HypercalcaemiaHypercalcaemiaHypercalcaemiaHypercalcaemia

The Hunt for the TumourThe Hunt for the TumourThe Hunt for the TumourThe Hunt for the Tumour

10 year old MN Labrador Cross

Presented at the SAH on 23/09/13 for further investigation of PU/PD

Past 3 months showing signs of:

PU/PD

Lethargy

Weight loss

Anorexia

Weakness

10 year old MN Labrador Cross

Presented at the SAH on 23/09/13 for further investigation of PU/PD

Past 3 months showing signs of:

PU/PD

Lethargy

Weight loss

Anorexia

Weakness

Yellow DogYellow DogYellow DogYellow Dog

HistoryHistoryHistoryHistoryFirst visit to vets on 09/08/13

Biochemistry:

Calcium 3.83 mmol/l

No other abnormalities

Urinalysis:

USG 1.010 (Isosthenuric)

pH 7

No other abnormalities

Second visit to vets on 19/08/13

Water deprivation test:

7am: USG 1.0095, weight 33.4kg

12pm: USG 1.009, weight 33.15kg

2pm: USG 1.012, weight 32.8kg

4pm: USG unable to get urine, weight 31.7kg

First visit to vets on 09/08/13

Biochemistry:

Calcium 3.83 mmol/l

No other abnormalities

Urinalysis:

USG 1.010 (Isosthenuric)

pH 7

No other abnormalities

Second visit to vets on 19/08/13

Water deprivation test:

7am: USG 1.0095, weight 33.4kg

12pm: USG 1.009, weight 33.15kg

2pm: USG 1.012, weight 32.8kg

4pm: USG unable to get urine, weight 31.7kg

History History History History • Results of the water deprivation test indicative of Diabetes

Insipidus.• Started on Desmopressin 0.1mg 1.5 tablets SID• Retested urine on 27/08/13

• USG 1.010• Drinking less, urinating the same but doing “bit poorly” per

owner• Changed Desmopressin to 2 tablets SID

• Retested urine on 09/09/13• USG 1.011• Drinking less, urinating the same, not interested in food, very

thin, lethargic• Retested urine on 16/09/13

• USG 1.010• Still unable to concentrate urine, not eating, lethargic, muscle

weakness

• Results of the water deprivation test indicative of Diabetes Insipidus.

• Started on Desmopressin 0.1mg 1.5 tablets SID• Retested urine on 27/08/13

• USG 1.010• Drinking less, urinating the same but doing “bit poorly” per

owner• Changed Desmopressin to 2 tablets SID

• Retested urine on 09/09/13• USG 1.011• Drinking less, urinating the same, not interested in food, very

thin, lethargic• Retested urine on 16/09/13

• USG 1.010• Still unable to concentrate urine, not eating, lethargic, muscle

weakness

Physical ExaminationPhysical ExaminationPhysical ExaminationPhysical ExaminationQuiet, alert and responsive

Thoracic auscultation and abdominal palpation were unremarkable

No evidence of any anal gland masses on rectal exam

Peripheral lymph nodes were unremarkable

BCS 2/5 and weighed 30.2kg

Quiet, alert and responsive

Thoracic auscultation and abdominal palpation were unremarkable

No evidence of any anal gland masses on rectal exam

Peripheral lymph nodes were unremarkable

BCS 2/5 and weighed 30.2kg

HaematologyHaematologyHaematologyHaematology

Mild Leukocytosis and left shiftMild Leukocytosis and left shift

BiochemistryBiochemistryBiochemistryBiochemistry

Marked Total Hypercalcaemia (4.24 mmol/l)

Hypophosphataemia

Hypercholesterolaemia

Ionised Calcium: 2.17 mmol/l consistent with HYPERCALCAEMIA!!

Marked Total Hypercalcaemia (4.24 mmol/l)

Hypophosphataemia

Hypercholesterolaemia

Ionised Calcium: 2.17 mmol/l consistent with HYPERCALCAEMIA!!

UrinalysisUrinalysisUrinalysisUrinalysis

USG 1.014

pH 6

Normal UPC ratio 0.04

USG 1.014

pH 6

Normal UPC ratio 0.04

HypercalcaemiaHypercalcaemiaHypercalcaemiaHypercalcaemiaH: hyperparathyroidism

A: addison’s disease; vitamin A toxicosis

R: renal disease

D: vitamin D toxicosis, dehydration

I: idiopathic

O: osteolytic (multiple myeloma)

N: neoplasia (anal sac adenocarcinoma, lymphoma)

S: spurious (lab error, lipemic sample causing false elevation of calcium)

H: hyperparathyroidism

A: addison’s disease; vitamin A toxicosis

R: renal disease

D: vitamin D toxicosis, dehydration

I: idiopathic

O: osteolytic (multiple myeloma)

N: neoplasia (anal sac adenocarcinoma, lymphoma)

S: spurious (lab error, lipemic sample causing false elevation of calcium)

Thoracic RadiographsThoracic RadiographsThoracic RadiographsThoracic RadiographsIncreased soft tissue opacity in cranial thorax, with splaying of the cranial lung lobes and elevation of the trachea

Loss of clarity of cranial cardiac silhouette

Cranial Mediastinal Mass (ie. LSA, thymic lymphoma)

Possible bony lesions affecting sternebrae 4 & 5 and the dorsal spinous processes of T4 and T9

Increased soft tissue opacity in cranial thorax, with splaying of the cranial lung lobes and elevation of the trachea

Loss of clarity of cranial cardiac silhouette

Cranial Mediastinal Mass (ie. LSA, thymic lymphoma)

Possible bony lesions affecting sternebrae 4 & 5 and the dorsal spinous processes of T4 and T9

Mediastinal Mass

Abdominal UltrasoundAbdominal UltrasoundAbdominal UltrasoundAbdominal UltrasoundSpleen diffusely mildly mottled (consistent of nodular hyperplasia, extramedullary haematopoises, reactive splenitis, congestion or infiltrative neoplasia).

Gall bladder mild wall thickening (consistent with previous or chronic cholecystitis).

Both kidneys cortices were diffusely bright and pelvis deverticuli were associated with mineralisations (consistent with age related changes or chronic renal disease).

Spleen diffusely mildly mottled (consistent of nodular hyperplasia, extramedullary haematopoises, reactive splenitis, congestion or infiltrative neoplasia).

Gall bladder mild wall thickening (consistent with previous or chronic cholecystitis).

Both kidneys cortices were diffusely bright and pelvis deverticuli were associated with mineralisations (consistent with age related changes or chronic renal disease).

Thoracic UltrasoundThoracic UltrasoundThoracic UltrasoundThoracic UltrasoundIn the cranial thoracic cavity cranial to the heart, there was a large heterogeneous mass.

Two round large hypoechoic slightly heterogeneous masses were identified as enlarged cranial mediastinal lymph nodes.

Ultrasound guided FNA of both mediastinal mass and lymph node: sadly non-diagnostic.

In the cranial thoracic cavity cranial to the heart, there was a large heterogeneous mass.

Two round large hypoechoic slightly heterogeneous masses were identified as enlarged cranial mediastinal lymph nodes.

Ultrasound guided FNA of both mediastinal mass and lymph node: sadly non-diagnostic.

PCRPCRPCRPCR

• FNA was submitted for PCR to enable us to see if a monoclonal population of lymphoid cells are present which would be consistent with lymphoma.

• Results:

• Polyclonal distribution suggesting presence of a mixed population of T-Cells.

• FNA was submitted for PCR to enable us to see if a monoclonal population of lymphoid cells are present which would be consistent with lymphoma.

• Results:

• Polyclonal distribution suggesting presence of a mixed population of T-Cells.

DiagnosisDiagnosisDiagnosisDiagnosis

Suspect T-cell Mediastinal Lymphoma

• Stage V substage b Lymphoma

Suspect T-cell Mediastinal Lymphoma

• Stage V substage b Lymphoma

Hypercalcaemia of Hypercalcaemia of MalignancyMalignancy

Hypercalcaemia of Hypercalcaemia of MalignancyMalignancy• Hypercalcaemia is a paraneoplastic syndrome in domestic animals and is

a great tumour marker.

• The 2 most common non-parathyroid neoplasms that cause persistent hypercalcaemia in dogs:

• Lymphoma (Lymphosarcoma)

• Adenocarcinoma of the apocrine glands of the anal sac

• Hypercalcemia of malignancy manifests as a result of three underlying pathological processes associated with neoplasia:

• interference with 1 alpha-hydroxylase activity, leading to unregulated conversion of calcidiol to active calcitriol and enhanced intestinal absorption of calcium

• hypersecretion of parathyroid releasing protein (PTHrP), a polypeptide structurally similar to intact parathyroid hormone

• heightened activity of interleukin-1, interleukin-6 and tumor necrosis factor. The production and secretion of these humoral mediators lead to pathologic increases in osteoclastic resorption, often without visible radiographic bone lesions.

• Hypercalcaemia is a paraneoplastic syndrome in domestic animals and is a great tumour marker.

• The 2 most common non-parathyroid neoplasms that cause persistent hypercalcaemia in dogs:

• Lymphoma (Lymphosarcoma)

• Adenocarcinoma of the apocrine glands of the anal sac

• Hypercalcemia of malignancy manifests as a result of three underlying pathological processes associated with neoplasia:

• interference with 1 alpha-hydroxylase activity, leading to unregulated conversion of calcidiol to active calcitriol and enhanced intestinal absorption of calcium

• hypersecretion of parathyroid releasing protein (PTHrP), a polypeptide structurally similar to intact parathyroid hormone

• heightened activity of interleukin-1, interleukin-6 and tumor necrosis factor. The production and secretion of these humoral mediators lead to pathologic increases in osteoclastic resorption, often without visible radiographic bone lesions.

TreatmentTreatmentTreatmentTreatmentFluid therapy with 0.9% NaCl

• providing additional sodium to renal tubules will diminish calcium reabsorption and increase calciuresis

Diuretics following rehydration

• furosemide will increase calcium excretion by the kidneys

Glucocorticoids

• dexamethasone reduce bone resorption of calcium, reduce intestinal calcium absorption, and increase renal calcium excretion

Calcitonin

• rapid calcium-lowering effect due to inhibitory effects on osteoclastic activity and renal tubular reabsorption of calcium.

Bisphosphonates

• act to lower serum calcium by reducing the number and action of osteoclasts

Fluid therapy with 0.9% NaCl

• providing additional sodium to renal tubules will diminish calcium reabsorption and increase calciuresis

Diuretics following rehydration

• furosemide will increase calcium excretion by the kidneys

Glucocorticoids

• dexamethasone reduce bone resorption of calcium, reduce intestinal calcium absorption, and increase renal calcium excretion

Calcitonin

• rapid calcium-lowering effect due to inhibitory effects on osteoclastic activity and renal tubular reabsorption of calcium.

Bisphosphonates

• act to lower serum calcium by reducing the number and action of osteoclasts

PlanPlanPlanPlanFurther investigation was discussed with the owner to be able to obtain a definitive diagnosis but this was declined.

Owners would like to trial palliative steroids. This will help reduce his hypercalcaemia and improve his appetite.

Prednisolone 25mg tablets and Zantac 150mg tablets.

Owners want to take him home for a few days and then euthanise.

Further investigation was discussed with the owner to be able to obtain a definitive diagnosis but this was declined.

Owners would like to trial palliative steroids. This will help reduce his hypercalcaemia and improve his appetite.

Prednisolone 25mg tablets and Zantac 150mg tablets.

Owners want to take him home for a few days and then euthanise.

The EndThe EndThe EndThe End