Hypocalcemia

Definition, Etiology, PathogenesisTop

Hypocalcemia is defined as a serum [Ca2+] <2.25 mmol/L (<9 mg/dL).

Causes:

1) Insufficient dietary calcium intake.

2) Impaired absorption of calcium from the gastrointestinal (GI) tract due to malabsorption syndromes or vitamin D deficiency.

3) Excessive deposition of calcium in soft tissues or bone due to acute pancreatitis, so-called hungry bone syndrome after parathyroidectomy, hyperphosphatemia, bisphosphonates, fluoride poisoning, or foscarnet.

4) Excessive urinary excretion of calcium due to treatment with loop diuretics, deficiency of or resistance to parathyroid hormone (PTH), or tubular acidosis.

5) Absolute or relative vitamin D deficiency due to impaired 25-hydroxylation of vitamin D in patients with liver disease, impaired 1-alpha-hydroxylation of 25(OH)D3 in patients with acute or chronic renal failure, inadequate absorption of vitamin D from the GI tract (celiac disease, cholestatic jaundice, pancreatic enzyme deficiency), increased vitamin D inactivation in patients treated with certain antiepileptic drugs (hydantoin derivatives and barbiturates), hyperphosphatemia, or tumor lysis syndrome.

6) PTH deficiency: Hypoparathyroidism.

7) Tissue resistance to PTH: Pseudohypoparathyroidism.

Pseudohypocalcemia is falsely low serum calcium levels caused by the presence of a gadolinium-containing contrast agent in blood.

Clinical FeaturesTop

Clinical manifestations of hypocalcemia result from the deficiency of ionized (biologically active) calcium and are mainly a consequence of nervous system and neuromuscular dysfunctions.

Hypocalcemia is manifested as tetany or its equivalents. An episode of tetany is characterized by numbness and symmetric tonic spasms of the muscles of the hand (“obstetrician’s hand”), which then extend to the muscles of forearms and arms, face (blepharospasm, “carp mouth”), chest, and lower limbs (equinovarus positioning), with preserved consciousness. Latent tetany may be demonstrated by the Chvostek sign (twitching of the facial muscles after tapping the facial nerve ~2 cm anterior to the earlobe, just below the zygomatic arch; see Figure 1 in Hypoparathyroidism), the Trousseau sign (carpal spasm causing the “obstetrician’s hand” induced by inflating a blood pressure cuff on the patient’s arm to a pressure 20 mm Hg above systolic blood pressure for 3 minutes; see Figure 2 in Hypoparathyroidism), or by triggering an episode of tetany through hyperventilation.

Other manifestations of hypocalcemia include seizures, hypotension, and papilledema. Electrocardiography (ECG) may reveal a long QT interval (due to the long ST interval). Chronic hypocalcemia is often asymptomatic, as ionized calcium levels are normal or near-normal.

DiagnosisTop

The diagnosis of hypocalcemia is based on measurement of serum [Ca2+] (<2.25 mmol/L [<9 mg/dL]). In patients with hypoalbuminemia and a normal pH level, add 0.2 mmol/L (0.8 mg/dL) for every 10 g/L of reduction in the plasma albumin level below 40 g/L (the corrected calcium level). A low ionized calcium level confirms deficiency of the biologically active form of calcium.

Tests performed to establish the underlying cause of hypocalcemia may include serum levels of creatinine, phosphate, magnesium, potassium, alkaline phosphatase, PTH, and vitamin D; 24-hour urinary calcium excretion; and imaging studies (to detect skeletal abnormalities, abnormal lymph nodes, and cancer).

TreatmentTop

1. Treatment of the underlying condition is the mainstay of the management of hypocalcemia.

2. In patients with symptomatic hypocalcemia (tetany), administer 20 mL of 10% calcium gluconate IV; repeat the injection if symptoms recur. Measure serum [Ca2+] every 4 to 6 hours (in patients with hypoalbuminemia measure ionized calcium levels). At the same time, start oral administration of calcium and vitamin D, usually in the form of active metabolites—alfacalcidol or calcitriol—in a dose of 0.5 to 2 microg/d. Refractory symptomatic hypocalcemia may be due to hypomagnesemia. In such cases ensure magnesium replacement.

3. In patients with chronic hypocalcemia where the underlying cause cannot be resolved, administer oral calcium 1000 to 2000 mg/d in the form of calcium carbonate (1 g of calcium carbonate contains 400 mg of calcium) or calcium acetate (1 g of calcium acetate contains 253 mg of calcium) combined with vitamin D, usually also in the form of active metabolites. Periodically measure serum or urine [Ca2+] (hypercalciuria is the first sign of overtreatment).

4. In patients with hypocalcemia due to excessive urinary calcium loss, administer thiazide diuretics, for example, oral hydrochlorothiazide 25 to 50 mg/d as accessory treatment (to reduce urinary calcium excretion).