Parathyroid Glands - Pathology

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Anatomy and Physiology

Anatomy and Physiology of the Parathyroid glands can be found here.

Hypercalcaemia

• Hypercalcaemia should not be ignored in an unwell animal.
  • The consequences of hypercalcaemia may be serious: prolonged untreated hypercalcaemia can lead to irreversible damage to many organs, particularly the kidneys.
  • There are multiple causes of hypercalcaemia, but if it is caught early a specific diagnosis and treatment are often possible.
• The clinical signs of hypercalcaemia are often vague.
  • Signs commonly include:
    • PU/PD
    • Anorexia
    • Dehydration
    • Weakness or lethargy
    • Vomiting
    • Prerenal azotaemia
  • More uncommonly, hypercalcaemia may present with:
    • Constipation
    • Cardiac arrhythmia
    • Seizures or twitching
    • Acute renal failure
    • Death
• Causes of hypercalcaemia may be:
  1. Nonpathologic
     • This may be due to:
       • Age - young animals have naturally higher calcium levels.
       • Lab error
       • Lipaemia
     • It is important to establish whether hypercalcaemia is true before persuing further diagnosis and treatment.
  2. Transient...
     • ...hypoadrenocorticism
     • ...haemoconcentration
     • ...hyperproteinaemia
  3. Pathological
     • Malignancy
     • Lymphoma
     • Anal sac adenocarcinoma
     • Renal failure
     • Hypervitaminosis D
     • Granulomatous disease
       • E.g fungal infections
     • Primary hyperparathyroidism
     • Skeletal lesions

Hypocalcaemia

• Hypocalcaemia is a relatively common finding in
  • Small animals
    • Most often associated with decreased albumin concentrations.
    • Usually clinically insignificant.
  • Farm animals
    • For example, dairy cows following parturition.
      • More clinically significant.
• Clinical signs may not always be present (i.e. clinically insignificant).
  • Clinical signs are most often seen in associated with lactation or post-operative causes.
  • When they seen, signs commonly include:
    • Facial rubbing
    • Muscle tremors or cramps
    • Stiff gait
    • Behavioural changes
  • The following are seen less commonly:
    • Panting
    • Pyrexia
    • Lethargy
    • Anorexia
    • Tachycardia or ECG abnormalities
    • Hypotension
    • Death
• Some causes of hypocalcaemia are also more common than others.
  • Common causes are:
    • Chronic renal failure
    • Hypoalbuminaemia
    • Eclampsia
    • Acute pancreatitis
    • Iatrogenic
    • Post thyroidectomy
    • Post parathyroidectomy
    • Blood transfusion
  • More uncommonly:
    • Lab error
    • Ethylene glycol toxicity
    • NaHCO₃ administration
    • Hypovitaminosis D
    • Hypomagnesaemia
    • Intestinal malabsorption
    • Primary hypoparathyroidism

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

Pseudo-Hyperparathyroidism

• Non-endocrine tumours may be capable of secreting hormones, or hormone-like factors.
  • A parathormone-like substance may be secreted in such a manner.

Apocrine Gland Adenocarcinoma

• Malignant tumours of the anal sac apocrine glands can produce PTH-related peptide (PTHrp).
  • This induces a pseudo-hyperparathyroidism and hypercalcaemia.

Lymphosarcoma

• 10 to 40% of cases in dogs may cause a pseudo-hyperparathyroidism.

Other Carcinomas

Some other carcinomas may also be capable of causing pseudo-hyperparathyroidism.

Hypoparathyroidism

• Hypoparathyroidism may result from primary gland hypofunction.
  • Gland hypofunction occurs due to:
    1. Destruction of secretory cells by a disease process.
       • For example, this may be immune mediated, or another inflammatory cause.
    2. A biochemical defect in synthetic pathway of the hormone.
       • These are usually genetic aberrations.
       • Defects in synthesis are not commonly identified in the veterinary species.