ESSENTIALS OF DIAGNOSIS
Usually asymptomatic but can cause cramps or tetany if severe.
Decreased serum parathyroid hormone (PTH), vitamin D, or magnesium levels.
Despite a low total serum calcium, calcium metabolism is likely normal if ionized calcium level is normal.
The most common cause of low total serum calcium is hypoalbuminemia. When serum albumin concentration is lower than 4 g/dL (40 g/L), serum Ca2+ concentration is reduced by 0.8–1 mg/dL (0.20–0.25 mmol/L) for every 1 g/dL (10 g/L) of albumin. True hypocalcemia (decreased ionized calcium) implies insufficient action of PTH or active vitamin D. Important causes of hypocalcemia are listed in Table 21–6.
Table 21–6.Causes of hypocalcemia. ||Download (.pdf) Table 21–6. Causes of hypocalcemia.
Decreased intake or absorption
Small bowel bypass, short bowel
Vitamin D deficit (decreased absorption, decreased production of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D)
Alcohol use disorder
Hypoparathyroidism, genetic or acquired (including hypo- and hypermagnesemia)
Post-parathyroidectomy (hungry bone syndrome)
Calcitonin secretion with medullary carcinoma of the thyroid
Decreased serum albumin1
Decreased end-organ response to vitamin D
Aminoglycoside antibiotics, plicamycin, loop diuretics, foscarnet
The most common cause of hypocalcemia is advanced CKD, in which decreased production of calcitriol and hyperphosphatemia both play a role (see Chapter 22). Rarely, primary hypoparathyroidism due to mutations of the calcium-sensing receptor inappropriately suppressing PTH release leads to hypocalcemia (see Chapter 26). Magnesium depletion reduces both PTH release and tissue responsiveness to PTH, causing hypocalcemia. Hypocalcemia in pancreatitis is a marker of severe disease. Elderly hospitalized patients with hypocalcemia and hypophosphatemia, with or without an elevated PTH level, are likely vitamin D deficient.
The hallmark sign of severe hypocalcemia (ionized calcium below 1 mmol/L) is tetany from increased neuromuscular irritability; this finding is generally uncommon with higher ionized calcium levels. Laryngospasm with stridor can obstruct the airway. Convulsions, perioral and peripheral paresthesias, and abdominal pain can develop. Less pronounced symptoms include fatigue, anxiety, and depression. Classic physical findings include Chvostek sign (contraction of the facial muscle in response to tapping the facial nerve) and Trousseau sign (carpal spasm occurring with occlusion of the brachial artery by a blood pressure cuff). QT prolongation predisposes to ventricular arrhythmias, though serious dysrhythmias are rare.
Serum calcium concentration is low (less than 8.5 mg/dL [2.1 mmol/L]). In true hypocalcemia, the ionized serum calcium concentration is also low (less than 4.6 mg/dL [1.15 mmol/L]). Serum phosphate is usually elevated in hypoparathyroidism or in advanced CKD, whereas it is suppressed in vitamin D deficiency.