One of my elderly female patients consulted me a few weeks ago because of a painful left wrist. I could not see much wrong on examination and she was quite well generally.
She was a slim woman and there was no evidence of synovitis or fracture in the wrist.
I wondered if she had tenosynovitis of the extensor tendons as she was tender over the dorsum of the wrist.
She was not taking any regular medication.
I arranged an X-ray and blood screen. I was surprised to find that she had raised calcium of 3.2mmol/l with a normal albumin and alkaline phosphatase.
My immediate thought was of bony metastases, given her advanced age of 87 years, and I referred her for an urgent bone scan. The radiologist rang me to ask why I had thought of metastases as her alkaline phosphatase was not raised.
I confessed my ignorance of calcium metabolism in the elderly and he suggested that a referral to our local geriatrician may be more appropriate.
When I started to investigate causes of hypercalcaemia in the elderly, I was surprised to find that it is relatively common and often benign.
This was not what I had been led to believe when working as an SHO, but the case-load I was seeing then was probably much younger.
The movement of calcium from bone to extracellular fluid, as well as its transport across the kidney and intestine, is regulated mainly by para-thyroid hormone (PTH) and 1,25-dihydroxyvitamin D.
The production of these hormones is regulated directly or indirectly by ionised calcium concentration itself.
The three major organs associated with calcium regulation - bone, intestine and kidney - all undergo age-associated changes that affect calcium transport and the response to calcium-regulating hormones.
The most important regulator of serum calcium concentration is PTH. There is an age-associated increase in the concentration of PTH.1 Although the reasons for this are not completely understood, it is believed to be due to the increase in end-organ resistance to PTH.
Any calcium level above 2.6mmol/l is defined as hypercalcaemia, but this has to be in association with normal albumin levels. Raised albumin levels can cause an artificially high calcium level.
It is useful to divide hypercalcaemia into mild and severe forms.
The rapidity with which the raised calcium levels develop is as important as the final level. Cases where the calcium level has been raised for a long time are almost all due to a raised PTH level.
Acute hypercalcaemia is often due to malignancy and causes the most severe problems for the patient (hence why most end up in acute care seen by SHOs).
Patients develop severe dehydration, as the increase in calcium level promotes fluid loss by the kidney, and an increase in serum concentration and further increase in calcium concentration. The patient is in a vicious circle of dehydration and reducing renal function.
Elderly patients are particularly prone to such hypercalcaemic crises because of age- associated reductions in renal function and they may also have limited access to fluids and a reduced thirst reflex.
The problem is confounded by the use of diuretics and the difficulty in detecting dehydration in some elderly patients.
Other signs and symptoms of hypercalcaemia include ill-defined neuromuscular or psychiatric symptoms. Depression, GI symptoms and constipation are also common.
Chronic hypercalcaemia can cause kidney stones, a decrease in bone mass and impairment of renal function.
Causes of hypercalcaemia
As discussed, the most common cause of hypercalcaemia is an increase in PTH secretion due to an adenoma or polyglandular hyperplasia.
The incidence increases with age but this may be because mild hyperparathyroidism is often undiagnosed for years. Rates of primary hyperparathyroidism are four times higher in women than men.
An increase in diagnosis occurs at the menopause and this may be because of the loss of the opposing effects of estrogen on PTH-stimulated bone resorption. When this occurs, the calcium levels may rise from high normal to abnormal.
In secondary hyperparathyroidism, the parathyroid glands are hyperplasic because of prolonged stimulation due to the calcium deficiency of renal failure.
Renal failure prevents vitamin D from promoting the absorption of calcium from the gut, as the kidneys normally convert inactive vitamin D to its active metabolite.
Renal transplantation may cause temporary hypercalcaemia as the parathyroid glands continue to be hyperplasic.
Elderly asymptomatic patients with hyperparathyroidism should be followed up. If their calcium level does not exceed 3.0mmol/l, then they usually do not require any treatment.
However, they must be warned to avoid dehydration, and bone density should be monitored as they are at risk of osteoporotic fractures.
Osteoporotic fractures in those with raised PTH levels may be an indication for surgery. Most patients regain bone mass after the parathyroid glands are removed.
This also reminds us that in patients with osteoporosis, it is necessary to check serum calcium and PTH levels before treating them with calcium and vitamin D tablets.
A minority of patients with osteoporosis will have raised calcium levels and hyperparathyroidism, and treatment with additional calcium will make matters worse.
This patient saw the geriatricians and was found to have mildly elevated PTH levels.
Bone density scanning confirmed low density and possibly her wrist pain was caused by sub-clinical bone fracture.
She was treated with a bisphosphonate and her wrist pain improved.
An isotope bone scan would have shown high uptake in her wrist, so perhaps would not have been a complete waste of time.
She did not require surgery for her hyperparathyroidism and is now doing well, but is monitored carefully.
- Dr Warburton is a GPSI in rheumatology in Ironbridge, Shropshire
1. Young G, Marcus R, Minkoff J R, et al. Age-related rise in parathyroid hormone in man: the use of intact and midmolecule antisera to distinguish hormone secretion from retention. J Bone Miner Res 1987; 2: 367-74.