Veterinary Society of
Surgical Oncology

GENERAL CONSIDERATIONS

Anatomy

  • parathyroid glands are salmon-coloured and distinct from the thyroid glands
  • 1 external and 1 internal parathyroid gland per thyroid gland
  • external parathyroid gland is on the cranial pole of the thyroid gland and external to its capsule
  • internal parathyroid gland are within the thyroid capsule in the caudal and medial aspects of the thyroid
  • external parathyroid gland is vascularized by a branch of the cranial thyroid artery
  • ectopic parathyroid tissue is present in 35%-50% of cats and 6%-100% of dogs and can be located anywhere from the base of the tongue to the heart base

PRIMARY HYPERPARATHYROIDISM

General Considerations

  • primary hyperparathyroidism is caused by excessive secretion of PTH from the parathyroid glands due to hyperplasia, benign adenoma, or malignant ADC of the parathyroid glands
  • parathyroid neoplasia is uncommon in dogs and rare in cats
  • 4 parathyroid glands (1 internal and 1 external on both thyroid glands)
  • hyperplastic or adenomatous changes can be observed in multiple parathyroid glands
  • 7% (5/72) dogs with primary hyperthyroidism have multiple parathyroid gland involvement, but only 1 involved all 4 parathyroid glands (multiple parathyroid gland involvement common in Keeshond)
  • secondary hyperplasia should be investigated if all 4 parathyroid glands are enlarged
  • neoplastic or hyperplastic parathyroid gland is usually palpable although surrounding thyroid tissue may make assessment difficult
  • histopathology: hyperplasia, adenoma, and ADC (rare)
  • differentiation of hyperplasia from adenoma is difficult
  • ectopic parathyroid tissue has been identified in the cranial mediastinum

Pathophysiology

  • parathyroid neoplasia causes excessive and autonomous PTH secretion from parathyroid chief cells
  • increased circulating levels of PTH results in:
  • increased calcium and phosphorus release from bone
  • increased calcium reabsorption and phosphorus excretion by the kidneys
  • increased calcium and phosphorus absorption in the intestines

Signalment

  • cats: Siamese over-represented
  • dogs: Keeshond while GSD, Poodles, and Labrador and Golden Retrievers are over-represented

Clinical Features

  • clinical signs are caused by a slow and progressive increase in serum calcium
  • polyuria-polydipsia is a common finding in dogs because of poor response of tubular cells to ADH
  • renal changes include interstitial nephritis and nephrocalcinosis
  • hypercalcemia induces vasoconstriction of afferent renal arterioles and decreases GFR
  • other findings include weakness, lethargy, inappetance, and calcium-based urolithiasis with UTI
  • lethargy, weakness, GI signs, and constipation are common findings in cats and is caused by decreased excitability of GI smooth muscle

Diagnosis

General Considerations

  • diagnosis of parathyroid hyperplasia or neoplasia has previously been a rule-out diagnosis followed by confirmation with surgical biopsy
  • primary hyperparathyroidism diagnosed in dogs when neoplasia and hypoadrenocorticism excluded
  • primary hyperparathyroidism diagnosed in cats when non-parathyroid neoplasia and CRF excluded
  • however, validated assays and ultrasonography have facilitated the diagnosis of primary hyperparathyroidism

Serum Biochemistry

  • mildly to markedly elevated serum total and ionized calcium caused by excessive autonomous secretion of PTH from the hyperplastic or neoplastic parathyroid glands
  • 50% of serum calcium is protein bound and hence diseases causing increased albumin or total protein may increase calcium measurements
  • 45% of serum calcium is unbound, ionized, and metabolically active
  • other abnormalities on serum biochemistry include low to normal serum phosphorus and mild to moderate increases in ALP secondary to bone resorption
  • uncomplicated primary hyperparathyroidism: normal renal function and isosthenuric or hyposthenuric urine
  • however, prolonged hypercalcemia may affect renal function

Parathyroid Hormone Assay

  • serum PTH levels may be normal to increased in cats and dogs with primary hyperparathyroidism
  • parathyroid hyperplasia suspected if normal serum PTH and increased ionized calcium

Ultrasonography

  • cervical ultrasonography can routinely identify parathyroid nodules < 5 mm
  • parathyroid nodules < 4 mm more likely to be primary or secondary parathyroid hyperplasia
  • parathyroid nodules ≥ 4 mm more likely to be parathyroid adenoma or carcinoma

Nuclear Scintigraphy

  • technetium-99m-sestamibi radionucleide scans can accurately identify parathyroid masses in humans
  • nuclear scintigraphy has the potential additional advantage of identifying ectopic parathyroid tissue
  • however, technetium-99m-sestamibi only has an 11% sensitivity, 50% specificity, and 27% overall accuracy for detecting and localizing hyper-functional parathyroid tissue (0% sensitivity for parathyroid hyperplasia and 25% sensitivity for parathyroid adenoma)
  • sensitivity, specificity, and accuracy are greater in humans when scintigraphy combined with ultrasonography

Treatment

Conservative Management

  • emergency management of hypercalcemia is rarely required in animals with primary hyperparathyroidism
  • symptomatic therapy should:
  • promote external loss of calcium
  • increase renal excretion of calcium
  • inhibit bone release of calcium
  • isotonic sodium chloride will ameliorate dehydration, expand extracellular fluid volume, increase GFR, increase calciuresis and natriuresis, and decrease calcium reabsorption by kidneys
  • furosemide and other loop diuretics can be used following rehydration to limit calcium reabsorption in ascending loop of Henle
  • corticosteroids can be used to inhibit prostaglandin, osteoclast-activating factor, vitamin D, and intestinal calcium absorption if the cause of hypercalcemia of malignancy is determined
  • salmon calcitonin (4.5 U/kg q 8 hr SC) rapidly reduces serum calcium levels, but this effect is transient
  • other treatments for severe hypercalcemia include mithramycin, bisphosphonates, and gallium nitrate

Percutaneous Ultrasound-Guided Ethanol Injection

  • ultrasound-guided injection of 96% ethanol into the parathyroid nodule
  • percutaneous injection of ethanol results in coagulative necrosis and vascular thrombosis
  • serum calcium, phosphorus, and PTH normalized within 5 days in all 8 dogs
  • complications: hypocalcemia in 50% (4/8), recurrence in 13% (1/8) after 1 month, and mild dysphonia

Percutaneous Ultrasound-Guided Radiofrequency Heat Ablation

  • ultrasound-guided radiofrequency heat ablation of parathyroid glands
  • radiofrequency treatment ablates tissue by thermal necrosis
  • number of treatments: 1 in 6 dogs, 2 in 2 dogs, and unsuccessful in 3 dogs
  • serum ionized and total calcium levels normalized within 48 hours in all 8 successfully treated dogs
  • serum PTH decreased within 24 hours in all 8 successfully treated dogs
  • hypocalcemia developed in 63% (5/8) successfully treated dogs and all required treatment
  • complication: transient and mild dysphonia

Parathyroidectomy

  • position: dorsal recumbency with neck extended and towel placed under neck
  • ventral midline skin incision from larynx to manubrium
  • skin incision continued through subcutaneous tissue and oblique fibres of sphincter coli muscle
  • sternohyoideus muscles are exposed and separated in midline to expose trachea
  • thyroid glands normally located immediately caudal to larynx on medial aspect of sternothyroideus muscles
  • abnormal parathyroid gland is usually well-defined at 1 pole of the thyroid gland
  • abnormal parathyroid gland is removed by blunt dissection
  • thyroidectomy is rarely required
  • remaining parathyroid glands are usually atrophied and will result in postoperative hypocalcemia
  • parathyroid hyperplasia is the most common cause of enlargement of all 4 parathyroid glands and removal of 1-3 parathyroid glands may ameliorate clinical signs of hypercalcemia
  • complete cervical area is examined for ectopic tissue if there is no evidence of parathyroid gland enlargement

Postoperative Management

  • 58% of dogs become hypocalcemic after surgical resection of a single parathyroid tumor
  • muscular (i.e., fasciculations, ataxia, and pain), cardiac (i.e., arrhythmias), and GI responses may be observed with sudden decrease in calcium following chronic adaption to severe hypercalcemia
  • suppressed parathyroid glands require 14-21 days to recover function
  • postoperative support of calcium homeostasis is correlated with degree of preoperative hypercalcemia
  • dogs with preoperative calcium > 14 mg/dL present a high risk and are managed with vitamin D and calcium supplementation to maintain calcium levels in low normal range for several days prior to gradual weaning
  • dogs with preoperative calcium < 14 mg/dL present a low risk for clinical hypocalcemia and should be hospitalized and monitored twice daily until calcium > 8.5 mg/dL
  • permanent vitamin D and calcium supplementation will be required if all 4 parathyroid glands are resected
  • hypocalcemia develops within 1-5 days of surgery
  • clinical signs: restlessness, weakness, muscle tremors, twitching, tetany, and seizures
  • treatment of hypocalcemia includes:
  • 10% calcium gluconate (0.5-1.5 mg/kg IV) at over 10-20 minutes initially
  • 10% calcium gluconate (10 ml added to 250 ml maintenance solution) at 60 ml/kg/day
  • maintenance with oral calcium gluconate (3-4 ml diluted 1:1 with isotonic saline q 6-8 hrs or 0.2-0.5 g/cat)
  • maintenance with vitamin D analogue dihydrotachysterol (0.015 mg/kg q 12 hr PO for 2 days, 0.01 mg/kg q 12 hr PO for 2 days, and then maintained at 0.005 mg/kg q 12 hr and tapered over 4-8 weeks)
  • ± calcitriol, which is an alternative to dihydrotachysterol, for prophylactic treatment of hypocalcemia (25 μg/cat or 0.05 μg/kg for dogs > 5 kg q 24 hr for 3 days and then tapered)
  • permanent hypoparathyroidism is likely if calcium does not return to normal within 14-21 days
  • spontaneous resolution of hypoparathyroidism due to reversible damage or hypoxia resulting from thyroidectomy or compensation by accessory parathyroid tissue

Prognosis

  • prognosis is excellent for uncomplicated primary hyperparathyroidism with normal renal function following definitive therapy (i.e., percutaneous ablation or surgical resection)
  • prognosis is guarded for animals with compromised renal function as renal function will only improve marginally following resolution of hypercalcemia

PARATHYROID TUMORS

Disease

PTH

Primary hyperparathyroidism

Malignant hypercalcemia

Secondary hyperparathyroidism

Vitamin D toxicity

Hypoadrenocorticism

Inflammatory disease

PTHrP

Calcium

Phosphorus

Vitamin D

BUN

+++

-

+++

N

N to ++

N to +

-

++

++

N

N

N to +

++

N to ++

+

++

N

+++

-

-

+++

++

+++

N to +

N

N

+

N to +

N

N

- to N

?

+

N

N to +

N

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