Endo Flashcards
1
Q
What is DMT1?
A
Disease of insulin deficiency caused by autoimmune destruction of beta-cells of the pancreas
2
Q
Who does DMT1 usually effect?
A
Manifests in childhood/puberty and patient usually lean
3
Q
What is LADA?
A
Latent autoimmune diabetes in adults. Slow burning variant with slower progression to insulin deficiency
4
Q
Risk factors of DMT1
A
Northern European
Family history
Associated with other autoimmune diseases
Environmental Factors
5
Q
What cells are destroyed in DMT1?
A
Autoimmune destruction by autoantibodies of Beta cells in the islets of Langerhans
6
Q
What effect does insulin deficiency have on the liver?
A
Causes the continued breakdown of liver glycogen (producing glucose and ketones).
Leads to glycosuria and ketonuria as more glucose is in the blood
7
Q
Effect of DMT1 in skeletal muscle and fats
A
There’s impaired glucose clearance which leads to an increased blood glucose.
8
Q
At what mmol/L can the body no longer absorb glucose?
A
10mmmol/L - you become thirsty and get polyuria as the body is trying to remove excess glucose
9
Q
What happens if T1 diabetics don’t have insulin?
A
Patients are prone to diabetic ketoacidosis
10
Q
Why does DKA occur?
A
Reduced supply of glucose (as sig decline in circulating insulin) and increase in fatty acid oxidation (due to increase in circulating glucagon)
11
Q
How does DKA lower the pH of blood?
A
Increased production of Acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them. Ketone bodies are v acidic so lower pH
12
Q
Consequences of acidification of the blood?
A
Impairs the ability for Hb to bind to oxygen
13
Q
Clinical sign of DKA
A
Breath smells like pear drops
14
Q
What does complete Beta cells destruction result in?
A
Absence of serum C-peptide
15
Q
DMT2 is a result of what?
A
Combination of insulin resistance and less severe insulin deficiency
16
Q
Epidemiology of DMT2
A
All populations enjoying an affluent lifestyle
Older - >30
Overweight around the abdomen
South Asian, african, caribbean
17
Q
Risk factors of DMT2
A
Family history Increasing age Obesity and poor exercise Ethnicity Environment - low birth weight, poor-nutrition early
18
Q
What other conditions is DMT2 associated with? (6)
A
Central obesity Hypertension Hypertriglyceridemia Decrease in HDL cholesterol Disturbed homeostatic variables Modest increase in pro-inflammatory markers
19
Q
Tell me about insulin binding in DMT2
A
Binds normally to a receptor on the surface of cells - insulin resistance develops post-receptor
20
Q
What are the levels of insulin in the blood like?
A
Circulating levels are higher due to hypersecretion by a depleted beta cell mass.
However, will begin to decline again after months or years due to secretory failure (starling curve of the pancreas)
21
Q
What is IGT and IFG?
A
IGT - impaired glucose tolerance
IFG - impaired fasting glucose
Lifestyle changes can be made at these times to prevent DMT2
22
Q
Acute presentation of young people with DMT1
A
Polyuria and nocturia - not enough glucose reabsorbed by kidneys which leads to more glucose in tubule urine and thus lots of water
Polydipsia - Loss of fluids and electrolytes which have to be replaced
Weight loss - fluid depletion and accelerated breakdown of fat and muscle
23
Q
Complications of DM
A
Staphylococcal skin infection Retinopathy Polyneuropathy ED Arterial disease resulting in MI or peripheral gangrene
24
Q
What is acanthosis nigricans
A
Present in patients with severe insulin resistance - blackish pigmentation at the nape of the neck and axilla
25
DIagnostic ranges for DMT1 & 2
Random plasma glucose >11.1 mmol/L
Fasting plasma glucose > 7mmol/L
Borderline cases
OGTT
- Fasting >7
- 2hrs after glucose >11.1
HbA1c > 48mmol/mol
26
What other tests do you run to diagnose DM
Screen urine for microalbuminuria
FBC, U&Es, Liver biochem, Fasting blood sample for cholesterol and triglycerides
Blood pH to test for DKA
27
Diabetes can be secondary to what conditions?
```
Pancreatitits
Trauma
Neoplasia of pancreas
Acromegaly
Cushing syndrome
Addisons
Drugs - Thiazide diuretics, Beta-blockers, immunosuppressives, Thyroid hormone
```
28
What is the MDT approach to DM treatment?
Education on disease and risks
Maintain lean weight, cease smoking and take care of feet
Encourage exercise
Low fat and sugar diet
29
Drug treatment for DMT1?
Synthetic human insulin via subcut injection
Short acting insulin given after a meal
Long acting insulin given before a meal
30
Complications of insulin treatment?
Hypoglycemia - most common
Injection site - lipohypertrophy
Insulin resistance
Weight gain - insulin makes people hungry
31
First line treatment of DMT2
```
Lifestyle and dietary changes
Nutrient load spread throughout day
BP control - RAMIPRIL
Hyperlipidaemia control - STATINS
ORLISTAT - reduces fat absoprtion
```
32
Second line treatment of DMT2?
ORAL METFORMIN
- reduces rate of gluconeogenesis
- Increases cells sensitivity to insulin
- helps with weight issue
- Reduces CVD risk in diabetes
ORAL GLICLAZIDE
- If metformin not working
- promotes insulin secretion
- ineffective in patients with no beta-cell mass
- Avoided in pregnancy
33
Contraindications of metformin
Heart failure, liver disease or renal disease
34
What is hyperosmolar hyperglycaemic state?
Life threatening emergency characterised by marked hyperglycemia, hyperosmolality and mild or no ketosis
Characteristic of uncontrolled type 2 diabetes mellitus
35
RIsk factors for hyperosmolar hyperglycaemic state
Infection - most common cause, particularly pneumonia
Consumption of glucose rich fluids
Thiazide diuretics or steroids
36
Pathophysiology of hyperosmolar hyperglycaemic state
Endogenous insulin levels are reduced but are still sufficient to inhibit hepatic ketogenesis but insufficient to inhibit hepatic glucose production
37
Presentation of hyperosmolar hyperglycaemic state
```
Severe dehydration
Decreased levels of consciousness
Hyperglycemia
Hyperosmolality
No ketones in blood or urine
Stupor or coma
Bicarb NOT LOWERED
```
38
Diagnosis of hyperosmolar hyperglycaemic state
Blood glucose > 11mmol/L
Urine stick testing shows heavy glycosuria
Plasma osmolality extremely high
Total body K+ low, serum K+ often raised due to absence of insulin which allows K+ to shift out of cells
39
Treatment of hyperosmolar hyperglycaemic state
Sensitive to insulin so lower rate of infusion
Fluid replacement
Low molecular weight heparin to reduce risk of thromboembolism, MI, stroke and arterial thrombosis
Restore K+ loss
Risk of cerebral oedema
40
Complications of diabetes
Reduced life expectancy
CV problems
CKD
Infections
41
Macrovascular complication of DM
Atherosclerosis which results in stroke, IHD and PVD
PVD can lead to lower limb amputation
42
Microvascular complications of DM
```
Diabetic retinopathy
- leading cause of blindness in the world
- causes microaneurysms which can burst
Diabetic nephropathy
Diabetic neuropathy
Cataracts
```
43
Causes of hypoglycemia in diabetics?
Due to insulin or sulphonylurea treatment
E.g. increased activity, missed meal, accidental overdose
44
Cause of hypoglycemia in non-diabetics
EXPLAIN
EX - exogenous drugs - insulin, alcohol binge with no food
P - pituitary insufficency
L - liver failure
A - addison's disease
I - Islets cell tumour & immune hypoglycemia
N - Non-pancreatic neoplasm
45
Treatment of hypoglycemia
Oral sugar and long-acting starch (toast)
46
What is the most common endocrine disorder?
Thyroid disease
47
What TSH and (T3 & T4) levels would you expect in Hyperthyroidism?
TSH - Low
T3 & T4 - High
48
What TSH and (T3 & T4) levels would you expect in Primary Hypothyroidism?
TSH - High
T3 & T4 - Low
49
What TSH and (T3 & T4) levels would you expect in Secondary Hypothyroidism?
TSH - Low
T3 & T4 - Low
50
Explain the TSH, T3 and T4 levels in hyperthyroidism?
Hyperthyroidism leads to more T3 and T4 being produced which suppresses TSH functions - So it's low.
Exception is a pituitary adenoma which secretes TSH - so it's high
51
Explain the TSH, T3 and T4 levels in hypothyroidism?
Primary - TSH levels are high as it's trying to stimulate more thyroid hormone release
Secondary (pituitary or hypothalamic) - TSH levels are low due to parts of the brain not working
52
What is the pathophysiology of Graves disease?
Autoimmune condition where TSH receptor antibodies cause 1hyperthyroidism.
TSH receptor antibodies mimic TSH and stimulate TSH receptors on the thyroid
53
What are the universal features of hyperthyroidism?
Imagine someone who's extremely stressed
```
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue Frequent loose Stools
Sexual dysfunction
```
54
Unique features of Grave's disease?
Exopthalmos - bulging of the eyeball due to inflammation and hypertrophy of the tissues behind the eyeball
Pretibial Myxoedema - deposits of mucin under the skin on anterior aspect of the leg. Gives a waxy, discoloured appearance
55
What drugs do you give to treat hyperthyroidism>
First line - Carbimazole (usually succesful in treating graves disease)
Second line - Propylthiouracil
Radioactive iodine
Beta blockers to treat Adrenalin related symptoms
Surgery
56
What is hashimoto's thyroiditis and what is it associated with?
Most common cause of hypothyroidism in developed world
Autoimmune inflammation of the thyroid gland.
Associated with anti-TPO antibodies and immunoglobulin antibodies
Initially causes a goitre and then atrophy of the thyroid gland
57
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
58
What else can cause hypothyroidism?
Hyperthyroidism treatments
Medications such as lithium
Central causes such as tumours, infection and radiation
59
Presentation and features of hypothyroidism?
```
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention
Heavy/irregular periods
Constipation
```
60
What is the management of hypothyroidism?
Replacement of thyroid hormone with levothyroxine
61
What is levothyroxine?
Synthetic T4 which metabolises to T3 in the body
62
What is Cushing's syndrome?
Refers to signs and symptoms that develop after prolonged abnormal elevation of cortisol
63
What is Cushing's disease?
A specific condition where a pituitary adenoma secretes excessive ACTH
64
Cushing's syndrome features? (Round in the middle, thin limbs and high levels of stress hormone)
```
Round moon face
Central obesity
Abdominal striae
Buffalo hump
Proximal limb muscle wasting
```
```
Hypertension
Cardiac hypertrophy
DMT2
Depression
Insomnia
```
Osteoporosis
Easily bruising and poor skin healing
65
Causes of Cushing's syndrome?
Exogenous steroids
Cushing's diseases
Adrenal adenoma
Paraneoplastic Cushing's
66
What is paraneoplastic Cushing's?
It's when excess ACTH is released from a cancer and stimulates excessive cortisol release.
Most common is Small Cell Lung Cancer
67
How to test whether someone has Cushing's Syndrome?
Dexamethasone Suppression Tests (DST)
68
Explain the Low Dose Dexamethasone Suppression Test
1mg of dexamethasone given at night and the levels of cortisol and ACTH are measured in the morning
Low cortisol --> normal
High/normal cortisol --> cushing's syndrome
69
Explain the High Dose Dexamethasone Test
8mg is given and it is used to work out the cause of the cushing's syndrome
Low cortisol -> Cushing's Disease
High/normal cortisol &
ACTH low -> Adrenal Cushings
ACTH high -> Ectopic ACTH
70
Treatment for Cushings?
Surgical removal of tumour
71
What is acromegaly?
The clinical manifestation of excessive growth hormone (GH)
72
Where is GH produced?
Anterior pituitary gland
73
Most common cause of unregulated GH secretion?
Pituitary adenoma
74
What is GHRH?
Growth hormone releasing hormone - can be secreted by lung or pancreatic cancers (V rare)
75
What happens if the pituitary adenoma grows too large?
Compresses the optic chiasm and leads to bitemporal hemianopia (loss of vision on outer half of both eyes)
76
Presentation of acromegaly
Headaches
bitemporal hemianopia
```
Prominent forehead and brow
Large nose
Large tongue
Large hands and feet
Large protruding jaw
Arthritis
```
Hypertrophic heart
Hypertension
DMT2
Colorectal cancer
77
Investigations for acromegaly
IGF-1 (raised)
Oral glucose tolerance test whilst measuring GH
MRI brain
Ophthalmology
78
Treatment of acromegaly
Surgical removal of the cancer
Pegvisomant
Somatostatin analogues
Dopamine agonists
79
What is Conn's syndrome?
Also known as primary hyperaldosteronism.
It's when the adrenal glands are directly responsible for producing too much aldosterone
80
What affect does aldosterone have on the kidney?
+Na reabsorption from the distal tubule
+K secretion from distal tubule
+H secretion from collecting ducts
81
What is the effect of aldosterone on the body?
Causes the BP to rise
82
What effect does Conn's have on serum renin levels
Serum renin will be low as it is suppressed by high BP
83
What is secondary Hyperaldosteronism
It's where excessive renin stimulating the adrenal glands causes more aldosterone to be produced
84
Management of Hyperaldosteronism?
Aldosterone antagonists:
Eplerenone
Spironolactone
Treat underlying cause
Surgery
85
Most common cause of secondary hypertension?
Hyperaldosteronism
86
What is adrenal insufficency?
It's when the adrenal glands don't produce enough steroids; notable cortisol and aldosterone
87
What is Addison's disease?
Condition where the adrenal glands have been damaged resulting in a reduction of the secretion of cortisol and aldosterone.
Also called primary adrenal insufficiency
88
Main cause of Addison's?
Autoimmune
89
What is secondary adrenal insufficency?
Inadequate Adrenocorticotropic hormone (ACTH) stimulating the adrenal glands resulting in low cortisol release
90
What causes 2* adrenal insufficiency?
Result of loss or damage to the pituitary
91
What is 3* adrenal insufficiency?
Inadequate release of Corticotropin releasing hormone (CRH) by the hypothalamus
92
Usual cause of 3* adrenal insuffiency?
When the patient is on long term oral steroids and is suddenly taken off of them resulting in the hypothalamus not 'waking up' quickly enough
93
Symptoms of adrenal insufficiency?
```
Fatigue
Nausea
Cramps
Abdo pain
Reduced libido
```
94
Signs of adrenal insuffiency?
Bronze hyper-pigmentation of the skin
| Hypotension
95
What are the regions of the adrenal glands? Cortex and medulla
GFR - Makes Good Sex
(from outside in)
Zona glomerulosa - Mineralcorticoids (aldosterone)
Zona fasciculata - Glucocorticoids (cortisol)
Zona reticularis - Androgens
Medulla - secretes catecholamines (adrenaline and noradrenaline)
96
Investigations for adrenal insuffiency?
```
Hyponatraemia
Hyperkalaemia
Early morning cortisol
*Short synACTHen test* - test of choice
(ACTH high in 1* and low in 2*)
```
97
Treatment of adrenal insufficiency?
Replacement steroids and electrolytes
Hydrocortisone replaces cortisol
Fludrocortisone replaces aldosterone
98
What is diabetes insipidus (DI)
Lack of ADH or lack of response to ADH. This prevents the kidneys from being able to concentrate urine and leads to polyuria and polydipsia
99
What are the two types of DI and explain them
Nephrogenic
- when the collecting ducts don't respond to ADH
Cranial
- when the hypothalamus doesn't produce ADH for the pituitary gland to secrete
100
What causes each type of DI?
Nephrogenic
- drugs, particularly lithium
- Mutations in genes
- Intrinsic kidney disease
- Electrolyte disturbance
Cranial
- Brain tumours
- Brain malformations
- Head injury
- Brain infection
101
Presentation of DI
```
Polyuria
Polydipsia
Dehydration
Postural hypotension
Hypernatreamia - water loss in excess of Na+ loss (Na becomes more concentrated)
```
102
Investigation for DI
Water deprivation test
No fluids taken for 8 hours
Urine osmolality measured and synthetic ADH (desmopressin) administered
8 hrs later urine osmolality measured again
Cranial
- After deprivation LOW
- After ADH HIGH
Nephrogenic
- After deprivation LOW
- After ADH LOW
Primary Polydipsia
- After deprivation High
- After ADH HIGH
103
Management of DI
Try and treat underlying cause
Desmopressin can be used
104
What is Phaeochromocytoma
Tumour of the adrenaline-secreting chromaffin cells which causes an excess of adrenaline to be released.
Adrenaline is usually released in bursts giving periods of worse symptoms
Presentation - fight or flight response
105
What is syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Excess ADH secretion due to the posterior pituitary or can be down to cancers such as small cell lung cancer
106
Symptoms of SIADH
```
Headache
Fatigue
Muscle aches and cramps
Confusion
Severe hyponatraemia - can cause seizures
```
107
How does SIADH cause hyponatraemia?
Excess water reabsorption dilutes sodium in the blood and patients gets euvolaemic hyponatraemia
108
Causes of SIADH (many)
```
Post-op from major surgery
Infection
Head injury
Medications
Meningitis
```
