Case of The Week

Chor Kuan and Judy

Patient details

Mrs LG
52 year old female
ICU nurse

HOPC

Hypercalcaemia
Ca 3.13
Asymptomatic
Stones, bones, abdominal groans,
psychological moans

Past medical history

Metastatic SCC - unknown primary (2015)

PET scan: metastasis left parotid, submandibular, left

axillary lymph node

1o hyperparathyroidism 2o to parathyroid
adenoma
Ca 3.22
(2.20 - 2.60)
PTH 47.5 (1.5 - 7.0)
Sestamibi: 2cm x 1.8cm x 2cm mass inferior pole left

thyroid

Left lower lobe thyroid nodule

US neck: 2cm x 1.9cm x 1.6cm hypervascular nodule
FNA: no malignancy

Past medical history

HTN
Hypercholesterolaemia
Piriformis syndrome

Medications

Rosuvastatin 5mg D
Pregabalin 150mg
Magmin BD
Phosphate BD

Allergies

Tramadol
Endone

Social history

Lives at home with husband

Non-smoker
Non-drinker

Examination

HR 80 regular, RR 16, O2 sats 99%RA,

BP 130/70, afebrile
Head and neck: submandibular mass,
multiple thyroid nodules
Chest: unremarkable
Abdomen: unremarkable
No bony tenderness along spine

Investigations

FBE: 98*/3.2*/186
UEC: 135/5.3*/111/18* Ur 8.7* Cr 92*
eGFR 62*
Alb 44
CMP: 3.31*/0.64*/0.68*
Corr Ca: 3.23
PTH: 123.5*
TSH 1.16

Issues

Hypercalcaemia 20 parathyroid
adenoma
Metastatic SCC, hyperparathyroidism,
thyroid nodule for surgical
management in 4 days

Management

IV fluid therapy
IV pamidronate 60mg
ENT R/V

Left total parotidectomy

Neck dissection
Removal of parathyroid adenoma
Removal of thyroid nodule

Currently

Day 3 post-op
Ca 2.12
Alb 33
Corr Ca 2.26

Discussion
Overview of Hypercalcemia

Content

Hypercalcemia
Symptoms
Causes of Hypercalcemia
Investigations
Management

Hypercalcemia

>90% of cases of hypercalcemia due to

hyperparathyroidism or malignancy
Primary hyperparathyroidism is common
especially in women aged 40-60 years
Usually due to adenoma of 1 of 4 parathyroid
glands
PTH-rP is responsible for up to 80% of
hypercalcemia in malignancy (eg: Squamous
Cell Carcinoma, Breast and Kidney)
PTH-rP act on same receptors as PTH and shares
the first 13 amino acids with PTH

Symptoms of
Hypercalcemia

Stones, Bones, Abdominal Groans

and Psychic moans

Renal or biliary stones

Bone Pain
Abdominal Pain, Nausea and Vomiting
Confusion, depression

Control of PTH
Plasma Ca2+

Kidney

PO

34

PTH

Decreased Renal excretion of calcium

Drugs (eg: diuretics and lithium)

excretion Ca

2+

ReabsorptionVitamin D 1-Hydroxylation

Causes of Hypercalcemia
Increased calcium absorption
Increased Ca2+
Increased Vit D
Increased Bone Reabsorption
Primary and Tertiary
Hyperparathyroidism
Malignancy
Hyperthyroidism

Intestinal
Ca2+ and PO43Absorption

Bone

Osteoclastic
Resorption

Release of
Ca2+ and PO43-

Investigations

What is the best first investigation to

determine the cause of hyper Ca2+?
Hyper Ca2+ normally supresses PTH
PTH best first test to identify cause of

hypercalcemia
If detectable (in or above normal range)
the patient must have
hyperparathyroidism

Investigations

What other investigations would you order?

Bloods
Serum Calcium
PTHrP (elevated in malignancy)
Serum ACE (elevated in Granulomatous disease; eg:

Sarcoidosis)
Tests for multiple myeloma
25-OH Vitamin D

Chest X-Ray (to survey for malignancy)

Whole body bone scan (for skeletal metastasis)
CT Scan/MRI

Management

Acute hypercalcemia
(serum calcium > 3mmol/L)
Adequate rehydration 3-4L saline/day
Loop Diuretics to promote calcium excretion

(Note not Thiazide which increase

reabsorption)
IV bisphosphanates (eg: pamidronate
disodium)
Identification of the cause and its subsequent
specific treatment (eg: corticosteroids for
sarcoid if indicated)

Evidence Based Medicine

Randomized trials have demonstrated the

efficacy of IV pamidronate for the treatment of
hypercalcemia due to excessive bone resorption
from malignancy, acute primary
hyperparathyroidism, immobilization,
hypervitaminosis D, and sarcoidosis
Trials show pamidronate is more effective in
managing hypercalcemia of malignancy than IV
etidronate or clodronate (70% versus 40%)

Stewart, A. F. (2005). Hypercalcemia associated with cancer. New England Journal of Medicine, 352(4), 373-379.
Gucalp, R., et al. (1992). Comparative study of pamidronate disodium and etidronate disodium in the treatment of
cancer-related hypercalcemia. Journal of clinical oncology, 10(1), 134-142.
Ralston, S. et al. (1989). Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia.
The Lancet, 334(8673)

Evidence Based Medicine

Zoledronic acidis considered to be the drug of

choice for malignancy-associated hypercalcemia
because it is more potent and effective than
pamidronate
Can be administered over shorter period of time
15 minutes vs 2 hours
pooled analysis of two phase III trials involving
275 patients with tumor-induced hypercalcemia,
single dose of ZA (either 4 mg or 8 mg) normalized

the corrected serum calcium concentration in 88% of

patients, compared with only 70% of those receiving
pamidronate (90 mg)
Rosen, L. S. et al (2004). Zoledronic acid is superior to pamidronate for the treatment of bone
metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer, 100(1), 3643.

References
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6.

Walker, B. R., Colledge, N. R., Ralston, S. H., & Penman, I. (2013).

Davidson's principles and practice of medicine. Elsevier Health Sciences.
Kalra, P. A. (4th Ed.). (2014). Essential revision notes for MRCP. PasTest.

Stewart, A. F. (2005). Hypercalcemia associated with cancer. New

England Journal of Medicine, 352(4), 373-379.
Gucalp, R., et al. (1992). Comparative study of pamidronate disodium
and etidronate disodium in the treatment of cancer-related
hypercalcemia. Journal of clinical oncology, 10(1), 134-142.
Ralston, S. et al. (1989). Comparison of three intravenous
bisphosphonates in cancer-associated hypercalcaemia. The Lancet,
334(8673)
Rosen, L. S. et al (2004). Zoledronic acid is superior to pamidronate
for the treatment of bone metastases in breast carcinoma patients
with at least one osteolytic lesion. Cancer, 100(1), 36-43.