Hypercalcaemia
This includes the commonest underlying diagnosis: primary hyperparathyroidism, and all other causes of hypercalcaemia.
Is there any relevant family history?
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.
Is there any history of excessive thirst, nocturia or other symptoms suggestive of renal colic?
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.
Have there been any bony symptoms: back pain or previous fractures suggestive of osteoporosis?
Hyperparathyroidism leads to calcium loss from the skeleton and is a strong risk factor for osteoporosis.
Has there been any mood change?
Tiredness, depression and low energy are all common, though not specific, symptoms of hypercalcaemia.
Has the patient lost any weight, developed nausea or anorexia?
All of these symptoms may occur with severe hypercalcaemia of any cause, however, they may also raise the suspicion of underlying malignancy.
Has the patient developed any other gastrointestinal symptoms?
Abdominal pain may be due to dyspepsia, peptic ulcer disease, constipation, or pancreatitis, all of which more commonly occur in the presence of hypercalcaemia.
Has the patient any symptoms or history of other underlying conditions? In particular, has the patient developed galactorhoea, amenorrhoea, loss of libido or erectile dysfunction?
These symptoms may be associated with elevated prolactin and hence suggest MEN1.
Is there any history of skin changes, pulmonary or renal disease?
These features may be suggestive of sarcoidosis or tuberculosis as an underlying cause.
Are there any other alarm symptoms that might suggest underlying malignancy?
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.
Has the patient's presentation occurred following a holiday in the sun?
These features may be suggestive of sarcoidosis or tuberculosis as an underlying cause, as vitamin D hydroxylation increases following UV exposure.
Are there any symptoms of thyrotoxicosis?
Untreated thyrotoxicosis may be associated with hypercalcaemia. This is usually mild, and responds to treatment of the underlying thyroid condition.
Are there any symptoms suggestive of hypoadrenalism?
Untreated Addison's disease may be associated with mild hypercalcaemia, which responds to glucocorticoid replacement therapy.
What is their medication and dietary history?
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.
Is the patient interested in surgery if appropriate?
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.