The blood results of a 75 year old who presents with lethargy, confusion and weight loss are shown below:
Patient value |
Normal range |
|
Sodium |
141 mmol/L |
135 – 145 |
Potassium |
3.8 mmol/L |
3.5 – 5.0 |
Chloride |
100 mmol/L |
97 – 109 |
Bicarbonate |
29 mmol/L |
24 – 32 |
Urea |
11.5 mmol/L |
3.0 – 8.0 |
Creatinine |
150 µmol/L |
70 – 110 |
Calcium |
4.69 mmol/L |
2.10 – 2.60 |
Phosphate |
0.4 mmol/L |
0.8 – 1.5 |
Albumin |
44 G/L |
38 – 48 |
a) What is the likely diagnosis?
b) What other biochemistry would you request and why?
c) Briefly explain the pathogenesis of the biochemical abnormalities.
d) Outline your management of this patient.
College Answer
a) What is the likely diagnosis?
Underlying malignancy
b) What other biochemistry would you request and why?
PTH to exclude primary hyperPTH – very high calcium indicates malignancy but patients with malignancy have higher incidence of hyperPTH than general population so both conditions can co-exist
c) Briefly explain the pathogenesis of the biochemical abnormalities.
Hypercalcaemia:
Malignancy:
- PTH rp (Parathyroid related peptide)
- Ectopic PTH
- Bone lysis
Increased PTH:
- Leading to increased osteoclast activity leads to hypercalcaemia by bone reabsorption. It also acts at renal tubule to reabsorb Ca++ and increases conversion 25-OHD to 1,25 (OH)2D increases intestinal absorption of Ca++
Elevated urea and creatinine:
- Secondary to hypovolaemia
d) Outline your management of this patient.
• Fluid replacement with NS
• Biphosphonates
• Calcitonin
• Steroids act by decreasing calcitriol
• Dialysis
• Treat underlying malignancy
• Parathyroidectomy if raised PTH
• (Diuretics no longer recommended)
Discussion
As for the diagnosis- the clue is in the age and the weight loss, and the college does sound as if they are asking for the one most likely diagnosis. But if one were to approach this on classical footing, one would be expected to regurgitate a small pool of differentials.
Primary endocrine causes
Paraneoplastic causes
|
Granulomatous disease
Drug-induced hypercalcemia
Random miscellaneous causes
|
One may wish to launch the following investigations:
- Alkaline phosphatase
- Serum PTH level
- CK
- Parathyroid hormone related peptide (PTHrp)
- Serum Vitamin D metabolite levels
- CXR - or better yet, CT chest - to look for obvious malignancy and granulomatous disease.
As for management, one would be well served to organise the response by the physiological aims of one's therapy:
- Dilute serum calcium
- Rehydration with IV fluids
- Decrease calcium resportion from bone
- Calcitonin
- Bisphosphonates
- Gallium nitrate
- Decrease calcium resportion from renal tubule
- Loop diuretics (this has fallen out of favour)
- Calcitonin
- Decrease calcium absorption from the gut
- Corticosteroids (also they decrease the 1,25-dihydroxyvitamin D production by monocytes within granulomae)
- Forcibly remove excess calcium from the circulation
- Haemodialysis
- EDTA administration (as chelating agent)