Primary hyperparathyroidism and concurrent hyperthyroidism in a cat

Abstract

A cat was presented for anorexia and vomiting.Hyperthyroidism and primary hyperparathyroidism were diagnosed. A thyroid adenoma and parathyroid adenoma, respectively, were responsible for these conditions. Unilateral thyroidectomy and parathyroidectomy successfully resolved both disorders.

An 8-year-old, castrated male, domestic shorthair cat was presented with a primary complaint of anorexia and vomiting for 5 d. The cat was approximately 5% dehydrated and appeared lethargic during the examination. His body weight (BW), 5 kg, was similar to that measured 77 d previously, when the cat was presented for routine vaccinations. A peripheral lymphadenopathy was not present.

Blood and urine samples were taken, and the cat was administered IV fluids (Normosol; Abbott Laboratories, Saint-Laurent, Quebec) at a flow rate of 34 mL/h, to replace the fluid deficit over 12 h and supply normal fluid maintenance requirements. Hypercalcemia (3.54 mmol/L; reference range, 1.61 to 2.68 mmol/L) and hypophosphatemia (1.30 mmol/L; reference range, 1.31 to 2.25 mmol/L) were the only significant abnormal findings on initial biochemical testing. Hemoconcentration was the only abnormality detected on hematologic testing (hematocrit 0.498; reference range, 0.240 to 0.450). Tests for feline leukemia virus and feline immunodeficiency virus were both negative. The urine specific gravity was 1.025. Abdominal and thoracic radiographs were taken and appeared normal. No masses were evident on ultrasonography of the abdomen.

In an effort to reduce the serum calcium level, IV fluids were switched to 0.9% sodium chloride for the next 24 h at a flow rate of 29 mL/h, double the normal fluid maintenance requirement. On repeat analysis, the serum calcium level was 3.49 mmol/L. Diuresis alone was not effective in significantly lowering the patient's calcium level.

The possible causes of the hypercalcemia included laboratory error, primary hyperparathyroidism, renal disease, granulomatous disease, malignancy with production of parathyroid hormone (PTH)-related peptide or interference with bone metabolism, hypervitaminosis D, and hypoadrenocorticism (1,2,3,4,5,6,7,8). Idiopathic hypercalcemia was also a consideration (9).

Calcium and phosphorus measurements can be affected by lipemia or hemolysis; these measurements are dependent on the laboratory method used, with false elevations common with lipemic serum. Hemolysis will often decrease phosphorus levels. However, the initial sample was not lipemic or hemolyzed, and the hypercalcemia was confirmed on another sample taken 24 h after the first test, making laboratory error or spurious interference unlikely as the cause of the hypercalcemia and hypophosphotemia (7). The absence of azotemia and the presence of a low serum phosphorus level indicated that the hypercalcemia was probably not due to primary renal disease (10).

The low specific gravity in the face of dehydration was attributed to the hypercalcemia, which counteracts the actions of antidiuretic hormone on the kidneys. In addition, hypercalcemia can result in renal damage through renal vasoconstriction and mineralization, which, in turn, leads to increases in serum urea (7). There was no evidence of skin or internal masses on the physical examination, radiographs of the abdomen and thorax, or abdominal ultrasonography, which made granulomatous disease and neoplasia less likely. Also, there was no evidence of increased globulin levels, which are commonly associated with multiple myeloma. Nevertheless, neoplasia is the most common cause of hypercalcemia in cats, with lymphoma and squamous cell carcinoma being the most common malignancies involved (11). Peripheral lymph nodes were not aspirated, because they were not palpably enlarged (10). Bone marrow was not aspirated, because the complete blood cell count (aside from the mildy elevated hematocrit resulting from dehydration) and the globulin level were within normal values (10). The history indicated no excess feeding of vitamin D or related compounds, and there was no history of accidental exposure to rodenticides containing cholecalciferol (4,7). The low serum phosphorus level also made toxicity, as well as hypoadrenocorticism and idiopathic hypercalcemia, an unlikely diagnosis (4,8,9). Primary hyperparathyroidism was considered the most likely cause of the hypercalcemia. An assay for intact PTH and an ionized calcium level would have been helpful to confirm primary hyperparathyroidism and rule out other causes of hypercalcemia prior to surgery. However, at the time, the turn-around time for the PTH assay was 7 to 10 d, and the animal was considered to be in too critical a condition to wait that long for a definitive diagnosis, owing to the possibility of permanent kidney damage.

The decision was made to surgically explore the ventral neck to examine the cat's parathyroid glands. Hyperthyroidism was not suspected at this time, because there was a documented lack of weight loss and no palpable thyroid mass. Anesthesia was induced by using ketamine hydrochloride (5 mg/kg BW) and diazepam (0.2 mg/kg BW), IV. Following endotracheal intubation, anesthesia was maintained with isoflurane. Upon surgical exploration, the right thyroid gland was found to be 2.2 cm × 1.0 cm (normal, 2.0 cm × 0.3 cm) (12). A mass, believed to be the external parathyroid gland, was present on the cranial pole. It measured 4.0 mm × 5.0 mm (normal, 1.0 mm × 5.0 mm) (13). The left external parathyroid gland appeared to be normal in size, but the left thyroid gland was slightly smaller (1.5 cm × 3 cm) than normal. A total right thyroidectomy and parathyroidectomy were performed. Recovery was uneventful. A serum thyroxine level was measured retrospectively on the original serum sample and found to be high (71 nmol/L; reference range, 19 to 50 nmol/L).

Within 4 d of the surgery, the cat's calcium and phosphorus levels had returned to within the reference ranges. The thyroxine level was low. Thyroxine supplementation was not provided. It was assumed that the low thyroid level would stimulate the remaining thyroid gland to restore the cat's thyroxine level to within reference range. The patient was eating and no longer vomiting. Fourteen days following the surgery, the cat's urine specific gravity was 1.042.

The excised tissue was submitted for histologic examination. It measured 2.5 cm × 1.0 cm and appeared as a homogenous, tan/red, slightly nodular, oval tissue with a discrete light tan mass at the cranial pole (0.5 cm in the greatest dimension). On routine hematoxylin and eosin- stained sections, the division into 2 proliferating cell types was evident. The larger portion of the gland was comprised of a multilobulated proliferation of glandular cells in discrete acinar configurations, with the center of the acinar arrangements containing eosinophilic colloidal material. Intermixed with these glandular arrangements were single strands of polyhedral cells with granular cytoplasm. Abutting the glandular elements was a discrete nodular mass of more basophilic, polyhedral cells with granular cytoplasm. A similar but smaller aggregate was also noted within the lateral border of the glandular tissue. This aggregate was one-tenth the size of the larger nodule and was not visible on the gross specimen. Immunoperoxidase staining for calcitonin, thyroglobulin, and PTH were performed on sections from the original paraffin block (Department of Veterinary Pathology, College of Veterinary Medicine, University of California, Davis, California, USA). The scattered cells stained positively for calcitonin, the glandular elements for thyroglobulin, and the discrete nodules for PTH. This was consistent with a diagnosis of parathyroid adenoma and thyroid adenoma.

Two years after the surgery, the patient is doing well. Serum thyroxine levels have gradually returned to within reference range, and there has been no recurrence of the hypercalcemia or hyperthyroidism, based on repeated serum biochemical analyses.

Primary hyperparathyroidism is uncommon in cats (1,2). Clinical signs attributed to this condition include anorexia, lethargy, vomiting, weakness, and weight loss (1,2,3). Regardless of the cause of the hypercalcemia, vomiting and anorexia are thought to be the result of reduced contractility of smooth muscle (4). Generalized motor weakness results from suppression of lower motor neurons by the elevated calcium levels (4). Clinical signs of cats with hyperthyroidism are similar to those of cats with hypercalcemia, except that many hyperthyroid cats have increased appetite in the face of weight loss (5).

Furosemide could have first been added to the treatment regime to help lower the calcium level until a PTH assay could be done. But medically managing this patient over 7 to 10 d in order to get a PTH level prior to surgery would have been expensive and challenging.

This cat did not have hypocalcemia after the surgery, as might have been expected and has been reported in cats after parathyroidectomy (1). The cat did have recognizable parathyroid tissue in the left thyroid gland and, surprisingly, a small remnant of the internal parathyroid on the same side as the parathyroid adenoma. This might indicate that the hypercalcemia had not been of sufficient duration to result in negative feedback and complete suppression of these glands. However, the small size of the left thyroid gland indicated that the hyperthyroidism was likely present long enough to have resulted in suppression of this gland, despite the lack of documented weight loss in the patient.

The cat's serum thyroxine levels have been measured on a routine basis every 6 mo since surgery. This is recommended following a unilateral thyroidectomy, as hyperthyroidism may recur due to adenomatous changes in the contralateral gland, ectopic tissue, or abnormal tissue left behind in situations of incomplete resection (14).

Although the cat in this case was diagnosed with 2 concurrent endocrine tumors, multiple endocrine neoplasia (MEN) syndrome, as classified in humans, is not a scheme applicable in this case. In humans, 2 major forms of MEN, type 1 and 2, occur and are related to a common gene defect (15). Tumors or hyperplasia of the parathyroid glands, the pancreatic islets, and the anterior pituitary are characteristic of MEN 1. Pheochromocytomas, medullary carcinoma of the thyroid gland, and parathyroid hyperplasia are seen with MEN 2A. In MEN 2B, medullary carcinoma of the thyroid gland, pheochromocytoma, and multiple ganglioneuromas of the lips and intestine are present. One case of MEN syndrome analogous to MEN 2B has been reported in a dog (16), but, like the cat described in this case, other reports of multiple endocrine neoplasia in dogs do not fit with the MEN syndrome classification (17,18).

This case demonstrates that hyperthyroidism and primary hyperparathyroidism can occur simultaneously in the cat. Whether the 2 conditions in this case had a common cause is unknown. CVJ