Almost every cause of a high calcium can be sorted with two numbers taken together. Plot the calcium against the PTH and you get four boxes — and only one of them is a surgical disease.
The phrase that earns marks
“A PTH that is normal in the face of a high calcium is not a normal PTH — it is inappropriately normal, and it means the same thing as a raised one. A healthy gland faced with hypercalcaemia should be completely suppressed.”
Primary hyperparathyroidism or malignancy?
Between them these two account for the large majority of hypercalcaemia, and the history separates them before any test comes back.
| Primary hyperparathyroidism | Malignancy | |
|---|---|---|
| Onset | Months to years | Days to weeks |
| Calcium | Usually under 12 mg/dL | Often above 13 mg/dL |
| PTH | High or inappropriately normal | Suppressed |
| Symptoms | Mild or absent | Marked — drowsy, vomiting, dehydrated |
| Mechanism | Autonomous gland | PTHrP, osteolytic metastases, myeloma, calcitriol from lymphoma |
| Outlook | Cured by an operation | A marker of advanced disease |
The order of investigation
Calcium and albumin → repeat to confirm → PTH, phosphate, magnesium, renal function and 25(OH) vitamin D → then a 24-hour urine calcium. Only when that panel says primary hyperparathyroidism do you ask for imaging.
Imaging does not make this diagnosis
A scan tells you where a gland is. It never tells you whether the patient has the disease, and a negative scan does not overturn the biochemistry or cancel the operation.
Asking about the history
Most primary hyperparathyroidism today is found on a routine biochemistry panel, so the textbook “stones, bones, abdominal groans and psychic moans” is a useful prompt and a misleading expectation. Ask about each explicitly — patients rarely volunteer fatigue or constipation as symptoms. Then ask the five that change management: how long the calcium has been abnormal, the drug history (thiazides, lithium, calcium and vitamin D supplements, antacids), red flags for cancer, stones and fractures, and the family history of hypercalcaemia, neck surgery or MEN syndromes.