Hpocalcaemia is less common than hypercalcaemia. Sympoccurs when serum calcium is <1.9 mmol/L, or at higher values if there is a rapid drop in calcium. The most common cause of hypocalcaemi ostsurgical hypoparathyroidism following thyroidectomy.
Post-thyroidectomy hypocalcaemia is often temporary, but can be permanent because of damage to or inadvertent removal of the parathyroid glands. Long-term follow-up is needed to assess recovery of parathyroid function.
A low serum calcium with low PTH presenting in adulthood suggests idiopathic or autoimmune hypoparathyroidism. This can accompany polyglandular autoimmune syndrome. In children, congenital hypoparathyroidism should be considered; for example, Di George’s syndrome is a rare condition associated with hypoparathyroidism, immunodeficiency and cardiac defects resulting from developmental failure of the third and fourth branchial arches.
Vitamin D deficiency
Severe vitamin D deficiency causes hypocalcaemia and should be considered in high-risk groups. In the neonate, severe vitamin D deficiency can present with seizures and tetany caused by hypocalcaemia. Typically, phosphate is low in vitamin D deficiency because of elevated PTH levels, unlike hypoparathyroidism where phosphate is high.
Hypomagnesaemia causes functional hypoparathyroidism, with normal or low PTH levels. Common causes of low magnesium include gastrointestinal loss, alcohol and drugs, particularly proton pump inhibitors.
High phosphate levels lead to hypocalcaemia by increased binding of free calcium. Causes include chronic kidney disease and phosphate administration.
Other causes of hypocalcaemia include cytotoxic drugs, pancreatitis, rhabdomyolysis and large volume drug transfusions (Figure 17.1).
Acute severe hypocalcaemia causes laryngospasm, prolonged QT interval and seizures, and is a medical emergency (Chapter 41). However, hypocalcaemia usually presents less acutely with muscle cramps, carpopedal spasm, peri-oral and peripheral paraesthesia, and neuropsychiatric symptoms.
Patients may have a positive Chvostek’s sign (facial spasm when the cheek is tapped gently with the finger) or Trousseau’s sign (carpopedal spasm induced after inflation of a sphygmomanometer).
Renal function, phosphate, vitamin D and PTH should be measured when the cause of hypocalcaemia is not clear (Figure 17.1). Hypocalcaemia associated with high phosphate and low PTH suggests hypoparathyroidism. Hypocalcaemia associated with low phosphate and high PTH is in keeping with vitamin D deficiency and secondary hyperparathyroidism (Figure 17.1). Demonstration of low vitamin D levels confirms a suspected diagnosis of severe deficiency. Magnesium deficiency should be excluded in refractory or unexplained hypocalcaemia. Parathyroid antibody levels should be checked in non-surgical hypoparathyroidism to exclude an autoimmune cause. In chronic hypoparathyroidism, brain imaging can reveal basal ganglia calcification, caused by high phosphate binding to calcium within tissues.
Calcium replacement is the mainstay of therapy. It is important to consider and reverse the underlying cause. Acute hypocalcaemia can be life-threatening and requires urgent treatment with intravenous calcium.
Vitamin D deficiency
Patients with severe vitamin D deficiency should be given a loading dose of cholecalciferol. A dose of 20,000 IU/week is given for 7 weeks followed by a maintenance dose of 1000–2000 IU/week.
Hypoparathyroidism is treated with alfa-hydroxylated derivates of vitamin D (e.g. 1-alfacalcidol or calcitriol). These have a shorter half-life than cholecalciferol and should not be used in simple vitamin D deficiency. The typical starting dose is 0.25 µg/ day 1-alfacalcidol, with dose titration according to clinical and biochemical responses. Oral calcium supplements (e.g. Sandocal and Adcal D3) are given in combination with alfacalcidol. The aim of treatment is to keep calcium levels at the lower end of the reference range to reduce the risk of nephrocalcinosis.
In the acute situation, precipitating drugs should be stopped and IV magnesium replacement started. This is usually given as MgSO4 24 mmol/24 hours. If chronic gastrointestinal loss or alcohol ingestion is the cause, appropriate specialist input is indicated to prevent recurrent symptoms.
This rare condition is caused by a mutation in the GS alpha subunit (GNAS1) which is coupled to the PTH receptor and leads to PTH resistance. It is characterised by hypocalcaemia and a high phosphate level, which would normally suggest hypoparathyroidism, but high PTH and normal vitamin D levels suggests PTH resistance rather than deficiency, hence the term pseudo-hypoparathyroidsm. Patients have a syndromic appearance with short stature, round face and short 4th and 5th ripheral resistance to TSH and gonadotrophins an also be seen in this rare condition.