Endocrine Flashcards
(198 cards)
1
Q
What virus is believed to have a link to type 1 diabetes?
A
Coxsackie B virus and
Human enterovirus
2
Q
Outline the pathophysiology that typically causes Type 1 diabetes.
A
- Autoimmune destruction of pancreatic β-cells leading to an insulin deficiency
- β cells express HLA antigens on MHC in response to an environmental event (potentially a virus)
- Activates a chronic cell mediated immune response leading to chronic insulitis
Up to 90% of people have autoantibodies
80-90% of beta cells need to be destroyed before symptoms usually appear for type 1 diabetes
3
Q
What are the most common key presentations of type 1 diabetes?
A
- Hyperglycaemia (above 11.1).
- Polyuria (passing urine frequently).
- Polydipsia (drinking water frequently)
- Weight loss
- Tiredness
4
Q
What are some other common key presentations of type 1 diabetes?
A
young age, weight loss, blurred vision, nausea, and vomiting, Abdo pain,
5
Q
What are the first line investigations for children in type 1 diabetes?
A
- Random plasma glucose (above 11)
- Fasting plasma glucose (above 7)
6
Q
What are the first line investigations for adults in type 1 diabetes?
A
Random glucose tolerance test if at GP - blood sugar of >11.1mmol/L
a glucose tolerance test.
In this test, a fasting blood glucose is taken after which a 75g glucose load is taken. After 2 hours a second blood glucose reading is then taken
If the patient is symptomatic:
• fasting glucose greater than or equal to 7.0 mmol/l
• random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
7
Q
What is the gold standard test for diagnosing type 1 diabetes? What is it a measurement of?
A
Glycohemoglobin test (HbA1c)
It measures Glycated haemoglobin, a form of haemoglobin that is measured to identify the three month average plasma glucose concentration
Reflects the degree of hyperglycaemia over the preceding 3 months greater than 6.5% (48 mmol/mol) indicates diabetes
8
Q
What are other diagnostic tests you do to confirm a diagnosis of type 1 diabetes?
A
- Plasma or urine ketones,
- C-peptide,
- Autoimmune markers
9
Q
GO OVER
What is the management of type 1 diabetes?
A
o Basal-bolus insulin (insulin glargine s/c)
o Pre-meal insulin correction dose
2nd line: Metformin and fixed insulin dose
10
Q
What are the side effects of insulin?
A
hypoglycaemia, weight gain, lipodystrophy
Lipodystrophy - where you loose fat in some regions, but gain it in others, like on Organs like the Liver
11
Q
What would you monitor for patients with diabetes?
A
Measure HbA1c levels every 3 months in children and every 3-6 months in adults
Make sure level is under 6.5% (48 mmol/mol)
Also monitor;
Blood Pressure
Kidney function
12
Q
What are the key presentations of someone coming in with suspected type 2 diabetes?
A
Having the risk factors eg
Older age
Overweight/obese
Being of a certain ethnic groups inc Black, south asiain,
And coming in with:
Fatigue
Polydipsia and polyuria (thirsty and urinating a lot)
Unintentional weight loss
Opportunistic infections
Slow healing
13
Q
What are some symptoms that a patient with Type 2 diabetes may complain of?
A
Polyphasia - Eating lots, Polydipsia, Drink, Polyuria - wee lots, unexplained weight loss
14
Q
What are some first line investigations to order for suspected Type 2 diabetes?
A
Fasting plasma glucose - Order after a minimum 8-hour fast. Positive result is ≥7.0 mmol/L (≥126 mg/dL)
2 hour post load glucose test after 75g oral glucose - Plasma glucose is measured 2 hours after 75 g oral glucose load Positive result is ≥11.1 mmol/L (≥200 mg/dL)
Random Plasma glucose - positive test is >11mmol/L
Bear in mind that a repeat confirmatory test is required for diagnosis in most cases.
15
Q
What is the gold standard test for type 2 diabetes, and what does it measure?
What is a positive result for this?
A
HbA1c
glycated haemoglobin how much glucose is attached to the haemoglobin molecule, shows blood glucose levels over the past 3 months
- HbA1c > 6.5% normal (48mmol/mol) = DIABETES DIAGNOSIS
16
Q
What other tests could be performed for suspected type 2 diabetes
A
Urine ketones, fasting lipid profile (high LDL), Albumin to creatine ratio*
17
Q
Outline some non medicinal management for someone with type 2 diabetes **(This is the first line treatment for T2DM)
A
Patient education about their condition and the lifestyle changes, advise that there is a possible cure.
Exercise and weight loss, stop smoking
Regarding food:
- Include high-fibre, low-glycaemic-index sources of carbohydrate in their diet, such as fruit, vegetables, wholegrains, and pulses
- Eat low-fat dairy products and oily fish
- Limit their intake of foods containing saturated and trans fatty acids.
Needs annual reinforcement and review
Optimise treatment for other illnesses, eg hypertension
18
Q
What is the second line treatment for someone with type 2 diabetes?
A
Medical management: First line: metformin titrated from initially 500mg once daily as tolerated.
Metformin is a “biguanide”. It increases insulin sensitivity and decreases liver production of glucose. It is considered to be “weight neutral” and does not increase or decrease body weight.
Management cardiovascular risks:
An ACE inhibitor or an angiotensin-II receptor antagonist
If an ACE inhibitor is not tolerated, use an angiotensin-II receptor antagonist instead
because metformin only increases insulin sensitivity instead of stimulating more insulin, it’ll rarely cause hypoglycaemia
19
Q
What monitoring do you need to continue to do for someone with type 2 diabetes?
A
Take HbA1c every 3 to 6 months. Measure blood pressure once a year, to look out for hypertension. Monitor for complications
20
Q
What complications can someone get from type 2 diabetes?
A
- Diabetic retinopathy
- Kidney disease
Diabetic foot - due to neuropathy
Cardiovascular disease - atherosclerosis, stroke TIA, CHD
Glucose sticks in the vessels everywhere - eyes, brains, Kidney,
21
Q
What does insulin do at muscle and fat cells?
A
Insulin binds to muscle and fat cells via receptors
Which leads to intracellular glut4 vesicles to go to bind to the plasma membrane, which means that glucose will go and enter the cell via these GLUT4 membranes
Glucose enters the cells
22
Q
What is the definition of diabetes?
A
Symptoms of Diabetes (3Ps) + Fasting plasma glucose > 7 mmol/l
OR
No symptoms - GTT (75g glucose) fasting > 7 or 2h value > 11 mmol/l (repeated on 2 occasions)
HbA1c of > 48mmol/mol (6.5%)
23
Q
Regarding Glucose, what do you see in Type 2 diabetes?
What do you see regarding glucose levels in a type 2 diabetic patient after they eat a meal?
A
Glucose levels, in general, are far higher than normal. When you eat a meal with T2DM, it takes alot longer for your blood sugar levels to come down again like in normal physiology.
24
Q
What is the main medical drug given to treat T1DM?
A
Using a combination of long-acting insulin (insulin detemir, degludec, or glargine) for basal dosing,
and rapid-acting insulin (insulin lispro, aspart, or glulisine) for bolus dosing
25
3rd line treatment for T2DM: What do Sulphonlureas
do? Give an example What are its side effects? 3rd line of treatment
***Eg - Gliclazide***
stimulate insulin release by **binding to Beta-cell receptors**
Improve glycaemic control (1-2% in HbA1c)
***give beta cells an extra kick to promote insulin***
Increase weight
Increase the risk of heart failure
Increase the risk of fractures
CI: Pregnancy & breastfeeding (can cross placenta & enter breast milk)
(May cause hypoglycaemia in newborns)
26
3rd line treatment for T2DM: What can SGLT2 inhibitors do, and what can they lead to, as side effects?
eg empagliflozin, canagliflozin, dapagliflozin
They block the reabsorption of glucose in the kidney, increase glucose excretion, and lower blood glucose levels
Make you pee lots of glucose out =UTI and Thrush
Peeing out glucose can make your body think you're in a fasting state - leading lipid break down - KETOACIDOSIS ***euglycaemic ketoacidosis***
27
What is the 3rd line of medication for T2DM?
When do you give a 3rd line treatment??
If HbA1c rises to 58mmol/mol, consider dual therapy or metformin and one of
either a sulfonylurea, - **(Gliclazide)**
DPP-4 inhibitor **(Sitagliptin)**
or
SGLT-2 inhibitor **(Dapagliflozin)**, or Glitazone. **(Pioglitazone)** The decision should be based on individual factors and drug tolerance.
**Most commonly metformin and an SU**
28
What insulin medication pattern do you see in T2DM
Just once a day, (Basal) sometimes twice (BD)
29
What is the difference between Basal and Bolus insulin dosing for Diabetes?
The two main ways to take insulin are bolus and basal.
Bolus insulin is the *quick-acting* delivery that you often take before mealtimes.
Basal insulin is *longer-acting* and helps keep your glucose levels steady day and night
30
Other types of diabetes - what is MODY?
“Maturity-onset diabetes of the young” Commonest type of monogenic diabetes (~1% diabetes)
Diagnosed <25y
Autosomal dominant
Non-insulin dependent
**Single gene defect** altering beta cell function
Tend to be non-obese
**Monogenic - caused a mutation of one gene only**
31
patients with MODY tend to be missed diagnosed as type 1 or early onset type 2. What are some features of MODY that make it different to type one and two?
Parent affected with diabetes
**Absence of islet autoantibodies**
Measurable C - Peptide - NOT SEEN ON SYNTHETIC INSULIN
32
What is the fifth line treatment for someone with T2DM?
Insulin. Start with Basal Dose
33
Give an example of
a Sulfonylurea
DPP4 inhibitors
SGLT-2 inhibitor
Glitazone
Gliclazide
Sitagliptin
Dapagliflozin
Pioglitazone
34
Medications for Type 2 diabetes
How do DPP4 inhibitors work?
Give an example
Side effects?
Inhibit DPP4 (so increase effect of incretins (GLP-1 and GIP) which stimulates insulin secretion
Incretin = A group of hormones released after eating & augment secretion on insulin (inhibited by DPP4)
DOES NOT CAUSE weight gain or weight loss
Sitagliptin
35
When would you start 4th line treatment for T2DM? What does it involve?
If HbA1c still 58mml/mol, consider triple therapy with:
Metformin + SU + DPP4 inhibitor
Metformin + SU + pioglitazone
Metformin + SU/pioglitazone + SGLT-2i
Insulin-based therapy
36
Brief description of what ketoacidosis is.
Ketoacidosis is High levels of ketones in the blood due to cells in the body initiating the process of ketogenesis for fuel.
The **ketone acids use up the bicarbonate buffer and the blood starts to become acidic.**
37
What is the basic pathophysiology of ketoacidosis?
nsulin deficiency leads to release of free fatty acids from adipose tissue (lipolysis), hepatic fatty acid oxidation, and formation of ketone bodies), which result in ketonaemia and acidosis, as the bicarbonate buffer from the kidneys is used up
38
What are the key presentations seen in a patient with Ketoacidosis?
**Known to have diabetes, and are unwell**
**Hyperkalaemia**
Polydipsia
polyuria, recent unexplained weight loss, or excessive tiredness,
**Acetone smell on breath**
Secondary:
Nausea
Abdominal pain[4][49]
Hyperventilation
Reduced consciousness.
39
What things would be seen on examination/investigation for someone with Ketoacidosis?
**Venous blood gas** of:
pH ≥7.0 indicates mild or moderate DKA.
pH <7.0 indicates severe DKA
Diabetes - blood glucose is >11.0 mmol/L
blood ketones are >3.0 mmol/L - Ketonemia
ketonuria (2+ or more on standard urine sticks)
40
What are the first investigations you would do for suspected Ketoacidosis?
What is the key one?
**Venous blood gas (key)**
Blood Glucose
Blood ketones
Urea and Electrolyte count
Urine stick for ketones
41
Why can serum potassium high in Ketoacidosis?
***(Insulin makes you hypokalaemic), as it move postassium into your cells***
Serum potassium can be high or normal in diabetic ketoacidosis, as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells.
42
Why can infection and MIs cause ketoacidosis?
***Infection (pneumonia, UTI)*** ==> due to the systemic response that it causes in the body **(eg adrenaline release leads to increased lipolysis, ketogenesis)**
Myocardial Infarction (provoke the release of counter-regulatory hormones likely to result in DKA in patients with diabetes.)
43
What would be in a differential diagnosis for Diabetic Ketoacidosis?
Hyperosmolar hyperglycaemic state (HHS)
Lactic acidosis
Starvation ketosis
Alcoholic ketoacidosis
44
DKA management - what do you give first?
IV fluids.
1. Give a fluid bolus of 500 mL of normal saline (0.9% sodium chloride) over 10 to 15 minutes if the initial systolic blood pressure (SBP) is <90 mmHg.
If BP is >90mmHg, give 1L of normal saline over 60 minutes.
45
DKA management - after the first round of IV fluids, what do you also give?
**Potassium and Insulin!!**
1. Add potassium to the **second litre of intravenous fluid** if serum potassium is ≤5.5 mmol/L ***(Insulin makes you hypokalaemic), as it move postassium into your cells ***
2. Start a fixed-rate intravenous insulin infusion (FRIII) according to local protocols; continue FRIII until DKA has resolved
Ensure intravenous fluids have already been started before giving a FRIII.
46
How do you monitor a patient with Ketoacidosis? (5 things)
Order hourly blood glucose and hourly blood ketones.
Perform a venous blood gas
(for pH, bicarb, K+) 60 minutes, 2 hours, and 2 hourly thereafter.
* Maintain the potassium level between 4.0 and 5.0 mmol/L.
* Maintain an accurate fluid balance chart.
- Keep an eye on GCS
47
Which diabetes would you see Ketoacidosis?
Seen in TYPE 1 DM
Won't get it in early TYPE 2 DM, but is possible later on 10 years
In Type 2, you do have some insulin, so some glucose can go in the cell
48
What are the classifications of Hypoglycaemia
Level 1 - Alert value Plasma glucose <3.9 mmol/l and no symptoms
Level 2 - Serious biochemical
Plasma glucose <3.0 mmol, patient has symptoms but can self treat, cognitive function is mildly impaired.
Level 3 - Patient has impaired cognitive function sufficient to require external help to recover (Level 3)
49
What does your body do at
a) 4.6
b)3.8
c) 3.5
d) 2.4-3
e)<1.5
mmol/L
of Glucose?
a) Stop secreting insulin
b) starts secreting glucagon
c) Adrenaline release - Causes neuroglypenic symptoms
d) Cognitive dysfunction
e) Reduced conscious level, convulsions, coma
50
How do you simply treat hypoglycaemia?
Recognise symptoms
Confirm need for treatment
Treat with 15g of fast acting carbohydrate
***RETEST*** in 15 mins to ensure blood glucose >4mmol/L
Eat a long - acting carbohydrate to prevent the recurrence of symptoms - because after you've used up the fast acting carb, but the insulin will still be in the body
**If unconscious, IV Glucose or IM Glucagon**
51
What is the predominant ketone body seen in DKA?
he primary ketone body involved in diabetic ketoacidosis is **acetoacetate**
52
What does Parathyroid Hormone do?
What cells in the parathyroid gland release it?
Increasaes Bone resorption
Increased Ca2+ in kidney
Increased Ca2+ absorption in gut, **through increased vit D**
**Decreases phosphate reabsorption in kidney**
All to increase serum calcium
**RELEASED FROM CHIEF CELLS IN THE PARATHYROID**
53
What are the signs of Hypocalcaemia?
CATS go numb:
● C - convulsions
● A - Arrhythmias
● T - Tetany (intermittent involuntary muscle contractions)
● S - spasms
● Numb - numbness
Hypocalcemia causes prolonged QT
Chvostek’s Sign
_ Cause spasms of facial nerve
Trousseau’s Sign
Fill up blood pressure cough more than systolic pressure for 5 mins- aggravated Italian hands
54
Signs of Hypocalcaemia - what is
a)Chvostek’s Sign
b)Trousseau’s Sign
a) Tap over the facial nerve
Look for spasm of facial muscles
b)Inflate the blood pressure cuff
to 20 mm Hg above systolic
for 5 minutes - makes hand spasm upwards, like aggrivated italian sign with hands
55
What are the main causes of Hypoparathyroidism? What is Di George Syndrome?
**DAMAGE TO PARATHRYOID GLAND!!** - WHAT WOULD CAUSE THIS:
Surgery/Chemotherapy on the neck to target cancer, that damages the Parathyroid gland
Genetic
Autoimmune disesases
*Magnesium Deficiency*
Syndromes, like Di George - Developmental abnormality of third and fourth branchial pouches
56
What is Pseudoparathyroidism? What would a patient with it look like?
How would you treat it?
Resistance to parathyroid hormone. It is a rare, hereditary condition
* Short stature
* Obesity
* Round facies
* Mild learning difficulties
* Subcutaneous ossification
* Short fourth metacarpal
**A FORM OF HYPOCALCAEMIA** , Treat as such
57
What are the symptoms of Hypercalcaemia?
Thirst, polyuria
* Nausea
* Constipation (gut isnt working properly)
58
What are some of the causes of Hypercalcaemia
Malignancy (Lymphoma, bone mets)
Primary Hyperparathyroidism
***^^^^Cause 90% of all hypercalcaemia***
Thiazides Diuretics (make you retain calcium)
59
What does Hypercalcaemia of malignancy
lead to?
Low PTH
so
Decreased Bone Resorption
Decreased Ca2+ reabsorption
Decreased Ca2+ absorption
60
What are the Symptoms of Hyperparathyroidism? (Bones and Stones)
Symptoms
Painful *bones*
Painful bone condition – typically **osteitis fibrosa cystica**
Renal stones
Calcium deposition in renal tubules causes **polyuria** and **nocturia**
Can lead to **kidney stones** and kidney failure
61
What are the Symptoms of Hyperparathyroidism? (Moans and Groans)
**Psychiatric moans** – effects on nervous system
- Fatigue
- Depression
**Abdominal groans** – GI symptoms
- Nausea
- Constipation
- Indigestion
- Polyuria
- Polydipsia (thirst)
62
What do you see on ECGs when there are disturbed calcium levels ?
If calcium is TOO HIGH, the QT interval gets SHORTER
If calcium is TOO LOW, the QT interval gets LONGER
63
What is secondary Hyperparathyroidism?
It's elevation of parathyroid hormone (PTH) due to hypocalcaemia.
64
Outline the aetiology and then pathophysiology of Secondary hyperparathyroidism.
Caused by **Insufficient vitamin D or chronic renal failure**
==> low absorption of calcium from the intestines, kidneys and bones,
==> Causes hypocalcaemia:
==> So parathyroid secretes More PTH, so Parathyroid glands become more bulky.
**Serum Calcium and Phosphate will remain low but PTH will be high**
65
What investigations would you order if you suspect hyperparathyroidism?
Serum Calcium
Serum PTH
25-hydroxyvitamin D level
Eradication of underlying malignancy is crucial for continued maintenance of normocalcaemia.
66
What is tertiary hyperparathyroidism? How would you treat it?
Development of parathyroid hyperplasia (more cells) after long-standing secondary hyperparathyroidism
most commonly in renal disease
So PTH will remain high even with calcium is high
(phosphate is also high)
Plasma calcium and PTH are both raised
Treated by parathyroidectomy
67
What do you give to treat Hypercalcaemia of malignancy?
Intravenous normal saline ==> *Reverses dehydration* (do first
**IV bisphosphonates** (most effective,) *block osteoclastic bone resorption* ===> (slower acting though)
**Calcitonin** interferes with renal tubular reabsorption of calcium, ==> more immediate.
All to stop more calcium entering the blood, and to loose it in the Kidney!
68
Hyperosmolar Hyperglycaemic state: what characterises it?
by marked hyperglycaemia, hyperosmolality and mild/no ketosis
Basically just mental dehydration
69
Hyperosmolar Hyperglycaemic state: Define Hyperosmolarity - what can it do?
Hyperosmolarity = the loss of water making the blood more concentrated than usual.
==>blood has a high concentration of salt (sodium), glucose, etc
***draws the water out of the body's other organs, including the brain.***
*In the case of Hyperglycaemia, high blood glucose makes you wee loads, dehydrating you, and drawing water out of bodies organs*
70
What are the common Causes of HHS?
Infection is the most common cause, ***mainly UTIs/pneumonia***
***Diabetes that is uncontrolled***
Or any trauma that provokes the release of counter-regulatory hormones (catecholamines, glucagon, cortisol, and growth hormone) and/or compromises water intake - eg MI/ Stroke/Sepsis
*In elderly patients, being bed-ridden and having an altered thirst response compromise access to water and water intake, leading to severe dehydration and HHS.*
71
What are some risk factors for HHS?
Illness, bed ridden, diabetes, older age. Little access to water
72
Outline the pathophysiology of HHS.
Why does it often present in T2DM?
HHS is extreme elevations in serum glucose concentrations and hyperosmolality , but **no ketosis.**
Seen in T2DM, where insulin produced is *sufficient to suppress lipolysis and ketogenesis* but not enough to promote glucose regulation
73
What are the key presentations/signs of someone with HHS?
Consider a diagnosis of hyperosmolar hyperglycaemic state (HHS) in any patient who is **unwell and has a raised blood glucose.**
Look for
- **Hypovolaemia**
- **Marked hyperglycaemia** (≥30 mmol/L [≥540 mg/dL]) **without significant hyperketonaemia** (ketones ≤3 mmol/L) or significant acidosis
- **High serum osmolality** (usually ≥320 mOsm/kg [≥320 mmol/kg]).
74
What are the main symptoms someone with HHS might have?
Polyuria
Polydipsia
Hypothermia
Weakness
Dehydration
Acute cognitive impairment measure GCS
Signs of the underlying cause.
*- Common causes include myocardial infarction, sepsis, and stroke*
75
What test would you run first if someone presented with the symptoms
of HHS?
Blood glucose -- v high >30mmol/L
Blood ketones - To make sure DKA is not involved
Venous Blood gas
Calculate Serum osmolality
ECG
Full blood count
U and Es
76
What would you look for on a venous blood gas for someone with suspected HHS?
A mild acidosis (pH >7.3, bicarbonate >15 mmol/L due to renal impairment secondary to dehydration.
=====>Lactic acidosis may be present due to sepsis.
Use a venous blood gas to monitor the patient’s biochemical progress (urea, electrolytes, glucose, serum osmolality, bicarbonate)
77
What is the first line of management for HHS?
Start IV fluids as soon as you suspect hyperosmolar hyperglycaemic state (HHS) Requested Critical care support if you cant get IV access
Give 1 L of 0.9% sodium chloride (normal saline) over 1 hour. Can give more rapidly if SBP is <90 mmHg
Think about treating underlying cause!!! MI, Stroke/Sepsis
78
After fluids, what next do you give for HHS?
***Start intravenous fluids before giving insulin.*** If not, could cause CV collapse
* Give 0.05 units/kg/hour if blood ketones >1 mmol/L and ≤3.0 mmol/L and the patient is not acidotic (venous pH ≥7.3 and bicarbonate >15.0 mmol/L),*
* Give 0.1 units/kg/hour if blood ketones >3.0 mmol/L or ketonuria (2+ or more) with a pH <7.3 and bicarbonate <15 mmol/L (i.e. mixed diabetic ketoacidosis and HHS),*
Think about treating underlying cause!!! - eg MI, Stroke/Sepsis
79
How can hypocalcaemia influence ECGs?
Hypocalcaemia
Prolonged ST Segment
Prolonged QT interval
80
What Serum osmolality would be positive for HHS?
Positive for HHS is >320 mOsm/L
81
How many types of Hyperparathyroidism are there?
How many types of Hypoparathyroidism??
What are the two main causes of Hypercalcaemia?
3 types of HYPERparathyroidism - Primary, Secondary, Tertiary
Just one Hypoparathyroidism - due to parathyroid damage) (No prim,sec,tert etc)
*Primary Hyperparathyroidism and Hypercalcaemia of malignancy are the two main causes of Hypercalcaemia*
82
Name the main causes of Hypocalcaemia.
Hypoparathyroidism - due to surgery/autoimmune/radiation @ parathyroid gland
Vit D deficiency
Alcohlism
Hyperphosphatemia or Lots of Bisphosphate meds
83
What are the main causes of hypercalcaemia?
c CHIMPANZEES- Calcium supplements,
Hydrochlorothiazide, Iatrogenic/Immobilisation, Multiple myeloma/Medication (lithium), Parathyroid
hyperplasia, Alcohol, Neoplasm, Zollinger ellison syndrome, Excessive Vit D, Excess Vit A, Sarcoidosis
Also Thyrotoxicosis
84
Name some causes of Hyperthyroidism.
Graves' disease
Other causes are:
- multinodular goiter, toxic adenoma
- inflammation of the thyroid, - --eating too much iodine,
-too much synthetic thyroid hormone.
A less common cause is a pituitary adenoma.[
85
What causes Graves Disease?
Stimulation of the thyroid by **TSH receptor antibodies**
Combination of genetic and environmental risk factors.
86
Normal Physiology: Outline the relationship between Hypothalamus, Anterior Pituitary and Thyroid gland, and how what they release influences each other.
HYPOTHALAMUS: Releases THYROTROPIN RELEASING HOROMONE
====> causes ANTERIOR PITUITARY GLAND TO RELEASE THYROID STIMULATING HOROMONE (THYOTROPIN)
The binding of TSH to thyroid gland promotes every aspect of T3 and T4 production - *Iodine pumping, Thyroglobulin synthesis, releasing of thyroid hormone in the blood*
T3 - NEGATVIE FEEDBAKC ON THE ANTERIOR PITIUARY TO STOP REALSING TSH
Thyroxine = T4 (4 iodine)
Triiodothronine = T3 (3 iodine)
87
Normal Physiology - What is T3 and T4? What is more active?
Thyroxine = T4 (4 iodine)
Triiodothronine = T3 (3 iodine)
T3 is more active than T4 (half life of 1-2 days vs 6-8 days)
**T4 is generally converted into T3** by enzymes known as deiodinases in target cells
Thus its often said that **T3 is the major thyroid hormone**, despite the fact that the concentration of T4 in the blood is much higher than that of T3
*T4 can be thought of as a RESERVOIR for additional T3*
88
What is the pathophysiology behind Graves Disease?
Serum **IgG antibodies called TSH receptor stimulating antibodies (TRAb)** bind to TSH receptors on the thyroid and stimulate T3/4 production
This results in excess secretion, hyperplasia of the thyroid follicular cells, hyperthyroidism and goitre
TSH receptor autoantibodies cause thyroid hormone hyperproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells. ===> Leads to clinical manifestations of hyperthyroidism
89
What are some signs of Grave's Disease?
- **Tremor**
- Tachycardia/AF
- Goitre
- **Hair loss/thin hair**
- **Lid lag/retraction**
- Hyperkinesia - increased muscle activity
- **Exophthalmos** – bulging of the eye out of the orbit
**** Weight loss
* Irritability
* Heat intolerance***
* Insomnia
* Diarrhoea
* Sweats
* Palpitations
Anxiety
***Pretibial myxedema*** specific to Grave's
90
What is the first line investigation you would do for expected Grave's Disease?
What would it show?
TSH levels test - it would be low, as lots of T3 and T4 being produced that is leading to the symptoms - so negative feedback.
91
What are the 4 main types of treatment you can give someone with Hyperthyroidism/Graves disease?
**Beta blockers** for rapid system control in attacks
Decreases SNS activation
***Carbimazole*** – anti-thyroid drug decreases the synthesis new thyroid hormone
**Potassium iodide** – to acutely block release of thyroid hormone from gland - Damage follicular cells (ionisation)
**Thyroidectomy** – removal of the thyroid gland leaving a small remnant in order to maintain thyroid function
92
Hyperthyroidism/ Grave's disease: What is a severe side effect of key anti thyroid drug, Carbimazole?
Severe side effect is agranulocytosis --- a deficiency of granulocytes in the blood, causing increased vulnerability to infection.
Due to the fact is depresses the activity of the bone marrow
***YOU MUST TELL THE PATIENTS THIS, AND THAT THEY MUST STOP THIS IF THEY GET SIGNS OF INFECTIONS EG SORE THROAT***
93
What is a "Thyroid Crisis"?
Thyroid crisis (Thyroid storm)
Rare life threatening condition
- Hyperpyrexia
- Tachycardia
- Extreme restlessness
Delirium, Coma, death
94
What are some causes for Hypothyroidism (Both Primary and Central)
Primary:
- Hashimoto's disease - most common cause of primary.
- Iodine deficiency - common in developing world and mountainous areas
- Sub-acute granulomatous (De Quervain's
- Other infections
- **Drug induced**
Central:
Pituitary adenomas (most common)
Other infections
Radiation
95
What are some risk factor for hypothyroidism
Iodine deficiency,
female, middle age, family history, treatment,
- turners and down syndrome.
-
radiation therapy to head and neck,
amiodarone and lithium use (both interfere with Thyroid hormone synthesis)
96
Outline the Pathophysiology of Hasimoto's Thyroiditis. What 2 things are specifically attacked?
It is caused by autoimmune inflammation of the thyroid gland.
It is associated with **antithyroid peroxidase (anti-TPO) antibodies** and **antithyroglobulin antibodies**
Initially it causes a goitre after which there is atrophy of the thyroid gland.
97
What are some key signs of Hypothyroidism/Hasimoto's Thyroiditis?
**Bradycardia**
Unexplained weight gain
**Slow reflexes, Ataxia**
Round Puffy face
**Immobile Ileus** - temporary arrest of Intestinal peristalsis
**ASCITES** - fluid in abdomen
98
What are some symptoms a patient might experience if they have any form Hypothyroidism?
**Hoarse voice**
Goitre - *lump or swelling on neck from thyroid gland*
Weight gain
**Constipation**
**Cold intolerance**
Menorrhagia – heavy periods
**Tiredness**
Lethargy
Poor memory
Puffy eyes
Arthralgia/myalgia
Symptoms of anaemia
99
What are the first line key investigations you would do for Hypothyroidism?
How would results for Primary and Secondary differ?
What would you tests for specifically in Hashimoto's, and what's more common here?
Thyroid function test
Measure Free T4 and TSH levels
○ Primary - High TSH, low free T4
○ Secondary – inappropriately low TSH, low T3/T4 (since issue is in pituitary)
In Hashimoto’s Thyroid antibodies
○ Thyroid antibodies (TPO) - **Look for Thyroperoxidases and Thyroglobulin antibodies**
***(TPO antibody more common than antithyroglobulin)***
100
What is the key drug you can give in Hypothyroidism? What do you aim for with it?
Thyroid hormone replacement agents such as **levothyroxine** Life long, oral, Start 25mcg (microgram)
LEVOTHYROXINE IS SYNTHETIC T4
With primary,
Primary – titrate dose *until TSH normalises*
Aim is to get **TSH to >0.5**
IN secondary, treat underlying pituitary issue!
101
Name some risk factors for thyroid Cancer.
Head and neck irradiation, female sex, Family history of thyroid cancer,
102
What are some key signs/presentations of Thyroid cancer?
**THINK SIGNS OF TUMOUR ON THYROID GLAND**
* Lymph node metastases
* Thyroid nodule with history of progressive increase in size
Enlarged lymph nodes
**Tracheal Deviation
Hoarse voice
Dysphagia** ***Difficulty swallowing***
Weight loss
103
What are some symptoms of Thyroid Cancer?
* Thyroid nodules – increased size, hardness and irregularity
* Dysphagia
* Hoarseness of voice – tumour pressing on recurrent laryngeal nerve
Symptoms of Hyper/Hypothyroidism
104
What are some key investigations you would do if you suspected Thyroid Cancer?
**THINK -NEED TO LOOK AT THYROID GLAND, AND TREAT SYMPTOMS**
* Fine needle aspiration cytology biopsy best for distinguishing between benign and malignant thyroid nodules
* Thyroid ultrasound
* Thyroid Function tests – hyper/hypothyroidism needs to be treated before surgery - Look for TSH
105
What type of antibodies bind to what specific receptors, as seen in Grave's Disease?
Formation of **IgG** antibodies to the TSH receptors on the Thyroid Gland
106
What is post partum thyroiditis? What symptoms would a patient with this disease experience? What is the prognosis?
Where the **immune system attacks the thyroid** within 6 months after giving birth.
So rise in T3 and T4 **(hyperthyroidism),**
Followed by a decrease in T3 and T4, (hypothyroidism)
*^^similar to De Quaverain*
Will normally correct over 12 months, but may need treatment
107
Name some drugs that can cause **Drug induced Thyroiditis**
Lithium (used to treat Bipolar)
Amiodarone (used to treat arrhythmias - can cause either Hyper or Hypo)
Interferons (used to treat cancer)
108
What does hormone hCG have on TSH, and what can this lead to?
Stimulates the release of it as it stimulates TSH receptors, which can lead to Gestational hyperthyroidism - resolves in second trimester
109
What are the 6 hormones secreted by the anterior pituitary?
Follicle-stimulating hormone (FSH)
Luteinising hormone (LH)
Adrenocorticotrophic hormone (ACTH)
Thyroid-stimulating hormone (TSH)
**Prolactin (PRL)
Growth hormone (GH)**
FLAT PIG
110
What is Cushing's Disease? How much Cushing syndrome is it responsible for?
Cushing’s Disease is used to refer to the **specific condition where a pituitary adenoma (tumour) secretes excessive ACTH.** *(Adrenocorticotropic hormone)*
Responsible for 70-80% **ENDOGENOUS** of Cushing syndrome
*Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.*
111
What are the 4 main causes of Cushing's Syndrome?
Either ACTH *(Adrenocorticotropic hormone)* Dependant
1. adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma - Cushing's Disease
2. Ectopic Cushing’s Syndrome – coming from elsewhere Due to paraneoplastic syndrome e.g. small cell lung cancer producing ACTH
or Non ACTH Dependant:
3. Exogenous - Oral Steroid Use **(Iatrogenic)**
4. An Adrenal adenoma or carcinoma, a tumour on the adrenal gland that releases Cortisol
Think Tumours of various locations, and exogenous steroid use
112
What are some signs and symptoms of Cushing's Syndrome?
○ Cataracts
○ Ulcers
○ Striae – purple strokes on skin
○ **Hypertension and hyperglycaemia (due to impaired glucose tolerance)**
○ Increased risk of infection – dampening of inflammatory response
○ Glucosuria - *due to the hyperglycaemia*
Truncal/central obesity
Moon face - FACIAL PLETHORA
Buffalo hump – fatty hump on upper back
Acne
Hirsutism – unwanted male pattern hair growth in women
Thin skin/bruising - EASY BRUSING
Osteoporosis
113
What are the first line investigations you would do for suspected Cushing's syndrome?
Late night salivary cortisol (would be elevated)
Blood glucose (would be elevated)
Urine pregnancy test (need to confirm not pregnant)
1 mg overnight dexamethasone suppression test morning cortisol Positive result : >50 nanomol/L
114
Cushing's: In a healthy human, what would you expect to see in the 1mg overnight Dexamethasone test and why?
Decreased Cortisol levels in blood, due to negative feedback that Dexamethasone would exert on the hypothalamus and the pituitary gland (so less ACTH and CRH as well)
It would suppress the morning spike of cortisol that you see when you retest in the morning.
115
In a patient with Cushing's, what would you expect to see in the 1mg overnight Dexamethasone test and why?
If they have Cushing's Disease, (Adenoma on Pituitary Gland), Then ACTH will still be high due to the tumour, so cortisol will not be suppressed. (Dexamethasone won't have made a difference)
morning cortisol >50 nanomol/L
116
Cushing's Investigations - if 1mg is abnormal, what would you expect to see if you give 8mg of Dexamethasone overnight in a patient that actually had:
a) Adrenal Adenoma/Carcinoma
b) Ectopic ACTH Tumour
c) Cushing's Disease
a) Low levels of ACTH, but high levels of Cortisol in the blood
b) High levels of both ACTH and cortisol in the blood
c) Low levels of Cortisol and low levels of ACTH -*as In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.*
117
How do we treat Cushing's Syndrome?
Depends on the cause!
If Exogenous, stop the steroids
or surgery to remove relevant tumour on either Pituitary gland/ or Ectopic. **trans sphenoid removal**
Remove adrenal glands (adrenalectomy)
Give drugs
118
What drugs can we give to treat Cushing's Syndrome?
**Steroidogenesis inhibitor** (osilodrostat, ketoconazole, metyrapone, mitotane, etomidate),
**Glucocorticoid receptor antagonist** (mifepristone) is occasionally used for mild hypercortisolism, or short term for severe hypercortisolism, before other therapies are undertaken
119
What are some complications of Cushing's Syndrome?
Adrenal Insufficiency secondary to adrenal suppression
Cardiovascular disease
Hypertension
Diabetes Mellitus
**imunosuppression** - as high levels of cortisol lead to immunosuppression
120
What is the difference between acromegaly and Gigantism?
Acromegaly = excessive production of growth hormone **occurring in adults after fusion of the epiphyseal plates** usually due to a pituitary somatotroph adenoma.
Gigantism = excessive production of growth hormone occurring **in children before fusion of the epiphyses of long bones** - gonna grow lots
121
What is the main cause of acromegaly?
What % is prolactin secreted?
What gene mutation is sometimes seen in acromegaly?
Due to a **pituitary somatotroph adenoma** in 95-99% of cases.
Prolactin co-secreted in 25% of cases .
Activating mutation in the **GNAS1 gene** is shown in 30% to 40% of somatotroph adenomas
122
Pathophysiology of Acromegaly - what can promote pituitary tumour development?
What does Excessive GH secretion lead to, directly that is seen in acromegaly?
Dysregulation of
*hormones
transcription factors
growth factors*
that all act on the pituitary can promote tumour development.
Pituitary somatotroph adenomas chronically secrete excessive GH, **which stimulates insulin-like growth factor 1 production**
Function of GH:
* Direct – acts on tissues such as liver, muscles, bones and fat to **induce metabolic changes**
123
What are some signs of Acromegaly you may see on examination?
* Morphological facial changes: frontal bossing, enlarged nose, prognathism (protuding jaw) and separation of teeth, macroglossia (massive tongue), large ears and nose
* Thick skin, *+ Skin tags*
* **Obstructive sleep apnoea**
* Deep voice
* **Hypertension**
* **HF**
Visual field defect (“bitemporal hemianopia”)
**Sweating**
**Headaches, due to pressure locally**
Increase in hands and feet (Show and ring size)
**Oligo/amenorrhea**
Joint pain
Development of **Skin Tags**
Fatigue
*More GH ==> Body works harder, so increase in Temperature/Sweat. Also, increased GH leads to more oil and sweat glands*
Elevated IGF-1, elevated GH
124
What are the first line investigation tests for acromegaly?
Serum GH and Serum IGF-1
125
What is the gold standard test of acromegaly?
* Oral glucose tolerance test
○ Normally a rise in blood glucose *will suppress GH levels*
○ Give glucose and then test GH levels – **if they remain high** this is diagnostic for acromegaly
126
What is the 1st line management for treatment of acromegaly?
What are some complications of this?
* 1st line - Transphenoidal surgical resection to remove the adenoma and correct compression of surrounding structures e.g. optic chiasm
○ Complications
§ Hypopituitary
§ Infection
§ Diabetes Insipidus
127
What are the most common type of pituitary tumours?
Prolactin-secreting pituitary adenomas
(Prolactinomas)
*Prolactinomas are the most common type of pituitary adenoma, constituting about 50% of these tumours*
128
What can be the consequences of a pituitary tumour that is putting pressure on local structures?
Headaches (due to stretching of the Dura)
Visual field defects
Cranial Nerve palsy
Hydrocephalus - *accumulation of cerebrospinal fluid (CSF) within the brain*
Pressure on Hypothalamic centres - so increased thirst, obesity, early puberty in children (precocious)
Cerebrospinal fluid rhinorrhoea (downward extension through the pituitary fossa) 🡪 CSF dripping out of the nose
129
What substance has an inhibitory effect on prolactin? What are the implications of this?
dopamine, so tumours inhibiting dopamine can cause hyperprolactinaemia.
130
What are some key symptoms some would experience with hyperprolactinaemia or a prolactinoma?
Increased prolactin ==> increased milk production in the breast (also **galactorrhoea)**
Menstruation stops **(amenorrhoea)**
*Infertility/ reduced fertility*
Visual deterioration - temporal hemianopia
131
Why can hyperprolactinaemia cause infertility?
as prolactin inhibits GnRH (Gonadotrophic releasing Hormone)
132
What key diagnostic tests would you do in suspected prolactinomas/hyperprolactinaemia?
Serum prolactin - *would be elevated*
Pituitary MRI
Computerised visual field examination
133
What is the main treatment you give for a prolactinoma?
Dopamine agonist **(inhibits Prolactin)**– CABERGOLINE or BROMOCRIPTINE
134
Name 4 conditions associated with pituitary adenomas.
Cushing's Disease - PA = too much ACTH = too much cortisol
Acromegaly - PA - Too much growth hormone = too much IGF-1
Prolactinoma - PA - Too much prolactin produced
Secondary Hyperthyroidism - Too much TSH - Too much Thyroxine
135
What does Aldersterone action lead to?
Aldosterone acts on the kidneys
Extracellular volume goes up
Renal blood pressure goes up
More Na+ and water retention
K+ excretion
Decreased Extracellular fluid of K+
136
What is Conn's Syndrome?
Conn’s syndrome refers ONLY to **PRIMARY Aldosterone producing adenoma**
A tumour in the adrenal gland!!
137
What does Conn's do, and what does this lead to?
* **Excess production of aldosterone, independent of RAAS causes**
○ **Increases K+ loss, Na+ and water retention** 🡪 raised BP
○ Decreased renin release
*○ Hypokalaemia*
138
What are some signs and symptoms of Conn's?
Hypertension
Increased risk of cardiac arrhythmias, particularly in patients with cardiac disease
Symptoms
**Polyuria, Nocturia**
Lethargy/tiredness
Muscle weakness
Paraesthesia
Headaches
Mood disturbance
139
What is a the first line basic investigation for suspected Conn's
Plasma potassium - Low in approx. 20% of patients with PA
140
What is the gold standard investigation for someone with Conns?
Aldosterone : Renin ratio
Positive result would be **>70 for aldosterone** in picomol/L
*(High aldosterone, low renin, as primary)*
141
What are some differential diagnosis for Conn's disease
Essential hypertension
Thiazide induced hypokalaemia in a patient with essential hypertension
Renal artery stenosis
Secondary hyperaldosteronism (too much renin and aldosterone)
142
What are the two main things you can do to treat Conn's?
* Laparoscopic adrenalectomy
Prescribe
* **Oral spironolactone** – *aldosterone antagonist* (K+ sparing diuretic)
143
What is Addison's disease?
Adrenal glands have been damaged, resulting in reduced **secretion of cortisol and aldosterone.**
Also called **primary adrenal insufficiency.**
144
What is the most common cause of Addison's disease in a) the world
b) The UK
Worldwide = TB
In UK = Autoimmune adrenalitis
145
What is the Pathophysiology behind Addison's?
**More importantly, what does it lead to?**
What antibodies may be seen?
Destruction of Entire adrenal cortex resulting in reduced glucocorticoid (cortisol), mineralocorticoid (aldosterone) and androgen production
**Adrenal antibodies – 21-hydroxylase** - *involved in biosynthesis of aldosterone and cortisol.*
Leads to symptoms, and Increased CRH and ATCH levels
146
What are some signs of Addison's disease (Primary Adrenal Insufficiency) that you would detect from examination?
*For each sign, what hormone abnormality is causing this?*
* Postural hypotension caused by salt and water loss **Lacking aldosterone**
* Bronzed Hyperpigmentation caused by excess ACTH in primary hypoadrenalism
* Vitiligo and loss of body hair in females due to dependence on adrenal androgens
* Hypoglycaemia - Steroids can increase blood sugar
REMEMBER – Tanned, Tired, Toned and Tearful
147
What are some symptoms a patient with Addisons/Adrenal insuffiency experience?
*Think why they are feeling these things!)*
**Lethargy** Lack of steroids
Feeling faint - LOW BP due to low Aldosterone
Dehydration - Due poor water retention due to Poor aldosterone
**Weight Loss - due to lack of steroids**
Abdominal Pain
Depression/tearfullness
* Impotence
Amenorrhoea - stopped period - due to lack of Androgens
148
An Addison Crisis is a presentation of severe Addison's disease. How would a patient in Addison Crisis present??
Presentation of Severe Addison's, *where the absence of steroid hormones* result in a life threatening presentation. Very unwell!!
They present with:
Reduced consciousness/confusion
Hypotension
Hypoglycaemia, **hyponatraemia and hyperkalaemia**
Muscle cramps
Hypovolemic Shock
149
How do you treat an Addisonian Crisis?
Urgently!
Give IV Fluids, and IV Hydrocortisone
Correct any hypoglycaemia
150
What are some first line investigations for Addisons?
What are the ATCH and cortisol levels seen in Primary and Secondary/Tertiary Hypoadrenalism
Morning Serum cortisol - less than <140 nanomols/L
Look at ATCH levels -
○ **HIGH ACTH with low or normal cortisol** confirms primary hypoadrenalism
○ **LOW ACTH and cortisol** indicate secondary or tertiary hypoadrenalism
151
What is the gold standard test for Addison's disease?
What antibodies are seen in Addisons?
* **Short ACTH stimulation test** (Synacthen test)
○ Take baselines cortisol
○ Give ACTH (synACTHen) then measure cortisol level –
§ In Addison’s – ***cortisol remains low after giving ACTH***
* Adrenal antibodies – **21-hydroxylase** - *involved in biosynthesis of aldosterone and cortisol.
152
What would be the plasma levels of
a) Renin
b) Sodium
c) Potassium
In Addisons disease, and why?
In addisons, would have high plasma renin , low sodium, high potassium) due to low aldosterone
153
What two main drugs can you give to treat Primary Adrenal insuffiecincy?
* Glucocorticoids - oral **Hydrocortisone**/prednisolone to replace cortisol
Mineralocorticoids - **fludrocortisone** to replace aldosterone
154
Outline what SIADH is (Syndrome of Inapproptiate ADH secretion)
Continued secretion of ADH despite plasma being very dilute 🡪 water retention, excess blood volume and hyponatraemia
Too much ADH
155
Name some things that can cause SIADH.
Malignancy eg Cancer tumours that secrete Ectopic ADH
Drugs
Head Injury, Meningitis
156
What Types of cancer has been known to secrete ectopic ADH? (3 locations)
lead to ectopic secretion of ADH. Seen in ***Small cell carcinomas of the lungs, Prostate and Pancreatic**
157
What kind of drugs have been known to cause SIADH?
Opiates,
Carbamazepine (anti epileptic) .
Chlorpropamide (to treat diabetes) SSRIs
Thiazide diuretic
158
What are some risk factors for SIADH?
The listed causes *(Malignancy, Drugs, Head Injury)*
Also
Recovering from major surgery
Including age >50 years, nursing home residence,
Presence of a postoperative state,
Pulmonary conditions (e.g., pneumonia),
CNS *(eg MS)* disease
Trauma
159
Outline the pathophysiology of SIADH that leads to hyponatraemia
But more water means **less RAAS so les Aldosterone released**, so more **Na+ secretion and loss into urine**
(body is removing sodium from blood that already has a low concentration of sodium) ==> NORMOVOLAEMIC yet HYPONATRAEMIC
*The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a* ***“euvolaemic hyponatraemia"***
160
What are some signs of SIADH?
* Concentrated urine
* Mild dilutional hyponatraemia – could lead to fits and coma
161
What are some symptoms of SIADH?
* Reduction in GCS and confusion with drowsiness
* Irritability
* Headaches
* Anorexia
* Nausea/Vomiting
162
How do you go about differentiating SIADH from Hyponatraemia?
Test by giving with 1-2L of 0.9% saline – sodium depletion WILL respond, SIADH will NOT
163
What is the diagnostic criteria for SIADH?
Diagnostic Criteria for SIADH:
- Hyperosmolar Urine
- Hypo osmolar Serum
- No hyper or hypovolaemia
- Hyponatraemia
Adrenal, Thyroid and renal function all normal
164
What is Potassium essential for in the body?
Maintaining the resting potentials in all muscles in the body, involving the heart
165
What does Hypokalaemia result in for
a) Smooth Muscle
b) Skeletal Muscle
c) Cardiac Muscle
*Remember the rule!*
**Hypo - Everything Slows**
a) Constipation
b) Weakness/Cramps
c) Arrhythmias and Palpitations
166
What does Hyperkalaemia result in for
a) Smooth Muscle
b) Skeletal Muscle
c) Cardiac Muscle
*Remember the rule!*
a) Smooth - Cramping
b) Skeletal - Weakness/Flaccid Paralysis *(Due to over contraction of muslces, become totally drained of energy)
c) Cardiac- Arrhythmias and arrest.
167
What are some causes of Hyperkalaemia?
Low levels of aldosterone in kidneys – adrenal insufficiency - as it gets rid of K+ in the urine
Certain Drugs
AKI - decreased filtration rate so more K+ is maintained in the blood
168
What drugs can cause Hyperkalaemia?
ACE inhibitors – block the binding of aldosterone to receptor
Diuretics that spare K+
NSAIDs
Heparin
169
What are some symptoms of Hyperkalaemia?
Typically, asymptomatic until high enough to cause cardiac arrest
Muscle weakness
Flaccid paralysis
Chest pain
Light-headedness
170
What are some symptoms of Hypokalaemia?
Metabolic acidosis causing Kussmaul’s respiration – low, deep, sighing inspiration and expiration
Tachycardia
ECG abnormalities
171
What are features of an ECG in a hyperkalaemic patient?
(Draw it!)
Tall tented T waves *(Normally smaller secondary wave)*
Wide, flat P waves *(Tiny initial wave)*
Wide QRS complex *(Big main wave)*
Look up a picture
172
How would you treat Mild Hyperkalaemia?
Treat underlying cause
Restrict Dietary potassium
Restriction of drugs causing hyperkalaemia
Loop diuretics e.g. **furosemide – increase urinary K+ excretion**
173
How would you treat severe Hyperkalaemia?
**Calcium gluconate** – decreases VF risk in the heart and protects myocardium by reducing excitability of cardiac myocytes
**Insulin and dextrose** – drives K+ into the cells
**Polystyrene sulphonate resin** – binds K+ in the gut decreasing uptake
174
Would you see on an ECG for someone with Hypokalaemia? Rhyme?
U waves
Small or inverted T waves
Depressed ST segments
Prominent U Wave
Long PR
Long QT
Rhyme – You have no Pot (K+) and no Tea (T Wave) but a Long PR and a Long QT, FOR YOU (Prominent U wave)
175
What treatment do you give for
a) Mild Hypokalaemia
b) Severe Hypokalaemia
Mild – Oral K+ e.g. oral Sando-K and spironolactone (K+ sparing)
Severe- IV K+
176
How can we think of serum/plasma osmolarity?
As a **Concentration** so high serum or urine osmolarity means **high concentration** of Solutes in the serum or urine
A Low Urine osmolarity would be low concentration of solutes in urine, as seen in Diabetes Insipidus
177
Normal Physiology - Outline the the relationship between Renin, Angiotensin 1 and Angiotensin 2.
Where is ACE made?
Renin cleaves **angiotensinogen** into angiotensin 1,
*Angiotensin 1* becomes *Angiotensin 2* by **Angiotensin converting enzyme ACE**,
This reaction happens in the lungs, where ACE is made.
178
What is secondary hyperaldosteronism?
Occurs when there is excessive **Renin** (and hence angiotensin II) which stimulates the adrenal glands to produce more **aldosterone**
179
What are some conditions that lead to secondary hyperaldosteronism - and why do they lead to it?
**Renal artery Stenosis**
Renal artery obstruction
Heart Failure
Which leads to *Blood pressure in the kidneys being* ***disproportionately lower than the blood pressure in the rest of the body, from decreased renal perfusion*** ===> Too Much Renin Released, leading to too much aldosterone release *(hyperaldosteronism)*
180
In primary aldosteronism, what would the renin/aldosterone ratio be?
High aldosterone and low renin
181
In secondary aldosteronism, what would the renin/aldosterone ratio be?
High aldosterone and high renin indicates secondary hyperaldosteronism
182
What is the main cause of Cushing's syndrome? What is the 2nd most common?
Most common cause of Cushing's **Syndrome** is is exogenous therapeutic steroid use
Then the second most common cause of Cushing’s syndrome is Cushing’s disease
183
Where do most Carcinoid tumours occur?
GI tract
Can also be in lung, and can metastisise elsewhere eg Liver
*Carcinoid syndrome generally does not occur until the disease is so advanced that it overwhelms the liver's ability to metabolize the released serotonin*
184
What two things do Carcinoid tumours secrete? What do they both do?
serotonin and kallikrein
Serotonin is involved with initiating peristalsis, and plays a role in bronchoconstriction
*In Carcinoid Syndrome, Serotonin can cause fibrous of heart valves, especially on the the right hand side.*
Kallikrein - leads to formation of bradykinin, one of the most potent vasodilators known. Therefore has great effect on Blood flow **(can cause flushing)**
185
What are some symptoms of Carcinoid syndrome?
**Flushing: The most important clinical finding is flushing of the skin**, usually of the head and the upper part of thorax. - *Due to vasodilation*
- Abdominal pain, due to Hepatomegaly , or bowel obstruction or bowel ischaemia,
- Diarrhoea - due to abdominal cramping, and abnromal peristalsis
- Carcinoid Heart disease - Serotonin leads to fibrous of right hand side heart valves
Bronchoconstriction, due to serotonin/histmaine, leads to Flushing, sneezing, and SOB
186
What are the two types of diabetes insipidus?
Cranial Diabetes Insipidus - Too little ADH from Posterior Pituitary Gland
Nephrogenic Diabetes Insipidus - Kidney not responding to ADH.
187
What can cause Nephrogenic Diabetes insipidus?
Drugs, particularly lithium used in bipolar affective disorder, and Demeclocycline
Mutations in gene that codes for the ADH receptor - so **Familial**
Kidney disease
Electrolyte disturbance (hypokalaemia and hypercalcaemia)
Renal Tubular Acidosis
188
What are some causes of Cranial Diabetes Insipidus?
Brain tumours
Head injury
Brain infections (meningitis, encephalitis and tuberculosis)
Brain surgery or radiotherapy
Pituitary Tumour
189
What are some symptoms of Diabetes Insipidus?
Polyuria/Nocturia
Polydipsia
Dehydration
190
What is the main test of choice for diagnosing Diabetes Insipidus?
What are other investigations you can use to test for Diabetes Insipidus?
The water deprivation test - main one
Also
Look at Serum and Urine Osmolarity
MRI of Hypothalamus
Plasma biochemistry
191
What does the water deprivation test look for? How does it work *(Two Parts)*? (Main investigation in Diabetes Insipidus)
It aims to determine whether kidneys continue to produce dilute urine despite dehydration.
You restrict fluid for 8 hours, and measure Urine osmolarity, which can check for Diabetes insipidus.
Then, give **Synthetic ADH** *(Desmopressin)* and recheck the urine osmolarity to distinguish between Cranial DI and Nephrogenic DI
192
What would urine osmolarity after Water deprivation in
a) A normal person
b) Someone with Diabetes Insipidus
a) Concentrated/high, but in normal ranges
b) Still low, (lots of urine produced) despite dehydration
193
After giving Synthetic ADH *(Desmopressin)* after water deprivation to test for DI, what would urine osmolarity be in
a) Cranial Diabetes Insipidus
b) Nephrogenic Diabetes Insipidus
a) Cranial - High urine osmolarity (as kidneys are still capable of responding to ADH)
b) Nephrogenic - Still low Urine osmolarity, as problem is not with the lack of ADH but the lack of response in the kidneys to it.
194
How do you treat
a) Cranial Diabetes Insipidus?
b) Nephrogenic Diabetes Insipidus?
a) Desmopressin - **Synthetic ADH**
b) Bendroflumethiazide Diuretic - **(Causes more Na+ secretion), so more water lost so body responds by reducing GFR)**
Treat underlying cause!
195
What are the signs/symptoms of Phaeochromocytoma?
**Symptoms of Adrenaline release!**
Anxiety
Sweating
Headache
Hypertension
Palpitations, tachycardia and paroxysmal atrial fibrillation
*Signs and symptoms tend to fluctuate with peaks and troughs relating to periods when the tumour is secreting adrenaline.*
196
What is the management of Phaechromocytoma?
Alpha blockers (i.e. phenoxybenzamine)
Beta blockers once established on alpha blockers
*^^To control the symptoms*
Adrenalectomy to remove tumour
*Patients should have symptoms controlled medically prior to surgery to reduce the risk of the anaesthetic and surgery.*
197
In primary aldosteronism, what would the renin/aldosterone ratio be?
High aldosterone and low renin
198
What are some investigations you would do for a carcinoid syndrome?
- **24 hr urine 5-hydroxyindoleacetic acid:** show increased levels - *(its a major metabolite of 5-HT/serotnin)* GOLD STANDARD
- **Chest X-ray/ chest or pelvis MRI/ CT:** to identify location
- **Ostreoscan:** injected radiolabelled somatostatin analogue, octreotide, to bind to the increased number of somatostatin receptors on tumour cells.
