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Emily Phase 2a > Endocrine > Flashcards

Endocrine Flashcards

1
Q

What is Type 1 Diabetes?

A
  • Type 4 hypersensitivity
  • autoimmune destruction of pancreatic beta cells (absolute insulin deficiency)
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2
Q

What are the risk factors for Type 1 diabetes?

A
  • Genetic predisposition
  • Geographical region = more common in Europeans than asians
  • Infectious agents = human enteroviruses
  • Dietary factors = supplementation with Vitamin D may be protective
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3
Q

What is the pathophysiology for Type 1 Diabetes?

A
  • Autoimmune pancreatic beta-cell destruction
  • Hyperglycaemia develops = insulin deficient
  • unable to utilise glucose in peripheral muscle and adipose tissue -> increased lipolysis + gluconeogenesis
  • long term leads to vascular complications = glycosylation of proteins
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4
Q

What are the signs and symptoms for Type 1 diabetes?

A

Main
- hyperglycaemia
- polyuria
- polydipsia

Other
- young age
- weight loss
- blurred vision
- nausea and vomiting
- abdominal pain
- tachypnoea
- lethargy
- coma

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5
Q

What are the investigations for Type 1 diabetes?

A

1st
- random plasma glucose & 2hr plasma glucose
T1D = ≥11.1 mmol/L
Normal = <11.1 mmol/L

  • fasting plasma glucose
    T1D = ≥7.0 mol/L
    Normal = <7.0 mol/L
  • HbA1c
    T1D = ≥ 6.5%
  • clinical diagnosis (adults)
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6
Q

When is an Oral Glucose Tolerance Test used?

A

In pregnancy - to test for gestational diabetes

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7
Q

Where is insulin and glucagon secreted?

A

Islets of langerhans
beta cells = insulin
alpha cells = glucagon

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8
Q

Define paracrine ‘crosstalk’

A

Communication between alpha and beta cells is physiological
- insulin release inhibits glucagon
vice versa

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9
Q

What is the process of secretion of insulin by beta cells?

A
  1. High levels of glucose in the blood
  2. Glucose enters beta cells through GLUT2 glucose transporter
  3. Glucose metabolised by glucokinase to produce ATP
  4. ATP will bind to potassium channels in membrane and close them
  5. Causes depolarisation
  6. Causing calcium voltage gated ion channels to open
  7. Calcium enters beta cell and
  8. Causes exocytosis
  9. Vesicles containing insulin release insulin into the blood
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10
Q

What is the action of insulin in muscle and fat cells?

A
  1. Insulin released into blood binds to insulin receptor on plasma membrane of muscle/fat cells
  2. Triggers an intracellular signalling cascade
  3. GLUT4 vesicles mobilisation to plasma membrane
  4. GLUT4 vesicles integration into plasma membrane
  5. Glucose entry into cell via GLUT4
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11
Q

What is the likelihood of developing type 1 diabetes from different family members?

A

Higher chance of getting the condition if the father has the condition
- mother = 2%
- father =8%
- both parents = 30%
- sibling = 10%
- identical twins = 40%

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12
Q

What are the microvascular and macrovascular complications of Type 1 diabetes?

A
  • diabetic neuropathy
  • retinopathy
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13
Q

What is diabetes mellitus?

A

A disorder of carbohydrate metabolism characterised by hyperglycaemia
- cause morbidity and mortality through acute/chronic hyperglycaemia

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14
Q

What are all the types of diabetes?

A
  • Type 1
  • Type 2
  • Maturity onset diabetes of youth (MODY) aka. monogenic diabetes
  • pancreatic diabetes
  • endocrine diabetes (acromegaly/cushings)
  • malnutrition related diabetes
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15
Q

What is the HbA1c?

A

Measures glucose level over the last 3 months
- glucose attaches to the haemoglobin so can measure how much glucose has attached since RBCs have a lifespan of 3 months

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16
Q

What does failure of insulin secretion lead to?

A
  • continued breakdown of liver glycogen (insulin or glucagon in communication, so one is always produced)
  • unrestrained lipolysis and skeletal muscle breakdown providing gluconeogenic precursors
  • inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake
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17
Q

What does failure to treat with insulin lead to?

A
  • increase in circulating glucagon (loss of local increases in insulin within the islets leads to removal of inhibition of glucagon release), further increasing glucose
  • perceived ‘stress’ leads to increased cortisol and adrenaline
  • progressive catabolic state and increasing levels of ketones
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18
Q

What is the aetiology of type 2 diabetes?

A
  • genes and environment
  • impaired insulin secretion/ insulin resistance
  • cause impaired glucose tolerance
  • lead to type 2 diabetes
  • leading to progressive hyperglycaemia and high free fatty acids
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19
Q

Why do beta cells stop working in Type 2 diabetes?

A
  • When pancreas has to work really hard over a long period of time to produce very high levels of insulin the beta cells start failing
  • as insulin resistance increases the pancreas tries to keep up but starts to fail
  • so less insulin produced, glucose not taken into cells, more glucose in blood, glucose starts sticking more to RBCs causing vascular complications
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20
Q

What is the pathogenesis of type 2 diabetes?

A
  1. Impaired insulin secretion
  2. hepatic insulin resistance
    - excessive glucose production
    - more glucose enters the blood stream
  3. Muscle/fat insulin resistance
    - impaired glucose clearance
    - less glucose enters peripheral tissues
  4. Hyperglycaemia
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21
Q

What are the key presentations for type 2 diabetes?

A

Hyperglycaemia with presence of risk factors

e.g. overweight, ethnic groups etc.

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22
Q

What are symptoms of type 2 diabetes?

A

Polydipsia
Polyuria
candidal infections,
skin infection,
UTIs,
fatigue,
blurred vison
uncommon symptoms

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23
Q

Does ketosis occur in type 2 diabetes?

A
  • early on the body still produces insulin inhibiting ketosis
  • as beta cells are destroyed, less insulin is produced
  • this then causes late stage ketosis
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24
Q

What causes insulin resistance?

A
  • from a high fat diet, more fat is deposited in liver and pancreas
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25
Q

What are first line investigations for type 2 diabetes?

A

Fasting glucose, 2-hour post load glucose (75g orally) random plasma glucose

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26
Q

What is the treatment of type 2 diabetes?

A
  • weight loss, exercise, healthier diet
  • Metformin
  • Sulphonylureas (gliclazide, glibenclamide)
  • thiazolidinediones
  • GLP-1
  • SGLT-1 inhibitors
  • DPP 4
  • Bariatric surgery (gastric bypass, sleeve gastroectomy )
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27
Q

How do DPP 4 inhibitors work?

A

Dipeptidyl-peptidase 4 is an enzyme present in vascular endothelial lining which inactivates the incretin hormone GLP and GLP-1

DPP-4 Inhibitors are competitive antagonists of the DPP-4 enzyme - enhancing the effects of both GIP and GLP-1

(Incretins slow gastric emptying , involved in insulin secretion)

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28
Q

How does metformin work?

A
  • Used to treat Type 2 and gestational diabetes
  • reduce production of glucose by the liver
  • decrease absorption of glucose by the gastrointestinal tract
  • increase target cell insulin sensitivity.

Metformin does not influence the production of insulin; it simply increases the body’s sensitivity to the hormone.

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29
Q

How is metformin excreted?

A

Unchanged in urine
via active tubular secretion

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30
Q

What are the side effects of Metformin?

A
  • lactic acidosis = when given with IV contrast (metformin held for 48hrs prior to contrast)
  • GI disturbances
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31
Q

How does Sulphonylureas work?

A
  • stimulates insulin release by binding to beta cell receptors (only works on people who are still producing some insulin)
  • improve glycaemic control
  • prevent gradual failure of insulin secretion
  • can cause hypoglycaemia
  • use gliclazide in most people
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32
Q

What is the action of thiazolidinediones?

A
  • bind to nuclear receptor PPARy
  • activate genes concerned with glucose uptake and utilisation and lipid metabolism
  • improve insulin sensitivity
    -need insulin for a therapeutic effect
  • glitazones rarely used
    e.g. pioglitazone - ACTOS
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33
Q

What is the action of GLP-1?

A

Glucagon like peptide-1
(secreted from L cells in the intestines)
- stimulates insulin secretion
- suppresses glucagon secretion
- slows gastric emptying
- reduces food intake
- increases beta cell mass and maintains Beta cell function
- improves insulin sensitivity
- enhances glucose disposal

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34
Q

What is the action of SGLT-2 inhibitors?

A
  • they block the reabsorption of glucose in the kidney (in type 2 diabetes there is too much glucose in the blood, so enables for it to be excreted quickly)
  • increase glucose excretion
  • lower blood glucose levels
  • reduce CV mortality
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35
Q

What are the side effects of SGLT2?

A
  • genital thrush (excreting more glucose in urine so provides good environment for bacteria to grow)
  • increased risk of euglycaemia ketoacidosis (peeing out glucose, so body goes into a state of starvation causing ketosis)
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36
Q

What is the initial management for type 2 diabetes?

A

1st lifestyle changes plus agree glycaemic (HbA1c) target
Adjunct of BP and lipid management

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37
Q

What is the management for acute type 2 diabetes?

A

HbA1c is above target 1st metformin plus lifestyle measures, cardiovascular risk reduction, and specific considerations

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38
Q

How would you manage type 2 diabetes?

A

Every 3 to 6 months (tailored to individual needs), until the patient’s HbA1c is stable on unchanging therapy *
Every 6 months once the patient’s HbA1c level and blood glucose-lowering therapy are stable.

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39
Q

What else would you monitor in a patient with type 2 diabetes?

A

Measure blood pressure at least once a year in an adult with type 2 diabetes without previously diagnosed hypertension or renal disease.

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40
Q

What are the most likely complications associated with type 2 diabetes?

A

Cardiovascular disease, congestive heart failure, stroke.
Diabetic ketoacidosis if very poorly managed

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41
Q

What are basal insulin?

A

Aims to keep blood glucose levels at consistent levels during periods of fasting

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42
Q

What are the different insulins used in Type 1 and 2?

A

Once-daily basal insulin
- only in Type 2

Twice daily mix insulin
- Both types

Basal-bolus therapy
- mostly in type 1
(rarely in type 2)

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43
Q

What are the advantages and disadvantages of basal insulin in type 2?

A

Advantages:
- simple for the patient, adjust insulin themselves
- less risk of hypoglycaemia at night

Disadvantages:
- doesn’t cover meals
- best used with long acting insulin analogues (expensive)

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44
Q

What is the advantages and disadvantages of pre-mixed insulin?

A

Advantages:
- can cover insulin requirements through most of the day
- don’t need to adjust

Disadvantages:
- not physiological
- requires consistent meal and exercise pattern
- increased risk for nocturnal hypoglycaemia

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45
Q

What 2 complications occur in the eyes in diabetic retinopathy?

A
  1. Leakage
    Basement membrane thickening
    Pericyte loss
    reduces junctional contact with endothelial cells
  2. Ischaemia/occlusion
    - Pericyte loss, endothelial cells respond by increasing turnover > thickening > ISCHAEMIA
    - Glial cells grow down capillaries > OCCLUSION
    - Ischaemia/Occlusion > Proliferation
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46
Q

What is diabetic nephropathy?

A

Disrupts filtration process of the kidney causing albumin to be excreted and reducing GFR

glomerulus changes > increase of injury glomerular > filtration of proteins > diabetic nephropathy

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47
Q

What are the consequence of diabetic peripheral neuropathy?

A
  • diabetic foot ulceration
  • pain or numbness (can’t fill pin in foot)
  • lower limb amputation
  • motor nerve damage
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48
Q

What is DESMOND?

A

Diabetes Education and Self Management for Ongoing and Newly Diagnosed

  • help educate people with diabetes
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49
Q

What is DAFNE?

A

Dose Adjustment For Normal Eating

Educational course to help people with Type 1 diabetes manage their insulin

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50
Q

What is MODY?

A

Maturity Onset Diabetes of the Young
- Autosomal dominant
- Non-insulin dependent
- Single gene defect altering beta cell function
- Tend to be non-obese
- acts more likely type 2 diabetes but is found in young people

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51
Q

What are the 2 types of MODY gene mutations that can occur affecting insulin sensitivity?

A

Transcription Factor MODY
- hepatic nuclear factor (HNF) mutation alter insulin secretion. reduce beta cell proliferation

Glucokinase Gene (GCK) mutation (MODY2)
- GCK is the glucose sensor of beta cells, rate determining step in glucose metabolism controlling the release of insulin
- no treatment required
- high amount of glucose needed to release insulin

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52
Q

When would people have MODY and not diabetes?

A
  • Parent affected with diabetes
  • absence of islet autoantibodies
  • evidence of no insulin dependence
  • C peptide persists, whereas in type 1 is negative
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53
Q

What is permanent neonatal diabetes?

A
  • diagnosed <6 months
    (small, epilepsy, muscle weakness)
  • mutations in Kir6.2 and SUR1 subunits of the beta cell ATP sensitive potassium channel
    -> mutations prevent closure of the potassium channel with ATP so beta cells unable to secrete insulin
  • sulphonylureas close Katp channel
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54
Q

What is maternally inherited diabetes and deafness (MIDD)?

A
  • mutations in mitochondrial DNA (always inherit mitochondria just from the mother)
  • loss of beta cell mass
  • wide phenotype
  • similar presentation to type 2
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55
Q

What is lipodystrophy?

A
  • selective loss of adipose tissue
  • associated with insulin resistance, dyslipidaemia, hepatic steatosis, hyperandrogegism, PCOS

(small lumps of fat appear when injecting insulin at the same ejection site, need to change around )

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56
Q

What are the acute and chronic complications of inflammation of the exocrine pancreas?

A

Acute: usually transient hyperglycaemia, due to increased glucagon secretion

Chronic Pancreatitis:
Alcohol
Alters secretions, formation of proteinaceous plugs that block ducts and act as a foci for calculi formation
Stop alcohol, treat with insulin

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57
Q

How is hereditary haemochromatosis an exocrine cause of diabetes?

A

Autosomal recessive – triad of cirrhosis, diabetes and bronzed hyperpigmentation
Excess iron deposited in liver, pancreas, pituitary, heart and parathyroids
Most need insulin

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58
Q

How is pancreatic neoplasia an exocrine cause of diabetes?

A
  • Common cause of cancer death (rather it is in the tail so can be removed easily surgically)
  • 4-5 resections per week at STH
  • Require sc insulin
  • Prone to hypoglycaemia due to loss of glucagon function
  • Frequent small meals, enzyme replacement
  • Insulin pumps
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59
Q

How is cystic fibrosis an exocrine cause of diabetes?

A
  • Cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7q22
  • Regulates chloride secretion (increased secretions)
  • Increased viscous secretions lead to duct obstruction in pancreas, and fibrosis
  • Incidence is 25 to 50% in adults
  • Ketoacidosis rare
  • Insulin treatment required (ducts blocked so can’t be released)
  • CF survival better, so microvascular complications increasing
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60
Q

How does acromegaly cause diabetes?

A
  • excessive secretion of growth hormone
    (similar to type 2)
  • insulin resistance rises, impairing insulin action in liver and peripheral tissues
    (reversible if cut tumour out)
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61
Q

How does cushings syndrome cause diabetes?

A
  • Hypercortisolaemia = increased gluconeogenesis so increased blood glucose levels
  • Hepatic glucose production increased through stimulation of gluconeogenesis via increased substrates (proteolysis and lipolysis)
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62
Q

How is pheochromocytoma an endocrine cause of diabetes?

A

Catecholamine, predominately epinephrine excess

Adrenaline decreases insulin levels, decreasing glucose uptake but increases gluconeogenesis

Higher blood glucose concentration
(reversible with surgery)

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63
Q

What drugs can induce diabetes?

A
  • Glucocorticoids increase insulin resistance
  • Thiazides / protease inhibitors (HIV) / antipsychotics – mechanisms not clearly understood
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64
Q

What are the current classifications of hypoglycaemia?

A

Level 1 = Alert value
(plasma glucose <3.9 mmol/l and no symptoms)

Level 2 = serious biochemical
(plasma glucose <3.0 mmol/l)

Level 3 = severe
(patient has impaired cognitive function sufficient to require external help to recover)

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65
Q

What effects does hypoglycaemia have on the body?

A
  • brain = cognitive dysfunction, blackouts, seizures
  • Heart = increased risk of myocardial ischaemia
  • musculoskeletal = fall, accidents
  • circulation = inflammation, blood coagulation abnormalities
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66
Q

What are the common symptoms of hypoglycaemia?

A
  1. Development of symptoms
    - autonomic = anxiety, hunger, sweat
    - neuroglycopenic = confusion, can’t focus, dizziness
    - non-specific = nausea, headache
  2. Low blood glucose
  3. Response to treatment with carbohydrate
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67
Q

What is the normal physiological response to prevent hypoglycaemia?

A
  1. inhibition of endogenous insulin secretion
  2. release of glucagon and adrenaline
  3. Liver breaks down glycogen and gluconeogenesis occurs
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68
Q

What is impaired awareness of hypoglycaemia?

A
  • people don’t realise they are hypo until they collapse on the floor
  • usually due to having frequent hypoglycaemia
  • glucose sensors in the brain turn off so no longer get symptoms
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69
Q

What are the causes of hypoglycaemia?

A
  • long duration of diabetes (lose glucagon after a few years)
  • use of drugs
  • tight glycaemic control with repeated episodes of non-severe hypoglycaemia
  • increasing age
  • sleeping (dampened response of glucagon and adrenaline, and can’t detect symptoms at night)
  • increased physical activity
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70
Q

What are the risk factors of severe hypoglycaemia?

A

Low HbA1c; high pre-treatment HbA1c in T2DM
Long duration of diabetes
A history of previous hypoglycaemia
Impaired awareness of hypoglycaemia (IAH)*
Recent episodes of severe hypoglycaemia
Daily insulin dosage >0.85 U/kg/day
Physically active (e.g. athlete)
Impaired renal and/or liver function

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71
Q

Strategies to prevent hypoglycaemia?

A

Discuss hypoglycaemia risk factors and treatment with patients on insulin or sulphonylureas
Educate patients and caregivers on how to recognize and treat hypoglycaemia
Instruct patients to report hypoepisodes to their doctor/educator

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72
Q

What is the treatment for hypoglycaemia?

A
  1. Recognize symptoms so they can be treated as soon as they occur
  2. Confirm the need for treatment if possible (blood glucose <3.9 mmol/l is the alert value)
  3. Treat with 15 g fast-acting carbohydrate to relieve symptoms
  4. Retest in 15 minutes to ensure blood glucose >4.0 mmol/l and re-treat (see above) if needed
  5. Eat a long-acting carbohydrate to prevent recurrence of symptoms
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73
Q

What is the action of the parathyroid hormone?

A

To maintain a high level of calcium in the blood

  • Increased calcium reabsorption (kidney)
  • increased calcium absorption (from gut due to vitamin D)
  • decrease in phosphate reabsorption
  • increase 1 alpha-hydroxylation of 25-OH VitD
  • increase bone remodelling and resorption (releases calcium into blood)
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74
Q

What are the consequences of hypocalcaemia?

A
  • parathesia
  • muscle spasm (premature labour, hands, feet, larynx)
  • seizures
  • basal ganglia calcification
  • cataracts
  • ECG abnormalities (long QT interval)
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75
Q

What is the calculation for corrected calcium?

A

corrected calcium = total serum calcium + 0.02*(40 - serum albumin)

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76
Q

What is Chvostek’ signs?

A

Tap over the facial nerve
- look for spasm of facial muscles
(in hypocalcaemia)

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77
Q

What is trousseau’s signs?

A

Initiate the blood pressure cuff to 20mm Hg above systolic for 5 mins
- If hypocalcaemia = this will initiate finger and hand spasms

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78
Q

What are the causes of hypoparathyroidism?

A
  • neck surgical
  • radiation
  • autoimmune (isolated, polyglandular type 1)
  • genetic
  • syndromes (Di George, HDR etc.)
  • infiltration (haemochromatosis, Wilson’s disease)
  • magnesium deficiency
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79
Q

What are the levels of PTH, Ca2+ and Phosphate in hypoparathyroidism?

A

Low PTH (inappropriate response)
Low Ca2+
High Phosphate

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80
Q

What is pseudohypoparathyroidism?

A

resistance to parathyroid hormone
leads to:
- short stature
- obesity
- mild learning difficulties

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81
Q

What are the levels of PTH, Ca2+ and Phosphate in pseudohypoparathyroidism?

A

High PTH (resistant to PTH)
Low calcium
High phosphate

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82
Q

What are symptoms and consequences of hypercalcaemia?

A
  • thirst, polyuria (pee out a lot of calcium)
  • nausea
  • constipation (gut muscle not working properly)
  • confusion -> coma

Develop
- renal stones
- ECG abnormalities (short QT)

Groans, Stones, Moans, Bones

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83
Q

What are the causes of hypercalcaemia?

A
  1. malignancy - some cancers produce PTHrP that responds like PTH, lymphoma
  2. primary hyperparathyroidism
  3. thiazides (make you retain calcium)
  4. thyrotoxicosis (excessive production of thyroid hormone)
  5. Sarcoidosis (abnormal collections of inflammatory cells)
  6. Familial hypocalciruic/benign hypercalcaemia
  7. immobilisation
  8. Milk-alkali
  9. Adrenal insufficiency
  10. pheochromocytoma
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84
Q

What happens in hypercalcaemia of malignancy?

A
  1. increase in calcium
  2. so PTH reduces
  3. decreases bone resorption, calcium absorption and reabsorption
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85
Q

What are the levels of PTH, Ca2+ and Phosphate in hypercalcaemia of malignancy?

A

Low PTH (appropriate)
High Calcium
Neutral phosphate

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86
Q

What are the consequences of primary hyperparathyroidism?

A
  1. Bone - osteoporosis (high PTH increased bone turn over)
  2. Stones - kidney stones
  3. Groans - psychic groans, confusion
  4. Moans - abdominal moans, constipation, acute pancreatitis
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87
Q

What are the levels of PTH, Ca2+ and Phosphate in primary hyperparathyroidism?

A

High PTH (Inappropriate)
High calcium
Low phosphate

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88
Q

What are the levels of PTH, Ca2+ and Phosphate in Vit D deficiency (secondary hyperparathyroidism)?

A

High PTH (appropriate)
Low calcium
Low phosphate

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89
Q

What 5 diseases can occur in the pituitary?

A
  1. benign pituitary adenoma
  2. craniopharygioma
  3. trauma
  4. apoplexy/ sheehans
  5. sarcoid/ TB
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90
Q

What are the 3 ways that pituitary tumours cause disease?

A
  1. Pressure on local structures
    - optic chiasm -> bitemporal hemianopia
    - cerebrospinal fluid rhinorhoea (through nose)
  2. Pressure on normal pituitary
    - hypopituitarism (pale, no body hair, central obesity)
  3. Functioning tumour (producing hormones)
    - prolactinoma
    - acromegaly (adults - large hands and long jaw) and gigantism (in kids - puberty doesn’t happen and suppress the GH)
    - Cushing’s disease
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91
Q

What are prolactinomas?

A

Prolactin producing tumour of the pituitary gland.
Benign lactotroph adenomas expressing and secreting prolactin (should be inhibited by dopamine)

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92
Q

What is the epidemiology of prolactinoma?

A
  • very high prevalence
  • more in women
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93
Q

What are the clinical features of a prolactinoma?

A
  • headache
  • visual field defect
  • CSF leak
  • Menstrual irregularity (with off LH and FSH)
  • infertility
  • galactorrhoea
  • low libido
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94
Q

What are the key diagnostic factors of prolactinomas?

A
  • presence of risk factors (women 20 to 50 yrs old)
  • amenorrhoea (absence of periods) or oligomenorrhoea (infrequent periods)
  • infertility
  • galactorrhoea
  • loss of sexual desire
  • erectile dysfunction
  • visual deterioration
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95
Q

Why must you take a careful drug history for prolactinoma?

A

Many psychiatric drugs are antidopiminergic therefore cannot inhibit prolactin

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96
Q

What is the treatment for prolactinomas?

A

Compared to other pituitary tumours the management is medical rather than surgical:

dopamine agonist
(negative feedback loop - more dopamine, reduces prolactin release and shrinks tumour)

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97
Q

What is acromegaly?

A

a rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma.
It is associated with increased morbidity and premature mortality if not appropriately treated.

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98
Q

What are the key diagnostic features for acromegaly?

A
  • coarsening of facial features
  • soft-tissue and skin changes
  • aural enlargement (hands, chin and feet)
  • excessive sweating
  • carpal tunnel syndrome
  • joint pain and dysfunction
  • snoring
  • alterations in sexual functioning
  • history or family history of inherited syndrome
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99
Q

What are the risk factors for acromegaly?

A
  • GPR101 over-expression
  • multiple endocrine neoplasia type 1 syndrome
  • isolated familial acromegaly
  • McCune-Albright syndrome (develop areas of scar tissue in their bones)
  • Carney complex (develop skin pigmentation and benign tumours)
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100
Q

What are the co-morbidities of acromegaly?

A
  • cerebrovascular events and headaches
  • arthritis
  • insulin-resistant and diabetes
  • sleep apnea
  • hypertension and heart diabetes
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101
Q

What are the treatment options for acromegaly?

A
  1. Pituitary tumour surgery - rapid fall in GH, based on size of tumour
  2. Medical therapy -
  3. Radiotherapy - conventional (multi-fractional) or stereotactic (single fraction)
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102
Q

What medical therapy is used for acromegaly?

A
  1. dopamine agonists - will switch off the GH
  2. Somatostatin analogues - inhibits multitude of hormones, short life span so use synthetic versions
  3. Pegvisomant - GH competitive antagonist, very strongly binds to GH receptor, so GH still secreted loads but just cannot bind (doesn’t work if tumour too big)
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103
Q

What is Cushing’s syndrome?

A

Cushing syndrome is the clinical manifestation of pathological hypercortisolism from any cause.

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104
Q

What’s the most common cause of Cushing’s syndrome?

A

Exogenous corticosteroid exposure

For example taking steroids e.g., prednisone

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105
Q

What is the difference between Cushing’s syndrome and Cushing’s disease?

A
  • Cushing’s syndrome disease is pathological hypercortisolism from any cause.
  • Cushing’s disease is hypercortisolism caused by a endogenous source e.g., pituitary adenoma
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106
Q

What is the most common cause of Cushing’s disease?

A

pituitary adenomas
(70-80%)
- increased release of adrenocorticotropic hormone (ACTH), causing increased release of cortisol from the zone fasciculata in the adrenal cortex
- regulate sleep rhythms

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107
Q

Name 2 other causes of Cushing’s disease?

A
  1. Ectopic neuroendocrine tumours
  2. Adrenal carcinoma
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108
Q

What is ACTH-dependant Cushing’s disease?

A

overproduction of ACTH which stimulates adrenal gland to secrete more cortisol.

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109
Q

What two types of tumour are ACTH-dependant causes of Cushing’s disease?

A

Pituitary adenoma, ectopic neuroendocrine ACTH secreting tumours

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110
Q

What is ACTH-independant Cushing’s disease

A

When there is excessive cortisol production without high levels of ACTH

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111
Q

What are the 6 hormones secreted by the anterior pituitary?

A

Adrenocorticotrophic hormone (ACTH)
Thyroid-stimulating hormone (TSH)
Luteinising hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin (PRL)
Growth hormone (GH)

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112
Q

What are the two hormones secreted by the posterior pituitary?

A

Oxytocin
Anti-diuretic hormone (ADH)

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113
Q

How does Cushing’s cause disease?

A

The clinical manifestations is due to excess tissue exposure to cortisol.
The degree to which symptoms present is due to the amount of excess.

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114
Q

What are some key presentations associated with Cushing’s?

A

Hypertension
Glucose intolerance
Premature osteoporosis
Facial plethora (redness)
Weight gain
Purple striae (stretch marks) on abdomen
Supraclavicular fulness, torso weight gain but weak arms
Absence of pregnancy, alcoholism, malnutrition

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115
Q

What are some key serum levels for Cushing’s?

A

Increased serum glucose, elevated cortisol in saliva, high urinary cortisol

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116
Q

What are the 4 main diagnostic tests for Cushing’s?

A
  1. Late night salivary cortisol (4nmol)
  2. 1mg overnight dexamethasone suppression test (50 nmol/litre),
  3. 24 hour urinary free cortisol.
  4. 48- hour 2 mg dexamethasone suppression testing
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117
Q

How do you perform a late night salivary cortisol test?

A

Samples are collected by saturating a collection swab with saliva or by passively drooling into a collection tube between 11 p.m. and midnight.
Sampling should be done on 2 separate nights

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118
Q

Why is the salivary test performed at night?

A

This is when cortisol levels are at their lowest. Will give the most accurate baseline figure

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119
Q

What is the 1mg overnight dexamethasone test

A

Patient is given 1 mg of dexamethasone at 11 p.m., and a plasma cortisol level is obtained the following morning at 8 a.m

morning cortisol >50 nanomol/L

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120
Q

What other test would be performed on a patient with suspected Cushing’s?

A

Pregnancy test

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121
Q

How would you treat Cushing’s disease?

A

First line : If an adenoma remove adenoma as that is the cause.

Adjunct: If only mild use or very severe (before surgery) use a steroidogenesis (pasireotide) inhibitor or a glucocorticoid receptor antagonist (mifepristone).

Monitor cortisol levels after removal of pituitary adenoma. May require hormone replacement due to dysfunction of HPA

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122
Q

How would you monitor Cushing’s?

A

Recurrence of adrenocorticotrophic hormone-dependent Cushing syndrome is common, with at least a 5% to 26% risk of recurrence at 5 years.

Patients who have achieved remission should be screened periodically (every 6-12 months) for recurrence of disease.

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123
Q

What is thelarche?

A
  • breast development
  • induced by oestrogen
124
Q

What are the features of a prepubertal and pubertal uterus?

A

prepubertal
- tubular shape
- endometrium single layer of cuboidal cells

pubertal
- pear shape
- endometrium increased thickness
- longer

125
Q

What is adrenarche?

A

Developmentally programmed peri-pubertal activation of adrenal androgen production
- mild advanced bone age, axillary hair, oily skin, mild acne, body odour
- age 6-8 years old

126
Q

What is precocious puberty? And the causes?

A

Early puberty

True:
- idiopathic
- CNS tumour - mainly due to a brain tumour especially in boys
- CNS disorders

Pseudo:
- Increased androgen secretion
- gonadotropin secreting tumours
- ovarian cyst
- oestrogen secreting neoplasm

127
Q

How do you treat precocious puberty?

A

Treatment with GnRH super agonist to suppress pulsatility of GnRH secretion

128
Q

What is constitutional delay of growth and puberty (CDGP)?

A
  • extreme of the normal physiologic variation
  • more common in boys
  • delay in bone maturation, delay in adrenarche
129
Q

What investigations are taken for Constitutional Delay of Growth and Puberty, CDGP?

A
  • complete red blood count
  • renal, LFT
  • LH, FSH
  • karyotyping (missing X chromosome in girls)
  • thyroid function, prolactin
  • DHEA, ACTH, cortisol
  • testosterone/oestradiol
  • x ray (delayed/advanced bone age)
130
Q

What antibodies are found in patients with autoimmune hypothyroidism?

A
  1. thyroglobulin
  2. thyroid peroxidase
131
Q

What is Graves’ disease?

A

An autoimmune disease associated with hyperthyroidism

132
Q

What are the 3 things that lead to Hyperthyroidism?

A
  1. overproduction of thyroid hormone
  2. leakage of performed hormone from thyroid
  3. ingestion of excess thyroid hormone
133
Q

What is the cause of Graves’ disease?

A

TSH (thyroid-stimulating hormone) receptor antibodies cause the hyperthyroid syndrome and underlie the extrathyroidal manifestations.

134
Q

Describe the epidemiology of Graves’ disease

A

2.5% prevalence.
More common in older age groups.
6 times more common in women.
20-50 cases per 100,000 per year

135
Q

Is graves’ disease more common in men or women?

A

Women (6x more likely)

136
Q

What is the aetiology of Graves’?

A

TSH receptor antibodies
Combination of genetic and environmental risk factors.
No specific genes but HLA linked.

137
Q

What are some risk factors for Graves’?

A

Family history of autoimmune disease (HLA-DR3)
Tobacco use
Female sex
Radiation
High iodine intake (increases TRH)
Lithium therapy

138
Q

What is the pathophysiology of Graves?

A

TSH receptor antibodies bind to thyroid
This causes increased thyroid hormone production
The increased production leads to thyroid hypertrophy
Symptoms occur as result of increase in thyroid hormone

139
Q

What are the key presentations for hyperthyroidism?

A

Presence of risk factors
Heat intolerance + increased sweating
Weight loss
Palpitations
Goitre
Orbitopathy

140
Q

What are some signs of Graves?

A

Elevated TSH receptor antibodies
Suppressed TSH levels
Elevated T3 and T4

141
Q

What are some other symptoms associated with Graves/hyperthyroidism?

A

Irritability
Cardiac flow murmur
Moist velvety skin
Scalp hair loss

142
Q

What is goitre?

A

Palpable and visible thyroid enlargement
- commonly sporadic or autoimmune

143
Q

What is goitre?

A

Palpable and visible thyroid enlargement
- commonly sporadic or autoimmune
- not specifically associated with hyper or hypo

144
Q

What are some Graves’ specific clinical signs?

A
  • diffuse goitre
  • thyroid eye disease
  • pretibial myxoedema (lesions of skin from deposition of hyaluronic acid)
  • acropachy (swelling of hands + clubbed fingers)
145
Q

What is thyroid associated ophthalmopathy?

A
  • swelling in extraocular muscles
  • present in most graves’ and autoimmune hypothyroidism patients
  • most likely due to an auto antigen in the extraocular muscle that cross reacts with a thyroid autoanitgen
146
Q

What are the investigations for hyperthyroidism?

A

Thyroid function tests to confirm biochemical hyperthyroidism:
primary = increased free T4, increased free T3, suppressed TSH
secondary = increased T4 and T3 but very high TSH

Diagnosis of underlying cause important because treatment varies

Clinical history, physical signs usually sufficient for diagnosis

Test for thyroid antibodies
Thyroid antibodies = TPO, Tg, TRAb

147
Q

What is the treatment for hyperthyroidism?

A
  • antithyroid drugs
  • radioiodine 131I
  • surgery (partial, subtotal thyroidectomy)
148
Q

What are some well known antithyroid drugs?

A

Thionamides:
- carbimazole
- propylthiouracil (used particularly in pregnant women)
- methimazole

149
Q

What do the antithyroid drugs do?

A
  • decrease synthesis of new thyroid hormone
  • PTU also inhibits conversion of T4 to T3
150
Q

Common side effects of thionamides?

A

(treat hyperthyroidism)

most common = rash
less common:
arthralgia (joint pain)
hepatitis
neuritis
thrombocytopenia
vasculitis
agranulocytosis

151
Q

Why is radioiodine used to treat hyperthyroidism?

A

iodine essential for thyroid hormone
- I actively transported by Na/I symporter into thyroid follicular cells

152
Q

How does radio iodine work?

A

Used to treat thyroid cancer
- radiation destroys thyroid gland and any other thyroid cells that take up iodine

153
Q

What are the early and long term effects of radio iodine?

A

Early effects of 131I:
necrosis follicular cells
vascular occlusion
occur over weeks to months

Long-term effects 131I:
shorter cell survival
impaired replication cells
atrophy and fibrosis
chronic inflammation resembling Hashimoto’s
late hypothyroidism

154
Q

What are the 3 types of hypothyroidism?

A

primary
- absence/dysfucntion of thyroid gland
- most cases due to Hashimoto’s thyroiditis

secondary/tertiray
- pituitary/ hypothalamic dysfunction

155
Q

What are the causes of hypothyroidism in adults?

A

PRIMARY
Hashimoto’s thyroiditis
131I therapy
Thyroidectomy
Postpartum thyroiditis
Drugs
Thyroiditides
Iodine deficiency
Thyroid hormone resistance

SECONDARY /
TERTIARY
Pituitary disease
Hypothalamic disease

156
Q

What drugs can cause hypothyroidism?

A
  • Iodine, inorganic or organic
    iodide
    iodinated contrast agents
    amiodarone (treat AF)
  • Lithium
  • Thionamides
  • Interferon - 
157
Q

What are the causes of hypothyroidism in children?

A

Neonatal hypothyroidism
Thyroid agenesis
Thyroid ectopia
Thyroid dyshormonogenesis
Others
Resistance to thyroid hormone
Isolated TSH deficiency

158
Q

Describe the pathophysiology of Hashimoto’s thyroiditis

A

T3 and T4 create negative feedback loop with TSH so low levels of T3 and T4 equal elevated TSH
In autoimmune lymphocytes, Thyroglobulin and thyroid peroxidase antibodies invade the thyroid causing damage (High iodine makes thyroid more antigenic).
This means less T4 and T3 are produced resulting in the clinical symptoms

159
Q

What are the clinical features of hypothyroidism?

A

Fatigue
Wt gain
Cold intolerance
Constipation
Menstrual disturbance
Muscle cramps
Slow cerebration
Dry, rough skin
Periorbital oedema
Delayed muscle reflexes
Carotenaemia
Oedema

EVERYTHING SLOWWW

160
Q

What are the hormone levels for primary hypothyroidism?

A
  • Increased TSH
    usually decreased [free T4], decreased [free T3]
    T4/ T3 may be low normal in mild hypothyroidism
    positive titre of TPO antibodies in Hashimoto’s
161
Q

What are the results of investigations for secondary hypothyroidism?

A

TSH inappropriately low for reduced T4 / T3
levels

162
Q

What is the treatment for hypothyroidism?

A

Treatment of choice = synthetic L-thyroxine (T4)

Older treatments - dessicated thyroid (pig and beef extracts) - inconsistent from batch to batch

T3 / T4 combination = T3 since it is active has a short acting nature and gives a massive spike of energy when first taken. T4 is longer acting and body enzymes naturally break it down into T3 without need ing a working thyroid.

163
Q

How should you monitor treatment for hypothyroidism?

A

In primary hypothyroidism:
dose titrated until TSH normalises
T4 half-life is long - check levels 6-8 weeks after dose adjustment

In secondary / tertiary hypothyroidism:
TSH will always be low
T4 is monitored

164
Q

How does hypothyroidism affect pregnancy?

A

Inadequate treatment
- gestational hypertension and pre-eclampsia
- placental abruption
- post partum haemorrhage

If untreated
- low birth weight
- preterm delivery
- neonatal goitre
- neonatal respiratory disease

165
Q

What to do if have pre-existing hypothyroidism in pregnancy?

A

Preconception counselling
- ideal pre-conception TSH <2.5 mIU/L
Increase dose by 30 %
Arrange TFT early pregnancy and titrate
Women require a dose increase in their thyroxine during pregnancy

166
Q

How does hyperthyroidism affect pregnancy?

A

If inadequately treated:
IUGR (intrauterine growth restriction - poor foetal growth)
Low birth weight
Pre-ecclampsia
Preterm delivery
Risk of stillbirth
Risk of miscarriage

167
Q

What is fetal thyrotoxicosis?

A

Transplacental transfer of TSH receptor antibodies
- occurs in 0.01% of cases
- start on anti-thyroid medication

168
Q

What is gestational thyrotoxicosis?

A

Gestational
- usually just in first half of pregnancy
- raised FT4/suppresses TSH
- stimulation of thyroid gland by hCG
- associated with hyperemesis gravidarum (severe nausea, vomiting)
- absence of thyroid autoimmunity

169
Q

What is postpartum thyroiditis?

A

Postpartum thyroiditis is an autoimmune condition similar to Hashimoto’s disease
- hypothyroidism
- strongly associated with positive thyroid peroxidase (TPO) antibodies
- thyroid becomes inflamed after having a baby

170
Q

What is amiodarone induced thyrotoxicosis?

A

Amiodarone = anti-arrhythmic drug AF, iodine rich

Type 1
Latent pre-existing
Low iodine areas
Iodine induced excess
Thyroid hormone release

Type 2
Normal Thyroid
Destructive

171
Q

Where is vasopressin and oxytocin produced?

A

They are made in the paraventricular nucleus and supraoptic nucleus and then transported to the posterior pituitary in the axoplasm of the neurones

172
Q

What are the 3 types of diseases associated with the posterior pituitary?

A
  1. Lack of vasopressin = AVP deficiency/cranial diabetes insidious
  2. Resistance to action of vasopressin = AVP resistance/nephrogenic diabetes insipidus
  3. Too much vasopressin release when it should not be released = syndrome of anti-diuretic hormone secretion
173
Q

What is diabetes insipidus?

A

Metabolic disorder characterised by an absolute or relative inability to concentrate urine
(changing name to arginine vasopressin resistance)

174
Q

What is the concentration in plasma measured in?

A

concentration in plasma = osmolality (mOsmol/kg)

measured by an osmometer - by freezing point

175
Q

How does vasopressin concentration change as osmolality increases?

A

Vasopressin increases in a linear fashion
- this then increases the concentration of the urine

176
Q

What are the key symptoms of diabetes insipidus/ AVP deficiency/resistance?

A

polydipsia
polyuria
no glycosuria

177
Q

What is primary polydipsia?

A

‘over drinking’
wash out concentration in the kidney so vasopressin is very ineffective

178
Q

What are the causes/risk factors of cranial diabetes insipidus?

A

Acquired:
Idiopathic
Tumours - craniopharyngioma, germinoma, metastases,
‘never’ anterior pituitary tumour
Trauma
Infections – TB, encephalitis, meningitis,
Vascular – aneurysm, infarction, Sheenan’s, sickle cell
Inflammatory - neurosarcoidosis, Langerhans’s histiocytosis, Guillain Barre, Granuloma

Primary:
genetic - autosomal dominant
Developmental - septo-optic dysplasia

179
Q

What are the causes of nephrogenic diabetes insipidus?

A

Acquired
- either reduction in medullary concentrating gradient or antagonism of effects of AVP

180
Q

What is the management of cranial DI?

A
  • treat any underlying condition
  • desmopressin
181
Q

What is the management of nephrogenic DI?

A
  • try and avoid precipitating drugs
  • congenital = free access to water and high dose of desmopressin
182
Q

What is the water deprivation test?

A
  1. put someone in a room without water and see how their body responds
  2. then give them desmopressin (synthetic version of vasopressin
  3. helps identify if AVP resistant or deficient
183
Q

What is hyponatraemia?

A
  • low sodium levels
  • common
  • most often caused by excess water rather than salt loss
184
Q

What are the symptoms of hyponatraemia?

A

No or mild symptoms

Moderate symptoms:
Headache
Irritability
Nausea / vomiting
Mental slowing
Unstable gait / falls
Confusion / delirium
Disorientation

Severe symptoms:
Stupor / coma
Convulsions
Respiratory arrest

185
Q

What happens to the brain in hyponatramia?

A
  1. gains water
  2. rapidly secretes sodium potassium chloride to allow brain expansion to stop
  3. loss of sodium, potassium and chloride
  4. results in loss of water
  5. results in adapted brain
186
Q

What are the investigations for hyponatramia?

A

General
- stop hypotonic fluids
- review drug card

Are they dehydrated or fluid overloaded?

specific
- plasma and urine osmolality
- urinary Na+
- glucose
- TFT’s

187
Q

What is syndrome of antidiuretic hormone secretion (SIADH)?

A
  • Too much AVP/ADH secreted, no negative feedback loop
  • low osmolality
  • plasma sodium is low (forced increase excretion of sodium to keep volume stable)
  • urine is inappropriately concentrated
  • water retention
  • increase GFR

Normal circulating volume!
(Euvolaemia NOT hypervolaemia!)
No oedema

188
Q

What are the most likely causes of SIADH?

A
  • lung abscess
  • Subdural haemorrhage
  • lymphoma
  • cerebrovascular accident
189
Q

What are tests results and essential criteria for the diagnosis of SIADH?

A
  • Hyponatraemia < 135 mmol/L
  • Plasma hypo-osmolality < 275 mOsm/Kg
  • Urine osmolality > 100 mOsm/Kg
  • Clinical euvolaemia
    No clinical signs of hypovolaemia (orthostatic decreases in blood pressure, tachycardia, decreased skin turgor, dry mucous membranes)
    No clinical signs of hypervolaemia (oedema, ascites)
  • Increased urinary sodium excretion > 30 mmol/L with normal salt and water intake
    Exclude recent diuretic use, renal disease, hypothyroidism, and hypocortisolism.
190
Q

What would urine tests in SIADH show?

A

Urine osmolality: in healthy individuals, if serum osmolality is low, urine osmolality should also be low as the kidneys should be working hard to retain solute. In SIADH, the excess of ADH results in water retention, but not solute retention. As a result, concentrated urine which is relatively high in sodium is produced, despite low serum sodium.

Urine sodium: raised in SIADH, despite low serum sodium concentration.

191
Q

What test would you perform first for SIADH?

A

Skin turgor and jugular venous pressure test

192
Q

What is SIADH management?

A
  • allow/facilitate increase in serum Na+
  • fluid restriction <1L/24hour
  • increase in Na+ per 24hrs if chronic
193
Q

What is the treatment for acute and chronic hyponatraemia secondary to SIADH?

A

Acute (24-48 hrs)
symptomatic = 3% saline
asymptomatic = fluid restriction

Chronic (48hrs +)
severe = 3% saline
Mild/asymptomatic = fluid restriction, vaptans (vasopressin receptor antagonist)

194
Q

What is osmotic demyelination syndrome?

A
  • white areas in the middle of the pons
  • massive demyelination of descending axons
  • hypokalaemia
  • due to hyponatraemia the brain shrinks in size
195
Q

What are the risk factors for osmotic demyelination syndrome?

A

Serum Na+ <105mmol/L
Hypokalaemia
Chronic excess alcohol
Malnutrition
Advanced Liver disease
>18mmol/L Na+ increase in 48 hou

196
Q

What is the treatment for osmotic demyelination syndrome?

A

Selective V2 receptor oral antagonist - ‘tolvaptan’
-competitive antagonist to AVP
cause a profound ‘aquaresis’
licensed for SIADH
-expensive tablet

(myelin sheath destroyed from rapid correction of low sodium levels = cause lots of water to be drawn out of the brain cells)

197
Q

What is the management of acute severe symptomatic hyponatraemia?

A
  1. Give IV saline
  2. check sodium
  3. repeat till sodium increase
198
Q

What are the four main types of thyroid cancer?

A

Follicular
Anaplastic
Medullary
Papillary
FAMP

199
Q

Is thyroid cancer more common in men or women?

A

Women

200
Q

What are risk factors for developing thyroid cancer?

A

Head and neck irradiation
Female sex
Genetic factors

201
Q

What is the most common pathophysiology of
a papillary carcinoma?

A

Papillary carcinoma tends to spread to local lymph nodes

202
Q

What is the common pathophysiology of a follicular tumour?

A

Follicular and Hurthle cells often spread haematogenous (carried by blood)

203
Q

How does anaplastic thyroid cancer spread?

A

Anaplastic thyroid cancer is a rare, aggressive, undifferentiated carcinoma with a high propensity for local invasion and metastatic spread.

204
Q

What are the key presentations for thyroid cancer?

A

Presence of risk factors
Palpable thyroid nodule

205
Q

What are some symptoms of thyroid cancer?

A

Hoarseness
Tracheal deviation
Dyspnoea
Dysphagia

206
Q

What is a first-line investigation for thyroid cancer

A

Normal TSH with reduced thyroid function

207
Q

What is the gold standard test for thyroid cancer?

A

Fine-needle biopsy

208
Q

What is a differential diagnosis for thyroid cancer?

A

A benign thyroid nodule

209
Q

How would you manage a follicular tumour?

A

The standard approach is surgery followed by radioactive iodine ablation and suppression of TSH for most patients

210
Q

How would you manage a medullary tumour?

A

Total thyroidectomy

211
Q

How would you treat an anaplastic tumour?

A

Total thyroidectomy and if that is not possible then with chemo/radio therapy

212
Q

How would you treat a thyroid lymphoma?

A

With radio and chemotherapy

213
Q

What are some disease related complications of thyroid cancer?

A

Airway obstruction
Secondary tumours

214
Q

What are some complications of a thyroidectomy?

A

Hypoparathyroidism due to damage to parathyroid glands
Recurrent laryngeal nerve damage

215
Q

What is the prognosis for a papillary/follicular carcinoma?

A

> 90% 10 year survival rate
- medullary is slightly worse due to more metastasis

216
Q

What is the prognosis for a anaplastic thyroid tumour?

A

Average survival of a few months after diagnosis

217
Q

What is the prognosis for a medullary tumour?

A

80% 5 year survival rate

218
Q

What is the prognosis for a primary thyroid lymphoma?

A

<50% 5 year survival rate

219
Q

What is ketoacidosis?

A

Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of
1. hyperglycaemia (or a history of diabetes),
2. ketonemia - raised plasma ketones
3. metabolic acidosis - with rapid symptom onset.

220
Q

What is the main cause of ketoacidosis?

A

Uncontrolled/undiagnosed diabetes

221
Q

What is the pathophysiology of ketoacidosis?

A

Reduced insulin concentration and insulin counter regulatory hormones leads to hyperglycaemia and electrolyte imbalance.

Insulin deficiency leads to release of fatty acids (lipolysis), hepatic fatty acid oxidation and increased formation of ketone bodies (hydroxybutyrate and acetoacetate (most common)).

This results in ketonemia and acidosis

222
Q

What are the key presentations of ketoacidosis?

A

Patients with known diabetes who are experiencing nausea, vomiting, abdominal pain, hyperventilation, dehydration and reduced consciousness
Or patients with suspected diabetes and these symptoms

223
Q

What are the common symptoms of ketoacidosis?

A

Nausea, vomiting, abdominal pain, hyperventilation, dehydration and reduced consciousness, polyuria, polydipsia

224
Q

What are some biochemical signs of ketoacidosis?

A

Hypokalaemia
high plasma osmolarity
blood ketones
hypotension
tachycardia

225
Q

What is the first line investigation for ketoacidosis?

A

Venous blood gas = to find low pH

226
Q

What blood PH indicates mild to moderate ketoacidosis?

A

Below normal but above 7

7-7.3

227
Q

What blood PH indicates severe ketoacidosis?

A

Below 7

228
Q

What is the gold standard test for ketoacidosis?

A

Urinary analysis

229
Q

What other tests would you order for a patient with ketoacidosis?

A

ECG, pregnancy test

230
Q

What are some differential diagnoses for diabetic ketoacidosis?

A

Hyperosmolar hyperglycaemic state,
Latic acidosis (order serum lactate).
Starvation/alcoholic ketoacidosis

231
Q

How would you monitor ketoacidosis?

A

order hourly blood glucose and hourly blood ketones.
Perform a venous blood gas for pH, bicarbonate, and potassium at 60 minutes, 2 hours and then every 2 hours after
Assess GCS

232
Q

What are some complications associated with ketoacidosis?

A

Hypokalaemia (due to high dose insulin therapy)
Arterial/venous thrombotic events
Cerebral oedema (main cause of death especially in children as brain swells and they have less room in their skull for this to occur)
Adult Respiratory Distress syndrome ARDS (occurs when too much fluid is given)

233
Q

What is the management/treatment of DKA?

A
  • rehydration
  • insulin
  • replacement of electrolytes
  • treat underlying cause

Treatment MUST be started without delay

234
Q

What are the different types of pituitary mass lesions?

A
  • Non-Functioning Pituitary Adenomas (silent)
  • Endocrine active pituitary adenomas
  • Malignant pituitary tumors: Functional and non-functional pituitary carcinoma
  • Metastases in the pituitary (breast, lung, stomach, kidney)
  • Pituitary cysts: Rathke’s cleft cyst, Mucocoeles, Others
235
Q

What is a craniopharyngioma?

A
  • A rise from squamous epithelial remnants of Rathke’s pouch
  • benign tumour infiltrates surrounding structures
  • ## solid, cystic, mixed, extends in suprasellar region
236
Q

What are the effects of a craniopharynhioma?

A

raised ICP,
visual disturbances,
growth failure,
pituitary hormone deficiency
weight increase

237
Q

What is a rathe’s cyst?

A
  • benign tumour on the pituitary gland
  • Derived from remnants of Rathke’s pouch
  • Single layer of epithelial cells with mucoid,
    cellular, or serous components in cyst fluid
  • Mostly intrasellar component, may extend into parasellar area
238
Q

What are the symptoms of rathe’s cyst?

A

Mostly asymptomatic and small
* Present with headache and amenorrhoea, hypopituitarism and hydrocephalus

239
Q

What is a meningioma?

A
  • Commonest tumour region (starts in meninges) after pituitary adenoma
  • Complication of radiotherapy
240
Q

What are the symptoms of a meningioma?

A
  • Associatedwithvisualdisturbanceand
    endocrine dysfunction
  • Usually present with loss of visual acuity, endocrine dysfunction and visual field defects
241
Q

What is a lymphocytic hypophysitis?

A
  • Inflammation of the pituitary gland due to an autoimmune reaction
    – Lymphocytic adenohypophysitis
    – Lymphocytic infindibuloneurohypophysitis – Lymphocytic panhypophysitis
242
Q

What is the epidemiology of lymphatic hypophysitis?

A

( inflammation of the pituitary gland due to autoimmunity.)

Incidence 1 per 9 million based on pituitary surgery
* LAH commoner in women - 6:1
* Age of presentation of LAH women: 35 years; men: 45 years – Pregnancy or postpartum

243
Q

What are non-functioning/silent pituitary adenomas?

A
  • tumour has to grow for you to recognise that there is a problem
  • doesn’t produce any hormones
244
Q

What is the main indicator of a non-functioning pituitary tumour?

A

If they present with visual disturbances!!

245
Q

What should you measure in pituitary disease?

A

Ft4
Free thyroxine test
Detects hyperthyroidism and hypothyroidism

246
Q

What is the likely diagnosis foe the following test results?

TSH: high
FT4: low

A

Primary hypothyroid

247
Q

What is the likely diagnosis foe the following test results?

TSH: low/normal
FT4: low

A

Hypopituitary

248
Q

What is the likely diagnosis foe the following test results?

TSH: low
FT4: high

A

Graves disease (toxic)

249
Q

What is the likely diagnosis foe the following test results?

TSH: high/normal
FT4: high

A

TSHoma (very rare)
OR
hormone resistance

250
Q

What is the normal hormone levels of FSH and LH pre, during and post puberty?

A

Prepuberty
oestradiol = low
LH = low
FSh = low but slightly higher than LH

Puberty
Oestradiol = increases
LH = pulsatile increases

Post menarche
oestradiol = increase through cycle
LH and FSH = surge in mid-cycle

251
Q

What are the hormones levels of LH, FSH and oestradiol in primary ovarian failure?

A

LH = high
FSH = higher than lH
Oestradiol = low
Same an menopause

252
Q

What are the hormones levels of LH, FSH and oestradiol in hypopituitary?

A

oligo or amenoohoes
Oestradiol = low
LH = low/normal
FSH = low/normal

253
Q

What is Conn’s syndrome?

A

Primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension.

254
Q

What is aldosterone?

A

Aldosterone is a mineralocorticoid, a steroid hormone released from the zona glomerulosa of the adrenal cortex

Causes sodium to be reabsorbed through ENaC to be pumped into the blood by the sodium/potassium pump.

In exchange, potassium is moved from the blood into the principal cell of the nephron. This potassium then exits the cell into the renal tubule to be excreted into the urine.

255
Q

What are the 3 types of adrenal insufficiency?

A
  1. primary
    - Addison’s disease
    - autoimmune attack on adrenal gland
  2. Secondary
    - hypopituitarism (destruction of pituitary gland)
    - deficiency in cortisol, ACTh
  3. Tertiary
    - suppression of Hypothalami-pituitary Adrenal axis (HPA)
    - from taking steroids (most common cause)
256
Q

What are the symptoms of adrenal insufficiency?

A
  • fatigue
  • weight loss
  • poor recovery from illness
  • adrenal crisis
  • headache

Past history:
- TB
- Post partum bleed
- cancer

257
Q

What are the signs of adrenal insufficiency?

A
  • pigmentation and pallor
  • hypotension
258
Q

What is the biochemistry of adrenal insufficiency?

A

Low Na = adrenal gland releases aldosterone which maintains water and salt balance
High K
Eosinophilia
Borderline elevated TSH

259
Q

What are the investigations for adrenal insufficiency?

A
  • early morning measurement of cortisol and ACTh
  • measure Renin/aldosterone
  • SynACTHen test = measure how well adrenal glands make cortisol
260
Q

What is the treatment for adrenal insufficiency?

A
  • hydrocortisone = replace low cortisol
  • fludrocortisone = replace low aldosterone in primary AS
261
Q

What are the sick day rule for steroid use?

A

Double steroid dose
- and 100mg hydrocortisone in adrenal crisis
(you cannot harm yourself in the short term taking extra steroids)

262
Q

What % of hypertension cases are caused by Conn’s?

A

It accounts for at least 5% of hypertensive patients

263
Q

What causes unilateral Conn’s and what % of cases does it make up?

A

Benign cortical adenomas correctable by unilateral laparoscopic adrenalectomy

Accounts for 30% of cases

264
Q

What causes bilateral Conn’s and what % of cases does it make up?

A

Bilateral adrenal hyperplasia in which hypertension responds well to aldosterone antagonist medicines.

Accounts for 70% of cases

265
Q

Name a form of genetically inherited Primary aldosteronism (PA)

A

Familial hyperaldosteronism type I (FH-I)

266
Q

What are some risk factors for Primary aldosteronism (PA)

A

Familial history of PA, family history of early onset hypertension/stroke

267
Q

Explain the pathophysiology of Conn’s

A

Aldosterone production is excessive to the body’s requirements, and autonomous to the RAAS.

This results in excessive Na+ absorption which leads to hypertension and suppression of RAAS and in severe cases low K+ (hypokalaemia) and metabolic acidosis (22%) of cases

268
Q

What are some microvascular complications of diabetes?

A
  1. Peripheral neuropathy- nerves in the body’s extremities, such as the hands, feet and arms, are damaged
  2. Retinopathy- damage to vessels in the eye
  3. Kidney disease, particularly glomerulosclerosis
269
Q

What are key presentations for Conn’s?

A

Hypertension, presence of risk factors, 20-70 years of age.

270
Q

What are signs of Primary Aldosteronism (PA)?

A

Low potassium,
high aldosterone to renin ratio

271
Q

What are some symptoms of PA

A

Polyuria, lethargy, mood disturbance, difficulty concentrating

272
Q

What are some investigations for getting a diagnosis of PA?

A

Plasma potassium- won’t be low only present in 20% of cases
Aldosterone /renin ratio

273
Q

What further tests could be done for a patient with suspected PA?

A

Genetic testing,
adrenal CT,
fludrocortisone suppression test

274
Q

What are some differential diagnosis for PA?

A

Idiopathic Hypertension- aldosterone/renin ratio will be normal.
Renal artery stenosis
Liddle syndrome- hypokalaemia and low renin but also low aldosterone levels

275
Q

How can you manage a patient with PA?

A

1st line: Unilateral adrenalectomy/bilateral adrenalectomy

adjunct preoperative aldosterone antagonists
adjunct postoperative aldosterone antagonists

276
Q

How would you monitor a patient who has undergone an adrenalectomy?

A

Plasma electrolytes, and aldosterone and renin levels should be monitored every 6 to 12

277
Q

How would you monitor a patient who is treating their PA through the use of aldosterone antagonists?

A

Electrolytes and renal function should be monitored regularly (e.g., every 3 to 6 months), watching for development of hyperkalaemia (for patients on medication)

278
Q

What are the complications associated with Conn’s?

A

Untreated: Stroke, MI, heart failure, AF, impaired renal function
Treatment: aldosterone antagonist induced hyperkalaemia

279
Q

What is the prognosis for PA?

A

Surgery leads to cure of hypertension in 50% to 60% of carefully selected patients
Medication leads to improved control of hypertension in most cases

280
Q

What test would you perform first for SIADH?

A

Skin turgor and jugular venous pressure test

281
Q

What hormones suppress appetite?

A
  • leptin
  • peptide YY
  • CCK
  • GLP 1
  • Glucose
282
Q

What are adipokines?

A

Cell signalling molecules (cytokines) produced by the adipose tissue that play functional roles in energy status of the body, inflammation, obesity etc.

283
Q

What are examples of adipokines?

A
  • adiponectin
  • leptin (main adipose signal to the brain)
  • resistin
  • interleukin 6
  • tissue necrosis factor
284
Q

Where is the centre of appetite regulation in the brain?

A

Hypothalamus

285
Q

What are the Tanner stages of puberty?

A

Tanners stages:
Stage 1 (prepubertal) - elevation of papilla only - no pubic hair
Stage 2 - breast bud forms - sparse, slightly pigmented hair on labia majora
Stage 3 - Breast begins to become elevated, extends beyond areola borders - hair becomes more coarse and curly
Stage 4 - increased size and elevation. Areola and papilla form secondary mound - adult like, but sparing medial thighs
Stage 5 - final size, areola returns but papilla remains projected - hair extends to medial thighs

286
Q

What are the 3 conditions that increase risk of metabolic syndrome?

A
  1. diabetes
  2. Hypertension
  3. obesity
287
Q

What is the criteria for diagnosing metabolic syndrome?

A

It is diagnostic if three or more of the criteria are present.
- Increased waist circumference (dependent on ethnicity) or a BMI >30
- Dyslipidaemia with raised triglycerides >150 mg/dL or reduced HDL-cholesterol
- Hypertension
- Impaired glucose tolerance

288
Q

What causes high T3&T4 levels in pregnancy?

A

Elevated oestrogen levels produced in pregnancy stimulate the expression of thyroid binding globulin (TBG) from the liver. As TBG binds to free thyroxine (fT4) and free triiodothyronine (fT3), an increase in TBG results in an initial lowering of fT4 and fT3. This in turn causes a secondary increase in thyroid-stimulating hormone (TSH).

Normal/high = TSH
High = T3, T4
normal = Free thyroxine (fT3, fT4)

289
Q

How are potassium levels affected by salbutamol and ramipril?

A

Regular nebuliser salbutamol = hypokalaemia

Ramipril can cause = hyperkalaemia

290
Q

What is the first line test for acromegaly?

A

Serum IGF-1
(an indirect measure of the average amount of growth hormone being produced by the body)

291
Q

Why is potassium given with insulin in DKA treatment?

A

Insulin moves glucose and potassium into the cells
- too much potassium taken into cells
- In a DKA must give potassium with insulin

292
Q

What ion do you need to monitor closely in DKA? And neumonic?

A

potassium

Managment: FIG PICK
Fluids
Insulin
Glucose
Potassium
Infection
Chart
Ketones

293
Q

Where is TRH released from?

A

Supraventricular nucleus of hypothalamus

294
Q

What is the function of DPP-4 inhibitors?

A
  • inhibits the breakdown of incretins
  • such as GLP-1 and GIP
  • they decrease appetite, increase insulin secretion, and inhibit glucagon secretion to lower blood glucose levels
    (treat diabetes)

e.g. Sitagliptin

295
Q

What is MEN?

A

Multiple Endocrine Neoplasia
- inherited autosomal dominant disorder
- tumours in endocrine glands

296
Q

What are the 3 main organs that MEN type I effect?

A

3 P’s
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia

Pituitary (70%)

Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)

297
Q

What are the 2 main organs that MEN type IIa effect?

A

2P’s
Parathyroid
Phaeochromocytoma

(medullary thyroid cancer)

298
Q

What is the main organ that MEN type IIb effects?

A

Pheochromocytoma

(medullary thyroid cancer)

299
Q

What are the 2 main types of incretins and where are they produced?

A

Gastric Inhibitory Peptide = glucose dependent + released from duodenum

Glucagon -like peptide = distal ileum

secreted on ingestion of glucose to stimulate insulin secretion from pancreatic β cells.

300
Q

What are the 5 main functions of cortisol?

A
  1. increases gluconeogenesis = increase blood glucose levels
  2. reduces reactivity of immune system = inhibition of prostaglandins + leukotrienes production
  3. Upregulation of alpha-1 adrenoceptors on arterioles = increase blood pressure
  4. decrease in osteoblast activity = reduce bone formation
  5. decrease fibroblast activity + collagen synthesis (delayed wound healing = purple stomach striae)
301
Q

What medication reduces thyroxine and how?

A

Carbimazole
- blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin

302
Q

What are the symptoms of a carcinoid tumour?

A

cutaneous flushing
recurrent diarrhoea = ↑ bowel motility
abdominal cramps
asthma-like wheezing

303
Q

What is the pathophysiology of hypercalcaemia of malignancy?

A

Hypercalcaemia of malignancy is caused by excessive secretion of parathyroid hormone released
peptide (PTHrP)

304
Q

What does hypercalcaemia look like on an ECG?

A

shortening of QT interval

305
Q

What is the first line investigation for hyperaldosteronism?

A

Aldosterone: renin ratio

306
Q

What is the difference between primary and secondary hyperaldosteronism?

A

primary = high ratio (of aldosterone :renin)
secondary = low ratio

307
Q

What is the main feature evident on a Urea and Electrolytes (U&E) blood test? (

A

hyperkalaemia

Emily Phase 2a (15 decks)

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