and ketones
- low C-peptide levels
84
Which diabetes specific antibodies are present in T1DM?
- anti-GAD
- islet cell antibodies
- insulin autoantibodies
85
How often is HbA1c monitored in T1DM? What is the target?
- every 3-6 months
- target 48mmol/mol or lower
86
What are typical blood glucose targets (not HbA1c) for T1DM?
- 5-7 mmol/l on waking
- 4-7mmol/l before meals
87
Why is weight loss a sign/symptom of T1DM?
- Excess fluid depletion and accelerated breakdown of fat and muscle due to insulin deficiency.
- More common in T1DM as there is complete insulin deficiency so lipolysis and proteolysis occur more quickly
- No glucose can enter cells in T1 but insulin is still produced in T2
88
What is the management of T1DM?
- monitoring dietary carbohydrate intake and monitoring blood sugar levels
- Subcutaneous insulin prescribed: background long acting insulin taken once a day and short acting insulin injected 30 mins before intake of carbs at meals
89
What are the sick day rules for T1DM?
- patient must not stop insulin due to DKA risk
- check BM more frequently: every 1-2hrs
- maintain normal meal patterns
- aim to drink at least 3L per day
90
What are the criteria for DKA?
- ketoacidosis: blood ketones > 3mmol/l
- hyperglycaemia: blood glucose > 11mmol/l
- acidosis pH < 7.3
91
What is the aetiology of DKA?
- untreated/undiagnosed T1DM
- infection/illness
92
What is ketoacidosis?
uncontrolled catabolism associated with insulin deficiency
93
What is the pathophysiology of DKA? (3 effects of insulin absence)
- inc gluconeogenesis and dec peripheral uptake > hyperglycaemia
- Hyperglycemia > osmotic diuresis > > dehydration + electrolyte loss
- Lipolysis for energy > inc in FFAs > oxidised to Acetyl CoA > ketone bodies (acidic) = Acidosis
94
How does DKA present?
- Nausea + Vomiting
- dehydration > can cause hypotension
- Abdominal pain
- acetone breath smell
- lethargy
- respiratory compensation for acidosis leading to hyperventilation (Kussmaul breathing)
95
How is DKA diagnosed?
- recognised from the clinical features
- confirmed by blood glucose and ABG
- U&E: raised due to dehydration
- urine dipstick - glycosuria and ketonuria
96
Why is insulin treatment for DKA dangerous?
- Insulin decreases blood potassium levels by redistributing K+ via the sodium-potassium pump
- this causes low serum K+ leading to hypokalaemia
- can lead to arrhythmia, weakness
97
How is DKA managed?
- fluid loss replaced with IV 0.9% saline
- follow with 0.9% NaCl/KCl
- give insulin 0.1 unit/kg/hr
- when BM < 14mmol/l start 10% dextrose at 125ml/hr (cont saline)
- continue long-acting insulin, stop short-acting
98
Why are both insulin and glucose given in DKA treatment?
inhibits gluconeogenesis and therefore ketone production
99
What are the criteria for DKA resolution?
- pH > 7.3
- ketones < 0.6 mmol/L
- bicarbonate > 15.0 mmol/L
100
What is a possible complication of DKA, in what timeframe and why?
- cerebral oedema
- occurs within 4-12 hrs
- the blood is initially very concentrated with high salt levels and is rapidly diluted
- osmotic shifts occur and water moves from the blood into tissues
- causes swelling of the brain
101
What are other complications of DKA?
- gastric stasis
- thromboembolism
- arrythmias
- AKI
102
What is the hyperosmolar hyperglycaemic state (diagnosis criteria)?
- hyperglycaemia: ≥30mmol/L
- hyperosmolality: ≥320mOsm/kg (due to inc serum glucose and potassium
- no ketoacidosis
103
What is the pathophysiology behind hyperosmolar hyperglycaemic state?
- some insulin still produced by pancreas
- sufficient to inhibit hepatic ketogenesis (preventing ketogenesis)
- insufficient to inhibit hepatic glucose prod
- leads to osmotic diuresis, loss of Na and K
- hyper viscosity of blood + volume depletion
104
What is the presentation of the hyperosmolar hyperglycaemic state?
- dehydration, polyuria, polydypsia
- lethargy, nausea, vomiting
- altered level of consciousness (low GCS)
- focal neurological deficits
- hyperviscoscity
105
How is the hyperosmolar hyperglycaemia state managed?
- fluid replacement: IV 0.9% NaCl solution
- 0.5-1L per hour
- insulin: should NOT be given unless blood glucose falls while giving IV fluids
- VTE prophylaxis
106
What are possible complications of HHS?
- MI and stroke due to hyperviscosity
107
What is the difference in how long HHS and DKA take to present?
- HHS comes on over day
- DKA presents within hours
108
What is the physiology of the parathyroid?
- 4 parathyroid glands
- chief cells produce PTH
- posterior aspect of thyroid
- produced in response to hypocalcaemia
109
How does PTH act at the bone?
- inc activity of osteoclasts
- responsible for bone resorption
- bone releases Ca and PO4 into blood
110
How does PTH act on the kidneys?
- inc hydroxylation and activation of vit D in proximal convoluted tubules
- inc Ca reabsorption from distal convoluted and inc PO4 excretion
111
How does PTH increase serum calcium?
- increases osteoclast activity
- Ca reabsorption in kidneys
- Inc vit D activity > more Ca absorbed in intestines
112
What is primary hyperparathyroidism?
- uncontrolled PTH
- leads to hypercalcaemia
113
What are the causes of primary hyperparathyroidism?
- solitary adenoma (MC)
- hyperplasia
- multiple adenoma
- carcinoma
114
What are the blood results in primary hyperparathyroidism?
- raised Ca, low PO4
- PTH raised or normal
115
How is primary hyperparathyroidism managed?
- definitive: total parathyroidectomy
- cinacalcet: calcimimetic
116
How does cinacalcet work?
- calcium sensing receptor agonist
- reduced PTH secretion
- therefore reduces serum calcium
117
What are the 3 criteria for conservative management of primary hyperparathyroidism?
1. Ca level <0.25mmol/L above normal
2. patient >50 years
3. no evidence of end-organ damage
118
What is secondary hyperparathyroidism?
- insufficient vitamin D or CKD > low calcium reabsorption
- causes hypocalcaemia
- more PTH excreted in response to low serum calcium
- leads to hyperplasia of glands
119
What are the blood results in secondary hyperparathyroidism?
- low/normal serum calcium
- high PTH
120
How is secondary hyperparathyroidism managed?
- treat underlying cause
- treat vit D deficiency if causing
- treat CKD - renal transplant
121
What is tertiary hyperparathyroidism?
- 2º continues for a long time
- hyperplasia: PTH baseline increases dramatically
- PTH levels remain high after 2º is treated
- high PTH and absent previous pathology > high calcium absorption + hypercalcaemia
- treated by surgical removal of PTH tissue
122
What are the criteria for surgical management for hyperparathyroidism?
- symptoms of hypercalcaemia
- end-organ disease: fractures, stones
- corrected Ca >2.85
123
What are possible complications of a parathyroidectomy?
- hypocalcaemia
- hoarseness
- cough
- due to damage to recurrent laryngeal nerve
124
What is the presentation of hyperparathyroidism?
- hypercalcaemia
- polydipsia, polyuria
- renal stones
- painful bones
- groans: constipation, nausea, vomiting
- moans: fatigue, depression
- pancreatitis
- hypertension
125
What bloods may be done for hyperparathyroidism?
- corrected calcium
- serum PTH
- vitamin D
- U&Es
126
What imaging may be done for hyperparathyroidism?
- DEXA scan
- USS of renal tract
- USS of neck
- nuclear imaging: sestamibi scan (for adenoma)
127
Which other conditions is hyperparathyroidism associated with?
- hypertension
- multiple endocrine neoplasia: MEN I and II
128
What is the pathophysiology of hypoparathyroidism?
- low PTH levels
- serum Ca can't be inc through bone and kidneys
- kidneys can't synthesise calcitriol
- serum phosphate inc due to dec excretion due to low PTH
129
What are the acquired causes of hypoparathyroidism?
- damage or removal of PTH glands
- haemochromatosis (iron), Wilson's (copper)
- radiation
- hyper/hypomagnasaemia
130
What are congenital/genetic causes of hypoparathyroidism?
- DiGeorge syndrome
- Autoimmune polyendocrine syndrome type 1 (APS-1)
- pseudohypoparathyroidism
131
What are risk factors for hypoparathyroidism?
- surgery
- chronic alcohol excess
- chronic malabsorption
- frequent transfusions
- PPIs
132
What is the pathophysiology behind the clinical features of hypoparathyroidism?
- increased neuromuscular excitability
- due to hypocalcaemia
133
What are the features of hypoparathyroidism?
- tetany: muscle twitching, spasm
- perioral paraesthesia
- stridor: laryngospasm
- seizure
- muscle pain and cramps
134
How is pseudohypoparathyroidism diagnosed? Differentiate type I, II and hypoparathyroidism
- low Ca, high PO4, high PTH
- measure urinary cAMP and phosphate levels
- in type I: neither rise
- type II: cAMP rises
- hypoPTH: both rise
135
What is pseudohypoparathyroidism?
- target cells in kidneys and bone insensitive to PTH
- PTH is still high
136
What are the features of pseudohypoparathyroidism?
- short stature
- shortened 4th and 5th metacarpals
137
What is seen on examination of hypoparathyroidism?
- Trousseau's: carpal spasm if brachial artery occluded by inflating BP cuff
- Chvostek's: tapping over parotid causes facial muscle twitch
- dry skin, brittle nails
- dental abnormalities
138
What is seen on ECG in hypoparathyroidism?
- prolonged QT interval
- due to hypocalcaemia
139
What do bloods show in hypoparathyroidism?
- hypocalcaemia
- low/inappropriately normal PTH
- high phosphate
140
What imaging may be done for hypoparathyroidism?
- renal USS: calculi due to inc Ca excretion
- MRI brain: basal ganglia calcification
- hand X-ray: shorter metacarpals (pseudo)
141
How is hypoparathyroidism managed acutely?
- correct hypocalcaemia
- severe (<1.9): 10-20ml calcum gluconate in 50-100ml of 5% glucose IV over 10 mins, with cardiac monitoring
- mild: oral calcium replacement
- low Mg: give IV Mg sulfate
142
How is hypoparathyroidism managed chronically?
- active vit D analogue e.g. calcitriol or alfacalcidol
- calcium rich diet
- PTH replacement therapy if uncontrollable
143
What are potential complications of hypoparathyroidism?
- ECG abnormalities > inc risk of CVD, IHD
- CKD
- cataracts
- depression, anxiety
- infection (UTI, RTI)
144
What is hypercalcaemia?
- adjusted serum calcium of >2.6mmol/L
145
What are the causes of hypercalcaemia?
- primary hyperparathyroidism
- malignancy
146
What is PTHrP?
- PTH related peptide
- secreted from cancer cells - squamous cell bronchial carcinoma
- has same effects as PTH but can't activate vit D
147
What are other causes of hypercalcaemia?
- sarcoidosis
- thyrotoxicosis
- drugs: thiazides
- Addison's
- acromegaly
148
What are features of hypercalcaemia?
- painful bones
- renal stones
- abdominal groans (constipation, n+v)
- moans (fatigue, depression, psychosis)
- corneal calcification
- shortened QT
- hypertension
149
How is hypercalcaemia managed?
- rehydration with saline (3/4 L per day)
- bisphosphonates following rehydration
- loop diuretics
- calcitonin
150
What are the mechanisms of hypercalcaemia of malignancy?
- secretion of PTHrP
- osteolytic metastases
- secretion of calcitriol
151
Which cancers is PTHrP associated with?
- renal
- ovarian
- endometrial
- squamous cell carcinoma
152
How does PTHrP secretion cause hypercalcaemia?
- stimulates osteoclastic resorption
- inhibits osteoblast formation of bone
- excess Ca release
- reduces Ca clearance in kidneys
153
How do osteolytic metastases cause hypercalcaemia?
- br ca and multiple myeloma
- local release of cytokines and chemokine > inc osteoclast activity
- reduced kidney clearance
154
What is calcitriol mediated hypercalcaemia?
- over expression of 1-α hydroxylase
- converts calcidiol to calcitriol
- excess calcitriol production
- inc intestinal absorption and inc osteoclast activity
155
What are examination findings of hypercalcaemia?
- dehydration
- hyporeflexia
- tongue fasciculations
- abdo distention (constipation)
- bony tenderness
156
Which medication classes are stopped in hypercalcaemia of malignancy?
- thiazide diuretics
- ca and vit d supplements
- lithium
157
What bisphosphonate is used in hypercalcaemia of malignancy?
- zoledronic acid
- disodium pamidronate
- take 3-4 days to work
158
What is osteomalacia?
- softening of bones 2º to low vit D levels
- leads to decreased bone mineral content
- rickets in children
159
What causes osteomalacia?
- vit D deficiency: diet, sunlight, malabsorption
- CKD
- drug induced
- inherited (hypophosphataemic rickets)
- liver disease
- coeliac
160
What are the features of osteomalacia?
- bone pain
- bone/muscle tenderness
- fractures (femoral neck common)
- proximal myopathy
161
How is osteomalacia investigated?
- bloods: low vit D, Ca, phosphate, raised ALP
- X-ray: translucent bands
162
How is osteomalacia treated?
- vit D supplementation (colecalciferol)
- loading dose of 4000IU OD for 10wks
- maintenance of 800-2000IU per day
- calcium supplementation
163
What are causes of hypoglycaemia?
- insulinoma
- liver failure
- alcohol: causes exaggerated insulin secretion
- self-administration of insulin
164
What is SIADH?
- hyponatraemia secondary to excess water retention
- euvolaemic
165
What is the pathophysiology of SIADH?
- excess, uninhibited ADH release
- kidneys reabsorb more water > dec urine output > inc water retention
- does not lead to fluid overload but dec electrolyte conc
166
Where is ADH produced and what is its function?
- hypothalamus
- stored in posterior pituitary
- increases water reabsorption in collecting ducts
167
What are causes of SIADH?
- malignancy: small cell lung cancer (ectopic ADH)
- neuro: stroke, SAH, SDH, meningitis
- infection: TB, pneumonia
- PEEP
168
What drugs can cause SIADH?
- sulfonylureas
- SSRIs, tricyclics
- carbamazepine
- vincristine
- cyclophosphamide
169
How does SIADH present?
- headache
- fatigue
- muscle aches and cramps
- confusion
170
How is SIADH investigated?
- urine osmolality: high >100mOsm/kg
- high urine sodium conc >40mmol/L
171
How is SIADH managed?
- slow correction
- fluid restriction
- demeclocycline: reduces responsiveness of collecting tubules to ADH
172
What temperatures define hypothermia?
- mild: 32-35ºC
- severe: <32ºC
173
What are risk factors for hypothermia?
- general anaesthesia
- substance abuse
- extreme age
- impaired mental state
174
What are signs of hypothermia?
- shivering
- cold, pale skin
- slurred speech
- confusion
175
How will symptoms differ in mild and moderate hypothermia?
- mild: tachypnoea, tachycardia, hypertension
- moderate: resp depression, bradycardia, hypotension
176
What is seen on ECG in hypothermia?
- acute ST elevation
- J waves
- Osborn waves
177
What is seen on hypothermia bloods?
- elevated Hb and haemltocrit (haemoconcentration)
- low platelets and WBC (sequestration in spleen)
- hypokalaemia
- peripheral insulin resistance
178
What other investigations should be done for hypothermia?
- ABG
- coagulation
- CXR
179
What is the management of hypothermia?
- remove wet/cold clothing
- warm with blankets
- secure airway and monitor breathing
- warm IV fluids
180
What is a possible consequence of rapid rewarming in hypothermia?
- peripheral vasodilation
- shock
181
What is Hashimoto's thyroiditis?
- autoimmune disorder
- hypothyroidism
- goitre
182
Which antibodies is Hashimoto's thyroiditis associated with?
- anti-thyroid peroxidase (TPO)
- anti-thyroglobulin (Tg)
183
What other conditions is Hashimoto's thyroiditis associated with?
- Addison's
- pernicious anaemia
- coeliac, T1DM, vitiligo
- MALT lymphoma
184
What are other causes of primary hypothyroidism?
- de Quervain's thyroiditis
- thyroidectomy
- drug therapy (lithium, carbimazole)
- iodine
185
What are features of hypothyroidism?
- cold intolerance
- weight gain
- lethargy
- constipation
- dry, cold, yellow skin
- non-pitting oedema
- dry scalp, loss of lateral eyebrows
- carpal tunnel
- dec deep tendon reflexes
186
What are features of a myxoedemic coma?
- hypothermia
- hypotension and bradycardia
- thin, brittle hair
- periorbital oedema
- reduced reflexes
187
How is myxoedemic coma treated?
- IV thyroid replacement
- IV fluids
- IV hydrocortisone
- correct electrolyte imbalance
188
In which patients should the initial starting dose of levothyroxine be lower and what should this dose be?
- over 50
- IHD
- severe hypothyroidism
- 25mcg
189
What is the normal starting dose for levothyroxine?
- 50-100mcg od
190
How can hypothyroidism be classified?
- primary: caused by thyroid gland
- secondary: external to thyroid e.g. pituitary
- congenital: underdeveloped/absent thyroid gland
191
What is subacute thyroiditis?
- occurs following viral infection
- transient inflammation of thyroid gland
- self-limiting
192
What are the 4 phases of subacute thyroiditis?
1. lasts 3-6 weeks: hyperthyroidism, goitre, raised ESR
2. 1-3 weeks: euthyroid
3. (weeks-months) hypothyroidism
4. normal
193
How is subacute thyroiditis investigated?
- thyroid scintagraphy
- globally reduced uptake of iodine-131
194
What is the management of subacute thyroiditis?
- self-limiting
- thyroid pain: aspirin/NSAID
- steroids if severe
195
After how long should a thyroxine dose change be checked?
- 8-12 weeks
196
What are side effects of thyroxine therapy?
- hyperthyroidism
- reduced bone mineral density
- worsening angina
- AF
197
What interactions does levothyroxine have?
- iron and calcium carbonate
- absorption of levothyroxine reduced
- give at least 4hrs apart
198
What is sick euthyroid syndrome?
- T3, T4 low
- TSH normal
- no treatment needed
199
What is subclinical hypothyroidism?
- high TSH
- normal T3, T4
- no obvious symptoms
200
How is subclinical hypothyroidism managed if TSH >10?
- if TSH >10mU/L and T4 normal
- consider levothyroxine if TSH >10
- 2 measurements 3 months apart
201
How is subclinical hypothyroidism managed if TSH 5.5-10?
- if <65y consider 6 month trial of levothyroxine
- 2 separate measurements 3 mo apart and symptoms of hypothyroid
- in >80: watch and wait
- asymptomatic: repeat TFT in 6mo
202
What is Graves' disease?
- autoimmune disease
- IgG Abs in response to TSH receptor
- MC cause of thyrotoxicosis
- women aged 30-50
203
What features are seen in Graves'?
- eye: exophthalmos, ophthalmoplegia
- pretibial myxoedema
- thyroid acropachy
- thyrotoxicosis symptoms
204
What is the triad of thyroid acropachy symptoms?
- digital clubbing
- soft tissue swelling of hands and feet
- periostea new bone formation
205
What antibodies are found in Graves' disease?
- TSH receptor stimulating antibodies
- anti TPO antibodies
206
What are the thyroid hormone levels in Graves' disease?
- inc T3 and T4 production as Abs bind to receptors
- thyroxine receptors activated and TSH suppressed
207
How can Graves' disease be investigated?
- diffuse, homogenous, increased uptake of radioactive iodine
208
How is Graves' disease managed?
- propranolol for adrenergic effects
- carbimazole if uncontrolled
209
What is a complication of carbimazole therapy?
- agranulocytosis
210
Describe starting dose and timing of carbimazole therapy for Graves' disease?
- start at 40mg and reduce gradually to maintain euthyroid
- continue for 12-18 months
211
What is block and replace therapy for Graves' disease?
- start carbimazole at 40mg
- add thyroxine when euthyroid
- treatment for 6-9 months
212
What are the contraindications to radio iodine treatment in Graves?
- pregnancy + avoid 4-6 months after
- age <16
- thyroid eye disease
213
When is radioiodine treatment used in Graves?
- resistance or relapse following anti thyroid
- majority of patients require thyroid supplementation after 5 years
214
What is toxic multinodular goitre?
- physiologically active nodules on thyroid fland
- unresponsive to TSH so cause thyrotoxicosis
215
What is investigation and management of toxic multi nodular goitre?
- nuclear scintigraphy: patchy uptake
- treatment: radioiodine therapy
216
What are features of thyrotoxicosis?
- weight loss
- manic, restless
- heat intolerance
- palpitations, tachycardia
- sweating
- diarrhoea
- oligomenorrhoea
- anxiety, tremor
217
What are features of thyroid storm?
- fever >38.5
- tachycardia
- confusion, agitation
- n+v
- hypertension
- heart failure
- abnormal LFTs
218
What precipitates thyroid storm?
- thyroid surgery
- trauma
- infection
- acute iodine load e.g. CT contrast
219
How is thyroid storm managed?
- symptomatic treatment
- β blockers e.g. IV propranolol
- anti-thyroid drugs
- dexamethasone: blocks T4 >T3
220
What are causes of thyrotoxicosis?
- Graves
- toxic multi nodular goitre
- acute phase of subacute thyroiditis, postpartum thyroiditis or Hashimoto's
- amiodarone therapy
- contrast
221
What is pheochromocytoma?
- neuroendocrine tumour of the chromatin cells in the medulla of the adrenal glands
- secretes large quantities of the catecholamine hormones noradrenaline and adrenaline
- stimulates the SNS and fight or flight response
222
What is the presentation of pheochromocytoma?
- hypertension
- anxiety
- sweating
- headache
- palpitations, tachycardia, paroxysmal AF
223
How is pheochromocytoma diagnosed?
- 24hr urine metanephrines: breakdown product of adrenaline with a longer half life
224
How is pheochromocytoma managed?
- α blockers first (phenoxybenzamine)
- β blockers
- surgical management is definitive
225
What is the difference between osteoporosis and osteopenia?
- osteoporosis: reduction in bone density: bone is weaker and more prone to fracture
- osteopenia: less severe reduction in bone density - precursor
226
# Shattered
What are the risk factors for osteoporosis?
- Steroid use
- Hyperthyroidism
- Alcohol
- Thin (low BMI)
- Testosterone (low)
- Early menopause
- Renal/liver failure
- Erosive/inflammatory bone disease
- Dietary low calcium
227
All males and females of what ages should be assessed for osteoporosis?
females = ≥65
males = ≥75
228
The presence of what risk factors mean younger people should be assessed for osteoporosis according to NICE guidelines?
- previous fragility fracture
- use of oral/systemic glucocorticoid
- history of falls
- FHx of hip fracture
- low BMI
- smoking
- alcohol intake > 14 units
229
What endocrine conditions may increase risk of secondary osteoporosis?
- hypogonadism
- low testosterone (men)
- premature menopause (women)
- diabetes
- Cushing's
230
Which medications increase risk of osteoporosis?
- Corticosteroids: oral dose for >3mo
- SSRIs
- PPIs
- Anti-epileptics
- Anti-oestrogens
231
What conditions increase risk of osteoporosis?
- RA
- 1º hyperparathyroidism
- CKD
- IBD, coeliac
- Hyperthyroidism
- Chronic liver disease
232
What is the pathophysiology behind osteoporosis?
- reduction in bone density
- osteoclast activity is higher than osteoblast activity causing large spaces in brittle bone
- fractures usually occur due to trauma or fall
233
What is the epidemiology of osteoporosis?
- older age
- female
- post-menopausal
- oestrogen is protective
234
How is osteoporosis managed?
- avoiding falls
- calcium supplementation with vit D
- glucocorticoids
- 1st line: bisphosphonates e.g. zoledronic acid
- 2nd line: Denosumab
235
How do bisphosphonates work and what are the side effects?
- interfere with osteoclasts and reduce their activity
- prevents reabsorption of bone
- side effect: osteonecrosis of jaw and auditory canal
- reflux and oesophageal erosion
236
What 2 scoring systems can be used to grade osteoporosis?
- DEXA scan: measures bone mineral density with T score of hip
- FRAX score: 10 year probability of major osteoporotic fracture
237
Describe DEXA scoring
- Normal: T ≥ -1.0
- Osteopenia -2.5 < T < -1.0
- Osteoporosis T ≤ -2.5
- Severe osteoporosis T ≤ -2.5 plus a fracture
238
How should osteoporosis be investigated?
- FRAX on women > 65 and men > 75, younger patients with risk factors
- If intermediate risk: offer DEXA, if high then offer treatment
239
How does Denosumab work?
- blocks osteoclast activity by binding to the RANK-ligand
240
What lifestyle advice is given for osteoporosis?
- exercise
- maintain healthy weight
- stop smoking
- reduce alcohol
- avoid falls
241
What bloods should be done for osteoporosis?
- FBC
- U&E
- LFTs
- bone profile
- CRP
- thyroid function
242
For which patients should a DEXA scan be offered (without calculating FRAX)?
- >50y/o w/ Hx of fragility fracture
- <40y/o w/ major risk factor for fragility fracture
243
How often should FRAX be recalculated?
- if calculated risk was borderline for intervention - recalculate after min 2 yrs
- due to change in the person's risk factors
244
What are the possible outcomes of FRAX scoring?
- Orange: DEXA scan if not already done to further refine their 10yr risk
- Red: DEXA scan if not already done to act as a baseline and guide drug treatment
245
What is the definition of a fragility fracture?
- a low-impact fracture from a standing height or less
246
What are the common sites of fragility fracture?
- vertebral
- hip (proximal femur)
- wrist (distal radius)
247
What are the 3 risks of surgery for diabetics?
- increased wound and resp infection
- increased post-op AKI
- increased length of hospital stay
248
When do diabetics having surgery need a VRIII?
- more than 1 meal missed
- poor glycaemic control
- risk of renal injury
249
Which diabetes medications are taken as normal if having surgery?
- DPP-4 inhibitors (-gliptins)
- GLP-1 analogues (-tides)
250
How are sulfonylureas adjusted for surgery?
- take as normal day prior
- if OD: omit (morning and afternoon)
- if morning op and BD: omit morning dose
- if afternoon op and BD: omit both doses
251
How are SGLT-2 inhibitors adjusted for surgery?
- take as normal day prior
- omit on day of surgery for morning and afternoon op
252
How are insulins adjusted for surgery?
- OD insulin: reduce by 20% day prior and day of
- BD: normal day prior
- halve morning dose and normal evening dose
253
What is phaeochromocytoma?
- a rare catecholamine secreting tumour
- arises from adrenal medulla
254
What are the features of phaeochromocytoma?
- hypertension
- headaches
- palpitations
- sweating
- anxiety
255
How is phaeochromocytoma investigated?
- 24h urinary collection of metanephrines
256
What is the management of phaeochromocytoma?
- α blocker
- β blocker
- surgery is definitive
257
What is Addison's disease?
- primary adrenal insufficiency
- impairment in synthesis and release of gluco and mieralocorticoids
258
What is the aetiology of Addison's disease?
- autoimmunity (MC in Europe)
- TB (MC worldwide)
- metastases
- meningococcal septicaemia
- HIV
- antiphospholipid syndrome
259
What are dermatological features of Addison's disease?
- hyperpigmentation (palmar creases)
- vitiligo
260
What features of Addison's occur due to hypocortisolism?
- fatigue increasing throughout day
- weakness
- unintentional weight loss
- anorexia
261
What features of Addison's occur due to hypoandrogenism?
- loss of libido and sexual function
- loss of axillary and pubic hair
262
What features of Addison's occur due to hypoaldosteronism?
- n+v
- salt craving
- dizziness
- abdo pain
- orthostatic hypotension
- tachycardia
263
How is Addison's disease investigated?
- short synacthen test
- plasma cortisol measured before and 30 mins after giving synacthen
- if cortisol remains low, adrenal cortex is unresponsive > confirms diagnosis
264
After Addison's has been confirmed, what investigations can be used to determine the aetiology?
- autoimmune antibodies
- adrenal CT/MRI
265
What is seen on U&E in Addison's?
- hyperkalaemia
- hyponatraemia
- volume depletion > elevated urea and creatinine
266
What is seen on VBG in Cushing's (glucose and pH)?
- hypoglycaemia
- metabolic acidosis
267
What is the management of Addison's?
- hydrocortisone (2-3 divided doses of 20-30mg, majority taken in AM)
- fludrocortisone
268
How is intercurrent illness managed in Addison's patients?
- glucocorticoid dose doubled
- fludrocortisone dose the same
269
What are the causes of Addisonian crisis?
- acute exacerbation
- steroid withdrawal
- inadequate sick day management
270
What are the symptoms of Addisonian crisis?
- confusion, syncope, lethargy, convulsions
- hypotension, tachycardia, hypothermia
- abdo pain
271
What is the management of Addisonian crisis?
- Hydrocortisone 100mg IM/IV > 200mg per 24h
- 1L saline over 30-60mins then 4-6L over 24h
MLA
flashcards
Decks in class (28)
# Cards
-
Renal148
-
Respiratory161
-
CV264
-
Derm109
-
Endocrinology271
-
Oncology72
-
Rheumatology226
-
3a Neuro228
-
3a Obstetrics247
-
GI303
-
Ophthalmology250
-
ENT102
-
Gynaecology286
-
Paeds resp117
-
Paeds GI130
-
Sexual Health105
-
Paeds endo26
-
Paeds cardio59
-
Haematology158
-
Ortho90
-
Anaesthesia + surgery4
-
Paeds neuro52
-
Paeds derm41
-
Paeds infectious68
-
Psychiatry269
-
Paeds MSK69
-
Paeds renal5
-
Paeds Genetics38
