Hypocalcemia – Diagnosis, Symptoms, and Treatment

What is Hypocalcemia?

Hypocalcemia is an electrolyte disorder characterized by low serum calcium levels. There are various causes, including chronic kidney disease, inadequate PTH production (hypoparathyroidism), vitamin D deficiency, and low abnormal magnesium metabolism (hypomagnesemia). Hypoparathyroidism may be caused by surgical removal of the parathyroid glands or due to autoimmune disease. Certain medications such as bisphosphonates for osteoporosis may also contribute to hypocalcemia.

The symptoms of acute hypocalcemia usually include tetany – this is a term for neuromuscular irritability. Patients also often develop numbness and paresthesias around the mouth as well as the hand and feet. Muscle spasms are another common manifestation. Severe cases result in laryngospasm, impaired cardiac function, seizure, and life-threatening cardiac arrhythmias.

What Causes Hypocalcemia?

Calcium is essential for functions such as cell signaling, hormone secretion, muscle contraction, and coagulation. Calcium levels are affected by critical regulators, including parathyroid hormone (PTH) and vitamin D. The kidneys are also an essential regulator of calcium metabolism. The kidneys are responsible for the synthesis of vitamin D via the enzyme alpha-hydroxylase. Low serum calcium levels (hypocalcemia) can be caused by a variety of conditions, including:

• Inadequate PTH production (hypoparathyroidism)
• Chronic kidney disease
• Vitamin D deficiency
• Abnormal magnesium metabolism (hypomagnesemia)
• Extravascular calcium deposition (pancreatitis, hyperphosphatemia)

Hypoparathyroidism may be caused by removing the parathyroid glands, which often occurs during thyroid, parathyroid, or radical neck surgery. Some patients develop hypoparathyroidism from autoimmune destruction of the parathyroid glands. Certain medications are also associated with hypocalcemia, including:

• Inhibitors of bone resorption
  • Bisphosphonates
  • Calcitonin
  • Denosumab
• Cinacalcet
• Calcium chelators (EDTA, citrate)
• Foscarnet
• Phenytoin

How Common is Hypocalcemia?

Hypocalcemia is a common condition that is often initially evaluated in the primary care clinic. The most common cause is kidney disease. Advanced cases often require referral to a nephrology (kidney) specialist, mainly if first-line measures are unsuccessful.

It is difficult to determine the precise incidence of hypocalcemia. The incidence is approximately 15%-88% in patients hospitalized in the intensive care unit. About 27% of individuals with thyroid removal surgery (thyroidectomy) have transient hypocalcemia, and about 1% develop permanent hypocalcemia.

Signs and Symptoms

Symptoms of hypocalcemia depend on how quickly calcium levels decrease and the severity of hypocalcemia. Acute symptomatic hypocalcemia often results in tetany, a form of neuromuscular irritability. Patients often experience:

• Numbness around the mouth
• Tingling (paresthesias) involving the hands and feet
• Muscle cramps

Non-specific symptoms often include fatigue, anxiety, and agitation. Severe cases may result in painful muscle contractions in the hands and feet (carpopedal spasm), laryngospasm, seizure, decreased cardiac function, and cardiac arrhythmia.

A classic physical examination sign that can suggest acute hypocalcemia is the Trousseau sign, characterized by carpopedal spasm when the blood pressure cuff is inflated. Chvostek sign is another finding characterized by contraction of the facial muscles caused by tapping just anterior to the ear.

Chronic hypocalcemia from hypoparathyroidism can result in cataracts, basal ganglia calcification, and dementia. Basal ganglia calcifications can lead to movement disorders such as Parkinson’s disease, which usually presents with bradykinesia (slow movement), rigidity, and tremor.

Diagnosis

Hypocalcemia diagnosis may be suggested based on symptoms and physical examination but is typically confirmed with laboratory studies. Your doctor will usually obtain a CMP (comprehensive metabolic panel), which contains a serum calcium concentration. If the calcium concentration is low, the laboratory value is typically confirmed by repeating the measurement with an ionized calcium level. This study is obtained to assess for a real decrease in serum calcium. Occasionally, your doctor will use a serum albumin level to calculate the corrected serum calcium concentration.

Once hypocalcemia is confirmed, your doctor will usually order additional tests to determine its cause. This typically includes a serum parathyroid hormone (PTH). They may also obtain serum magnesium, phosphate, and vitamin D level.

Hypocalcemia Medication and Treatment

The treatment of hypocalcemia depends on its severity and cause. Severe, symptomatic hypocalcemia (e.g., Calcium < 7.5 mg/dL) is typically corrected with intravenous calcium therapy.

Individuals with less severe hypocalcemia accompanied by mild symptoms are often treated with oral calcium supplements (e.g., calcium carbonate, calcium citrate). Common calcium supplement brands include Caltrate, Citrucel, OsCal, and Tums. Patients with hypocalcemia due to kidney disease often requires correction of hyperphosphatemia with phosphate binders (PhosLo – calcium acetate) and repletion of low vitamin D levels. Those with coexisting hypomagnesemia should typically receive intravenous magnesium sulfate or oral magnesium supplementation.

Patients with vitamin D deficiency require vitamin D supplementation. Initial treatment often includes 50,000 international units of vitamin D2 or D3 weekly for 6-8 weeks, followed by 800-1000 international units of vitamin D3 daily. Most patients with hypoparathyroidism require calcium and vitamin D supplementation for their lifetime. Individuals with hypoparathyroidism that do not maintain adequate calcium levels with calcium and vitamin D supplements may benefit from therapy with Natpara (recombinant parathyroid hormone).

References:

1. Hannan FM, Thakker RV. Investigating hypocalcemia. BMJ 2013; 346:f2213. - https://www.ncbi.nlm.nih.gov/pubmed/23661111
2. Thakker R. Hypocalcemia: pathogenesis, differential diagnosis, and management. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, American Society of Bone and Mineral Research 2006; 6:213. - https://jhu.pure.elsevier.com/en/publications/primer-on-the-metabolic-bone-diseases-and-disorders-of-mineral-me-6
3. Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 2010; 298:F485. - https://journals.physiology.org/doi/full/10.1152/ajprenal.00608.2009