The symptoms of severe hypocalcemia can be remembered with the mnemonic 'CATS go numb': Convulsions, Arrhythmias, Tetany and numbness of hands, feet and lips. More general the signs include [8] -

• numbness or tingling around the mouth, in hands and feet (paraesthesia)
• muscle spasms of the face, hands or feet,
• muscle cramps and laryngeal spasms
• neuromuscular excitability, epileptic seizures and tetany, 
• depression,
• memory loss,
• dry scaley skin, hair loss and brittle nails,
• hallucinations,
• cataracts,
• basal ganglia calcification, 
• cardiomegaly,
• positive Chvostek’s and Trousseau’s signs.

Chronic hypocalcaemia (a year or longer) can lead to cataracts.

Chvostek’s sign is when a tapping the lower part of the cheekbone produces facial spasm.
Trousseau’s sign creates carpal spasm by inflating a sphygmomanometer cuff and keeping the cuff pressure above systolic blood pressure.

ECG changes include an intermittent QT lengthening which reflects the potential for life-threatening cardiac electrical instability and thus ventricular tachycardia

Laboratory analysis of blood sample will identify reduced levels of free calcium in hypocalcaemia.

However, a complete diagnosis of the underlying cause requires assessment of the state of the parathyroid glands, the kidneys and the plasma magnesium concentration [9].

Treatment depends on the severity of the hypocalcaemia and the underlying cause.

Severe disease requires supplementation of calcium ions by parenteral injection, usually as calcium gluconate, with oral supplements for long-term treatment. These latter may be prescribed as calcium carbonate, chloride, lactate or gluconate [10].

Underlying renal disease will require injections of calcitonin plus supportive treatment for other aspects of the kidney disease.

Oral vitamin D supplements can increase calcium absorption from the gastro-intestinal tract.

Where hypoparathyroidism is the underlying cause, treatments can include oral calcium, calcitonin or other drugs.

When there is hypomagnesaemia at the same time as hypocalcaemia, the levels of both minerals must be corrected to allow hypocalcaemia reduction.

The prognosis is generally very favourable for correcting hypocalcaemia. However, it is important to identify the underlying causes and not all of these can be corrected. The cataracts of chronic hypocalcaemia cannot be reversed.

Calcium is an important mineral in the human body. Not only it is a major component of bones and teeth but about 1% of the total calcium of the body circulates in the blood where it is essential for normal blood clotting and for normal nerve and muscle activity. In bones, the calcium ion combines with phosphate ions to form the strong calcium phosphate crystals. In the blood some calcium ions combine in complexes with proteins and other compounds but many remain in a free form. Normally about 47% calcium in the plasma is of the free form and the larger proportion, 53% of it, is in complexes (40% attached to albumin and 15% bound to citrates, lactates, phosphates and sulphates). It is the free calcium ions which are critical to the performance of nerves and muscles, not the calcium in bone or vascular complexes [2].

When there are inadequate circulating calcium ions, neuromuscular abnormalities develop.

The four main causes of hypocalcaemia are [3] –

1. Hypoparathyroidism,
2. failure to produce calcitonin (1, 25-dihydroxyvitamin D),
3. low levels of plasma magnesium,
4. inadequate level of calcium or vitamin D.

Other causes include: 

• eating disorders like anorexia or bulimia
• prolonged vomiting (e.g for viral disease)
• exposure to mercury and hydrofluoric acid
• excessive dietary magnesium or zinc
• iatrogenic effect – chelation therapy for heavy metal exposure (especially EDTA), osteoporosis treatments (e.g. biphophonates and denosumab), treatment of hypercalcemia, phosphate enemas in children.
• toxic levels of phosphate (e.g in enemas mistakenly swallowed)
• acute and chronic renal failure
• pancreatitis

Neonatal hypocalcemia can be found in babies with very low birth weights (less than 1500 grams) or premature with a gestational age of less than 32 weeks.

It is interesting to note that many animals suffer from hypocalcemia after losing large amounts of calcium in their placental fluids at parturition in their milk during lactation. There seems to be a strong possibility that many mild cases of post-natal depression may be related to hypocalcemia [4].

Maintenance and control of the plasma calcium level is performed by the parathyroid hormone from the parathyroid gland. This acts on the kidneys where it stimulates production of calcitrol (1,25-dihydroxyvitamin D), the active form of vitamin D. Calcitrol stimulates the absorption of calcium from the diet as well as its mobilisation from bone to maintain or raise the levels of calcium ions in the plasma [5].

Hypocalcemia can therefore by caused by abnormalities in either the parathyroid gland or the kidneys. Parathyroid performance can be disturbed by a damage or surgical removal during thyroidectomy and radical resection of cancer surgery. Autoimmune and congenital hypoparathyroidism can result in destruction or absence of calcium-sensing receptors. There is also a condition called pseudohypoparathyroidism in which there is insensitivity to the biological activity of parathyroid hormone receptors.

Vitamin D levels are critical and can be inadequate because of low dietary levels, pronounced absorption, inadequate exposure to sunlight needed to cause effective metabolism or defective metabolic pathways [6].

Low plasma magnesium levels (hypomagnesaemia) can also lead to hypocalcaemia. These may be brought about by alcoholism or by a disease that prevent the correct fat absorption. Magnesium is required for correct functioning of the parathyroid hormone in maintaining blood calcium levels [7].

It is important that the daily requirements of calcium and vitamin D are met every day, either with food or through supplements.

Lifestyle choices should be made to avoid alcohol consumption and make sure that adequate levels of sunlight are received by the body for a correct vitamin D metabolism – in colder climates with shorter day length it is highly possible that many individuals might not receive enough sunlight on their skin due to protective clothing.

The normal concentration of free ionized calcium in the blood is between 4.65 – 5.25 mg/dL (1.16 – 1.31mmol/L); Hypocalcemia is the syndrome when the blood calcium level falls below this range and severe hypocalcaemia occurs with levels are below 3 mg/dL.

The most prominent signs relate to the nerve inactivity with paraesthesia of the hands, feet and around the mouth and lips with more severe signs of convulsion, arrhythmias and tetany. Treatment can be successfully performed by either intravenous calcium gluconate or oral supplementation with various calcium salts. However it is important to identify and correct the underlying cause [1].

Definition: Hypocalcaemia occurs when the level of circulating free calcium ions is less than 4.65 mg/dL (1.16 mmol/L) and results in potentially life-threatening disturbance to nerve and muscle activity.

Cause: Inadequate levels of circulating calcium ions in the plasma lead to poor nerve transmission and muscle weakness. The most common causes of hypocalcaemia are low parathyroid hormone levels, failure to produce calcitonin (the active form of vitamin D), low circulating magnesium levels or inadequate calcium or vitamin D uptake. Underlying causes could include eating disorders, prolonged vomiting in viral disease, toxicity by certain metals or drugs, acute and chronic renal failure and inadequate exposure to sunlight for conversion of active Vitamin D (calcitonin).

Symptoms: The signs of hypocalcaemia can be remembered with the mnemonic ‘CATS go numb’. This translates as “convulsions, arrhythmias, tetany and numbness of the hands, feet and around the mouth and lips. Other signs include positive Chvostek’s and Trousseau’s signs, depression, memory loss and hallucinations. Tissue deterioration is reflected in dry scaly skin, hair loss and brittle nails and, after more than a year of chronic hypocalcaemia, cataracts can also be seen.

Diagnosis: Clinical signs and history allow a tentative diagnosis with confirmation by laboratory electrolyte analysis. An ECG will identify an intermittent QT lengthening which reflects electrical insensitivity and, potentially, life-threatening ventricular tachycardia.
Underlying causes from the clinical history should be identified by further testing.

Treatment: Calcium supplementation, orally or intravenously depending on the severity of the condition, will offer a good clinical response,  but further treatment may be required to correct the underlying pathology.

Prevention: Adoption of good lifestyle practices – diet and exposure to sunshine – correct smost simple causes; the cases of more complicated pathology will require specific programmes.

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