Week 4 Flashcards
(236 cards)
1
Q
What is acromegaly caused by
A
Excess growth hormone
2
Q
Describe the process of releasing growth hormones and its negative feedback mechanism
A
1) GHRH (growth hormone releasing hormone) released from the hypothalamus into anterior pituitary gland
2) This stimulates the somatotropes in anterior pituitary gland to secrete GH (growth hormone) into the blood
3) GH stimulates the release of IGF-1 from the liver
The release of IGF-1 and GH inhibits the release of GHRH and stimulates the release of somatostatin
Somatostatin is a negative regulator of GH as well
3
Q
Role of somatostatin in growth hormone production
A
Inhibits release of growth hormone
4
Q
What is IGF-1
A
Insulin-like growth factor released by the liver which stimulates systemic body growth and has anabolic effects
5
Q
What is gigantism
A
Excess growth hormone during childhood causing unusually tall stature and rapid growth
6
Q
Which cells secrete GH in the anterior pituitary gland
A
Somatotropes
7
Q
Most common cause of acromegaly
A
Pituitary adenoma
8
Q
Acromegaly can be caused by malignancy in which cells of the pituitary gland
A
Somatotropes
9
Q
Causes of acromegaly
A
Pituitary adenoma
Ectopic release of GH
Ectopic release of GHRH
Hypothalamic tumours
10
Q
Which cancers can cause ectopic release of GHRH
A
Carcinoid (neuroendocrine tumour)
Small cell lung cancer
11
Q
Symptoms of acromegaly
A
Large hands and feet
Frontal bossing
Bulging out of lower jaw (prognathism)
Macroglossia
Obstructive sleep apnea
Enlarged nose
Visual loss
Headaches
Joint pain
12
Q
What can cause visual loss
A
Pituitary adenomas compressing the optic chiasm
13
Q
What is usually seen due to tumours compressing the optic chiasm
A
Bitemporal hemianopia
14
Q
What is bitemporal hemianopia
A
partial blindness where vision is missing in the outer half of both the right and left visual field
15
Q
Which conditions are at increased risk due to acromegaly
A
Hypertension
CVD
Colon cancer
Insulin resistance
Osteoporosis
16
Q
Why may acromegaly cause obstructive sleep apnea
A
Due to enlarged nasopharynx; acromegaly causes thickened soft tissues
17
Q
Why may hypopituitarism occur in acromegaly
A
Due to large pituitary adenoma causing infarction of pituitary tissue hence impairing function of the rest of the pituitary gland
18
Q
What lab tests can be done to diagnose acromegaly
A
IGF-1 level
Oral glucose tolerance test
19
Q
Why is IGF-1 level measured instead of GH
A
Because GH level is highly variable whereas IGF-1 is relatively constant hence more reliable
20
Q
When should you do glucose tolerance test for acromegaly
A
If IGF-1 is raised or uncertain to confirm the diagnosis
21
Q
What would the lab test results be for acromegaly (IGF-1 levels and glucose tolerance test)
A
Raised IGF-1 level
GH level not suppressed after administration of glucose
22
Q
Why would the GH level be suppressed after administration of glucose in normal healthy people
A
Because GH acts like glucagon which would be suppressed due to high levels of insulin
23
Q
Why may growth decrease if you eat lots of refined sugars and carbs during childhood
A
Because these food raises insulin level the most which would inhibit GH secretion
24
Q
Except IGF-1 level and glucose tolerance test, what other tests may be done for acromegaly if patients present certain symptoms
A
MRI / CT / PET scan
Visual field test
Test for deficiencies in other pituitary hormones
25
Management of acromegaly
Surgery is first line
Drugs second
Radiotherapy third
26
What drugs may be used for acromegaly
Somatostatin analogues
GH antagonists (but not really used)
27
Examples of somatostatin analogues
Lanreotide
Octreotide
Sandostatin LAR
28
Effects of somatostatin analogues
Reduces GH (remember somatostatin is a negative regulator for GH)
Shrinks tumour
Relieves headache
29
Side effects of somatostatin analogues
Local stinging
Flatulence
Diarrhea
Abdominal pain
Gallstones
30
Why is GH antagonist last line for drug therapy
It doesn't shrink tumour size
Decreases IGF-1 but serum GH concentration may increase
31
When is radiotherapy used to treat acromegaly
For those where surgery and drug therapy failed
32
Why is radiotherapy avoided in those of reproductive age
It can cause hypopituitarism and it is associated with thyroid cancer
33
Describe the structure of the adrenal gland
Outer layer - cortex, made of 3 layers
Center- medulla
34
What are the 3 layers of the cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
35
Function of adrenal gland
Synthesis and release of steroid hormones and catecholamines
36
Which steroid is synthesised and released by zone glomerulosa
Mineralcorticoids
37
Which layer of the adrenal cortex secretes glucocorticoids
Zona fasciculata
38
Which hormones are secreted by zone reticularis
Adrenal androgens
39
What does the medulla of adrenal gland secrete
Catecholamines
40
Main glucocorticoid secreted by the adrenal gland
Cortisol
41
Main mineralocorticoid secreted by the adrenal gland
Aldosterone
42
What are the catecholamines secreted by the adrenal medulla
Epinephrine (adrenaline)
Norepinephrine (noradrenaline)
Dopamine
43
Which cells make up the most of medulla
Chromaffin cells
44
What is the starting material for the synthesis of all steroids
Cholesterol
45
Aldosterone is regulated by which systems
Renin-angiotensin system
46
Cortisol and androgens are regulated by which system
Hypothalamis-pituitary- adrenal axis (HPA)
47
What factors can trigger the production of CRH from hypothalamus
Stress
Time of day
Illness
48
Describe the HPA axis
Hypothalamus secretes CRH in response to stress/illness/time of day -> CRH stimulates the release of ACTH from anterior pituitary gland -> ACTH travels through blood to the adrenal cortex to stimulate the synthesis and secretion of cortisol
49
Describe how dose cortisol level vary throughout the day
Highest during the day
Lowest in the night
50
Describe the renin-angiotensin system
1) trigger factors stimulating release of renin from kidneys
2) Renin cleaves angiotensin into angiotensin I
3) ACE cleaves angiotensin I into angiotensin II
4) Angiotensin II exerts its effects and stimulates release of aldosterone and ADH
51
Function of RAAS
to regulate blood pressure and fluid balance
52
What are the triggers for RAAS
Decrease in blood pressure (renal hypotension)
Sympathetic stimulation
Reduced sodium
53
Where is ACE found
Vascular endothelium of the lungs
54
How does angiotensin II increase blood pressure
Stimulate release of aldosterone
Stimulate release of ADH
Stimulate vasoconstriction
Increases sodium reabsorption at proximal tubule (hence water)
55
How does aldosterone increase blood pressure
Increases sodium retention by increasing sodium potassium channels in epithelial sodium channels in distal tubule
= increases sodium reabsorption and potassium excretion
56
How does ADH increase blood pressure
Insert aquaporin channels to increase permeability of the collecting duct to water
Increase sodium reabsorption at ascending limb of loop of hence (hence water)
= more water retained instead of excreted into urine
57
Why does high level of aldosterone lead to lower levels of potassium
Because aldosterone increases the activity of sodium potassium pump which pumps sodium in and potassium out.
58
How do steroids exert an action
Bind to intracellular receptors to affect transcription of certain genes
59
Cortisol (glucocorticoids) actions on circulation
Increase cardiac output
Increase in blood pressure
Increase in renal blood flow and filtration rate
60
Cortisol actions on metabolism
Increases blood sugar
Increases lipolysis
Increases proteolysis
Increases osteoclast activity
61
Effect on bones due to long term steroid use
Accelerated osteoporosis
62
Immunological effects of the cortisol
Decrease in capillary diltatation
Decrease in macrophage activity
Decrease in leukocyte migration
Dcrease in inflammatory cytokine production
63
Use of steroids
Suppress inflammation
Suppress immune system
64
Examples of when is steroid used
Asthma
RA
Ulcerative colitis, Crohn's disease (IBD)
65
Effects of aldosterone through binding to mineralocorticoid receptor
Regulates blood pressure
Sodium/Potassium balance
Regulation of extracellular volume
66
What is Addison's disease
= primary adrenal insufficiency (including all the primary causes)
67
Most common primary cause of adrenal insufficiency
Autoimmune destruction
68
Primary causes of adrenal insufficiency (Addison's)
Autoimmune destruction
Surgery
Trauma
Infections
Haemorrhage (Waterhouse Friderichsen Syndrome)
Sarcoidosis / neoplasm
69
Which infection is associated with Addison's
TB
70
Most common secondary cause of adrenal insufficiency
Chronic exogenous steroid
71
How may excess exogenous steroid lead to adrenal insufficiency
1. steroids exert negative feedback on ACTH production hence ACTH may be suppressed for a long term -> Unable to produce enough ACTH during metabolic stress when they stop taking steroids -> adrenal insufficiency
2. atrophic adrenal glands unable to respond to ACTH
72
Secondary causes of adrenal insufficiency
Excess exogenous steroid
Panhypopituitarism
CRH deficiency
73
Addison's disease is associated with which other autoimmune diseases
T1 diabetes
Autoimmune thyroiditis (Hashimoto's / grave's)
Pernicious anemia
74
Clinical features of adrenal insufficiency
Unexplained weight loss / anorexia
Skin hyperpigmentation
Fatigue
Hypotension
Hypoglycaemia
Abdominal pain
Vomiting
Loss of pubic hair / axillary hair
75
Mneumonic for symptoms of adrenal insufficiency (W STEROID)
Sugar and sodium low
Tired
Electrolyte imbalance (hyperkalaemia and hyponatraemia)
Reproductive changes (loss of pubic hair / axillary hair)
O lOw blood pressure
Increased skin pigmentation
Diarrhea and vomiting
76
What causes skin hyperpigmentation in Addison's disease
Due to high ACTH level stimulates melanocytes to produce melanin
77
Why would there be high ACTH levels in Addison's disease
Due to low level of steroids -> less negative feedback -> ACTH and CRH not inhibited
78
Lab tests for adrenal insufficiency
Blood tests - Na+, K+ levels, glucose level
ACTH levels
SYNACTHEN test
Renin/aldosterone level
21 hydroxylaze autoantibodies
CT scan / MRI
79
What is synacthen test for adrenal insufficiency
Injection of synthetic ACTH and measure cortisol level before and 30 minutes after injection
80
Synacthen test that suggests adrenal insufficiency
low cortisol level 30 minutes after injection
81
Renin Aldosterone level that suggests adrenal insufficiency
High renin
Low aldosterone
82
What Na+ and K+ levels can suggest adrenal insufficiency
Hyponatraemia
Hyperkalaemia
83
What is the characteristic trio of lab results suggesting adrenal insufficiency
Hypoglycaemia
Hyponatraemia
Hyperkalaemia
84
Management of Adrenal insufficiency
Hydrocortisone
+ Fludrocortisone if aldosterone is insufficient
(usually both are used)
Sick day rules and education
85
Hydrocortisone is the synthetic replacement for which steroid
Cortisol
86
What are the sick day rules for adrenal insufficiency
Double the dose during moderate intercurrent illness
Self inject IV hydrocortisone during severe intercurrent illness
Cannot miss a dose of steroids, they need steroids for life
87
What is Addisonian (adrenal) crisis
Exacerbation of adrenal insufficiency where the absence of steroid hormones can lead to life-threatening situations
88
Symptoms of Addisonian (adrenal) crisis
Hypotension
Reduced consciousness
hypoglycaemia
Hyponatraemia
Hyperkalaemia
Very unwell
89
Management of Addisonian crisis
Do not delay treatment, treat ASAP
IV hydrocortisone
IV fluid resuscitation
Treat underlying cause
Monitor electrolytes, blood pressure continuously
90
What can trigger Addisonian crisis
Acute illness
Trauma
Infection
Withdrawal / forgot to take steroids
these causes stress which increases demand for cortisol
91
What happens to the adrenal gland in absence of ACTH / CRH
Atrophy due to long term failure to be exposed to and stimulated by ACTH / CRH
92
What are some differences in clinical features between primary and secondary adrenal insufficiencies
Primary adrenal insufficiency causes skin hyperpigmentation but secondary adrenal insufficiency will not due to no increase in ACTH
Aldosterone will not be affected because it is regulated by renin-aldosterone system instead of by ACTH / CRH
Secondary does not have hyperkalaemia
93
What may be excluded in the management of secondary adrenal insufficiency
The use of fludrocortisone because aldosterone is not deficient
94
Pathogenesis of osteoporosis
Activity of osteoclasts > activity of osteoblasts leading to decrease in bone density (bone loss)
95
When do people achieve their peak bone mass
Usually in their 20s
96
What are the regulating factors for peak bone mass
Genetics (70-80 %)
Body Weight
Sex hormones
Diet
Exercise
97
Is a higher peak bone mass beneficial
Yes, it is more protective against osteoporosis
98
Common fracture sites due to osteoporosis
Neck of femur
Humeral neck
Vertebral body
Distal radius
99
What can a fracture in the vertebral body lead to
Loss in height
Kyphosis due to vertebral bodies compressing into each other
100
What happens to the ribcage in severe kyphosis
Rests on the pelvis and causes discomfort
101
Risk factors of osteoporosis
Female
Age
Post-menopausal women
Oestrogen deficiency
Long term use of steroids
Alcohol, smoking
Malabsorption
Vit D / calcium deficiency
Endocrine disorders
Rheumatoid arthritis
Chronic liver disease
102
Why are post menopausal women at risk of osteoporosis
Due to reduced oestrogen level
103
Why does steroid use increases risk of osteoporosis
Increases osteoclast activity
104
What GI conditions can cause malabsorption hence increase risk for osteoporosis
IBD
Coeliac
105
What endocrine disorders increases risk of osteoporosis
Acromegaly
Hyperparathyroidism
Cushings
Diabetes
106
Investigations for osteoporosis
Tests to exclude non-osteoporotic low impact fractures
Fragility Fracture risk assessment ( may be skipped under certain circumstances)
DXA scan
Deficiencies in vitamin D / Calcium
107
Which online assessment tools are used to calculate the fragility fracture risk score
QFracture (preferred)
FRAX
108
When should 10-year fragility fracture risk score be calculated
Before DEXA scan except certain circumstances
109
Under what circumstances allow patients to be sent for DXA scan directly instead of calculating their fragility fracture risk first
>50 female that has previous fragility fractures
<40 with major risk factors for fragility fractures
110
Why is QFracture preferred over FRAX
Because FRAX underestimates certain factors
111
What factors does FRAX underestimate
Long term use of steroids
History of multiple fragility fractures
Heavy drinking and smoking
112
What should be done to those with a intermediate risk of fragility fracture close to recommended threshold + with associated risk factors
Send for DXA
Even though they did not reach the threshold, it is still important to send them for DXA because they present with risk factors and also because the online assessment tools may underestimate risk of certain factors
113
What does T score in DXA scan represent
The number of standard deviations a patient's bone density is from the average for a healthy young adult of the same gender
114
Interpret the T scores from DXA
Normal = T > -1
Osteopenia = -2.5 < T < -1
Osteoporosis = T
115
Management for those with T score > -2.5
Advise on changing habits that are risk factors for osteoporosis
Treat the conditions that are risk factors for osteoporosis
Repeat DXA within 2 years
116
Management for those with T score
Begin drug treatment
Advise on lifestyle changes
117
What drugs are used to treat osteoporosis
Bisphosphonates
Denosumab
Teriparatide
HRT (hormone replacement therapy)
118
Examples of bisphosphonates used for osteoporosis
Alendronate
Zoledronic acid
119
What are bisphosphonates and what are their effects
Analogues of pyrophosphate which is absorbed onto the bone and taken up by osteoclasts. This induces death of osteoclasts
120
Side effects of bisphosphonate
GI disturbance
Headache
Oesophagitis
Osteonecrosis (rare)
Atypical femoral fracture (rare
121
What can be used for a osteoporotic patient who cannot tolerate oral preparations
Yearly injection of zoledronic acid
122
First line drug used for osteoporosis
Bisphosphonate (aledronate)
123
What are the alternatives for bisphosphonate
Denosumab
Teriparatide
Romosozumab
124
What is denosumab and its actions
It is a mAB. It binds to RANKL to inhibit this receptor which inhibits the activity of osteoclasts
125
Who should be considered to be given HRT
early menopausal women
Young post-menopausal women
126
Side effects of HRT
Breast tenderness
Leg cramps
Changes in mood
Increases risk of blood clots, breast cancer and endometrial cancer
127
What lifestyle advices should be given to all patients with osteoporosis
Smoking cessation
Reduce alcohol consumption
Regular weight bearing exercises
128
What differentials should be taken into account when a patient presents with low impact fractures
Pathological fracture due to metastases / primary bone cancer?
Any secondary causes such as endocrine diseases / chronic liver or kidney diseases
129
What is Cushing's syndrome
A condition caused by excess cortisol
130
Types of causes of Cushing's syndrome
ACTH dependent
ACTH independent
Exogenous cause
131
ACTH dependent causes of Cushing's syndrome
Pituitary adenoma (Cushing's disease)
Ectopic ACTH poduction
Ectopic CRH production
132
What conditions can cause ectopic ACTH production
Carcinoid / carcinoma
Small cell lung cancer
133
Which lung cancer can cause ectopic ACTH production
Small cell lung cancer
134
ACTH independent causes of Cushing's
Nodular hyperplasia
Adrenal adenoma
Adrenal carcinoma
135
What is the most common endogenous cause of Cushing's
Pituitary adenoma
136
What is the most common cause of Cushing's
Excess / long term use of glucocorticoids (steroids)
= iatrogenic
137
What conditions may require long term use of steroids
Asthma
Rheumatoid arthritis
IBD
Organ transplants
138
How does long term steroid use lead to adrenal cortex atrophy
Long term steroid use causes chronic suppression of ACTH. This eventually leads to atrophy of the adrenal gland due to long term failure to be exposed and respond to ACTH
139
Clinical features of Cushing's
Easy bruising due to thinning of skin
Facial swelling and redness
Proximal myopathy
Buffalo hump
Increased abdominal fat
Striae
Hyperpigmentation in ACTH dependent causes of Cushing's
140
Cushing's syndrome can increase the risk of which conditions
Hypertension
Osteoporosis
Diabetes
Obesity
141
What is buffalo hump
collection of fat accumulated on the back of the neck
142
Sequence of investigations for Cushing's
1) do tests to establish that there is excess cortisol
2) do tests to find the underlying cause
143
What investigations can be done to establish that there is excess cortisol
24 hour urinary free cortisol
Low dose dexamethasone suppression test
Late night salivary cortisol measurement
144
Describe the low dose dexamethasone suppression test
Dexamethasone is a strong glucocorticoid
Low dose dexamethasone should be able to suppress ACTH level in normal people (negative feedback). In patients with excess ACTH, low dose will not be able to suppress it.
Excess ACTH suggests excess cortisol due to ACTH dependent causes
145
What feature of cortisol will be absent in patients with Cushing's syndrome when we test them with late night salivary cortisol measurement
Diurnal variation of cortisol
146
Investigations for identifying the cause of Cushing's syndrome
Plasma ACTH
High dose dexamethasone suppression test
MRI/ CT / PET scan
Petrosal sinus sampling
147
Why is plasma ACTH level tested first in order to find the underlying cause of Cushing's
To see whether the excess cortisol is due to ACTH independent / dependent causes
148
What is the high dose dexamethasone suppression test used for
To differentiate between pituitary adenoma and ectopic ACTH prodcution that is causing Cushing's
149
Describe the result of high dose dexamethasone in patients with pituitary adenoma
High dose dexamethasone will be able to suppress ACTH level if the patient has pituitary adenoma. This is because the pituitary adenoma is less responsive towards normal negative feedback but it is more responsive towards high dose glucocorticoids
150
Describe the result of high dose dexamethasone in patients with ectopic ACTH production
ACTH level not suppressed
151
When is petrosal sinus sampling used for Cushings
Invasive sampling that is used if imaging / other investigations have been insufficient to reach a diagnosis
152
Describe the petrosal sinus sampling
Invasive procedure sampling ACTH level from the veins draining pituitary gland
153
If suspecting a patient with Cushing's who is on long term steroid therapy, what investigations should you suggest
Low and high dose dexamethasone will not be useful.
Advise to lower steroid use
154
Management of Cushing's syndrome
GRADUALLY stop steroids if Cushing's was due to long term steroid use
Surgery
Drugs
155
Why should you gradually stop steroids instead of abruptly to treat a patient with Cushing's
Abruptly stopping it can cause Addisonian crisis because the patients are likely to have developed suppression of their normal endogenous steroid production
= abruptly stopping it will lead to supply of steroid < demand = exacerbation of adrenal insufficiency
156
What drugs can be used to treat Cushing's
Ketoconazole
Metyrapone
Mitotane
157
When are drugs used in the management of Cushing's
In preparation for surgery to temporarily reduce glucocorticoid level
Long term in patients who are unfit for surgery
158
What is pseudo-Cushing's
When patients present with symptoms like Cushing's but does not have Cushing's
159
What is the difference between pseudo-Cushing's and Cushing's
Psuedo-Cushing's still has diurnal variation for cortisol but Cushing's does not
160
What can cause pseudo-Cushing's
Chronic alcoholism
161
What is primary aldosteronism
Excess of aldosterone independent of the renin-angiotensin-aldosterone system
162
Causes of primary aldosteronism
Bilateral idiopathic hyperplasia
Aldosterone producing adenoma (Conn's adenoma)
Unilateral hyperplasia
Familial hyperaldosteronism
Adrenal carcinoma
163
What is the most common cause of primary aldosteronism
Bilateral idiopathic hyperplasia
164
Hallmark features of primary aldosteronism
Hypertension
Hypokalaemia
165
Does hypokalaemia occur in all patients with primary aldosteronism
No, only 30% of patients will have hypokalaemia.
166
Who should you suspect that may have primary aldosteronism
Those with moderate - severe hypertension
Those with resistant hypertension
Those with hypertension + sleep apnea
Those with hypertension + adrenal mass
Those with hypertension + family history of primary aldosteronism / family history of early onset stroke
167
Sequence of investigations for primary aldosteronism
1) establish that there is excess aldosterone
2) confirm diagnosis of PA
3) Find underlying cause of PA
168
What investigations can be done to establish that there is excess aldosterone
Measure aldosterone:renin ratio
Raised = excess aldosterone
169
What investigations can be done to confirm the diagnosis of primary aldosteronism
Saline suppression test
If saline does not suppress aldosterone = primary aldosteronism
170
What investigations can be done to find the underlying cause of primary aldosteronism
CT of adrenal gland
Adrenal vein sampling
171
When should adrenal vein sampling be used
To differentiate between bilateral and unilateral hyperplasia
To see whether the excess aldosterone was due to an adrenal adenoma or not
172
What does the management of primary aldosteronism depend on
Whether it is unilateral / bilateral
173
Management of primary aldosteronism (unilateral)
Unilateral adrenalectomy
Mineralocorticoid receptor antagonist
174
When is mineralocorticoid receptor antagonist used in the management of primary aldosteronism
Used to temporarily reduce aldosterone level to prepare patients for surgery
To be used as a long term treatment if the patient is unfit for surgery
175
Management of primary aldosteronism (bilateral)
Mineralocorticoid receptor antagonists
176
Examples of mineralocorticoid receptor antagonists
Spironolactone
Eplerenone
177
What is a side effect of spironolactone but not eplerenone
Gynaecomastia
178
What drugs can be used if mineralocorticoid receptor antagonists are not tolerated
ENaC inhibitors
179
What causes congenital adrenal hyperplasia (CAH)
21 hydroxylase deficiency
180
What is the function of 21 hydroxylase
It is an enzyme in adrenal gland required for conversion of progesterone into aldosterone and cortisol
181
How does 21 hydroxylase deficiency affect the steroid level
Because 21 hydroxylase is not there to convert progesterone into aldosterone and cortisol, there will be extra progesterone around.
The extra progesterone is diverted to produce more testosterone
182
Classic steroid levels seen in congenital adrenal hyperplasia
Low aldosterone
Low cortisol
High testosterone
183
Types of congenital adrenal hyperplasia
Typical: more severe form normally presented at birth / before birth
Non-typical: milder form normally presented at childhood /early adulthood
184
Clinical features of CAH
Adrenal insufficiency symptoms
(poor weight gain, fatigue, skin hyperpigmentation)
Adrenal crisis
Excess androgen symptoms
Genital ambiguity
Irregular periods
185
What are the excess androgen symptoms
Facial hair
Short
Early puberty
Deep voice
Rapid growth during childhood but final height is still shorter than average
186
What symptoms may not be presented in non-classic CAH
Aldosterone insufficiency (e.g. hypotension)
187
Investigations for CAH
Check serum concentrations of progesterone, testosterone and androgen precursors
188
Management for CAH
Cortisol replacement (hydrocortisone)
Aldosterone replacement in some
Surgical correction
-e.g. for those with genital ambiguity
Avoid overusing steroid treatment
189
What is hypercalcaemia
When the serum calcium concentration is greater than 2.6 mmol
190
Normal level of serum calcium
2.2 - 2.6 mol
191
Where can calcium be found
Mostly in bones
1% in intracellular and extracellular compartments
192
What is the function of calcium in intracellular compartments
For intracellular signalling
193
What is the function of calcium in extracellular compartments
Mostly free or bound to albumin
194
What is corrected level of calcium
Serum calcium level taking into account the calcium bound to albumin as well
195
Which factors regulate extracellular concentration of calcium
Calcitonin
PTH
Vitamin D
196
Which cells produce calcitonin
Parafollicular cells in thyroid gland
197
How is a decrease in calcium level regulated
1) Decrease in calcium level detected by CaSR in parathyroid glands
2) This stimulates the release of PTH from parathyroid glands
3) PTH stimulates
- the release of calcium from large calcium stores in bones
- increase in reabsorption of calcium in renal tubule
- activation of vitamin D
198
What happens when vitamin D is activated
Increases absorption of calcium in enterocytes from food
199
Causes of hypercalcaemia
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Malignancy
Thyrotoxicity
Thiazides, lithium
Vitamin D toxicity
Familial hypocalciuric hypercalcaemia
Granulomatous diseases (TB, sarcoidosis)
200
What can cause vitamin D toxicity
Ingestion of excess vitamin D
Sarcoidosis
Lymphoma
201
What is primary hyperparathyroidism
Excessive release of PTH causing hypercalcaemia
202
How do malignancies cause hypercalcaemia
Some tumours can secrete PTHrP which mimics the actions of PTH
Some tumours can increase osteoclastic activity -> break down of bones -> release calcium stored
203
How do thiazides cause hypercalcaemia
increasing calcium reabsorption into the distal convoluted tubule in exchange for sodium.
Thiazide function: reduces sodium and water reabsorption to decrease blood pressure
204
What is primary hyperparathyroidism
excess production of PTH by parathyroid gland
205
Causes of primary hyperparathyroidism
Parathyroid hyperplasia
Parathyroid gland adenoma
Parathyroid carcinoma
206
What is the most common cause of primary hyperparathyroidism
Parathyroid adenoma
207
What is tertiary hyperparathyroidism
When the glands become autonomous after a period of prolonged secondary hyperparathyroidism, producing excessive PTH even after the cause of hypocalcaemia has been corrected
208
Most common cause of tertiary hyperparathyroidism
Chronic kidney disease
209
What is secondary hyperparathyroidism
increased secretion of PTH in response to low calcium because of kidney, liver, or bowel disease
210
Causes of secondary hyperparathyroidism
Vitamin D deficiency
Conditions that lead to loss of extracellular Ca2+
Calcium malabsorption / inadequate Ca2+ intake
Conditions causing abnormal PTH activity
211
What conditions can lead to loss of extracellular Ca2+
Pancreatitis
Rhabdomolysis
212
Presentation of rhabdomyolysis
Pain in proximal muscle
Myalgia
213
Causes of rhabdomyolysis
Severe hypothyroidism
Statins
214
Investigations for rhabdomyolysis
Creatinine Kinase (high)
215
What conditions can cause abnormal PTH activity
Kidney disease
Pseudohypoparathyroidism
216
What is pseudohypoparathyroidism
PTH resistance - cells unable to respond to PTH so low calcium. Low calcium triggers more PTH secretion hence high PTH
217
Does secondary hyperparathyroidism lead to hypercalcaemia
No, it mostly leads to low or normal calcium levels.
218
Effect of PTH on Ca2+ and phosphate leves
Increases calcium reabsopriton
Decreases phosphate reabsorption
219
Describe the lab results indicating primary hyperparathyroidism
High calcium
High / normal PTH
Decreased PO4 3-
Increased ALP
220
Describe the lab results indicating secondary hyperparathyroidism
Low / normal Calcium
High PTH
High PO4 3- in kidney disease
but low PO4 3- in vitamin D deficiency
221
Describe the lab results indicating tertiary hyperparathyroidism
High calcium
High PTH
High PO4 3- (since tertiary is usually due to chronic kidney disease)
222
What is familial hypocalciuric hypercalcaemia
Inherited condition causing hypercalcaemia due to mutation in CaSR
223
CaSR function in the kidneys
Increase excretion of Ca2+ in urine when serum Ca levels are high
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Difference between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism
Hypocalciuric in FHH but not in PH
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Clinical features of hypercalcaemia
Stones - renal calculi
Thrones - polyuria, constipation
Abdominal Groans- pancreatitis, abdominal pain
Moans- depression, psychosis
Bones- fragility fracture, bone pain
Hypertension
Dehydration
Thirst
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How does chronic hypercalcaemia cause hypertension
Causes calcium deposits in the vessels leading to increased rate of hypertension and CVD
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Investigations for hypercalcaemia
Serum Calcium
Serum PTH
LFT
Bone profile
24 hour Urinary calcium
Bone scan
X ray / US
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What test results do you need confirm the diagnosis of primary hyperparathyroidism
Raised Ca
Raised PTH
Urine calcium level not elevated
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What test is done to exclude familial hypocalciuric hypercalcaemia
24 hour urinary calcium - urinary calcium will be low in FHH whereas it will be normal in Primary hyperparathyroidism
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Management of hypercalcaemia
IV fluids resuscitate
Bisphosphonates
Surgery
Cinacalet
Steroids
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What is the treatment for granulomatous disease e.g. sarcoidosis and TB
steroids
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When do patients with hypercalcaemia need to be admitted and resuscitated using IV fluids
If the patient has acute kidney injury / dehydrated
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First line treatment for primary hyperparathyroidism
Surgery
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What if patients with primary hyperparathyroidism doesn't want surgery
Cinacalet first
then Bisphosphonate
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Why is bisphosphonate therapy third line for hypercalcaemia caused by primary hyperparathyroidism
Because it increases bone density but it does not prevent more renal stones
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PTH effect on phosphate
increase in PTH decrease phosphate
because phosphate forms insoluble salts with calcium which reduces plasma calcium level and since PTH wants to increase calcium, phosphate level needs to decrease
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