Surgical Disease and Hypercalcemia

Hypercalcemia is defined as a serum or plasma total calcium level exceeding the normal level. Reference ranges vary considerably among laboratories however a serum calcium concentration > 12mg/dl is considered to be a clinically important elevation and a repeated calcium elevation warrants clinical investigation. Routine calcium levels reported on chemistry profiles are Total calcium, of which 50% is ionized (the metabolically active form) , 40% is protein bound (to albumin) and 10% calcium complexes. In the dog serum calcium concentration is adjusted for albumin level by subtracting the albumin level from the total Ca++ level and adding 3.5.;this yields a corrected calcium level in mg/dl. This method is not accurate in cats. Recently, (2005) it has been suggested that ionized calcium must be measured directly in order to obtain the most accurate level and prevent misdiagnosis of disease especially in dogs with chronic renal failure.

It should be noted that lipemia or hemolysis MAY cause severe artifactual elevation of calcium concentration depending upon the method being used to measure calcium concentration.

The most common cause of hypercalcemia in the dog is cancer. In the cat, idiopathic hypercalcemia is rather common especially in those animals with upper urinary tract calculi but hypercalcemia may also be cancer caused in the cat. The differential diagnosis for hypercalcemia follows:

I. Causes of Hyperclacemia

Growth (Puppies)

Hypercalcemia of Malignancy

• Lymphoma

• Anal sac adenocarcinoma

• Myeloma

• SCC

• Mammary tumors

• Thyroid carcinoma

• Bone tumors

• Melanoma

• Colonic carcinoma

• Testicular cancer

Primary hyperparathyroidism

• Adenoma

• Hyperplasia

• Renal failure

• Hypoadrenocorticism

• Hypervitmainosis D

• Hemoconcentration

• Idiopathic (Cats)

II. Pathophysiology

1. Neoplasia involving bone may produce osteoclast activating factor leading to Calcium mobilization.

2. Primary hyperparathyroidism = Excess PTH

3. Solid tumors including lymphoma produce PTH related protein PTHrP which is not measaured by assays that measure the intact PTH molecule.

4. Hypervitaminosis D= Absorption of excess calcium from the Gi tract

5. Renal failure= Decreased calcium excretion, hemoconcentration, secondary hyperparathyroidsism

6. Idiopathic= Cats= Unknown

III. Clinical and Diagnostic approach

1. Hypercalcemia often detected on routine blood work. What is a significant elevation? Repeat of the test often indicated. What is the ionized calcium level?

2. Are there clinical signs relative to hypercalcemia? Signs of hyperclacemia including PU/PD, anorexia or hyporexia, lethargy, and weakness, constipation, and calcium uroliths. Uncommonly, neurologic signs and muscle fasiculations may be seen. Cardiac arrythmias are also possible. Signs usually begin at 15 mg/dL.

3. Clinical signs related to the underlying disease process may be more apparent such as lymphadenopathy (LSA), bone pain with bone, lameness and possible neuro defects with myeloma, vomiting with Renal failure and Vit D intoxication.

1. Evaluate renal values and phosphorous levels. If azotemia and hyperphosphatemia are present with normal electrolytes then primary renal failure or Vit D intoxication are likely.

2. If Ca, Phosphorous, BUN and creatitnine are elevated with a normal sdium hypoadrenocorticism should be suspected and an ACTH response test performed.

3. If Ca is elevated and phosphorous is normal or low and no azotemia, the major DDX include malignancy caused hypercalcemia and Primary hyperparathyroidism.

4. Consider measuring PTH levels, PTHrP levels, and ionized calcium levels. We send this test package to Michican State University, Cost= $ 60.00, turn-around time is rather quick, 3-4 days. Depending upon results

5. Consider

• REEXAMINE (or examine) lymph nodes

• DO A RECTAL exam being careful to palpate anal sacs for abnormalities and more rostrally and dorsally for the sublumbar lymph nodes

• Palpate mammary glands and/or testicles

• Consider ultrasound examination of the neck looking for parathyroid/thyroid mass

• Consider search for occult neoplasia

• Thoracic radiographs (pulmonary mets or mediastinal masses)

• Abdominal ultrasound

• Lymph node aspirate and cytologic evaluation

IV. Hypercalcemia Management, Medical and Surgical

1. Medical Mangement- Treatment is indicated if clinical signs are present, dehydration or azotemia are present, if the Ca is > 16 mg/dl or if the Ca x Po4 product is > 70.

• Normal (0.9%) Saline fluid of choice IV

• Corticosteroids

• Furoseamide

2. Apocrine Gland Adenocarcinoma

• Don't forget to take 3-view thoracic radiographs prior to surgery

• Remove primary tumor, by anal sacculectomy and tumor excision with clean margins if possible.

• Tumor may be small and contained in the anal sac or more invasive into surrounding tissue

• Goal is complete removal, this may involve excision of external anal sphincter on the involved side which will decrease anal tone but the animal should remain continent

• If sublumbar (iliac) lymph nodes are enlarged celitotmy and excision of enlarged nodes is indicated. Depending upon size, this surgery varies from relatively easy to impossible . There are LARGE vascular structures in the area, notably the aorta and its principle branches. The nodes are carefully dissected free from the surrounding vascular structures using hemostats and "peanuts" which are useful in developing dissection planes.

• Survival varies with this tumor but prolonged palliation is possible (depending on the stage of disease)if the disease is treated aggressively.

• Mean survivals range from 8-16 months depending upon stage of disease, we've had dogs go out 2 and 3 years respectively with aggressive management. Studies in the literature document long term survival with aggressive metastaectomy of iliac lymph nodes and other tumor in this area.

3. Primary Hyperparathyroidism

• Primary hyperparathryoidsim is usually casued by a parathyroid adenoma

• Hyperplasia is also described, differentiation is difficult in time between hyperplasia and adenoma

• Ultrasound assessment of the 4 parathyroids in the dog VERY useful.

• >4mm in diameter= Adenoma or rarely adenocarcinoma

• <4 mm in diameter = Hyperplasia

• If adenomas are located in the external parathyroid gland on the cranial pole of the thryroid, excision of the tumor only is performed. Care is taken to preserve the recurrent laryngeal nerve.

• If the mass involves an internal parathyroid I excise the thyroid and parathyroid on the affected side. Again, the recurrent laryngeal nerve should be preserved.

• Be sure to examine each thryroid and parathyroid for abnormalities. Multiple nodules/adenomas have been reported.

• Surgery is usually simple, management of potential postoperative HYPOCALCEMIA can be more challenging.

• Rapid decline in calcium expected (1-3 days) due to atrophy of the remaining "normal" glands.

• If serum Ca concentration is > 14-15 mg/dl preoperatively it is recommended to begin prophylactic Vit D therapy preoperatively.

• Parenteral calcium supplementation may be needed if clinical signs such as stiffness or muscle fasciculations develop due to hypocalcemia

• We measure calcium 2x daily during the first several days postoperatively.

• We are shooting for low normal calcium levels (high single digits) and then tapering of Vit D over weeks to months.

n I have no experience with the reported use of ethanol injections for treatment of this disease.