Description

• Deficient secretion of parathyroid hormone (PTH)
• Acute hypoparathyroidism with associated hypocalcemia results in tetany, muscle cramps, carpopedal spasm, irritability, altered mental status, convulsion, stridor, and tingling of the circumoral area, hands, and feet.
• Chronic: Lethargy, personality changes, anxiety, blurry vision, parkinsonism, mental retardation
• Acquired hypoparathyroidism:
  • Surgical: Removal or damage to parathyroid glands or their blood supply. Thyroid, parathyroid, or radical neck surgery for head and neck cancers
  • Autoimmune: Isolated or combined with other endocrine deficiencies in polyglandular autoimmune (PGA) syndrome
  • Deposition of heavy metals in gland: Copper (Wilson's disease) or iron (hemochromatosis, thalassemias), radiation-induced destruction, and metastatic infiltration
  • Functional hypoparathyroidism: Associated with hypomagnesemia. Hypermagnesemia
  • 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
• System(s) affected: Endocrine/Metabolic; Musculoskeletal; Nervous; Bones; Kidneys; Parathyroid

• 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 or APS-1.

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.

Epidemiology

More common in women. Affects all ages.

Incidence
Most common after surgical procedure of the anterior neck. Transient hypoparathyroidism is seen after 24.1% of thyroidectomies, whereas permanent hypoparathyroidism 1.2–3.8%.

Prevalence
Wide variation. Autosomal-dominant hypocalcemia with hypercalciuria (ADHH): 1/70,000 typically in infancy with hypocalcemic seizures

Risk Factors

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

• Genetic defects may result in X-linked or in autosomal-recessive hypoparathyroidism due to abnormal parathyroid gland development. Associated with mutations in the transcription factor glial-cell missing B (BCMB)
• Mutations in transcription factors or regulators of parathyroid gland development:
  • Hypoparathyroidism may present as a component of a larger genetic syndrome (APS-1 or DiGeorge syndrome) or in isolation (X-linked hypoparathyroidism).
  • May be autosomal–dominant (DiGeorge), autosomal recessive (APS-1), or X-linked recessive (X-linked hypoparathyroidism)
  • Congenital syndromes:
    • http://22q11.2 deletion syndrome, familial hypomagnesemia, hypoparathyroidism with lymphedema (1)
    • Hypoparathyroidism with sensorineural deafness
    • ADHH: Mutations gain-of-function of the CaSR gene suppressing the parathyroid gland, without elevation of PTH
  • PGA syndrome type 1: Mucocutaneous candidiasis, hypoparathyroidism, and Addison disease

General Prevention

Intraoperative identification and preservation of parathyroid tissue

Pathophysiology

• PTH is involved in the control of serum ionized calcium levels:
  • Mobilizes calcium and phosphorus from bone stores
  • Stimulates formation of 1,25-dihydroxy-vitamin D
  • Stimulates reabsorption of calcium in the distal convoluted tubule and phosphate excretion in proximal tubule
• Loss of PTH action results in hypocalcemia, hyperphosphatemia, and hypercalciuria.
• Magnesium is crucial for PTH secretion and activation of the PTH receptor; hypo- or hypermagnesemia may result in functional hypoparathyroidism.

Etiology

• Postsurgical: Transient, intermittent or permanent irradiation
• Autoimmune: Genetic gain-of-function mutation in calcium-sensing receptor
• Infiltrative: Metastatic carcinoma, hemochromatosis, Wilson disease, granulomas
• Hypo- (alcoholics) or hypermagnesemia: Chronic iron overloads

Commonly Associated Conditions

• DiGeorge syndrome
• PGA syndrome type 1
• Multiple endocrine deficiency autoimmune candidiasis (MEDAC) syndrome
• Juvenile familial endocrinopathy
• Hypoparathyroidism
• Addison disease
• Moniliasis (HAM) syndrome: A polyglandular deficiency syndrome, possibly genetic, characterized by hypoparathyroidism