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Clinical Calcium Homeostasis Flashcards

1
Q

what is calcium level threshhold for mild hypercalcemia?

A

<3.0mmol/L
Often asymptomatic and does usually require urgent correction

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2
Q

what is calcium level threshhold for moderate hypercalcemia?

A

3.0-3.5mmol/L
May be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated

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3
Q

what is calcium level threshhold for severe hypercalcemia?

A

> 3.5 mmol/L
Requires urgent correction due to risk
of dysrhythmia and coma

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4
Q

what are parathyroid mediated causes of hypercalcaemia?

A

Primary
hyperparathyroidism
(sporadic)

Inherited variants
*Multiple endocrine
neoplasia (MEN)
syndromes
*Familial isolated
hyperparathyroidism
*Hyperparathyroidismjaw tumor syndrome

Familial hypocalciuric
hypercalcemia

Tertiary
hyperparathyroidism
(renal failure)

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5
Q

what are non-parathyroid mediated causes of hypercalcaemia?

A

Hypercalcaemia of
malignancy
*PTHrp
*Activation of extrarenal 1
alpha-hydroxylase
(increased calcitriol)
*Osteolytic bone
metastases and local
cytokines

Vitamin D intoxication

Chronic granulomatous
disorders
*Sarcoid, TB, Berylliosis,
Histioplasmosis,
Wegener’s

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6
Q

what are medication mediated causes of hypercalcaemia?

A

Thiazide diuretics

lithium

teriparatide

excessive vitamin A

theophylline toxicity

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7
Q

what are mmiscellaneous causes of hypercalcaemia?

A

hyperthyroidism

acromegaly

pheochromocytoma

adrenal insufficiency

immobalisation

parenteral nutrition

milk alkali syndrome

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8
Q

what are renal clinical features of hypercalcaemia?

A

polyuria

polydipsia

nephrolithiasis

distal renal tubular acidosis

nephrogenic diabetes insipidus

acute and chronic renal dysfunction

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9
Q

what are gastrointestinal clinical features of hypercalcaemia?

A

anorexia

vomiting

bowel hypomotility

pancreatitis

peptic ulcer disease

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10
Q

what are musculoskeletal clinical features of hypercalcaemia?

A

muscle weakness

bone pain

osteopenia/osteoporosis

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11
Q

what are neurological clinical features of hypercalcaemia?

A

decreased concentration

confusion

fatigue

stupor

coma

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12
Q

what are cardiovascular clinical features of hypercalcaemia?

A

shortening of QT interval

bradycardia

hypertension

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13
Q

what should be covered in the history in diagnosis of hypercalcaemia?

A

– Symptoms of
hypercalcaemia
– Systemic enquiry
– Medications
– Family history

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14
Q

what should be covered in examination in diagnosis of hypercalcaemia?

A

Lymph nodes
– Concerns about
malignancy (breast, lung
etc.)

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15
Q

what should be covered in investigation for diagnosis of hypercalcaemia?

A

– U&Es
– Ca
– PO4
– Alk phos
– Myeloma screen
– Serum ACE
– PTH

consider ecg

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16
Q

what are the stepwise investigations that should be done for hypercalcaemia?

A
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17
Q

who does primary hyperparathyroidism most commonly affect?

A

Female: male = 3:1
* Incidence peaks 50-60
years

  • Most patients are
    asymptomatic at
    diagnosis
  • Most cases are sporadic
    but has been associated
    with neck irradiation or
    prolonged lithium use
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18
Q

what are causes of primary hyperparathyroidism?

A

85% parathyroid
adenoma

  • 15% four gland
    hyperplasia
  • <1% MEN type 1 or 2A
  • <1% parathyroid
    carcinoma
  • Often present for years
    prior to diagnosis
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19
Q

Presentation of primary hyperparathyroidism has changed over the decades, the presentation has become much more asymptomatic why is this?

A

likely due to frequent blood testing previously people would have presented with diseases like osteoporosis and renal caliculi

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20
Q

what investigations are done for primary hyperparathyroidism?

A

Ca, PTH

  • U&Es: check renal function
  • Abdominal imaging: renal calculi
  • DEXA: osteoporosis
  • Spot urinary calcium/creatinine ratio: Excl. FHH
  • 24 hour urinary calcium: If elevated, more likely

to be recommended for surgery
* Vitamin D

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21
Q

what imaging can also be done in investigating primary hyperparathyroidism?

A

para thyroid ultrasound

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22
Q

why is imaging done for primary hyperparathyroidism?

A

Imaging helps to localise adenoma so surgeon can have a targetted approach with smaller incisions
The purpose is not to confirm the diagnosis which has already been done through biochemical tests

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23
Q

what is first line investigation for adults over 65?

A

4D CT

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24
Q

what is indication for surgery in primary hyperparathyroidism?

A
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25
what medical managements are done for primary hyperparathyroidism?
Medical management – Generous fluid intake – Vitamin D replacement Cinacalcet (acts as a calcimetic, i.e. mimics the effect of calcium on the calcium sensing receptor on Chief cells, this leads to a fall in PTH and subsequently calcium levels)
26
what are risks or surgery for primary hyperparathyroidism?
Bleeding, haematoma, wound infection, hypercalcaemia ussually temporary Sometimes remaining parathyroid glands gone to sleep and takes time to wake up Recurrent laryngeal nerve injury very rare
27
what is familial hypocalciuric hypercalcaemia?
Autosomal dominant disorder of the calcium sensing receptor * Benign, no therapy indicated * Positive family history, screen young family members for diagnosis. * PTH may be normal or slightly elevated * No evidence of abnormal parathyroid tissue on ultrasound or isotope scan
28
what does Hypocalciuric mean?
Low levels of urinary calcium
29
Most-tumour associated hypercalcaemia is ____ Unless an endocrine tumour, prognosis usually _____
mild poor
30
what are different malignancies associated with hypercalcaemia?
31
how many types of multiple endocrine neoplasia are there?
MEN type 1 MEN type 2A
32
what are features of MEN type 1?
Primary hyperparathyroidism Pancreatic Pituitary
33
describe incidence and prevalence of MEN type 1?
>95% of MEN 1 will have hyperparathyroidism * MENIN mutation (Chr 11) * 2-4% of cases of PHP may be MEN 1 * Usually presents in the 2nd to 4th decade of life * Multi-gland involvement, High Recurrence Risk
34
describe incidence and prevalence of MEN type 2A?
RET mutation * 20-30 % of MEN2A have hyperparathyroidism * Usually milder disease than in MEN 1
35
what are features of MEN type 2A?
Medullary thyroid cancer – Phaeochromocytoma – Primary hyperparathyroidism
36
how is hypercalcaemia primarily managed?
Rehydration – 0.9% Saline 4-6 litres over 24 hours – Monitor for fluid overload – Consider dialysis if severe renal failure
37
how is hypercalcaemia managed following rehydration treatment?
After rehydration, intravenous bisphosphonates – Zolendronic acid 4mg over 15 mins – Give more slowly and consider dose reduction if renal impairment – Calcium will reach nadir at 2-4 days
38
what is second line management for hypercalcaemia?
39
what is the serum calcium range for acute hypocalcaemia?
Serum Calcium <2.20 (reference range 2.20-2.60mmol/L)
40
what are acute clinical features of hypocalcaemia?
41
what are chronic features of hypocalcaemia?
42
what are common signs of hypocalcaemia?
Trosseau’s sign Chovstek’s sign
43
what is Chovstek’s sign?
44
what is Trosseau’s sign?
45
what are causes of hypocalcaemia?
* Disruption of parathyroid gland due to total thyroidectomy. May be temporary or permanent * Following selective parathyroidectomy (usually transient & mild) * Severe vitamin D deficiency * Mg2+ deficiency (which drug can cause this?) * Cytotoxic drug-induced hypocalcaemia * Pancreatitis, rhabdomyolysis and large volume blood tranfusions
46
hypoparathyroidism low PTH causes?
47
High PTH (secondary hyperparathyroidism in response to hypocalcemia) causes?
48
drug causes of hypocalcaemia?
49
what should be covered in the history in relation to hypocalcaemia?
Symptoms – Ca & Vit D intake – Neck surgery – Autoimmune disorders – Medications – Family history
50
what should be covered in the examination in relation to hypocalcaemia?
Neck scars
51
what should be covered in the investigations in relation to hypocalcaemia?
ECG – Serum calcium – Albumin – Phosphate – PTH – U&Es – Vitamin D – Magnesium
52
what would investigations show in vitamin D deficiency and hypoparathyroidism?
53
what might hypoparathyroidism result from?
agenesis (e.g. DiGeorge syndrome) – destruction (neck surgery, autoimmune disease) – Infiltration (e.g. haemochromatosis or Wilson’s disease) – reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesaemia) – Resistance to PTH
54
what is Pseudohypoparathyroidism,?
presents in childhood refers to a group of heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH. It is characterized by hypocalcemia, hyperphosphatemia and, in contrast to hypoparathyroidism, elevated rather than reduced PTH concentrations
55
how is pseudohypoparathyroidism characterised?
It is characterized by hypocalcemia, hyperphosphatemia and, in contrast to hypoparathyroidism, elevated rather than reduced PTH concentrations
56
what are clinical features of pseudohypoparathyroidism?
Albright’s heriditary Osteodystrophy (AHO): Obesity, short stature, shortening of the metacarpal bones that can occur in some patients with Pseudohypoparathyroidism AHO alone without abnormalities of calcium or parathyroid hormone (pseudopseudohypoparathyroidism)
57
what is the treatment for mild hypocalcaemia?
* Commence oral calcium tablets * If post thyroidectomy repeat calcium 24 hours later * If vit D deficient, start vitamin D * If low Mg2+, stop any precipitating drug and replace Mg2+
58
what is the calcium serum for mild hypocalcaemia?
Asymptomatic, >1.9mmol/L
59
what is the treatment for severe hypocalcaemia?
This is a medical emergency * Administer IV calcium gluconate * Initial bolus (10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV over 10 minutes with ECG monitoring) * The initial bolus can be repeated until the patient is asymptomatic and/or calcium levels significantly increased * A Calcium gluconate infusion can then follow (100ml of 10% calcium gluconate in 1litre of 0.9% saline or 5% dextrose and infuse at 50-100ml/h) * Aim to achieve normocalcaemia * Treat the underlying cause
60
what is the serum calcium for severe hypocalcaemia?
Symptomatic or <1.9mmol/L
61
what advice in relation to vitamin D should be given to those with hypocalcaemia?
Advice regarding dietary sources * Most tablets contain a combination of vitamin D and calcium * Maintenance dose ~400- 1000 international units * Higher loading dose required (e.g. 3200 units daily for 12 weeks)
62
what is important to note about vitamin D replacement therapy?
Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy
63
what is the scottish governments advice on prevention of hypocalcaemia?
Everyone age 5 years and above should consider taking a daily supplement of 10 micrograms vitamin D, particularly during the winter months (October – March).
64
what are dietary sources of calcium?
milk, cheese and other dairy foods * green leafy vegetables – such as broccoli, cabbage and okra, but not spinach * soya beans * Tofu * nuts * bread and anything made with fortified flour * fish where you eat the bones – such as sardines and pilchards
65
what are functions of calcium?
Bone formation * Cell division & growth * Muscle contraction * Neurotransmitter release
66
describe metabolism of calcium?
67
what proportion of calcium is bound to plasma?
– 40% bound (mainly to albumin) – 15% non-ionised or complexed to citrate, PO4 etc. – 45% ionised (or free)
68
what is normal range of plasma calcium?
Normal range 2.20-2.60 mmol/l
69
how do we calculate free calcium?
– Increased albumin decreases free calcium – Decreased albumin increases free calcium – Adjust Ca2+ by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l
70
how does acidosis affect ionised calciuim?
Acidosis increases ionised calcium thus predisposing to hypercalcaemia
71
what are sources of vitamin D?
Vitamin D is also found in a small number of foods. Good food sources are: * oily fish – such as salmon, sardines and mackerel * eggs * fortified fat spreads * fortified breakfast cereals * some powdered milks
72
describe the parathyroid glands?
Usually 4 glands get their name as they sit beside the thyroid glands The chief cells secrete parathyroid hormone / PTH Oxyphil cells are larger but less abundant than chief cells
73
how is vitamin d metabolised?
Vitamin d is hydroxylated in the liver to its inactive form of vitamin d This is activated in the kidney which is partly controlled by PTH Inactive vitamin d is the major circulatinng form of vitamin d, it has a half life of two to three weeks and has seom activity at the bone and in the intestine but is less potent than activated vitamin d
74
how do cheif cells respond to changes in calcium concentrations?
Chief cells respond directly to changes in calcium concentrations * Alterations in ECF Ca2+ levels are transmitted into the parathyroid cells via calcium-sensing receptor (CaSR) * PTH is secreted in response to a fall in calcium
75
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Endocrine (35 decks)

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