QuestionSBA
QuestionChoice
This patient is likely vitamin D-deficient due to parathyroid gland removal during total thyroidectomy surgery. Correcting the hypocalcaemia is the first port of call due to her having had a seizure. Vitamin D replacement is important for long-term management.
52969
c
Oral high-dose vitamin D
QuestionChoice
This would be the treatment of choice for mild hypocalcaemia. This patient likely has profound hypocalcaemia due parathyroid gland removal during total thyroidectomy surgery. This patient has had serious complication of hypocalcaemia, including a seizure, and therefore IV calcium gluconate is the most appropriate initial treatment.
52968
b
Oral calcium carbonate
QuestionChoice
This patient has had a seizure, terminated by one dose of lorazepam. Phenytoin is given after multiple unsuccessful doses of lorazepam 10 min apart. The likely cause of the seizure is hypocalcaemia and therefore it is best to treat the underlying cause to prevent further seizures.
52970
d
Phenytoin
QuestionChoice
This patient likely has hypocalcaemia, secondary to parathyroid gland removal during total thyroidectomy. The sign elicited on examination is Chvostek sign, one of the two signs for hypocalcaemia, the other being Trousseau's. Trousseau's sign is carpopedal spasm when a blood pressure cuff is applied and inflated on the arm. The patient has also presented with a seizure, suggesting profound hypocalcaemia. An ECG would also be an important investigation due to these patients being at risk of prolonged QTc and subsequent torsades de pointes.
52967
a
IV calcium gluconate
QuestionChoice
This patient has had a seizure, which has terminated with one dose of lorazepam. If she had another seizure then another dose may be given as part of the emergency management. However, given that there are no current seizures, treating the underlying cause to prevent further episodes is the best next step. Therefore, calcium gluconate is the best answer.
52971
e
Lorazepam
QuestionComment
Great question author
24168
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subscriber
Edema Contusion
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warra question
25780
User
subscriber
a1 ramzy
QuestionComment
I would like half a mark for realising its hypocalcaemia
61448
User
subscriber
Acute Myopathy
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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2391
Hypocalcaemia
Topic
5
Endocrinology
10654
Hypocalcaemia can occur after total thyroidectomy, presenting with seizures and Chvostek's sign; immediate treatment includes intravenous calcium gluconate.
A 32-year-old woman is brought to A&E by ambulance accompanied by her mother. She was discharged from hospital 3 d ago after a total thyroidectomy for papillary thyroid cancer. Today, her mother witnessed her having a tonic-clonic seizure, which terminated after a single dose of lorazepam provided by paramedics. There have been no further seizures. On examination, gentle tapping over the facial nerve produces spasm of her face ipsilaterally.

What is the first-line initial treatment for her diagnosis?
a