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Clinical Consults What’S Your Diagnosis?

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Clinical Consults What’S Your Diagnosis? Volume 11 | Issue 10 | December 2019 Clinical Consults What’s Your Diagnosis? PATIENT HISTORY RECTAL EXAMINATION— SIGNALMENT: “Chelsea” is a 7.5-year-old female spayed Labradoodle. Weight Important In Every Sick and Well Patient! 70 lb/34 kg. PERTINENT PAST HISTORY: “Chelsea” has been a very healthy dog. She has experienced historical intermittent urinary Donna J. Spector , DVM, DACVIM, Internal Medicine tract infections (UTIs) but no other major systemic issues. She eats dry adult commercial dog food. She is current on recommended vaccinations and takes monthly preventatives as recommended by TABLE 1. her primary care veterinarian. “CHELSEA’S” BLOODWORK CURRENT HISTORY: “Chelsea” had recently Calcium (ref. range 8.4-11.8 mg/dL) 18.9 mg/dL begun experiencing an increase of urination Phosphorus (ref. range 2.5-6.1 mg/dL) 2.9 mg/dL and urinary accidents in the house. The owner initially did not describe an BUN (ref. range 9-31 mg/dL) 42 mg/dL accompanying increase of water drinking. (ref. range 0.5-1.5 mg/dL) 1.6 mg/dL The owner brought in a free-catch urine Creatinine sample for analysis which revealed pyuria ALKP (ref. range 5-160 U/L) 177 U/L (20-30 WBC/hpf) and rare bacteria. “Chelsea” was prescribed amoxicillin 500 mg USG 1.012 PO BID for 7 days to treat a presumptive UTI. The owner reported the amoxicillin helped Chelsea” was diagnosed with severe hypercalcemia and mild renal failure likely secondary to the with the clinical signs for a short period but severe hypercalcemia. An Internal Medicine consultation was recommended ASAP. “Chelsea” became polydipsic and polyuric fairly soon after stopping and within one month she began experiencing mild INTERNAL MEDICINE EVALUATION stranguria. She was rechecked at this time The owners reported “Chelsea” to have a picky appetite and she had lost a total of 10 pounds in the and physical examination was reportedly previous 12 months. She had experienced a mild amount of vomiting but was still having normal stool unremarkable. Amoxicillin was refilled for 14 quality. The owner felt she was quite lethargic and drinking and urinating excessively. The owners days. When her clinical signs of pu/pd and were still reporting some degree of stranguria and mild tenesmus. Upon physical examination, “Chelsea” stranguria were persistent, “Chelsea” was bright, alert and responsive, and well hydrated with normal thoracic and cardiac auscultation. Her returned for bloodwork 10 days later. A abdomen palpated normally. She had normal external genitalia. When her tail was lifted you could see lateral abdominal radiograph revealed no an asymmetric bulge in the left perianal region. On rectal examination, she had a very large stones (see Figure 1). See Table 1 for her (>6cm) irregular anal gland mass. Palpable sublumbar lymphadenopathy was also be noted on rectal bloodwork abnormalities. exam. The concern was for anal gland adenocarcinoma with associated paraneoplastic hypercalcemia. FIGURE 1. FIGURE 2. and other carcinomas also cause hypercalcemia of malignancy. Idiopathic hypercalcemia is a common differential for hypercalcemia in cats – but not dogs. Clinical Signs Dogs with hypercalcemia may be asymptomatic or they may have clinical signs of lethargy, vomiting, constipation, diarrhea, polyuria, polydipsia, weakness, twitching and/or seizures. Many patients with hypercalcemia (especially related to primary hyperparathyroidism) suffer from uroliths and may have associated pollakiuria, hematuria and/or stranguria. Physical Examination A thorough physical examination is an Clinical Note: “Chelsea’s” examination returned one week later at which time her absolute necessity in the workup of demonstrates the importance of performing a ionized calcium was 1.86 mmol/L – hypercalcemia and must involve palpation of thorough rectal examination on every patient improved but still moderately to markedly long bones, mammary glands, lymph nodes, presented for urinary complaints. “Chelsea’s” elevated. Surgery was performed to remove prostate, all organs, anal sacs, etc. A retinal anal gland mass must have been present for the the anal gland mass and her sublumbar examination must be included to evaluate preceding several months and could have been lymph nodes. Surgery was relatively thoroughly for fungal disease. identified at an earlier stage in the disease uneventful and histopathology confirmed process. All patients presenting for urinary and apocrine gland adenocarcinoma with Laboratory Abnormalities gastrointestinal complaints but also EVERY metastasis to the sublumbar lymph node. Marked lipemia, hemolysis, hemoconcentration healthy patient at an annual examination should Her hypercalcemia resolved immediately and hyperproteinemia can falsely elevate total be undergoing rectal examination! post-operatively. serum calcium. It is always prudent to obtain a second sample on a fasted (non-lipemic), Review of the abdominal radiographs (see DIAGNOSIS non-hemolyzed sample prior to pursuing Figure 1) revealed ventral deviation of the additional diagnostics for hypercalcemia. colon which was concerning for sublumbar Apocrine gland adenocarcinoma Clinical Note: All abnormalities in serum total lymphadenopathy. An abdominal ultrasound – left calcium always warrant further investigation! and three-view thoracic radiographs were The CBC usually has non-specific changes. recommended for further staging of this disease. Sublumbar lymph node metastasis The chemistry panel will reveal hypercalcemia Paraneoplastic hypercalcemia and the phosphorus concentration may give Abdominal ultrasound revealed markedly enlarged sublumbar lymph nodes (7.5 cm long x 3.5 cm wide) with a diffusely infiltrated DISCUSSION TABLE 2. appearance (see Figure 2). There was no A detailed discussion of hypercalcemia and MOST COMMON CAUSES OF HYPERCALCEMIA other lymphadenopathy or ascites noted. A apocrine gland adenocarcinoma is beyond fine needle aspirate of the enlarged lymph the scope of this article and the reader is Hypercalcemia of malignancy – lymphoma, nodes was obtained and revealed metastatic directed to the listed references. multiple myeloma, anal gland adenocarcinoma, adenocarcinoma. The thoracic radiographs other carcinomas revealed no cardiac or pulmonary abnormalities. Hypercalcemia Hypoadrenocorticism Etiology Primary hyperparathyroidism There are many causes of hypercalcemia in An ionized calcium was performed and was Nutritional secondary hyperparathyroidism markedly elevated at 2.44 mmol/L (ref. range dogs (see Table 2). The most common 1.12-1.4 mmol/L). “Chelsea” was admitted etiology in dogs is hypercalcemia of Osteolytic disease to the hospital for intravenous saline diuresis. malignancy. Neoplasia will be diagnosed in Acute or chronic renal failure Once her azotemia resolved, an injectable approximately 2/3 of dogs with hypercalcemia. Vitamin D toxicosis dosage of zoledronic acid was administered Lymphoma is an extremely important Granulomatous disease (blastomycosis, to help control her hypercalcemia and make differential, although anal gland histoplasmosis, etc.) her a more stable surgical candidate. She adenocarcinoma (AGAA), multiple myeloma clues as to etiology. Low to normal phosphorus Clinical Note: I find it helpful to pull ionized Treatment of Hypercalcemia levels are generally consistent with calcium and serum PTH levels at the same Treatment is aimed at identifying and then hypercalcemia of malignancy or primary time so they are matched samples. I submit treating the underlying cause. However, hyperparathyroidism. If serum phosphorus is the ionized calcium to the laboratory for emergency medical management is often elevated, renal disease, vitamin D toxicosis and evaluation and freeze the time-matched PTH required while diagnostic tests are being hypoadrenocorticism may be more likely. sample. If the ionized calcium returns as performed. Dogs typically show adverse elevated, I will then add-on/submit the PTH clinical signs at serum calcium concentrations Advanced Diagnostic Testing sample. This avoids the patient having to >15 mg/dL. Patients with serum calcium An ionized calcium should always be come back for another sampling and helps concentrations >18 mg/dL are usually quite ill performed in the evaluation of a total serum avoid the expense of another ionized calcium and require intervention. calcium elevation. Total serum calcium exists as it is imperative that the PTH be analyzed in three fractions: 1) protein bound, 2) at the same time as the ionized calcium. Dehydration exacerbates hypercalcemia by complexed or chelated to a variety of increasing renal tubular absorption of calcium, substances such as citrate, lactate, carbonate Parathyroid hormone-related Protein (PTHrP) decreasing renal calcium excretion through and 3) ionized. The ionized calcium, which assay is a humoral factor made by some reduced GFR and by hemoconcentration. makes up about 50% of total serum calcium, neoplastic cells. It has a structure and Correction of dehydration with intravenous fluid is the biologically active form of calcium. The function similar to PTH so is capable of therapy helps reduce the severity of protein bound calcium serves as a storage pool causing hypercalcemia. PTHrP is hypercalcemia. After dehydration is corrected, for the ionized form. Clinical Note: If the autonomously secreted by cancer cells and is diuresis with physiologic saline promotes ionized calcium is within normal limits, the not suppressed by serum calcium levels. continued renal excretion of calcium. hypercalcemia is not pathologic and does not Absence
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