Pediatric Hypoparathyroidism

Updated: Aug 05, 2015
  • Author: Pisit (Duke) Pitukcheewanont, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
  • Print
Overview

Background

Hypoparathyroidism results from defective synthesis or secretion of parathyroid hormone (PTH), end-organ resistance, or inappropriate regulations that result from the activated or antibody-stimulated calcium-sensing receptor (CaSR). [1] These defects can be inherited or acquired. PTH secretion by the parathyroid glands (prime regulators of serum calcium concentration) maintains serum calcium within a strict range. Biochemical hallmarks of hypoparathyroidism include hypocalcemia and hyperphosphatemia. Severe hypocalcemia presents with seizures, stridor, prolonged QTc, and tetany.

Electrocardiogram (ECG) findings in severe hypocal Electrocardiogram (ECG) findings in severe hypocalcemia.
Next:

Pathophysiology

Mature PTH is an 84–amino acid protein. Production and secretion of PTH are regulated by a G protein–coupled calcium-sensing receptor. Unlike other protein hormones, its production and secretion are stimulated by decreased intracellular calcium concentrations, which reflect serum calcium concentrations. PTH exerts its action through the PTH receptor, which is another member of the G protein–linked receptor family.

The net effects of PTH activity are an increase in serum calcium and a decrease in serum phosphate. PTH acts directly on bone to stimulate bone resorption and cause calcium and phosphate release. PTH acts directly on the kidney to decrease calcium clearance and to inhibit phosphate reabsorption. By stimulating renal 1-alpha-hydroxylase activity, PTH increases serum concentrations of 1,25-dihydroxyvitamin D, the active form of vitamin D and, thus, indirectly stimulates calcium and phosphate absorption by the gut through the actions of vitamin D. The phosphaturic effect of PTH offsets the increases of serum phosphate driven by increased bone resorption and GI absorption.

Hypoparathyroidism results in loss of both the direct and indirect effects of PTH on bone, the kidney, and the gut. Calcium and phosphate release from bone is impaired, calcium absorption from the gut is limited, calciuria develops despite hypocalcemia, and retention of phosphate from the urine causes increased plasma phosphate levels.

Previous
Next:

Epidemiology

Frequency

United States

The incidences of idiopathic hypoparathyroidism and pseudohypoparathyroidism (PHP) have not been determined in the United States. Rates following surgical procedures such as thyroidectomy vary depending on the extent of the surgery and experience of the surgeon.

International

In Japan, a recent survey found the prevalence of idiopathic hypoparathyroidism to be 7.2 cases per million people and the prevalence of PHP to be 3.4 cases per million people.

Mortality/Morbidity

Complications of hypoparathyroidism result from hypocalcemia.

  • Neurologic: Neuromuscular irritability, paresthesias, muscle cramping, tetany, or seizures. However, patients can be asymptomatic. Neck muscle cramping can cause dystoniclike neck movements.
  • Cardiac: Prolongation of the QTc interval. Affected individuals may be asymptomatic or experience syncope, seizure, or death due to arrhythmias, such as polymorphic ventricular tachycardia.
  • Respiratory: Laryngospasm, a form of tetany, can lead to stridor and significant airway obstruction.

Sex

Hypoparathyroidism is equally prevalent in males and females.

Age

Age of onset depends on the etiology of hypoparathyroidism. Transient hypoparathyroidism is common during the first few days of life in preterm infants, infants of mothers with diabetes mellitus, infants of mothers with hypercalcemia, and infants with a prolonged delay in parathyroid gland responsiveness.

Transient hypoparathyroidism in newborns usually presents with hypocalcemia; however, it can recur during the adolescent period as seen in some patients with DiGeorge Syndrome.

In general, patients with DiGeorge syndrome present during the first few weeks of life. In patients with velocardiofacial syndrome (DiGeorge variant) and autoimmune and PTH resistance syndromes (pseudohypoparathyroidism), hypocalcemia tends to present as late as adolescence.

Previous