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Diseases of the parathyroid glands (Proceedings)

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Nov 01, 2010

Calcium is involved in many cellular and extracellular processes that include neuromuscular transmission, muscle contraction/tone, hormone secretion, bone homeostasis, coagulation, membrane transport systems, and other cell regulatory pathways. Calcium is measured as ionized (active form, roughly 50%) or total (ionized + albumin bound + anion bound). The extracellular fluid ionized calcium is tightly regulated by interactions between the parathyroid glands, bone, the intestinal tract, and kidneys. Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid glands primarily in response to low extracellular ionized calcium.1 Increased ionized calcium stops the secretion of PTH. Parathyroid hormone stimulates calcium and phosphorus absorption from the bone via increased activity of osteoclasts.1 Parathyroid hormone increases calcium reabsorption in the distal convoluted tubule and decreases phosphorus reabsorption in the proximal renal tubules so more calcium is retained and more phosphorus lost.1 Parathyroid hormone also increases the production of 1,25-dihydroxyvitamin D by the kidneys which increases calcium absorption from the intestinal tract. 1,25-dihidroxyvitamin D also provides negative feedback to the parathyroid glands. Vitamin D3 (cholecalciferol) is produced from 7-dehydrocholesterol which is found in high concentration in the skin. Vitamin D3 is then converted to 25-hydroxyvitamin D in the liver and 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitamin D in the kdineys. 1,25-dihydroxyvitamin D inhibits its own synthesis. Hypercalcemia also inhibits 1,25-dihydroxyvitamin D. High serum ionized calcium, in addition to inhibiting PTH secretion, stimulates calcitonin release from the C cells of the thyroid gland. Calcitonin decreases serum calcium and phosphorus by decreasing osteoclastic activity within the bone. Calcitonin also promotes phosphorus excretion via inhibition of phosphorus reabsorption in the proximal renal tubules.

Differentials for Hypercalcemia



     • Lab error
     • Granulomatous disease - infectious
          o Coccidioidiomycosis
          o Blastomycosis
          o Histoplasmosis
          o Aspergillosis
          o Schistosomiasis
     • Increased osteoclastic activity
     • Granulomatous disease
          o Septicemia
          o Neoplasia
     • Primary hyperparathyroidism
     • Vitamin D toxicosis
     • Hypoadrenocorticism
     • Renal Failure (Acute & Chronic)
     • Nutritional Secondary Hyperparathyroidism
     • Iatrogenic
     • Idiopathic (cats)
     • Neolpasia
          o Lymphosarcoma*
          o Apocrine gland anal sac adenocarcinoma*
          o Multiple myeloma*
          o Other carcinomas
          o Melanoma
          o Testicular interstitial cell tumors
          o Thymoma

Primary Hyperparathyroidism

Etiology

Primary hyperparathyroidism (PHPTH) is an uncommon disease in dogs and very rare in cats. Most masses are single adenomas with less than 10% occurring as adenocarcinomas. There is a report of a single cat with bilateral cystadenomas and primary hyperparathyroidism. There have also been reports of hyperplasia of the parathyroid glands in dogs and cats leading to PHPTH.

Signalment

This is a disease that typically affects middle aged to older dogs and cats. There is no sex predilection. In the Keeshonden, PHPTH is inherited as an autosomal dominant trait. There is also a single report of an inherited form of PHPTH in German shepherd dog littermates.

Clinical Findings

Clinical signs may be absent and hypercalcemia found incidentally. In fact in one group of dogs with PHPTH, 88/210 owners brought their dogs in to be evaluated for reasons unrelated to PHPTH.2 The most common signs are polyuria, polydipsia, decreased appetite, weight loss, lethargy, and lower urinary tract signs. Vomiting, diarrhea, constipation, seizures, and renal osteodystrophy are less common.Signs may be present for months to years prior to presentation. Cats most often present with anorexia, lethargy and vomiting. Parathyroid glands are normally not palpable in dogs and cats. Masses are not palpable in dogs with PHPTH but may be in cats.

Laboratory Evaluation

There are no significant abnormalities on the CBC. Total serum calcium is increased consistently. Ionized calcium is increased in most animals but may be normal. Phosphorus is usually low or low normal. Kidney values may be elevated in dogs and catsIf renal values are increased they present a diagnostic dilemma, is this an animal with renal failure and a secondary form of hyperparathyroidism? Does this animal have concurrent renal disease and PHPTH? Or is this an animal with PHPTH and renal disease secondary to mineralization? Typically dogs with CRF have hyperphosphatemia and a normal to low ionized calcium whereas with PHPTH phosphorus is normal to low with an increase in ionized and total calcium. With PHPTH, urine may be minimally concentrated, isosthenuric or hyposthenuric. Liver enzymes are elevated in some dogs and cats with PHPTH.Uroliths and urinary tract infections are fairly common in dogs so calcium-containing crystalluria, hematuria, pyuria, proteinuria, and bacteruria may also be present. Urinary tract infections and calculi are rare in cats.

Assays for PTH currently utilized are either a two-site immunoradiomimetric assay or sandwich ELISA available and validated for the dog and cat. PTH is normal to increased in dogs and cats with PHPTH.2 The importance is that as calcium increases PTH should decrease, which does not occur with PHPTH.

Diagnostic Imaging

Radiography may be used to evaluate for other causes of hypercalcemia, concurrent disease, urinary tract calculi and boney changes (renal osteodystrophy). Local invasion and distant metastases have not been reported with malignant tumors. Parathyroid tumors are readily identifiable utilizing ultrasoundParathyroid adenomas are round, hypoechoic and tend to be over 4 mm in size. Hyperplastic nodules (CRF, nutritional secondary) tend to be smaller than adenomas.15,20 The majority of animals have a single enlarged parathyroid but a few have 2 enlarged parathyroid glands.