Hyperparathyroidism

From Dog
Histological appearance of a parathyroid carcinoma showing marked anisokaryosis and anisocytosis[1]

Hyperparathyroidism is a rare endocrine disease of older dogs characterized by parathyroid gland hyperactivity and elevated parathyroid hormone levels[2].

Three forms of hyperparathyroidism are recognized in dogs:

  • Primary hyperparathyroidism - ↑Ca, ↓P, ↑PTH - benign parathyroid neoplasia, parathyroid adenoma, parathyroid carcinoma
  • Secondary nutritional hyperparathyroidism - ↓Ca, ↓P, ↑PTH - parathyroid hyperplasia
  • Secondary renal hyperparathyroidism - ↓Ca, ↑P, ↑PTH - parathyroid hyperplasia

Primary hyperparathyroidism is caused by autonomously functioning neoplastic or hyperplastic parathyroid 'chief' cells. Keeshonden are predisposed due to an autosomal-dominant genetic mutation with age-related penetrance[3].

Nutritional secondary hyperparathyroidism is usually caused by dietary mineral imbalances, such as diets that are low in calcium or vitamin D, or diets containing an excessive amount of phosphorus, such as feeding an all-meat diet[4][5][6]. This condition may also be caused by type II rickets (vitamin D-independent)[7].

Secondary renal hyperparathyroidism results from decreased calcitriol production resulting in phosphorus retention and resultant calcium excretion due to chronic renal disease or juvenile renal dysplasia or polycystic kidney disease. In dogs, young growing animals are preferentially affected, likely because their bones are more sensitive to the action of PTH[8].

Clinically affected dogs present with polyuria, polydipsia, reduced activity and stiff gait (due to bone changes). Spontaneous fractures of limb and jaw are not uncommon[9] and facial swelling due to 'rubber jaw' has been reported[10].

Blood tests usually reveal hypercalcemia (normal 1.0 - 3.0 mmol/L), hypophosphatemia and normal or increased serum parathyroid hormone (normal 3 - 17 μmol/L) and parathyroid hormone-related protein levels[11]. Calcitriol levels may be normal or elevated (normal 60 - 250 nmol/L)[12]. Elevated parathyroid hormone levels can be elevated in other diseases such as hyperadrenocorticism[13].

Serum calcium exists as ionized calcium (up 56% of total serum calcium) protein bound calcium (30%) and complexed calcium. Free calcium is the portion of total serum calcium that is biologically active and should be measured when assessing pathology[14].

Ultrasonography may reveal enlarged or lobulated parathyroid glands, which must be distinguished from the thyroid gland which can be co-involved in neoplastic diseases[15].

Radiographs often reveal diffuse osteopenia of limb and skull and thinning of the cortices, polyostotic deformities associated with fracture remodeling, along with a floating dental arcade[16].

A differential diagnosis would include other causes of polyuria/polydipsia such as diabetes insipidus or causes of persistent hypercalcemia such as paraneoplasitc hypercalcemia (polyostotic lymphoma, osteosarcoma, anal sac adenocarcinoma), chronic renal disease, hypoadrenocorticism and vitamin D toxicosis. Additionally, parathyroid hormone levels can be elevated in association with inflammatory bowel disease[17] and hypoalbuminaemia, usually with a concurrent hypocalcemia[18]. Bone abnormalities can also be observed in rickets and osteogenesis imperfecta.

Primary hyperparathyroidism is usually treated by surgical thyroidectomy, percutaneous ultrasound-guided ethanol ablation or percutaneous ultrasound-guided heat ablation[19]. These procedures have a relative risk of complications, most commonly hypocalcemia[20]. Treatment with calcitriol and vitamin D supplements can be instituted to help avoid this postoperative complication.

Secondary renal hyperparathyroidism can be treated with dietary phosphorus restriction, intestinal phosphate binders, and calcitriol supplementation, which may slow the progression of renal disease[21].

References

  1. Sakals SA et al (2010) Diagnosing the etiology of hypercalcemia in a dog: a case of primary hyperparathyroidism. Vet Pathol 47(3):579-581
  2. Jores K & Kessler M (2011) Primary hyperparathyroidism in the dog. Diagnosis, therapy and postoperative management in 19 dogs. Tierarztl Prax Ausg K Kleintiere Heimtiere 39(6):389-396
  3. Goldstein RE et al (2007) Inheritance, mode of inheritance, and candidate genes for primary hyperparathyroidism in Keeshonden. J Vet Intern Med 21(1):199-203
  4. Taylor MB et al (2009) Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef. J Am Vet Med Assoc 234(8):1041-1048
  5. De Fornel-Thibaud P et al (2007) Unusual case of osteopenia associated with nutritional calcium and vitamin D deficiency in an adult dog. J Am Anim Hosp Assoc 43:52–60
  6. Agarwal A et al (2009) Hyperparathyroidism and malnutrition with severe vitamin D deficiency. World J Surg 33:2303–2313
  7. LeVine DN et al (2009) Hereditary 1,25-dihydroxyvitamin D-resistant rickets in a Pomeranian dog caused by a novel mutation in the vitamin D receptor gene. J Vet Intern Med 23(6):1278-83
  8. Polzin DJ et al (2004) Chronic Kidney Disease. In: Ettinger SJ, Feldman EC, editors. Textbook of Veterinary Medicine. 6th ed. 2 . St. Louis, Missouri: Elsevier. pp:1756–1785
  9. Roux P (2007) Mandibular fracture in a Lhasa Apso with secondary renal hyperparathyroidism. Schweiz Arch Tierheilkd 149(6):277-279
  10. de Fornel-Thibaud P et al (2007) Unusual case of osteopenia associated with nutritional calcium and vitamin D deficiency in an adult dog. J Am Anim Hosp Assoc 43(1):52-60
  11. Mellanby RJ et al (2006) Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism. Vet Rec 159(25):833-838
  12. Vanbrugghe B et al (2011) Clinical and computed tomography features of secondary renal hyperparathyroidism. Can Vet J 52(2):177-180
  13. Tebb AJ et al (2005) Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations. J Small Anim Pract 46(11):537-542
  14. Schenck PA & Chew DJ (2005) Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs. Am J Vet Res 66:1330–1336
  15. Liles SR et al (2010) Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs. Vet Radiol Ultrasound 51(4):447-452
  16. Carmichael DT et al Renal dysplasia with secondary hyperparathyroidism and loose teeth in a young dog. J Vet Dent 12:143–146
  17. Mellanby RJ et al (2005) Hypocalcaemia associated with low serum vitamin D metabolite concentrations in two dogs with protein-losing enteropathies. J Small Anim Pract 46(7):345-351
  18. Gow AG et al (2011) Hypovitaminosis D in dogs with inflammatory bowel disease and hypoalbuminaemia. J Small Anim Pract 52(8):411-418
  19. Rasor L et al (2007) Retrospective evaluation of three treatment methods for primary hyperparathyroidism in dogs. J Am Anim Hosp Assoc 43(2):70-77
  20. Arbaugh M et al (2012) Evaluation of preoperative serum concentrations of ionized calcium and parathyroid hormone as predictors of hypocalcemia following parathyroidectomy in dogs with primary hyperparathyroidism: 17 cases (2001-2009). J Am Vet Med Assoc 241(2):233-236
  21. Stillion JR & Ritt M (2009) Renal secondary hyperparathyroidism. Compend Contin Educ Vet 31(6):E1-E11