Endocrine Flashcards
(569 cards)
1
Q
What is the difference between endocrine and exocrine secretion?
A
Endocrine = secrete directly into the bloodstream, without ducts Exocrine = secrete through ducts to a site of action
2
Q
What are the 3 types of hormone action?
A
- Endocrine - blood-borne, acting at distant sites
- Paracrine - acting on nearby adjacent cells
- Autocrine - feedback on same cells that secreted that hormone
3
Q
What 7 organs comprise the major endocrine system?
A
- Pituitary
- Thyroid
- Parathyroid
- Adrenal
- Pancreas
- Ovary
- Testes
4
Q
Are water-soluble hormones stored in vesicles or synthesised on demand?
A
Water soluble hormones are stored in vesicles
5
Q
How do water soluble hormones get into cells?
A
They bind to cell surface receptors
6
Q
Give an example of a water soluble hormone
A
Peptides - TRH, LH, FSH
Monoamines
7
Q
Are fat soluble hormones stored in vesicles or synthesised on demand?
A
Fat soluble hormones are synthesised on demand
8
Q
How do fat soluble hormones get into cells?
A
They diffuse into the cell
9
Q
Give an example of a fat soluble hormone
A
Steroids - cortisol, thyroid hormone
10
Q
What are the differences between the half-life and clearance of water soluble and fat soluble hormones?
A
Water soluble = short half life and fast clearance
Fat soluble = long half life and slow clearance
11
Q
Name 4 hormone classes
A
- Peptides
- Amines
- Iodothyrosines
- Cholesterol derivatives and steroids
12
Q
Give 5 examples of a peptide hormones
A
- Insulin
- Growth hormone
- ADH
- CRH
- Somatostatin
13
Q
Give an example of an amine hormone
A
Noradrenaline and adrenaline
14
Q
Describe the pathway of adrenaline synthesis
A
Phenylalanine –> L-tyrosine –> L-dopa –> Noradrenaline –> Adrenaline
15
Q
Name the enzyme that breaks down noradrenaline and adrenaline
A
Catechol-O-methyl transferase (COMT)
16
Q
What are noradrenaline and adrenaline broken down into?
A
Normetadrenaline and metadrenaline
17
Q
Name 3 sites of hormone receptor location
A
- Cell membrane
- Cytoplasm
- Nucleus
18
Q
Where in the cell are peptide cell receptors located?
A
On the cell membrane
19
Q
Where in the cell are steroid hormone receptors located?
A
In the cytoplasm
20
Q
Where in the cell are thyroid/vitamin A and D cell receptors located?
A
In the nucleus
21
Q
Give 5 ways in which hormone action is controlled
A
- Hormone metabolism
- Hormone receptor induction
- Hormone receptor down-regulation
- Synergism - combined effects of 2 hormones amplified (e.g. glucagon and adrenaline)
- Antagonism - one hormone opposes other hormone (e.g. glucagon and insulin)
22
Q
What are the 2 types of feedback control?
A
- Negative feedback - response causes response loop to shut off
- Positive feedback - response causes more response to occur
23
Q
What layer of the trilaminar disc is the anterior pituitary derived from?
A
Ectoderm (Rathke’s pouch)
24
Q
What is the posterior pituitary derived from?
A
The floor of the ventricles
25
Name the 6 hormones that the anterior pituitary produces
1. TSH - thyroid stimulating hormone
2. FSH - follicle stimulating hormone
3. LH - luteinising hormone
4. ACTH - adrenocorticotrophic hormone
5. Prolactin
6. GH - growth hormone
26
Name the 2 hormones secreted form the posterior pituitary
1. Oxytocin
| 2. ADH - antidiuretic hormone
27
Where are the posterior hormones synthesised?
In the hypothalamus
oxytocin = paraventricular nucleus
ADH = supraoptic nucleus
28
How are oxytocin and ADH transported form the hypothalamus to the posterior pituitary?
Transported down the icons of the hypothalamic hypophyseal tract
29
Give 2 functions of oxytocin
1. Milk secretion
| 2. Uterine contraction
30
What is the function of ADH?
It acts on the collecting ducts of the nephron and increased insertion of aquaporin 2 channels --> water retention
Causes vasoconstriction
31
Give the 6 hypophysiotropic hormones released by the hypothalamus
1. Thyrotropin-releasing hormone (TRH)
2. Corticotrophin-releasing hormone (CRH)
3. Gonadotrophin-releasing hormone (GRH)
4. Growth hormone releasing hormone (GHRH)
5. Somatostatin
6. Dopamine
32
Describe the thyroid axis
Hypothalamus --> TRH --> Anterior pituitary --> TSH --> thyroid --> T3 and T4
T3 and T4 have a negative effect on the hypothalamus and the anterior pituitary
33
Which has a longer half life, triiodothyronine or thyroxine?
T3 has a half life of 1 day and T4 has a half life of 5-7 days
34
What would be the effect on TSH if you had an under active thyroid?
TSH would be raised as you have less T3/4 being produced so no negative feedback
35
What would a low TSH tell you about the action of the thyroid?
Indicates an over active thyroid
| Lots of T3/4 being produced so more negative feedback on the pituitary and therefore less TSH
36
Give 4 functions of thyroid hormones (T3 and T4)
1. Accelerates food metabolism
2. Increases protein synthesis
3. Stimulation of carbohydrate metabolism
4. Enhances fat metabolism
5. Increase in ventilation rate
6. Increase in cardiac output and heart rate
7. Brain development during foetal life and postnatal development
8. Growth rate accelerated
37
Describe the mechanism of ACTH
Hypothalamus --> CRH --> Anterior pituitary --> ACTH --> adrenal cortex (zona fasciculata) --> glucocorticoid synthesis (cortisol)
Cortisol has a negative feedback on the hypothalamus and the anterior pituitary
38
Give 3 functions of cortisol in response to stress
1. Mobilises energy sources - lipolysis, gluconeogenesis, protein break down
2. Vasoconstriction
3. Suppresses inflammatory and immune responses
4. Inhibits non-essential functions - growth and reproduction
39
Describe the mechanism of LH and FSH
Hypothalamus --> GnRH --> anterior pituitary --> FSH/LH --> ovaries/testes
40
What cells does FSH act on?
```
Ovaries = Granulosa cells
Testes = Sertoli cells
```
41
What cells LH act on?
```
Ovaries = theca cells
Testes = Leydig cells
```
42
What is the function of granulosa cells?
Stimulated by FSH to convert androgens into oestrogen using aromatase
43
What is the function of theca cells?
Stimulated by LH to produce androgens that diffuse into granulosa cells to be converted into oestrogen
44
What is the function of Sertoli cells?
Produce Mullerian inhabiting factor (MIF) and inhibin and activins which acts on the pituitary gland to regulate FSH
Stimulates spermatogenesis
45
What is the function of leydig cells?
Stimulated by LH to produce testosterone
46
Describe the GH axis
Hypothalamus --> GHRH (+) or Somatostatin (-) --> anterior pituitary --> GH --> Liver --> IGF-1
47
What is the function of GH?
Stimulates growth and protein synthesis
48
What is the function of IGF-1
It induces cell division, cartilage and skeletal growth and protein synthesis
49
Briefly describe the mechanism of prolactin
Hypothalamus --> dopamine (-) --> anterior pituitary --> prolactin
50
What would happen to serum prolactin levels if something was to impact on the pituitary stalk and block dopamine release?
Prolactin levels would increase
51
Give 3 reasons that result in pituitary dysfunction
1. Tumour mass effects
2. Hormone excess
3. Hormone deficiency
52
Define appetite
Desire to eat food
53
Define satiety
Feeling of fullness - disappearance of appetite after a meal
54
Define overweight/obesity
Abnormal or excessive fat accumulation that may impair health
55
Give 5 risks of obesity
1. Life expectancy decreases by 10 years
2. Type 2 diabetes
3. Hypertension
4. Coronary artery disease
5. Stroke
6. Osteoarthritis
7. Obstructive sleep apnea
8. Carcinoma
56
Where is leptin expressed and what is its effect on appetite?
```
Expressed in white fat
Suppresses appetite (Anorexigenic)
```
57
Where is ghrelin expressed and what is its effect on appetite?
```
Expressed in the stomach
Stimulates appetite (orexigenic)
```
58
Name 2 other hormones that decrease appetite
1. Insulin
2. PYY 3-36
3. CKK
4. Glucagon-like peptide (GLP)
59
Give 5 parathyroid hormone actions
1. Increase Ca2+ reabsorption
2. Decrease phosphate reabsorption
3. Increase 1 alpha-hydroxylation of 25-OH vit D
4. Increase bone remodelling (bone resorption >bone formation)
5. Increase Ca2+ absorption because of increase 1,25(OH)2D (no direct effect)
60
When serum calcium levels are low, what are PTH levels?
PTH levels are high
61
When serum calcium levels are high, what are PTH levels?
PTH levels are low
62
What is the effect of hyperparathyroidism on serum calcium levels?
Hyperparathyroidism --> hypercalcaemia
63
Name 4 symptoms of hyperparathyroidism
```
Hyperparathyroidism = hypercalcaemia
1. Renal/biliary stones
2. Bone pain
3. Abdominal pain
4. Depression, anxiety, malaise
Stones, Bones, Groans and Moans
```
64
Give 2 causes of primary hyperparathyroidism
Parathyroid adenoma
Hyperplasia
Increase PTH --> increase calcium --> decrease phosphate
65
Describe the pathophysiology of secondary hyperparathyroidism
Becomes hyperplastic to increase secretion of pTH to compensate chronic hypocalcaemia
Often due to CKD
66
How does tertiary hyperparathyroidism occur?
Prolonged uncorrected hypertrophy - glands become autonomous producing excess PTH
67
What blood results would you see in the 3 types of hyperparathyroidism?
```
Primary = hypercalcaemia
Secondary = low serum calcium
Tertiary = Raised calcium and PTH
```
68
Describe the treatment for hyperparathyroidism
```
Primary = surgical removal of adenoma
Secondary = calcium correction and treatment of the underlying cause
Tertiary = Calcium mimetic (cinacalcet) and possibly a total or subtotal parathyroidectomy
```
69
How does a calcium mimetic work?
Increases sensitivity of parathyroid cells to calcium so less PTH secretion occurs
70
What is the affect of hypoparathyroidism on serum calcium levels?
Hypoparathyroidism --> hypocalcaemia
71
Give 5 symptoms of hypoparathyroidism
Hypoparathyroidism = hypocalcaemia
1. Spasm
2. Paraesthesia around mouth and lips
3. Convulsions
4. Tetany
5. Cramps
6. Confusion
7. Chvosteks sign - tap over facial nerve and look for spasm of facial nerves
8. Trousseaus sign - inflate BP cuff 20 mmHg above systolic for 5 mins = hand spasm
9. QT prolongation
72
Name 4 causes of hypoparathyroidism
1. Transient
2. Can follow anterior neck surgery
3. Genetic - defects in PTH gene
4. Autoimmune - DiGeorge syndrome
73
What are blood results for someone with hypoparathyroidism?
```
Calcium = Low
PTH = Low
Phosphate = High
```
74
What is the treatment for hypoparathyroidism?
```
Acute = IV calcium
Persistant = Vitamin D analogue (alfacalcidol)
```
75
Give 3 causes of Hypercalcaemia
1. Primary hyperparathyroidism
2. Malignancy
3. Vitamin D toxicity
4. Myeloma
76
What is the treatment for hypercalcaemia?
Loop diuretic to return calcium to normal (furosemide)
Calcitonin
If Primary hyperparathyroidism = surgical removal
77
Give 2 ECG changes that you might see in someone with hypercalcaemia
1. Tall T waves
| 2. Shortened QT interval
78
Name 3 causes of hypocalcaemia
1. Increase serum phosphate due to CKD (most common) or phosphate therapy
2. Reduced PTH function due to primary hypoparathyroidism, post thyroidectomy and parathyroidectomy
3. Vitamin D deficiency due to reduced exposure of light
79
How would you diagnose hypocalcaemia?
Detailed history
eGFR to search for CKD
PTH levels
Vitamin D levels
80
How would you treat hypocalcaemia?
Acute = IV calcium
Persistent in vitamin D deficiency = vitamin D supplement
Persistent in hypoprarythroidism = alfacalcidol
81
Give 2 ECG changes that you might see in someone with hypocalcaemia
1. Small T waves
| 2. Long QT interval
82
What does the parathyroid control?
Serum calcium levels
| A low serum calcium triggers the release of PTH and a high serum calcium triggers c-cells to release calcitonin
83
What hormone does the parathyroid secrete and what is its function?
PTH - secreted in response to low serum calcium
84
What is released by c-cells in the parathyroid in response to high serum calcium?
Calcitonin
85
What biochemical test might you want to do to establish the cause of hypercalcaemia?
PTH measurement
86
What disease is described as being a 'disorder of carbohydrate metabolism characterised by hyperglycaemia'?
Diabetes mellitus
87
What are the 4 cells that make up the islets of langerhans?
1. Beta cells (70%)
2. Alpha cells (20%)
3. Delta cells (8%)
4. Polypeptide secreting cells
88
What do beta cells produce?
Insulin
89
What to alpha cells produce?
Glucagon
90
What do delta cells produce?
Somatostatin
91
What is the importance of alpha and beta cells being located next to each other in the islets of langerhans?
Enables them to 'crosstalk'
92
Describe the mechanism of insulin secreting from beta cells
1. Glucose binds to beta cells
2. Glucose metabolism occurs
3. ADP --> ATP
4. Causes K+ channels to close
5. Membrane depolarisation occurs
6. Calcium channels open allowing influx
7. Insulin is released
93
Describe the insulin action at muscle and fat cells
1. Insulin binds to membrane receptors
2. Intracellular signalling cascade is stimulated
3. GLUT-4 mobilisation to plasma membrane
4. GLUT-4 integrates into plasma membrane
5. Glucose enters cells via GLUT-4
94
Describe the physiological process that occur in the fasting state in response to low blood glucose
Low blood glucose = high glucagon and low insulin
- Glucogenolysis and gluconeogenesis
- Reduced peripheral glucose uptake
- Stimulates the release of gluconeogenic precursors
- Lipolysis and muscle breakdown
95
Describe the effect on insulin and glucagon secretion int he fasting state
Fasting state = low blood glucose
| Raised glucagon and low insulin
96
How many precursors are needed for gluconeogensis?
3
97
Describe the physiological processes that occur after feeding in response to high blood glucose
High blood glucose = high insulin and low glucagon
- Glycogenolysis and gluconeogenesis are suppressed
- Glucose is taken up by peripheral muscle and fat cells
- Lipolysis and muscle breakdown suppressed
98
Describe the effect on insulin and glucagon secretion after feeding
Insulin is high, glucagon is low
99
Give 3 effects of insulin
1. Suppresses hepatic glucose output - decrease glycogenolysis and gluconeogenesis
2. Increases glucose uptake into insulin sensitive tissues
3. Suppresses lipolysis and breakdown of muscle
100
Give 3 effects of glucagon
1. Stimulates hepatic glucose output - increases glycogenolysis and gluconeogenesis
2. Reduces peripheral glucose uptake
3. Stimulates lipolysis and breakdown of muscle
101
Give 3 ways in which diabetes Mellitus can cause morbidity and mortality
1. Acute hyperglycaemia which if untreated leads to acute metabolic emergencies, diabetic ketoacidosis (DKA) and hyperosmolar coma
2. Chronic hyperglycaemia leading tissue complications - macrovasculaa and microvascular
3. Side effects of treatment - hyperglycaemia
102
What type are gestational and medication induced diabetes refereed to?
Type 2 diabetes mellitus
103
Describe the natural history of T1DM
Genetic predisposition + trigger --> insulitis, beta cell injury --> pre-diabetes --> diabetes
104
T1DM is characterised by impaired insulin secretion. Describe the pathophysiological consequence of this
Severe inducing deficiency --> glycogenolysis/gluconeogensis/lipolysis all not suppressed and reduced peripheral glucose uptake --> hyperglycaemia and glycosuria
Perceived stress --> cortisol and adrenaline secretion --> catabolic state --> increased plasma ketones
105
Is T1DM characterised by a problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion - severe insulin deficiency
106
Describe the pathophysiology of T1DM
Beta cells express HLA antigens
| Autoimmune destruction --> beta cell loss --> impaired insulin secretion
107
At what are do people with T1DM present?
Usually present in childhood
108
Name 3 symptoms of DM
Thirst (fluid and electrolyte losses)
Polyuria (due to osmotic diuresis)
Weight loss
109
Describe the epidemiology of T1DM
```
Onset younger (<30 years)
Usually lean
More Northern European ancestry
```
110
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons fasting plasma glucose be if they were diabetic?
Fasting plasma glucose >7 mmol/L
111
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons random plasma glucose be if they were diabetic?
Random plasma glucose >11 mmol/L
112
What might someone's HbA1c be if they have diabetes?
>48 mmol/L
113
What happens to C-peptide in T1DM?
C-peptide reduces
114
How do you treat T1DM?
```
Education
Glycaemic control through diet (low sugar, low fat, high starch)
Insulin – twice daily and with meals
Regular activity and healthy BMI
BP and hyperlipidaemia control
```
115
Give 6 complications to Diabetes Mellitus
1. Diabetic ketoacdiosis
2. Diabetic nephropathy
3. Diabetic retinopathy
4. Diabetic neuropathy
5. Hyperosmolar hyperglycaemic nonteotic coma
6. Stroke, ischaemic heart disease, peripheral vascular disease
116
Give 2 potential consequences of T1DM
1. Hyperglycaemia
| 2. Raised plasma ketones --> ketoacidosis
117
How is insulin administered in someone with T1DM?
Subcutaneous injections
118
Other than SC injections, how else can insulin be administered?
Insulin pump
119
Describe the different types of subcutaneous insulins that can be given to people with T1DM
1. Ultra fast acting - Humalog - taken before eating in conjunction with a long acting insulin at night
2. Long-acting insulin - insulin Glargine - taken before going to bed
3. Pre-mixed insulin - NovoMix - taken twice daily
120
Give 4 potential complications of insulin therapy
1. Hyperglycaemia
2. Lipohypertrophy at injection site
3. Insulin resistance
4. Wight gain
5. Interference with life style
121
What is the affect of cortisol on insulin and glucagon?
Inhibits insulin
| Activates glucagon
122
Describe the pathophysiology of diabetic ketoacidosis
No insulin --> lipolysis --> FFA's --> oxidised in the liver --> ketone bodies --> ketoacidosis
123
Name 3 ketone bodies
1. Acetoacetate
2. Acetone
3. Beta hydroxybutyrate
124
Where does ketogenesis occur?
Liver
125
Give 5 signs of diabetic ketoacidosis
1. Hypotension
2. tachycardia
3. Kassmaul's respiration
4. Breath smells of ketones
5. Dehydration
126
Would you associate ketoacidosis with T1 or T2 DM?
Type 1
127
Give 3 microvascular compilation of DM
1. Diabetic retinopathy
2. Diabetic nephropathy
3. Diabetic peripheral neuropathy
128
Give 2 macrovascular complications fo DM
CV disease
| Stroke
129
What is the main risk factor for diabetic complications?
Poor glycemic control
130
What is the treatment for someone presenting with ketoacidosis?
1. ABCDE
2. IV normal saline
3. IV soluble insulin via syringe driving and sliding scale
4. Restore potassium levels
5. Look for underlying cause
131
Give 3 endocrine diseases that can cause diabetes
1. Cushing's
2. Acromegaly
3. Phaeochromocytoma
132
What class of drugs can cause diabetes?
Steroids
Thiazies
Anti-psychotics
133
Is T2DM characterised by problem with insulin secretion, insulin resistance or both?
Characterised by impaired insulin secretion and insulin resistance
134
Describe the aetiology of T2DM
Genetic predisposition and environmental factors
135
Describe the pathophysiology of T2DM
Impaired insulin secretion and resistance --> impaired glucose tolerance --> T2DM --> hyperglycaemia and high FFAs
136
Why is insulin secretion impaired in T2DM
Due to lipid deposition in the pancreatic islets
137
Give 3 risk factors for insulin resistance in T2DM
1. Obesity
2. Physical inactivity
3. Family history
138
What happens to insulin resistance, insulin secretion and glucose levels in T2DM?
Insulin resistance increase
Insulin secretion decreases
Fasting and post-prandial glucose increase
139
Why do you rarely see diabetic ketoacidosis in T2DM?
Insulin secretion is impaired but there are still low levels of plasma insulin
Low levels of insulin prevent muscle catabolism and ketogenesis
140
By how much has the beta cell mass reduced in T2DM when diagnosis usually occurs?
50% of normal beta cell mass
141
Describe the epidemiology of T2DM
Onset older (>30)
Usually overweight
More common in African/Asian populations
More common in general
142
Describe the treatment pathway for T2DM
1. Lifestyle changes - lose weight, exercise, healthy diet and control of contributing conditions
2. Metformin
3. Metformin and sulfonylurea
4. Metformin + sulfonylurea + insulin
5. Increase insulin dose as required
143
How does metformin work in treating T2DM?
Increase insulin sensitivity and inhibits glucose production
144
How does sulfonylurea work in treating T2DM?
Stimulates insulin release
145
Give a potential consequence of taking Sulfonylurea for the treatment of T2DM
Hypoglycaemia
146
What is hypoglycaemia classified as?
Plasma glucose <3.9 mmol/L and if <3.0 mmol/L it is severe hypoglycaemia
147
Give 5 symptoms of hypoglycaemia
1. Hunger
2. Sweating
3. Tachycardia
4. Anxious
5. Shaking
6. Confusion
7. Weakness
8. Vision changes
148
Why does hypoglycaemia continuously get worse?
Glucagon is not produced so rely only on adrenaline and the threshold for adrenaline release gradually lowers after time
149
What are 5 risk factors of hypoglycaemia for those with T1DM?
1. History of severe episodes
2. HbA1c < 48 mmol/L
3. long duration of diabetes
4. Renal impairment
5. Impaired awareness of hypoglycaemia
6. Extremes of age
150
What are 5 risk factors of hypoglycaemia for those with T2DM?
1. Advancing age
2. Cognitive impairment
3. Depression
4. Aggressive treatment of glycaemia
5. Impaired awareness of hypoglycaemia
6. Duration of MDI insulin therapy
7. Renal impairment and other co-morbidities
151
Give 3 impacts of non-severe hypoglycaemia
1. Reduced quality of life
2. Cause fear of hypoglycaemia
3. Causes psychological morbidity
152
Give 6 consequences of hypoglycaemia
1. Seizures
2. Comas
3. Cognitive dysfunction
4. Fear
5. Decrease in qualitative life
6. Accidents
153
Briefly describe the treatment of hypoglycaemia
Recognise symptoms
Confirm the need for treatment (blood glucose <3.9 mmol/L)
Treat with 15g of fast-acting carbohydrate
Retest in 15 mins to ensure blood glucose >4.0 mmol/L and retreat if necessary
Eat a long acting carbohydrates to prevent recurrence
154
Why are patient with diabetes at a particular risk of hypoglycaemia?
In Diabetes there are defects in the physiological defences to hypoglycaemia and there is reduced awareness
155
What does prevention of hypoglycaemia include?
Eduction
Correct choice of therapy
Adjusting glucose targets in those at high risk
Specialist support from a MDT
156
Is insulin secretion or insulin resistance the driving force of hyperglycaemia in T2DM?
Hepatic insulin resistance is the driving force
157
Give a potential consequence of acute hyperglycaemia
Diabetic ketoacidosis and hyperosmolar coma
158
Give a potential consequence of chronic hyperglycaemia
Mirco/macrovascular tissue complications
159
A man presents with a history of weight loss, polyuria and nocturia. He is very unwell. The GP performs a capillary blood glucose which is found to be 17.2mmol/l. What is the most likely diagnosis of this mans symptoms?
Type 1 Diabetes Mellitus
160
Name 5 possible diseases of the pituitary
1. Benign pituitary adenoma
2. Craniopharygioma
3. Trauma
4. Apoplexy/Sheehans
5. Sarcoid/TB
161
Give 3 potential consequences of a pituitary tumour
1. Pressure on local structures - e.g. optic chasm = bilateral hemianopia
2. Pressure on normal pituitary (lack of function) - Hypopituitarism
3. Functioning tumours - e.g. Cushing's, acromegaly, prolactinoma
162
Describe the growth hormone secretion from the anterior pituitary
It is secreted in a pulsatile fashion and increases during deep sleep
163
What is acromegaly?
Overgrowth of all organ systems due to excess growth hormone in adults
164
What is gigantism?
Excess GH production in children before fusion of the epiphyses of the long bones
165
Give 5 symptoms of acromegaly
1. Change in appearance
2. Increase in size of hands and feet
3. Excessive sweating
4. Headache
5. Tiredness
6. Weight gain
7. Amenorrhoea
8. Deep voice
9. Arthralgia
166
Give 5 signs of acromegaly
1. Prognathism - jaw protrusion
2. Interdental separation
3. Large tongue
4. Spade like hands and feet
5. Tight rings
6. Bitemporal hemianopia
167
What can cause acromegaly?
A benign pituitary adenoma producing excess GH
168
Describe the epidemiology of acromegaly
1/200,000
Average age is 40 years
Mean duration of symptoms is 8 years
Reduces life expectancy by 10 years
169
What complications are associated with acromegaly?
1. Arthritis
2. Cerebrovascular events
3. Hypertension and heart disease
4. Sleep apnea
5. T2DM
6. Colorectal cancer
170
What investigation might you do on someone who you suspect has acromegaly?
1. Plasma GH levels can exclude acromegaly
2. Serum IGF-1 and GH = raised
3. Oral glucose tolerance test
4. MRI pituitary
171
What does the plasma GH level need to be to exclude acromegaly?
<0.4 ng/ml
172
What is the diagnostic test for acromegaly?
Oral glucose tolerance test - failure of glucose to suppress serum GH
173
What are the treatment options for acromegaly?
1. Transsphenoidal surgical resection
2. Radiotherapy
3. Medical therapy
174
Give 3 potential complications of transsphenoidal surgical resection for the treatment of acromegaly
1. Hypopituitarism
2. Diabetes insidious
3. Haemorrhage
4. CNS injury
5. Meningitis
175
What does the success of pituitary surgery depend on?
Size of the tumour and surgeon
176
What type of radiotherapy is usually used to treat acromegaly?
Stereotactic radiotherapy - highly specific so less radiation to surrounding tissues
177
What types of medical therapy can be used to treat acromegaly?
Dopamine agonists - Cabergoline
Somatosatin analogues - octreotide/ianreotide
GH receptor antagonists - pegvisomant
178
Give 3 advantages of using dopamine agonists in the treatment of acromegaly
1. No hypopituitarism
2. Oral administration
3. Rapid onset
179
Give 2 disadvantages of dopamine agonists in the treatment of acromegaly using
1. Can be ineffective
| 2. Risk of side effects
180
Name a dopamine agonist that can be used as a treatment for acromegaly
Cabergoline
181
Why can somatostatin analogues be used in the treatment of acromegaly?
They inhibit GH release
182
Why can GH receptor antagonists be used in the treatment of acromegaly?
They suppresses IGF-1
183
What is prolactinoma?
Lactotroph cell tumour of the pituitary
| Prolactin secreting tumour
184
Name the 2 types of prolactinoma
1. Microprolactinoma = most common, >90%
| 2. Macroprolactinoma = >10mm
185
Describe the epidemiology of prolactinoma
Incidence is 10/100,000
Prevalence is 90/100,000
Women > men
186
Give 3 causes of prolactinoma
1. Pituitary adenoma
2. Anti-dopaminergic drugs
3. Head injury
187
Give 6 signs of prolactinoma
1. Infertility
2. Galactorrhoea
3. Amenorrhoea
4. Loss of libido
5. Hypogonadism
6. Visual field defects and headaches due to local effect of tumour
188
Briefly describe the pathophysiology of Prolactinoma
Increased release of prolactin can cause galactorrhoea and can inhibit FSH and LH
189
What test do you do to diagnose prolactinoma?
Measure serum prolactin
190
What is the treatment for prolactinoma?
Dopamine agonists - cabergoline, bromocriptine
- remarkable shirked with macro adenoma
Occasionally transsphenoidal pituitary resection
191
What is Cushing's Syndrome?
Chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
192
What is Cushing's Disease?
When Cushing's syndrome is caused by a pituitary tumour so excess glucocorticoids due to inappropriate ACTY secretion
193
Give 8 signs/symptoms go Cushing's disease
1. Central obesity
2. Moon face
3. Hypertension
4. Skin thinning and bruising
5. Abdominal striae
6. Mood changes - depression, lethargy, irritability
7. Osteoporosis
8. Muscle wasting
9. Weight gain
10. Gonadal dysfunction
11. Immune dysfunction
12. Acne
194
What can cause Cushing's syndrome?
| And are they ACTH dependent or independent?
1. Adrenal tumour (adenoma or carcinoma) = ACTH independent
2. Exogenous steroid (excess glucocorticoid administration) = ACTH independent
3. Pituitary tumour (causes excess ACTH production) = ACTH dependent
4. Ectopic ACTH syndrome (too much ACTH stimulating too much Cortisol) = ACTH dependent
195
What is a differential diagnosis of Cushing's syndrome?
Pseudo-Cushing's = excessive alcohol consumption can mimic the clinical and biochemical signs but resolved on alcohol recession
196
Describe the epidemiology of Cushing's syndrome
10/1,000,000
Higher incidence in Diabetes
2/3 cases are Cushing's disease
197
How can you diagnose Cushing's syndrome?
1. Overnight dexamethasone suppression test - failure to suppress cortisol
2. Late night salivary cortisol - loss of circadian rhythm so cortisol is raised
3. Urinary free cortisol = raised
4. Loss of circadian rhythm
198
How does a dexamethasone suppression test work?
Give synthetic steroids that suppress pituitary and adrenals and then measure the cortisol
In Cushing's there is no suppression of cortisol
199
What happens after a official diagnosis of Cushing's syndrome has been made?
Figure out if it is ACTH dependent or independent
| CT and MRI of adrenals and pituitary
200
What is the treatment for Cushing's syndrome?
Tumours = surgical removal
| Drugs to inhibit cortisol synthesis - metyrapone, ketoconazole
201
What are some complications associated with Cushing's Syndrome?
Hypertension
Obesity
Death
202
What is the circadian system?
Body clock that regulates your body
| Clear rhythm of cortisol production follows circadian rhythm
203
When do cortisol levels peak?
At around 8:30 am
204
What's the primary cue that synchronises an organism's biological rhythms?
Light
205
What is adrenal insufficiency?
Adrenocortical insufficiency resulting in a reduction of mineralocorticoids, glucocorticoids and androgens
206
Name the 3 types of adrenal insufficiency
1. Primary - Addison's disease (adrenal glands not working)
2. Secondary - Hypopituitarism (lack of ACTH)
3. Tertiary - Suppression of HPA due to presence of exogenous glucocorticoids
207
Give 5 primary causes of adrenal insufficiency
1. Addison's disease (autoimmune destruction of the adrenal cortex)
2. Congenital adrenal hyperplasia (CAH)
3. TB
4. Adrenal metastases
5. Drugs
6. Haemorrhage
7. Infection
208
Give 6 symptoms of adrenal insufficiency
1. Tanned - pigmentations
2. Fatigue
3. Tearful
4. Weight loss
5. Headaches
6. Abdominal cramps
7. Myalgia
8. Poor recovery from illness
9. Adrenal crisis
209
What is the treatment for adrenal insufficiency?
Hormone replacement - any steroids - hydrocortisone
| In Primary adrenal insufficiency (Addison's disease) replace aldosterone with fludrocortisone
210
Give 3 secondary causes of adrenal insufficiency
1. Hypopituitarism
2. Withdrawal from long term steroids
3. Infiltration
4. Infection
5. Radiotherapy
211
What biochemical investigations might you do in someone who you suspect has adrenal insufficiency?
0900 Cortisol and ACTH
Renin = elevated in primary
U+E (decrease sodium, increase potassium due to decrease aldosterone - increase in calcium and urea)
Synacthen test - > 450 nmol/L = AI unlikely
212
What results of cortisol and ACTH tests suggest adrenal insufficiency is likely?
Cortisol >500 nmol/L = AI unlikely
Cortisol <100 nmol/L = AI likely
ACTH > 22 ng/L = primary
ACTH < 5 ng/L = secondary
213
What investigations would you do to determine whether Adrenal insufficiency is primary or secondary?
```
Primary = adrenal antibodies, very long chain fatty acids, imaging and genetics
Secondary = any steroids?, imaging and genetics
```
214
Adrenal crisis is a common presentation of adrenal insufficiency. Give 6 features of an adrenal crisis
1. Hypotension
2. Fatigue
3. Fever
4. Hypoglycaemia
5. Hyponatreamia
6. Hyperkalameia
215
What is the management of adrenal crisis?
Immediate Hydrocortisone 100mg
Fluid resuscitation - saline (IV)
Hydrocortisone 50-100 mg 6 hourly
In primary start fludocortisone
216
What would sodium and potassium levels be in someone with adrenal insufficiency?
Hyponatraemia = low sodium
Hyperkalaemia = high potassium
Lack of aldosterone and so less sodium reabsorbed and less potassium excreted
217
Give a sign of Cushing's syndrome that is due to impairments in carbohydrate metabolism
Diabetes Mellitus
218
Give a sign of Cushing's syndrome that is due to electrolyte disturbances
1. Sodium retention
| 2. Hypertension
219
People with Cushing's syndrome may have immune dysfunction. Give a consequence of this
Increased susceptibility to infection
220
Why is it important to take a drug history when speaking to someone with potential Cushing's?
To exclude exogenous glucocorticoid exposure as a potential cause
221
When might you see signs of hypercortisolism without Cushing's Disease?
1. Pregnancy
2. Depression
3. Alcohol dependence
4. Obesity
222
Briefly describe the mechanism of thyroid destruction
Cytotoxic (CD8+) T cell mediated
thyroglobulin and Thyroid peroxidase (TPO) antibodies may cause secondary damage (alone have no effect)
Antibodies against the TSH receptor may block the effect of TSH (uncommon)
223
What are the main 3 types of cells that cause thyroid destruction?
1. Cytotoxic T cells
2. Thyroglobulin
3. TPO antibodies
224
Briefly describe the pathophysiology of Grave's disease
Autoimmune disease
TSH receptor antibodies stimulate thyroid hormone production
Leads to hyperthyroidism
High circulating levels of thyroid hormone, with a low TSH
225
Give 5 Gravers opthlmopathy signs
1. Exophthalmos eyes (bulging)
2. Lid lag stare
3. Redness
4. Conjunctivitis
5. Pre-orbital oedema
6. Bilateral
7. Extra ocular muscle swelling
226
Give 5 symptoms of Grave's disease that don't include opthalmopathy signs
1. Weight loss
2. Increased appetite
3. Irritable
4. Tremor
5. Palpitations
6. Goitre
7. Diarrhoea
8. Heat intolerance
9. Malaise
10. Vomiting
227
Give 5 signs of Grave's disease that don't include opthalmopathy signs
1. Tachycardia
2. Arrhythmias (e.g. AF)
3. Warm peripheries
4. Muscle spasm
5. Pre-tibial myxoedema (raised purple lesions over the shins)
6. Thyroid acropachy (clubbing and swollen fingers)
228
Name 5 risk factors for Graves disease
1. Female
2. Genetic association
3. E.coli
4. Smoking
5. Stress
6. High iodine intake
7. Autoimmune diseases
229
Name 5 autoimmune diseases associated with thyroid autoimmunity
1. T1DM
2. Addison's disease
3. Pernicious anaemia
4. Vitiligo
5. Alopecia areata
6. Rheumatoid arthritis
230
What would you see histological in someone with Graves disease?
Lymphocyte infiltration and thyroid follicle destruction
231
What is goitre?
Palpabel and visible thyroid enlargement
232
Why does goitre occur and when is is most commonly found?
Due to TSH receptor stimulation resulting in thyroid growth
| Seen in hypo and hyperthyroidism
233
Name 4 types of sporadic non toxic goitre
1. Diffuse --> physiological --> Graves
2. Multi nodular
3. Solitary nodule
4. Dominant nodule
234
Define hyperthyroidism
Overactivity of the thyroid gland
235
Define thyrotoxicosis
Excess of thyroid hormone in the blood (can be used interchangeably with hyperthyroidism)
236
Name the 3 mechanisms of how hyperthyroidism may come about
1. Overproduction of thyroid hormone
2. Leakier of preformed hormone from the thyroid
3. Ingestion fo excess thyroid hormone
237
Give 5 causes of hyperthyroidism
1. Grave's disease
2. Toxic adenoma
3. Toxic multi nodular goitre
4. Ectopic thyroid tissues (metastases)
5. Drugs
6. De quervain's thyroiditis
238
Name 4 drugs which can induce hyperthyroidism
1. Iodine
2. Amiodarone
3. Lithium
4. Radioconstrast agents
239
Give 6 clinical signs feature of hyperthyroidism
1. Weight loss
2. Tachycardia
3. Hyperphagia
4. Anxiety
5. Exophthalmos
6. Tremor
7. Heat intolerance
240
What investigations are done to diagnose hyperthyroidism?
```
Thyroid function tests
Diagnosis of underlying cause
Clinical history, physical signs
Thyroid antibodies
Isotope uptake scan
```
241
What are the realist so thyroid function rests in primary hyperthyroidism?
Increase in T4 and T3 with low levels of TSH (due to negative feedback)
242
What are the realist so thyroid function rests in secondary hyperthyroidism?
Increase in T4 and T3 but inappropriately high TSH
243
What are the 4 main treatments for hyperthyroidism?
1. Beta blockers
2. Anti-thyroid drugs
3. Radioiodine
4. Surgery - partial/total thyroidectomy
244
Why are beta blockers used?
For rapid control of symptoms
245
Give examples of anti-thyroid drugs and why are they used?
Carbimazole, methimazole, proplythiouracil (PTU) - (thionamides)
Decreases synthesis of new thyroid hormone by targeting thyroid peroxidase
PTU also inhibits conversion of T4 to T3
246
What are the 2 strategies of treatment using anti-thyroid drugs?
1. Thionamides titration regime
| 2. Block and replace regime with T4 for Graves
247
Give 4 poor prognostic factors of those on anti-thyroid drugs
1. Severe biochemical hyperthyroidism
2. Large goitre
3. Male
4. Young age of disease onset
248
Give 5 side effects of anti-thyroid drugs
1. Rash
2. Arthralgia
3. Hepatitis
4. Neuritis
5. Vasculitis
6. Agranulocytosis - very serious
249
Why can radioiodine be used as a treatment for hyperthyroidism?
Emit beta particle that destroy thyroid follicle and therefore reducing the production fo thyroid hormones
250
What are 4 long term dose effects fo radioiodine treatment?
1. Shorter cell survival
2. Impaired replication of cells
3. Atrophy and fibrosis
4. Chronic inflammation resembling Hashimoto's
5. Late hypothyroidism
251
Give 4 potential consequences of a partial thyroidectomy
1. Bleeding
2. Hypoglycaemia
3. Hypothyroidism
4. Recurrent laryngeal nerve palsy
252
What is a complication of hyperthyroidism?
Thyroid crisis/storm
253
Briefly explain thyroid crisis/storm
Rapid deterioration of thyrotoxicosis
Hyperpyrexia, tachycardia and extreme restlessness
Delirium --> coma --> death
254
What is the treatment for a thyroid crisis?
Large doses of oral carbimazole, oral propranolol, oral potassium iodide and IV hydrocortisone
255
Define hypothyroidism
Under-activity of the thyroid gland
256
Name the 3 types of hypothyroidism
1. Primary - absence/dysfunction of thyroid gland
2. Secondary - reduced TSH from anterior pituitary
3. Tertiary - associated with treatment withdrawal
257
Briefly describe the pathophysiology of primary hypothyroidism
Aggressive destruction of thyroid cells by various cell and antibody mediated immune processed
Antibodies bind and block TSH receptors
Inadequate thyroid hormone production and secretion
258
Briefly describe the pathophysiology of secondary hypothyroidism
Reduced release or production of TSH so reduced thyroid hormone release
259
Briefly describe the pathophysiology of tertiary hypothyroidism
Thyroid gland overcompensates until it can reestablish correct concentration fo thyroid hormone
260
Name 4 causes of primary hypothyroidism
1. Autoimmune thyroiditis - Hashimoto's
2. Post partum thyroiditis
3. Post thyroidectomy
4. Drug induced
5. Iodine deficiency
6. Primary atrophic hypothyroidism
261
Give 2 examples of iatrogenic causes of hypothyroidism
1. Thyroidectomy
| 2. Radioiodine therapy
262
Give an example of a transient cause of primary hypothyroidism
Post-partum thyroiditis
263
Name 4 drugs that can cause hypothyroidism
1. Carbimazole (used to treat hyperthyroidism)
2. Amiodarone
3. Lithium
4. Iodine
264
Name 3 casques of secondary hypothyroidism
1. Hypopituitarism
2. Hypothalamic disease
3. Isolated TSH deficiency
265
Why can amiodarone cause both hypo and hyperthyroidism?
Because it is iodine rich
266
Give 5 symptoms of hypothyroidism
1. Goitre
2. Weight gain
3. Menorrhagia
4. Malar flush
5. Cold intolerance
6. Energy level fall
7. Depression
267
Give 5 signs of hypothyroidism
BRADYCARDIC
1. Bradycardia
2. Reflexes relax slowly
3. Ataxia (cerebellar)
4. Dry, thin hair/skin
5. Yawning/drowsy/coma
6. Cold hands
7. Ascites
8. Round puffy face
9. Defeated demeanor
10. Immobile
11. Congestive cardiac failure
268
What investigations are conducted to diagnose hypothyroidism?
Thyroid function tests
| Thyroid antibodies
269
What are the TFT results for primary hypothyroidism?
High TSH
| Low T4 and T3
270
What are the TFT results for secondary hypothyroidism?
Inappropriately low TSH for low T4 and T3
271
Name 3 antibodies that may be present in the serum in someone with autoimmune thyroiditis
1. TPO (thyroid peroxidase)
2. Thyroglobulin
3. TSH receptor
272
What is the treatment for primary hypothyroidism?
Thyroid hormone replacement - levothyroxine
| Resection of obstructive goitre
273
Name a complication of hypothyroidism
Myxoedema coma
274
Briefly explain a myxoedema coma
Severe hypothyroidism
Reduced level of consciousness, seizures, hypothermia
IV/oral T3 and glucose infusion needed
275
What is Hashimoto's thyroiditis?
Hypothyroidism due to aggressive destruction of thyroid cells
276
Give 3 symptoms of Hashimoto's thyroiditis
1. Rapid formation of Goitre
2. Dyspnoea or dysphagia
3. General hypothyroidism symptoms
277
Name 3 triggers of Hashimoto's thyroiditis
1. Iodine
2. Infections
3. Smoking
4. Stress
278
What diagnostic test are conducted for Hashimoto's thyroiditis?
TFTs - high TSH
| Thyroid antibodies - high TPO antibodies
279
What is the treatment for Hashimoto's thyroiditis?
Levothyroxine
| Resection fo obstructive goitre
280
Name a complication fo Hashimoto's thyroiditis
Hyperlipidaemia
281
What is a sequelae to Hashimoto's thyroiditis?
Hashimoto's encephalopathy
282
What disease would you treat with Carbimazole?
Hyperthyroidism/Graves disease
283
What disease would you treat with Levothyroxine?
Hypothyroidism
284
Give 5 metabolic changed that occur in pregnancy
1. Increase erythropoietin, cortisol and noradrenaline
2. High cardiac output
3. High cholesterol and triglycerides
4. Pro thrombotic and inflammatory state
5. Insulin resistance
6. Plasma volume expansion
285
Give 5 gestational syndromes
1. Pre-eclamsia
2. Gestational diabetes
3. Obstetric cholestasis
4. Gestational thyrotoxicosis
5. Postnatal depression
6. Post partum thyroiditis
286
At what week are foetal thyroid follicles and T4 synthesised?
Week 10
287
Why can hCG activate TSH receptors and cause hyperthyroidism?
hCG and TSH are glycoprotein hormones with very similar structure
hCG can therefore activate TSH receptors
288
Is hypothyroidism or thyrotoxicosis more common in pregnancy?
Hypothyroidism is more common in pregnancy
289
How can you differentiate between Grave's disease and gestational thyrotoxicosis?
Graves - symptoms predate pregnancy, symptoms are severe during pregnancy, goitre and TSH-R antibodies present
Gestational thyrotoxicosis - symptoms do not predate pregnancy, lots of N/V - hyperemesis gravid arum associated. No goitre or TSH-R antibodies
290
Give 4 potential consequences of untreated hypothyroidism in pregnancy
1. Gestational hypertension
2. Placental abruption
3. Post partum haemorrhage
4. Low birth weight
291
Give 4 potential consequences of untreated hyperthyroidism in pregnancy
1. Intrauterine growth restriction
2. Low birth weight
3. Pre-eclampsia
4. Preterm delivery
292
What pregnant women do you screen for risk of hypothyroidism in their pregnancy?
```
Age >30
BMI >40
Miscarriage
Personal or FH
Goitre
Anti TPO
T1DM
Amiodarone, lithium or contrast use
```
293
What type of receptor does vasopressin bind to?
G-protein couples transmembrane domain receptors
V1a - vasculature
V1b - pituitary
V2 - renal collecting ducts
294
What is the release of vasopressin controlled by?
Osmoreceptors in hypothalamus - day to day
| baroreceptors in brainstem and great vessels - emergency
295
How much of the human body is fluid?
60% = 42L
296
How much water makes up the:
a) ECF
b) ICF
a) 14 L - 10.5L interstitial, 3.5L intravascular
| b) 28L
297
What is the primary cation in ICF?
K+
298
What is the primary cation in the ECF?
Na+
299
What are the primary anions in the ECF?
Cl- and HCO3-
300
What are the units for osmolality?
mOsmol/Kg
301
Define osmolality
Concentration of all solutes per kilogram of water in plasma
302
What is the effect of water excess on thirst and ADH secretion?
Decreased thirst and decreased ADH
| Reduced intake and increased excretion
303
What is the effect of water deficit on thirst and ADH secretion?
Increased thirst and increased ADH
| Increase water intake and reduced secretion
304
What GPCR does ADH bind to on renal tubules?
V2
305
What is the volume of insensible losses?
500 ml/day
306
Briefly describe the thirst axis
Water deficit causes secretion of ADH which acts on principal cells of CDs
ADH binds to adenyl cyclase couple V2R
Kinase action results in insertion of aquaporin 2 channels in apical membrane of CD
Increased water permeability so increase water absorption
307
Give an equation for plasma osmolality
Plasma osmolality = 2[Na+] + [glucose] + [urea]
308
What is the range for normal osmolality?
282-295 mOsmol/kg
309
Name 3 disease associated with the posterior pituitary
1. Cranial diabetes insipidus - lack of ADH
2. Nephrogenic diabetes insipidus - resistance to action of ADH
3. Syndrome of antidiuretic hormone secretion - too much ADH release inappropriately
310
Define diabetes insipidus
Passage of large volumes (>3L/day) of dilute urine due to impaired water reabsorption in the kidney due to hypo secretion or insensitivity to ADH
311
Name the 2 types of DI
1. Cranial DI = hyposecretion
| 2. Nephrogenic DI = insensitivity
312
Give 5 signs of DI
1. Excessive urine production - >3L/day (polyuria)
2. Severe thirst (polydipsia)
3. Very dilute urine - <300 mOsmol/Kg
4. Hypernatraemia
5. Dehydration
313
Give 4 causes of cranial DI
1. Tumours
2. trauma
3. Infections
4. Idiopathic
5. Genetic - mutations in ADH gene
314
Give 4 causes of nephrogenic DI
1. Osmotic diuresis (DM)
2. Drugs
3. CKD
4. Metabolic - hypercalcaemia, hypokalaemia
5. Genetic - mutation in ADH receptor
315
Give 3 possible differential diagnosis's of DI
1. DM
2. Hypokalaemia
3. Hypercalcaemia
316
What investigations might you do to determine whether someone has diabetes insipidus?
1. Measure 24hr urine volume - >3L/day = suggests DI
2. Plasma biochemistry - hypernatraemia
3. Water deprivation test - urine will not concentrate when asked nor to drink
4. U+Es - confirm it isn't a more common causes of polyuria
5. MRI of hypothalamus - confirm cranial DI
317
What is the treatment for cranial DI?
Treat underlying condition
Thiazide diuretics, carbamazepine, chlorpropamide - sensitise renal tubules to endogenous vasopressin
Desmopressin - high activity at V2 receptor
318
What is the treatment for nephrogenic DI?
Free access to water
Very high dose desmopressin
Treatment of causes
Thiazide diuretics - offset water losses
NSADs - inhibits prostaglandin synthesis which locally inhibit ADH action
319
Do you have hyponatraemia or hypernatraemia in diabetes insipidus?
Hypernatraemia
320
Give 4 causes of polyuria
1. Hypokalaemia
2. Hypercalcaemia
3. Hyperglycaemia
4. Diabetes insipidus
321
What is SIADH?
Syndrome of inappropriate ADH secretion
Continuous ADH secretion inspire of plasma hypotonicity, leading to retention of water and excess blood volume and thus hyponatraemia
322
Give 4 symptoms of SIADH
1. Anorexia
2. Nausea
3. Malaise
4. Headache
5. Confusion
6. Fits and coma with severe hyponatraemia
323
Give 4 causes of SIADH
1. Disordered hypothalamic pituitary secretion or ectopic production of ADH
2. Malignancy
3. CNS disorders - meningitis, brain tumour, cerebral haemorrhage
4. TB
5. Pneumonia
6. Drugs
324
Describe 5 features of the essential criteria for SIADH
1. Hyponatraemia - <135 mol/L)
2. Plasma hypo-osmolality - <275 mOsmol/Kg
3. High urine osmolality
4. Clinical euvolaemia
5. Increased urinary sodium excretion with normal salt and water intake
325
Name 3 diseases you must exclude in someone you suspect could have SIADH
1. Renal disease
2. Hypothyroidism
3. Hypocortism
4. Recent diuretic use
326
Describe the treatment for SIADH
1. Restrict fluid - <1L/day
2. Give salt
3. Loop diuretics - furosemide
4. ADH-R antagonists - vaptans - primate water excretion with no loss of electrolytes
5. Demeoclocycline - inhibitor of ADH
327
How do you treat asymptomatic SIADH?
Fluid restriction
328
How do you treat very symptomatic SIADH?
Give 3% saline (hypertonic)
329
Would you expect a patient with SIADH to be hypovolaemic, euvolaemic or hypervolaemic?
Euvolaemic
330
Would you associate SIADH with hyponatraemia or hypernatraemia?
Hyponatraemia - <135 mmol/L
331
Would you associate SIADH with plasma hypo-osmolality or hyper-osmolality?
Plasma hypo-osmolality - <275 mOsmol/Kg
332
Would you associate SIADH with a high to low urine osmolality?
High urine osmolality
333
Define hyponatraemia
<135 mmol/L
| Biochemically severe = serum sodium <125 mmol/L
334
Give 4 signs of hyponatraemia
1. Anorexia
2. Confusion
3. Headache
4. Lethargy
5. Weakness
335
Give 4 causes of hyponatraemia
1. SIADH
2. Sodium deficiency
3. Renal failure
4. Malignancy
336
Give 4 ways in which you can classify hyponatraemia
1. Biochemical - mild, moderate, severe
2. Symptoms - mild, moderate, severe
3. Aetiology - hypovolaemic, euvolaemic, hypervolaemic
4. Acuity of onset - Acute (<48hrs), Chronic
337
What is the treatment for acute hyponatraemia?
Give a bolus dose of saline
338
What stimulates the posterior pituitary to release ADH?
Osmoreceptors in the hypothalamus detect raised plasma osmolality
Posterior pituitary is signalled to release ADH
339
Name the suprasellar neoplasm that can result from benign cysts and calcification of Rathke's pouch
Craniopharyngioma
340
Give 4 signs of Craniopharyngioma
1. Raised ICP
2. Visual disturbances
3. Growth failure
4. Puberty affected - pituitary hormone deficiency
5. Weight gain
341
Give 4 signs of Rathke's Cyst
1. Headache
2. Amenorrhoea
3. Hypopituitarism
4. Hydrocephalus
342
Give 4 local effects a pituitary adenoma
1. Headaches
2. Visual field defects - bitemporal hemianopia
3. Cranial nerve palsy and temporal lobe epilepsy
4. CSF rhinorrhoea
343
What investigations are done when pituitary dysfunction is suspected?
Hormonal tests
| If hormonal tests are abnormal or tumour mass effect perform MRI pituitary
344
What do you test the thyroid axis for in pituitary disease?
Measure Free T4 and TSH
345
What is the affect of hypothyroidism on TSH and T4 levels?
TSH high
| T4 low
346
What is the effect of hypopituitarism on TSH and T4 levels?
TSH low
| T4 low
347
What is the affect of hyperthyroidism on TSH and T4 levels?
TSH low
| T4 high
348
What do you test the gonadal axis for in pituitary disease?
Measure 0900h fasted testosterone and LH/FSH
349
What is the effect of primary hypogonadism on testosterone and FSH/LH levels?
Testosterone low
| FSH/LH high
350
What is the effect of hypopituitarism on testosterone and FSH/LH levels?
Testosterone low
| FHS/LH low
351
When should serum testosterone be measure?
At 9am due to circadian rhythm
352
Are the levels of oestradiol and FSH/LH low or high before puberty?
Very low levels in serum
353
What is the effect of primary ovarian failure on oestradiol and FSH/LH levels?
FSH/LH high
| Oestradiol low
354
What is the effect of hypopituitarism on oestradiol and FSH/LH levels?
FSH/LH low
| Oestradiol low
355
What do you test the HPA axis for in pituitary disease?
Measure 9am cortisol and synacthen
356
What is the effect of primary adrenal insufficiency on cortisol and ACTH levels and response to synacthen test?
Cortisol low
ACTH high
Synacthen - poor response
357
What is the effect of hypopituitarism on cortisol and ACTH levels and response to synacthen test?
Cortisol low
ACTH low
Synacthen - poor response
358
What do you test the GH/IGF1 axis for in pituitary disease?
Perform IGF-1 and GH stimulation test
| Insulin stress test and glucagon test
359
What can lead to elevated levels of prolactin?
1. Stress
2. Drugs
3. Pressure on pituitary stalk
4. Prolactinoma
360
Why is dynamic hormone testing used?
Dynamic stimulation or suppression test may be useful in select cases to further evaluate pituitary reserve and/or for pituitary hyper function
361
What is the best radiological evaluation for the pituitary?
MRI - better visualisation fo soft tissue and vascular structures
362
T1DM can be associated with autoimmunity. What 4 antibody tests are conducted to try and diagnose this?
1. ANti GAD
2. Pancreatic islet cell antibodies
3. Islet antigen-2 antibodies
4. ZnT8
363
What do free fatty acids do?
Impair glucose uptake
Transported to liver --> gluconeogenesis
Oxidised to form ketone bodies
364
Name 3 ketone bodies
1. Beta hydroxybutyrate
2. Acetoacetate
3. Acetone
365
Does diabetic ketoacidosis occur in T1 or T2 DM?
Type 1
366
Describe the triad of DKA
1. Hyperglycaemia - blood glucose >11 mmol/L
2. Acidaemia - blood pH <7.3 or plasma bicarbonate <15 mmol/L
3. Raised plasma ketones - urine ketones >2+
367
Give 4 causes of DKA
1. Unknown
2. Infection
3. Treatment error - not administering enough insulin
4. Having undiagnosed T1DM
368
Give 5 symptoms of DKA
1. Polyuria
2. Polydipsia
3. Weight loss
4. Nausea and vomiting
5. Confusion
6. Weakness
369
Give 3 signs of DKA
1. Hyperventilation
2. Dehydration
3. Hypotension
4. Tachycardia
5. Coma
370
What is the treatment for DKA
Rehydration (3L in first 3 hours)
Insulin
Replacement of electrolytes - K+
Treat underlying cause
371
Give 4 potential complications of untreated DKA
1. Cerebral oedema
2. Adult respiratory distress syndrome
3. Aspiration pneumonia
4. Thromboembolism
5. Death
372
In what class of drugs does metformin belong?
Biguanide
373
Give an example of a sulfonylurea
Tolazamide
| Gliclazide
374
What are the physiological defences to hypoglycaemia?
Release of glucagon and adrenaline
375
What are the symptoms of hypoglycaemia?
Autonomic - sweating, tremor, palpitations
Neuroglycopenic - confusion, drowsiness, incoordination
Severe neuroglycopenic - convulsions, coma
376
Name 3 other types of diabetes other than T1DM, T2DM and DI
1. Maturity onset diabetes of the young (MODY)
2. Permanent neonatal diabetes
3. Maternal inherited diabetes and deafness
377
Name 3 exocrine causes of Diabetes
1. Inflammatory - actue/chronic pancreatitis
2. Hereditary haemochromatosis
3. Pancreatic neoplasia
4. Cystic fibrosis
378
Name 3 endocrine causes of Diabetes
1. Acromegaly
2. Cushing's syndrome
3. Peochromocytoma
379
What is Pheochromocytoma?
A rare catecholamine secreting tumour in the adrenal medulla (chromatin cells)
380
Name the 2 types of pheochromocytoma
1. Familial type - more NAd
| 2. Sporadic - more Ad
381
Give 6 symptoms of pheochromocytoma
1. Headache
2. Sweating
3. Tachycardia
4. Hypertension
5. Palpitations
6. Tremor
7. Anxiety
8. Nausea/vomiting
9. Confusion
382
What investigations might you do in order to diagnose someone with pheochromocytoma?
Bloods - raised WCC, increased plasma metadrenaline and normetadrenaline
24hr urine collecting for urinary catecholamine and metabolites (metanephrines)
383
What is the treatment for pheochromocytoma?
1. Alpha blocker - phenoxybenzamine
2. Beta blockers
3. Surgery resection of tumour
384
What is the major complication of surgery on a patient with a pheochromocytoma?
Can stoke out during surgery due to rapid effect of adrenaline on the BP
385
What is the major concern in someone with pheochromocytoma?
Dangerous cause of hypertension
386
17 year old man presents with intermittent headaches and anxiety. He is sweating and vomiting. His BP is 223/159 and his pulse is 115. What is the likely cause?
Phaeochromocytoma crisis
| Hypertension and tachycardia = phaeochromocytoma until proved otherwise (especially in younger patients)
387
What is the management of a phaeochromocytoma crisis?
Non-competitive alpha-blocker e.g. phenoxybenzamine
Excision of paraganglioma
Biochemistry: measure plasma and serum metanephrines
388
What are the 3 main sites where microvascular complications of Diabetes cause particular damage?
1. Retina = retinopathy
2. Glomerulus = nephropathy
3. Nerve sheath = neuropathy
389
How long after a young patient has been diagnosed do microvascular complications start to manifest?
10-20 years after diagnosis
390
Give 5 risk factors for diabetic retinopathy
1. Long duration DM
2. Poor glycaemic control
3. Hypertensive
4. On insulin treatment
5. Pregnancy
6. High HbA1c
391
Describe the pathophysiology of diabetic retinopathy
Micro-aneurysms --> pericyte loss and protein leakage --> occlusion --> ischaemia
392
How can diabetic retinopathy be sub-divided?
```
R1 = non-proliferative/background
R2 = pre-proliferative
R3 = Proliferative
```
393
What would you see in someone with an R1 retinopathy grade?
Non-proliferative/background
Micro-aneurysms
Intraretinal haemorrhages
Exudates
394
What would you see in someone with an R2 retinopathy grade?
Pre-proliferative
Venous bleeding
Growth of new vessels
395
What would you see in someone with an R3 retinopathy grade?
Proliferative
| New blood vessel on disc
396
What is the treatment for diabetic retinopathy?
Regular screening to assess visual acuity
| Laser therapy treats neovascaularisation - doesn't improve sight but stabilises
397
What are the main risks of laser treatment of diabetic retinopathy?
Loss of night vision and peripheral vision
398
What is diabetic maculopathy?
Fluid form leaking vessel is cleared poorly in macular area causing macula oedema which distorts and thickens the retina at the macula
Leads to loss of central vision
399
What is the hallmark of diabetic nephropathy?
Development of proteinuria and progressive decline in renal function
400
What happens to the glomerular basement membrane in someone with diabetic nephropathy?
On microscopy there is thickening of the glomerular basement membrane
401
Give one way in which the presentation of diabetic nephropathy differs between T1 and T2DM
T1DM - microalbuminuria develops 5-10 years after diagnosis
| T2DM - microalbuminuria is often present at diagnosis
402
Give 2 risk factors for diabetic nephropathy
1. Poor blood pressure
| 2. Poor blood glucose control
403
Describe the treatment for diabetic nephropathy
1. Glycaemic and BP control
2. Angiotensin receptor blockers/ACE inhibitors
3. Proteinuria and cholesterol control
404
What is the commonest form of diabetic neuropathy?
Distal symmetrical neuropathy
405
Give 5 risk factors for diabetic neuropathy
1. Poor glycaemic control
2. Hypertension
3. Smoking
4. High HbA1c
5. Overweight
6. Long duration DM
406
What do isolated mononeuropathies result from in diabetic neuropathy?
Occlusion of vasa nervorum - small arteries that provide blood supply to peripheral nerves
407
Why do more diffuse neuropathies arise in diabetic neuropathy?
Accumulation of fructose and sorbitol which disrupts the structure and formation of the nerve
408
Give 3 major clinical consequences of diabetic neuropathy
1. Pain
2. Autonomic neuropathy
3. Insensitivity
409
Describe the pain associated with diabetic neuropathy
Burning
Paraethesia
Allodynia - triggering of pain from stimuli that doesn't usually cause pain
410
What is autonomic neuropathy in relation to diabetic neuropathy?
Damage to the nerves that supply body structures that regulate function such as BP, HR, bowel/bladder emptying
411
Give 5 signs of autonomic neuropathy in diabetic neuropathy
1. Hypotension
2. HR affected
3. Diarrhoea/constipation
4. Incontinence
5. Erectile dysfunction
6. Dry skin
412
What are the consequences of insensitivity as a result of diabetic neuropathy?
Insensitivity --> foot ulceration --> infection --> amputation
413
Describe the distribution of insensitivity as a result of diabetic neuropathy
Glove and sticking distribution - starts in the toes and moves proximally
414
Describe the treatments for diabetic neuropathy
1. Improve glycaemic control
2. Antidepressants
3. Pain relief
415
Give 5 ways in which amputation can be prevented in someone with diabetic neuropathy
1. Screening for insensitivity
2. Education
3. MDT foot clinics
4. Pressure relieving footwear
5. Podiatry
6. Revascularisation and antibiotics
416
What are the 4 main threats to skin and subcutaneous tissues in someone with diabetic neuropathy
1. Infections
2. Ischaemia
3. Abnormal pressure
4. Wound environments
417
Would there be increased or decreased pulses in diabetic neuropathic foot?
Decreased foot pulses
418
Peripheral vascular disease is a complication of Diabetes. Give 6 signs of acute ischaemia
1. Pulseless
2. Pale
3. Perishing cold
4. Pain
5. Paralysis
6. Paraesthesia
419
Name 4 infections poorly controlled diabetes can lead to
1. UTIs
2. Staphylococcal infection of skin
3. Mucocutaneous candidiasis
4. Pyelonephritis
5. TB
6. Pneumonia
420
Why does the site of insulin injection need to be varied day to day?
Can cause lipohypertrophy if the same site is used everyday
421
Name 4 non insulin treatments for diabetes
1. Metformin
2. Sulphonylurea
3. Incretin based agents
4. Thiazolidinediones (TZDs)
5. SGLT-2 inhibitors
422
Why is metformin the first line therapy for diabetes?
Associated with less weight gain and less hypoglycaemia than insulin and sulfonylurea
423
When is sulfonylurea considered as treatment for diabetes?
In individuals:
- Who are not overweight (as causes weight gain)
- Require rapid response due to hyperglycaemia symptoms
- Are unable to tolerate metformin or where metformin is contraindicated
424
How do incretin based agents treat diabetes?
Influence glucose homeostasis via:
- glucose dependent insulin secretion
- postprandial glucagon suppression
- slowing gastric emptying
425
Give examples of Thiazolidinediones (TZDs)
Rosiglitazone and Pioglitazone
426
How do Thiazolidinediones treat diabetes?
Effective glucose lowering agents
427
Define puberty
Puberty describes the physiological, morphological and behavioural changes as the gonads switch from infantile to adult forms
428
What is the first sign of puberty in girls?
Menarche
429
What is the first sign of puberty in boys?
First ejaculation, often nocturnal
430
What hormone is responsible for regulating the growth of the breast and female genitalia?
Ovarian oestrogen
431
Which hormones are responsible for controlling the growth of pubic and axillary hair in females?
Ovarian and adrenal androgens
432
What are the roles of testicular androgen in Male puberty?
1. development of external genitalia
2. Growth of pubic and axillary hair
3. Deepening of voice
433
What scale is used to describe the physical development based on external sex characteristics?
Tanner scale
434
Give 5 consequences of androgen deficiency in a male
1. Loss of libido
2. High pitched voice
3. Loss of facial, axillary, limb and pubic hair
4. Loss of erections
5. Poorly developed scrotum and penis
435
What is thelarche?
Breast development
436
What hormone is thelarche controlled by and how long is thelarche?
Controlled by oestrogen and is completed in about 3 years
437
Describe the 3 stages of thelarche
1. Ductal proliferation
2. Site specific adipose deposition
3. Enlargement of areola and nipple
438
What are the main differences between a prepubertal and adult uterus?
```
Prepubertal = tubular shape
Adult = Pear shape with a thicker endometrium
```
439
What is adrenarche?
Maturation of the adrenal gland - the development of the zone reticular cells
Peri-pubertal adrenal androgen production
440
Give 2 signs of adrenarche
1. Body odour
| 2. Mild acne
441
What is pubarche?
Growth of pubic hair
442
What is precocious puberty?
Onset of secondary sexual characteristics before 8 (girl) or 9 (boy) years old
443
What must you rule out as a cause of precocious puberty in boys?
Brain tumour
444
What is the treatment for precocious puberty?
GnRh super agonist to suppress pulsatility of GnRH secretion
445
What is Precocious pseudopuberty?
Secreting tumours leading to hormone excess
446
Name 3 causes of Precocious puberty
1. Idiopathic
2. CNS tumours
3. CNS disorders
447
Name 3 causes of Precocious pseudopuberty
1. Increased androgen secretion
2. Gonadotrophin secreting tumours
3. Ovarian cyst
4. Oestrogen secreting neoplasm
448
What is delayed puberty?
Absence of secondary sexual characteristics by 14 (girl) or 16 (boy) years old
449
Which is the most likely causes of delayed puberty in boys?
Constitutional delay - runs in the family, late menarche in mum or delayed growth spurt in father
450
Give 3 consequences of delayed puberty
1. Psychological problems
2. Reproduction defects
3. Reduced bone mass
451
Give 5 functional causes of delayed puberty
1. Anorexia
2. Bulimia
3. Over exercising
4. CKD
5. Drugs
6. Stress
7. Sickle cell
452
What investigations might you do in someone with delayed puberty?
1. FBC - red cell count especially
2. U+Es
3. LH/FSH measurements
4. TFTs
5. Karyotyping for Turners
453
What must you rule our in girls with delayed puberty and short stature?
```
Turner syndrome (45X)
They might also have recurrent ear infections
```
454
Name the 3 types of Hypogonadism
1. Primary = Hypergonadotropic hypogonadism
2. Secondary = Hypogonadotropic hypogonadism
3. Tertiary = Hypogonadotropic hypogonadism
455
What is Hypergonadotropic hypogonadism?
Primary gonadal failure - Testes or ovarian failure
456
Briefly describe the mechanism of Hypergonadotropic hypogonadism
- Gonads not working properly so less oestrogen/testosterone
- Increase in GnRH as less negative feedback
- Increase in LH and FSH
- Hypogonadism occurs
457
Give 2 causes of primary hypogonadism
Hypergonadotropic hypogonadism
1. Klinefelter's Syndrome (47XXY)
2. Tuner's Syndrome (45X)
458
What is the effect of Hypergonadotropic hypogonadism on FSH/LH and oestrogen/testosterone levels?
```
FSH/LH = high
Oestrogen/testosterone = low
```
459
What is Hypogonadotropic hypogonadism?
Secondary gonadal failure = problem with pituitary
OR
Tertiary gonadal failure = Problem with hypothalamus
460
Briefly describe the mechanism of secondary hypogonadism
- Less FSH and LH
- So less activation at gonads
- Girls = no response to feedback so oestrogen decreases
- Boys = no response to feedback so testosterone decreases
461
Briefly describe the mechanism of tertiary hypogonadism
- Less GnRH produced
- So less FSH and LH
- So less activation at gonads
- Girls = no response to feedback so oestrogen decreases
- Boys = no response to feedback so testosterone decreases
462
Give 2 causes of Hypogonadotropic hypogonadism
1. Kallmann's Syndrome
| 2. Tumours - craniopharyngiomas, germinomas
463
What is the effect of hypogonadotropic hypogonadism on FSH/LH and oestrogen/testosterone levels?
```
FSH/LH = low
Oestrogen/testosterone = low
```
464
What is the treatment for hypogonadism?
Hormone replacement therapy
- Males = testosterone gel/injections
- Females = Ethinyl oestradiol or oestrogen (tablet or transdermal), progesterone added once full oestrogen dose reached
465
What is Turner syndrome?
Patient is missing an X chromosome - 45X
| Primary gonadal failure (hypergonadotropic hypogonadism)
466
Give 3 signs of Turner syndrome
1. Short stature
2. Delayed puberty
3. CV and renal malformations
4. Recurrent otitis media
467
What is Klinefelter's Syndrome?
Male patient has an extra X chromosome - 47XXY
| Primary gonadal failure (hypergonadotropic hypogonadism)
468
Give 2 signs of Klinefelter's Syndrome
1. Azoospermia
2. Gynaecomastia (enlargement of male breast tissue)
3. Increased risk of breast cancer
4. Testicular size <5ml
469
Why might someone with Klinefelter's Syndrome have fertility problems?
Azoospermia - semen contain no sperm
470
Give 4 symptoms of Klinefelter's Syndrome
1. Reduced pubic hair
2. Tall stature
3. reduced IQ
4. Small testicles <5ml
471
What cancer is someone with Klinefelter's Syndrome at an increased risk of developing?
Breast cancer
472
What syndrome is characterised by a congenital deficiency of GnRH?
Kallmann's Syndrome
473
What is Kallmann's Syndrome?
Congenital deficiency of GnRH
| Secondary gonadal figure - hypogonadotropic hypogonadism
474
What must you test in a person who you suspect has Kallmann syndrome?
Smell - 75% are anosmia
475
How is Kallmann syndrome inherited?
X linked recessive or dominant
476
What is hirsutism?
Excess hair growth in women in a male pattern
477
What is the cause of hirsutism?
Increased androgen production by the ovaries or adrenal glands
Most commonly polycystic ovary syndrome
478
What diseases are associated with polycystic ovary syndrome?
1. Insulin resistance - T2DM
2. Hypertension
3. Hyperlipidaemia
4. CV disease
479
Give 5 symptoms of polycystic ovary syndrome
1. Amenorrhoea
2. Oligomenorrhoea
3. Hirsutism
4. Acne
5. Overweight
6. Infertility
480
What criteria can be used to make a diagnosis of polycystic ovary syndrome?
Rotterdam diagnostic criteria
1. Menstrual irregularity
2. Clinical or biochemical evidence of hyperandrogenism
3. Polycystic ovaries on USS
481
Describe the treatment for polycystic ovary syndrome
1. Hirsutism therapy - shaving/waxing excess hair OR oestrogen (e.g. OCP)
2. Menstrual disturbance therapy - cyclic oestrogen/progesterone
3. Metformin can improve hyperinsulinaemia and regulates menstrual cycle
482
A 27-year- old woman comes to see you because she is having infrequent periods (oligomenorrhoea). You note, on examination, that she has facial acne and is overweight. What is the most likely diagnosis? Give 3 other signs you might see in this patient
```
Polycystic ovary syndrome
Other signs:
1. Hirsutism
2. Amenorrhoea
3. Infertility
```
483
Give 2 clinical signs of hypervolaemia
1. Ascites
| 2. Oedema
484
Give 3 clinical signs of hypovolaemia
1. Hypotension
2. Tachycardia
3. Decreased skin turgor
4. Dry mucus membranes
485
pH 7.1; pCO2 1.2 kPa; pO2 11.1 kPa; Bicarbonate 4mmol/l.
| Interpret this blood gas result
Severe metabolic acidosis
486
Give 3 causes of severe metabolic acidosis
1. Diabetic ketoacidosis
2. Severe sepsis
3. Uraemia
4. Lactic acidosis
487
What is Conn's syndrome?
Primary hyperaldosteronism
| High aldosterone levels independent of RAAS activation - H20 and sodium retention and potassium excretion
488
What are the 2 main signs of Conn's syndrome?
1. Hypertension
2. Hypokalaemia
Sodium will be normal or slightly raised
489
Give 3 symptoms of Conn's syndrome
| A deficiency in which electrolyte causes these?
1. Muscle weakness
2. Tiredness
3. Polyuria
Due to potassium deficiency
490
What can causes Conn's syndrome?
```
Adrenal adenoma (2/3)
Bilateral adrenal hyperplasia (1/3)
```
491
What hormone is raised in Conn's syndrome and what hormone is reduced?
Where are these hormones synthesised?
1. Aldosterone is raised - synthesised in the zone glomerulosa
2. Renin is reduced - synthesised in the juxta-glomerular cells
492
What investigations might you do in someone to confirm a diagnosis of Conn's syndrome?
1. Bloods - U+E, renin (low), aldosterone (high)
| 2. Plasma aldosterone renin ratio - initial screening - raised = further tests
493
Give 4 ECG changes you might see in someone with Conn's syndrome
1. Increased amplitude and width of P waves
2. Flat T waves
3. ST depression
4. Prolonged QT interval
5. U waves
494
What is the treatment for Conn's syndrome?
1. Laparoscopic adrenalectomy (adenoma)
| 2. Aldosterone antagonist - Spironolactone (hyperplasia)
495
What is adrenal hyperplasia?
Defective enzymes mediating the production of adrenal cortex products - low levels of cortisol and high levels of male hormones
496
How does adrenal hyperplasia present?
Salt loss
Females - ambiguous genitalia with common urogenital sinus
Males - no signs at brith, subtle hyperpigmentation and possible penile enlargement
497
Briefly describe the pathophysiology of adrenal hyperplasia
Defective 21-hydroxylase --> disruption of cortisol biosynthesis
With or without aldosterone deficiency and androgen excess
498
What diagnostic test would be done to confirm adrenal hyperplasia?
Serum 17-hydorxyprogesterone (precursor to cortisol) = high
499
What is the treatment for adrenal hyperplasia?
Glucocorticoids - hydrocortisone
Mineralocorticoids - control elecytrolytes
If salt loss - sodium chloride supplement
500
What is hyperkalaemia?
Excess of potassium
Serum K+ >5.5 mmol/L
Serum K+ >6.5 mmol/L = medical emergency
501
Give 3 symptoms of hyperkalaemia
1. Weakness
2. Palpitations
3. Tachycardia
4. Chest pain
502
Give 3 causes of hyperkalaemia
1. AKI
2. Drug interferences - NSAIDs, K+ sparing diuretics, ACEi
3. Metabolic acidosis
4. DKA
5. Excess K+
503
What ECG changes might you see in someone with hyperkalaemia?
1. Tall tented T waves
2. Widened QRS
3. Small P wave
4. Prolonged PR
504
What is the treatment for hyperkalaemia?
Dietary potassium restriction
| Loop diuretic
505
What is a complication for someone with hyperkalaemia?
Myocardial infarction --> death
506
What is hypokalaemia?
Deficiency in potassium
Serum K+ <3.5 mmol/L
Serum K+ <2.5 mmol/L = medical emergency
507
Give 5 symptoms of hypokalaemia
1. Muscle weakness
2. Hypotonia
3. Hyperflexia
4. Tetany
5. Palpitations
6. Arrhythmia
7. Nausea and vomiting
8. Cramps
508
Give 3 causes of hypokalaemia
1. Diuretics
2. Hyperaldosteronism (Conn's syndrome)
3. Insulin
4. D+V
5. Renal disease
509
What ECG changes might you see in someone with hypokalaemia?
1. Increased amplitude and width of P waves
2. ST depression
3. Flat T waves
4. U waves
5. QT prolongation
510
What is the treatment for hypokalaemia?
Treat underlying causes
Withdraw harmful medication (diuretics or laxatives)
Normalise magnesium as well as potassium
511
What are 2 possible complications of hypokalaemia?
1. Cardiac arrhythmias
| 2. Sudden death
512
Name 5 types of thyroid cancer
1. Papillary
2. Follicular
3. Anaplastic
4. Lymphoma
5. Medullary
513
What types of thyroid cancers are usually asymptomatic thyroid nodule (usually hard and fixed)?
Papillary
Follicular
Anaplastic
514
How does a lymphoma of the thyroid present?
Rapidly growing mass in the neck
515
How does a medullary cancer of the thyroid present?
Diarrhoea
Flushing episodes
Itching
516
Why is an anaplastic cancer of the thyroid one of the most aggressive cancers?
Cancer of the follicular cells of the thyroid but doesn't retain original cell features like iodine uptake or synthesis of thyroglobulin
517
What hormone does a medullary cancer of the thyroid produce?
Calcitonin from C cells
518
What is the most common form of thyroid cancer?
Papillary - 70%, young people, 3x more common in women
| Follicular - 20%
519
What investigations can you do to confirm a thyroid cancer?
Fine needle aspiration
| For a Medullary cancer - elevated serum calcitonin
520
What is the treatment for thyroid cancer?
```
Papillary and follicular
- total thyroidectomy
- ablatie radioactive iodine
Anaplastic and lymphoma
- external radiotherapy to provide relief
- largely palliative
Medullary
- total thyroidectomy and prophylactic central lymph node dissection
```
521
What is a carcinoid tumour?
Serotonin secreting tumour which tend to express somatostatin receptors
522
What are the types of carcinoid tumour?
1. Foregut
2. Midgut
3. Hind gut
523
Name 5 effects of serotonin
1. Bowel function
2. Mood
3. Clotting
4. Nausea
5. Bone density
6. Vasoconstriction
7. Increase force of contraction and HR
524
Name 3 symptoms of a carcinoid tumour
1. Pain
2. Weight loss
3. Palpable mass
525
What is carcinoid syndrome?
Carcinoid tumour where there is hepatic involvement
526
What are 4 more symptoms of carcinoid syndrome?
1. Bronchospasm
2. Diarrhoea
3. Skin flushing
4. Right sided heart lesion
527
What is a carcinoid crisis?
When a carcinoid tumour outgrows its blood supply or is handled too much during surgery - mediators flow out
528
Name 3 events that occur due to a carcinoid crisis
1. Vasodilation - due to bradykinin
2. Hypotension - due to ACTH which increases cortisol
3. Tachycardia - due to serotonin
4. Bronchoconstriction - due to bradykinin
5. hyperglycaemia - due to glucagon and ACTH
529
How do you treat a carcinoid crisis?
High dose somatostatin analogue - octreotide
530
Briefly describe the pathophysiology that begins a carcinoid tumour
Derived from enterchromaffin cells
| Tend to secrete bioactive compounds --> serotonin, bradykinin precursors --> carcinoid syndrome
531
What investigations can be done to diagnose a carcinoid tumour?
Urine - high volume of 5-hydroxyindoleacetic acid (breakdown product of serotonin)
Liver ultrasound
Octreoscan - radio labelled ocreotide hits the somatostatin receptors
532
What is the treatment for a carcinoid tumour?
Somatostatin analogue - octreotide/lanreotide
| Surgical resection - reduce tumour mass
533
Which of the following is not under the control of the pituitary gland?
a. Thyroid
b. Adrenal cortex
c. Adrenal medulla
d. Testis
e. Ovary
c) Adrenal medulla
534
Which of the following statements is false?
a. The pituitary gland lies in the sella turcica
b. The pituitary gland weight around 0.5g
c. ACTH is secreted from the pituitary during stress
d. The pituitary regulates calcium metabolism
e. The anterior and posterior pituitary are distinct on an MRI scan
d) The pituitary regulates calcium metabolism
535
In men all the following are mainly produced in the adrenal cortex except
a. DHEAS
b. Testosterone
c. Aldosterone
d. 17-PH progesterone
e. Androstenedione
b) Testosterone
536
Which of the following regarding ADP (vasopressin) is false?
a. ADP levels have a linear relationship with serum osmolality
b. Is produced in the pituitary gland
c. Stimulates reabsorption of water in the collecting duct of the nephron
d. In hypotension baroreceptors predominantly activate ADH production and secretion
e. Further ADP production is no longer effective once urine osmolality has reaches a plateau
b) Is produced in the pituitary gland
537
Hypothalamic hormones act to mainly stimulate the release of all these hormones except?
a. ACTH
b. GH
c. TSH
d. Prolactin
e. LH
d) Prolactin
538
Where is growth hormone’s main site of action to stimulate IGF1 release?
a. Bone
b. Liver
c. Adrenal cortex
d. Muscle
e. Pancreas
b) Liver
539
The following are typical features of excess growth hormone secretion except?
a. Polyuria
b. Joint pains
c. Sweating
d. Hypotension
e. Headaches
d) Hypotension
540
The following hormones all have a circadian rhythm except?
a. Cortisol
b. Testosterone
c. DHEA
d. 17OH progesterone
e. Thyroxine (T4)
e) Thyroxine (T4)
541
Typical features of cortisol deficiency include the following except?
a. Hypotension
b. Muscle aches
c. Weight loss
d. Hyperglycaemia
e. Lethargy
d) Hyperglycaemia
542
A 38-year-old lady presented with weight gain, menorrhagia and constipation. She is most likely to be suffering from?
a. Cushing’s syndrome
b. Addison’s disease
c. Primary hypothyroidism
d. Graves disease
e. Acromegaly
c) Primary hypothyroidism
543
Which test would you likely want to perform in a patient with proximal muscle weakness, purple striae and thin skin?
a. Synacthen test
b. Overnight dexamethasone suppression test
c. Insulin tolerance test
d. Glucagon test
e. Skin allergy test
b) Overnight dexamethasone suppression test
544
A 24-year-old girl presented with hirsutism, oligomenorrhoea and acne. What test wold you likely carry out?
a. Ultrasound adrenal
b. Ultrasound ovaries
c. MRI ovaries
d. CT scan adrenals
e. Prolactin
b) Ultrasound ovaries
545
The following may cause nephrogenic diabetes insipidus except?
a. Lithium
b. Myeloma
c. Amyloidosis
d. Hyperkalaemia
e. Hypercalcaemia
b) Myeloma
546
A 54-year-old gentleman presented with hyponatraemia. All the following conditions need excluding before confirming SIADH except?
a. Hypothyroidism
b. Hypovolaemia
c. Euvolaemia
d. Adrenal insufficiency
e. Diuretic use
c) Euvolaemia
547
A 66-year-old gentleman had a serum sodium of 124 mmol/l, serum osmolality 265 mmol/l and a urine sodium of 52 mmol/l. What would you like to perform first?
a. Chest X-ray
b. CT brain
c. Skin turgor and jugular venous pressure test
d. Thyroid function tests
e. Synacthen test
c) Skin turgor and jugular venous pressure test
548
The following are most likely causes of SIADH except?
a. Multiple sclerosis
b. Lung abscess
c. Subdural haemorrhage
d. Lymphoma
e. Cerebrovascular accident
a) Multiple sclerosis
549
A 28-year-old presented with a microprolactinoma? What is the most unlikely symptom?
a. Galactorrhoea
b. Oligomenorrhoea
c. Decreased sexual appetite
d. Headaches
e. Visual field defects
e) Visual filed defects
550
18. The following suppress appetite except?
a. Peptide YY
b. Ghrelin
c. CCK
d. GLP1
e. Glucose
b) Ghrelin
551
The main adipose signal to the brain is?
a. CCK
b. Neuropeptide y
c. Leptin
d. Agouti-related peptide
e. Adiponectin
c) Leptin
552
A 65-year-old lady is diagnosed with SIADH. Her sodium is 123mmol/l. What is your first line of management?
a. If she is symptomatic, I will treat with fluid restriction
b. If she is asymptomatic, I will treat with hypertonic saline
c. If she is asymptomatic, I will treat with fluid restriction
d. If she is asymptomatic, I will repeat the sodium level the next day
e. If she is asymptomatic, I will give normal saline
c) If she is asymptomatic, I will treat with fluid restriction
553
A patient with Addison’s disease presents with a chest infection. What do you do?
a. Omit his steroids to avoid immunosuppression
b. Stop his steroids as they have precipitated a chest infection
c. Double his steroid dose whilst unwell
d. Keep him on his usual steroid dose
e. None of the above
c) Doublers this steroid dose whilst unwell
554
22. The following tests are typical of secondary hypogonadism
a. Low LH; High testosterone
b. Low LH; Low testosterone
c. High prolactin; high testosterone
d. Low FSH; Low prolactin
e. None of the above
b) Low LH; Low testosterone
555
Typical features of hypogonadism in a male include the following except?
a. Decreased sweating
b. Joint and muscular aches
c. Decreased sexual appetite
d. Decreased hair growth
a) Decreased sweating
556
A patient has a noon testosterone level below the normal range. What will you do?
a. Treat with testosterone gel
b. Repeat the test at 0900h and check for symptoms
c. Repeat the test at noon to keep things equal
d. Refer to endocrinology
e. Ignore it
b) Repeat the test at 0900h and check for symptoms
557
Osmoreceptors are found in the:
a. Subfornical organ
b. Organum vasculosum of the lamina terminalis
c. Hypothalamus
d. All of the above
e. None of these
d) All of the above
558
The first line treatment for a patient with a symptomatic prolactinoma is usually?
a. Radiotherapy
b. Transphenoidal surgery
c. Dopamine agonists
d. Transfrontal surgery
e. Somatostatin analogues
c) Dopamine agonists
559
Typical visual field defect of a patient with a large pituitary mass is?
a. Unilateral quadrantanopia
b. Bitemporal hemianopia
c. Complete unilateral visual field loss
d. Complete bilateral visual field loss
e. None of the above
b) Bitemporal hemianopia
560
Satiety is?
a. The physiological feeling of no hunger
b. Inhibited by activation of POMC neurons
c. The physiological feeling of hunger
d. Induced by ghrelin release
e. Enhanced by Agouti-related peptide
a) The physiological feeling of no hunger
561
The centres of appetite regulation in the brain are mainly found in the?
a. Pituitary
b. Cerebellum
c. Hypothalamus
d. Basal ganglia
e. Brain cortex
c) Hypothalamus
562
What is peripheral vascular disease?
Decreased perfusion to the peripheries due to macrovascular disease
563
What is the treatment for peripheral vascular disease?
Stop smoking
Walk through the pain
Surgical intervention
564
What investigations can be done on someone you think has PVD?
Doppler pressure studies
Duplex arterial imaging
Doppler ultrasound
565
What are the main objective of T2DM treatment?
Reducing risk - CVD, CKD and microvascular complications
| Reducing weight - Increase exercise, decrease dietary fat
566
What lifestyle interventions can be put in place for someone with T2DM?
```
Compliance
Lifestyle and patient eduction
30 minutes of exercise a day
Dietitian
Local educational programmes
```
567
How do DPP4 inhibitors work as a treatment for T2DM?
Competitive antagonist of DPP4 enzyme (enhance effects of GIP and GLP1)
So they inactivate incretin hormones GIP and GLP1
568
What are thiazolidinediones contraindicated by?
CCF, high risk fractures and macula oedema
569
How do SGLT-2 inhibitors work as a treatment for T2DM?
Increases renal excretion of glucose
| Risk of hypotension
