Block 34 Week 5 Flashcards
1
Q
What is cushings caused by?
A
- cause by prolonged exposure to excess of glucocorticoids
2
Q
causes of cushings?
A
- exogenous cause - use of glucocorticoids - the most common cause
- endogenous - excess production of glucocorticoids by the body - very rare
3
Q
cushings disease?
A
- Cushing’s disease, which refers to cases caused by a pituitary adenoma, is responsible for the majority of endogenous cases.
4
Q
ACTH dependent cushings?
A
- ACTH dependent: cortisol excess is driven by ACTH, either from the pituitary or ectopic sources.
5
Q
ACTH independent cushings?
A
- ACTH independent: cortisol excess is independent of ACTH. Includes exogenous causes (consumption of cortisol) and adrenal lesions (adenomas, carcinomas).
6
Q
HPA axis?
A
- CRH from paraventricular nucleus of hypothalamus
- ATCH from corticotrophs of AP
- cortisol release from adrenal cortex
- negative fedback on CRH and ACTH
7
Q
ACTH excess is a feature of both?
A
ACTH excess is a feature of both Addison’s disease (primary adrenocortical insufficiency) and ACTH dependent Cushing’s syndrome - hyperpigmentation
8
Q
what causes ACTH dep cushings?
A
- due to the excess production of ACTH.
- When exogenous causes are excluded, ACTH dependent causes are responsible for 80% of all Cushing’s syndrome.
- Cushings disease involves excess ACTH.
9
Q
ACTH dependent cushings - ectopic production?
A
- Ectopic ACTH production: This may be seen as a paraneoplastic syndrome in lung cancers where malignant cells produce ACTH and are not subject to normal negative feedback mechanisms.
10
Q
ACTH dependent cushings - ectopic CRH production?
A
- Ectopic CRH production: Rarely CRH may be produced by malignant tissue resulting in increased ACTH and cortisol production.
11
Q
ACTH independent cushings?
A
- presence of normal ACTH production
- endogenous administration
- primary adrenal lesions
12
Q
ACTH independent cushings - endogenous admin?
A
- Endogenous administration: Prolonged exposure to exogenous glucocorticoids is the most common cause of Cushing’s syndrome. Results in suppression of CRH and ACTH.
13
Q
ACTH independent cushings - primary adrenal lesions?
A
- Primary adrenal lesions: tumours (adenomas, carcinomas and hyperplasia) may result in cortisol excess and suppression of CRH and ACTH.
14
Q
symptoms of cushings syndrome
A
- Tiredness
- Depression
- Weight gain
- Easy bruising
- Amenorrhoea
- Reduced libido
- Striae
15
Q
signs of cushings syndrome
A
- Acne
- Moon facies
- Plethora
- Buffalo hump
- Hypertension
- Proximal muscle weakness
- Hyperpigmentation(in ACTH dependent causes)*
16
Q
definitive test in cushings?
A
dexamethasone suppression test
17
Q
other tests used in cushings?
A
- 24 hr urinary cotisol
- midnight cortisol
18
Q
24 hr urinary cortisol?
A
- 24 hr urinary cortisol - often initial tests in suspected cushings syndrome
- Three or more collections are usually needed.
- Levels 3-4x normal are highly suggestive of Cushing’s syndrome.
- creatinine levels need to be measured
19
Q
midnight cortisol?
A
- demonstrates loss of normal circadian pattern
- Cortisol levels can be salivary or blood-based
20
Q
low dose dexamethasone suppression tets?
A
- dexamethasone given at 11pm and serum cortisol is then measured at 8am
- In a normal individual, the administration of dexamethasone should suppress the morning rise in serum cortisol.
- However, in patients with Cushing’s syndrome, there is a lack of suppression,
21
Q
dexamethasone CRH test?
A
- less commonly used
- dexamethasone is given for a period following by administration of CRH
- Serum cortisol (and ACTH) levels can then be measured.
- It may help distinguish between Cushing’s and hypothalamus-pituitary-adrenal axis dysregulation
22
Q
establishing cause of cushings - first test?
A
- plasma ACTH is the first test done to find a cause
- Suppressed / undetectable ACTH: Indicative of an ACTH independent cause of Cushing’s syndrome.
- Raised / inappropriately normal ACTH: Suggestive of an ACTH dependent cause.
23
Q
Imaging
first line for suspected ACTH independent cushings?
A
- majority is caused by adrenal pathology
- in patients with suspected ACTH independent Cushing’s syndrome a CT of the adrenal glands is normally the first line investigation.
- Further tests may include MRI adrenal glands and PET/CT.
24
Q
first line in ACTH dependent cushings?
A
- high dose dexamethasone suppression test
- Pituitary adenomas(Cushing’s disease): High levels of dexamethasone are able to suppress ACTH production.
- Ectopic production: Despite high dose dexamethasone, ectopic tissues will not be suppressed and continue to produce ACTH.
25
ACTH dependent cushings - distinguishing causes?
cushings disease: high levels of dexamethasone will suppres ACTH production
ectopic production: no ACTH suppression
26
other tests for a pituitary adenoma?
* other tests: pituitary adenoma or malignancy - CTs and MRIs
* Petrosal sinus sampling is an invasive test that may be used to help identify a microscopic pituitary adenoma
27
exogenous cushings management
* gradual withdrawal from glucocorticoids
* stopping could result in addisonian crisis
28
gold standard for managing cushings disease?
* Transsphenoidal surgery is the gold-standard for treatment of Cushing's disease.
* microadenomectomy
* subtotal resections of the AP
29
medical management of cushings disease?
Metyrapone can be used, an inhibitor of 11β-hydroxylase, that leads to a reduction in cortisol synthesis.
30
Pituitary irradiation?
* This may be used in children and young people w CD or those in whom surgical techniques have failed.
* Effects are not immediate and takes around 6-12 months to have maximal effect.
31
adrenalectomy?
* In those in who all other therapies for CS have failed bilateral adrenalectomy may be used.
* This mandates lifelong glucocorticoid and mineralocorticoid replacement.
32
management of adrenal lesions ?
* surgical resection
* unilateral adrenal adnoma - curative tx
* Following surgery patients will need a tapering course of exogenous steroids for a period of time as their endogenous CRH and ACTH will be suppressed.
33
# Tx
Bilateral adrenal hyperplasia?
In patients with overt Cushing's bilateral adrenalectomy may be offered. Following this patients require replacement of glucocorticoids and mineralocorticoids
34
causes of cushings syndrome - CAPE?
* Cushings disease
* Adrenal adenoma
* paraneoplastic syndrome
* Exogenous steroids
35
Skin pigmentation?
* In a patient with Cushing’s syndrome, the pigmentation allows you to determine the cause as excess ACTH, either from Cushing’s disease or ectopic ACTH.
* This sign is absent in an adrenal adenoma or exogenous steroids.
36
Lack of cortisol suppression in resp to dexamethasone suggests ?
cushings syndrome
37
dexamethasone suppression results
IMAGE
38
types of dexamethasone suppression test?
* Low-dose overnight test (used as a screening test to exclude Cushing’s syndrome)
* Low-dose 48-hour test (used in suspected Cushing’s syndrome)
* High-dose 48-hour test (used to determine the cause in patients with confirmed Cushing’s syndrome)
39
bloods in CS?
* Full blood count may show a high white blood cell count
* U&Es may show low potassium if an adrenal adenoma is also secreting aldosterone
40
# Findings causes
Other tests for cushinhs?
* MRI brain for a pituitary adenoma
* CT chest for small cell lung cancer
* CT abdomen for adrenal tumours
41
what suggests syndrome of inappropriate ADH secretion?
The presence of euvolaemic hyponatraemia, with high urine osmolality (> 100 mOsm/kg) and high urine sodium (> 40 mmol/L),
42
cushings can cause?
DM
43
Sheehan syndrome?
Sheehan syndrome describes hypopituitarism caused by ischemic necrosis due to blood loss and hypovolaemic shock.
44
features of Sheehans syndrome?
* agalactorrhoea
* amenorrhoea
* symptoms of hypothyroidism
* symptoms of hypoadrenalism
45
Asherman's syndrome?
Asherman's syndrome, or intrauterine adhesions, may occur following dilation and curettage. This may prevent the endometrium responding to oestrogen as it normally would.
46
ABG in CS?
hypokalaemic metabolic alkalosis
47
Ectopic ACTH from lung cancer -
ACTH and cortisol remain high
48
high dose dexa test results?
A high dose of dexamethasone exerts negative feedback on pituitary neoplastic ACTH-producing cells (Cushing's disease), but not on ectopic ACTH-producing cells or adrenal adenoma (Cushing's syndrome).
49
Squamous cell carcinomas?
- smokers
- central location
- raised calcium
50
small cell lung cancer?
- smokers
- 'sentral' location
- syndromes - SIADH, ACTH
51
subacute thyroditis?
suggested by the tender goitre, hyperthyroidism and raised ESR. The globally reduced uptake on technetium thyroid scan is also typical
52
what can precipitate thyroid eye disease?
radioiodine therapy can precipitate thyroid eye disease but a majority of patients eventually require thyroxine replacement
53
CD results?
In Cushing's disease, cortisol is not suppressed by low-dose dexamethasone but is suppressed by high-dose dexamethasone - problem at pituitary
54
hashimotos is associated w development of?
MALT lymphoma
55
ABPi >1
An ABPI value of >1 can indicate vessel calcificaiton common in diabetes
Peripheral arterial disease will cause an ABPI value to be decreased, and a reduced ABPI is indicative of peripheral arterial disease
56
< 0.5 ABPI
<0.5 = severe arterial disease - PAD
57
ABPI 0.5-0.8 =
suggests presence of arterial disease or mixed arterial/venous disease - PAD or mixed PAD and PVD
58
ABPI > 1.3 =
>1.3 = suggests presence of arterial calcification, such as in some people with diabetes, RA, systemic vasculitis, atherosclerotic disease and advanced chronic renal failure.
59
electrolytes abn in addisons?
- hyponatreamia
- hyperkalaemia
- weight loss
60
what points to osteomalacia?
- low calcium and phosphate
- raised ALP
61
Sick euthyroid syndrome?
- low T3/ T4 levels
- inappropriately normal TSH
62
The first-line diagnostic test for Cushing's syndrome is a
low dose dexamethasone suppression test
63
how does myxoedema coma present?
Myxoedema coma typically presents with confusion and hypothermia.
64
how does an addisonian crisis present?
Addisonian crises typically feature malaise, nausea and vomiting, abdominal pain, and muscle cramps and paraesthesia,
65
thyrotoxic storm presentation ?
A thyrotoxic storm is a complication of hyperthyroidism that features hyperthermia, tachycardia, vomiting, and agitation.
66
commonest cause of AD in the uK?
The commonest cause of Addison's disease in the U.K is autoimmunity
67
AD electrolyte abn?
Addison's disease causes a metabolic acidosis with a normal anion gap
67
TRUELove and witts criteria?
T - Temp > 37.8
R - Rate > 90
U - (Uh)naemia Hb < 105
E - ESR >3
68
first line for acute mesenteric ischaemia?
lactate levels
69
AF+ abdo pain ->
mesenteric ischaemia
70
features of IMA?
- Acute
- Painful
- AF
+- bloody stool
71
IC?
- transient
- not so painful
- bloody diarhhea
- no history of AF (especially in SBA)
72
Ix and Mx of IC?
- do x ray = thumbprinting (especially splenic area)
- less pain, transient = conservative
73
What does perinicous anaemia predispose to?
gastric carcinoma
74
if C diff doesn't respond to first line vancomycin then
If C. difficile does not respond to first-line vancomycin , oral fidaxomicin should be used next, except in life-threatening infections
75
barretts oesophagus inc risk of?
- oesophageal adenocarcinoma
- achalasia
- risk of sq cell carcinoma of oesophagus
- when found endoscopic intervention needs to be done
76
mesenteric ischaemia triad?
triad of CVD, high lactate and soft but tender abdomen
77
Subclinical hyperthyroidism is associated with?
atrial fibrillation, osteoporosis and possibly dementia
78
Hormones produced by pituitary?
* Growth Hormone (GH)
* Adrenocorticotropin (ACTH)
* Thyrotropin (TSH)
* Prolactin
* FSH & LH
* ADH
* Oxytocin
79
hormones of pituitary
80
Cell types of pituitary?
* somatotropes - 30-40%
* corticotropes - 20%
* thyrotropes
* gonadotropes
* lactotropes
81
most common cell type in the pituitary?
somatotropes
82
hypopituitarism - symptoms
* Tiredness
* Weight loss
* Decreased libido
* Increased sensitivity to cold
* Loss of appetite
* Infertility
* Irregular periods
* Loss of body or facial hair
* Short stature
83
acromegaly presentation?
- bitemporal hemianopia
- sleep apnoea
- poor dentition
- poorly controlled T2DM, insulin resistance
- HTN, cardiomyopathy, heart failure
84
screening test for acromegaly?
* screening tests - IGF-1. random GH
85
confirmatory test of acromegaly?
GT test
86
other tests for acromegaly?
* imaging MRI pituitary
87
Random GH level - acromegaly?
* little value in diagosis
* GH secretion is pulsatile
* stimulated by a variety of factors like fasting exercise stress and sleep
88
IGF-1 measurement?
* Long half-life
* To assess GH secretion
* Screen for acromegaly
* Monitor response to treatment
| First line test for acromegaly. OGTT is second line
89
What impacts IGF-1 levels?
* IGF-1 concentrations vary with age
* Starvation, obesity and diabetes mellitus IGF-1
* pregnancy IGF-1
90
glucose tolerance test in acromegaly?
* Baseline GH level
* Ingestion of 75g oral glucose
* GH measured at 30, 60, 90 and 120 mins
* Failure to suppress GH levels to < 1ug/L
* Paradoxical rise
91
Tx options for acromegaly
* surgery
* radiotherapy
* medical
92
CS image showing symptoms
93
most common cause of CS
exogenous steroids
94
epidemiology of CS?
* female to male incidence is 1.5
* peak age of incidence: 25-40
95
Effects of glucocorticoids?
1. Increase glucose production
2. Inhibit protein synthesis
3. Increase protein breakdown
4. Stimulate lipolysis
5. Immunologic and inflammatory responses
96
important signs in cushings
* Spontaneous ecchymoses
* Purple striae
* Proximal myopathy
* Osteoporosis
* Hypokalemia
97
HPT axis?
* hypo: TRH
* AP: TSH
* thyroid: T4 and T3
98
HPA axis?
* hypo: CRH
* AP: ACTH
* adrenals: cortisol releasse
99
Cross talk between HPA and HPT?
* The pituitary-thyroid and pituitary-adrenal axes exhibit cross-talk and mutual regulation, with hormones from one axis influencing the function and secretion of hormones in the other axis.
* For example, cortisol can modulate thyroid hormone metabolism and activity, while thyroid hormones can affect adrenal steroidogenesis and cortisol metabolism.
100
how pituitary affects individuals clinically?
hormonal imbalances, vision changes, menstrual irregularities, infertility, growth abn, life threatening adrenal insufficiency
101
how adrenal diseases affect ppl clinically?
fatigue, weakness, weight changes, mood disturbances, blood pressure fluctuations, electrolyte imbalances, and metabolic disturbances. In severe cases, adrenal crises can occur, posing immediate danger to life.
102
how thyroid disease affect ppl clinically?
affecting metabolism, energy levels, mood, heart rate, weight, and reproductive health. If left untreated, these conditions can lead to complications such as heart disease, infertility, or thyroid storm (in hyperthyroidism)
103
social impacts of endocrine disorders?
* work and productivity: fatigue, mood changes, cognitive impairment
* QOL
* financial burden - Managing these chronic conditions often requires regular medical appointments, medications, and sometimes surgical interventions, which can lead to financial strain due to healthcare costs and lost income.
104
visible symptoms of some endocrine disorders?
* The visible symptoms of some endocrine disorders, such as weight changes or mood swings, may lead to stigma or misunderstanding from others. Additionally, living with a chronic illness can contribute to feelings of anxiety, depression, or isolation.
105
initial Ix of thyroid disease?
* TFTs
* imaging such as US for further evaluation of nodules
106
Ix for adrenal disease?
* cortisol levels
* ACTh stimulation test
* aldosterone and renin levels
* DHEA-S levels
107
Ix of pituitary disease?
* ACTH
* GH
* TSH
* LH
* FSH
* prolactin levels
108
imaging in endocrine disorders?
* MRI: with contrast is the preferred imaging modality for evaluating pituitary gland structure
* CT scan if MTI CI
* visual field testing - pituitary tumour can compress optic chiasm -> visual disturbances
109
PP produces?
* 2 hormones: oxytocin and ADH - periventricular and supraoptic nuclei.
* ADH is produced by the hypothalamus and stored by PP
110
ADH?
* inc water permeability and reabs in CDs
* increases total peripheral resistance
111
SIADH?
* excessive ADH secretion
* e.g. SCLC
* Continual ADH production occurs independent of serum osmolality, leading to abnormally low serum sodium levels (dilutional hyponatreamia) , highly osmolar urine and high urinary sodium levels.
112
Causes of SIADH?
* SIADH has a variety of causes, including brain injury, malignancy, drugs, infection, and hypothyroidism.
113
Risk of SIADH after ?
* paticular risk in transsphenoidal pituitary surgery (which is done for cushings disease)
114
Sx of SIADH?
* Headache
* Confusion
* Lethargy
* Anorexia
115
signs of SIADH?
* Seizures
* Reduced GCS
* Coma
* Myoclonus
* Ataxia
* Hyporeflexia
* Asterixis
116
Ix results in SIADH?
* renal function - hyponatreamia
* low serum osmolarity
* urine osmolarity- high above 100
* high urine sodium
117
Clinical signs of acromegaly
118
DI?
* Diabetes insipidus is characterised by the passage of vast volumes of dilute urine.
* deficiency/ resistance to ADH
* In some cases, as much as 20 litres of urine can be produced in 24 hours, leading to rapid dehydration and potentially death.
119
What are the causes of neurogenic DI?
* Mutations in vasopressin gene
* Malignancy: pituitary adenomas, craniopharyngiomas/metastases
* Trauma
* Infection: Meningitis
* Vascular: Sheehan’s Syndrome
120
Other causes of central/ neurogenic DI?
* Sarcoidosis (formation of granulomas in the pituitary gland)
* Haemochromatosis (deposition of iron in the hypothalamus and pituitary gland)
121
When does nephrogenic DI occur?
when ADH cannot bind to their receptors in the kidney.
122
causes of nephrogenic DI?
* Mutations in ADH receptor gene or aquaporin-2 gene
* Metabolic: hypercalcaemia, hyperglycaemia, hypokalaemia
* Drugs
* Chronic renal disease
* Amyloidosis
123
Acquired causes of nephrogenic DI?
* lithium
* hypercalacemia
* hypokalaemia
* instrinic renal disease
* post obst uropathy
124
Clinical features of DI reflect the inability to concentrate urine. The classic symptoms are:
* Polyuria
* Polydipsia
* Nocturia
* produces very large amounts of dilute urine
125
DI - signs of dehydration?
* dehydration - dry membranes, prolonged cap refill, hypotension
126
Ix of DI?
- Water deprivation test
- urine analysis
- desmopressin challenge test
127
DI - Water dep test?
In central DI, urine osmolality remains low despite dehydration, whereas in nephrogenic DI, urine osmolality increases following administration of exogenous ADH (desmopressin acetate)
128
urine analysis?
* urine analysis: In patients with DI, urinalysis typically reveals low urine osmolality (< 300 mOsm/kg) despite hypernatremia and plasma hyperosmolality.
129
Desmopressin challenge test?
In patients with central DI, desmopressin typically results in a significant increase in urine osmolality.
130
bloods for DI?
* FBC
* Renal function (check for renal impairment and hypokalaemia)
* Plasma osmolality
* Plasma glucose
* HbA1c
* Bone profile (check calcium)
131
urine tests for DI?
* 24-hr urine collection
* Urine specific gravity
* Urine osmolality
132
central/ neurogenic DI Mx?
Desmopressin
133
risk of using desmopressin?
- water retention -> hyponatreamia
- can occur as the synthetic ADH is not suppressible as ADH would be in normal physiology when plasma osmolality
134
nephrogenic DI Mx?
* diuretics - thiazide
* desmopressin in non hereditary forms of nephrogenic DI
135
most common cause of hypopituitarism?
* compression of the pituitary gland by non-secretory pituitary macroadenoma (most common)
136
other causes of hypopituitarism?
* pituitary apoplexy
* Sheehan's syndrome: postpartum pituitary necrosis secondary to a postpartum haemorrhage
* hypothalamic tumours e.g. craniopharyngioma
* trauma
* iatrogenic irradiation
* infiltrative e.g. hemochromatosis, sarcoidosis
137
hypopit - ACTH deficiency?
* tiredness
* postural hypotension
138
hypopit - LH/ FSH deficiency?
* amenorrhoea
* infertility
* loss of libido
* low TSH
* feeling cold
* constipation
139
hypopit - low prolactin?
* problems with lactation
140
hypopit - features of the underlying cause?
* pituriary macroadenoma → bitemporal hemianopia
* pituitary apoplexy → sudden, severe headache
141
Mx of hypopit?
* treatment of any underlying cause (e.g. surgical removal of pituitary macroadenoma)
* replacement of deficient hormones
142
what is acromegaly caused by?
* acromegaly is caused by an excess of GH production related to a pituitary adenoma
143
how does acromegaly present?
* tends to present with macrognathia, frontal bossing and enlargement of hands and feet.
* Presentation may also be related to the aetiology - e.g. mass effect of a pituitary adenoma resulting in visual field defects and headache.
144
acromegaly is assoc w systemic conditions like?
CVD, DM
145
GH/ somatotropin is released by?
somatotropic cells of the AP
146
GH release pathway?
* Growth hormone releasing hormone (GHRH) is released from the arcuate nucleus of the hypothalamus.
* At the AP GH is released
* this stimulates release of IGF-1
147
GH secretion is?
pulsatile, IGF-1 has more stable levels
148
IGF-1?
* produced and released by the liver
* This axis features negative feedback, in which IGF-1 and GH release leads to the inhibition of GHRH and stimulation of somatostatin release.
149
What accounts for over 90% of cases of acromegaly?
pituitary adenomas - Growth hormone secreting somatotroph adenomas are the commonest cause of acromegaly.
150
gigantism?
excess GH secretion in childhood prior to fusion of the epiphyseal growth plates
151
other causes of acromegaly (rare)
* Ectopic release of GH: May be seen in neuroendocrine tumours.
* Ectopic release of GHRH: Related to tumours including carcinoid and small cell lung cancer
* Excess hypothalamic release of GHRH: Related to hypothalamic tumours.
152
acromegaly tends to have a
insidious onset
153
CF of acromegaly - GH excess?
* Acromegaly leads to enlargement of hands, feet, lips and nose.
* Examination should look for wide spaced teeth, prognathism (large forehead) and frontal bossing.(protrusion of lower jaw)
154
acromegaly - men?
may be deepening of voice
155
syndrome associated w acromegaly?
Carpal tunnel
156
CFs of acromegaly - mass effects?
* macroadenomas can lead to this
* headaches common
* visual changes - pressure on the optic chiasm -> bilateral hemianopia
157
acromegaly - macroadenomas can impair pituitary function ->
* In women menstrual dysfunction is seen, ED in men
* In up to 30% of patients concomitant hyperprolactinaemia is seen.
158
features of hyperprolactinaemia?
- galactorrhea
- dysmenorrhoea
- hypogonadism
- infertility
159
GH and IGF-1 excess can lead to:
* inc CV disease - HTN, cardiomyopathy, HF
* insulin resistance -> T2DM
* obstructive sleep apnoea
* organomegaly - heart, liver, lungs, prostate and kidneys
* CRC and diverticulosis - inc risk
* thyroid enlargement & inc incidence of thyroid cancer
* headache - mass effect or result of GH excess
160
diagnosis of acromegaly?
* IGF1 levels
* high - confirms diagnosis -> image
* equivocal: carry out oral glucose tolerance test
160
acromegaly inc risk of?
- T2D
- OSA
- CRC & diverticulosis
- thyroid cancer
161
Oral GTT in acromegaly?
* Serum GH can be measured before and after glucose stimulation.
* In healthy individuals, GH release is suppressed following the administration of exogenous glucose.
* In patients with acromegaly, GH levels are unsuppressed.
162
pituitary MRI in acromegaly?
* Images pituitary - adenoma?
* Rarely other causes may be found including hypothalamus tumours and pituitary carcinoma.
163
further Ix of acromegaly - GHRH levels?
Elevated levels indicate excess production from a hypothalamus tumour or ectopic source.
164
CT CAP in acromegaly?
Used to look for evidence of tumours that may lead to acromegaly through GH or GHRH production (e.g. small cell lung cancer, carcinoid).
165
what is the first line in acromegaly?
* transphenoidal surgery
* microadenomas tend to have better results than macroadenomas
166
transphenoidal surgery?
- CD and acromegaly
167
when are medical therapies used for acro?
Medical treatments may be used in patients who are not operative candidates or where surgery fails to achieve biochemical cure.
168
Mx of acro - octerotide?
* Somatostatin analogs (e.g. Octreotide): given as a monthly injection it reduces the release of GH and may cause shrinkage of tumours.
169
Acro Mx - GH antagonists?
* Growth hormone antagonists (e.g. Pegvisomant): given as daily injection, lowers IGF-1 levels.
170
Acro Mx - dopamine agonists?
(e.g. Bromocriptine): can reduce the release of GH, though they are only effective for a small proportion. Advantage is they can be given as a tablet.
171
radiotherapy in acro??
* where surgery and medical management fails
* rarely used as primary therapy
* The biochemical response to radiotherapy can be slow, taking years.
172
why is radiotherapy for acro avoided in reproductive age grs?
* Risks include the development hypopituitarism; therefore, it is generally avoided in those of reproductive age.
173
cancer screening w acro?
* inc risk of thyroid and CRC
* CRC screening from age 40
174
patients w acro presenting w ? should be referred on a 2 week wait pathway
palpable nodularities
175
prognosis of acro?
* inc mortality
* inc risk of OSA and CV complications
176
Diastolic murmur + AF → ?
mitral stenosis
177
How does lymphoma present?
* incidental raised WBC
* lymphadenopathy - usually painless, neck or groin
* sweats - drenching sweats, often at night
- weight loss
- splenomegaly
178
pruitis is especially seen in
Hodgkins lymphoma
179
Sx of myeloid disorders?
* weight loss
* fatigue - anemia, non specific
* splenomegaly - feelings of fullness in abd, left upper quadrant pain, early satiety
* intermittent fevers
180
Features of BM failure?
* tiredness
* bruising
* infections - pneumocytis jiveroki with hodgkins lymphoma
* anemia - MCV may be raised
* neutropenia
* thrombocytopenia
181
which infection can occur paticularly w hodgkins lymphoma?
pneumocystis jiveroki
182
bone pains?
* bone pains - myeloma usually but any haem malignancy
183
other features of BM failure?
* osteolytic lesions - inhibition of osteoblasts
* localised/ generalised pain
* malignancies that cause expansion of the bone marrow can cause diffuse bone pain
* e.g. myelofibrosis, acute leukemias
184
why can haem malignancies cause gout?
- high cell turnover
* assoc w myelofibrosis and myeloproliferative disorders
185
paraneoplastic features of haem maligancies?
* skin rashes
* vasculitis
* arthropathy
* immune cytopenias
186
red flags of haem cancer?
* painless lymphadenopathy
* weight loss
* night sweats
187
# causes
Anaemia - Reduced Hb and reduced MCV ?
* Iron deficiency
* Thalassaemias and haemoglobinopathies
* Lead poisoning
* Sideroblastic anaemias
* Anaemia chronic disease (but this is mostly normocytic)
188
Anaemia - normal MCV?
* Anaemia chronic disease
* Acute blood loss
* Bone marrow failure syndromes
* Malignant infiltration
* Mixed haematinic deficiencies
* Haemolysis
189
Inc MCV anaemia?
* Megalobalstic anaemias
* Liver disease
* Alcohol
* Hypothyroidism
* Myelodysplasia
* Malignant infiltration
* Haemolysis
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Causes of decreased red cell production ?
* iron def
* megaloblastic anemia
* haemoglobinopathies
* anemia of chronic disease
* anemia renal disease
* BM failure
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relative anaemias?
* preg
* dilutional
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inc ref cell production?
* Hereditary causes
* Membrane defects
* Enzymopathies
* Haemoglobinopathies
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acquired causes of anaemia?
* Acute blood loss
* Haemolytic disorders (immune and non-immune).
* Hypersplenism
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IDA profile?
* ferritin low
* iron low
* transferrin high
* transferrin saturation low
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haemachromatosis profile?
* high ferritin and iron
* low transferrin
* high transferrin sat
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AOCD profile?
* ferritin is normal/ high
* iron low
* transferrin low
* transferiin sat low
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IDA vs AOCD?
* transferrin is high in IDA but low in AOCD
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Haemolytic anaemia?
* ferritin is high
* iron high
* transferrin sat: low
* transferrin: normal/ low
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megaloblastic anaemia?
* B12 and folate deficiency.
* Raised bilirubin and lactate dehydrogenase (LDH) due to ineffective erythropoiesis.
200
AOCD causes ?% of anaemias over 65?
20
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AOCD involves?
* MCV normal/ low
* non-progressive anemia
* B12/Folate/Ferritin normal.
* Iron/transferrin/transferrin saturation low.
* Main differential myelodysplasic syndromes.
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profile of haemolytic anaemia?
- macrocytic anaemia
- reticulocytosis
- rasied LDH and bilirubin
- polychromasia
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inherited causes of haemolytic anaemia - red cell defects?
* Hereditary spherocytosis
* Hereditary elliptocytosis
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inherited causes of haem anaemia - hb abn?
* Thalassaemias
* Sickle cell anaemia
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inherited causes of haem anaemia - metabolic defects?
* Glucose-6-phosphate dehydrogenase deficiency
- pyruvate kinase fef
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IDA slide
207
Megaloblastic anaemia histology
image
208
drug indused haemolysis histology
209
IDA appearance on histology?
* washed out
* pale center - halo look
* small red cells, microcytic hyperchromic anemia
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Megaloblastic anaemia appearance?
* large
* oval appearance of RBC - oval macroytes
* red cell precursors - normocytes
* abn WBC - hypersegmented neutrophil
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comps of megaloblastic anaemia?
* subacute degen of the SC -> demylination -> paraperesis
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hereditary spherocytosis - appearance
* circ dense red cells w no central pallor
* spherical shape instead of biconcave
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histology of myeloma?
* malignant plasma cells
* Monoclonal immunoglobulin (M band)
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myeloma features?
1.Renal dysfunction, hypercalcaemia, bone damage, anaemia.
2.>1 bone lesion on whole body MRI/CT/PET-CT.
3.Free light chain ratio >100.
4. >60% plasma cells in bone marrow.
215
myeloma tends to present in which age gr?
70s normally
216
presentation of myeloma?
* pain from osteolytic bone lesions
* renal issues
* anemia
* bone problems
* infections
* amyloidosis
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blood film of myeloma?
* rouleax formation
* Increased levels of abnormal plasma cells in the blood can cause red blood cells to stick together, forming stacks known as rouleaux formation.
* This can appear as linear stacks of red blood cells on the blood film.
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lab features of myeloma?
–Raised calcium
–Raised urea & creatinine
–Raised total protein
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prognostic protein in myeloma?
beta-2 microglobulin
220
what is usually elevayed in myeloma?
- ESR and plasma viscosity
- bone marrow has inc plasma cells
221
what else is seen in myeloma- bands
* M band in serum.
* M band in urine (BJP).
* Serum free light chains.
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abn in myeloma?
* immunoelectrophoresis - marked immune paresis
* most cases produce IgG
223
what is diagnostic of myeloma?
* if more than 10% of WBC in the marrow are plasma cells -> diagnostic of myeloma
224
myeloma bone lesions?
* myeloma bone lesions won't show up on a radionucleotide bone scan
* other lesions e.g. met breast cancer will bc theyre hypermetabolic
* in myeloma these are areas of reduced bone density so won't show
225
Tx of myeloma?
*Solitary plasmacytomas radiotherapy.
*MGUS and asymptomatic Myeloma (chains of <100) do not require therapy.
226
myeloma bone disease?
bisphophonates
227
Myeloma - for patients under 70?
* Thalidomide/lenalidomide/bortezomib containing combination therapy.
* autologous stem cell transplant with high dose Melphalan.
* Bisphosphonate for myeloma-bone disease.
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genetics of sickle cell?
* recessive - 2 copies of the defective hb gene needed - 2x HbS
* chromosome 11 for beta chains
* 1 hbs gene: sickle cell trait
229
thalassemias vs haemoglobinpathies?
* decreased production of alpha or beta chains - thalassemias
* mutant variant of these chains - haemaglobinopathies
230
normal vs Hbs?
* normal: HbA
* Hbs: 2 abn beta chains
231
sickle cell trait?
* sickle cell trait offers protection against malaria bc sickle cells are less suitable for malaria parasites
* sickle cell is endemic in sub saharan africa and areas of the middle east
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SCA -large risk of ?
sepsis
233
why is sepsis high risk in SCA?
* Underlying immune dysfunction related to hyposplenism.
* Mainly encapsulated bacteria.
* Highest risk under the age of 5 years.
234
Reducing sepsis risk in SCA?
* Role of pneumococcal vaccination and prophylactic penicillin in children w SCA
235
painful vaso-occlusive crisis?
* reccurent episodes of bone pain
* often in thighs, arms, ribs, pelvis, spine
* children are more affected in small bones of the hands and feet
236
Sickle cell crises can be triggered by?
* crises can be triggered by stress or infection
* exposure to cold
* Mx: rest/ rehydration
* simple analgesia
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SCA - acute chest syndrome?
* serious comp
* children or adults
* history of painful crisis in ribs w assoc inc breathlessness
238
SCA - AC syndrome - chest XR?
* hypoxemic - abn chest XR - infiltrates in lungs can be seen
239
Mx of acute chest syndrome?
* analgesia for pain
* red cell exchange for hypoxia - aims to reduce HbS levels down to less than 30%
240
leg ulceration w SCA?
* vasoocclusion of small vessels
* over medial and lateral malleolus
* can be chronic and recurrent
241
SCA comps - vascular?
* children and adults
* stenosis of ICA due to hyperplasia
242
screening w SCA?
* All children w sickle cell should be screened for ICA stenosis using transcranial dopplers
* if found, transfusion required
243
MX of stroke w SCA?
hypertransfusion - reg transfusion of red cells to suppress HbS
244
SCA - anaemic crisis?
* can suddenly worsen
* infection w parovirus can cause an aplastic crisis
* in young children there can be splenic sequestration in which blood pools
245
Hb levels on a FBC?
* low levels - anemia
* high levels - dehydration, polycythemia vera
246
WBC on a FBC?
* leukopenia - bone marrow disorders, viral infections
* leukocytosis - infections, inflammation, leukemia
247
Platelet count on FBC?
* thrombocytopenia
* thrombocytosis - inflammation, infection, bone marrow disorder
248
MCV on FBC
* Low MCV indicates microcytic anemia, often due to iron deficiency.
* High MCV suggests macrocytic anemia, commonly caused by vitamin B12 or folate deficiency, alcohol
249
Bone marrow aspiration?
* bone marrow aspiration and biopsy provides direct observation of RBC precursors
* The presence of abnormal maturation (dyspoiesis) of blood cells and the amount, distribution, and cellular pattern of iron content can be assessed
* only done when: anemia is unexplained, more than one cell lineage abn - a.g. anemia and leukopenia, suspected primary bone marrow disorder e.g. leukemia
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