Hypocalcaemia

Question 1

Hypocalcaemia is defined as a serum corrected calcium concentration < …mmol/L.

Answer 1

Hypocalcaemia is defined as a serum corrected calcium concentration < 2.2 mmol/L.

Question 2

Hypocalcaemia can lead to …

Answer 2

Hypocalcaemia can lead to dangerous cardiac arrhythmias and requires urgent identification and treatment. The normal serum calcium concentration is 2.2-2.6 mmol/L and this should be corrected for albumin.

Question 3

Hypocalcaemia is a common electrolyte abnormality with a wide range of causes. It is commonly seen in …

Answer 3

Hypocalcaemia is a common electrolyte abnormality with a wide range of causes. It is commonly seen in chronic kidney disease (CKD) and vitamin D deficiency. Acute symptomatic hypocalcaemia is most often seen following thyroidectomy (removal of the thyroid gland) which can disrupt the parathyroid glands that are needed for in parathyroid hormone (PTH) secretion.

Question 4

Acute symptomatic hypocalcaemia is most often seen following …

Answer 4

Acute symptomatic hypocalcaemia is most often seen following thyroidectomy (removal of the thyroid gland) which can disrupt the parathyroid glands that are needed for in parathyroid hormone (PTH) secretion.

Question 5

Acute hypocalcaemia can be further divided as follows:

Answer 5

Mild - corrected calcium ≥ 1.9 mmol/L

Severe - corrected calcium < 1.9 mmol/L

Question 6

Calcium is distributed between bone and the intra- and extra-cellular compartments.

The majority of body calcium, 99%, is stored in ….

Approximately 1% of total body calcium is found within the .. compartment. Here it plays a key role in intracellular signalling.

Around 0.1% of total body calcium is found within the extracellular pool, this is divided into:

Ionised (~ 50%) - metabolically active, or ‘ionised’, free pool of calcium.
Bound (~ 41%) - bound to albumin (90%) and globulin (10%).
Complexed (~ 9%) - forms complexes with phosphate and citrate.

Answer 6

The majority of body calcium, 99%, is stored in bone.

Approximately 1% of total body calcium is found within the intracellular compartment. Here it plays a key role in intracellular signalling.

Around 0.1% of total body calcium is found within the extracellular pool, this is divided into:

Ionised (~ 50%) - metabolically active, or ‘ionised’, free pool of calcium.
Bound (~ 41%) - bound to albumin (90%) and globulin (10%).
Complexed (~ 9%) - forms complexes with phosphate and citrate.

Question 7

The balance between stored calcium and the extracellular pool of calcium is a closely regulated process. It is controlled by the interaction of three hormones; …

Answer 7

The balance between stored calcium and the extracellular pool of calcium is a closely regulated process. It is controlled by the interaction of three hormones; parathyroid hormone (PTH), vitamin D and calcitonin.

Question 8

Serum calcium levels may be ‘corrected’ by adjusting them for the … level.

Answer 8

Serum calcium levels may be ‘corrected’ by adjusting them for the albumin level.

Question 9

It is estimated that the serum calcium concentration falls by 0.25 mmol/L (0.8 mg/dL) for every 10 g/L (1 g/L) fall in serum albumin concentration. This can be calculated manually using the following formula:

Answer 9

Corrected calcium (mg/dL) = serum calcium (mg/dL) + 0.8 x (4.0 - serum albumin [g/dL])

Question 10

There are multiple causes of hypocalcaemia that are broadly be divided into four groups:

Answer 10

Hypocalcaemia with raised PTH (discussed below)
Hypocalcaemia with low PTH (discussed below)
Hypocalcaemia related to magnesium metabolism
Medication-induced hypocalcaemia

Question 11

… is a common cause of hypocalcaemia because it impairs the action of PTH leading to resistance.

Answer 11

Hypomagnesaemia is a common cause of hypocalcaemia because it impairs the action of PTH leading to resistance. This predominantly occurs at markedly low magnesium levels (< 0.4 mmol/L). In more severe hypomagnesaemia it can cause a reduction in PTH secretion. Therefore, when assessing a patient with hypocalcaemia it is important to check and replace magnesium. If severe hypomagnesaemia is present, calcium will not improve without normalisation of magnesium.

Rarely, hypermagnesaemia (markedly raised levels e.g. > 2.5 mmol/L) can cause hypocalcaemia through suppression of PTH secretion.

Question 12

Several medications can cause hypocalcaemia by various mechanisms: (list 4)

Answer 12

Bisphosphonates (bind calcium in bone and inhibit osteoclasts)
Calcium chelators (e.g. citrate used to inhibit coagulation in banked blood)
Denosumab (monoclonal antibody to RANK ligand)
Cinacalcet (calcimimetic that mimics the action of calcium on calcium-sensing receptors)

Question 13

What is a very common cause of hypocalcaemia. Linked to poor diet and absence of ultraviolet light?

Answer 13

Vitamin D deficiency is a very common cause of hypocalcaemia. Linked to poor diet and absence of ultraviolet light.

Question 14

Chronic kidney disease - how can it cause hypocalcaemia?

Answer 14

This can cause hypocalcaemia through:

Reduced activation of vitamin D
Reduced renal absorption of calcium
Reduced renal excretion of phosphate

Question 15

CKD can lead to a marked rise in PTH in response to hypocalcaemia known as ..

Answer 15

CKD can lead to a marked rise in PTH in response to hypocalcaemia known as secondary hyperparathyroidism.

Question 16

Pseudohypoparathyroidism

Answer 16

When peripheral tissue is unresponsive to the effects of PTH due to an alteration in the PTH receptor, the condition is known as pseudohypoparathyroidism. The condition presents in childhood with characteristic features.

The reason for the term ‘pseudo’ is because the biochemical picture is similar to a lack of PTH (hypoparathyroidism) with hypocalcaemia and hyperphosphataemia. However as it is due to resistance to PTH rather than reduced secretion the PTH is elevated.

Question 17

Many conditions lead to the sequestration of calcium. This causes hypocalcaemia and an appropriate rise in PTH in an attempt to normalise the serum calcium concentration.

Causes include:

Answer 17

Tumour lysis syndrome: release of intracellular phosphate which binds to plasma calcium
Rhabdomyolysis: similar mechanism to tumour lysis syndrome
Acute pancreatitis: free fatty acids released in the inflammation are thought to bind and cause precipitation of calcium
Osteoblastic metastases: deposition of calcium around metastatic sites. Usually seen in breast and prostate cancer.

Question 18

Hypocalcaemia secondary to low PTH is classically seen following … surgery

Question 19

Hypocalcaemia with a low PTH is most commonly related to surgery, which can occur following any neck surgery (e.g. thyroid, parathyroid, dissection for cancer). Post-surgical hypocalcaemia can be divided into three types:

Answer 19

Transient: usually from disruption of blood supply or removal of 1-2 glands. May last days, weeks or months. Seen in 20% after surgery for thyroid cancer
Intermittent: recurrent episode of hypoparathyroidism and subsequent hypocalcaemia due to poor PTH reserve
Permanent: requires life-long treatment. Affects up to 3% undergoing surgery for thyroid cancer.

Question 20

Additionally, abnormal parathyroid gland development, as seen in … syndrome, can result in hypocalcaemia.

Answer 20

Additionally, abnormal parathyroid gland development, as seen in DiGeorge syndrome, can result in hypocalcaemia.

Question 21

Untreated, hypocalcaemia can cause …

Answer 21

Untreated, hypocalcaemia can cause dangerous cardiac arrhythmias and seizures.

Question 22

Acute hypocalcaemia is characterised by … and muscle ….

Answer 22

Acute hypocalcaemia is characterised by paraesthesia and muscle spasms.

Question 23

Symptoms of hypocalcaemia

This usually occurs at calcium concentrations < 1.9 mmol/L

Answer 23

Paraesthesia (numbness and tingling sensation, usually located peri-orally and in the fingers/toes)
Muscle cramps
Wheezing
Voice changes (laryngospasm)
CNS disturbance (seizures, irritability, confusion)
Chest pain (angina)
Palpitations (arrhythmias)

Question 24

Two classical eponymous signs are associated with hypocalcaemia:

Answer 24

Trousseau’s sign: development of carpopedal spasm* following inflation of a blood pressure (BP) cuff above systolic BP
Chvostek’s sign: tapping over the course of the facial nerve in the pre-auricular area causes muscle spasms (seen as twitching of the face, mouth or nose)

Question 25

… sign: development of carpopedal spasm* following inflation of a blood pressure (BP) cuff above systolic BP
… sign: tapping over the course of the facial nerve in the pre-auricular area causes muscle spasms (seen as twitching of the face, mouth or nose)

Answer 25

Trousseau’s sign: development of carpopedal spasm* following inflation of a blood pressure (BP) cuff above systolic BP
Chvostek’s sign: tapping over the course of the facial nerve in the pre-auricular area causes muscle spasms (seen as twitching of the face, mouth or nose)

Question 26

The diagnosis of hypocalcaemia is based on a serum corrected calcium < … mmol/L.

Answer 26

The diagnosis of hypocalcaemia is based on a serum corrected calcium < 2.2 mmol/L.

Question 27

Usual investigations to determine the underlying cause include: (of hypocalcaemia)

Answer 27

Bone profile
Urea & electrolytes
Vitamin D
Parathyroid hormone
Magnesium
ECG (low calcium can cause a prolonged QT interval and arrhythmias)

Question 28

Acute severe hypocalcaemia (< 1.9 mmol/L) is a …

Answer 28

Acute severe hypocalcaemia (< 1.9 mmol/L) is a medical emergency.

Question 29

Mild hypocalcaemia (≥ 1.9 mmol/L) management

Answer 29

Oral calcium supplements (e.g. Sandocal 2 tablets BD or Adcal D3 1-3 tablets BD)
Vitamin D replacement: if vitamin D deficiency the cause:
Weekly loading: 25,000-50,000 IU weekly for 6-8 weeks. Then daily dosing
Daily dosing: 800-2000 IU per day.
Alternate day rapid loading regimens available
Magnesium replacement: if hypomagnesaemia the cause:
Intravenous: magnesium sulphate 2-5 g (1g = 4 mmol) in 100-250 mls of normal saline over 1-4 hours (always follow local policy and requires cardiac monitoring)
Oral: Magnesium glycerophosphate 2 tablets (1 tablet = 4 mmol) three times a day, OR Magnesium aspartate 6.5g sachet (1 sachet = 10 mmol) twice a day.

Question 30

Severe hypocalcaemia (< 1.9 mmol/L or symptomatic at any level)

Answer 30

Give intravenous calcium gluconate: 10ml of 10% calcium gluconate in 100mls 0.9% sodium chloride or 5% dextrose over 10-20 mins. Can be given neat over 3 minutes if required. Needs cardiac monitoring.
Consider repeat dose: repeated doses can be given until asymptomatic.
Follow-up infusion: 100 mls of 10% calcium gluconate in 1L of 0.9% sodium chloride or 5% dextrose. This should be given at a rate of 50-100 ml/hour. Adjust based on response, continue cardiac monitoring.
Calcium monitoring: calcium should be checked after 1-2 hours of initial dose and then monitor 4-6 hourly.
Treat co-existent pathology: replace vitamin D or magnesium if deficiency identified.

Question 31

Chronic hypocalcaemia

Answer 31

Patients with chronic hypocalcaemia require investigation into the underlying cause, common causes include CKD or vitamin D deficiency. In these cases, treatment of the underlying cause and management with vitamin D supplementation is usually sufficient. Patients with CKD may require additional measures due to secondary hyperparathyroidism.

Question 32

The presence of hypocalcaemia and a low serum parathyroid hormone (PTH) is highly suggestive of ….

Answer 32

The presence of hypocalcaemia and a low serum parathyroid hormone (PTH) is highly suggestive of hypoparathyroidism.

Question 33

Classically, hypocalcaemia in the context of a low PTH is seen following thyroid or parathyroid surgery. The problem is most commonly transient but can be permanent in up to 3% of cases. Occasionally, hypocalcaemia with a low PTH may be secondary to autoimmune destruction of the parathyroid glands known as …. This typically causes a low PTH, low calcium and raised phosphate.

Chronic kidney disease, acute pancreatitis, tumour lysis syndrome and vitamin D deficiency all classically cause hypocalcaemia with a raised PTH. The rise in PTH is an appropriate response to a fall in calcium level.

Answer 33

Classically, hypocalcaemia in the context of a low PTH is seen following thyroid or parathyroid surgery. The problem is most commonly transient but can be permanent in up to 3% of cases. Occasionally, hypocalcaemia with a low PTH may be secondary to autoimmune destruction of the parathyroid glands known as hypoparathyroidism. This typically causes a low PTH, low calcium and raised phosphate. Chronic kidney disease, acute pancreatitis, tumour lysis syndrome and vitamin D deficiency all classically cause hypocalcaemia with a raised PTH. The rise in PTH is an appropriate response to a fall in calcium level.

Question 34

Hypocalcaemia is a very common abnormality seen in …

Answer 34

Hypocalcaemia is a very common abnormality seen in chronic kidney disease (CKD).

Question 35

… occurs when the peripheral tissue is unresponsive to the effects of PTH due to an alteration in the PTH receptor. The condition presents in childhood with characteristic features.

Answer 35

Pseudohypoparathyroidism occurs when the peripheral tissue is unresponsive to the effects of PTH due to an alteration in the PTH receptor. The condition presents in childhood with characteristic features. The reason for the term ‘pseudo’ is because the biochemical picture is similar to a lack of PTH (hypoparathyroidism) with hypocalcaemia and hyperphosphataemia. However, as it is due to resistance to PTH rather than reduced secretion the PTH is elevated.

Question 36

The majority of calcium is stored in which part of the body?

Answer 36

The majority of body calcium, 99%, is stored in bone.

Question 37

Question 4.
A 42-year-old woman presents to the emergency department with abdominal pain and nausea. She has a background of a thyroidectomy 10 years ago for a thyroid nodule. On examination, she has mild epigastric pain, but otherwise, the abdomen is soft. Observations are HR 98 bpm, BP 141/85 mmHg, RR 20, Sats 94% on room air, T 37.3º. When the blood pressure cuff is inflated on her left arm she develops severe cramping in her left hand. Electrolyte levels have been requested that show potassium 3.6 (3.5-5.0 mmol/L), sodium 141 (135-145 mmol/L), calcium 1.5 (2.2-2.6 mmo/L), magnesium 0.34 (0.85 to 1.10 mmol/L).

Which of the following best describes this clinical sign?

A	Paraesthesia
B	Chvostek's sign
C	Murphy's sign
D	Trousseau's sign
E	Cullen's sign

Answer 37

Trousseau’s sign refers to the development of carpopedal spasm following inflation of a blood pressure (BP) cuff above systolic BP.