Hyperparathyroidism

Parathyroid adenoma. Image courtesy of Biomed Archive.

Primary

• Primary hyperparathyroidism is caused by glandular hyperplasia or neoplasia.
  

  Parathyroid hyperplasia. Image courtesy of Biomed Archive.
• Rare.

Secondary

• Secondary hyperparathyroidism causes fibrous osteodystrophy or "rubber jaw".
• In secondary hyperparathyroidism, the gland is overactive due to another condition coexisting in the body, rather than a primary parathyroid gland defect.
• There are two common forms of secondary hyperparathyroisism:
  1. Nutritional Hyperparathyroidism
     • This includes Metabolic Bone Disease.
  2. Renal Hyperparathyroidism
• Both forms result in increased osteoclastic resorption of bone and deposition of fibro-osteoid matrix that fails to mineralise.
  • Flat bones of the skull swell.
  • Fibrous tissue is seen around the tooth roots.
  • Bone softens in adult animals.
    • This is what gives rise to the term "rubber jaw".
    • Long bones become soft with thin cortices.
      • These fracture easily.

Nutritional Hyperparathyroidism

Secondary hyperparathyroidism - "rubber jaw". Image courtesy of Biomed Archive.

• Nutritional hyperparathyroidism is also known as nutritional osteodystrophy.
• This occurs most commonly in:
  • Young, fast-growing animals
  • Animals with a poor diet, for example:
    • Swine fed unsupplemented cereal grain
    • Dogs and cats fed all-meat diets
    • Horses fed bran
      • In this case, nutritional hyperparathyroidism is known as "bran disease".

Pathogenesis

• Pathogenesis follows low calcium/high phosphate diets.
  • These lead to decreased serum calcium levels, stimulating PTH release.
  • The increase in PTH gives an increase in bone resorption, causing pathology.

Pathology

• Gross
  • Severe cases may show:
    • Maxillary and mandibular swelling
    • Teeth lost or buried in soft tissue
    • Nasal and frontal bone enlargement, leading to dyspnoea
    • Long bone fracture
    • Detatchment tendons and ligaments
  • Early or less severe cases are characterised by shifting lameness and ill thrift.
• Histological
  • Osteoclastic resorption
  • Fibrous replacement

Metabolic Bone Disease

• Metabolic bone disease affects lizards in captivity, particularly young green iguanas
• The condition is caused by:
  • Dietary deficiency of calcium and vitamin D
    • For example, due to poor lighting (which diminishes viatmin D production).
  • Dietary excess of phosphorus
  • Certain toxicities
  • Diseases of the kidneys, liver or parathyroid
    • This aetiology is rare
• Clinical signs include:
  • Lethargy
  • Inability to support weight
  • Rounded skull
  • Spontaneous fractures
  • Adult animals also show signs of hypocalcaemia
• The skeleton shows reduced density on radiography.

Renal Hyperparathyroidism

• Renal Hyerparathyroidism is mostly seen in the dog as an expression of chronic renal disease.

Pathogenesis

Parathyroid hyperplasia in renal hyperparathyroidism. Image courtesy of Biomed Archive.

1. Chronic renal disease results in reduced glomerular filtration.
2. As glomerular filtration is reduced, phosphate is retained. Chronic renal failure also causes inadequate vitamin D production in the kidneys.
3. Hyperphosphataemia develops due to phosphate retention.
   • Hypocalcaemia also occurs, as high levels of phosphate depress calcium levels.
4. PTH is released in an attempt to maintain the correct blood calcium:phosphorous ratio. This can have several effects:
   • Parathyroid hyperplasia
     • I.e. renal secondary hyperparathyroidism.
   • Soft tissue mineralisation
     • Particularly seen in dogs
     • Calcium is commonly deposited in the subpleural connective tissue of the intercostal spaces.
     • Calcification also occurs in other sites, e.g. stomach wall, lungs, kidneys.
   • Increased bone resorption
     • This causes fibrous osteodystrophy, or "rubber jaw".

Pathology

"Rubber jaw" in renal osteodystrophy. Image courtesy of Biomed Archive.

• Pathology seen in renal hyperparathyroidism is very similar to that seen in nutritional hyperparathyroidism.
• Gross
  • The major gross presentation is a fibrous osetodystrophy, or rubber jaw.
    • The maxillae and mandible appear swollen.
    • Radiographically, bone shows reduced density, and teeth hence appear embedded in soft tissue.
    • However, only a few cases of chronic renal disease show such severe bone lesions.
  • Other lesions may also be seen.
    • Intercostal muscles may be calcified.
    • Bone marrow lesions may cause anaemia.
    • The lung may show oedema, and have calcified alveolar walls.
• Histological
  • Osteoclastic resorption
  • Fibrous replacement

From musculoskeletal

• Can arise in a number of ways but single common factor is elevated PTH
• Results in increased resorption of bone and replacement by fibrous connective tissue

Primary hyperparathyroidism

• This is increased production of PTH not related to calcium or phosphorus levels
• Due to parathyroid neoplasia or bilateral idiopathic parathyroid hyperplasia
• Rare

Secondary hyperparathyroidism

• Regardless of pathogenesis, the result is:
  • Increased osteoclastic resorption of bone and deposition of fibro-osteoid matrix that fails to mineralise
  • Flat bones of the skull swell, including maxillary and nasal bones
  • Long bones become soft with thin cortices which fracture easily

Renal osteodystrophy (Image sourced from Bristol Biomed Image Archive with permission)

• Renal hyperparathyroidism
  • Pathogenesis:
    • Chronic renal failure
      • -> Retention of phosphate (due to reduced glomerular filtration) and inadequate production of vitamin D by kidneys
        • -> Hyperphosphataemia and hypocalcaemia (high P depresses Ca)
          • -> Increased PTH output
            • -> Increased bone resorption
              • -> Fibrous osteodystrophy - increased osteoclastic resorption of cancellous and cortical bone + proliferation of fibrous tissue
  • Mainly in dogs
  • Affects whole skeleton but mainly skull
  • Bones soft and pliable
  • Canine teeth easily removed - rubber jaw
  • Microscopically - Osteodystrophia fibrosa (above = fibrous osteodystrophy) +/- osteomalacia

• Nutritional hyperparathyroidism (nutritional osteodystrophy)
  • Also called fibrous osteodystrophy, “rubber jaw” or “bran disease”
  • More common in young, fast-growing animals
  • Pathogenesis:
    • Low calcium / high phosphate diets
      • -> Decreased calcium levels in serum
        • -> Parathyroid gland stimulated (may become enlarged)
          • -> Increased PTH
            • -> Increased bone resorption
  • Caused by poor diet
    • Cattle and sheep - usually mild disease
    • Swine fed un-supplemented cereal grain, usually mild disease
    • Dogs/cats fed all-meat or offal diets (Ca:P often as high as 1:20)
      • Few weeks after weaning
      • Provision of calcium alone correct the problem
      • Very brittle bones -> sponataneous fractures
      • Extreme porosity of the whole skeleton on radioghraphs
    • Horses fed bran
      • Very susceptible to high phosphorus diet
      • Any time after weaning, susceptibility declines after seventh year
      • Early signs:
        • Mild changes of gait
        • Stiffness
        • Transient shifting lameness
      • Advanced signs:
        • Swelling of mandible and maxilla - 'Big head'
        • Dyspnoea caused by swelling of nasal and frontal bones
        • Teeth lost or buried in softened jaw
        • Fractures from mild trauma
        • Detached tendons and ligaments
        • Histologically:
          • Marked loss of bone
          • Replacement by proliferative tissue
      • Often called Osteodystrophia fibrosa