Pathology Flashcards
1
Q
What is Cushing’s syndrome
A
An excess of cortisol
Can have many origins
2
Q
What are some of the potential causes of Cushing’s syndrome
A
Pituitary - caused by tumour in corticotroph cells (usually microadenomas)
Adrenal - caused by adrenal adenoma/carcinoma
Ectopic - some lung, thymus and pancreas cancers etc produce ACTH
Exogenous steroids - excess drug intake
Alcohol and depression
3
Q
What are the symptoms of Cushing’s syndrome
A
Cushingoid faces - moon-like, fat Acne Hirsutism Abdominal striae and central obesity Interscapular and supraclavicular fat pads- buffalo hump Proximal myopathy - wasting, thin limbs Osteoporosis Hypertension Impaired glucose tolerance - DM Thin skin - easy bruising Psychosis - euphoria or depression Thirst and polyuria Immunosuppression - prone to infection
4
Q
What can cause cervical lymphadenopathy
A
infective, malignancy or haematological (leukaemia/lymphoma)
5
Q
What is the most accurate way to diagnose cervical lymphadenopathy
A
Aspiration
6
Q
What symptoms may be associated with cervical lymphadenopathy
A
Systemic symptoms: fever, weight loss, sweats
Specific symptoms: hoarseness, cough, dyspnoea
7
Q
What is a dermoid cyst
A
Rare congenital cysts
8
Q
Describe the presentation of a cystic hygroma
A
posterior triangle
Seen in kids (usually first year of life)
Can be large and cause pressure symptoms
Can be filled with lymph
9
Q
Where would you find a branchial cyst
A
upper anterior triangle
10
Q
What is a pituitary adenoma
A
Derived from cells of the anterior pituitary
Relatively common
Either sporadic or associated with MEN1 (multiple endocrine neoplasia syndromes )
Further classified by cell type/ hormone produced
Large ones can cause local mass effects such as visual defects
11
Q
Describe the effect of a tumour that secretes prolactin
A
Most common functional pituitary adenoma - prolactinoma
Leads to infertility, amenorrhea, galactorrhea, gynaecomastia and lack of libido (late presentation)
May also present with structural effects
12
Q
Describe the effect of a tumour that secretes growth hormone
A
Second most common type of functional tumour
Causes increase in insulin like growth factor which stimulates growth of bone, cartilage and connective tissue
Can lead to diabetes, hypertension and carpal tunnel name
Get gigantism or acromegaly
13
Q
Describe the effect of a tumour that secretes ACTH
A
Causes Cushing’s disease
Usually caused by a micro-adenoma
Causes bilateral adrenocortical hyperplasia
14
Q
What is a craniopharyngioma
A
Derived from remnants of Rathke’s pouch
Type of internal cranial tumour
Slow growing, often cystic and may calcify
Can arise in the vicinity of the pituitary
15
Q
What are the symptoms of a craniopharyngioma
A
Headaches and visual disturbances
Children may have growth retardation
16
Q
Describe diabetes insipidus
A
Caused by a lack of ADH function
Can be central - due to ADH deficiency
Can be caused by trauma, tumours, inflammatory disorders
Can be nephrogenic due to renal resistance to ADH
17
Q
What causes SIADH
A
An excess of ADH
Many causes:
- Ectopic production of ADH – paraneoplastic syndrome from cancer
- CNS infections
- Intracranial bleeds
- ADH analogues like desmopressin or drugs which stimulate its action (SSRIs)
- Idiopathic or hereditary
18
Q
What can cause adrenal hyperfunction
A
Hyperplasia
Adenoma
Carcinoma
19
Q
What can cause adrenal hypofunction
A
Acute - Waterhouse-Friderichsen
Chronic - Addison’s disease
20
Q
Describe congenital adrenocortical hypoplasia
A
Group of autosomal recessive disorders
Caused by deficiency/ lack of enzyme required for steroid biosynthesis
This blocks other pathways and leads to increased androgen production
Baby girls with this will present with ambiguous genitalia
Reduced cortisol stimulates ACTH release and cortical hyperplasia
21
Q
Describe acquired adrenocortical hyperplasia
A
Caused by endogenous ACTH production
Can be a pituitary adenoma (Cushing’s) or ectopic ACTH production (e.g. SC lung cancer)
Leads to bilateral adrenal enlargement
22
Q
What are adrenogenital syndromes
A
Defects in enzymes in the production of adrenal hormones lead to accumulation of precursors which can then be diverted to other endpoints – e.g. produce testosterone instead of cortisol
23
Q
Which age group tends to be affected by adrenocortical tumours
A
Mainly adults
Can affect younger patients - Li-Fraumeni syndrome
24
Q
How do adrenocortical tumours present
A
Incidental finding (radiology, autopsy)
Hormonal effects
Mass lesion
Carcinomas with necrosis can cause fever
25
Describe the presentation of adrenocortical adenoma
Well circumscribed, encapsulated lesions
Usually small
Yellow / yellow brown cut surface (lipid)
Composed of cells resembling adrenocortical cells
Well differentiated, small nuclei, rare mitoses
Can be functional, but more likely not
Often an incidental finding - usually small
26
Are adrenocortical carcinomas common
No - they are rare
27
Are adrenal carcinoma non-functional or functional
More likely to be functional and malignant
28
Where do adrenocortical carcinomas usually spread to
Local invasion – retroperitoneum, kidney
Metastasis – usually vascular (liver, lung and bone)
Peritoneum and pleura
Regional lymph nodes
29
What features are suggestive of an adrenocortical carcinoma
```
Large size
Haemorrhage and necrosis
Frequent mitoses, atypical mitoses
Lack of clear cells
Capsular or vascular invasion
```
30
What can cause primary hyperaldosteronism
Conn's syndrome
Adenoma
Diffuse or nodular hyperplasia of both adrenal glands
It is autonomous production of aldosterone
31
What can cause hypercortisolism
Cushing's
Steroid therapy - iatrogenic
ACTH secreting tumours - endogenous or exogenous
32
List causes of acute adrenocortical insufficiency
Rapid withdrawal of steroid treatment
Crisis in patient with chronic insufficiency
Massive adrenal haemorrhage
33
List causes of chronic adrenocortical insufficiency
- Addison's disease
- Autoimmune adrenalitis
- Infections e.g. TB, H|V
-Metastatic malignancy (lung or breast)
Unusual causes include amyloid, sarcoidosis and haemochromatosis
34
Do symptoms of chronic adrenocorticoid insufficiency appear immediately
NO
| Symptoms only appear once 90% of the gland is damaged
35
What are the symptoms and signs of Addison's disease
```
Weakness, fatigue, anorexia, nausea, vomiting, weight loss, diarrhoea
Hypotension
Dehydration
Increased pigmentation
K+ retention and Na+ loss
Decreased glucocorticoids
```
36
What can cause a crisis in Addison's disease and what are the signs
Stress – infection, trauma, surgery
Vomiting, abdominal pain, hypotension, shock and death
37
What are the 2 types of adrenal medullary tumours
Phaeochromocytoma
Neuroblastoma
38
Which age group is mainly affected by neuroblastoma
Children
Usually diagnosed around 18 months
40% diagnosed in infancy
39
Describe a neuroblastoma
40% arise in the adrenal medulla – the remainder mostly along the sympathetic chain
Composed of primitive appearing cells but can show maturation and differentiation towards ganglion cells
Age and stage important for prognosis
Spreads to bones
40
What is a phaeochromocytoma
A neoplasm derived from chromaffin cells of the adrenal medulla
Secrete catecholamines - excess nor-adrenaline and adrenaline
Rare cause of secondary hypertension
41
What are the signs and symptoms of phaeochromocytoma
Hypertension - paroxysmal episodes common during stress, exercise etc
Can lead to cardiac failure, infarction and arrhythmias
Urinary excretion of catecholamines and metabolites can be detected
paroxysmal sweating
Headache
Pallor
Tachycardia
Anxiety/fear
42
Describe the appearance and behaviour of a phaeochromocytoma
Characteristically tumour cells form nests
If malignant they tend to be large and necrotic
Propensity for skeletal metastasis
Other sites include regional lymph nodes, liver and lung
43
What kind of test would you do if there is too much of a hormone
Dynamic suppression test
| Introduce a change artificially and see if hormone levels decline in the way you'd expect
44
What kind of test would you do if there is too little of a hormone
Dynamic stimulation test
| Try to stimulate hormone release and if it works it suggests the tissue is functional
45
What is classified as a microadenoma
Tumour less than or equal to 1cm
46
What is classified as a macroadenoma
Tumour greater than or equal to 1cm
47
What symptoms might you get with a pituitary adenoma that is very large
Compression of optic chiasm - causes bitemporal hemianopia
Compression of other surrounding cranial nerves (3,4,6) - loss of some eye movements
Headache
48
What symptoms might you get with a pituitary adenoma that is supressing hormone release
Hypoadrenalism – not enough cortisol
Hypothyroid – due to lack of TSH
Hypogonadism – due to lack of FSH/LH (may result in amenorrhea, loss of libido and erectile dysfunction)
Diabetes insipidus – no ADH
GH deficiency - children stop growing, low mood, poor muscle function in adults
Loss of prolactin - only noticed in lactating mums
49
List the physiological causes of raised prolactin
Breast feeding
Pregnancy
Stress
Sleep
50
List the pharmacological causes of raised prolactin
Dopamine antagonists- metoclopramide
Anti-psychotics
Anti-depressants - TCA, SSRIs
Cocaine
51
List the pathological causes of raised prolactin
Hypothyroidism
Stalk lesions - caused by surgery or severe trauma (e.g. RTA)
Prolactin secreting tumour of the pituitary – prolactinoma (most common pituitary tumour)
52
Which other hormone has a mild stimulatory effect on prolactin production
TRH
53
What are the symptoms of prolactinoma in women
```
Galactorrhoea - milk production
Menstrual irregularity
Amenorrhoea
Infertility
Tend to present early as they notice the symptoms - obvious
```
54
What are the symptoms of prolactinoma in men
```
Impotence
Visual field abnormality
Headache
Anterior pituitary malfunction
Tend to present later with mass effects
```
55
What investigations can be done if you suspect a prolactinoma
Serum Prolactin concentration - would be high
This is only normal in breastfeeding mums
MRI of pituitary - look for adenoma
Visual field test - bitemporal hemianopia
Pituitary Function tests - may be other hormones affected
56
How do you treat prolactinoma
Only pituitary adenoma which is amenable to medical therapy - Dopamine agonists
Cabergoline is usually 1st line as has the least side effects
Other drugs in this class are - bromocriptine (only one safe in preganacy) and quinagolide
57
List potential side effects of dopamine agonists
nausea/vomiting
low mood
may cause fibrosis of heart valves etc
58
What causes acromegaly
GH excess - most commonly from tumour
59
What are the symptoms of acromegaly
Giant due to bone growth (before epiphyseal fusion)
Thickened soft tissues - skin, large jaw, sweaty, large hands, prominent brow (frontal bossing)
Increased shoe size and large hands
Snoring/Sleep apnoea due to thickened nasopharynx
Tiredness
Hypertension and cardiac failure
All soft tissue and organs enlarge (hepato, spleno and cardiomegaly)
Overgrowth of bone leads to premature arthritis
Headaches
Diabetes mellitus
Local pituitary effects - visual fields, hypopituitarism
Early CV Death
Colonic polyps and colon cancer
60
What causes the headaches in acromegaly
Increased dynamic blood flow - vascular effect of condition
61
How would you diagnose acromegaly
IGF1 levels tested - usually raised as GH stimulates its release
Then do a glucose tolerance test - suppression test for GH (will not be suppressed if affected)
Visual field examination
MRI of pituitary
62
How do you treat acromegaly
Drugs to help symptoms include: somatostatin analogues such as sandostatin
GH antagonist - pegvisomant
May use dopamine agonists
Pituitary surgery - trans-sphenoidal
If GH still high after then can use radiotherapy and drugs
63
What are the side effects of somatostatin analogues
```
Local Stinging
Short term:
Flatulence
Diarrhoea
Abdominal pains
```
Long term:
Gallstones - stop gallbladder contracting
64
When are dopamine agonists more effective in acromegaly
If the pituitary tumour causing the excess GH is co-secreting prolactin
65
How does pegvisomant work
GH antagonist - Binds to the growth hormone receptor and blocks its activity
Does not decrease tumour size
IGF1 levels decrease but GH stays the same or increases
66
Obesity has similar presentations to Cushing's - how you differentiate
```
Cushing's is characterised by:
Thin Skin
Proximal myopathy
Frontal balding in women
Conjunctival oedema (chemosis)
Osteoporosis
```
You wont see these symptoms in classic obesity
67
Describe the screening test for Cushing's
Overnight 1mg dexamethasone suppression test
Measure cortisol levels the next morning - if still high it is considered abnormal and Cushing's should be suspected
The dexa should supress the ACTH and therefore cortisol
68
What is the definitive test for Cushing's
```
If screening (overnight dexa) test is positive then carry out a low dose dexamethasone suppression test
Give 2mg of dexa per day for 2 days
measure cortisol 6 hrs after last dose
If still >130 nmol/l then definitely Cushing's
```
69
What is the high dose dexamethasone test used for
Determines what the type of Cushing's it is
| If cortisol level is supressed by the high dose then it's pituitary in origin
70
How do you treat pituitary Cushing's
Hypophysectomy and external radiotherapy if recurs
| Trans-sphenoidal removal of the causative tumour
71
How do you treat adrenal Cushing's
bilateral adrenalectomy - remove glands
72
How do you treat ectopic Cushing's
Remove source
| OR bilateral adrenalectomy
73
What drugs can be used in the treatment of Cushing's
Metyrapone - only if other treatments fail or not suitable in elderly, side effects common
Ketoconazole - hepatotoxic
Both stop synthesis of cortisol
Pasireotide LAR - somatostatin analogue
74
What can cause hypopituitarism (low pituitary action)
```
Pituitary tumours
Secondary metastatic tumours
Local brain tumours - mass effect if nearby
Granulomatous disease - TB, sarcoidosis
Vascular disease - polyarteritis
Trauma - RTA
Hypothalamic disease - e.g. syphilis
iatrogenic - surgical mistake
Autoimmune - sheenan disease post-partum
Infection - meningitis
```
75
What are the symptoms of anterior hypopituitarism
```
Menstrual irregularities (F)
Infertility, impotence
Gynaecomastia (M)
Abdominal obesity
Loss of facial hair (M)
Loss of axillary and pubic hair (M and F)
Dry skin and hair
Hypothyroid faces
Growth retardation - in kids
```
76
How can you treat hypothyroidism
Thyroxine - 100-150mcg/day
77
How can you treat low cortisol levels
Hydrocortisone
10-25 mg/day
Day and night
78
How can you treat low GH levels
GH nightly as SC injection
| It increases muscle mass, bone density and improves cardiac function
79
How do you treat low testorone levels
Testosterone replacement
IM injection every 3-4 weeks or 10-14 weeks depending on type
Can get skin gels
80
What are the risks of testosterone replacement
Prostate enlargement - doesn't cause cancer
Polycythaemia - too many blood cells
Hepatitis
81
List the causes of diabetes insipidus
Familial - isolated or part of DIDMOAD
Idiopathic - 50%
Due to trauma such as RTA
Rarely: tumours, sarcoidosis, meningitis
82
What conditions are included in DIDMOAD
Diabetes insipidus
Diabetes mellitus
Optic atrophy
deafness
83
How do you test for diabetes insipidus
Water deprivation test
Stimulation test – trying to cause ADH release (patient should try and retain water to counteract test)
Measure plasma and urine osmolality and then stop patient drinking from 8am-4pm. If they have DI then urine will continue to be inappropriately diluted and plasma osmolality increases
84
How do you treat cranial diabetes insipidus
Give desmopressin - synthetic ADH
Can be in nasal spray, tablet or injection forms
Titrate dose according to plasma sodium and symptoms
85
List common causes of midline neck swellings
Thyroid pathology
Thyroglossal cyst
Dermoid cyst
86
List common causes of anterior triangle swellings
Lymph nodes
Branchial cyst
Salivary gland pathology
Carotid body tumour
87
List common causes of posterior triangle swellings
lymphadenopathy
| cystic hygroma
88
What is Conn's syndrome
An excess of aldosterone
Caused by a tumour presents in the cells of the zona glomerulosa which secretes excess aldosterone
Results in high NaCl and water levels in the body
Low potassium due to Na/K ATPase action
89
What are the symptoms of Conn's syndrome
Hypertension - increase in Na resorption causes water to follow which increases circulating volume
Hypokalaemia
Will have a high aldosterone and unrecordable renin
90
Describe adrenal hyperplasia
Cause of secondary hypertension
Usually occurs bilaterally
Similar symptoms to Conn's
91
How do you diagnose primary aldosteronism
Plasma aldosterone and renin are measured in the blood and expressed as a ratio
If ratio is >750 then do a saline suppression test (give 2L saline and would expect aldosterone to decrease due to RAAS feedback)
If it is not fully supressed then confirmation of primary aldosteronism (e.g, Conns)
Would then do a CT adrenal to determine if Conn's or hyperplasia
92
What conditions are included in primary aldosteronism
Conn's syndrome
| adrenal hyperplasia
93
How do you treat Conn's syndrome
Surgery
| Remove the adenoma laparoscopically
94
How do you treat adrenal hyperplasia
Aldosterone receptor antagonist - e.g. spironolactone or eplerenone
Spironolactone comes with lots of side effects (gynaecomastia and hyperkalaemia)
95
How does Cushing's affect DHEA levels
Increased secretion due to higher ACTH levels
As it's the prohormone to the sex hormones you get excess testosterone
Can get acne, amenorrhea, frontal balding, facial hair growth, lack of libido and impotence
96
What are the symptoms of adrenaline hypersecretion
```
Hypertension
Increased heart rate and strength
Pallor or excessive flushing
Arrhythmias
Palpatation
Sweating
Headaches
Anxiety
Polyuria and polydipsia
Slows digestion - ileus
```
97
Why is phaechromocytomas called 10% tumours
```
10% extra-adrenal
10% are malignant (mets)
10% bilateral
10% occur in children
10% are part of an associated hereditary syndrome
```
98
How would you diagnose phaeochromocytomas
Urinary catecholamines and metabolites collected and measured over 24hrs
Typically do this over 2-3 days
If abnormal you do a CT or MRI to look for tumours
Then do more specific MIBG scan - type of nuclear medicine scan that looks for tumour/mets by attaching radioactive marker to MIBG (adrenaline precursor)
99
How do you treat phaeochromocytomas
Surgery to remove the tumour - usually lap
Alpha and beta blockade to counteract symptoms before surgery
If malignant tumour then chemo can be used
100
List primary causes of primary adrenal insufficiency
```
Addison's disease - autoimmune condition
Congenital Adrenal Hyperplasia
Adrenal TB
Malignancy
Adrenal haemorrhage
Haemochromatosis
```
101
List secondary causes of adrenal insufficiency
Due to lack of ACTH stimulation
Iatrogenic (excess exogenous steroid) - most common
Pituitary/hypothalamic disorders - e.g. tumour
102
Addison's disease only becomes symptomatic once most of the damage is done - true or false
True
| Usually only once 90% of the adrenal gland is destroyed
103
How would you diagnose Addison's
```
Blood tests:
Low Na and high K+
Hypoglycaemia
ACTH levels - will be high
High renin and low aldosterone
Adrenal antibodies
```
Short synacthen test - give ACTH injection then measure cortisol
104
How do you treat adrenal insufficiency
DONT DELAY - START TREATMENT
Give steroids (hydrocortisone IV) and fluid (saline to replace Na)
Give fludrocortisone as aldosterone replacement
Basically syntehtically replace the missing hormones
Give sick day rules and identification
105
Adrenal insufficiency can be fatal if not treated - true or false
TRUE
106
How are steroids used in treatment
Suppression of inflammation, the immune system and replacement treatment
Treats allergic disease, inflammatory disease, malignant
107
Do you get hyperpigmentation with secondary adrenal insufficiency
NO
| Pigmentation caused by excess ACTH which is low in secondary causes
108
What are the implications of long term steroid treatment
Supresses ACTH production - negative feedback acts on anterior pituitary
Unable to properly respond to stress
Need extra dose when ill
Cannot stop suddenly - need gradual withdrawal over 4-6 weeks
109
How do you diagnose primary aldosteronism
Measure plasma aldosterone and renin
If ratio is raised then carry out saline suppression test -should supress aldosterone and renin – if that doesn’t happen (e.g. aldosterone high) then you can get biochemical diagnosis of alsosteronism
Then confirm subtype through CT or adrenal vein sampling
110
What are the symptoms of classical congenital adrenal hyperplasia
Males:
Adrenal insufficiency
Poor weight gain
Females
Genital ambiguity
111
What are the symptoms of non-classical congenital adrenal hyperplasia
```
Hirsute
Acne
Oligomenorrhoea
Precocious puberty
Infertility or sub-fertility
```
112
How do you treat CAH
```
Glucocorticoid replacement
Some need mineralocorticoid
Achieve max growth potential in kids
Control androgen excess
Restore fertility
```
113
List the biochemical changes seen in phaeochromocytoma
```
Hyperglycaemia
May have low potassium
High haematocrit - raised Hb conc
Mild hypercalcaemia
Lactic acidosis
High catecholamines
```
114
How do you diagnose phaechromocytoma
Confirm catecholamine excess: 24hr urine test or plasma levels
Identify source by MRI, MIBG or PET scan
115
How do you treat phaechromocytoma
```
Full α and β- blockade (A before B) - phenoxybenzamine and propranolol
Fluid and/or blood replacement
Surgery to remove tumour
Chemo if malignant
Genetic and family testing
```
116
What are the symptoms of hypercalcaemia
```
Increased stimulation of smooth muscle, nerves and heart
Tiredness
Confusion
Depression and lethargy
May have abnormal ECG
Arrhythmia
Kidney stones
Muscle weakness - decreased excitability
Constipation
Polyuria and polydipsia
Osteoporosis
```
117
What are the symptoms of hypocalcaemia
Muscle tetany - increased excitability
Pins and needles in extremities
Extreme cases can cause contraction of respiratory muscle - breathing issues and even death by asphyxiation
118
What are the symptoms of hyperparathyroidism
```
Hypercalcaemia - associated symptoms
Renal stones
Osteoporosis
Low serum phosphate
High PTH and calcium
```
119
What are the 3 types of hyperparathyroidism
Primary - caused by overactive parathyroid gland
Secondary - physiological response to low calcium
Tertiary - parathyroid becomes autonomous after years of secondary
120
How do you diagnose hyperparathyroidism
Raised serum calcium
Raised serum PTH
Increased urine calcium excretion
Do a sestimibi scan - overactive gland will take up labelled solution if primary hyperparathyroidism
121
How do you treat hyperparathyroidism
Surgical removal of causative adenoma - only if suffering with renal issues or severe osteoporosis
High fluid intake
Avoid high calcium and Vit D diet
Bisphosphonates are mainly a holding measure
122
What causes hypoparathyroidism
Lack of cells in the parathyroid gland which secrete PTH
Can be genetic: Di George Syndrome (absence of glands)
Acquired - destruction via malignancy in gland or autoimmune disease
123
What are the symptoms of hypoparathyroidism
Symptoms of hypocalcaemia
Chvostek's sign
Trousseau's sign
Fractures due to high remodelling
124
What is Chvostek's sign
Twitching of facial muscle when you gently tap the facial nerve
125
What is Trousseau's sign
Inflating a BP cuff at systolic pressure will cause tetany of hand muscles
126
How do you diagnose hypoparathyroidism
Blood tests: hormone and serum electrolyte
| Look for low PTH, low Ca, high phosphate
127
How do you treat hypoparathyroidism
Calcium and Vitamin D supplements
128
what causes pseudohypoparathyroidism
Genetic receptor abnormality leading to resistance of PTH hormone
129
Describe the blood electrolyte levels in pseudohypoparathyroidism
Increased PTH
Low Ca
High phosphate
130
What are some complications of pseudohypoparathyroidism
```
Subcutaneous calcification
Mental retardation
Blunting of 4th metacarpal
Obesity
Bone abnormalities
```
131
List causes of vitamin D deficiency
Lack of sunlight absorption - winter, skin pigmentation, not outdoors enough
Lack of absorption of prohormone - poor diet or malabsorption
Problem with hormone activation - liver failure
132
what does vitamin D deficiency result in
Decreased absorption of Ca and phosphate
PTH secretion increases to compensate but this causes more bone reabsorption - weaker and less dense bones
Lack of mineralisation which causes low bone quality
Leads to rickets and Osteomalacia
133
Describe rickets
Occurs in kids with low vit D
Bones become soft - legs bow under their weight, skull bones are soft and tender, widened epiphyses at wrists, abnormalities of costochondral joints
134
describe Osteomalacia
Similar to rickets but in adults
Low mineralisation leads to increased fracture risk
Bone and muscle tenderness
Gait deformity
135
What is the most common cause of female infertility
PCOS
136
List some potential causes of amenorrhea
```
PCOS
Anorexia nervosa
Bulimia nervosa
Depression
Endocrine disorders
Pregnancy
Premature menopause or ovarian failure
```
137
What is oestradiol
Potent oestrogen produced by the ovary
138
Which cancer is most likely to spread to the adrenals
Lung
139
What is a periosteal reaction
Reacts when the bone has been attacked or damaged
Thick rind appearing around bone
Periosteum becomes hypertrophic in cancers (often lung)
140
Describe a diffuse bone abnormality
all bones are too brittle
all bones are too soft
tends to be a systemic problem
Includes osteoporosis, rickets, Osteomalacia and Paget's
141
Describe a focal bone abnormality
Occurs in a single location
| Can be traumatic, neoplastic, inflammatory or degenerative
142
Which bones are most commonly fractured in osteoporosis
proximal femur
sacrum and pubic rami
thoracolumbar vertebral bodies
distal radius
143
Describe the appearance of lytic bone destruction
Medullary lucency and loss of trabeculae
Loss of inner cortex
Complete loss of cortex
Potential for pathological fracture
144
Describe the appearance of sclerotic bone lesions
Subtle medullary density and loss of trabeculae
Spreading zone of density which includes cortex
Featureless white bone
Expansion of bone
Most commonly caused by prostate and breast cancer
145
What is the definition of osteoporosis
Progressive systemic skeletal disease characterised by low bone mass and deterioration of bone tissue, with a increase in bone fragility and susceptibility to fracture
146
Bone is constantly undergoing remodelling - true or false
TRUE
| continuous cycle
147
Describe how bone mass changes with age
Increases as we grow up
Peaks at around 30 and is maintained until mid-late 40's
Starts to decrease as we age
Accelerated in women due to menopause
148
Which factors contribute to bone loss
```
Sex hormone deficiency
Body weight
Genetics
Diet
Immobility
Diseases
Drugs especially glucocorticoids, aromatase inhibitors
```
149
In which sex is osteoporosis more common
Women
150
List common fracture sites in osteoporosis patients
Neck of femur
Vertebral body
Distal radius
Humeral neck
151
What can multiple vertebral fractures lead to
Thoracic kyphosis
152
Fracture incidence increases with age - true or false
True
153
How do you measure bone density
DEXA scan
| Compares bone density to peak young adult level and an age matched group
154
What are the risk factors for fragility fracture
Non-modifiable: age, gender, ethnicity, previous fracture, family history, early menopause, co-existing disease
Modifiable - bone density, alcohol, weight, smoking, inactivity, certain medications
155
Who do you assess for fracture risk
Anyone >age 50 years with risk factors
Anyone under 50 years with very strong clinical risk factors:
Early menopause
Glucocorticoids
156
As bone density decreases, fracture risk increases - true or false
True
157
List some secondary causes of low bone density/osteoporosis
Endocrine: Cushing's, hyperthyroidism, hyperparathyroidism
GI: Coeliac, IBD, chronic liver disease
Chronic kidney disease
CF or COPD
158
Which lifestyle factors can be modified to manage osteoporosis
```
Exercise: high intensity strength training and low impact weights
Avoid excess alcohol
Avoid smoking
Fall prevention
Increased dietary calcium
```
159
Which drugs can be used in the treatment of osteoporosis
```
Calcium & vitamin D supplementation
Bisphosphonates
Denosumab
Teriparatide
HRT
SERMS (Selective Estrogen Receptor Modulators)
Testosterone
```
160
How do bisphosphonates work
Anti-resorptive agents
Prevent bone loss at all sites vulnerable to osteoporosis - ingested by osteoclasts and cause cell death
Reduce risk of hip and spine fracture
161
Give examples of bisphosphonates
Aledronate
| Risedronate
162
When is zoledronic acid given in treatment of osteoporosis
Given if they cannot tolerate the bisphosphonate oral therapy
Annual IV infusion for 3 years
163
How does denosumab work
fully human monoclonal antibody which binds to target and inhibits development and activity of osteoclasts
Decreases bone resorption and increases bone density
Given as SC injection every 6 months
164
What are the side effects of desonumab
Hypocalcaemia, eczema, cellulitis
165
How does teriparatide work
It is recombinant parathyroid hormone - mimics its action
Stimulates bone growth rather than reducing bone loss
Only used in a small number
166
Describe the effects of corticosteroids on bone health
Reduction of osteoblast activity and lifespan
Suppression of replication of osteoblast precursors
Reduction in calcium absorption
Inhibition of gonadal and adrenal steroid production
Increases fracture risk - dose dependent
167
Describe Paget's disease of bone
Abnormal osteoclastic activity followed by increased osteoblastic activity
Results is abnormal bone structure with reduced strength and increased fracture risk
May be single or multiple sites
168
Which bones are commonly affected by Paget's
long bones, pelvis, lumbar spine and skull predominantly
169
Incidence of Paget's decreases with age - true or false
False
It increases
Rare in the under 40's
170
How does Paget's present
Bone pain
Deformity
Deafness
Compression neuropathies
Can be asymptomatic and an incidental finding
171
How do you treat Paget's
Analgesia
| Bisphosphonates
172
What is osteogenesis imperfecta
Rare group of genetic disorders mainly affecting bone
Mostly caused by defects in collagen genes
Most are autosomal dominant
Different forms to mild to severe
173
What are the signs and symptoms of osteogenesis imperfecta
Increased fracture risk - may present with fracture
Hypermobility
Blue sclera
dentinogenesis imperfecta - teeth issues
More severe present with childhood fractures
Mild may not present until adulthood
174
How do you manage osteogenesis imperfecta
No cure
Fracture fixation
Surgery to correct deformities
Bisphosphonates
175
What are the most common endocrinopathies
Thyroid issues and diabetes
176
In general how do you approach the diagnosis of an endocrine issue
First look for a phenotype
Then can do biochemical tests
Then look to imaging to try and find an anatomical issue (CT best for adrenal and MRI for pituitary)
177
Loss of pituitary hormones usually occurs all at once - true or false
False
Loss of pituitary hormone is often sequential as some areas more susceptible to being squeezed by mass
Gonadotrophins lost first then ACTH then TSH
178
Non-functional or non-secreting adenomas present with structural symptoms first - true or false
True
They don't secrete any hormones so don't get these affects
Secreting ones produce hormones so these effects usually make you sick first
179
Which pituitary hormones are released at a steady state
FSH,LH and TSH
| Therefore any low readings would be a true low
180
Which pituitary hormones are not released at a steady state
GH and ACTH
Growth hormone is released in spikes so may get a false low if you catch it at the wrong time
ACTH is diurnal - big spike in the morning
These ones require a stimulation or suppression test
181
What is Sheehan syndrome
Pituitary dysfunction following post-partum hemorrhage
| The drop in BP caused ischaemia and necrosis of pituitary and results in loss of function
182
List tumours can affect the pituitary
Pituitary adenoma
Craniopharyngioma
Cerebral and secondary tumours
183
Which infections can lead to pituitary hypofunction
Meningitis
Syphilis
HIV/AIDs
184
List some iatrogenic causes of pituitary hypofunction
Cranial radiation
| Removal of the pituitary
185
What is the most common cause of pituitary hormone excess
Most common cause is a secreting adenoma - present earlier than non-secreting
Benign - don't met but do cause symptoms
186
How does excess FSH and LH present
No real clinical symptoms
Gonads don't make a high level of hormone in response
Usually present later with structural effect from pituitary
187
Which types of tumours can produce ACTH
Small cell lung cancer and other neuroendocrine tumours can produce huge amounts of ACTH
188
How does excess ACTH lead to hyper pigmentation
ACTH cleaved from pro-hormone POMC
Other products include melanocyte stimulating hormone
Therefore if you have increased ACTH production you get excess MSH which leads to pigmentation
189
How can you determine the source of excess ACTH
Measure ACTH and cortisol levels
If an adrenal issue then cortisol would be high and ACTH low
If caused by exogenous steroids then ACTH and cortisol will both be low If a pituitary issue then ACTH high and cortisol low
190
Which is the only pituitary tumour that does not require neurosurgery
Prolactinoma - responds to medical therapy
| All others require surgery
191
How do you access the pituitary surgically
Trans-sphenoidal
| Put scope up the nose
192
What is the function of oxytocin
Triggers let-down reflex in breastfeeding mums
193
What is the function of ADH
Conserves water
Binds to receptors in the kidney which causes recruitment of AQP2 to the cell membrane
This AQP2 allows water to move back into the blood
Also causes vasoconstriction
Overall increase in BP
194
How does diabetes insipidus present
Presents with increased urination, very dilute urine, constant thirst
195
What can cause diabetes insipidus
Can be caused by production issue in pituiatry or lack of recognition by kidney receptors
196
What happens to plasma osmolality in diabetes insipidus
It is very high - sodium and urea are high
| In contrast urine osmolality is very low (peeing out a lot of water
197
What is the main determinant of plasma osmolality
Sodium
Other solutes include: potassium, urea and glucose
198
What is osmolality
The concentration of a solution expressed as the total number of solute particles per kilogram
199
How do you differentiate between cranial and nephrogenic diabetes insipidus
After the water deprivation test you give artificial ADH
If a cranial issue their urine will immediately concentrate, if nephrogenic there will be no effect (get them to drink to recover instead!)
200
What is the main differential for suspected diabetes insipidus
Psychogenic polydipsia
Excessive water drinking which means they flush their kidneys so much they lose the concentration gradient and cannot concentrate anymore
201
At what point must you stop a water deprivation test for diabetes insipidus
Must stop if they lose >3% of body weight as they dehydrate very quickly
Therefore they are weighed throughout
202
How do you treat nephrogenic diabetes insipidus
It is very hard. Look for and reverse underlying causes if there.
Sometimes massive ADH dose can cause some retention.
May use thiazide diuretics.
Must carry a warning card that if unconscious they need fluids stat
203
How do you treat SIADH
Treat underlying cause
Fluid restriction - 1-1.5L per day (unpleasant as brain will be telling them to drink)
Demeclocycline - old antibiotic which uncouples AQP2 from the receptor (expensive now)
Tolvaptan - holy grail V2 receptor antagonist but very expensive
204
How does SIADH present
Presents with confusion, lethargy, normovolaemic (no dehydration or overload), symptoms of underlying cause
Low plasma osmolality and urine is very high
Low sodium
205
What causes the confusion in SIADH
Caused by swelling in the brain as excess water moves into the cells
206
What must you exclude before diagnosing SIADH
Always need to exclude hypothyroid and low cortisol as they present similarly on biochemistry
207
All cortical hormones from the adrenals are derived from what
Cholesterol
208
What is the risk of excessive sodium shift
Central pontine myelinosis - loss of myelin in the midbrain (pons)
Nerves will then dysfunction - pain, dysphagia, dysarthria, diplopia. LOC
209
What is the maximum acceptable sodium shift
No more than 8mmol/L shift in 24 hours
210
ACTH acts on which zones of the adrenal glands
All 3 zones stimulated by ACTH but only glucocorticoids negatively feedback on ACTH
211
Where is aldosterone produced
Adrenal glomerulosa
212
What is the purpose of aldosterone
Activates NaK ATP channel and resorbs Na in the kidney
| Na absorption which water follows - increased circulating volume and BP
213
You tend to lose all 3 hormones in adrenocortical disease - true or false
True
214
How does adrenocortical deficiency present
```
Weight loss
Lethargy
Diarrhoea
Hypotension,
Hypoglycaemia
Hyperpigmentation due to excess ACTH
Hyponatraemia and hyperkalaemia (due to aldosterone loss)
Lack of cortisol leads to hypoglycaemia
```
215
Why MUST you give alpha blockers before beta in the treatment of phaeochromocytoma
If you give beta first it can kill them
| If beta blocked all adrenaline goes to alpha receptors causing massive vasoconstriction, hypertension and stroke
216
Why does phaeochromocytoma cause labile BP
- BP labile as the adrenaline acts on alpha receptors which cause vasoconstriction and in response
217
You see a patient newly diagnosed with Addison’s disease. What advice should you give them about their steroid medication in the event of becoming unwell or going for surgery?
They will need to increase their corticosteroid medication dose
