Endocrine Flashcards
(626 cards)
1
Q
Name 5 diseases of the pituitary.
A
- Benign pituitary adenoma
- Craniopharyngioma
- Trauma
- Sheehans
- Sarcoid / TB
2
Q
What are the three vital presentation points of pituitary tumour?
A
- Pressure on local structures
- Pressure on normal pituitary function - HYPOPITUITARISM
- Functioning tumour - HYPERPITUITARISM
3
Q
What local structure is at risk with a pituitary tumour? What is the outcome?
A
Optic chiasm, causing bitemporal hemianopia
4
Q
What does hypopituitarism (as a result of a pituitary tumour) look like in males?
A
- Pale
- No body hair (9 months to occur)
- Central obesity
- Effeminate skin
5
Q
What does hypopituitarism (as a result of a pituitary tumour) look like in females?
A
- Loose body hair
- Sallow complexion
6
Q
What is the main danger with hypopituitarism?
A
Cortisol deficiency can be fatal
7
Q
What three outcomes can hyperpituitarism cause?
A
- Prolactinoma
- Acromegaly
- Cushing’s
8
Q
What is a prolactinoma?
A
Benign pituitary adenoma results in an increase in prolactin production
9
Q
What is the clinical presentation for prolactinoma?
A
- Usually young women
- Increased milk production
- Galactorrhoea
- Reduced fertility
- Amenorrhoea
10
Q
How do you treat prolactinoma?
A
Dopamine agonist which inhibits prolactin release
e.g. CABERGOLINE
11
Q
What is acromegaly?
A
Excessive production of growth hormone by the pituitary
12
Q
What is the clinical presentation of acromegaly?
A
- Thick, greasy, sweaty skin
- Enlarged organs (e.g. cardiomegaly increasing risk of heart disease)
13
Q
What is Cushing’s disease?
A
Increased production of ACTH by pituitary (causing increased CTH)
14
Q
What is the clinical presentation for Cushing’s?
A
- Too much cortisol
- Central obesity
- Bruising
- Thin skin
- Osteoporosis
- Ulcers
- Purple stretch marks
15
Q
Define diabetes mellitus.
A
Syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance, or both
16
Q
What does hyperglycaemia cause?
A
Serious microvascular or macrovascular problems
17
Q
What are some microvascular problems caused by hyperglycaemia?
A
- Retinopathy
- Nephropathy
- Neuropathy
18
Q
What are some macrovascular problems caused by hyperglycaemia?
A
- Strokes
- Renovascular disease
- Limb ischaemia
- Heart disease
19
Q
What are the normal blood glucose levels?
A
3.5-8.0mmol/L
20
Q
Where does glucose homeostasis take place?
A
Liver
21
Q
How is glucose stored in the liver?
A
As glycogen
22
Q
If blood glucose is high, how does the liver react?
short term and long term hyperglycaemia
A
Short term - glycogenosis
Long term - Lipogenesis
23
Q
If blood glucose is low, how does the liver react?
short term and long term hypoglycaemia
A
Short term - glycogenolysis
Long term - gluconeogenesis
24
Q
How much glucose is produced and utilised each day?
A
~200g
25
Where is the majority of glucose derived from?
Hepatic gluconeogenesis
26
What fuel does the brain use?
Glucose, metabolised to CO2 + H₂O
27
Why can't the brain use free fatty acids for fuel?
They cannot cross the blood brain barrier
28
Does insulin affect the brain's uptake of glucose?
No, glucose uptake is obligatory and is independent of insulin
29
What do muscles and fat respond to with regards to insulin absorption?
They have insulin-responsive glucose transports, and absorb glucose in response to postprandial peaks in glucose and insulin
30
How does muscle tissue store and use glucose?
Stored as glycogen
| Metabolised to lactate or CO2 + H₂O
31
How does fat use glucose?
As a substrate for triglyceride synthesis
32
What is the product of lipolysis of triglycerides?
Lipolysis of triglycerides releases FAs + glycerol, and the glycerol is used as a substrate for hepatic gluconeogenesis
33
What does insulin do?
- Suppresses hepatic glucose output
| - Increases glucose uptake into insulin sensitive tissues
34
How does insulin suppress hepatic glucose output?
Decreases glycogenolysis and gluconeogenesis
35
How does insulin increase glucose uptake into insulin sensitive tissues?
- Causes glycogen and protein synthesis in muscles
- Causes fatty acid synthesis in fats
- Suppresses lipolysis and ketogenesis
36
Describe biphasic insulin release
- Pancreatic B-cells sense the rising glucose levels and aim to metabolise it by releasing insulin
- First phase response is RAPID release of stored insulin
- If glucose levels remain high, second phase is initiated (new insulin is synthesised and released)
37
What does glucagon do?
- Increases hepatic glucose output
- Reduces peripheral glucose uptake
- Stimulates peripheral release of gluconeogenic precursors
- Stimulates lipolysis and ketogenesis
38
How does glucagon increase hepatic glucose output?
Increases glycogenolysis and gluconeogenesis
39
What other hormones are involved in glucose regulation?
- Adrenaline
- Cortisol
- Growth hormone
These increase glucose production in liver and reduce its utilisation in fat and muscle
40
Where is insulin coded for on the genome?
Chromosome 11
41
Which cells produce insulin?
Beta cells of the Islets of Langerhans of the pancreas
42
What is the precursor for insulin?
Proinsulin
43
What is the structure of proinsulin? What happens when proinsulin becomes insulin?
- Alpha and beta chains of insulin joined together by a C peptide
- Proinsulin is cleaved from C peptide and then is used to make insulin
- Insulin is packaged into insulin secretory granules
44
What is the difference between naturally produced insulin and synthetic insulin?
Synthetic insulin does not have a C peptide
45
What happens to insulin immediately after it is secreted into the blood?
It enters the portal circulation and is carried to the liver
46
How much insulin is extracted and degraded in the liver?
~50%
47
What is the main action of insulin in the fasting state?
Regulate glucose release by the liver
48
What is the main action of insulin in the post-prandial state?
Promote glucose uptake by fat and muscle
49
Are cell membranes inherently permeable to glucose?
No, GLUT proteins are required
50
How does insulin cross the cell membrane?
Specialised glucose-transporter (GLUT) proteins carry it across the membrane
51
What does GLUT-1 do?
Enables basal non-insulin-stimulated glucose uptake into many cells
52
What does GLUT-2 do?
Transports glucose into beta-cells and enables them to sense blood glucose levels
53
Where are GLUT-2 proteins found?
In beta-cell in the Islets of Langerhans mainly
| also found in renal tubules and hepatocytes
54
How do GLUT-2 proteins work?
They are low affinity transports that only allows glucose into the beta-cells when there is a high glucose concentration
Thus, they are able to detect high glucose levels and trigger the release of insulin in response
55
What does GLUT-3 do?
Enables non-insulin-mediated glucose uptake into brain neurones and placenta
56
What does GLUT-4 do?
Mediates peripheral action of insulin
It is the channel through which glucose is taken up into muscle and fat tissue cells following stimulation of the insulin receptor by insulin binding to it
57
Describe insulin receptors
Glycoprotein, coded for on the short arm of chromosome 19, which straddles cell membranes
58
What happens when insulin binds to an insulin receptor?
It activates tyrosine kinase, and initiates a cascade response
One consequence of the cascade response is the migration of GLUT-4 transporters to the cell surface, thus increasing transportation of glucose into the cell
59
What does hypoglycaemia stimulate?
Release of glucagon, which stimulates;
- Glycogenolysis (glycogen -> glucose)
- Gluconeogenesis (lactic acid / amino acids -> glucose)
60
Diabetes may occur secondary to other conditions, including...
- Pancreatic pathology (e.g. pancreatectomy, chronic pancreatitis, haemochromatosis)
- Endocrine diseases (e.g. acromegaly and Cushing's disease)
- Drug induced (commonly by thiazide diuretics and corticosteroids)
- Maturity onset of diabetes of youth (MODY)
61
Are type 1 diabetics usually older or younger?
Younger (<30yrs)
62
Are type 2 diabetics usually older or younger?
Older (>30yrs)
63
Are type 1 diabetics usually lean or overweight?
Lean
64
Are type 2 diabetics usually overweight or lean?
Overweight
65
Which ethnic groups are at higher risk of developing type 1 diabetes?
Northern European (particularly Finland)
66
Which ethnic groups are at higher risk of developing type 2 diabetes?
Asian, African, Polynesian, and Native American
67
Which type of diabetes is hereditary 90% of the time?
Type 1
68
Which type of diabetes is an autoimmune disease?
Type 1
69
Which type of diabetes causes ketonuria?
Type 1
70
What are the clinical features of type 1 diabetes?
- Insulin deficient
- Higher risk of ketoacidosis
- Insulin dependent
71
What are the clinical features of type 2 diabetes?
- Partial insulin deficiency initially
- Potentially in a hyperosmolar state
- Will eventually need insulin when B-cells fail
72
Define diabetes mellitus type 1 (DMT1).
Disease of insulin deficiency, usually caused by autoimmune destruction of beta-cells of the pancreas
73
When is DMT1 typically manifested?
In childhood, reaching peak incidence at puberty
74
What is LADA?
Latent autoimmune diabetes in adults
- 'Slow burning' variant of DMT1 with slower progression to insulin deficiency
75
Describe the aetiology of DMT1
- Autoimmune (auto-antibodies forming against insulin and islet beta cells)
- Idiopathic
- Genetic susceptibility
76
What other autoimmune diseases is DMT1 associated with?
- Autoimmune thyroid
- Coeliac disease
- Addison's disease
- Pernicious anaemia
77
What environmental factors can contribute to DMT1?
- Dietary constituents
- Enteroviruses (e.g. Coxsackie B4)
- Vitamin D deficiency
- Clean environments
78
How does DMT1 affect the liver?
Continued breakdown of liver glycogen (producing more glucose and ketones), leading to glycosuria and ketonuria, as there is more glucose in the blood
79
How does DMT1 affect skeletal muscles and fats?
- Blood glucose increases
- When blood glucose >10mmol/L, the body can no longer absorb glucose
- Therefore, you become thirsty and get polyuria as the body attempts to remove excess glucose
80
What happens if DMT1 patients don't take their insulin?
DIABETIC KETOACIDOSIS
81
Describe diabetic ketoacidosis
- Results from a reduced supply of glucose (since there will be a significant decline in circulating insulin) and an increase in FA oxidation (due to increase in circulating glucagon)
- Increased production of acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them
- Ketone bodies (pH 3.5) lowers pH of blood, causing ketoacidosis
82
What is the major consequence of acidification of the blood?
Impaired ability of haemoglobin to bind to oxygen
83
What does the presence of ketones in the blood do to a patients breath?
Causes it to smell of peardrops (ketones)
84
What are the consequences of excess fat breakdown in ketoacidosis?
- Acidotic
- Anorexic
- Dehydration, leading to AKI
- Hyperglycaemia
- Death
85
What results from the eventual complete beta-cell destruction DMT1?
Absence of serum C-peptide
86
What is diabetes mellitus type 2 (DMT2)?
Combination of insulin resistance and less severe insulin deficiency
87
Who tends to get DMT2?
- Populations enjoying an affluent lifestyle
- >30yrs
- Overweight (lack of exercise, calorie / alcohol excess)
- South Asian, African, Caribbean, middle eastern and Hispanic ancestry
88
What is the link between DMT2 and low birth weight?
Association between low weight (as a result of poor nutrition) and birth and 12months with glucose intolerance in later life
This is thought to be caused by poor nutrition impairing beta-cell development and function
89
What is the difference in insulin uptake between healthy people and DMT2 patients?
Insulin stills binds to its receptor normally, but insulin resistance develops post-receptor
90
How much is the mass of beta cells reduced by at the time of diagnosis of DMT2?
~50%
91
At autopsy, what does the pancreas of a DMT2 patient look like?
Amyloid deposition in the islets of the pancreas, derived from a peptide (amyloid) co-secreted with insulin
92
What is an early sign of DMT2?
Loss of first phase of normal biphasic insulin release
93
What is established DMT2 associated with?
Hypersecretion of insulin from depleted beta-cell populations
94
What are circulating insulin levels like in DMT2 patients?
Higher than in healthy individuals, but inadequate to restore normal glucose homeostasis
95
Why are insulin levels higher in DMT2 patients?
Increased glucose production from liver (due to inadequate suppression of gluconeogenesis)
- Reduced glucose uptake by peripheral tissues (insulin resistant)
96
How does hyperglycaemia and lipid excess affect beta cells?
Toxic to beta cells (glucotoxicity), which causes further beta cell loss and deterioration of glucose homeostasis
97
What is the Starling curve of the pancreas?
Circulating insulin levels are typically higher than in non-diabetics following diagnosis and tend to rise further, only to decline again after months or years due to eventual secretory failure
98
Do DMT2 patients become ketoacidotic?
No, even a small amount of insulin can halt the breakdown of fat and muscle into ketones
99
Do DMT2 patients get glycosuria?
Yes
100
What is prediabetes?
Preliminary phase of impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
101
What is prediabetes useful for?
It is a unique window for lifestyle intervention to prevent full DMT2 progression
102
Which is more likely to progress to DMT2; IFG or IGT?
IGT
103
If a patient has IGT, what are the...
a) fasting plasma glucose levels
b) oral glucose tolerance of 2hrs glucose levels
Fasting plasma glucose <7mmol/L
Oral glucose tolerance of 2hrs glucose > 7.8-11mmol/L
104
If a patient has IFG, what are the fasting plasma glucose levels?
Fasting plasma glucose 6.1-7mmol/L
105
What is the typical clinical presentation for DMT1?
- Leaner
- Marked polydipsia
- Marked polyuria
- Weight loss
- Ketosis
106
What is the typical clinical presentation for DMT2?
- Overweight in abdominal area
- Polydipsia
- Polyuria
- Weight loss
- Ketosis (only when very advanced with total insulin deficiency)
LESS MARKED THAN DMT1
107
How long is the history for a patient presenting with DMT1?
Usually 2-6 week history
108
What is the classic triad of symptoms for a patient presenting with DMT1?
- Polyuria and nocturia
- Polydipsia
- Weight loss
109
Why does DMT1 cause polyuria and nocturia?
- Glucose draws water into urine by osmosis
| - Not enough glucose can be reabsorbed as kidneys have reached renal maximum reabsorptive capacity
110
Why does DMT1 cause polydipsia?
Due to loss of fluid and electrolytes from excess glucose and thus water being lost in urine
111
Why does DMT1 cause weight loss?
- Fluid depletion and accelerated breakdown of fat and muscle secondary to insulin deficiency
112
What is the subacute presentation of diabetes?
- Less marked acute presentation symptoms (e.g. polyuria, polydipsia, etc.)
- Lethargy
- Visual blurring (due to glucose-induced changes in refraction)
- Pruritus vulvae or balantis (due to Candida infection)
113
What are the complications of diabetes that patients might present to their GP with?
- Staphylococcal skin infections
- Retinopathy found by optician
- Polyneuropathy causing tingling and numbness in feet
- Erectile dysfunction
- Arterial disease resulting in MI or peripheral gangrene
114
Who is asymptomatic diabetes more common in?
Older people, who have raised renal threshold for glucose
115
What can you not use as a diagnostic criteria in asymptomatic diabetes?
Glycosuria is NOT diagnostic for diabetes, but indicates the need for further investigations
116
What might you observe on the skin in a physical examination that suggests severe insulin resistance?
Acanthosis nigerians - blackish pigmentation at nape of neck and in axillae
117
At what value is the random plasma glucose concentration diagnostic for diabetes?
Random plasma glucose >11.1mmol/L = DIABETES DIAGNOSIS
118
At what value is the fasting plasma glucose concentration diagnostic for diabetes?
Fasting plasma glucose > 7mmol/L = DIABETES DIAGNOSIS
119
What is the difference in diagnosing diabetes between symptomatic and asymptomatic patients?
In symptomatic patients, you only need ONE abnormal blood glucose conc. value
In asymptomatic patients, you need TWO abnormal blood glucose conc. values
120
If you do an oral glucose tolerance test on a patient who is FASTING, what result is diagnostic for diabetes?
OGTT: Fasting > 7mmol/L = DIABETES DIAGNOSIS
121
If you do an oral glucose tolerance test on a patient who 2 hours after glucose, what result is diagnostic for diabetes?
OGTT: 2 hours after glucose > 11.1mmol/L = DIABETES DIAGNOSIS
122
What test can detect IGT?
Oral glucose tolerance tests (OGTT)
123
If you do an oral glucose tolerance test on a patient who is FASTING, what result is diagnostic for IGT?
OGTT: Fasting < 7mmol/L = IGT DIAGNOSIS
124
If you do an oral glucose tolerance test on a patient who 2 hours after glucose, what result is diagnostic for IGT?
OGTT: 2 hours after glucose > 7.8-11.0mmol/L = IGT DIAGNOSIS
125
What does HbA1c measure?
Measures amount of glycated haemoglobin, thus tells you glucose concentration
126
At what level is HbA1c diagnostic for diabetes?
HbA1c > 6.5% normal = DIABETES DIAGNOSIS
HbA1c > 48mmol/mol = DIABETES DIAGNOSIS
127
How do you assess kidney disease in diabetic patients?
Screen urine for microalbuminuria
128
Why do you look at blood pH in diabetics?
To look for metabolic acidosis (high H+ and low HCO3-, due to ketoacidosis)
Seen in DMT1 and advanced DMT2
129
What approach is vital to treating DMT1 and DMT2?
MDT approach
130
What must you do to a patient with newly diagnosed diabetes?
Educate them on the disease and risks
131
What lifestyle factors can you amend to help control diabetes?
- Maintain lean weight
- Stop smoking
- Take care of feet
- Regular physical activity
132
What should the diet of a diabetic look like to aid in good glycemic control?
- Low in sugar
- High in starchy carbohydrates with low glycemic index (e.g. pasta)
- High in fibre
- Low in fat
133
How do you treat hypertension in diabetics?
ACE-inhibitors
e.g. RAMIPRIL
134
How do you treat hyperlipidaemia in diabetics?
Statins
e.g. SIMVASTATIN
135
What is the treatment for DMT1 patients who have been in ketoacidosis?
Insulin
136
What is the standard treatment for DMT1 patients who are lean and under 40?
Insulin
137
How do you ensure good control of DMT1?
Educate patients on self-adjusting insulin doses
138
How can DMT1 patients get help with their treatment?
- Phone support (24/7 nurse)
- Aware of how to modify diet and avoid binge drinking
- Ensure their partner knows how to avoid hypoglycaemia (e.g. sugary drinks)
139
How do DMT1 patients administer insulin?
Via subcutaneous injection into abdomen, thighs, or upper arm
140
What must an insulin-dependent diabetic do with regards to the DVLA?
Legal obligation to inform the DVLA
141
What happens if DMT1 patients don't change injection sites frequently?
Lipohypertrophy (fatty lumps)
142
What does the finger pricking glucose test tell a DMT1 patient?
- Before meal test informs about long-acting insulin doses
| - After a meal test informs about short-acting insulin doses
143
What are short-acting insulins?
- Start working within 30-60 minutes and last 4-6 hours
- Given 15-30 minutes before meals in patients on multiple dose regimens, and by continuous IV infusion during labour, medical emergencies, surgery, and patients using insulin pumps
144
What are short-acting insulin analogues?
- Fast onset and short duration but DO NOT IMPROVE DIABETIC CONTROL
- Reduced carry-over effect compared to soluble insulin
- Used with evening meal in patients who are prone to nocturnal hypoglycaemia
145
What are longer-acting insulins?
- Insulin premixed with retarding agents (either protamine or zinc)
- Can be intermediate (12-24 hours) or long-acting (more than 24hrs)
- Protamine insulins are known as isophane or NPH insulins
- Zinc insulins are known as lente insulins
146
Why does the insulin dose in newly diagnosed DMT1 patients have to be closely monitored in the beginning of treatment?
In many patients who present acutely with diabetes, there is some recovery of endogenous insulin secretion soon after diagnosis, and the insulin dose may need to be reduced
147
What is the most appropriate treatment for younger DMT1 patients?
Multiple injection regimen which improves control and allows greater meal flexibility
148
What are the complications of insulin treatment?
- Hypoglycaemia
- Injection site lipohypertrophy
- Insulin resistance
- Weight gain (insulin increases appetite)
149
What is the first line treatment for DMT2?
- Lifestyle and dietary changes
- Spread nutrient load
- Blood pressure control
- Hyperlipidaemia control
- Exercise
- Weight loss
150
How does a spread nutrient load help control DMT2?
Nutrient load should be spread throughout the day to reduce swings in blood glucose
151
How does orlistat help with obesity?
It is an intestinal lipase inhibitor, which reduces the absorption of fat from diet
152
When should you integrate second line treatments for DMT2?
When first line treatments have failed to control hyperglycaemia
153
What is the first thing you try in second line treatment of DMT2?
A biguanide, e.g. ORAL METFORMIN
154
What does oral metformin do?
- Reduces rate of gluconeogenesis in liver
- Increases cells insulin sensitivity
- Helps with weight issues
- Reduces CVS risk in diabetes
155
What are the side effects of oral metformin?
- Anorexia
- Diarrhoea
- Nausea
- Abdo. pain
156
What are the contraindications for biguanides (e.g. oral metformin)?
- Heart failure
- Liver disease
- Renal disease
Induce lactic acidosis
157
If HbA1c >53mmol/L 16 weeks after starting a biguanide, what should you do?
Prescribe a sulfonylurea (e.g. ORAL GLICLAZIDE)
158
What does oral gliclazide do?
Promotes insulin secretion
159
Who can you not use sulfonlyureas on?
- Pregnant women
| - Patients without functional beta-cell mass
160
What are the side effects of sulfonylureas?
- Hypoglycaemia
| - Weight gain
161
What must you remember when prescribing sulfonylureas to patients with renal impairment?
You can only use sulfonylureas which are primarily excreted by the liver
162
Which sulfonylurea should you use in the very elderly?
Oral tolbutamide, since it has a very short duration of action
163
What course of action should you take if at 6 months the HbA1c > 57mmol/L?
- Consider adding insulin (e.g. ISOPHANE INSULIN or a long-acting analogue)
- Consider a glitazone (e.g. ORAL PIOGLITAZONE) which replaces metformin and sulfonylureas
- Consider sulfonylurea receptor binders (e.g. ORAL NATEGLINIDE)
- Consider glucagon-like peptide analogues (GLPs)
164
What do glitazones do?
Increase insulin sensitivity
165
What are the side effects of glitazones (e.g. oral pioglitazone)?
- Hypoglycaemia
- Fractures
- Fluid retention
166
What contraindicates the use of glitazones?
- Congestive heart failure
| - Osteoporosis
167
How do you take sulfonylurea receptor binders?
30mins before a meal
168
When do you usually see diabetic ketoacidosis?
- Previously undiagnosed diabetes
- Interruption of insulin therapy
- Stress of intercurrent illness (e.g. surgery, infection)
169
Why do you never see DKA in non-advanced DMT2?
There is some residual insulin left which is enough to prevent hepatic ketogenesis
170
What is the most common error of DMT1 management which leads to DKA?
Patients reducing or omitting insulin because they feel unable to eat, owing to nausea or vomiting
INSULIN MAY NEED ADJUSTING BUT MUST NEVER EVER BE STOPPED
171
Briefly summarise DKA
Ketoacidosis is a state of uncontrolled catabolism (break down) associated with insulin deficiency
172
What happens in the total absence of insulin?
- Unrestrained increase in hepatic gluconeogenesis
| - Peripheral uptake of glucose by tissues is reduced
173
How do high circulating glucose levels affect urination?
It causes osmotic diuresis, leading to dehydration and loss of electrolytes
Glycosuria (high glucose in urine) draws water into the urine via osmosis
174
Why does glycosuria lead to dehydration?
Glucose in urine draws water out of circulation and into the urine, causing dehydration
175
How do high circulating glucose levels affect plasma osmolality and renal perfusion?
```
> High circulating glucose levels
> Glycosuria
> Osmotic diuresis
> Increased plasma osmolality
> Decreased renal perfusion
```
176
How does peripheral lipolysis lead to metabolic acidosis?
> Increase in circulating free fatty acids (FFAs)
> FFAs broken down into acetyl-CoA in hepatocytes
> Acetyl-CoA converted into ketone bodies in mitochondria
> Ketone bodies accumulate and cause metabolic acidosis
177
What bodily function contributes to dehydration and loss of electrolytes?
Vomiting
178
How does the respiratory system try to counteract acidosis?
Respiratory compensation of acidosis leads to hyperventilation
179
How does dehydration affect acidosis?
Progressive dehydration impairs renal excretion of H+ ions and ketones, aggravating acidosis
180
What happens when the body's pH falls below 7?
pH dependent enzyme systems in many cells function less effectively
181
What are 'stress hormones' and how do they affect the progression of ketoacidosis?
- Adrenaline, noradrenaline, glucagon, and cortisol
| - Released in response to dehydration
182
What is the clinical presentation of a patient with DKA?
- Ketone breath
- Ketonuria
- Dehydration
- Drowsiness
- Vomiting
- Sunken eyes
- Reduced tissue turgor
- Dry tongue (SEVERE cases)
- Kussmaul's respiration (respiratory compensation)
- Disturbance of consciousness
- Abdominal pain
- Low fever
183
What is Kussmaul's respiration?
Deep, rapid breathing
184
What is the blood glucose for DKA diagnosis?
> 11mmol/L - HYPERGLYCAEMIA
185
What is the plasma ketone value for DKA diagnosis?
> 3mmol/L - RAISED PLASMA KETONES
186
How do you measure plasma ketones in a suspected DKA patient?
Finger prick sample and near-patient meter that measures beta-hydroxybutyrate (major ketone)
187
What is the blood pH for DKA diagnosis?
pH < 7.3 - ACIDAEMIA
188
What is the bicarbonate value for DKA diagnosis?
bicarbonate < 15mmol/L - METABOLIC ACIDOSIS
189
How do you test for glycosuria and ketonuria in a suspected DKA patient?
Urine stick test
190
What would urea and creatinine values be like for a DKA patient?
Raised as a result of dehydration
191
What would the total body K+ values be like for a DKA patient?
Low / hypokalaemic, as a result of osmotic diuresis
192
What causes the difference between total body K+ values and serum K+ values?
Serum K+ is often raised due to absence of insulin, which allows K+ to shift out of cells
193
What would the FBC look like for a DKA patient?
May show raised white cell count even in absence of infection
194
What tests would you run on a suspected DKA patient to look for infection?
- Blood cultures
- CXR
- Urine microscopy
195
Why would you look for infection in a DKA patient?
Infection can trigger DKA
196
What tests would you run on a suspected DKA patient to look for MI?
- ECG
| - Cardiac enzymes
197
Why would you look for an MI in a DKA patient?
MI can trigger DKA
198
What is the immediate treatment for DKA patient?
- Immediate ABC management
- Replace fluid loss with 0.9% saline - 3L in 3hrs
- Restore electrolyte loss (K+)
- Restore acid-base balance over 24hrs
- Replace deficient insulin - give insulin AND glucose
199
How is acid-base balance restored in DKA patients?
The kidneys usually restore it themselves once circulating volume has been restored
200
Why do you give insulin and glucose to a patient with DKA?
- Give glucose to prevent hypoglycaemia
| - Give both to inhibit gluconeogenesis and thus ketone production
201
What are the complications of DKA management?
- Hypotension
- Coma
- Cerebral oedema
- Hypothermia
- Pneumonia (late complication)
- DVT (late complication)
202
If a DKA patient develops hypotension as a complication of treatment, how do you address this?
Increase circulating volume with saline
203
If a DKA patient falls into a coma, what do you do?
Insert a nano-gastric tube to prevent aspiration
204
Why would a DKA patient develop cerebral oedema as a complication of their treatment?
Rapid lowering of blood glucose, thus osmolality of blood
205
How long do the symptoms of DKA take to develop?
A few days
206
What is hyperosmolar hyperglycaemic state?
A life-threatening emergency, characterised by marked hyperglycaemia, hyperosmolality, and mild/no ketosis, and is usually the result of uncontrolled DMT2
207
Who tends to get hyperosmolar hyperglycaemic state?
Patients in middle / later life with undiagnosed diabetes
208
What are some of the risk factors associated with a hyperosmolar hyperglycaemic state?
- Infection (most common)
- Consumption of glucose rich fluids
- Concurrent medication (e.g. thiazide diuretics or steroids)
209
Describe the pathophysiology of a hyperosmolar hyperglycaemic state?
Endogenous insulin levels are reduced but are still sufficient to inhibit hepatic ketogenesis but insufficient to inhibit hepatic glucose production
210
What is the clinical presentation of a hyperosmolar hyperglycaemic state?
- Severe dehydration (secondary to osmotic diuresis)
- Decreased level of consciousness (secondary to elevation of plasma osmolality)
- Hyperglycaemia
- Hyperosmolality
- No ketones in blood or urine
- Stupor / coma
- Bicarbonate is NOT LOWERED
211
What are the blood glucose values for hyperosmolar hyperglycaemic state?
> 11mmol/L - HYPERGLYCAEMIA
212
What does a urine stick test show for a suspected hyperosmolar hyperglycaemic state patient?
Heavy glycosuria
213
What is the plasma osmolality like for a HHS patient?
Extremely high
214
What is the total body K+ value like for HHS patients?
Low as a result of osmotic diuresis, but serum is high due to absence of insulin which allows K+ to shift out of cells
215
What is the complication of treating HHS patients with insulin?
They are more sensitive, so you give a lower rate of infusion
216
What is the treatment for a HHS patient?
- Slow rate of insulin infusion
- Fluid replacement with 0.9% saline
- Low molecular weight heparin (e.g. SC ENOXAPARIN)
- Restore electrolyte loss
217
Why do you give a low molecular weight heparin to HHS patients?
Reduce the risk of thromboembolism, MI, stroke, and arterial thrombosis which patients are at a greater risk of due to hyperosmolality
218
What is a potential complication of treating HHS patients?
Risk of cerebral oedema - rapid lowering of blood glucose, and thus osmolality of blood
219
How does diabetes affect life expectancy?
Even well managed diabetes reduces life expectancy
220
What percentage of premature deaths in diabetics is caused by cardiovascular problems?
70%
221
What percentage of premature deaths in diabetics is caused by chronic kidney disease?
10%
222
What causes the associated complications of diabetes (er.g. CVD, CKD, etc)
Degree and duration of hyperglycaemia
223
Diabetes is a risk factor for atherosclerosis, TRUE OR FALSE?
True, and is worsened when combined with smoking, hypertension, and hyperlipidaemia
224
How much more likely are diabetics to have a stroke than healthy people?
Twice as likely
225
How much more likely are diabetics to have an MI than healthy people?
4x as likely, and MIs are more likely to be silent
226
What causes peripheral vascular disease?
Decreased perfusion to peripheries due to atherosclerosis
227
How much more likely are peripheral vascular disease patients to have lower limb amputation than healthy people?
15-40x
228
What are the symptoms of peripheral vascular disease?
Intermittent claudication and rest pain
229
What are the signs of peripheral vascular disease?
- Diminished / absent pedal pulses
- Coolness of feet & toes
- Poor skin and nails
- Absence of hair on feet and legs
230
How can you detect peripheral vascular disease?
Doppler ultrasound
231
How do you treat peripheral vascular disease?
- Walking through claudication pain (encourages formation of new collaterals)
- Surgical intervention
232
Which gender is at higher risk of macrovascular complications of DM?
Females, as DM removes the vascular advantage conferred by the female sex
233
How can you modify risk factors to prevent macrovascular complications of DM?
- Aggressive BP control
- Smoking cessation
- Statin treatment
- ACE inhibitor treatment (or angiotensin receptor blocker if intolerant)
234
Which branch of complications is specific to diabetes?
Microvascular complications
235
Which three sites are in particular danger of vessel damage with DM?
- Retina
- Glomerulus
- Nerve sheath
236
How long does it take for microvascular damage to manifest after diabetes diagnosis?
~ 10-20 years in young patients
237
What is the most common cause of blindness in the working population?
Diabetic retinopathy
238
What are the greatest risk factors for diabetic retinopathy (DR)?
- Long duration DM
- Poor glycemic control
- Hypertensive
- Insulin treatment
- Pregnancy
239
How do you reduce the risk of getting DR?
Keeping HbA1c below 7%, since each % increase increases DR progression exponentially
240
At diagnosis, what percentage of diabetics have early stage retinal damage?
~ 30%
241
What are microaneurysms of the retina of diabetics with background retinopathy?
Metabolic consequence of poorly controlled diabetes, causing intramural pericyte death and thickening of basement membrane of small blood vessels
242
What causes haemorrhages on the retina of diabetics with background retinopathy?
Breach of microaneurysms resulting in leakage of fluid into the retina
The fluid is cleared into the retinal veins, leaving behind protein and lipid deposits, resulting in hard exudates which are bright yellowish and white in colour
243
Describe pre-proliferative DR.
- Micro-infarcts within retina due to occluded vessels cause "cotton wool spots" - sign of retinal ischaemia
- Haemorrhage and venous bleeding
244
Describe proliferative DR.
- Consequence of damage to retinal blood vessels and resultant retinal ischaemia
- Ischaemia results in release of vascular growth factors (VEGF)
245
What do vascular growth factors do?
- Cause new blood vessels to grow in retina
- Some are inside retina (GOOD)
- Some emerge through retina and lie on surface (BAD)
- Causes stress within the eye and can result in poorly supported vessels bleeding
- Small haemorrhages give rise to pre-retinal haemorrhages
- Further bleeding causes vitreous haemorrhages which lead to sudden loss of vision
- Collagen tissue grows along margins of new vessels and form fibrotic bands, which can contract and pull on retina, causing further haemorrhage and tractional retinal detachment
246
Describe maculopathy.
Fluid from leaking vessels is cleared poorly in the macular area (since its anatomy differs from the rest of the retina)
247
What happens to the retina in maculopathy in DR?
It is distorted and thickened at the macula
248
How do you treat DR?
Laser therapy - it doesn't improve sight but it stabilises deterioration and prevents progression
249
What are the risks of laser therapy to treat DR?
- Loss of night vision
| - Loss of peripheral vision
250
How long after diagnosis of glomerular disease (as a complication of diabetes) does it take for clinical nephropathy to manifest?
15-25 years after diagnosis
251
How many diabetics suffer from clinical nephropathy secondary to glomerular disease?
25-35% of patients diagnosed under 30yo
252
Describe diabetic nephropathy
Thickening of basement membranes of glomerulus due to poor glycemic control, leading to microalbuminuria
253
What chemical present in the blood is an early warning sign of impending renal problems?
Albumin - MICROALBUMINURIA
254
What happens if you test for microalbuminuria using a conventional dipstick?
It shows up negative for proteins
255
How do you diagnose microalbuminuria?
Urine albumin:creatinine ratio > 3
256
How does microalbuminuria progress?
> Intermittent albuminuria
> Persistent proteinuria
> Induces transient nephrotic syndrome
257
What will a blood test of a patient with diabetic nephropathy show?
- Normochromic normocytic anaemia
| - Raised ESR
258
How do you treat diabetic nephropathy?
Aggressive treatment of blood pressure with ACE inhibitors (e.g. RAMIPRIL) or angiotensin receptor blockers (e.g. CANDESARTAN)
259
What should you NOT give someone with diabetic nephropathy?
Oral hypoglycaemic agents which are partially excreted via the kidneys
260
What action needs to be taken with a diabetic nephropathic's insulin?
Their insulin sensitivity increases so you need to lower insulin doses
261
What is the prognosis for diabetic nephropathy?
Many patients will develop end stage kidney disease and require dialysis and kidney transplants (eventually)
262
How many diabetics have diabetic neuropathy?
30-35%
263
What is the most common form of diabetic neuropathy?
Distal symmetrical neuropathy
264
How do isolated mononeuropathies form?
Occlusion of vasa nervorum
265
What are vasa nervorum?
Small arteries that provide blood supply to peripheral nerves
266
How do more diffuse neuropathies form?
The accumulation of fructose and sorbitol which disrupts the structure and function of the nerve
267
What are the risk factors for diabetic neuropathy?
- Hypertension
- Smoking
- HbA1c
- Diabetes duration
- BMI
268
What are the 'pain' clinical features of diabetic neuropathy?
- Allodynia (triggering of pain from stimuli that do not normally cause pain)
- Paraesthesia (abnormal dermal sensation with no apparent cause, e.g. tingling)
- Burning and pain (as though walking on broken glass) - WORSE AT NIGHT
269
What are the 'autonomic' clinical features of diabetic neuropathy?
- Postural hypotension
- Gastroparesis
- Diarrhoea
- Constipation
- Incontinence
- Erectile dysfunction
270
What are the 'insensitivity' clinical features of diabetic neuropathy?
"Glove and stocking" sensory loss
271
What can sensory loss of the feet lead to in diabetics?
Foot ulceration, infection, and amputation
272
Describe the 'mononeuritis multiplex' clinical feature of diabetic neuropathy
- Abrupt onset and sometimes painful
- Isolated palsies to nerves of external eye muscles (III & VI) are most common
- Characteristic feature of diabetic CN3 lesion is that pupillary reflexes are retained owing to sparing of the pupillomotor fibres
273
Describe the 'diabetic amyotrophy' clinical feature of diabetic neuropathy
- Typically seen in older men
- Painful asymmetrical wasting of quadriceps and other pelviformal muscles
- Knee reflexes diminished / absent
- Associated with poor glycaemic control but resolves with control
274
How do you treat diabetic neuropathy?
- Good glycaemic control
- Paracetamol
- Tricyclic antidepressants (e.g. AMITRIPTYLINE)
- Anticonvulsants (e.g. GABAPENTIN or PREGABLIN)
- Opiates (e.g. TRAMADOL)
- Transcutaneous nerve stimulation
- Avoidance of weight bearing
275
What is a serious consequence of insensitivity associated with diabetic neuropathy?
Diabetic foot ulceration
276
What percentage of diabetics experience a diabetic foot ulcer (DFU) in their lifetime?
15%
277
Describe the pathology of DFU
> Neuropathy increases risk of 'silent trauma' - patient injures foot but doesn't realise
- Neuropathy results in dry skin on feet, which means they are susceptible to cracking
> Causes ulcer formation
> Ischaemia means ulcer cannot heal
> Causes infection and eventually amputation
278
What is the clinical presentation of a DFU?
Painless, punched-out ulcer of foot in an area of a thick callus
279
How can you manage DFUs?
- FEET SCREENINGS
- Education
- Check feet daily (to detect ulcers early)
- Check shoes for sharps before putting them on
- Tie laces loosely
- Keep feet away from heat and check bath temperatures before stepping in
280
What are the four main threats to skin and subcutaneous tissue in diabetics with diabetic neuropathy?
- Infection - can take hold RAPIDLY
- Ischaemia
- Abnormal blood pressure - must not put pressure on a DFU
- Wound environment - use dressings that absorb & remove exudes
281
Why can poorly controlled diabetes lead to increased susceptibility to infections?
It impairs the function of polymorphonuclear leucocytes and confers
282
Which infections does poorly controlled diabetes confer an increased susceptibility to?
- UTIs
- Boils and abscesses
- Staphylococcal skin infections
- Mucocutaneous candidiasis
- Rectal abscesses
- Pyelonephritis
- Staphylococcal and pneumococcal pneumonia
- TB
- G-ve bacterial pneumonia
283
What can infections lead to in diabetics?
- Loss of glycaemic control
| - Ketoacidosis
284
What causes lipohypertrophies in diabetics?
Using the same injection site frequently
285
How can childhood diabetes affect the skin in later life?
Skin contractures are a common consequence of childhood diabetes
286
How can you demonstrate skin contractures in a patient?
> Ask them to join their hands as if in prayer
> Metacarpopalangeal and interphalangeal joints cannot be opposed
287
What is the most common endocrine emergency?
Hypoglycaemia
288
What is the definition of hypoglycaemia?
Plasma glucose < 3mmol/L
289
What is the aetiology of hypoglycaemia in diabetics?
Insulin or sulphonylurea treatment
- Increased activity
- Missed meals
- Overdose (accidental or non-accidental)
290
What is the aetiology of hypoglycaemia in non-diabetics?
- EXogenous drugs (e.g. insulin, alcohol binge with no food)
- Pituitary insufficiency
- Liver failure
- Addison's disease
- Islets cell tumour (insulinoma) & Immune hypoglycaemia
- Non-pancreatic neoplasm (e.g. fibrosarcomas and haemangiopericytomas)
Remember: EXPLAIN
291
What are the autonomic clinical presentation features of hypoglycaemia?
- Sweating
- Anxiety
- Hunger
- Tremor
- Palpitations
- Dizziness
292
What are the neuroglycopenic clinical presentation features in hypoglycaemia?
- Confusion
- Drowsiness
- Visual trouble
- Seizures
- Coma
293
How do you diagnose hypoglycaemia?
Fingerpick blood during attack (on filter paper if at home) then send for analysis
294
What do you look for in the blood if you have a suspected hypoglycaemic patient?
- Glucose
- Insulin
- C-peptide
- Plasma ketones
295
Why would a patient be hypoglycaemic hyperinsulinaemic?
- Insulinoma
- Sulfonylurea or insulin injection (only if no C-peptide in serum)
- Congenital
296
Why would a patient have low insulin and high ketones?
- Alcohol
- Pituitary insufficiency
- Addison's disease
297
How do you treat hypoglycaemia if a patient can eat?
Oral sugar and long-acting starch (e.g. toast)
298
How do you treat hypoglycaemia if a patient cannot swallow?
50% glucose IV or IM glucagon (if no IV access)
299
If a diabetic is hypoglycaemic what is it important you do?
Re-educate them on insulin use and safety
300
What is the most common endocrine disorder?
Thyroid disease
301
Which sex is more likely to get thyroid disease?
Females
302
What is the prevalence of hyperthyroidism?
2.5%
303
What is the prevalence of hypothyroidism?
5%
304
What is the most common clinical presentation of thyroid disease?
Goitre (5-15%)
305
What is a goitre?
A swelling of the thyroid gland that causes a palpable lump to form in the front of the neck which will move when you swallow
306
Why do goitres form in hyperthyroidism?
(e.g. in Grave's) there is excess stimulation of the TSH receptor, which stimulates the thyroid to produce more hormone and grow larger
307
Why do goitres form in hypothyroidism?
When the pituitary detects low thyroid levels, it produces more TSH which in turn stimulates TSH receptors on the thyroid, resulting in thyroid enlargement (aka. a goitre)
308
Where are goitres endemic?
In iodine deficient areas
309
What are the three physical descriptions of goitres?
- Diffuse
- Nodular
- Solitary
310
What causes a diffuse goitre?
- Graves' disease
- Hashimoto's thyroiditis
- De Quervain's
311
What causes a nodular goitre?
- Adenoma / cyst
| - Carcinoma
312
Define 'thyrotoxicosis'
Excess of thyroid hormones in blood
313
What are the mechanisms for thyrotoxicosis?
- Overproduction of thyroid hormones (hyperthyroidism)
- Leakage of preformed hormone from thyroid
- Ingestion of excess hormone
314
What causes leakage of preformed hormones from thyroid?
Follicular cells being destroyed by either infection or autoimmunity, thereby releasing 2-3 months supply of hormone
315
What causes hyperthyroidism?
- Graves' disease (MOST COMMON)
- Toxic multi-nodular goitre
- Toxic adenoma (benign)
- Ectopic thyroid tissue (metastases)
- Exogenous (iodine/T4 excess)
- De Quervain's thyroiditis (post-viral)
316
What is myxoedema?
Swelling of the skin and underlying tissues, giving a waxy appearance
317
What are the two categories of hypothyroidism?
Primary and secondary hypothyroidism
318
What are the causes of primary hypothyroidism?
- Primary atrophic hypothyroidism (PAH)
- Hashimoto's thyroiditis
- Iodine deficiency
- Post-thyroidectomy / radio iodine / anti-thyroid drugs
- Lithium / amiodarone
319
What is the definition of primary hypothyroidism?
Reduced T4, and thus reduced T3
320
What causes secondary hypothyroidism?
Hypopituitarism
321
What is the definition of secondary hypothyroidism?
Reduced TSH from anterior pituitary
322
What is Graves' disease?
Autoimmune induced excess production of thyroid hormone
323
Describe the epidemiology of Graves' disease?
- Most common cause of hypothyroidism (2/3rds of cases)
- More common in females
- Typical onset at 40-60yrs
324
What is a common trigger for hypothyroidism in women?
Post-partum
325
What are the risk factors for Graves' disease?
- Post-partum
- Genetics
- E.coli and other G-ve organisms
- Smoking
- Stress
- High iodine intake
- Vitiligo (AID)
- Addison's disease (AID)
- Pernicious anaemia (AID)
- Myasthenia gratis (AID)
- DMT1 (AID)
326
Why do E.coli and other G-ve organisms cause Graves' disease?
They contain TSH-binding sites so may initiate pathogenesis via 'molecular mimicry'
327
Describe the pathophysiology of Graves' disease
> Serum IgG antibodies specific for Graves' disease (TSH receptor stimulating antibodies, TSHR-Ab) bind to TSH receptors in thyroid
> Stimulates thyroid hormone production (T3 & T4) - antibodies behave like TSH
> Results in excess secretion of thyroid hormones and hyperplasia of thyroid follicular cells
> Hyperthyroidism and diffuse goitre
328
What is the ophthalmological clinical presentation SPECIFIC to Graves' disease?
- Retro-orbital inflammation and extraocular muscle swelling
- Eye discomfort, grittiness, increased tear production, photophobia, diplopia, reduce acuity
- Exophthalmos (protruding eye appearance)
- Proptosis (eye protrudes beyond orbit)
- Conjunctival oedema
- Corneal ulceration
- Ophthalmoplegia (paralysis of eye muscles)
329
How do you examine opthalmopathy?
CT scan or MRI of orbit
330
How can you conservatively treat eye deformities in Graves' disease?
- Smoking cessation
| - Sunglasses
331
How can you pharmacologically / surgically treat eye deformities in Graves' disease?
- IV methylprednisolone
- Surgical decompression
- Eyelid surgery
332
What is the dermopathy clinical presentation SPECIFIC to Graves' disease?
- Pretibial myxoedema (raised, purple-red symmetrical skin lesions over the anterolateral aspect of the shin)
- Thyroid acropachy (clubbing, swollen fingers and periosteal bone formation)
333
What are toxic multi-modulate goitres?
Nodular goitres that secrete thyroid hormones
334
What is the epidemiology for toxic multi-nodular goitres?
- Elderly people
- Common in older women
- Iodine deficient areas
335
What is the prognosis of drug therapy on toxic multi-nodular goitres?
Rarely produces prolonged remission
336
How many hyperthyroidism cases can be attributed to solitary toxic adenomas / nodules?
~ 5%
337
What is De Quervain's thyroiditis?
Transient hyperthyroidism, resulting from acute inflammation of the thyroid, probably due to viral infection
338
What usually accompanies De Quervain's thyroiditis?
- Fever
- Malaise
- Neck pain
339
How do you treat De Quervain's thyroiditis?
Treat with asipirin
Only give prednisolone for severely symptomatic cases
340
Which drugs can cause drug-induced hyperthyroidism?
- Amiodarone
- Iodine
- Lithium
341
What is amiodarone?
Anti-arrhythmic drug
342
Why can amiodarone cause both hyperthyroidism and hypothyroidism?
Hyperthyroidism - due to high iodine content of amiodarone
Hypothyroidism - since it inhibits the conversion of T4 to T3
343
What is the general clinical presentation for hyperthyroidism?
(i.e. all types, not specific to Graves')
HINT: There are 19
- Palpitations
- Diarrhoea
- Weight loss & appetite increase
- Oligomenorrhoea (infrequent periods)
- (potential) Infertility
- Heat intolerance (i.e. sweating a lot)
- Irritability / behaviour change
- Tremor
- Hyperkinesis
- Warm (peripheral vasodilation)
- Proximal myopathy and myoatrophy
- Lymphadenopathy and splenomegaly
- Anxiety
- Palmar erythema, warm moist palms, & fine hand tremor
- Lid lag and 'stare'
- AF (in elderly)
- Tachycardia (in elderly)
- Excessive height or growth rate (in children)
- Behaviour problems (e.g. hyperactivity) (in children)
344
What is the differential diagnosis for hyperthyroidism, and what should you look for to differentiate?
Anxiety
Look for;
- eye signs
- diffuse goitre
- proximal myopathy and atrophy
345
What test do you do to diagnose hyperthyroidism?
Thyroid function test (TST)
346
What are the results of a thyroid function test (TST) which would diagnose hyperthyroidism?
- Suppressed TSH
| - Raised T4 & T3 - DIAGNOSTIC
347
Why is TSH suppressed in someone with hyperthyroidism?
Due to negative feedback produced by hyperthyroidism
348
How would the TST results differ between primary and secondary hyperthyroidism?
TSH will be very elevated in secondary hyperthyroidism, as the problem is with the pituitary
Thus, negative feedback does not work to suppress pituitary TSH output
349
What antibodies will you find in the blood of someone with hyperthyroidism?
- Thyroid peroxidase (TPO)
- Thyroglobulin antibodies
(Only found in 80% of Graves' patients)
350
How do you differentiate between Graves' and a toxic adenoma of the thyroid?
Ultrasound
351
How do you diagnose someone with Graves', as opposed to another type of hyperthyroidism?
- Raised TSH receptor stimulating antibodies (TSHR-Ab) - DIAGNOSTIC OF GRAVES'
- Mild neutropenia
352
How do you rapidly control the symptoms of hyperthyroidism?
Beta-blockers, e.g. PROPANOLOL
353
Name 2 anti-thyroid drugs
- Propylthiouracil (PTU)
| - Carbimazole
354
What does propylthiouracil do?
Stops the conversion of T4 to T3
355
What does oral carbimazole do?
- Blocks thyroid hormone biosynthesis
| - Immunosuppressive effects (which will affect Graves' progression)
356
What strategies can you use when treating hyperthyroidism with carbimazole?
Describe them
- Titration therapy
> oral carbimazole for 4 weeks, then reduce doses according to thyroid function test
> TST: TSH, T4, T3
- Block-replace therapy
> oral carbimazole + thyroxine (T4)
> less of a risk of developing hypothyroidism
357
What is the risk of discontinuing drug treatment with Graves' disease?
Half of those with Graves' disease relapse with treatment discontinuation after 2 years
358
What are the side effects of anti-thyroid drugs?
- Agranulocytosis (main SE) - results in severe leukopenia
- Rash (common)
- Arthralgia
- Hepatitis
- Vasculitis
359
What is the risk of agranulocytosis with anti-thyroid drug treatment?
If they get a sore throat, mouth ulcers, and fevers you must STOP DRUG TREATMENT IMMEDIATELY
360
How can you treat hyperthyroidism?
- Beta-blockers (treats symptoms, not hyperthyroidism)
- Anti-thyroid drugs
- Radioactive iodine
- Surgery
361
What drug do you give in radioactive iodine treatment of hyperthyroidism?
Radioactive I(131)
362
What contraindicates radioactive iodine treatment of hyperthyroidism?
Pregnancy and breast feeding
363
Can you take antithyroid drugs and radioactive iodine at the same time?
No - you must stop antithyroid drugs 4 days before giving iodine
364
Why is radioactive iodine useful for treating hyperthyroidism?
Iodine is essential for thyroid hormone production, so it is readily taken up by the thyroid gland
365
Why is radioactive iodine an effective treatment for hyperthyroidism?
The radioactive iodine accumulates and results in local irradiation and tissue damage, with return to normal function over 4-12 weeks
366
What are the side effects of radioactive iodine treatment of hyperthyroidism?
- Discomfort in the neck
| - Initial hyperthyroidism (as you stop all anti-thyroid treatment)
367
When would you recommend surgery for hyperthyroidism?
- Patients with large goitres
- Poor response to drugs
- Severe side effects to drugs
368
Who gets subtotal thyroidectomies?
Patients who have been rendered euthyroid (normal functioning gland)
369
Who gets total thyroidectomies?
Patients with;
- large goitres
- suspicion of malignancy in a nodule
- Graves'
370
What do you need to do to prepare for thyroid surgery to treat hyperthyroidism?
- Stop anti-thyroid drugs 10-14 days before
| - Give potassium iodide to reduce vascularity of gland
371
What is the consequence of surgery to treat hyperthyroidism?
Patients become hypothyroid
372
What are the complications of thyroid surgery?
- Tracheal compression from post-operative bleeding
- Laryngeal nerve palsy resulting in hoarse voice
- Transient hypocalcaemia (due to removal of parathyroid gland too)
373
What are the complications of hyperthyroidism?
Thyroid crisis / thyroid storm - MEDICAL EMERGENCY
374
What is a thyroid storm / crisis?
Rare, life-threatening condition in which there is a rapid deterioration of thyrotoxicosis - RAPID T4 INCREASE
375
What are the features of thyroid storm?
- Hyperpyrexia
- Tachycardia
- Extreme restlessness
- Eventual delirium, coma, and death
376
What usually precipitates a thyroid crisis?
- Stress
- Infection
- Surgery
- Radioactive thyroid therapy in an unprepared patient
377
How do you treat thyroid storm?
- Oral carbimazole
- Oral propanolol
- Oral potassium iodide (to acutely block the release of thyroid hormone from gland)
- IV hydrocortisone (to inhibit peripheral conversion of T4 to T3)
378
Define hypothyroidism
Underactivity of the thyroid gland; may be primary (from disease of the thyroid) or much less commonly secondary to hypothalamic or pituitary disease
379
What is the chief cause of hypothyroidism?
Iodine deficiency
380
What is the most common cause of hypothyroidism in areas with no iodine deficiency?
Autoimmune / atrophic hypothyroidism
381
What is the prevalence of hypothyroidism?
0.1-2%
382
Which sex is more likely to get hypothyroidism?
Females
383
What is autoimmune hypothyroidism associated with?
Other autoimmune diseases (e.g. DMT1, pernicious anaemia, etc.)
384
Which conditions is hypothyroidism associated with?
- Turner's syndrome
- Down's syndrome
- Cystic fibrosis
- Primary biliary cirrhosis
- Ovarian hyper-stimulation
385
What causes autoimmune / atrophic hypothyroidism?
Antithyroid antibodies leading to lymphoid infiltration of the gland and eventual atrophy and fibrosis
386
Do you get goitres with autoimmune / atrophic hypothyroidism?
No - the thyroid / goitre atrophies
387
Describe the epidemiology of autoimmune / atrophic hypothyroidism
- More common in females
- Incidence increases with age
- Associated with other autoimmune conditions
388
Describe the epidemiology of Hashimoto's thyroiditis
- More common in females (60-70yrs)
| - Most common in middle age
389
Do you get goitres with Hashimoto's thyroiditis?
Yes - Hashimoto's thyroiditis produces atrophic changes with regeneration that result in goitre formation, due to lymphocytic and plasma cell infiltration
390
What does the thyroid feel like with Hashimoto's thyroiditis?
Firm and rubbery
391
What is thyroid peroxidase?
Essential enzyme for the production and storage of thyroid hormone
392
What do you blood results show in Hashimoto's thyroiditis?
Thyroid peroxidase antibodies (TPO-Ab) are present in high titres
393
How do you treat Hashimoto's thyroiditis?
Levothyroxine therapy to shrink the goitre
394
What is postpartum thyroiditis?
Transient phenomenon following pregnancy, which may cause hyperthyroidism, hypothyroidism, or the two sequentially
395
What is thought to be the cause of postpartum thyroiditis?
Modifications to the immune system necessary in pregnancy
396
How can postpartum thyroiditis progress?
It is usually self-limiting, but when conventional antibodies are found there is a high chance of it progressing to permanent hypothyroidism
397
What is postpartum thyroiditis often diagnosed as?
Postpartum depression
398
What does 'iatrogenic' mean?
Caused by treatment or examination
399
What are the iatrogenic causes of hypothyroidism?
- Thyroidectomy
| - Radioactive iodine treatment
400
Which drugs can induce hypothyroidism?
- Carbimazole
- Lithium
- Amiodarone
- Interferon
401
Do goitres form with iodine deficiency?
Yes
402
What is the difference between hypothyroid and euthyroid?
Hypothyroidism - underractive thyroid
Euthyroid - normal functioning thyroid
403
What are the symptoms of hypothyroidism?
- Hoarse voice
- Goitre
- Constipation
- Cold intolerant
- Weight gain
- Menorrhagia
- Myalgia
- Tired, low mood, dementia
- Myxoedema - accumulation of mucopolysaccharide in SC tissue
404
What are the clinical signs of hypothyroidism?
- Bradycardia
- Reflexes relax slowly
- Ataxia (cerebellar)
- Dry, thin hair/skin
- Yawning/drowsy/coma
- Cold hands +/- temperature drop
- Ascites
- Round puffy face
- Defeated demeanour
- Immobile +/- Ileus (temporary arrest of intestinal peristalsis)
- Congestive cardiac failure
Remember: BRADYCARDIA
405
What is the clinical presentation of a child with hypothyroidism?
- Slow growth velocity
- Poor school performance
- Arrest in puberty (sometimes)
406
If a young woman comes in with query hypothyroidism, when can you exclude this from your differential diagnoses?
If she has oligomenorrhoea, amenorrhoea, menorrhagia, infertility, or hyperprolactinaemia
407
If an elderly person comes in with query hypothyroidism, when can you exclude this from your differential diagnoses?
If they have cognitive impairment
408
What are the results of a TFT if someone has hypothyroidism?
- Raised serum TSH (confirms PRIMARY hypothyroidism)
| - Low serum free T4 - DIAGNOSTIC
409
What would you find in the blood of someone with Hashimoto's thyroiditis?
- Thyroid antibodies
- Organ specific-antibodies
e.g. TPO-Ab
410
What would the blood results be for someone with hypothyroidism?
- Anaemic
- Raised serum aspartate transferase from muscle / liver
- Increased serum creatinine kinase levels (myopathy)
- Hypercholesterolaemia
- Hyponatraemia (increase in ADH and impaired free water clearance)
411
What is the treatment for hypothyroidism?
Lifelong thyroid hormone replacement e.g. LEVOTHYROXINE (T4)
412
What do you have to do if you diagnose a patient with ischaemic heart disease with hypothyroidism?
Start levothyroxine on a lower dose and use with caution
413
What is the aim with hypothyroidism treatment?
Aim is normal TSH conc. which can be achieved with levothyroxine, but too much can completely suppress TSH and risks AF and osteoporosis
414
How do you monitor primary hypothyroidism?
- Titrate dose until TSH normalises
| - Check T4 levels 6-8 weeks after dose adjustment
415
How do you monitor secondary hypothyroidism?
- TSH will always be low
| - Monitor T4
416
What are the complications of hypothyroidism treatment with levothyroxine?
Myxoedema coma
417
What is myxoedema coma?
Severe hypothyroidism (reduced T4) which may result in confusion and coma (especially in the elderly)
418
What is the clinical presentation of myxoedema coma?
- Hypothermia
- Cardiac failure
- Hypoventilation
- Hypoglycaemia
- Hyponatraemia
419
How do you treat someone with myxoedema coma?
- IV / Oral T3
- Glucose infusion
- Gradual rewarming
420
Describe the epidemiology of thyroid carcinoma
- Not common
- 400 deaths pa in the UK
- More common in females
421
What is the risk factor for thyroid carcinoma?
Radiation
422
What are the five types of thyroid carcinoma? How common are they?
- Papillary (70%)
- Follicular (20%)
- Anaplastic (<5%)
- Lymphoma (2%)
- Medullary cell (5%)
423
Describe papillary thyroid carcinomas
- Well differentiated
- More common in young people
- Local spread
- Good prognosis
- Arise from thyroid epithelium
424
Describe follicular thyroid carcinomas
- Middle age
- Spread to lung / bone
- Good prognosis (usually)
- Well differentiated
- Arise from thyroid epithelium
425
Describe anaplastic thyroid carcinomas
- Very undifferentiated
- Arise from thyroid epithelium
- Aggressive
- Local spread
- Poor prognosis
426
Where do medullary cell thyroid carcinomas arise from?
Calcitonin C cells of thyroid gland
427
Over 90% of thyroid carcinomas secrete what?
Thyroglobulin
428
Do thyroid glands still function hormonally even if they are cancerous (thyroid carcinomas)?
No - thyroid carcinomas are minimally active hormonally
429
What can you use as a tumour marker for thyroid carcinomas?
Thyroglobulin
430
What do 90% of thyroid carcinomas present as clinically?
Thyroid nodules
431
In 5% of thyroid carcinoma cases, what else do they present with?
- Cervical lymphadenopathy
| - Lung, cerebral, hepatic, or bone metastases
432
What appearance of the thyroid gland should make you think 'thyroid carcinoma'?
- Increases in size
- Hardens
- Irregular shape
433
Why might patient with thyroid carcinomas go to the doctor?
- Dysphagia (difficulty swallowing)
| - Hoarseness of voice
434
How do you distinguish between benign and malignant nodules?
Fine need aspiration cytology biopsy
435
Before you operate on a thyroid carcinoma, what do you need to do?
A blood test to check if patient is hypothyroid or hyperthyroid, as this needs to be treated before surgery
436
How can you differentiate between benign and malignant thyroid tumours?
Ultrasound of thyroid
437
How can you treat thyroid carcinomas?
- Radioactive iodine therapy
- Levothyroxine
- Chemotherapy
- Thyroidectomies
438
Why should you give levothyroxine to patients with thyroid carcinomas?
To keep TSH reduced as it is a growth factor for the cancer
439
What is the specific treatment for papillary / follicular thyroid carcinomas?
- Total thyroidectomy
| - Ablative radioactive iodine
440
What is the specific treatment for anaplastic thyroid carcinomas and lymphomas?
- External radiotherapy (for brief respite)
| - Mainly palliative
441
What is the specific treatment for medullary thyroid carcinomas?
- Thyroidectomy
| - Lymph node removal
442
Define Cushing's syndrome
General term which refers to chronic, excessive, and inappropriately elevated of circulating cortisol, whatever the cause
443
What mimics Cushing's syndrome?
Alcohol excess
444
Define Cushing's disease
Specifically refers to excess glucocorticoids, resulting from inappropriate ACTH secretion from the pituitary due to tumour
445
Where is cortisol released from?
Zona glomerulosa of the adrenal cortex
446
What are the functions of cortisol?
- Increases carbohydrate and protein catabolism
- Increases deposition of fat and glycogen
- Na+ retention
- Increased renal K+ loss
- Diminished host response to infection
447
What determines CRH and cortisol release?
Circadian rhythms and stress
448
When are CRH / cortisol levels the highest?
7/9am
449
When are CRH / cortisol levels the lowest?
Midnight
450
What is the most common cause of Cushing's syndrome?
Oral steroids, i.e. glucocorticoid therapy
451
What is the most common endogenous cause of Cushing's syndrome?
Raised ACTH
452
What is the main cause of raised ACTH?
Pituitary adenoma (Cushing's disease)
453
When might people normally have high cortisol levels?
- Alcohol pseudo-Cushing's syndrome
- Depression
- Obesity
- Pregnancy
454
What are the two categories of causes of Cushing's syndrome?
- ACTH-dependent causes (RAISED ACTH)
| - ACTH-independent causes (LOW ACTH due to negative feedback from raised cortisol)
455
How does Cushing's disease result in Cushing's syndrome?
Benign ACTH-secreting pituitary adenoma causes bilateral adrenal hyperplasia
456
Describe the epidemiology of Cushing's disease
- Equal prevalence in men and women
| - Peak age is 30-50yrs
457
What is ectopic ACTH production?
An ACTH-producing tumour elsewhere the body (particularly small cell lung cancers and carcinoid tumours)
458
What are the three main causes of ACTH-dependent Cushing's syndrome?
- Cushing's disease (MOST COMMON)
- Ectopic ACTH production
- ACTH treatment (e.g. for asthma)
459
What are the two ACTH-independent causes for Cushing's syndrome?
- Adrenal adenoma (benign tumour of adrenal gland that releases cortisol)
- Iatrogenic (e.g. administration of glucocorticoid, e.g. PREDNISOLONE)
460
What is the clinical presentation of Cushing's syndrome?
- Obesity
- Plethoric complexion with moon face
- Mood change
- Proximal weakness
- Gonadal dysfunction
- Muscle atrophy
- Thin skin that bruises easily
- Purple striae (breasts, abdomen, thighs)
- Acne
- Increased BP
- Failure for children to grow tall despite excess weight
- Infections
- Osteoporosis
- Hyperglycaemia
461
What is the fat distribution like in patients with Cushing's syndrome?
Typically central, affecting trunk, abdomen, and neck
462
Why are patients with Cushing's syndrome more susceptible to infections?
Cortisol has anti-inflammatory and poor healing properties
463
What is the differential diagnosis for Cushing's syndrome?
Pseudo-Cushing's syndrome
464
What causes pseudo-Cushing's syndrome and how do you treat it?
- Alcohol excess
| - 1-3 weeks of alcohol abstinence
465
When diagnosing Cushing's syndrome, what is it important you do?
Take a careful drug history, as it can be caused by oral steroids
466
If the random plasma cortisol results show increased levels in a suspected Cushing's syndrome patient, what should you do?
Proceed to 1st line test
467
What external factors may make random plasma cortisol blood results come up high?
- Illness
- Time of day
- Stress
468
What is the basis for the first line test in Cushing's syndrome?
Dexamethasone should, in a healthy patient, send negative feedback to the pituitary and hypothalamus resulting in decrease ACTH and thus reduced cortisol
The first line test is to give oral dexamethasone
469
Describe the first line test for Cushing's syndrome
> 1mg oral dexamethasone 00:00
> Measure serum cortisol at 8am
> Normally there will be cortisol suppression < 50nmol/L
> In Cushing's syndrome there will be no suppression
470
What is a positive test for Cushing's with the overnight dexamethasone suppression test?
No suppression of cortisol
471
What is the alternative to the overnight dexamethasone suppression test?
Urine free cortisol over 24 hours
472
Describe the urine free cortisol test
- Take >2 measurements in 24 hours
| - Cortisol is bound to albumin, when capacity is reached, cortisol will spill out into the urine
473
What do you do if you have a suspected Cushing's syndrome patient, dexamethasone is not suppressed in the first line test?
Perform a 48 hour dexamethasone suppression test
474
Describe the 48 hour dexamethasone test
> Oral dexamethasone 4x a day for 2 days
> Measure cortisol at 0hrs and 48hrs
> In Cushing's, there will be no suppression
475
What do you do both overnight and 48 hour dexamethasone suppression tests are positive (i.e. there is suppression)?
Check plasma ACTH
476
What do you do if 1st and 2nd line tests for Cushing's syndrome are positive, and plasma ACTH is undetectable?
- Perform CT/MRI of adrenal glands to detect adenomas or carcinomas
- If there is no mass, do adrenal vein sampling
477
What do you do if 1st and 2nd line tests for Cushing's syndrome are positive, and plasma ACTH is detectable?
- Distinguish if the cause is from the pituitary or an ectopic ACTH production
- Perform HIGH dose dexamethasone suppression test
OR
- Perform corticotropin releasing hormone (CRH) test
478
How do you perform a CRH test?
> Human IV CRH given
> Measure cortisol at 120 minutes
> Cortisol will rise with pituitary disease, but NOT with ectopic ACTH production
479
What do you do if CRH test shows that cortisol responds to CRH?
- Cushing's disease is likely
| - Pituitary MRI to locate neoplasm
480
What do you do if CRH test shows that cortisol does not respond to CRH?
- Hunt for ectopic source of ACTH
- IV contrast CT of chest, abdomen, and pelvis
- MRI of neck, thorax, and abdomen
- CXR to look at lungs for small cell lung cancer
481
What is the treatment for iatrogenic Cushing's syndrome?
Stop steroids!
482
What is the treatment for Cushing's disease?
- Surgical selective removal of pituitary adenoma (trans-sphenoidal approach)
- Bilateral adrenalectomy (remove both adrenal glands)
483
Why might you do a bilateral adrenalectomy to treat Cushing's disease?
- Source is unlocatable
| - Cushing's syndrome recurs post-operatively
484
What is Nelson's syndrome?
Increased skin pigmentation due to significantly increased ACTH from an enlarging pituitary tumour, as the adrenalectomy will remove negative feedback
485
What is the complication of a bilateral adrenalectomy?
Nelson's syndrome
486
How do you treat Nelson's syndrome?
Pituitary radiotherapy
487
How do you treat an adrenal adenoma?
Adrenalectomy
488
How do you treat an adrenal carcinoma?
- Adrenalectomy
- Radiotherapy
- Adrenolytic drugs (e.g. MITOTANE)
489
How do you treat ectopic ACTH?
- Surgery if tumour is located and hasn't spread
- Drugs that inhibit cortisone synthesis (e.g. METYRAPONE, KETOCONAZOLE, FLUCONAZOLE are used pre-op or if awaiting effects of radiation)
490
How is growth hormone secreted?
In a pulsatile fashion under the control of two hypothalamic hormones;
- Growth hormone releasing hormone (GHRH) - STIMULATES GH secretion
- Somatostatin (SST) - INHIBITS GH secretion
491
What molecule in high concentration inhibits GH secretion?
Glucose
492
What molecule inhibits GH secretion?
Ghrelin, which is synthesised in the stomach
493
How does GH exert its action?
- Indirectly through induction of insulin-like growth factor (IGF-1)
- Directly on tissues, such as liver, muscle, bone, or fat to induce metabolic changes
494
Where is insulin-like growth factor synthesised?
Liver and other tissues
495
Define gigantism
Excessive GH production in children BEFORE fusion of epiphyses of the long bones
496
Define acromegaly
Excess GH in adults
497
Describe the epidemiology of acromegaly
- Rare
- Equal prevalence in males and females
- Incidence is highest in middle age
498
What is the most common cause of acromegaly?
Benign GH-producing pituitary adenoma
499
Aside from a pituitary adenoma, what else can cause acromegaly?
Hyperplasia, e.g. ectopic GH-releasing hormone from a carcinoid tumour
500
What is a risk factor for acromegaly?
5% are associated with MEN-1 (multiple endocrine neoplasia-1)
501
Describe the pathophysiology of acromegaly?
> Increased GH (either secreted due to pituitary tumour or due to ectopic carcinoid tumour) travels to tissues (e.g. liver) where it binds to reporters
> Increase in IGF-1
> Stimulates skeletal and soft tissue growth
> Causing 'giant-like' appearance and symptoms
502
What can happen if a benign GH-producing pituitary tumour expands>
It can suppress surrounding structures and cause headaches and visual field loss
503
What are the symptoms of acromegaly?
- Headaches - very common
- Increased size of hands & feet (acral enlargement)
- Excessive sweating
- Visual deterioration
- Snoring
- Wonky bite - malocclusion
- Increase weight
- Decreased libido
- Amenorrhea
- Arthralgia and backache
- Acroparaesthesia (tingling and numbness of the extremities)
504
What are the signs of acromegaly?
- Skin darkening
- Coarsening face with wide nose
- Prognathism (relationship between mandible/maxilla with base of skull)
- Big supraorbital ridge
- Interdental seperation
- Rings become tight
- Fatigue
- Deep voice
- Carpal tunnel syndrome in 50%
Large tongue - macroglossia
505
What are the co-morbidities / complications associated with acromegaly?
- Impaired glucose tolerance (40%)
- Diabetes mellitus (15%)
- Sleep apnea (due to excess soft tissue in larynx)
- Hypertension
- Left ventricular hypertrophy
- Cardiomyopathy
- Arrhythmias
- Ischaemic heart disease
- Stroke
- Colon cancer
- Arthritis
506
What substances are raised in the blood of a patient with acromegaly?
- Glucose
- Ca2+
- Phosphate
507
When doing a blood test, what results mean you can exclude acromegaly from your suspicions?
- Random GH is undetectable
- GH < 0.4ng/ml
- Normal IGF-1
508
Is a detectable value of GH diagnostic for acromegaly? Why?
Not necessarily, since;
- GH secretion is pulsatile
- GH increases in stress, sleep, puberty, and pregnancy
509
If GH is detected in the blood of someone with suspected acromegaly, what do you do?
Proceed to glucose tolerance test (GTT)
510
Describe the GTT use for diagnosis of acromegaly
Can be diagnostic for acromegaly if there is no suppression of glucose, as glucose should inhibit GH release
511
How can you use IGF-1 values in diagnosis of acromegaly?
- Almost always raised in acromegaly
| - Fluctuates less than GH - DIAGNOSTIC
512
If someone has a benign pituitary adenoma pressing on their optic chiasm, how will this affect their vision?
Bilateral hemianopia
513
If you suspect a patient's acromegaly is due to benign GH-producing pituitary adenoma, what do you do to confirm this?
- MRI scan of pituitary fossa
| - Pituitary function test to look for partial / complete hypopituitarism
514
What non-clinical thing can you use to help you with your diagnosis of acromegaly?
Old photos for comparison
515
What is the first line treatment for a benign pituitary adenoma?
Trans-sphenoidal surgery to remove tumour and correct any compression caused by it
516
If surgery fails to correct GH/IGF-1 hypersecretion, what can you do?
- Treat with somatostatin analogues (SSAs) (e.g. IM OCTREOTIDE or IM LANREOTIDE)
- GH receptor antagonists (e.g. SC PEGVISOMANT)
- Dopamine agonists (e.g. ORAL CABERGOLINE or ORAL BROMOCRIPTINE)
517
How do somatostatin analogues help treat acromegaly?
They inhibit GH release, like GH secretion
518
What are the side effects of using somatostatin analogues?
- GI and abdominal cramps
- Flatulence
- Loose stools
519
Why would you give someone GH receptor antagonists to treat acromegaly?
They are intolerant to somatostatin analogues
520
What do GH receptor antagonists do?
Suppress IGF-1
521
What are the pros and cons of using dopamine agonists to treat acromegaly?
Cons;
- not as effective as GH receptor antagonists and SSAs
Pros;
- rapid onset
- oral administeration
- no hypopituitarism
522
What are the benefits of using stereotactic radiotherapy to treat acromegaly?
- More accurate than conventional radiotherapy
| - Better tumour localisation and irradiation whilst reducing radiation to normal brain tissue
523
What affects prolactin release?
Negative feedback by dopamine from hypothalamus
524
What does raised prolactin lead to?
- Lactation
| - Inhibition of gonadotropin releasing hormone resulting in reduced LH/FSH, and thus reduced testosterone / oestrogen
525
What is the most common hormonal disturbance of the pituitary?
Prolactin
526
What is the difference between the onset of hyperprolactinaemia in men and women?
- Presents earlier in women (with menstrual disturbance)
| - Presents later in men (with erectile dysfunction)
527
What are the four causes / risk factors for hyperprolactinaemia?
- Prolactinoma
- Pituitary stalk damage
- Drugs
- Physiological
528
What is a prolactinoma?
Tumour of pituitary which results in prolactin release
529
How does pituitary stalk damage lead to hyperprolactinaemia?
Less dopamine to the anterior pituitary, so disinhibition of prolactin
530
What can cause damage to pituitary stalk?
- Pituitary adenomas
- Surgery
- Trauma
531
What is the most common cause of hyperprolactinaemia?
Drug usage
532
Which drugs are most likely to cause hyperprolactinaemia?
- Metoclopramide
| - Ecstasy
533
What is the clinical presentation for someone with hyperprolactinaemia?
- Amenorrhoea / oligomenorrhoea
- Infertility
- Galactorrhea
- Low libido
- Low testosterone in men
- Erectile dysfunction and reduced facial hair in men
- Local effect of tumour:
- Headache
- Visual defect e.g. bitemporal hemianopia as affecting optic chiasm
534
How do you diagnose hyperprolactinaemia?
Measure basal prolactin level - it will be VERY high
535
What is difference between treating prolactinomas and treating other benign pituitary adenomas?
It is more effective to treat prolactinomas medically rather than surgically
536
How do you treat prolactinoma?
Dopamine agonists (e.g. ORAL CABERGOLINE or ORAL BROMOCRIPTINE)
537
How do dopamine agonists affect prolactinomas?
In particular, how do they affect macroadenomas?
How do they affect microadenomas?
Massive shrinkage of the tumour
Remarkable sight-saving shrinkage of macroadenoma
Microadenomas respond to small doses of dopamine agonists once / twice a week
538
What is Conn's syndrome also known as?
Primary hyperaldosternism
539
Describe Conn's syndrome
Excess production of aldosterone, independent of the renin-angiotensin system
> resulting in increased sodium, and thus water retention (increasing BP) and decreased renin- release
540
Describe the epidemiology of Conn's syndrome
Rare condition accounting for <1% of all hypertension
541
Describe the aetiology of hyperaldosteronism
- 2/3rds - adrenal adenoma that secretes aldosterone - CONN'S SYNDROME
- 1/3rd - bilateral ardenocortical hyperplasia
542
What are the risk factors for hyperaldosteronism?
Hypertension in patients;
- under 35 with no FHx
- with accelerated hypertension
- with hypokalaemia before diuretic surgery
- resistant to conventional antihypertensive therapy (i.e. more than 3 drugs)
- with unusual symptoms
543
Describe the pathophysiology of hyperaldosteronism
> Disorder of adrenal cortex characterised by excess aldosterone production
> leading to Na+ and water retention, and K+ loss (balance charge)
> thus, hypokalaemia and hypertension
> due to aldosterone producing carcinoma (Conn's) or adrenocortical hyperplasia
544
What is the clinical presentation of hyperaldosteronism?
- Often asymptomatic
- Hypertension
- Hypokalaemia
545
What is the clinical presentation of hypokalaemia?
- Weakness / cramps
- Paraesthesia
- Polyuria
- Polydipsia
546
What is secondary hyperaldosteronism?
Excess renin (and hence angiotensin II) which stimulates aldosterone release
547
What causes secondary hyperaldosteronism?
- Renal artery stenosis
- Accelerated hypertension
- Diuretics
- Congestive heart failure
- Hepatic failure
548
What does the ECG look like for someone with Conn's syndrome?
Hypokalaemia ECG;
- Flat T waves
- ST depression
- Long QT
549
What is the first test you run when trying to diagnose Conn's syndrome? What is a positive result for Conn's?
Plasma aldosterone:renin ratio (ARR)
Aldosterone is MUCH higher - NOT DIAGNOSTIC but used for screening
550
What do you need to do 6 weeks before running an ARR test?
Stop spirolactone and eplerenone
551
What test result is diagnostic for Conn's syndrome?
Increased plasma aldosterone levels that are not suppressed with 0.9% saline infusion or fludrocortisone administration (a mineralocorticoid) - DIAGNOSTIC
552
How do you differentiate between adrenal adenomas and adrenal hyperplasia?
CT or MRI scan or adrenal glands
553
How do you treat Conn's syndrome?
- Laparoscopic adrenalectomy
| - Aldosterone antagonist (e.g. ORAL SPIRONOLACTONE for 4 weeks pre-op to control BP and K+)
554
What is Addison's disease?
Primary hypoadrenalism
555
Describe Addison's disease
Destruction of the entire adrenal cortex resulting in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and sex steroid (androgens) deficiency
556
Describe the epidemiology of Addison's disease
- Very rare - 0.8 per 100,000
- Can be fatal
- Marked female preponderance
557
What are the causes of Addison's disease?
- Autoimmune adrenalinitis
- TB
- Adrenal metastases
- Long term steroid use
- Opportunistic infections in HIV
- Adrenal haemorrhage / infarction
558
What is the most common cause of Addison's disease in the UK?
Autoimmune adrenalinitis (80%)
559
What is autoimmune adrenalinitis?
Destruction of the adrenal cortex by organ-specific antibodies, with 21- hydroxylase as the common antigen
560
How does long term steroid use cause Addison's disease?
It will prevent ACTH release via negative feedback mechanisms
561
How does Addison's disease differ from hypothalamic-pituitary disease?
Addison's = all steroids are reduced
Hypothalamic-pituitary disease = glucocorticoids (e.g. cortisol) are reduced
562
Why do you get hyperpigmentation in Addison's disease?
> Reduced cortisol
> Increased CRH and ACTH production
> Increased ACTH -> hyperpigmentation
563
What is the clinical presentation of Addison's disease?
- Lethargy, depression, low mood & self esteem
- Anorexia & weight loss
- Vitiligo
- Nausea and vomiting
- Tanned skin - ‘bronze’
- Diarrhoea, constipation and abdominal pain
- Impotence/amenorrhea
- Postural hypotension
- Lean build
- Dizzy
- Dehydration
564
What are the signs of critical deterioration in someone with Addison's disease?
- Shock - decreased BP, tachy.
- Raised temperature
- Coma
565
Why are patients with Addison's disease prone to vitiligo?
Loss of adrenal androgen
566
Why are patients with Addison's disease prone to postural hypotension?
Loss of aldosterone, resulting in hypovolaemia
567
When should you think of Addison's disease in patients?
If they have unexplained pain or vomiting
568
What do the blood tests of someone with Addison's show?
- Hyponatraemia
- Hyperkalaemia
- Hypoaldosteronism
- Low cortisol
- Uraemia
- Raised Ca2+
- Eosinophilia
- Anaemia
569
Why is the blood of an Addison's patient hyponatraemic and hypokalaemia?
Decrease in aldosterone
570
Why does Addison's disease result in eosinophilia?
Cortisol has anti-inflammatory effects, so reduction in cortisol results in raised white cells
571
What test can you use to diagnose Addison's disease?
Short ACTH stimulation test
572
Describe the short ACTH stimulation test
Measure plasma cortisol before and 30 mins after IM TETRACOSACTIDE
Addison's is excluded if after 30 mins, cortisol > 55nmol/L
573
How can you diagnose a patient with autoimmune adrenalitis?
21 hydroxyls antibodies are detected in blood
574
If you took a blood sample from a patient with Addison's disease at 9am, what would you find?
High ACTH levels
575
How do you treat an Addison's patient who is seriously ill or hypotensive on presentation?
- IV hydrocortisone
- IV 0.9% saline
- Glucose infusion (if hypoglycaemic)
576
How do you treat Addison's disease?
Replace steroids; take 1-3x a day;
- Glucocorticoids (e.g. ORAL HYDROCORTISONE / PREDNISOLONE)
- Mineralocorticoids (e.g. ORAL FLUDROCORTISONE)
577
Under what circumstances should you double the medication for a patient with Addison's disease?
- Infection
- Trauma
- Surgery
- Nightshifts at work
578
When should you increase the dose of medication for an Addison's patient?
- During pregnancy
| - Before strenuous exercise
579
What is the presentation for adrenal crisis?
- Nausea
- Vomiting
- Abdominal pain
- Muscle cramps
- Confusion
580
How do you treat adrenal crisis?
IV hydrocortisone
581
What is secondary hypoadrenalism?
Not an issue with the adrenal glands, but with the pituitary gland
582
What are the causes of secondary hypoadrenalism?
- Iatrogenic
| - Hypothalamic-pituitary disease
583
Describe the iatrogenic cause of secondary hypoadrenalism
Long term steroid therapy leading to suppression of the pituitary-adrenal axis
584
Describe the pathophysiology of secondary hypoadrenalism
> reduction in the release of ACTH
> decreased glucocorticoid (cortisol)
- Mineralocorticoid production remains unaffected
585
What is the clinical presentation of secondary hypoadrenalism?
- Vague symptoms of feeling unwell
| - No skin hyperpigmentation since ACTH is reduced
586
How do you diagnose secondary hypoadrenalism?
- ACTH levels are low
| - Mineralocorticoid levels are fine
587
How do you treat secondary hypoadrenalism?
- Oral hydrocortisone
OR
- Adrenal glands will recover if you ween patient off long-term steroids, but this is a long and difficult process
588
Describe the Thirst Axis
1. ADH is synthesised in hypothalamus
2. It migrates in neurosecretory vesicles along axonal pathways to posterior pituitary
3. Large drop in BP / blood volume is detected by osmoreceptors or baroreceptors which stimulates ADH release
4. ADP acts on principal cells of collecting duct on kidney
5. Binds to adenyl-cyclase couple vasopressin receptor (V2R) where kinase actions result in insertion of aquaporin 2 channels into apical membrane of collecting duct
6. Water permeability of collecting duct increases
7. Increased water reabsorption causing very concentrated urine
589
What determines secretion of vasopressin?
Plasma osmolality (i.e. blood water concentration)
590
What does vasopressin do?
- Increases water reabsorption from collecting duct
| - Widespread arteriolar vasoconstriction
591
Describe the relationship between osmolality and vasopressin
Linear, as blood gets more concentrated, the amount of vasopressin (and thus water that gets reabsorbed) increases
592
Define diabetes insipid (DI)
The passage of large volumes (>3L/day) of dilute urine due to impaired water reabsorption in the kidney
593
What causes the impaired water reabsorption in the kidneys in DI?
- Reduced ADH secretion from posterior pituitary (CRANIAL DI)
- Impaired response of the kidney to ADH (NEPHROGENIC DI)
594
What are the causes of cranial DI?
- Idiopathic
- Congenital defects in ADH gene
- Disease of the hypothalamus
- Tumour:
> metastases
> posterior pituitary tumour
- Trauma (e.g. neurosurgery)
- Infiltrative disease (e.g. sarcoidosis)
595
What are the causes of nephrogenic DI?
- Hypokalaemia
- Hypercalcaemia
- Drugs (lithium chloride, glibenclamide)
- Renal tubular acidosis
- Sickle cell disease
- Prolonged polyuria of any cause
- Familial - mutation of ADH receptor
596
What is the clinical presentation for diabetes insipidus?
- Polyuria
- Compensatory polydipsia
- NO GLYCOSURIA
- Hypernatraemia;
- Lethargy
- Weakness
- Irritability
- Confusion
- Coma
- Fits
- Dehydration
597
What can hypernatraemia cause?
- Lethargy
- Weakness
- Irritability
- Confusion
- Coma
- Fits
598
What are the differential diagnoses for diabetes inspidus?
- DM
- Hypokalaemia
- Hypercalcaemia
All of which look similar to DI because they cause polyuria and polydipsia
599
How do you confirm polyuria?
Measure urine volume
If urine volume < 3L/day it is unlikely to be DI
600
How do you differentiate DI and DM?
Check blood glucose
High - DM
Normal - DI
601
What does the water deprivation test aim to do?
Aims to determine whether kidneys continue to produce dilute urine despite dehydration
602
Describe the water deprivation test
Measure serum and urine osmolality, urine volume, and body weight hourly for up to 8 hours during fasting and without fluids
603
What is a normal response of the body during the water deprivation test?
Serum osmolality remains within normal range, but urine concentration rises
604
What are diagnostic results for DI of the water deprivation test?
Serum osmolality rises without adequate concentration of urine
605
How do you differentiate between cranial and nephrongenic DI?
Give IM desmopressin
Urine will not be concentrated in nephrogenic DI but it will be in cranial DI
606
How do you treat cranial DI?
- MRI of head to find cause
| - Give synthetic analogue of ADH (e.g. ORAL DESMOPRESSIN)
607
How do you treat nephrogenic DI?
- Treat the cause (usually renal disease)
- Thiazide diuretics (e.g. ORAL BENDROFLUMETHIAZIDE)
- NSAIDS (e.g. IBUPROFEN)
608
Why do you give thiazide diuretics to treat nephrogenic DI?
They will produce mild hypovolaemia, which will encourage the kidneys to take up more Na+ and water in the proximal tube, thereby offsetting water loss
609
Why do you use ibuprofen to treat nephrogenic DI?
They will lower urine volume and plasma Na+ by inhibiting prostaglandin synthase
*Prostaglandins locally inhibit action of ADH
610
Define syndrome of inappropriate secretion of ADH (SIADH)
Continued secretion of ADH despite plasma being very dilute, leading to retention of water and excess blood volume, and thus hyponatraemia
611
What are the four categories of causes of SIADH?
- Tumours
- Pulmonary lesions
- Metabolic causes
- CNS causes
- Drugs
612
What tumours cause SIADH?
- Small-cell carcinoma of lung
- Prostate
- Thymus
- Pancreas
- Lymphoma
613
What pulmonary lesions cause SIADH?
- Pneumonia
- TB
- Lung abscess
- Asthma
- Cystic fibrosis
614
What is the metabolic cause of SIADH?
Alcohol withdrawal
615
What are the CNS causes of SIADH?
- Meningitis
- Tumours
- Head injury
- Subdural haematoma
- SLE
616
What drugs can cause SIADH?
- Chlorpropamide (sulfonylurea for DMT2)
- Carbamazepine (anti-convulsant)
- Cyclophosphamide (immunosuppressant)
- Vincristine (chemotherapy)
- SSRIs
617
What is the clinical presentation for SIADH?
- Anorexia/nausea and malaise
- Weakness and aches
- Reduction in GCS and confusion with drowsiness
- Fits and coma
SYMPTOMS ARE A RESULT OF HYPONATRAEMIA
618
What do the blood results of someone with SIADH show?
- Low serum Na+
- Euvolaemia
- Low plasma osmolality
- NO hypokalaemia
- NO hypotension
- NO hypovolaemia
- Normal renal, adrenal, and thyroid function
619
What is the urine Na+ concentration in someone with SIADH?
High urine Na+ > 30mmol/L
620
How do you differentiate between SIADH and salt&water depletion?
Test with 1-2L of 0.9% saline
- Sodium depletion will respond
- SIADH will NOT respond
621
How do you treat SIADH?
- Try to treat underlying cause
- Restrict fluid intake to 500-1000ml daily
- Hypertonic saline (if really symptomatic) - concentrate with salt
- Give ORAL DEMECLOCYCLINE daily
- Give vasopressin antagonist (e.g. ORAL TOLVAPTAN) daily
- Salt and loop diuretic (e.g. ORAL FUROSEMIDE)
622
Why do you restrict fluid intake in someone with SIADH?
To increase Na+ concentration and reduce symptoms
623
Why do you give hypertonic saline to someone with SIAD?
Stops the brain from swelling as it keeps water out by attractive forces of Na+
- In emergencies, give the highest possible dose of Na+ to prevent cerebral oedema
624
Why do you give someone with SIADH oral demeclocycline?
It induces nephrogenic DI (inhibits the action of ADH on kidneys)
625
What are the side effects of oral demeclocycline?
- Photosensitive rash
| - Nephrotoxicity
626
Why do you give someone with SIADH a vasopressin antagonist?
Treats hyponatraemia by promoting water excretion with no loss of electrolytes
