Description

• Deficient or absent secretion of parathyroid hormone (PTH), a major hormone regulator of serum calcium and phosphorus levels in the body (1)
• Acute hypoparathyroidism: tetany that is mild (muscle cramps, perioral numbness, paresthesias of hands and feet) or severe (carpopedal spasm, laryngospasm, heart failure, seizures, stridor)
• Chronic: often asymptomatic; lethargy, anxiety/depression, urolithiasis and renal impairment, dementia, blurry vision from cataracts or keratoconjunctivitis, parkinsonism or other movement disorders, mental retardation, dental abnormalities, and dry, puffy, coarse skin
• System(s) affected: endocrine/metabolic, musculoskeletal, nervous, ophthalmologic, renal

Pediatric Considerations

• May occur in premature infants
• Neonates born to hypercalcemic mothers may experience suppression of developing parathyroid glands.
• Congenital absence of parathyroids
• May appear later in childhood as autoimmune

Geriatric Considerations
Hypocalcemia is fairly common in elderly, however, rarely secondary to hypoparathyroidism.

Pregnancy Considerations

• Use of magnesium as a tocolytic may induce functional hypoparathyroidism.
• For women with hypoparathyroidism, calcitriol requirements decrease during lactation.

Epidemiology

More common in women; affects all ages

Incidence

• Most common after surgical procedure of the anterior neck, particularly when the surgeon performs few anterior neck dissections (<50–100 thyroidectomies/parathyroidectomies per year).
• Transient hyperparathyroidism is common (6.9–46% of thyroidectomies), whereas permanent hypoparathyroidism differs depending on surgeon and facility expertise.

Prevalence

• Affects 24 to 37/100,000 persons per year in the United States (1)
• Genetic disorders account for <10% of all hypoparathyroidism, but represent a large proportion of cases in children.

Etiology and Pathophysiology

• PTH aids in regulating calcium homeostasis:
  • Mobilizes calcium and phosphorus from bone stores
  • Increases calcium absorption from the intestine by stimulating formation of 1,25-dihydroxy vitamin D
  • Stimulates reabsorption of calcium in the distal convoluted tubule and phosphate excretion in proximal tubule
• Reduced or absent PTH action results in hypocalcemia, hyperphosphatemia, and hypercalciuria.
• Acquired hypoparathyroidism
  • Surgical: removal or damage to parathyroid glands or their blood supply/enervation during neck surgery for thyroidectomy/parathyroidectomy, or neck surgery for head and neck cancers (2)
  • Autoimmune: isolated or combined with other endocrine deficiencies in polyglandular autoimmune (PGA) syndrome
  • Deposition of heavy metals in gland: copper (Wilson disease) or iron (hemochromatosis, thalassemias), radiation-induced destruction, and metastatic infiltration
  • Functional hypoparathyroidism: may result from hypomagnesemia or hypermagnesemia because magnesium is crucial for PTH secretion and activation of the PTH receptor
  • Congenital
    • Calcium-sensing receptor (CaSR) abnormalities: hypocalcemia with hypercalciuria
    • HDR or Barakat syndrome: deafness, renal dysplasia
    • Familial: mutations of the TBCE gene; abnormal PTH secretions
    • 22q11.2 deletion syndrome
• Autoimmune: genetic gain-of-function mutation in CaSR
• Infiltrative: metastatic carcinoma, hemochromatosis, Wilson disease, granulomas

Genetics

• X-linked or in autosomal recessive mutations in the transcription factor glial cell missing B (GCMB)
• Mutations in transcription factors or regulators of parathyroid gland development
  • Component of a larger genetic syndrome (APS-1 or DiGeorge syndrome) or in isolation (X-linked hypoparathyroidism) (3)
  • May be autosomal dominant (DiGeorge), autosomal recessive (APS-1), or X-linked recessive (X-linked hypoparathyroidism) (3)
  • Congenital syndromes
    • 22q11.2 deletion syndrome, familial hypomagnesemia, hypoparathyroidism with lymphedema (3)
    • Hypoparathyroidism with sensorineural deafness
    • ADHH: mutations gain-of-function of the CaSR gene suppressing the parathyroid gland, without elevation of PTH
  • PGA syndrome type I: mucocutaneous candidiasis, hypoparathyroidism, and Addison disease

Risk Factors

Neck surgery and neck trauma, neck malignancies, family history of hypocalcemia, PGA syndrome

General Prevention

Intraoperative identification and preservation of parathyroid tissue

Commonly Associated Conditions

• DiGeorge syndrome
• Bartter syndrome
• PGA syndrome type I
• Multiple endocrine deficiency autoimmune candidiasis (MEDAC) syndrome
• Juvenile familial endocrinopathy
• Addison disease
• Moniliasis (HAM) syndrome: a polyglandular deficiency syndrome, possibly genetic, characterized by hypoparathyroidism