Hypocalcemia

History and Epidemiology

Hypocalcemia occurs when there is too little calcium in the bloodstream. The normal range of calcium is 8.5 to 10.5 mg/dl (4.3 to 5.3 mEq/L or 2.2 to 2.7 mmol/L).¹ This reference range may differ by 0.5 mg/dl depending on the testing laboratory. Hypocalcemia may be fatal if left untreated.² Symptoms of hypocalcemia can include muscle weakness, paresthesia, and arrhythmia, among others.

The prevalence of hypocalcemia can vary widely across different subpopulations, with 18% of hospitalized patients reported as hypocalcemic and to up 85% of patients in the ICU.³ There is limited data about the incidence of hypocalcemia in the general population.² The prevalence of permanent hypocalcemia after thyroidectomy ranges from 0.4% to 33%.²

Hypocalcemia Risk Factors

Risk factors for hypocalcemia include:

• Vitamin D deficiency due to low intake or absorption, liver problems, acute or chronic renal failure, treatment with anticonvulsant drugs, or high blood level of phosphate^{1, 2, 4}
• Parathyroid hormone deficiency due to genetic causes, such as DiGeorge syndrome, thyroidectomy, radiation, cancer, parathyroid gland autoantibodies, or low blood level of magnesium²
• Other causes, such as blood transfusions, sudden increase in bone deposition of calcium due to treatment with bisphosphonates or denosumab, use of cinacalcet, cisplatin, or foscarnet, osteoblastic metastasis, pancreatitis or rhabdomyolysis, pseudohypoparathyroidism, or pregnancy²

Hypocalcemia Presentation & Diagnosis

The clinical presentation of hypocalcemia may range from life-threatening to asymptomatic. Symptoms of hypocalcemia can include:

• Seizures in cases of severe hypocalcemia
• Tetany, which may occur with respiratory alkalosis, paresthesia and numbness of the fingertips and mouth (may also include the face and limbs)
• New-onset depression or anxiety, or paranoia and hallucinations.^{1, 2}

Symptoms of chronic hypocalcemia can include cataracts, defects in the enamel of the teeth, brittle hair and nails, and lower blood pressure.¹

Diagnostic Hypocalcemia Workup

Serum calcium and albumin should be drawn to confirm the diagnosis of hypocalcemia.² An ECG should be done to check for prolongation of the QT interval, which may lead to heart block.²

The presence of Trousseau’s sign or Chvostek’s sign can provide confirmation of hypocalcemia.¹ Trousseau’s sign is an involuntary contraction of muscles in the hand and wrist, also known as a carpopedal spasm. There is flexion in the wrist, thumb, and metacarpophalangeal joints and extension of the interphalangeal joints. This is checked by compressing the upper arm with a blood pressure cuff inflated above the patient’s known systolic blood pressure for 3 minutes. Chvostek’s sign is a twitch of the facial muscles that occurs when a clinician taps the facial nerve. 

If hypocalcemia is confirmed, further lab tests should be run for magnesium, phosphorus, parathyroid hormone, and vitamin D to identify the cause. An X-ray may be beneficial to rule out bone cancer, rickets, or osteomalacia.

Differential Diagnosis for Hypocalcemia

Hypocalcemia may present similarly to other conditions including acute pancreatitis, acute renal failure, high phosphate level, low magnesium level, and hypoparathyroidism.²

Hypocalcemia Management (Nonpharmacotherapy and pharmacotherapy)

Hypocalcemia treatment depends on the cause of hypocalcemia, the severity of symptoms, and the level of calcium in the body. The condition should be reverified through repeat measurement of ionized calcium or a total serum calcium corrected for albumin before hypocalcemia treatment.²

Patients with severe symptoms (such as carpopedal spasms, seizures, or tetany), EKG changes (such as prolonged QT interval), and who develop hypocalcemia very quickly should receive intravenous calcium. The typical dosage is 1 to 2 grams of calcium gluconate, or 1 gram of calcium chloride given as an infusion over 10 to 20 minutes. If the patient’s calcium level remains low, a continuous infusion of calcium gluconate may be given.

Asymptomatic patients and patients with mild symptoms may be given oral calcium carbonate or calcium citrate. The typical dosage is 1500 to 2000 mg elemental calcium per day divided into 2 or 3 doses. Vitamin D should be given along with calcium to aid in absorption. Patients receiving proton pump inhibitors should be given calcium citrate instead of calcium carbonate which requires an acid to be absorbed.

Low magnesium and vitamin D deficiency should be corrected before treating hypocalcemia because either could be the cause of hypocalcemia.² Patients with chronic kidney disease and vitamin D deficiency should be treated with 50,000 IU ergocalciferol weekly for 8 to 12 weeks. After that, 1000 to 5000 IU cholecalciferol should be given daily. Patients with hypoparathyroidism should receive a synthetic form of parathyroid hormone to correct this problem.⁵

Monitoring Side Effects, Adverse Events, Drug-Drug Interactions

Hypocalcemia has a good prognosis if the underlying cause is found and corrected.² People who have undergone complete parathyroidectomy or gastric bypass surgery may require ongoing high doses of vitamin D and calcium to maintain normal levels.

Possible side effects of vitamin D supplementation can include anemia, weight loss, nausea and decreased appetite, constipation, osteoporosis, aches, stiffness, and weakness, calcification of soft tissue, mental problems, and changes in renal function.⁵

Possible side effects of calcium supplementation can include upset stomach and vomiting, burping, decreased appetite, metallic taste, dry mouth, constipation, and increased urination.⁶

To prevent issues with absorption, patients receiving calcium supplements should separate their dose of calcium from the following drugs by about 2 hours: digoxin, etidronate, phenytoin, tetracycline, and levothyroxine.⁶

Patients receiving vitamin D supplements should be instructed about possible drug-drug interactions which include:⁷

• Orlistat. Orlistat may decrease vitamin D absorption. Advise patients to take vitamin D several hours before their dose of orlistat.
• Statins. Atorvastatin, simvastatin, and lovastatin are metabolized by CYP3A4 and may interfere with vitamin D absorption. Healthcare providers should consider switching patients to a different statin, such as pravastatin, if vitamin D is being prescribed for long-term use.
• Rifampin and isoniazid. These drugs may interfere with the absorption of vitamin D.
• Mineral oil. Mineral oil may affect the absorption of fat-soluble vitamins, including vitamin D.
• Thiazide diuretics. Patients with low levels of parathyroid hormone who take thiazide diuretics with vitamin D may be at an increased risk for hypercalcemia.

References

1. Goldstein DA. Serum Calcium. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 143.

2. Goyal A, Anastasopoulou C, Ngu M, Singh S. Hypocalcemia. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing: 2022. Accessed July 18, 2022.

3. Catalano A, Chilà D, Bellone F, et al. Incidence of hypocalcemia and hypercalcemia in hospitalized patients: Is it changing?. J Clin Transl Endocrinol. 2018;13:9-13. doi:10.1016/j.jcte.2018.05.004

4. Tredici P, Grosso E, Gibelli B, Massaro MA, Arrigoni C, Tradati N. Identification of patients at high risk for hypocalcemia after total thyroidectomy. Acta Otorhinolaryngol Ital. 2011;31(3):144-148.

5. U.S. National Library of Medicine DailyMed. Ergocalciferol capsule. September 17, 2021. Accessed July 18, 2022.

6. U.S. National Library of Medicine Medline Plus. Calcium Carbonate. 2022. Accessed July 18, 2022.

7. Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: A systematic review of the literature. Nutr Clin Pract. 2013;28(2):194-208. doi:10.1177/0884533612467824

Author Bio

Jen Seabright, PharmD, is a freelance medical writer based in Pittsburgh, PA.

Commonly Asked Patient Questions

Can vitamin D therapy treat hypocalcemia?

Vitamin D therapy can be used to treat hypocalcemia, a condition in which there is an abnormally low level of calcium in the blood. Vitamin D helps increase the absorption of dietary calcium from the intestines and promotes its release from bone stores into circulation when needed. This helps replenish depleted calcium levels and thus reduce symptoms associated with hypocalcemia.

Why does hypocalcemia cause tetany?

Hypocalcemia causes tetany due to its effects on nerve conduction. Calcium plays an important role in maintaining normal electrical excitability of nerves and muscles, so when it falls below normal levels, the ability for these tissues to respond normally is impaired, leading to uncontrolled muscle spasms known as tetany.

Is Hungry Bone Syndrome (HBS) a form of severe hypocalcemia?

Hungry Bone Syndrome (HBS) is a form of severe hypocalcemia that occurs after parathyroidectomy surgery for hyperparathyroidism or other conditions involving too much parathyroid hormone production. In this state, large amounts of skeletal calcium are mobilized rapidly into circulation as part of a compensatory mechanism for restoring serum calcium concentrations back towards normal values; however, this process leaves behind “hungry” bones that are unable to recover their lost mineral content quickly enough without supplementation via diet or medication.

Can renal failure cause hypocalcemia?

Yes, renal failure can cause hypocalcemia. When the kidneys are not functioning properly, they cannot reabsorb enough calcium from urine, leading to low levels of circulating calcium in the blood. In addition, impaired kidney function may lead to changes in hormones that regulate bone metabolism and vitamin D activation, both of which play important roles in maintaining normal serum calcium concentrations. Renal failure may also lead to decreased production of parathyroid hormone (PTH), an essential hormone for regulating serum calcium levels as well as phosphate balance; this too can result in hypocalcemia.