Concurrent chronic lymphocytic leukemia and primary hyperparathyroidism in a mule.

A 26-year-old mule gelding was evaluated for chronic weight loss and decreased appetite. The mule had been losing weight and intermittently hypophagic for approximately 7 months. Laboratory analysis of whole blood and plasma identified severe total hypercalcemia, marked hypophosphatemia, markedly increased parathyroid hormone concentration, and marked lymphocytosis. A sestimibi scan intended to identify parathyroid gland tissue was nondiagnostic. Results of flow cytometry and PCR for antigen receptor rearrangement (PARR) were consistent with a B cell lymphoproliferative disorder, likely chronic lymphocytic leukemia (CLL). Although not previously described concurrently, these conditions may sometimes arise together, complicating definition of the underlying mechanism for weight loss and hypercalcemia in aged equids.

Ionized hypercalcemia in 238 cats from a referral hospital population (2009-2019).

BACKGROUND: Ionized calcium concentration ([iCa]) is more sensitive for detecting calcium disturbances than serum total calcium concentration but literature on ionized hypercalcemia in cats is limited. Urolithiasis is a possible adverse consequence of hypercalcemia. HYPOTHESIS/OBJECTIVES: To describe clinical details of diagnoses associated with ionized hypercalcemia in cats and association with urolithiasis. ANIMALS: Cats (238) seen between 2009 and 2019 at a referral hospital with [iCa] above the normal reference interval. METHODS: Observational cross-sectional study. Signalment, serum biochemical and imaging findings were reviewed for cats with ionized hypercalcemia considered to be clinically relevant (>1.41 mmol/L). Data were summarized by cause of hypercalcemia (i.e., diagnosis). RESULTS: Diagnoses for the 238 cats with [iCa] >1.41 mmol/L included: acute kidney injury (AKI; 13%), malignancy-associated (10.1%), idiopathic hypercalcemia (IHC; 10.1%), chronic kidney disease/renal diet-associated (8.4%), iatrogenic (5.5%), primary hyperparathyroidism (2.1%), vitamin D toxicity (2.1%) and granulomatous disease (1.7%). In 112 cases (47.1%), no cause for ionized hypercalcemia could be determined (n = 95), hypercalcemia was transient (n = 12), or the cat was juvenile (<1 year; n = 5). Urolithiasis was identified in 83.3% of AKI, 72.7% of iatrogenic, 61.1% of CKD/renal diet-associated and 50% of IHC cases that were imaged (<50% for other diagnoses). Diagnoses with a high proportion of concurrent total hypercalcemia included primary hyperparathyroidism (100%), vitamin D toxicity (100%), malignancy-associated (71.4%), granulomatous disease (66.7%) and IHC (65.2%). CONCLUSIONS AND CLINICAL IMPORTANCE: Ionized hypercalcemia was most commonly associated with kidney diseases, neoplasia or IHC. The proportion of urolithiasis cases varied by diagnosis.

Surgical description and outcome of ultrasound-guided minimally invasive parathyroidectomy in 50 dogs with primary hyperparathyroidism.

OBJECTIVE: To describe the surgical technique and clinical outcome of minimally invasive parathyroidectomy for primary hyperparathyroidism (PHPT) in the dog. ANIMALS: Fifty client-owned dogs with PHPT that underwent minimally invasive parathyroidectomy. STUDY DESIGN: Retrospective cohort study. METHODS: An ultrasound-guided mini lateral approach was made via a plane established between the sternocephalicus muscle and sternohyoideus muscles to expose the thyroid gland and enlarged parathyroid gland. Abnormal parathyroid glands were removed en bloc via partial thyroidectomy. The technique for bilateral disease was similar, the skin incision was made on midline and moved laterally to develop the above-mentioned plane of dissection. Age, sex, breed, bodyweight, ultrasound findings, histopathological diagnosis, surgical time, preoperative clinical signs, and clinical outcome were extracted from the records for descriptive statistics. RESULTS: A total of 62 glands were surgically removed, including 17 hyperplastic glands (17/62, 27.4%), 34 adenomas (34/62, 54.8%), and two carcinomas (2/62, 3.2%). Hypercalcemia resolved shortly after surgery in 44 dogs (44/45, 97.8%). One dog had recurrent hypercalcemia (1/45, 2.2%), one dog had persistent hypercalcemia (1/45, 2.2%), two dogs had permanent hypocalcemia requiring life-long calcitriol supplementation (2/45, 4.4%), and one dog died from clinical hypocalcemia (1/45, 2.2%). CONCLUSION: Minimally invasive parathyroidectomy was associated with a low morbidity and led to favorable outcomes in 44/45 dogs in this series. CLINICAL SIGNIFICANCE: The results of this study supports the use of minimally invasive parathyroidectomy to treat PHPT in dogs.

Treatment of primary hyperparathyroidism in a Miniature Horse using chemical ablation of abnormal parathyroid tissue localized by 3-phase computed tomography.

A 15-year-old Miniature Horse mare with persistently increased plasma calcium (total and ionized) and serum parathyroid hormone concentrations was presented for suspected primary hyperparathyroidism. Ultrasonography of the thyroid region identified an enlarged heterogeneous mass axial to the right thyroid lobe suggestive of an enlarged parathyroid gland, which was further confirmed using sestamibi nuclear scintigraphy and 3-phase computed tomography. Percutaneous ultrasound-guided ethanol ablation of the mass, a method not previously described in the horse, was performed under general anesthesia resulting in rapid normalization of plasma ionized calcium and serum parathyroid hormone concentrations. Ablation of abnormal parathyroid gland tissue may be a suitable alternative to surgical resection in certain cases of primary hyperparathyroidism in the horse.

Minimally invasive video-assisted parathyroidectomy in dogs: Technique description and feasibility study.

OBJECTIVE: To describe a minimally invasive approach to the parathyroid gland for the treatment of primary hyperparathyroidism. STUDY DESIGN: Surgical technique description and clinical case report. ANIMALS: Five canine cadavers and 5 client-owned dogs with primary hyperparathyroidism. METHODS: A surgical technique for minimally invasive video-assisted parathyroidectomy (MIVAP), described for humans, was adapted for dogs. With the dog in dorsal recumbency, a 15 mm incision was made on the midline, 1 finger width caudal to the cricoid cartilage of the larynx. A 5 mm 30° rigid endoscope was inserted into the peritracheal space with the aid of a blunt suction dissector, and fine elevators. The parathyroid was subsequently removed using electrocautery and blunt and sharp dissection. The technique was refined in 5 cadaver dogs to assess feasibility, and was subsequently performed in 5 clinical cases. RESULTS: A minimally invasive approach to the parathyroid gland was possible and allowed successful removal of a parathyroid mass in 5 dogs without complication. The use of fluid ingress was trialed in 1 cadaver and not found to be helpful. The use of a blunt suction dissector greatly facilitated dissection of the peritracheal space. CONCLUSION: Minimally invasive video-assisted parathyroidectomy is feasible in dogs and was not associated with complications in 5 clinical cases. CLINICAL SIGNIFICANCE: Minimally invasive techniques tend to reduce morbidity and are popular with pet owners. This study demonstrates that a minimally invasive technique may be considered for parathyroidectomy in dogs.

Ambidirectional cohort study on the agreement of ultrasonography and surgery in the identification of parathyroid pathology, and predictors of postoperative hypocalcemia in 47 dogs undergoing parathyroidectomy due to primary hyperparathyroidism.

OBJECTIVE: To investigate (1a) agreement of ultrasonographic, surgical, and histopathologic findings in the diagnosis of a neoplastic etiology underlying primary hyperparathyroidism (PHPT), (1b) the ability of ultrasonographically determined parathyroid gland size to distinguish between malignant (carcinoma) and non-malignant (hyperplasia, adenoma) pathology, and (2) variables associated with postoperative hypocalcemia in dogs undergoing surgical treatment of PHPT. STUDY DESIGN: Ambidirectional cohort study. ANIMALS: Forty-seven client owned dogs with PHPT (34 retrospective; 13 prospective). METHODS: Data were extracted from medical records. Method agreements were explored using Cohen's Kappa statistic. A receiver operating characteristic curve (ROC) was used to determine a cut-off separating parathyroid pathologies. Univariable and multivariable models assessed associations between postoperative hypocalcemia and potential risk factors. RESULTS: Agreement of ultrasound and surgery for number and side of affected glands was 31/47 (65.9%) and 34/47 (72.3%), respectively. In 37/47 (78.7%) cases, parathyroid tissue was correctly assessed as pathologic by the surgeon. An ultrasonographic cut-off of ≥8.0 mm (ROC AUC = 0.82) best distinguished malignant from benign pathologies. Dogs with a preoperative serum ionized calcium (iCa) concentration ≥1.75 mEq/L had 7.5 times greater odds of becoming hypocalcemic postoperatively. CONCLUSION: A fair agreement existed between ultrasonographic and surgical findings in dogs with PHPT. A parathyroid mass ≥8.0 mm on ultrasonographic examination was suggestive of malignancy, while dogs with a preoperative serum iCa concentration ≥1.75 mEq/L were at increased risk for postoperative hypocalcemia in this study. CLINICAL SIGNIFICANCE: This study supports the use of bilateral cervical surgical exploration to identify abnormal parathyroid glands for the treatment of PHPT.

Primary Hyperparathyroidism in a Quarter Horse Mare Associated With a Chief Cell Adenoma.

Primary hyperparathyroidism is rare in large animal species, and little is known regarding its pathophysiology, endocrine and electrolyte derangements, diagnosis, medical management, and prognosis. This report describes the clinicopathologic diagnosis of a parathyroid (PT) gland chief cell adenoma in a 12-year-old Quarter Horse mare, including PT hormone (PTH) and electrolyte disarrangements associated with the neoplasia, the surgical removal of the adenoma, and medical management of the case. This report also describes for the first time the use PTH immunohistochemistry to confirm the nature of this neoplasia in a horse.

Primary Hyperparathyroidism Associated With Atypical Headshaking Behavior in a Warmblood Gelding.

A 14-year-old Zweibrücker Warmblood gelding was presented for evaluation of lethargy and headshaking. The horse had a history of bouts of lameness in different limbs and back problems. It also had many mild colic episodes in the past. Results of repeat laboratory tests had shown persistent hypercalcemia (4.8 mmol/L; reference interval [RI]: 2.0-3.2 mmol/L) for 1.5 years and later on hypophosphatemia (0.4 mmol/L; RI: 0.5-1.3 mmol/L) and mild hypermagnesemia (1.0 mmol/L; RI: 0.5-0.9 mmol/L). Parathyroid hormone (PTH) concentration was within the RI. Other causes of hypercalcemia, such as renal failure, vitamin D toxicosis, and granulomatous disease, and nutritional secondary hyperparathyroidism were ruled out. Furthermore, there was no evidence of neoplastic disease. Parathyroid hormone-related protein was measured but inconclusive. A diagnosis of primary hyperparathyroidism was established on the basis of hypercalcemia, hypophosphatemia, low fractional excretion of calcium, and high fractional excretion of phosphorus in combination with a PTH secretion refractory to high calcium levels. Because of the bad prognosis, the owner decided to euthanize the horse. Results of postmortem examination were unremarkable. Hypercalcemia should always be considered abnormal, and further examinations need to be performed to proof hypercalcemia and subsequently find the cause. The main differential diagnoses are renal insufficiency and humoral hypercalcemia of malignancy, but also rare diseases, such as hyperparathyroidism, have to be taken into account.

Primary hyperparathyroidism due to a cystic parathyroid adenoma in a cat.

A 15-year-old neutered female domestic shorthair cat was presented for weight loss, polydipsia/polyuria, and lethargy. A large fluctuant mass was palpated in the ventral right cervical region. Biochemistry results were consistent with primary hyperparathyroidism. Parathyroid hormone level in the fluid was higher to that observed in the plasma, consistent with a cystic parathyroid lesion. Right parathyroidectomy and thyroidectomy were performed without complications. Ionized calcium normalized within a few hours. Histopathology yielded a diagnosis of cystic parathyroid adenoma. Follow-up showed complete recovery of clinical signs and normalization of ionized calcium. This case shows an uncommon presentation of feline primary hyperparathyroidism secondary to a cystic parathyroid adenoma and is, to our knowledge, the first case presented with a large palpable mass in which parathyroid hormone concentration was measured. This report highlights the value of selective hormonal analyses of the cystic fluid to confirm the origin of the cystic lesion pre-operatively.

Perioperative characteristics, histological diagnosis, and outcome in cats undergoing surgical treatment of primary hyperparathyroidism.

OBJECTIVE: To report perioperative characteristics, complications, histopathologic diagnosis and outcome in cats undergoing surgical treatment for primary hyperparathyroidism (PHPT). STUDY DESIGN: Multi-institutional, retrospective case series. ANIMALS: Thirty-two client-owned cats. METHODS: Medical records of cats treated with surgical removal of 1 or more parathyroid gland(s) with confirmed histopathologic evaluation were reviewed. Cats were divided into preoperative ionized calcium (iCa) groups corresponding to the 33rd, 67th, and 100th percentiles of the preoperative iCa results of the study population. Follow-up consisted of phone conversation with owners or primary veterinarian. RESULTS: Ionized calcium was above reference range in all cats (median 1.8 mmol/L [interquartile range, 1.5-1.9]). Abnormal tissue was excised after cervical exploration in all cats. The most common histopathologic diagnoses were parathyroid adenoma in 20 of 32 (62.5%) cats and parathyroid carcinoma in 7 of 32 (21.9%) cats. At discharge, 6 of 32 (18.8%) cats had hypercalcemia, 5 of 32 (15.6%) had hypocalcemia, and 21 of 32 (65.6%) were normocalcemic. Preoperative iCa did not correlate with postoperative iCa. The median follow-up time was 332 days (range, 7-3156). Overall median survival time was 1109 days (95% CI, 856-1332). Survival time was not associated with preoperative iCa group, hypocalcemia at discharge, hypercalcemia at discharge, or diagnosis of carcinoma. CONCLUSION: In this cohort of cats, parathyroid adenoma was the most common cause of PHPT, and surgical treatment resulted in very good median survival time. Preoperative iCa was not predictive of postoperative hypocalcemia. CLINICAL SIGNIFICANCE: Surgical parathyroidectomy for treatment of PHPT in cats provides a favorable prognosis.

Effect of Prophylactic Calcitriol Administration on Serum Ionized Calcium Concentrations after Parathyroidectomy: 78 Cases (2005-2015).

BACKGROUND: Prophylactic administration of calcitriol has been suggested to mitigate the risk of hypocalcemia after parathyroidectomy. The effect of calcitriol on postoperative serum ionized calcium concentrations has not been evaluated in dogs after parathyroidectomy. HYPOTHESIS/OBJECTIVES: To determine the effect of prophylactic calcitriol administration on postoperative serum ionized calcium (iCa) concentrations in dogs with primary hyperthyroidism (PHPTH) treated by parathyroidectomy. ANIMALS: Seventy-eight dogs with primary hyperparathyroidism treated surgically. METHODS: Multi-institutional retrospective case study. Medical records from 2005 to 2015 were evaluated. Dogs were included if they had a diagnosis of PHPTH and had surgery to remove parathyroid tissue. Serum iCa concentrations were monitored for a minimum of 2 days postoperatively. Two study groups were evaluated: calcitriol administration and no calcitriol administration. RESULTS: Serial postoperative iCa concentrations measured at 12-hour time intervals for 2 days postoperatively were positively associated with preoperative iCa concentrations. This association was evident at each time interval, and the effect of preoperative iCa concentrations on postoperative iCa concentrations decreased as time elapsed (12 hours, P < 0.0001; 24 hours, P < 0.0001; 36 hours, P < 0.04; and 48 hours, P = 0.01). Prophylactic calcitriol administration was not found to be significantly associated with postoperative iCa concentrations or its rate of decrease after parathyroidectomy. CONCLUSION AND CLINICAL IMPORTANCE: We found no protective value in administering calcitriol prophylactically to prevent hypocalcemia in the immediate postoperative period (48 hours) after parathyroidectomy. Preoperative iCa concentrations had a significant positive association with postoperative iCa concentrations throughout the monitoring period.

[Diagnostic approach and management of hypercalcaemia in dogs exemplary of primary hyperparathyroidism]. / Diagnostische Aufarbeitung und Management der Hyperkalzämie des Hundes am Beispiel des primären Hyperparathyreoidismus.

Hypercalcaemia can be caused by many different diseases. This article summarizes the causes, pathophysiologic mechanisms and diagnostic procedures as well as treatment recommendations. The main focus is on hypercalcaemia in primary hyperparathyroidism (PH), complemented by a case report. An elevated total calcium level should generally be investigated and verified by measurement of ionized calcium concentration. The further diagnostic approach depends on the phosphate level. Tumour screening, measurement of parathormone and parathromone-related protein and sonography of parathyroid glands may be necessary. If the calcium-phosphate-product exceeds 60 mg/dl, there is a risk of tissue mineralisation and a rapid treatment of hypercalcaemia is required. For acute therapy, sodium chloride infusion, furosemide and glucocorticoids can be used. Glucocorticoids should only be given after strict indication and after a definite diagnosis. For long-term management, bisphosphates, particularly alendronate, are increasingly used successfully. Causal therapy of PH can be performed by parathyreoidectomy, heat ablation or ethanol ablation. Thereafter, particularly in cases of severe preoperative hypercalcaemia, hypocalcaemia can occur. Treatment is performed using vitamin D3 (calcitriol), which may also be given preoperatively in cases of severe hypercalcaemia. A concomitant oral calcium supplementation using calcium carbonate as medication of choice is contentious. Due to a potential relapse after successful excision of the affected parathyroid gland in PH, the serum calcium level should be monitored periodically.

Feline hyperparathyroidism: pathophysiology, diagnosis and treatment of primary and secondary disease.

PRACTICAL RELEVANCE: Hyperparathyroidism exists in primary and secondary forms. Primary hyperparathyroidism has typically been considered a disease that uncommonly affects cats, but this condition is more prevalent than previous diagnoses would suggest. Secondary hyperparathyroidism may be caused by either nutritional influences (ie, nutritional secondary hyperparathyroidism) or chronic kidney disease (ie, renal secondary hyperparathyroidism). Tertiary hyperparathyroidism has yet to be documented in veterinary medicine, but it is possible that this condition occurs in some cats following longstanding renal secondary hyperparathyroidism. CLINICAL CHALLENGES: Diagnosis of this group of calcium metabolic disorders presents a number of challenges for the clinician. For example, clinical signs can be non-specific and, especially in the case of primary hyperparathyroidism, there is often a low index of suspicion for the disease; careful sample handling is required for testing of parathyroid hormone (PTH) and ionized calcium levels; and there is currently no feline-specific assay for PTH, which has implications for test sensitivity and interpretation of results. AIMS: This article briefly outlines PTH and calcium physiology by way of introduction to a review of PTH measurement and interpretation. Various forms of feline hyperparathyroidism are then described, encompassing diagnosis and treatment options.

Primary hyperparathyroidism caused by a parathyroid carcinoma in a 16-year-old male neutered cat with concurrent chronic kidney disease.

A 16-year-old domestic shorthaired cat with chronic kidney disease was presented with a subacute history of weakness and anorexia. Severe hypercalcaemia was identified and attributed to a cervical mass, diagnosed as a parathyroid carcinoma after surgery. Renal function, as evaluated by plasma creatinine, initially worsened during hypercalcaemia but fully returned to previously documented values two months post-operatively.

[Primary hyperparathyroidism in the dog. Diagnosis, therapy and postoperative management in 19 dogs]. / Primärer Hyperparathyreoidismus beim Hund. Diagnose, Therapie und postoperatives Management bei 19 Patienten.

OBJECTIVE: Retrospective evaluation of diagnosis and outcome in 20 dogs with primary hyperparathyroidism. MATERIAL AND METHODS: In 20 dogs primary hyperparathyroidism was diagnosed and 19 patients were treated via parathyroidectomy, 10 additionally with partial thyroidectomy. Medical records of the dogs were reviewed for signalment, clinical features, laboratory findings and results of histopathologic examination. In some cases postsurgical rehabilitation of calcium metabolism required substitution with calcium and vitamin D preparations. RESULTS: Mean age of the dogs was 11.5 years. The most common clinical signs comprised polydipsia, polyuria, reduced activity, and stiff gait. Laboratory findings were moderate to extensive hypercalcaemia, low or low-normal serum phosphorus concentrations and normal or increased serum parathyroid hormone concentrations. None of the dogs had an elevated parathyroid hormone-related polypeptide level. Histological examination revealed 11 adenomas, six carcinomas and two glandular hyperplasias. Postsurgical management of calcium homeostasis was challenging in some cases. CONCLUSION: Tumours of the parathyroid gland can be easily treated by parathyroidectomy and usually have a good prognosis. CLINICAL RELEVANCE: With careful interpretation of laboratory findings of a patient presenting with hypercalcaemia and ruling out other causes of hypercalcaemia diagnosis of primary hyperparathyroidism can be easily achieved and successfully treated byparathyroidectomy.

Canine primary hyperparathyroidism.

Primary hyperparathyroidism is a common cause of hypercalcemia in dogs. The diagnosis requires careful interpretation of test results, and treatment involves removal of the affected gland(s).

Validation of a rapid parathyroid hormone assay and intraoperative measurement of parathyroid hormone in dogs with benign naturally occurring primary hyperparathyroidism.

OBJECTIVES: To (1) validate a rapid chemiluminescent parathyroid hormone (PTH) assay, (2) determine it's usefulness locating a parathyroid nodule(s), and (3) determine if >50% decrease in PTH corresponds with excision of autonomously functioning parathyroid tissue. STUDY DESIGN: Prospective cohort study. ANIMALS: Dogs (n=12) with naturally occurring primary hyperparathyroidism and 25 healthy dogs. METHODS: The assay was validated with linearity, precision, and intermethod comparison. Preoperative and postoperative systemic plasma PTH concentrations, measured from saphenous venous blood, were compared. Intraoperative local PTH concentrations were measured in right and left jugular venous blood before and after surgical excision of the grossly abnormal parathyroid gland(s). RESULTS: Within run and day-to-day precisions were acceptable (coefficient of variation <15%). Dilutional parallelism was used to demonstrate high correlation between measured and calculated PTH concentrations (R(2)=0.99). The assay methods had good correlation but numerical results of the rapid assay were usually lower than the immunoradiometric assay. Seven of 12 dogs had uniglandular disease and five had multiglandular disease. Systemic and local PTH concentrations decreased >50% in all the dogs after excision of the parathyroid gland(s). Mean preoperative systemic plasma PTH concentrations were significantly higher than mean postoperative systemic concentrations. Local PTH concentrations could not be used reliably to differentiate the side of the autonomously functioning gland(s). Hypercalcemia resolved postoperatively in all the dogs. CONCLUSION: This assay measures PTH in dogs. Rapid PTH measurement provided documentation of decreased PTH concentration after removal of autonomously functioning parathyroid tissue. CLINICAL RELEVANCE: Use of this assay allows documentation of a significant decrease in PTH concentration after excision of autonomously functioning parathyroid tissue.

Primary hyperparathyroidism in dogs and cats.

The most common cause of primary hyperparathyroidism in dogs and cats is a solitary adenoma involving an extracapsular parathyroid gland. The prognosis is excellent if the affected parathyroid gland is removed. Nonsurgical methods are discussed, although there are no current data to support any benefit over conventional surgery. The common postoperative complication to consider is hypocalcemia. Hypocalcemia can be successfully managed in these animals if it is anticipated and treated promptly.