Haley presented one week ago for vomiting, lethargy and some loos stool. Hx of hyperthyroidism, on methimazole. Hx UTI previously and asthma as a young cat (has not required tx since using pred briefly years ago).
PE- mild murmur, thin, BP 145 sytstolic
Labs – initial TCa 13.3, iCa 1.65, BUN 38 (normal creat), PCV/TP 34/9, T4 4.4 (4.8 high end of normal), glucose 221, UA – SpG 1.040, ++++proteinuria, glucosuria, on cytology there are some cocci (no WBCs noted), occasional renal tubular cells and transitional epithelial cells
Haley presented one week ago for vomiting, lethargy and some loos stool. Hx of hyperthyroidism, on methimazole. Hx UTI previously and asthma as a young cat (has not required tx since using pred briefly years ago).
PE- mild murmur, thin, BP 145 sytstolic
Labs – initial TCa 13.3, iCa 1.65, BUN 38 (normal creat), PCV/TP 34/9, T4 4.4 (4.8 high end of normal), glucose 221, UA – SpG 1.040, ++++proteinuria, glucosuria, on cytology there are some cocci (no WBCs noted), occasional renal tubular cells and transitional epithelial cells
U/S – enlarged kidneys, right kidney has irregular border and shadowing renoliths; one ureterolith seen on right w/ mild distension of ureter, but not distended further distally. Scant effusion around rounded splenic head. Some thickening of submucosa in sections of jejunum.
Radiographs – Mild peribronchiolar pattern in lungs, radiodense fecal material in colon, some mineralization in kidneys, fluid filled small bowel loops
FNA of right kidney – low cellularity, some peripheral blood (did 3-4 aspirates on 2 different attempts and received same results)
FNA of spleen -extramedullary hematopoeisis
Repeat iCa and TCa 4 days later – both WNL, TCa 10.9, iCa 1.32. HCT was 27% (had been 36 at presentation). Glucose WNL.
Problems/Rule outs – hypercalcemia appears to be spurious so not sure how much to pursue (originally were going to do parathyroid and PTHrp testing), progressing hyperthyroidism (was 1.6 on treatment one year ago, so we increased dose given high normal result this time), irregular kidneys (infiltrative ds/lymphoma, pyelonephritis, nephroliths w/o current evidence of obstruction), non regenerative anemia, anorexia/vomiting (rule out unregulated T4, IBD/GI lymphoma).
My options at this point would be PARR on the slides submitted and intestinal biopsies since I did appreciate some thickening in the submucosa. Just wondering what your impression of the images provided and where you might go next? I really appreciate any input on this case – of course a great cat and nice owners.
Comments
With the anemia, elevated
With the anemia, elevated BUN, GI signs would look at the GI tract (lymphoma, IBD, ulceration). There is renal disease but not convinced that it is cause of all the problems but lymphoma and pyelonephritis important DDx. As stated hypercalcemia is spurious but lymphoma is possible, however, generally should have constant hypercalcemia. Top-normal T4 should not give you uncontrolled hyperthyroidism.
Would go for urine culture and sensitivity, PARR, intestinal biopsies.
With the anemia, elevated
With the anemia, elevated BUN, GI signs would look at the GI tract (lymphoma, IBD, ulceration). There is renal disease but not convinced that it is cause of all the problems but lymphoma and pyelonephritis important DDx. As stated hypercalcemia is spurious but lymphoma is possible, however, generally should have constant hypercalcemia. Top-normal T4 should not give you uncontrolled hyperthyroidism.
Would go for urine culture and sensitivity, PARR, intestinal biopsies.
Thank you! Very helpful.
Thank you! Very helpful. Waiting on PARR now.
Usually fna of lsa kidneys
Usually fna of lsa kidneys are pretty exfoliative and give you a solid monocellular population so i doubt thats the case here. With the ill-defined fat in the renal pelvis and the sand movelent embedded pyelo possible and hypervascular or mildly inflamed kidney often gives bloody fna results. Maybe check for occult cns or spinal signs for cns lsa but I dont see ny lsa here in this kidney as the cm junction is clean as is the capsule.
Here is the latest on feline hypercalcemia form the Curbside guide on the hot plate for release Nov 15:)
Feline Hypercalcemia
http://www.sonopath.com/FelineHypercalcemia
Description: Feline hypercalcemia can be a frustrating diagnosis for practitioner and concerned cat owner alike. When making a diagnosis of hypercalcemia, it is important to consider the physiology of calcium homeostasis. Calcium levels measured using standard chemistry profiles represent the total serum calcium, which is comprised of: i) calcium bound to proteins complexed with anions, such as citrate and phosphate, and ii) ionized or “free” calcium, which is the metabolically active form of the element. The total calcium level should not, however, be used to make a diagnosis of hypercalcemia, as it is influenced by the patient’s acid-base status and by various bound proteins, specifically albumin. To this end, the formula used to correct for calcium is based on albumin levels. Only theionized calcium level can be utilized to arrive at an accurate diagnosis of hypercalcemia.
Causes of Hypercalcemia:
1. Hyperparathyroidism
Benign adenomas of the parathyroid gland create an excess of parathyroid hormone (PTH), which in turn stimulates calcium release from bones and increases renal reabsorption of calcium while promoting phosphorus excretion. A diagnosis can be made by evaluating a paired PTH/ionized calcium sample. Generally, high PTH combined with elevated ionized calcium is indicative of primary hyperparathyroidism; however, one may find that even when ionized calcium is high, PTH levels may still fall within the “normal” range. An inappropriately “high-normal” PTH level, in conjunction with an elevated ionized calcium level, may therefore indicate primary hyperparathyroidism, especially if it is clinically consistent with the signalment (primarily geriatric patients) and clinical findings. In such cases, reevaluation of the panel in 6 weeks is recommended to determine whether the PTH is trending upwards. Sonographic examination of the parathyroid glands can also be performed, as hypertrophy of a single parathyroid or an associated nodule may be discovered. It is common for patients with hyperparathyroidism to also display hypophosphatemia, which may aid in the diagnosis of borderline cases.
2. Renal Disease
It has long been thought that renal failure is a common cause of hypercalcemia, primarily because it increases calcium complexes, which in turn lead to elevated total serum calcium. Yet, ionized calcium frequently remains at normal levels during renal failure, and patients in these circumstances are not truly hypercalcemic. Some cats with renal compromise do display both elevated ionized calcium and PTH (tertiary hyperparathyroidism). Although the mechanism is unclear, it is thought that parathyroid glands affected by chronically elevated calcium levels become autonomous (i.e., they no longer respond to calcium levels). In fact, the elevated level of calcium becomes dependent on excess PTH instead of PTH rising in response to low blood calcium levels. There has been evidence of this in human renal transplant patients who continue to be hypercalcemic after successful transplantation, and is corroborated further by sonographic evaluations that reveal global hypertrophy of the parathyroid glands. These patients also tend to become azotemic and hyperphosphatemic, which is consistent with renal compromise.
3. Hypercalcemia of Malignancy
A variety of neoplastic conditions are related to hypercalcemia, the most common in cats being lymphoma and squamous cell carcinoma of the head and neck. Other causes include carcinomas originating in other tissues, multiple myeloma, leukemia, and sarcomas (e.g. osteosarcoma and fibrosarcoma). Hypercalcemia of malignancy is caused primarily by systemic humoral factor stimulation, which further incites osteoclastic activity. The most important factor is a fetal protein called PTH related protein (PTHrp). This protein acts like PTH and can be detected in the serum. It should be noted that although a positive result indicates hypercalcemia of malignancy, a negative result does not rule it out. Moreover, hematopoietic bone neoplasms, such as multiple myeloma or leukemia, or primary or metastatic bone tumors, can cause local osteolytic effects. In multiple myeloma, plasma cells also secrete an osteoclastic activation factor. Further diagnostics should include, at a minimum, a thorough physical examination, abdominal ultrasound, and thoracic radiographs. A tissue biopsy or aspirate, or a bone marrow evaluation may also be necessary. Skeletal radiographs or bone scans may also be required to help diagnose bone or hematopoietic neoplasia. Interestingly, hypercalcemia related to lymphoma often resolves abruptly with chemotherapy. Hypercalcemia related to carcinoma (if inoperable) and other neoplasms may be managed by glucocorticoid therapy and fluid administration as well as bisphosphonates.
4. Idiopathic Hypercalcemia
Also called “benign hypercalcemia,” idiopathic hypercalcemia frustrates veterinarians and cat owners alike. It refers to a condition where the total calcium is mildly to moderately elevated (usually < 15mg/dl) and ionized calcium is high, yet no cause can be identified. PTH is normal or low, and PTHrp is not detectable. Some patients display no obvious clinical signs, while others present with nonspecific clinical signs, including weight loss, anorexia, vomiting, and constipation. In addition, signs associated with calcium urolithiasis (i.e., dysuria, stranguria, hematuria, abdominal pain) may exist as these patients are predisposed secondarily to increased calciuresis. Note that this diagnosis can be made only after all other potential causes of hypercalcemia have been ruled out.
5. Less Common Causes of Hypercalcemia
Vitamin D toxicity needs to be ruled out and a thorough evaluation of the patient’s history should be obtained to determine whether accidental ingestion might have occurred. Vitamin D levels can also be evaluated in the serum. Granulomatous diseases, particularly fungal infections, can also lead to a hypercalcemic state and osteolytic lesions, depending on the site of infection. Elevated globulin levels may be seen and fungal serology should be evaluated.
Treatment: Treatment is indicated if calcium is chronically elevated (> 13 mg/dl), patients display clinical signs or calcium urolithiasis, or there are signs of renal failure. Patients in renal failure require diuresis and should undergo monitoring of their calcium blood level. It should be noted that diuretics that increase calciuresis may incite urolithiasis and should be avoided. Other effective treatments that may help include diet change and pharmaceutical intervention. Typically, alkalinizing diets are lower in calcium and phosphorus, help raise the pH, which may correct hypercalcemia, and decrease calciuresis, thereby diminishing the likelihood of calcium oxalate stone formation. High fiber diets may help decrease calcium absorption from the intestine; however, the nutrient content should be evaluated thoroughly as some of these diets may contain elevated levels of calcium and phosphorus. Renal diets are less acidifying and lower in calcium and phosphorus; however, they are also lower in protein, which is not ideal for most cats, and diminished phosphorus may stimulate calcitriol production. Homemade calcium-restricted diets and low carbohydrate/high protein diets may also be helpful in managing hypercalcemia. Ideally, wet food should be administered as it helps to reduce urine concentration and diminish the formation of calcium-based uroliths.
Glucocorticoids aid in decreasing intestinal calcium absorption but may increase renal excretion; monitoring the development of uroliths is therefore indicated. Glucocorticoids have been shown to decrease ionized calcium levels, yet high dosages appear to be necessary (1-2 mg/kg/day). In general, the owner should be prepared to repeat diagnostics (i.e., blood work, ultrasound, radiographs) to evaluate for emerging neoplasia, especially if the patient displays continued or worsening clinical signs. If the patient is nonresponsive, then alendronate (Fosamax) should be given at 10 mg/cat once a week and can be up-titrated to 30 mg/cat/week if necessary. Bisphosphonates act by inhibiting osteoclastic bone reabsorption through the obstruction of enzymatic pathways. These have been shown to be useful in both reducing hypercalcemia and potentially inhibiting tumor angiogenesis. (Note: Oral bisphosphonates can result in esophageal damage and strictures in people.) Give 5-6 ml of water following the administration of a pill as a preventative; alternatively, injectable forms can be utilized.
One can follow an algorithm-based approach to diagnosing hypercalcemic cats based on serum phosphorus levels:
éPO4 è Renal Failure èevaluate renal enzymes, urinalysis, blood pressure
Vitamin D Toxicity è evaluate serum vitamin D concentration and history
Osteolytic Disease è thorough physical examination, skeletal radiographs,
+/- fungal serology
êPO4 è Hyperparathyroidism è evaluate PTH level and ionized calcium; ultrasound of parathyroid glands
Malignancy è thorough physical examination, abdominal ultrasound, thoracic radiographs, PTHrp, and ionized calcium +/- tissue biopsy/aspirate or bone marrow evaluation
References:
Audrey K and Cook AK. Cats & calcium: the causes & consequences of hypercalcemia. Proceedings from the American College of Veterinary Internal Medicine and Canadian Veterinary Medical Association, Montreal, QC, June 3-6, 2009.
Chew D, Carothers M. Hypercalcemia. Vet Clin North Am Small Pract 1989;2:265-87.
Chew DJ, Schenck PA, Jaege JQ. Clinical disorders of hypercalcemia and hypocalcemia in dogs and cats.
Proceedings from the American College of Veterinary Internal Medicine, Charlotte, NC, June 4-7, 2003.
Hostutler RA, Chew DJ, Jaeger JQ, et al. Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia. J Vet Intern Med 2005;19(1):29-33.
Midcliff A, Chew D, Randolf J, et al. Idiopathic hypercalcemia in cats. J Vet Inter Med 2000;6:619-26.
Peterson ME. Hypercalcemia in dogs & cats: differential diagnosis & treatment. Proceedings from the
Western Veterinary Conference, Las Vegas, NV, February 19-23, 2012.
Peterson ME. Pitfalls in the management of idiopathic hypercalcemia in cats. Proceedings from the American College of Veterinary Internal Medicine, Seattle, WA, June 11-15, 2013.
SavaryKC, Price GS, Vaden SL.Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997)
J Vet Intern Med 2000;14(2):184-89.
Whitney JL, Barrs VR, Wilkinson MR, et al. Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. J Feline Med Surg 2011;13(2):129-34.
Thank you, Eric. I thought
Thank you, Eric. I thought the kidney should exfoliate better w/ lsa, but helpful to have you confirm that. This is a frustrating case – owners willing to do a lot, but one step at a time.