QuestionSBA
QuestionChoice
Hypomagnesaemia can lead to hypocalcaemia, and it is important to check magnesium levels after urgent treatment has been started
32307
e
Check serum magnesium levels
QuestionChoice
ECG monitoring is essential as severe hypocalcaemia can lead to a prolongation of the QT interval, which in turn can trigger arrhythmias
32305
c
IV calcium gluconate
QuestionChoice
PTH testing is important to determine the aetiology of hypocalcaemia. However, severe hypocalcaemia should be treated urgently. In this case, the recent thyroid surgery is likely to be the cause, and PTH levels would likely be low due to disruption of the parathyroid glands during surgery
32306
d
Urgent parathyroid hormone (PTH) level testing
QuestionChoice
This is severe hypocalcaemia which is defined as a serum calcium level of < 1.9 mmol/L or symptomatic with any calcium level below the reference range.

It is a medical emergency that should be managed with 10-20mL of IV calcium gluconate in 50-100mL of 5% dextrose over 10 mins. This should be followed up with a calcium infusion.

ECG monitoring is essential as hypocalcaemia can lead to a prolongation of the QT interval, which in turn can trigger arrhythmias
32303
a
IV calcium gluconate with cardiac monitoring
QuestionChoice
Oral calcium replacement can be used for asymptomatic patients with a serum calcium of > 1.9 mmol/L. It is not suitable for severe hypocalcaemia
32304
b
Oral calcium replacement
Concept
Chapter
# Summary

Hypocalcaemia refers to an abnormally low serum calcium, adjusted for serum albumin concentration. A calcium of below 2.2 mmol/L is generally considered low although laboratory reference ranges may vary slightly. Causes include vitamin D deficiency, hypoparathyroidism, acute pancreatitis, chronic kidney disease and hypomagnesaemia. Symptoms usually occur when adjusted calcium falls below 1.9 mmol/L, and include muscle cramps, spasms and paraesthesias (classically perioral). Signs include carpopedal spasm and tetany. Investigations include an ECG, bone profile, parathyroid hormone (PTH) level, magnesium, U&Es and a vitamin D. Management involves treating the underlying cause and giving calcium supplementation - oral if mild (e.g. Calcichew tablets) and intravenous (e.g. calcium gluconate) if severe or symptomatic. Vitamin D and/or magnesium supplementation should be given if required. 

# Definition

The normal range for serum calcium is approximately 2.2-2.6 mmol/L. This is adjusted for serum albumin levels, which is important as approximately 40% of serum calcium is bound to albumin and so when albumin levels are low, serum calcium will be underestimated. 

99% of the body's calcium is stored in the skeleton and is crucial for the mineralisation of bone. It has many other roles in important functions such as muscle contraction, cardiac pacemaker activity, clotting, cell membrane stability and permeability.

Hypocalcaemia refers to an adjusted serum calcium of 2.2 mmol/L or lower.

# Aetiology

- Hypoparathyroidism
    - Iatrogenic due to parathyroid or thyroid surgery or radiotherapy
    - Autoimmune (may be part of a polyglandular syndrome)
    - Infiltration e.g. malignancy, thalassaemia, amyloidosis, Wilson's disease, haemochromatosis
    - Congenital e.g. DiGeorge syndrome (cleft palate, thymic aplasia, facial dysmorphism, cardiac defects and parathyroid agenesis)
- Hypomagnesaemia (causes reversible functional hypoparathyroidism)
- Vitamin D deficiency
    - Lack of sun exposure
    - Malnutrition
    - Malabsorption (e.g. due to pancreatic insufficiency)
    - Abnormal metabolism due to chronic kidney or liver disease
- Medications 
    - Calcimimetics (e.g. cinacalcet)
    - Bisphosphonates
    - Loop diuretics
    - Cisplatin
    - Foscarnet
    - Phenytoin
    - Ketoconazole
- Genetic conditions such as autosomal dominant hypocalcaemia (due to a gain-of-function mutation in the calcium-sensing receptor (CaSR) gene) 
- Pseudohypoparathyroidism
    - PTH resistance due to genetic mutations in its signalling pathway
    - Manifests with hypocalcaemia, hyperphosphataemia and elevated PTH
    - May be associated with Albright hereditary osteodystrophy, where patients have a short stature, obesity, brachymetacarpals (especially the 4th and 5th digits), developmental delay and subcutaneous ossifications
- Alkalosis causes a fall in ionised calcium (the metabolically active form) due to increased binding to albumin 
    - This may be a respiratory alkalosis e.g. due to a panic attack or tachypnoea due to pneumonia or pulmonary embolism
    - Metabolic alkalosis may occur due to prolonged vomiting or excessive bicarbonate administration
- Massive blood transfusion (as the citrate added to products to prevent clotting chelates calcium)
    - The same mechanism leads to hypocalcaemia in plasmapheresis (plasma contains citrate)
- Renal replacement therapy with citrate used as an anticoagulant also causes chelation of calcium
    - Any form of continuous renal replacement therapy causes ongoing magnesium and calcium loss
- Acute pancreatitis (due to saponification of calcium)
- Hungry bone syndrome
    - Usually occurs after parathyroidectomy
    - There is prolonged PTH exposure with net bone resorption which suddenly shifts towards osteoblastic activity once PTH falls
    - There is a resulting influx of minerals into bone leading to hypocalcaemia and hypophosphataemia
- Hyperphosphataemia (as phosphate binds with calcium), e.g. due to:
    - Chronic kidney disease
    - Tumour lysis syndrome
    - Rhabdomyolysis
- Sepsis may lead to hypocalcaemia - this is multifactorial due to the effects of systemic inflammation on calcium homeostasis

# Signs and Symptoms

Mild cases of hypocalcaemia (calcium > 2 mmol/L) are usually asymptomatic - once calcium falls below 2 the following symptoms may occur:

- Paraesthesias (typically periorally and affecting the digits)
- Muscle cramps
- Muscle spasms
- Anxiety and depression
- Confusion
- Weakness and fatigue
- Myalgia
- Dry skin
- Coarse hair 
- Brittle nails 

Signs include:

- Hyperreflexia
- Muscle fasciculations
- Chvostek's sign - tapping the facial nerve where it passes in front of the ear provokes muscular spasm of the face 
- This indicates neuromuscular hyperexcitability
- Trousseau's sign of latent tetany - inflating a blood pressure cuff above the patient's systolic level and keeping this on for up to three minutes causes spasm of the forearm and hand muscles
- The wrist and metacarpophalangeal joints flex, the fingers adduct and the distal and proximal interphalangeal joints extend
- Hypotension (rarely)
- Bradycardia
- Decreased consciousness
- Delirium
- Papilloedema 
- Skin changes e.g. eczema, dermatitis, hyperpigmentation
- Patchy alopecia
- Transverse grooving of nails

# Differential Diagnosis

- **Pseudohypocalcaemia** occurs due to hypoalbuminaemia - total calcium will be low in these patients (hence the importance of correcting serum calcium for albumin levels)
- **Contamination of blood bottles** with EDTA or citrate will lead to artefactual hypocalcaemia - hyperkalaemia will also be seen with EDTA and hypernatraemia with sodium citrate

# Investigations

**Bedside:**

- **ECG** may show a prolonged QTc or rarely arrhythmias (e.g. atrial fibrillation)
- **Blood gas** to rapidly confirm hypocalcaemia (NB blood gas machines measure ionised calcium only so the reference ranges are significantly lower)
- **Urine dip** may be positive for protein in CKD or falsely positive for blood due to myoglobinuria in rhabdomyolysis

**Blood tests:**

- **Bone profile** to confirm hypocalcaemia and check phosphate levels
- **PTH levels** are helpful to help identify a cause - they will be low in hypoparathyroidism and high for example in vitamin D deficiency or pseudohypoparathyroidism
- **Full blood count** may show anaemia related to chronic disease (e.g. chronic kidney disease) or leukocytosis in sepsis
- **U&Es** to look for chronic kidney disease
- **CRP** to screen for inflammation for example in sepsis
- **Magnesium** to check for hypomagnesaemia
- **LFTs** to check albumin; liver function may be deranged in some causes e.g. metastatic malignancy 
- **Vitamin D level** to look for deficiency
- **Amylase** if pancreatitis is suspected
- **Creatine kinase** if rhabdomyolysis is suspected

**Special tests:**

- **Genetic testing** may be offered to patients with a suspected genetic mutation e.g. autosomal dominant hypocalcaemia

# Management 

**Conservative:**

- Identification and management of the underlying cause is key e.g. stopping causative medications where possible
- Ensure oral intake of calcium is adequate (700 mg/day is recommended for most adults; patients with osteoporosis should have double this)
- Patients with ECG changes require cardiac monitoring as well as urgent intravenous calcium replacement (see below)
- Some patients with mild asymptomatic hypocalcaemia e.g. due to critical illness do not require treatment and should be monitored

**Medical:**

- Mild hypocalcaemia (calcium 1.9 mmol/L or higher) can be treated with oral replacement e.g. Calcichew 2 tablets twice a day
- Severe hypocalcaemia (calcium < 1.9 mmol/L or symptomatic) should be treated urgently with intravenous calcium replacement 
- For example, 10-20 ml of calcium gluconate 10% in 5% glucose over 10 minutes
- This can be repeated if necessary or followed by a calcium gluconate infusion
- Vitamin D supplementation should be provided if low - colecalciferol (vitamin D3) is the usual supplement prescribed however other compounds may be required e.g. alfacalcidol (1α-hydroxycholecalciferol) in CKD
- Replace magnesium if low (see hypomagnesaemia chapter for details) - hypocalcaemia is unlikely to resolve if magnesium is still low

# Complications

**Complications of acute hypocalcaemia:**

- Seizures - may be generalised motor or absence seizures, or focal
- Arrhythmias - e.g. torsades de pointes due to QTc prolongation
- Laryngospasm - common in infancy but rarer in adults
- Bronchospasm - also uncommon in adults, may mimic an asthma exacerbation

**Complications of chronic hypocalcaemia:**

- Cataracts - typically bilateral, not reversible with correction of hypocalcaemia
- Dental disease - e.g. enamel hypoplasia, increased risk of caries
- Basal ganglia calcification - may be asymptomatic or lead to movement disorders, parkinsonism or dementia

# References

[Patient UK - Hypocalcaemia](https://patient.info/doctor/hypocalcaemia)

[BNF - Calcium imbalance](https://bnf.nice.org.uk/treatment-summaries/calcium-imbalance/)

[GGC Medicines UK - Management of Hypocalcaemia](https://handbook.ggcmedicines.org.uk/guidelines/electrolyte-disturbances/management-of-hypocalcaemia/)

[The Internet Book of Critical Care - Hypocalcaemia](https://emcrit.org/ibcc/hypocalcemia/)

[Life in the Fast Lane - Hypocalcaemia ECG library](https://litfl.com/hypocalcaemia-ecg-library/)
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Hypocalcaemia
Topic
36
Clinical Chemistry
6461
A 32-year-old man who had thyroid surgery three days ago presents with numbness and tingling in his fingertips. He also reports intermittent muscle spasms.


Bloods shows a serum calcium level of 1.8 mmol/L (normal range 2.2-2.6 mmol/L).


Which of the following is the next best step in management?
a