Hypocalcemia

Endocrinology > Hypocalcemia

Key points
Symptomatic hypocalcemia requires immediate medical attention. The method (orally or
intravenously) and speed of replacement will depend on the severity of the symptoms. Tetany
and seizures require immediate intervention with intravenous calcium replacement.

Background
Description

Defined as total serum calcium of <8.5 mg/dL or ionized calcium of <4.6 mg/dL
Total serum calcium levels must be corrected for serum albumin levels. Ionized
calcium levels do not require such correction
Acute, severe hypocalcemia is a medical emergency
Major factors that influence the serum calcium concentration are parathyroid hormone
(PTH), vitamin D, and serum phosphorus level
Hypocalcemia most commonly occurs with vitamin D deficiency, chronic renal
failure, hypoparathyroidism (typically due to neck surgery, rarely from autoimmune
destruction or congenital abnormality)
Cardinal features are muscle spasm, irritability, tetany, paresthesias, seizures, and
cardiac dysrhythmias
Seizures may occur with severe hypocalcemia
Chronic hypocalcemia often responds to treatment with vitamin D derivatives and
calcium
Approximately 40% of serum calcium is ionized (free), while the other 60% is
complexed, primarily to albumin. Only the ionized calcium is transported into cells and
metabolically active. Decreases in the ionized (free) fraction of calcium cause symptoms
Hypoalbuminemia alters total serum calcium concentration without affecting the
ionized calcium. Serum total calcium concentration falls approximately 0.8 mg/dL for every
1 g/dL reduction in the serum albumin concentration

Epidemiology
Incidence and prevalence:

Incidence and prevalence are difficult to estimate because hypocalcemia is a multifactorial diagnosis.
Postsurgical hypoparathyroidism is decreasing as thyroid and parathyroid surgery techniques improve
Decreases in total serum calcium are quite common in ill patients, but ionized calcium typically remains
normal
In renal failure the use of prophylactic calcium has reduced the incidence of renal osteodystrophy
Autoimmune polyglandular syndrome is extremely rare with perhaps 0.04 cases/1000 patients/year
Demographics:

May occur at any age

Genetic predisposition in pseudohypoparathyroidism, genetic hypoparathyroidism, and vitamin D
receptor abnormalities

Causes and risk factors

Causes
Common causes:

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Hypocalcemia with high PTH

Chronic kidney disease: increased serum phosphorus and reduced renal hydroxylation of 25hydroxy-vitamin D to 1,25-dihydroxy-vitamin D
Vitamin D deficiency: decreased 25-hydroxylation in the liver, decreased 1-hydroxylation in the
kidney, poor intake by mouth or malabsorption coupled with minimal exposure to ultraviolet light
Hypocalcemia with low PTH
Hypoparathyroidism after neck surgery; also may be autoimmune, genetic, infiltrative, postradiation, or idiopathic
Deregulation of PTH: can occur due to mutations in the signal peptide sequence of preproPTH
and mutations of the calcium sensing receptor (CaSR) on the parathyroid gland
Acute pancreatitis
Severe hypomagnesemia due to suppression of parathyroid hormone (PTH) release
Sepsis or severe illness: most likely a combination of reduced calcitriol production, impaired secretion of
PTH, and end-organ PTH resistance

Rare causes:

Medications: anticonvulsants, antimicrobials (foscarnet, ketoconazole, pentamidine); agents used to

treat hypercalcemia
Massive acute hyperphosphatemia (calcium chelation-tumor lysis, rhabdomyolysis)
Large-volume citrated blood transfusion (calcium chelation)
Osteoblastic malignancy
Pseudohypoparathyroidism
Risk factors
Hypoparathyroidism
Acute pancreatitis
Vitamin D deficiency
Chronic kidney disease

Associated disorders

Epilepsy (in adults or in children): hypocalcemia secondary to anticonvulsant therapy

HIV: hypocalcemia due to calcium chelation in foscarnet therapy
Chronic liver disease: defective hydroxylation of vitamin D
Intestinal malabsorption
Tuberculosis: isoniazid therapy
Intensive care unit stay (probably related to underlying severe illness)

Screening
Summary approach

Screening for hypocalcemia after thyroid/parathyroid surgery and in chronic kidney disease should be
undertaken after surgery. Vitamin D deficiency should be corrected before thyroid/parathyroid surgery in order to
avoid prolonged hypocalcemia postoperatively
Treatment is easy to instigate and cost-effective, with a rapid resolution of symptoms

Primary prevention
Summary approach

Patient should maintain a diet that is sufficient in fat-soluble vitamins (including D) and dietary calcium

Alcohol intake should be moderate to avoid the risk of hypomagnesemia

Patient should get a moderate amount of sun exposure to maintain appropriate vitamin D hydroxylation
in the skin

Preventive measures

Alternative medications containing calcium are available, and these may be of benefit in patients who
have dietary calcium deficiency
A family history of tetany or seizures in childhood may indicate a risk of genetic hypo- or
pseudohypoparathyroidism