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Hypercalcaemia
The 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
Yellow Dog
History
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
• 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 Examination
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
Haematology
Mild Leukocytosis
and left shift
Biochemistry
Marked Total Hypercalcaemia
(4.24 mmol/l)
Hypophosphataemia
Hypercholesterolaemia
Ionised Calcium: 2.17 mmol/l
consistent with
HYPERCALCAEMIA!!
Urinalysis
USG 1.014
pH 6
Normal UPC ratio
0.04
Hypercalcaemia
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 Radiographs
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 Ultrasound
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 Ultrasound
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.
PCR
• 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.
Diagnosis
Suspect T-cell Mediastinal Lymphoma
• Stage V substage b Lymphoma
Hypercalcaemia of Malignancy
• 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
Treatment
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
Plan
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 End

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Hypercalcaemia of Malignancy

  • 2. 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 Dog
  • 3. History 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
  • 4. 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
  • 5. Physical Examination 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
  • 7. Biochemistry Marked Total Hypercalcaemia (4.24 mmol/l) Hypophosphataemia Hypercholesterolaemia Ionised Calcium: 2.17 mmol/l consistent with HYPERCALCAEMIA!!
  • 9. Hypercalcaemia 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)
  • 10. Thoracic Radiographs 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
  • 11. Abdominal Ultrasound 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).
  • 12. Thoracic Ultrasound 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.
  • 13. PCR • 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.
  • 14. Diagnosis Suspect T-cell Mediastinal Lymphoma • Stage V substage b Lymphoma
  • 15. Hypercalcaemia of Malignancy • 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
  • 16. Treatment 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
  • 17. Plan 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.