Endocrinology Flashcards
1
Q
What are the main components of the end crime system
A
Pituitary Thyroid Parathyroid Adrenal glands Pancreas Ovary Testes
2
Q
What is endocrinology
A
Study of hormones (And gland of origin), their receptors, their intracellular signalling pathways and their associated disease
3
Q
What is an endocrine gland
A
A gland that pours hormones into the bloodstream
4
Q
What is an exocrine gland
A
A gland that pours secretions through a duct to a site of action
5
Q
Define paracrine
A
Acting on adjacent cells
6
Q
Define Autocrine
A
Feedback on same cell that secreted that hormone
7
Q
How are water soluble hormones transported
A
Unbound
8
Q
How are fat soluble hormones transported
A
Protein bound
9
Q
Where do water soluble hormones interact with target cell
A
Bind to a surface receptor
10
Q
Where do fat soluble hormones interact with target cell
A
Diffuse into cell and bind to receptors in the cytoplasm
11
Q
What is the half life of water soluble and fat soluble hormones
A
Water soluble = short
Fat soluble = long
12
Q
What is the clearance rate of water soluble hormones and fat soluble hormones
A
Water soluble = Fast
Fat soluble = Slow
13
Q
What is an example of a water soluble hormone
A
Peptides (TRH, LH and FSH) and monoamines
14
Q
What is an example of a fat soluble hormone
A
Thyroid hormones and steroids (Cortisol)
15
Q
Where are water soluble hormones stored
A
In vesicles
16
Q
Where are fat soluble hormones stored
A
Synthesised on demand not stored
17
Q
What are the different hormone classes
A
Peptides Amines Iodothryonines Cholesterol derivatives Steroids
18
Q
Give an example of a peptide hormone and name some of its properties
A
INSULIN
Stored in granules
Water soluble
Released in pulses
19
Q
Describe the synthesis, packaging, storage and secretion of a peptide hormone
A
Synthesis = preprohormone to pro hormone Packaging = pro hormone to hormone Storage= hormone Secretion = hormone
20
Q
Give an example of an amine hormone
A
Adrenaline, noradrenaline, dopamine
21
Q
What is the precursor molecule for Amine hormones and describe the pathway for noradrenaline synthesis
A
Phenylalanine –> L-tyrosine –> L-DOPA –> Dopamine –> Nad –> AD
22
Q
What enzyme is required to convert noradrenaline into adrenaline
A
Catechol-O-methyl-transferase
23
Q
Why do iodothyronines need to be bound to proteins and what protein are they bound to
A
Because they are not water soluble
Thyroid binding globulin
24
Q
Where are the hormone receptors located
A
Cell wall for peptides
Cytoplasm for steroids
Nucleus for thyroid hormones
25
What controls the action of a hormone
1. Hormone metabolism - increased metabolism reduces function
2. Hormone receptor induction
3. Hormone receptor down regulation
4. Syngergism
5. Antagonism
26
what are the hypophysiotropic hormones that move down the hypothalmaic-axis to the anterior pituitary
Corticotropin releasing hormone
Growth hormone releasing hormone
Thyrotropin releasing hormone
Gonadotropin releasing hormone
Dopamine
27
What are the 6 Peptide hormones secreted by the anterior pituitary (FLATPIG)
```
FSH
LH
ACTH
TSH
Prolactin
GH
```
28
What are the 5 different cell types in the anterior pituitary
```
Gonadotrophs
Corticotrophs
Thyrotrophs
Lactotrophs
Somatotrophs
```
29
Prolactin secretion is inhibited by what
Dopamine
30
Which two peptide hormones are stored in the posterior pituitary
Oxytocin and ADH
31
Which hypothalamic cell type synthesises ADH
Supra-optic nucleus
32
Which hypothalamic cell type synthesises oxytocin
Paraventricular nucleus
33
What are the two main functions of oxytocin
1. Ejection of milk during breast feeding
| 2. Stimulates the contraction of the uterine smooth muscle during labour
34
On what sort of receptor do all pituitary and hypothalamic hormones act on
GPCRs
35
Which stimuli causes the release of ADH
```
Drop in blood pressure
Increase in blood osmolality
Nausea
Vomiting
Exercise
Stress
```
36
What stimuli inhibit the release of ADH
Caffeine
| Alcohol
37
What are the functions of thyroid hormone
```
Accelerate food metabolism
Increase protein synthesis
Stimulation of CHO metabolism
Enhance fat metabolism
Increase ventilation rate
increase Cardiac output
Brain development during foetal life
Acceleration of growth rate
```
38
What is the effect of leptin and insulin on appetite
Have a net effect of increasing satiety and reducing appetite
39
What is the effect of gherkin on appetite
Increases appetite and stimulates food intake
40
When is parathyroid hormone released?
In response to a decrease in serum calcium
41
What are the effects of an increase in parathyroid hormone secretion
1. Increase Ca2+ absorption in kidney
2. Increase bone resorption
3. Increase Ca2+ reabsorption from the gut
4. Increase alpha hydroxylation of 25-OH bit D (Calcitriol) in the kidney
42
What is the set point for serum calcium
1.1mmol/l
43
Why is It important that calcium levels are regulated
Important for function of nerves and muscles as dysregulatedcalcium leads to ECG chnages with depolarisation and depolarisation moving closer or further apart
44
Describe what happens to vitamin D when it is absorbed from sunlight
Hydroxlated in the liver to 25-hydroxy vitamin D where it is taken to the kidney and hydroxylated again to form 1,25-(OH) D = calcitriol
45
What stimulates the release of calcitriol
Low plasma Ca2+
Low plasma phosphate
PTH
46
What is the effect of calcitriol
INCREASE Ca2+ levels
increase Ca2+ and phosphate absorption in the gut
Inhibit PTH release
Enhanced bone turnover
increased Ca2+ and phosphate reabsorption by the kidneys
47
How do correct for calcium
Serum calcium + 0.02 * (40-serum albumin)
48
What are the consequences of hypocalcaemia
```
Parathesia (Numbness and tingling)
Muscle spasm (Hands, feet, larynx)
Seizures
Basal ganglia calcification
Cataracts
Long QT interval on ECG
Chvostek's sign
Trosseau's sign
```
49
What is Chvosteks sign
Sign of neuromuscular irritability - tap over the facial nerve and look for spasms of the ipsilateral facial muscle
50
What is Trosseau's Sign
Inflate the blood pressure cuff to 20mmHg above systolic for 5 minutes which causes carpopedal spasm
51
What are the causes of hypocalcaemia
Vitamin D deficiency
| Hypoparathyroidism
52
What are the causes of hypoparathyroidism
1. Syndromes ie. Di George
Genetic
2. Surgical ie. surgery to the neck such as thyroid or cancer
3. Radiation - cancer treatment
4. Autoimmune - isolated against parathyroid gland or polyglandular
5. Infiltration - haemochromatosis (iron) or Wilsons Disease (Copper)
6. Magesium deficiency
53
What happens in hypoparathyroidism
1. Decreased PTH
2. Decreased renal Ca2+ absorption
3. Increased renal phosphate reabsorption
4. Decreased bone resorption
5. Decreased formation of 1,25-OH 2D leading to decreased intestinal calcium absorption
6 = decreased serum calcium
54
What happens in pseudohypoparathyroidism
Resistance to PTH so get no calcium metabolism response ie
- No increases in bone resorption
- no increased Ca2+ absorption in the gut
55
What are the symptoms of pseudohypoparathyroidism
```
Short stature
Obesity
Round facies
Mild learning difficulties
Subcutaneous ossification
SHORT 4th METACARPAL
```
56
What are the symptoms of hypercalcaemia
```
Thirst
Polyuria
Nausea
Constipation
Confusion leading to coma
Renal stones
ECG abnormalities = short QT
```
57
What are the most common causes of hypercalcaemia
1. Malignancy including bone mets which destroy bone and release calcium, myeloma, PTH releasing protein secreting tumours, lymphoma full of macrophages that convert Via D to 1,25 via D
2. Primary Hyperparathyroidism
58
What are the other causes of hypercalcaemia
```
Thiazides
Thyrotoxicosis
Sarcoidosis
Familial hypocalciuric
Immobilisation
Milk-alkali
Adrenal insufficiency
Phaechromocytoma
```
59
What are the consequences of primary hyperparathyroidism
BONES = osteitis fibres cystic and osteoporosis
Kidney/biliary STONES
Psychic GROANS = confusion
Abdominal MOANS = constipation and acute pancreatitis
polyuria
60
What is the main cause of primary hyperparathyroidism
Single benign adenoma on one of the parathyroid glands
More rarely caused by 4 gland hyperplasia disease
61
What are the mechanism of hyperparathyroidism
1. Increased PTH
2. Increase bone resorption
3. Increase renal reabsorption of calcium
4. Increased calcium absorption
5 = hypercalcaemia
62
Where might you see patients with tertiary hyperparathyroidism
In patients with renal disease because renal failure means they cant activate Via D so cant absorb calcium leading to hypocalcaemia, this leads to increased PTH secretion and PT glands become hyperplasic and autonomous leading to hypercalcaemia
63
Where does the pituitary lie in terms of the BBB
Pituitary lies outside the BBB
64
How does the anterior pituitary receive a blood supply?
Receives blood through a portal venous circulation from the hypothalamus called the hypathalmo-hypophyseal portal veins
65
What are the 5 hormone producing cell types in the anterior pituitary
```
Somatotrophs
Lactotrophs
Gonadotrophs
Thyrotrophs
Corticotrophs
```
66
Describe the thyroid axis of the anterior pituitary
Thyrotropin releasing hormone passes down the hypothalamic axis to the anterior pituitary where it acts on thyrotroph cells to released TSH. TSH causes the release of T4 and T3 from the thyroid
67
Which thyroid hormone is the active form
T3 is the active form so T4 needs to be deiodinated to become active
68
Describe the gonadal axis of the anterior pituitary
Hypothalamus releases gonadotrophin releasing hormone that acts on the anterior pituitary gonadotroph cells to release LH and FSH
69
Which two hormones potentiate the release of LH and FSH from the anterior pituitary
Inhibin and testosterone
70
Describe the HPA axis of the anterior pituitary
Corticotrophin releasing hormone released from the hypothalamus act on the anterior pituitary to cause the release of ACTH which acts on the adrenal glands to cause the release of cortisol
71
Describe the GH/IGF-I axis of the anterior pituitary
GHRH (Promotes) and somatostatin (Inhibits) are released from the hypothalamus and either cause or inhibit the release of GH from the anterior pituitary which causes the release of IGF-I from the liver
72
Describe the dopamine axis of the hypothalamus
Dopamine released from the hypothalamus inhibits the release of prolactin from the lactotrophs of the anterior pituitary
73
What are the 6 different presentations of pituitary disease
1. Benign pituitary adenoma
2. Craniopharyngioma (Common in children and affects appetite)
3. Trauma
4. Apoplexy (Bleed into pituitary causing pituitary expansion reducing the function of nearby structures
5. /Sheehans (During pregnancy the pituitary expands and drop in blood pressure causes the pituitary to infarct
6. Sarcoid/TB
74
What can pituitary tumours cause
1. Pressure on local structures (Optic chiasm (Bitemporal hemianopia) or oculomotor nerves - large tumour can compress brainstem or cause CSF leak)
2. Pressure on normal pituitary = HYPOpituitarism (Lack of pituitary function)
3. High functioning tumour (HYPERpituitarism)
75
What does hypopituitarism cause in males
Paleness due to loss of testosterone and ACTH
No body hair
Central obesity
76
What does hypopituitarism cause in females
Loose body hair
Sallow complexion
77
What does hyperpituitarism cause
1. Prolactinoma = increased prolactin = increased milk production and reduced fertility
2. Acromegaly and gigantism
3. Cushing's Disease
78
What are the three layers of the adrenal cortex
GFR = Makes Good Sex
Zona glomerulosa = Mineralocorticoids (Aldosterone)
Zona Fasciculata = glucocorticoids (Cortisol)
Zona Reticularis = Androgens
79
What is Cushing's disease?
Chronic, elevated and inappropriate elevated levels of circulating plasma glucocorticoids (Cortisol) due to innapropriate ACTH secretion from pituitary tumour
80
What are the functions of cortisol
```
Increased carbo and protein breakdown
Increased deposition of fat and glycogen
Na+ Retention
Increased renal K+ loss
Diminished host response to infection
```
81
What is the most common cause of Cushing's disease
Excess endogenous glucocorticoids
82
What are the clinical features of Cushing's Disease
1. Child puts on weight but loses height
2. Obesity - fat redistributed to central trunk (Buffalo hump)
3. Repeated skin brushing
4. Thinned scalp hair
5. Hirsutism
6. Acne
7. Facial plethora (Ruddy and swollen)
8. Moon face
9. Gonadal dysfunction (Irregular periods and erectile dysfunction)
10. Purple striae on abdomen, breasts and thighs
11. Impaired glucose tolerance
83
What are the causes of Cushing's Disease
1. Exogenous steroids
2. Tumour of pituitary producing too much ACTH = too much cortisol
3. Ectopic tumour in the lung producing too much ACTH
4. Adrenal tumour making too much cortisol
84
What are the ACTH dependent causes of Cushing's disease
1. ACTH secreting pituitary adenomA
| 2. ECTOPIC ACTH syndrome ie. Small cell lung cancer and carcinoid tumours
85
What are the ACTH independent causes of Cushing's disease
Adrenal adenoma which is a cancer of the adrenal gland that releases cortisol
86
What are the three main tests used in the diagnosis of Cushing's Disease?
1. urinary free cortisol = Cortisol usually bound to albumin so when binding capacity is exceeded the cortisol will spill into the urine
2. Low dose dexamethosone suppression test = give synthetic sterioids that suppresses pituitary and adrenal and measure the cortisol levels - in healthy patient the dexamethasone causes negative feedback causing decreased ACTH and cortisol, in Cushing's disease there will be no suppression
3. Late night/midnight serum or salivary cortisol
87
What is the surgical treatment for Cushing's disease
Transphenoidal surgery to remove the pituitary tumour
Bilateral adrenalectomy
88
What is the surgical treatment for an ectopic tumour causing Cushing's
Remove the source - bilateral adrenalectomy
89
What is the surgical treatment for Adrenal adenoma
Adrenalectomy
90
What is the radiotherapy treatment option for Cushing's disease
Adjuvant (primary) therapy
91
Which hormone inhibits the release of GH
Somatostatin
92
Which hormone increases the release of GH
Growth hormone release hormone
93
How does a growth hormone secreting tumour lead to the clinical features of acromegaly
GH causes the release of IGF-I from the liver which leads to the enlargement of parts of the body including large extremities and increased height before fusion of the epiphyses
94
What is gigantism
Excessive GH in children before the fusion of the epiphyses of the long bones
95
What is acromegaly
Excess GH in adults
96
What is the cause of acromegaly and gigantism
benign pituitary GH producing adenoma which causes increased GH secretion which causes increased IGF-I release from the liver which further stimulates skeletal and soft tissue growth
97
What are the co-morbidities associated with acromegaly
```
Hypertension and heart disease
Sleep apnoea
Cerebrovascular events
Arthritis
Insulin resistant diabetes
```
98
How do we diagnose acromegaly
clinical features
GH
IGF-I
99
What are the clinical features of acromegaly
1. Acral enlargement (increased size of hands and feet)
2. Arthralgias
3. Maxofacial change
4. Excessive sweating
5. Headache
6. Hypogonadal symptoms
7. Acroparathesia (Numbness and tingling of extremities
8. Tiredness
9. Weight gain
10. Amenorrhoea
11. Deep voice
12. Goitre
100
What are the signs of acromegaly
```
Skin darkening
Coarsening of face and wide nose
Prognathism
Big supraorbital ridge
Large tongue
Tight rings
```
101
How Is acromegaly diagnosed using the oral glucose tolerance test?
Use the glucose tolerance test - giving glucose suppresses GH release in a normal person but in acromegaly the GH secretion increases following glucose
102
What are the objectives of acromegaly treatment
1. Restoration of basal GH and IGF-1 levels
2. Relief of symptoms
3. Reversal of visual and soft tissue changes
4. Prevention of further skeletal deformity
5. Normalisation of pituitary function
103
What are the treatment options for acromegaly
Pituitary surgery
Medical therapy
Radiotherapy
104
What are the surgical options for acromegaly
Removal of the tumour (transphenoidaly) leads to rapid fall in GH
105
What does the success of pituitary surgery depend on
1. Size of the tumour
| 2. Surgeon skill level
106
What are the radiotherapy options for acromegaly
Stereotactic single fraction radiotherapy which uses highly specific proton beam to minimise radiation to surrounding tissues
Gamma knife
LINAC
Proton beam
107
When is conventional radiotherapy effective in acromegaly
When the tumour is extended and GH levels are high
108
What are the disadvantages of radiotherapy in the treatment of acromegaly
Delayed response
Hypopituitarism
Rare secondary tumours
Rare visual defects
109
What is the medical therapy options for acromegaly
1. Dopamine agonists ie. Cabergoline which weakly controls IGF-I
2. Somatostatin analogues ie. octreotide and lanreotide which inhibit GH release
3. Growth hormone receptor antagonist
110
When are dopamine agonists useful?
In GH and prolactin co-secreting tumours as they dramatically shrink the tumour and control the secretion of GH
111
What are the advantages of dopamine agonists for acromegaly
No hypopituitarism
Oral administration
Rapid onset
112
What are the disadvantages of dopamine agonists for acromegaly
Ineffective
| Side effects
113
What is prolactinoma
Tumour of the pituitary resulting in the excessive prolactin release - can be micro or macro adenoma
114
What are the clinical features of prolactinoma
```
Menstrual irregularity/amenorrhoea
Infertility
Galactorrhea
Low libido
Low testosterone in men
Erectile dysfunction
Reduced facial hair
Visual field defects and headaches due to the local effect of the tumour
```
115
How do you manage prolactinoma
Medical rather than surgical
| Dopamine agonists such as cabergolide usually shrink the macroadenoma
116
Where is the bodies clock?
Suprachiasmatic nuclei
117
What is Addinson's Disease
Primary hypoadrenalism - destruction of the entire adrenal cortex resulting in mineralocorticoid (Aldosterone), glucocorticoid (Cortisol) and sex steroid deficiency
118
What are the causes of primary hypoadrenalism
1. Autoimmune adrenalitis (Destruction of the adrenal cortex by specific antibodies)
2. Congential adrenal hyperplasia
3. Adrenoleukodystrophy
4. Mets, haemorrhage and infection
5. Infection (TB) and infiltration (Amyloid)
119
What is secondary hypoadrenalism
Lack of ACTH = hypopituitarism
120
What are the causes of secondary hypoadrenalism
```
Pituitary macroadenoma
Apoplexy
Hypophysitis
Met, infiltration, infection
Radiotherapy
Congenital
```
121
What are the causes of tertiary hypoadrenalism
Suppression of the HPA due to presence of exogenous glucocorticoids such as steroids, inhalers and creams
122
What are the symptoms Addinson's
```
Fatigue
Tearful
Weight loss
Poor recovery from illness
Adrenal crisis
Headache
Lethargy
Vitiligo
Tanned skin
Pigmentation
```
123
How do we diagnose Addinson's
Measure cortisol and ACTH levels at 0900
If cortisol <100nmol/l then adrenal insufficiency likely
if ACTH<5ng/l = secondary
If ACTH >22ng/l = primary
124
What is the treatment for Addison's disease
Hydrocortisone twice or three times daily at a dose to replace the lost cortisol levels (15-25mg)
125
What is a normal blood glucose range
3.5-8.0mmol/l
126
What happens in the fasting state?
Low blood glucose = high glucagon and low insulin
Glucose released mainly from the liver
- glycogen breakdown (Glycogenolysis)
- Gluconeogenesis
- Reduced peripheral glucose uptake
- Stimulates release of gluconeogenic precursors
- Lipolysis and muscle breakdown
Glucose is delivered to insulin independent tissues
127
What happens in the post prandial state
High blood glucose = high insulin and low glucagon
Glycogenolysis and gluconeogenesis are suppressed
Glucose taken up by peripheral muscle and fat cells
Lipolysis and muscle breakdown is suppressed
- 40% glucose to liver and 60% to muscle
- Ingested glucose helps to replenish glycogen stores in liver and muscle
- High insulin and glucose levels suppress lipolysis and FFA levels fall
128
How is insulin secreted by B cells
1. Glucose enters B cell via GLUT2 transporter and glucokinase
2. Glucose undergoes metabolism to glucose-6-phosphate which generates ADP
3. ADP closes the potassium channel causing depolarisation of the cell membrane
4. Depolarisation causes calcium channels to open enabling a Ca2+ influx
5. Insulin released from insulin secretory granules
129
How does insulin act at fat and muscle cells
1. Insulin acts on the receptor
2. Causes an intracellular cascade
3. cascade causes GLUT4 vesicles to be moved to the plasma membrane which stimulates entry of glucose in the tissue
130
What are the effects of insulin
1. Suppress hepatic glucose output (Decreased glycogenolysis and gluconeogenesis)
2. increase glucose uptake into fat and muscle (Muscle = glycogen synth) (Fat = FFA synthesis)
3. Suppresses lipolysis and the breakdown of muscle
131
Why does insulin have a biphasic release
First phase is rapid release of pre-stored insulin
if glucose levels remain high then a second phase Is initiated which takes longer as more insulin has to be synthesised
132
What are the effects of glucagon
1. Increases hepatic glucose output (Increases glycogenolysis and gluconeogenesis)
2. reduced peripheral glucose uptake
3. Stimulate peripheral release of gluconeogeneic precursors (glycerol and AAs)
- lipolysis
- Muscle glycogenolysis and breakdown
133
What is diabetes mellitus
A disorder of carbohydrate metabolism characterised by hyperglycaemia
134
What is the defining criteria of diabetes
Symptoms and random plasma glucose >11mmol/l
Fasting plasma glucose >7mmol/l
No symptoms - glucose tolerance test fasting >7 or 2hr value >11
135
What is the pathogenesis of T1 diabetes
An insulin deficiency disease characterised by the loss of beta cells due to autoimmune destruction. Insulin deficiency leads to continued breakdown of liver glycogen producing ketones and glucose leading to glycosuria and ketonuria
136
When does the clinical onset of diabetes begin?
10% of beta cells remain
137
What does a failure of insulin secretion result in
1. Continued liver glycogen breakdown
2. Lipolysis and skeletal muscle breakdown producing gluconeogenic precursors
3. Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake
138
Describe the process of ketoacidosis
1. Absence of insulin leads to hyperglycaemia and rising ketones
This is because increased production of acetyl-CoA leads to ketone body production that exceeds the ability of the peripheral tissues to oxidise them
139
What are the causes of type 2 diabetes
Impaired insulin secretion and insulin resistance
140
What are the effects of impaired insulin action?
Reduced muscle and fat uptake of glucose after eating
Failure to suppress lipolysis and high circulating FFA's
Abnormally high glucose output after a meal
141
What are some of the risk factors for T2 diabetes
```
Family history
Increasing age
Obesity
Lack of exercise
Ethnicity (Middle East and SE Asia)
```
142
What are the two types of insulin
Basal insulin
| Prandial/meal type insulin (Rapid Acting)
143
Individuals with T1 diabetes need what sort of insulin
Long acting
144
Individuals with T2 diabetes need what sort of insulin
Short acting
145
When is basal insulin used
To control blood glucose between meals and during the night to ensure that the blood glucose concentration remains between 5-7mmol/l
146
What are the advantages of basal insulin for T2 diabetics
Simple - adjust insulin themselves based on fasting glucose
Less risk with hypoglycaemia at night
147
What are the disadvantages of basal insulin for T2 diabetics
Doesn't cover meals and are best used with long acting insulin analogues which are expensive
148
What are the advantages of pre-mixed insulin for T2 diabetics?
Both basal and prandial components are covered in single preparation which covers insulin requirements for most of the day
149
What are the disadvantages of pre-mixed insulin for T2 diabetics
Not physiological so requires a consistent meal and exercise pattern
Risk of nocturnal hypoglycaemia
Cannot separately titrate individual components
150
Define hypoglycaemia
Low plasma glucose causing impaired brain function <3.9mmol/l
151
What are the autonomic symptoms of hypoglycaemia
```
Trembling
Palpitations
Sweating
Anxiety
Hunger
```
152
What are the neuroglycopenic symptoms of hypoglycaemia
```
Difficulty concentrating
Confusion
Weakness
Drowsiness, dizziness
Vision changes
Difficulty speaking
```
153
When blood glucose falls below 3.8mmol/l, what hormone is produced
Glucagon
154
When blood glucose falls below 3.5mmol/l, what hormone is produced
Adrenaline
155
When blood glucose falls below 3.2mmol/l what happens
Neuroglycopenic symptoms are observed
156
What are the risk factors for severe hypoglycaemia in T1DM
```
History of severe episodes
HbA1c <6.5%
Long duration of diabetes
Renal impairment
Extremes of age
Impaired awareness of hypoglycaemia
```
157
What are the risk factors for severe hypoglycaemia in T2 diabetes
```
Advancing age
Cognitive impairment
Depression
Aggressive glycaemia treatment
Duration of insulin therapy
Renal impairment
Impaired awareness of hypoglycaemia
```
158
Describe the patient education approaches for someone with hypoglycaemia
1. Discuss hypo risk factors and treatments with patient on insulin
2. Educate patients on how to recognise and treat hypo
3. Instruct patients to report hypo episodes to doctor
4. consider enrolling patients with frequent hypo episodes in blood glucose awareness training programme
159
How can we treat hypoglycaemia
15g fast-acting carbohydrate to relieve the symptoms
160
Name the 5 types of hormone producing cell in the anterior pituitary
```
Sommatotrophs
Lactotrophs
Corticotrophs
Thyrotrophs
Gonadotrophs
```
161
What are the 6 peptide hormones released from the anterior pituitary
```
FSH
LH
TSH
GH
Prolactin
ACTH
```
162
Describe the thyroid acxis
1. Thyrotropin releasing hormone passes down hypothalamic axis to anterior pit where it acts on thyrotroph cells to release TSH
2. TSH acts on the thyroid causing release of T3 and T4
3. T3 and T4 negatively feedback to reduce the secretion of TSH and TRH
4. T3 is the active form so T4 must be converted by de-iodinases to T3
163
Describe the HPA axis
1. Corticotrophin releasing hormone released from the hypothalamus acts on the corticotrophin cells of the anterior pituitary release ACTH
2. ACTH causes the release of cortisol from the adrenal glands
3. ACTH switches off secretion of the pituitary and hypothalamic hormones
164
Describe the GH/IGF-I Axis
1. GHRH and somatostatin are released from the hypothalamus
2. If more GHRH is released then GH is released
3. If more somatostatin is released there is decreased GH release
4. GH causes the release of IGHF-I which feeds back
165
What inhibits the release of prolactin
Dopamine
166
What are the 5 different presentations of pituitary disease?
1. Benign pituitary adenoma
2. Craniopharyngioma
3. Trauma
4. Apoplexy (Bleed into pituitary causing pituitary expansion thus reducing function of nearby structures) /Sheehans (During pregnancy the pituitary expands and drop in blood pressure causes pituitary to infarct
5. Sarcoid/TB
167
What are the 3 presentation points of a pituitary tumour
1. Pressure on local structures
- ie. optic chiasm causing bitemporal hemianopia
- Oculomotor nerve causing eye movement difficulties
- CSF leak/brainstem compression
2. Pressure on normal pituitary
- Leads to hypopituitarism
3. High functioning tumour (Hyperpituitarism)
- Prolactinoma
- Acromegaly and gigantism
- Cushings
168
What are the signs seen in a male with hypopituitarism
Pale due to loss of testosterone and lack of ACTH causes loss of pigment
No body hair
Central obesity
169
What are the signs seen in a female with hypopituitarism
Loose body hair
| Sallow complexion
170
What are the three layers of the adrenal cortex
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
171
What does the zona glomerulosa produce
Mineralocorticoids (Aldosterone)
172
What does the Zona fasciculate produce
Glucocorticoids (Cortisol)
173
What does the zona reticularis produce
Androgens
174
What does the adrenal medulla produce
Catecholamines (Adrenaline and noradrenaline)
175
Define Cushing's syndrome
Chronic, excessive and inappropriate elevated levels of circulation plasma cortisol (Glucocorticoid)
176
What is the normal cause of the elevated glucocorticoids seen in Cushing's disease
Inappropriate ACTH secretion from the pituitary gland due to a tumour
177
What are the functions of cortisol
```
Increased carbo and protein breakdown
Increased deposition of fat and glycogen
Na+ retention
Increased renal K+ loss
Diminished response to infection
```
178
Describe the clinical presentation of Cushing's Disease
Obesity - fat distribution to central trunk (Buffalo hump)
Plethoric complexion (Ruddy and swollen)
Moon face
Hirsutism
Hypertension
Muscle thinning
Thinned scalp hair
Mood changes (Depression, lethargy, irritable)
Proximal weakness
Gonadal dysfunction(Irregular period and erectile dysfunction)
Failure of children to grow tall despite excess weight
Osteoporosis
Impaired glucose tolerance
Skin that bruises easily
Purple striae on abdomen, breasts and thighs
179
What can cause Cushing's disease
1. Adrenal tumour (Adenoma or carcinoma)
2. Pituitary tumour (Cushing's Disease)
3. Exogenous Steroids
4. Ectopic ACTH syndrome
180
What are the ACTH dependent causes of Cushing's
1. Cushing's disease where there is bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma
2. Ectopic ACTH syndrome where there is an ACTH secreting tumour elsewhere in the body normally small cell lung cancer or carcinoid tumours
181
What are the ACTH independent causes of Cushing's Disease
1. Adrenal Adenoma which is a tumour of the adrenal gland which raises cortisol production
2. Iatrogenic causes such as administration of glucocorticoids such as prednisolone
182
Why is taking a careful drug history important in Cushing's disease
Because Cushing's can be caused by oral steroids
183
What are the diagnostic tests for Cushing's Disease
1. Urinary free cortisol
2. Overnight Dexamethasone suppression test
3. Late night serum/salivary cortisol
184
Describe the urinary free cortisol diagnostic test for Cushing's
Cortisol is bound to albumin normally so when the binding capacity is exceeded the cortisol will spill into the urine as is the case in Cushing's patients
185
Describe low dose dexamethasone suppression test for Cushing's patients
Give patient a synthetic steroid that suppresses the pituitary and adrenal gland and then measure the cortisol levels
In healthy patient the dexamethasone causes decreased ACTH and reduced cortisol
In healthy patient there will be no suppression
186
Once a diagnosis of Cushing's disease has been confirmed, what is the next test?
Measure plasma ACTH to determine whether it is ACTH independent or dependent Cushing's disease
If ACTH is undetectable = adrenal tumour is likely
If ACTH Is detectable then distinguish between ectopic and pituitary with high dose dexamethasone or corticotrophin releasing hormone test
187
Describe the corticotrophin hormone releasing test used to determine if ACTH depend t Cushing's has a pituitary or ectopic cause
Give CRH
| If cortisol rises then pituitary disease, if it doesn't then ectopic ACTH likely
188
What is the treatment for ACTH dependent Cushing's disease
Surgical removal of pituitary adenoma by trans-sphenoidal surgery or bilateral adrenalectomy
189
What is the treatment for Ectopic ACTH secreting tumour
Remove the tumour or bilateral adrenalectomy
190
What is the treatment for an adrenal carcinoma
Adrenalectomy
191
Define gigantism
Excessive growth hormone in children before the fusion of the epiphyses of the long bones
192
Define acromegaly
Excess growth hormone in adults
193
What are the causes of Acromegaly
Benign pituitary GH producing adenoma or ectopic carcinoid tumour
Increased GH from these tumours travels to the liver where it binds to receptors and increases insulin like growth factor which stimulates the skeletal and soft tissue growth giving rise to giant like appearance
194
What are the co-morbidities associated with acromegaly
```
Hypertension
Heart disease
Sleep apnoea
Cerebrovascular events
Arthritis
Insulin resistant diabetes
```
195
What are the symptoms of Acromegaly
1. Acral enlargement (increase feet and hand size)
2. Headaches
3. Excessive sweating
4. Maxillofacial changes
5. Acroparathesia (Tingling and numbness of extremities)
6. Arthralgias
7. Hypogonadal symptoms
196
What are the signs of acromegaly
1. Skin darkening
2. Coarsening of face and wide nose
3. Prognathism
4. Big supraorbital ridge
5. Fatigue
6. Deep voice
197
What diagnostic criteria can be used to exclude acromegaly diagnosis
Random GH <0.4ng/ml and normal IGF-I
198
Why is a high plasma value of GH non diagnostic in acromegaly
Because GH secretion is pulsatile and GH often increases in stress, puberty, sleep and pregnancy
199
What test is used to determine acromegaly
Glucose tolerance test can be diagnostic if there is no suppression of glucose as glucose should normally inhibit GH release
200
What are the objectives of treatment in acromegaly
1. restore basal GH and IGF-I to normal
2. Relieve symptoms
3. Reverse visual and soft tissue changes
4. Prevent further skeletal deformity
5. Normalise pituitary function
201
What are the surgical treatment options for acromegaly
Trans-sphenoidal surgery to remove tumour or correct tumour compression on surrounding structure (Optic chiasm)
202
Describe the radiological approaches for treatment of acromegaly
Stereotactic radiotherapy provides better tumour localisation and irradiation whilst reducing damage to normal brain tissue
(Gamma knife, proton beam, LINAC)
203
Describe the medical approaches to management of acromegaly
1. Somatostatin Analogues (IM Octreotide and IM Lanreotide) - inhibit GH release
2. GH receptor antagonist (Pegvisomant)
3. Dopamine Agonist (Oral Cabergoline or oral bromocriptine) - weakly control IGF-I
204
What are the effects of prolactin secretion
Lactation
| Inhibition of GnRH which reduces LH/FSH and thus reduced oestrogen and testosterone
205
What are the causes of prolactinoma
1. pituitary tumour resulting in excess prolactin secretion
2. Pituitary stalk damage causing less dopamine and less inhibition of prolactin
3. Antidopaminergic drugs
206
What is the clinical presentation of prolactinoma
1. Galactorrhoea/Amenorrhoea
2. Infertility
3. Low libido
4. Low testosterone
5. Erectile dysfunction and reduced facial hair
207
How do you diagnose prolactinoma
Measure basal prolactin levels and they will be very high
208
What are the treatment options for prolactinoma
medical better than surgical
1. Dopamine agonists ie. Oral cabergoline or oral bromocriptine
- Shrink the tumour
- Shrink macro adenoma
209
Where in the body is the main body clock
Suprachiasmatic nuclei
210
What is Addison's disease?
Destruction of the entire adrenal cortex resulting in mineralocorticoid, glucocorticoid and sex steroid deficiency
211
What are the causes of primary adrenal insufficiency (Where the adrenal gland doesn't work)
```
Addisons Disease
Autoimmune adrenalitis
TB
Congenital adrenal hyperplasia
Adrenoleukodystrophy
Mets (From lung, kidney and breast), haemorrhage and infection
```
212
What are the causes of secondary adrenal insufficiency (Lack of ACTH)
```
Hypopituitarism
Pituitary macroadenoma
Apoplexy
Hypophysitis
Mets, Haemorrhage and infection
Congenital
```
213
What are the causes of tertiary adrenal insufficiency (Suppression of HPA due to presence of exogenous glucocorticoids)
Steroids, inhalers, creams
214
Describe the pathophysiology of Addisons
Destruction of the entire adrenal cortex resulting in reduced glucocorticoid, mineralocorticoid and sex androgen production
Reduced cortisol levels feedback to increased CRH and ACTH production causing hyperpigmentation
215
Describe the clinical presentation of Addison's disease
```
Fatigue
Weight loss
Poor recovery from illness
Adrenal crisis
Headache
Lethargy
Vitiligo
Tanned skin
Pigmentation of skin
Diarrhoea
Postural hypotension
```
216
What are the diagnostic biochemical signs of Addison's
Hyponatraemia and hyperkalaemia due to decreased aldosterone
Hypoglycaemia due to low cortisol
Hypoaldosteronism
Eosinophilia
217
Describe the synACTHen test for diagnosing Addison's
Measure cortisol before and 30 mins after IM Tetracosactide
Addison's excluded if 30 min cortisol >550nmol/L
218
Other than synACTHen, name another test for diagnosing Addison's
```
Adrenal antibodies
(21 hydroxyls antibody detected in autoimmune adrenalitis)
```
219
What is the treatment for Addison's
IV hydrocortisone
| Steroids 3x daily to mimic circadian rhythm
220
What are the common symptoms of an adrenal crisis
```
Hypotension and cardiovascular collapse
Fatigue
Fever
Hypoglycaemia
Hyponatraemia and hyperkalaemia
```
221
What are the treatment options for adrenal crisis
Immediate hydrocortisone (100mg)
Fluid resuscitation
Fludrocortisone
222
T3 is known as
Triiodothyronine
223
T4 is known as
Thryoxine
224
Describe the physiology of thyroid hormone production
1. Circulating iodide actively transported with Na+ across basolateral membrane into follicular cells
2. Iodide ion transported to apical membrane of follicular cell and moved into colloid
3. In colloid, iodide oxidised to iodine which binds to tyrosine found on thyroglobulin molecules under the influence of thyroid peroxidase
4. Tyrosine can either bind one iodine (monoiodotyrosine) or two iodine (Diiodotyrosine)
5. When thyroid is stimulated, T1 and T2 molecules are cleaved from tyrosine backbone and join to create T3 to T4
6. For thyroid hormones to be secreted into the blood, extensions of the colloid facing portion of follicular cells engulf portions of colloid by endocytosis
7. TSH from pituitary stimulates movement of T3 and T4 containing colloid into secretory cells
8. Iodated thyroglobulin is brought into contact with lysosomes and proteolysis of the thyroglobulin results in release of T3 and T4 which are able to diffuse out of the follicular cells into the blood
225
Which is more prevalent, hyper or hypothyroidism
Hypothyroidism
226
What is a goitre
Swelling of the thyroid gland that causes a palpable lump in front of the neck that moves up and down during swallowing
227
Why does a goitre develop?
TSH stimulation which causes the thyroid to grow in size
228
What is the most common presentation of thyroid disease
Goitre
229
What are the 2 main causes of goitre
1. Hyperthyroidism - Graves disease where there is excessive TSH receptor stimulation causing thyroid to produce more hormones and grow larger
2. Hypothyroidism -
Pituitary detects low thyroid levels so produces more TSH which stimulates TSH receptors on the thyroid resulting in thyroid enlargement
230
Define thyrotoxicosis
Excess thyroid hormone in the blood
231
What are the 3 mechanisms for increased production of thyroid hormone
1. Overproduction of thyroid hormones (Hyperthyroidism)
2. Leakage of pre-formed thyroid hormone (Can occur if follicular cells are destroyed by infection or autoimmune)
3. Ingestion of excess hormone
232
What are the 7 causes of hyperthyroidism?
1. Grave's disease
2. Toxic multi nodular goitre
3. Toxic Adenoma (Benign)
4. Ectopic thyroid tissue
5. Exogenous Iodine (T4 excess)
6. De Quervain's thyroiditis (Transient hyperthryoidism resultingg from acute inflammation of thyroid following viral infection)
7. Drug induced (Amiodarone iodine, lithium)
233
What are the causes of primary hypothyroidism
1. Primary atrophic hypothyroidism (Autoimmune)
2. Hashimoto's thyroiditis (Autoimmune)
3. Post-partum thyroiditis
3. Iodine deficiency
4. Post-thyroidectomy
5. Drug induced (Lithium, carbimazole, amiodarone)
234
What is the cause of secondary hypothyroidism
Hypopituitarism - reduced TSH from anterior pituitary
235
What is Grave's disease?
Autoimmune induced excess production of thyroid hormone
236
Describe the pathophysiology of Grave's disease
1. Serum antibodies (TSHR-Ab) bind to TSH receptors in the thyroid
2. Stimulates thyroid hormone production
3. Results in excess secretion of thyroid hormones and hyperplasia of thyroid follicular cells
237
What are the risk factors for thyroid autoimmunity
1. Female
2. Genetic - association with HLA-B8, DR3 and DR2
3. Smoking
4. Stress
5. High iodine intake
238
What autoimmune diseases are associated with thyroid autoimmunity
```
T1DM
Addison's Disease
Pernicious Anaemia
Vitiligo
Myasthenia Gravis
```
239
What is the clinical presentation of Grave's Disease
Swelling in neck
Red, puffy protruding eyes
Graves Opthalmopathy
240
What is Grave's Opthomalopathy
Retro-orbital inflammation and swelling of extra ocular muscles
- eye discomfort
- increased tear production
- Photophobia
- Exophthalmos
- Redness
- lid lag stare
241
What is the clinical presentation of hyperthyroidism
| Everything goes up
```
Weight loss
increased appetite
irritable
goitre
Tachycardia
Hyperphagia
Anxiety
Tremor
Heat intolerance
sweating
Diarrhoea
Lid lag and stare
menstrual disturbance
palpitations
Irritability
Hyperkinesis
```
242
What are the diagnostic tests for hyperthyroidism
Thyroid function tests
Thyroid antibodies
Isotope uptake scan
243
What would a thyroid function test result be for someone with primary hyperthyroidism
increased free T3
Increased free T4
Suppressed TSH because high T3 and T4 negatively feedback to the anterior pituitary to turn of TSH production
244
What would the thyroid function test result be for someone with secondary hyperthyroidism
Increased free T3
increased free T4
Innapropriately high TSH because the issue is with the pituitary
245
What is the treatment for hyperthyroidism
1. Beta blockers (propranolol) for symptoms
2. Anti-thyroids - thionamides
(Propylthiouracil - stops T4 to T3 conversion)
(Carbimazole - blocks thyroid hormone biosynthesis by blocking TPO)
3. Radioactive iodine
4. Surgery - total thyroidectomy
246
What are the 2 strategies for thionamide administration?
(i) Titration - give carbimazole for 4 weeks then reduce dose according to thyroid function tests
(ii) Block-replace therapy - carbimazole + thyroxine
247
What are the side effects of thionamides
AGRANULOCTOSIS (Low WBC) (sore throat, mouth ulcers, fevers)
```
Rash
Arthralgia
Hepatitis
Neuritis
Vasculitis
```
248
What are the effects of 131 Iodine radiotherapy
Emits B particles that result in ionisation of thyroid cells causing direct damage so thyroid hormone production is decreased
249
What is primary hypothyroidism
Underactivity of the thyroid due to disease of the thyroid gland
250
What is secondary hypothyroidism
Underactivity of the thyroid gland due to hypothalamus or pituitary disease
251
What are the 5 main causes of primary hypothyroidism
```
Primary atrophic hypothyroidism
Hashimoto's thyroiditis
Iodine deficiency
Post-thyroidectomy
Lithium
```
252
What are the clinical symptoms of hypothyroidism
```
Fatigue
Weight gain
Cold intolerance
Constipation
Goitre
Hoarse voice
Menstrual disturbance (Menorrhagia- heavy bleeding)
Muscle cramps
Tired
```
253
What are the clinical signs of hypothyroidism (BRADYCARDIC)
```
Bradycardia
Ataxia
Dry thinned hair/skin
Yawning
Cold hands
Ascites
Round puffy face
Defeated demeanour
Immobile
Congestive cardiac failure
```
254
Would would the thyroid function test result be for someone with primary hypothyroidism
Increased TSH but low T3 and T4
255
What would the thyroid function test result be for someone with secondary hypothyroidism
TSH inappropriately low for reduced T4/T3
256
What is the treatment for hypothyroidism
Life long hormone replacement therapy - Oral levothyroxine
Dose needs to be titrated until TSH normalises in primary hypothyroidism - check T4 levels 6-8 weeks later
Secondary hypothyroidism then monitor T4 because TSH will always be low
257
Where is vasopressin produced
paraventricular nucleus
258
Where is oxytocin produced
Supra-optic nucleus
259
Describe osmotic regulation
Osmoreceptor sends afferent projections to the PVN and SON sensing the osmolality of the blood - this determines whether they fire and release vasopressin or not
260
What receptor does vasopressin bind to
```
GPCR V1a (Vasculature)
GPCR V2 ( Renal collecting tubes)
GPCR V1b (Pituitary)
```
261
The release of vasopressin is controlled by what 2 factors
(i) Osmoreceptors in the hypothalamus (Day to day)
| ii) Baroreceptors in the brainstem and great vessels (Emergency
262
Describe distribution of fluid in the body
Extracellular (14L)
- Intravascular (3.5L)
- INterstitial (10.5L)
Intracellular (28L)
263
What ions are mostly prevalent In the extracellular fluid
Sodium
Chloride
Bicarbonate
264
What ions are most prevalent in the intracellular fluid
Potassium
Magnesium
Phosphate
265
Describes what happens in terms of fluid regulation when there is excess water
1. Fall in plasma osmolality and influx of water into cells increasing intracellular water content
2. This reduces thirst and suppresses the release of vasopressin tush's decreasing water intake and increasing water excretion
3. Overall effect is decrease in amount of water in the body
266
What are the insensible water losses from the body each day
(i) 0.1L from stool
(ii) 0.1L from sweat
(iii) 0.3L from respiration
= 500ml total
267
Describe the mechanism of action of vasopressin
1. Vasopressin binds V2 receptors stimulating intracellular cascade
2. Binding V2 receptors leads to activation of Gs which activates adenylate cyclase
3. Leads to increased formation of cAMP
4. cAMP activates pKA which phosphorylates micro tubular subunits that aggregate to form AQP2
5. AQp2 inserted into apical membrane
6. AQP2 enables water to be reabsorbed and returned to bloodstream
7. When the stimulus is removed, AQP2 is removed from apical membrane by endocytosis
268
Define Osmolality
Concentration in the plasma mOsmol/Kg)
269
What is a normal plasma osmolality?
282-295mOsmol/kg
270
How do you calculate plasma osmolality
2x Na+ conc + glucose conc + urea conc
271
A lack of vasopressin is associated with what condition
Cranial diabetes insipidus
272
Resistance to the action of vasopressin is associated with what condition
Nephrogenic diabetes insipidus
273
Too much vasopressin release when it shouldn't be released is associated with what condition
Syndrome of inappropriate anti-diuretic hormone secretion (SIADH)
274
What are the three most common symptom seen in diabetes insipidus
Polyuria
Polydipsia
No glycosuria
275
How do we diagnose diabetes insipidus
Measure 24 hour urine volume =
DI unlikely if dilute urine volume <3L/day
Water deprivation test - urine will not concentrate when asked not to drink
Serum Oslo >300 and urine Oslo <200 is consistent with DI
Normonatraemia or hypernatraemia
276
What are the 6 acquired causes of cranial diabetes insipidus
1. Idiopathic
2. Tumours
3. Trauma
4. Infections
5. Vascular
6. Inflammatory
277
What tumours can cause acquired diabetes inspidus
Craniopharyngioma
Germinoma
Metastases
Never an anterior pituitary tumour
278
What infections can cause acquired diabetes inspidus
TB
Encephalitis
Meningitis
279
What vascular conditions can cause acquired diabetes insipidus
Aneurysm
Infarction
Sheenan's
Sickle Cells
280
What inflammatory conditions can cause acquired diabetes insipidus
Neurosarcoidosis
Langerhans Histiocytosis
Guillain Barre
Granuloma
281
What are the primary causes of diabetes insipidus
Genetic
- Wolfram syndrome
Developmental
- Septo-optic dysplasia
282
What is the pathophysiology of nephrogenic diabetes insipidus
In X-linked there is a V2 receptor defect
In autosomal there is an aquaporin 2 defect
283
What are the causes of nephrogenic diabetes insipdus
```
Osmotic diuresis (Diabetes)
Drugs (Lithium, tetracycline)
Chronic renal impairment
Post obstructive nephropathy
Metabolic - hypercalcaemia/hypokalaemia
Renal infiltration (Amyloid)
```
284
How does the water deprivation test work
Don't give the patient water - if they have DI they will still pass out dilute urine and their urine osmolality will increase
Give 2ug of desmopressin that acts at V2 receptor - kidney can respond in cranial but not in nephrogenic
285
How do we manage cranial diabetes insipidus?
Treat underlying condition
| Desmopressin - high activity at the V2 receptor analogue (Tablets, nasal spray or injection)
286
How do we manage nephrogenic diabetes insipidus?
Avoid precipitating drugs
| Free access to water alongside high dose of desmopressin
287
What is normal serum sodium level
Between 135 and 144mmol
288
What is the definition of hyponatraemia
Serum sodium <135mmol
| Biochemically severe = serum sodium <125mmol
289
Name 7 moderate symptoms of hyponatraemia
1. Headache
2. irritability
3. Nausea and vomiting
4. Mental slowness
5. Unstable gait
6. Confusion and delirium
7. Disorientation
290
Name 3 severe symptoms of hyponatraemia
1. Stupor/coma
2. Convulsions
3. Respiratory arrest
291
What are the causes of hyponatraemia
Hypovolaemia
| Hypervolaemia
292
What is syndrome of innappropriate secretion of ADH (SIADH)
Continued ADH secretion despite plasma being dilute leading to water retention, excess blood volume and hyponatraemia, concentrated urine
293
What are the 4 different causes of SIADH (Name a few for each)
1. CNS Disorders (Guillain barre, meningitis, encephalitis)
2. Respiratory Causes (Pneumonia, TB, Severe asthma)
3. Tumours (Lung carcinoma, prostate, thymus)
4. Drugs (Chlorpropamide, Carbamazepine, SSRIs)
294
What diagnostic signs are needed to diagnose SIADH?
```
Low serum sodium (<135mmol/L)
High urine sodium
Low plasma osmolality
High urine osmolality >100mOsm/Kg
Normal circulating blood volume
```
295
How do you manage SIADH
1. treat the underlying cause
2. Restrict fluid intake <1L/24 hour
3. Give oral demeclocycline which induces nephrogenic diabetes (Inhibits ADH action on kidneys)
4. If sodium <115mmol an patient is fitting then saline
5. Selective V2 receptor oral antagonist (Tolvaptan) which promotes water excretion
296
What are the different types of pituitary mass lesion
1. Non functioning adenoma (Prolactinoma)
2. Malignant pituitary tumours
3. Metastasis in pituitary
4. Pituitary cysts (Rathke's cleft cyst)
5. Developmental abnormalities (Craniopharygioma)
6. Primary CNS tumours (Optic glioma)
7. Vascular tumours (Hemangioblastoma)
8. Malignant systemic disease (Hodgkins and non Hodgkins lymphoma)
9. Granulomatous Disease (Neurosarcoidosis and tuberculosis)
297
What is a craniopharyngioma
Arises from the squamous epithelial remnants of Rathke's pouch
Benign tumour that does not infiltrate surrounding tissues
298
What are the symptoms of craniopharyngioma
```
Raised ICP
Visual disturbance
Growth failure
Pituitary hormone deficiency
Weight increase
```
299
What is Rathke's Cyst
Derived remnants of Rathke's pouch
300
What are the symptoms of Rathke's cyst
Headache
Amenorrhoea
Hypopituitarism
Hydrocephalus
301
What is a meningioma?
Commonest tumour of region after pituitary adenoma
302
What are the symptoms associated with meningioma
Visual disturbance, endocrine dysfunction
303
What is lymphocytic adenohypophysitis
Inflammation of the pituitary gland due to an autoimmune reaction
304
What are the local mass effect of a pituitary tumour
1. Visual defects (Bitemporal hemianopia)
2. CSF rhinorrhoea
3. Headaches
4. Cranial nerve palsy
305
Raised TSH and low T4 would be suggestive of what condition
Primary hypothyroidism
306
Low T4 with normal or low TSH is suggestive of what condition
Hypopituitarism
307
Suppressed TSH with High T4 is suggestive of what condition
Grave's disease
308
High T4 with normal or high TSH is suggestive of what condition
TSHoma
309
What is the definition of diabetes?
Symptoms and random plasma glucose >11mmol/L
Fasting plasma glucose >7mmol
No symptoms need oral glucose tolerance test fasting >7 or 2h value >11mmol/l
HbA1c 48mmol/mol
310
What are the 6 common presenting features of diabetes?
1. Thirst
2. Polyuria
3. Weight loss and fatigue
4. Hunger
5. Puritis vulvae and balanitis
6. Blurred vision
311
What features would be suggestive of someone with type 1 diabetes
1. Onset in childhood (5-15yr)
2. Lean body hiatus
3. Acute onset of osmotic symptoms
4. Prone to ketoacidosis
5. higher levels of islet autoantibodies
312
What are the clinical features of newly diagnosed T1 diabetes
1. Weight loss
2. Short history of severe symptoms
3. urinary ketones
313
What features would be suggestive of someone with type 2 diabetes
1. Present in over 30's
2. Onset is gradual
3. Family history
314
Type 1 diabetes is associated with what autoimmune conditions
Hypothyroidism
Addison's
Coeliac Disease
315
What happens if T1 diabetes is missed?
Insulin deficiency causes continued fat breakdown leading to formation of glycerol and free fatty acids
FFA's impair glucose uptake and are transported to the liver to provide energy for gluconeogenesis
FFA are oxidised to form ketone bodies (Beta hydroxybutyrate, acetone, acetoacetate)
Rising glucose and ketones escape into the urine and lead to osmotic diuresis and falling circulating volume
Ketones are weak organic acids and cause anorexia and vomiting and eventually lead to circulatory collapse and death
316
What is the definition of diabetic ketoacidosis
1. Hyperglycaemia (Plasma glucose <50mmol/l)
2. Raised plasma ketones (Urine ketones >2+)
3. Metabolic Acidosis (Plasma bicarbonate <15mmol/l
317
What are the 4 causes of diabetic ketoacidosis
1. Unknown
2. Intercurrent illness (infection, MI)
3. Treatment errors (Stop/reduce insulin)
4. Previously undiagnosed diabetes
318
What are the symptoms of DKA
1. Develops over days
2. Polyuria and polydipsia
3. Nausea and vomiting
4. Weight loss
5. weakness
6. Abdominal pain
7. Drowsiness/confusion
319
What are the signs of DKA
1. Hyperventilation
2. Dehydration (Loss of 5-6L)
3. Hypotension
4. Tachycardia
5. Coma
320
What is the biochemical diagnosis of DKA
1. Hyperglycaemia (<50mmol/l)
2. K+ high on presentation followed by drop due to acute K+ shift out the cell with acidosis then driven back into cells with drop in insulin
3. HCO3- <15mmol/l
4. Urea and creatine raised due to pre-renal failure
5. Urinary ketones >2+
6. Blood ketones >3.0
321
What is the management for diabetic ketoacidosis
1. Rehydration (3L in first 3hrs)
2. Insulin
3. Replace electrolytes
4. Treat underlying cause
5. Treatment must be started without delay
6. Follow DKA hospital protocol
322
What are the potential complications of DKA
(i) Cerebral oedema in children
(ii) Adult respiratory distress syndrome
(iii) Thromboembolism
(iv) Aspiration Pneumonia
323
What are the three microvascular complications of diabetes
1. Nephropathy
2. Neuropathy
3. Retinopathy
324
What symptoms might you see if you give someone too much insulin
1. Shaking
2. Fast heartbeat
3. Sweating
4. Dizziness
5. Anxious
6. Hunger
7. Impaired vision
8. weakness fatigue
9. Headache
10. Irritable
325
What is maturity onset diabetes of the young (MODY)
Autosomal dominant non insulin dependent diagnosed in <25yr
Single gene defect alters beta cell function
326
What is transcription factor MODY
Where hepatic nuclear factor mutations alter insulin secretion and reduce beta cell proliferation
327
Which patients are likely to be MODY
Pateitns with parents with diabetes
Absence of islet autoantibodies
Evidence of non insulin dependence
328
What is permanent neonatal diabetes
Diagnosed <6 months
Mutations in the Kir6.2 and SUR1 subunits of beta ATP sensitive K+ channel - mutations prevent the closure of the channel so beta cells unable to secrete insulin
329
What is maternal inherited diabetes and deafness
Result of mutations in mitochondrial DNA resulting in loss of beta cell mass
Similar presentation to T2 diabetes
330
Name 5 diseases of the exocrine pancreas
1. Inflammation
2. Hereditay hemochromatosis (Excess iron deposition)
3. Deposition (Amyloidosis and cystinosis)
4. Pancreatic Neoplasia
5. Cystic fibrosis (Viscous secretions lead to duct obstruction)
331
What are the endocrine causes of diabetes
1. Acromegaly
2. Cushing's syndrome
3. Phaechromocytoma
332
What drugs can induce diabetes
Glucocorticoids
Thiazides
Protease inhibitors
Antipsychotics
333
Define puberty
Physical, morphological and behavioural changes as gonads switch from infantile to adult forms
334
What are the definitive signs of puberty in the male and female
Male = first ejaculation
Female = menarche
335
What are secondary sexual characteristics in girls
Ovarian oestrogen regulate the growth of breast and genitalia
Ovarian and adrenal androgens control pubic hair and axillary hair
336
What are the secondary sexual characteristics in boys
Testicular androgens lead to external genitalia and pubic hair growth growth and enlargement of laryngeal muscles
337
What is thelarche
Breast development induced by oestrogen
338
How does the uterus change during puberty
Tubular to pear shape
Increase in length and volume
Endometrium thickness increases
339
How do the ovaries change during puberty
Increase in volume
| Become multi cystic
340
How does the vagina change during puberty
```
Red colour Dullens
Epithelium thickens
Becomes acidic
Produces secretions
Increases in length
```
341
What are the effects of oestrogen on the female external genitalia
```
Labia minora and major increase in size and thickness
Rugation
Hymen thickens
Clitoris enlarges
Vestibular glands begin secretion
```
342
Define precocious puberty
Onset of secondary sexual characteristics before 8yrs (Girl) 9yrs (boy)
343
Defined delayed puberty
Absence of secondary sexual characteristics by 14 yrs (girl) 16yrs (boy)
344
In precocious puberty, brain tumours are most commonly seen in boys or girls
Boys
345
How would you determine if an individual has precocious puberty or precocious pseudo puberty
GnRH test - inject GnRH and measure after the 30-60 minutes
HPG axis should become activated causing a rise in LH and FSH - in pseudo puberty, there will be no rise in Lh or FSH
346
what are the causes of true precocious puberty
Idiopathic
CNS tumours (Optic glioma)
CNS disorders (Encephalitis)
Psychosocial
347
What are the causes of precocious pseudo puberty
Increased androgen secretion
Gonadotrophin secreting tumours
Oestrogen secreting neoplasm
348
What are the indications in girls for investigation of delayed puberty
(i) Lack of breast development by 13 years
(ii) More than 5 years between breast development and menarche
(iii) Lack of pubic hair by 14
(iv) Absent menarche by 15-16
349
What are the indications in boys for the investigation of delayed puberty
(i) Lack of testicular enlargement by age 14
(ii) Lack of pubic hair by 15
(iii) More than 5 years to complete genital enlargement
350
Describe primary hypogonadism in the female
Ovary fails so oestrogen drops - lack of feedback leads to LH and FSh increase
351
Describe secondary hypogonadism in the female
Hypothalamus and pituitary fail so LH and FSH are low meaning there is no response to feedback leading to oestrogen decrease
352
Describe primary hypogonadism in the male
testis fail leading testosterone to drop and the lack of feedback causes Lh and FSH to rise
353
Describe secondary hypogonadism in the female
Hypothalamus and pituitary fail leading to low FSH and LH and no response to feedback so testosterone decreases
354
Give a cause of primary hypogonadism.
Klinefelter's syndrome - extra X chromosome
355
What is the affect of primary hypogonadism on testosterone and FSH/LH levels?
Testosterone will be low.
| - FSH/LH will be high.
356
What is the affect of hypopituitarism on testosterone and FSH/LH levels?
- Testosterone will be low.
| - FSH/LH will be low.
357
When should serum testosterone be measured?
At 9am due to circadian rhythm.
358
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.
359
What is the treatment for hypogonadism?
Testosterone gel/injection.
360
What syndrome is characterised by a congenital deficiency of GnRH?
Kallmann's syndrome.
361
Are the levels of oestradiol and FSH/LH low or high before puberty?
Before puberty there are very low levels of these hormones in the serum.
362
What is the affect of primary ovarian failure on oestradiol and FSH/LH levels?
- FSH/LH is high.
| - Oestradiol is low.
363
What is the function of ADH?
It acts on the collecting ducts of the nephron and increases insertion of aquaporin 2 channels -> there is H2O retention.
364
Which has a longer half life, triiodothyronine or thyroxine?
Thyroxine has a half life of 5-7 days whereas triiodothyronine has a half life of only 1 day.
365
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 and so no negative feedback.
366
What would a low TSH tell you about the action of the thyroid?
A low TSH indicates an over-active thyroid. Lots of T4 and T3 is being produced and so there is more negative feedback on the pituitary and less TSH.
367
Give 3 functions of thyroid hormones (T3/4).
1. Food metabolism.
2. Protein synthesis.
3. Increased sympathetic action e.g. CO and HR.
4. Heat production.
5. Needed for growth and development.
368
Give 3 functions of cortisol in response to stress.
1. Mobilises energy sources -> lipolysis, gluconeogenesis and protein break down.
2. Vasoconstriction.
3. Suppresses inflammatory and immune repsonses.
4. Inhibits non-essential functions e.g. growth and reproduction.
369
Briefly describe the mechanism of LH and FSH.
Hypothalamus -> GnRH -> AP -> FSH/LH -> ovaries/testes.
FSH acts on granulosa cells to produce oestrogen and sertoli cells to stimulate spermatogenesis. LH acts on theca cells to produce androgens or leydig cells to produce testosterone
370
What cells does FSH act on?
In the ovaries: granulosa cells.
| - In the testes: sertoli cells
371
What cells does LH act on?
In the ovaries: theca cells.
| - In the testes: leydig cells.
372
What is the function of theca cells?
Theca cells are stimulated by LH to produce androgens that diffuse into granulosa cells to be converted into oestrogen.
373
What is the function of granulosa cells?
Granulosa cells are stimulated by FSH to convert androgens into oestrogen using aromatase.
374
What is the function of sertoli cells?
Sertoli cells produce MIF (mullerian inhibiting factor) and inhibin and activin which acts on the pituitary gland to regulate FSH.
375
What is the function of leydig cells?
Leydig cells are stimulated by LH to produce testosterone.
376
What is the function of IGF-1?
It induces cell division, cartilage and skeletal growth and protein synthesis
377
Describe growth hormone secretion from the anterior pituitary.
It is secreted in a pulsatile fashion and increases during deep sleep
378
What investigations might you do on someone who you suspect has acromegaly?
1. Plasma GH levels can exclude acromegaly - not diagnostic!
2. Serum IGF-1 levels raised.
3. Oral glucose tolerance test - diagnostic!
4. MRI of pituitary.
379
Give 3 potential complications of trans-sphenoidal surgical resection for the treatment of acromegaly.
1. Hypopituitarism.
2. Diabetes insipidus.
3. Haemorrhage.
4. CNS injury.
5. Meningitis.
380
Hypothyroidism: name 3 anti-bodies that may be present in the serum in someone with autoimmune thyroiditis.
1. TPO (thyroid peroxidase).
2. Thyroglobulin.
3. TSH receptor.
381
Give 2 examples of iatrogenic causes of hypothyroidism.
1. Thyroidectomy.
| 2. Radioiodine therapy.
382
Name 3 drugs that can cause hypothyroidism.
1. Carbimazole (used to treat hyperthyroidism).
2. Amiodarone.
3. Lithium.
383
Why can amiodarone cause hypo/hyperthyroidism?
Because it is iodine rich.
384
Give 5 causes of thyrotoxicosis.
Thyrotoxicosis - excess thyroid hormone due to any cause:
1. Increased production e.g. Grave's, toxic adenoma.
2. Leakage of T3/4 due to follicular damage.
3. Ingestion.
4. Thyroiditis.
5. Drug induced
385
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).
386
With what disease would you associated pre-tibial myxoedema and thyroid acropachy?
Grave's disease.
387
What would you see histologically in someone with Grave's disease?
Lymphocyte infiltration and thyroid follicle destruction.
388
Give 3 potential complications of a partial thyroidectomy.
1. Bleeding.
2. Hypocalcaemia.
3. Hypothyroidism.
4. Recurrent laryngeal nerve palsy
389
Give 5 metabolic changes that occur in pregnancy.
1. Increased EPO, cortisol and NAd.
2. High CO.
3. High cholesterol and triglycerides.
4. Pro thrombotic and inflammatory state.
5. Insulin resistance.
390
Give 5 gestational syndromes.
1. Pre-eclampsia.
2. Gestational diabetes.
3. Obstetric cholestasis.
4. Gestational thyrotoxicosis.
5. Postnatal depression.
6. Post partum thyroiditis
391
At what week are foetal thyroid follicles and T4 synthesised?
Week 10.
392
Why can hCG activate TSH receptors and cause hyperthyroidism?
HCG and TSH are glycoprotein hormones with very similar structures. HCG can therefore activate TSH receptors
393
Is hypothyroidism or thyrotoxicosis more common in pregnancy?
Hypothyroidism is more common in pregnancy.
394
How can you differentiate between Grave's disease and gestational thyrotoxicosis?
- Grave's: 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 gravidarum associated. No goitre or TSH-R antibodies.
395
Give 3 potential consequences of untreated hypothyroidism in pregnancy.
1. Gestational hypertension.
2. Placental abruption.
3. Post partum haemorrhage,
4. Low birth weight.
5. Neonatal goitre.
396
Give 3 potential consequences of untreated hyperthyroidism in pregnancy.
1. Intra-uterine growth restriction.
2. Low birth weight.
3. Pre-eclampsia.
4. Risk of still birth/miscarriage
397
How many carbon precursors are needed for gluconeogenesis?
3.
398
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would the results of the oral glucose tolerance test be if someone was diabetic?
Fasting plasma glucose >7mmol/L and 2-hour value >11mmol/L.
399
What might someone's HbA1c be if they have diabetes?
>48mmol/mol.
400
What is the affect of cortisol on insulin and glucagon?
Cortisol inhibits insulin and activates glucagon.
401
T1DM is characterised by impaired insulin secretion. Describe the pathophysiological consequence of this.
Severe insulin deficiency -> glycogenolysis/gluconeogensis/lipolysis all not suppressed AND reduced peripheral glucose uptake -> hyperglycaemia and glycosuria.
Perceived stress -> cortisol and Ad secretion -> catabolic state -> increased plasma ketones.
402
Describe the pathophysiology of diabetic ketoacidosis.
No insulin -> lipolysis -> FFA's -> oxidised in liver -> ketone bodies -> ketoacidosis.
403
Name 3 ketone bodies.
- acetoacetate.
- acetone.
- beta hydroxybutyrate.
404
What is the affect of primary adrenal insufficiency on cortisol and ACTH levels?
- Cortisol is low.
| - ACTH is high.
405
What is the affect of hypopituitarism on cortisol and ACTH levels?
- Cortisol is low.
| - ACTH is low.
406
What can lead to elevated levels of prolactin?
1. Stress.
2. Drugs.
3. Pressure on the pituitary stalk.
407
Give 5 signs of diabetes insipidus.
1. Excessive urine production (>3L/24h).
2. Very dilute urine - <300 mOsmol/Kg.
3. Severe thirst.
4. Hypernatraemia.
5. Dehydration.
408
What is the treatment for neurological diabetes insipidus?
Desmopression.
409
Give 4 causes of polyuria.
1. Hypokalaemia.
2. Hypercalcaemia.
3. Hyperglycaemia.
4. Diabetes insipidus.
410
What is Cushing's disease?
A set of signs/symptoms resulting from inappropriate ACTH secretion from the pituitary.
ACTH dependent.
411
What is the treatment for Cushing's syndrome?
1. Surgical removal of pituitary tumours.
| 2. Drugs to inhibit cortisol synthesis e.g. metyrapone, ketoconazole.
412
Give 3 symptoms of SIADH.
1. Anorexia.
2. Nausea.
3. Malaise.
4. Headache.
5. Confusion.
413
What is Conn's syndrome?
Primary hyperaldosteronism - high aldosterone levels independent of RAAS activation -> H2O and sodium retention and potassium excretion.
414
What are the 2 main signs of Conn's syndrome?
1. Hypertension.
2. Hypokalaemia.
Sodium will be normal or slightly raised.
415
Give 3 symptoms of Conn's syndrome. A deficiency in which electrolyte causes these symptoms?
1. Muscle weakness.
2. Tiredness.
3. Polyuria.
Due to potassium deficiency - hypokalaemia.
416
What can cause Conn's syndrome?
Adrenal adenoma.
417
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 zona glomerulosa.
2. Renin is reduced - synthesised by the juxta-glomerular cells.
418
What investigations might you do in someone to confirm a diagnosis of Conn's syndrome?
1. Bloods - U+E, renin (low) and aldosterone (high).
2. Plasma aldosterone renin ratio can be used as an initial screening test - raised ratio indicates the need for further tests.
419
Give 4 ECG changes that 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.
420
What is the treatment for Conn's syndrome?
1. Laparoscopic adrenalectomy.
| 2. Spironolactone (aldosterone antagonist).
421
Describe the treatment for hyperparathyroidism.
1. High fluid intake, low calcium diet.
2. Excision of adenoma.
3. Correct underlying cause.
4. Parathyroidectomy.
422
Give 5 symptoms of hypoparathryoidism.
Hypoparathyroidism -> hypocalcaemia:
1. Spasm.
2. Paraesthesia around mouth and lips.
3. Anxious/irritable.
4. Seizures.
5. Increased muscle tone.
6. Confusion.
7. Dermatitis.
8. Impetigo herpetiformis.
9. QT prolongation
423
What is the treatment for hypoparathyroidism?
Calcium supplements.
424
Give 5 causes of hypocalcaemia.
1. Dietary insufficiency.
2. Anticonvulsant therapy.
3. CKD.
4. Vitamin D deficiency.
5. Osteomalacia.
6. Hypoparathyroidism.
425
Give 2 ECG changes that you might see in someone with hyperparathyroidism.
Hyperparathyroidism -> hypercalcaemia and so:
1. Tall T waves.
2. Shorted QT interval.
426
Give 2 ECG changes that you might see in someone with hyoparathyroidism.
Hyoparathyroidism -> hypocalcaemia and so:
1. Small T waves.
2. Long QT interval
427
What is phaeochromocytoma?
A rare catecholamine secreting tumour in the adrenal medulla.
428
Give 5 symptoms of phaeochromocytoma.
Classic triad of:
1. Headache.
2. Sweating.
3. Tachycardia.
Also:
4. Hypertension.
5. Palpitations.
6. Tremor.
7. Arrhythmia.
8. Confusion.
429
What investigations might you do in order to diagnose someone with having a phaeochromocytoma?
Bloods - raised WCC, increased plasma metadrenaline and normetadrenaline.
430
What is the treatment for phaeochromocytoma?
1. Alpha blocker e.g. phenoxybenzamine.
2. Beta blockers.
3. Surgical resection of tumour.
431
What is the major concern in someone with phaeochromocytoma?
Phaeochromocytomare are a dangerous but treatable cause of hypertension.
432
Describe the different types of subcutaneous insulins that can be given to people with T1DM.
1. Ultra-fast acting e.g. Humalog - taken before eating in conjunction with a long-acting insulin at night.
2. Long-acting insulin e.g. insulin glargine - taken before going to bed.
3. Pre-mixed insulin e.g. NovoMix - taken twice daily.
433
What is adrenal insufficiency?
Adrenocortical insufficiency resulting in a reduction of mineralocorticoids, glucocorticoids and androgens.
434
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.
435
What investigations might you do in someone who you suspect has adrenal insufficiency?
1. Bloods - FBC, U+E (↓Na+ and ↑K+ - due to ↓ aldosterone - ↑Ca2+, ↑Urea).
2. ↓ Glucose.
3. ACTH stimulation test - Addison's will not respond.
436
Give 3 causes of hypokalaemia.
1. Diuretics.
2. D+V.
3. Conn's syndrome.
4. Insulin.
437
Give 5 symptoms of hypokalaemia.
1. Muscle weakness.
2. Hypotonia.
3. Hyporeflexia.
4. Palpitations.
5. Arrhythmia.
6. Nausea and vomiting.
7. Cramps.
438
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.
439
Give 3 causes of hyperkalaemia.
1. AKI.
2. NSAIDs.
3. Metabolic acidosis.
4. K+ sparing diuretics.
440
Give 3 symptoms of hyperkalaemia.
1. Weakness.
2. Palpitations.
3. Tachycardia.
4. Chest pain.
441
What ECG changes might you see in someone with hyperkalaemia?
1. Tall tented T waves.
2. Wide QRS.
3. Small P waves.
442
Give 3 causes of hypercalcaemia.
1. Hyperparathyroidism.
2. Hypercalcaemia of malignancy.
3. Vitamin D toxicity.
4. Myeloma.
443
How can hypercalcaemia be treated?
1. IV normal saline.
2. IV furosemide.
3. IV calcitonin.
444
Give 4 potential complications of untreated DKA.
1. Oedema.
2. Adult respiratory distress syndrome.
3. Aspiration pneumonia.
4. Thromboembolism.
5. Death.
445
Give 3 endocrine diseases that can cause diabetes.
1. Cushing's.
2. Acromegaly.
3. Phaeochromocytoma.
446
What class of drugs can cause diabetes?
1. Steroids.
2. Thiazides.
3. Anti-psychotics.
447
Give 3 secondary causes of adrenal insufficiency
.1. Hypopituitarism.
2. Withdrawal from long term steroids.
3. Infiltration.
4. Infection.
5. Radiotherapy.
448
Define hyponatraemia.
Serum sodium <135mmol/L.
449
Give 3 signs of hyponatraemia.
1. Anorexia.
2. Confusion.
3. Headache.
4. Lethargy.
5. Weakness.
450
What is the treatment for acute hyponatraemia?
Give a bolus dose of saline.
451
Would you associate SIADH with hyponatraemia or hypernatraemia?
Hyponatraemia <135mmol/L.
452
Would you associate SIADH with plasma hypo-osmolality or hyper-osmolality?
Plasma hypo-osmolality <275mOsm/Kg.
453
Would you associate SIADH with a high or low urine osmolality?
High urine osmolality.
454
What scale is used to describe physical development based on external sex characteristics?
Tanner scale.
455
Describe the 3 stages of thelarche.
1. Ductal proliferation.
2. Adipose deposition.
3. Enlargement of areola and nipple.
456
What is adrenarche?
Maturation of the adrenal gland - the development of the zona reticularis cells.
Peri-pubertal adrenal androgen production -> body odour and mild acne.
457
What must you rule out as a cause of precocious puberty in boys?
Brain tumour!
458
What is the treatment for precocious puberty?
GnRH super agonist to suppress pulsatility of GnRH secretion
459
What is the most likely cause of delayed puberty in boys?
Constitutional delay - runs in the family; late menarche in mum or delayed growth spurt in father.
460
Give 3 consequences of delayed puberty.
1. Psychological problems.
2. Reproduction defects.
3. Reduced bone mass.
461
What must you rule out in girls with delayed puberty and short stature?
Turner Syndrome (45X)!
They might also have recurrent ear infections
462
Give 5 functional causes of delayed puberty.
1. Anorexia.
2. Bulimia.
3. Over exercising.
4. CKD.
5. Drugs.
6. Stress.
7. Sickle cell.
463
What investigations might you do in someone with delayed puberty?
1. FBC - red cell count especially.
2. U+E.
3. LH/FSH measurements.
4. TFT's.
5. Karyotyping for Turners.
464
What is hypergonadotropic hypogonadism?
- Testes or ovarian failure
465
What is the affect of hypergonadotropic hypogonadism on FSH/LH and oestrogen/testosterone?
High FSH/LH low oestrogen/testosterone.
466
Give 2 examples of hypergonadotropic hypogonadism.
1. Turner Syndrome (45X).
| 2. Klinefelter's syndrome (47XXY).
467
What is hypogonadotropic hypogonadism?
Secondary gonadal failure!
| - Hypopituitary or problems with the hypothalamus.
468
What is the affect of hypogonadotropic hypogonadism on FSH/LH and oestrogen/testosterone?
Low FSH/LH and low testosterone/oestrogen
469
Give an example of hypogonadotropic hypogonadism.
Kallman syndrome.
470
What is Turner syndrome?
In Turner syndrome the patient is missing an X chromosome - 45X. It is an example of primary gonadal failure (hypergonadotropic hypogonadism).
471
Give 3 signs of Turner syndrome.
1. Short stature.
2. Delayed puberty.
3. CV and renal malformations.
4. Recurrent otitis media.
472
What is Klienfelter's syndrome?
In Klinefelter's syndrome the patient has an extra X chromosome - 47XXY. It is an example of primary gonadal failure (hypergonadotropic hypogonadism).
473
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.
474
Why might someone with Klinefelter's syndrome have fertility problems?
Azoospermia - semen contains no sperm.
475
Give 4 symptoms of Klinefelter's syndrome.
1. Reduced pubic hair.
2. Tall stature.
3. Reduced IQ.
4. Small testicles (<5ml
476
What cancer is someone with Klinefelter's at an increased risk of developing?
Breast cancer.
477
What is Kallman syndrome?
Congenital deficiency of GnRH. It is an example of secondary gonadal failure -
hypogonadotropic hypogonadism.
478
What must you test in a person who you suspect has Kallman syndrome?
Smell! 75% are ansomia.
479
How is Kallman syndrome inherited?
X linked recessive or dominant.
