This includes the commonest underlying diagnosis: primary hyperparathyroidism, and all other causes of hypercalcaemia.
Hypercalcaemia may run in families for several reasons. FamiliaI hypocalciuric hypercalcaemia is important to diagnose in order to prevent unnecessary investigation of family members.
Hypercalcaemia can also occur as part of multiple endocrine neoplasia type 1 (and to a lesser extent type 2) and is frequently the first manifestation of the syndrome.
Long standing hypercalcaemia leads to a failure of urinary concentrating capacity - nephrogenic diabetes insipidus. The commonest manifestation of this is increased thirst, followed by polyuria and nocturia. Increased urinary calcium loss also predisposes to renal stone formation and hence renal colic.
Hyperparathyroidism leads to calcium loss from the skeleton and is a strong risk factor for osteoporosis.
Tiredness, depression and low energy are all common, though not specific, symptoms of hypercalcaemia.
All of these symptoms may occur with severe hypercalcaemia of any cause, however, they may also raise the suspicion of underlying malignancy.
Abdominal pain may be due to dyspepsia, peptic ulcer disease, constipation, or pancreatitis, all of which more commonly occur in the presence of hypercalcaemia.
These symptoms may be associated with elevated prolactin and hence suggest MEN1.
These features may be suggestive of sarcoidosis or tuberculosis as an underlying cause.
A change in bowel habit and dyspepsia may both be symptoms of hypercalcaemia for example but, depending on the clinical picture, may warrant formal investigation.
These features may be suggestive of sarcoidosis or tuberculosis as an underlying cause, as vitamin D hydroxylation increases following UV exposure.
Untreated thyrotoxicosis may be associated with hypercalcaemia. This is usually mild, and responds to treatment of the underlying thyroid condition.
Untreated Addison's disease may be associated with mild hypercalcaemia, which responds to glucocorticoid replacement therapy.
In particular, dietary supplements and antacids or other medications for dyspepsia are frequently high in calcium.
Lithium use is also associated with hypercalcaemia, which may respond to lithium withdrawal. However, the presence of lithium does not preclude the possibility of classic primary hyperparathyroidism, and so investigation should be performed as normal, and surgical treatment may still be effective.
Bisphosphonate treatment also leads to elevations in PTH, and so should be stopped for at least six weeks before repeating the biochemical assessment.
It is worth establishing whether patients would be interested in surgery at the start of investigation. Patients who are not agreeable to, or not fit for surgery, should not undergo localising studies if hyperparathyroidism is confirmed.