Education Resource from the Society for Endocrinology
M Davies
University of Manchester, Manchester Royal Infirmary
Summer School 15-18 July 2003
University of Manchester, Hulme Hall, Manchester, UK
Hypercalcaemia, ie elevation of the serum ionised calcium concentration, occurs when the normal homeostatic mechanisms controlling the serum ionised calcium concentration fail. The hormonal control of serum calcium depends upon a functioning parathyroid gland renal axis and hypercalcaemia can arise as a result of a primary disturbance of this axis eg primary hyperparathyroidism or despite a compensatory reduction in the parathyroid renal axis eg malignant hypercalcaemia.
The most important factors in delineating hypercalcaemia are to determine whether hypercalcaemia is responsible for the patients symptoms and secondly to decide whether the hypercalcaemia is parathyroid or non-parathyroid in origin since over 90% of hypercalcaemic cases in a hospital setting will be from either primary hyperparathyroidism or malignant hypercalcaemia.
Symptomatic hypercalcaemia with anorexia, nausea, vomiting, constipation, polyuria and polydypsia is unusual if the albumin corrected serum calcium is below 3-25mmol/l. Patients who are otherwise well where hypercalcaemia has been discovered fortuitously will either have primary hyperparathyroidism or a variant, familial hypocalciuric hypercalcaemia (F.H.H) (caused by a missense mutation in the calcium sensing receptor). Ill patients may be so because of an underlying disease with hypercalcaemia present due to co-existent primary hyperparathyroidism, or because the whole clinical picture including the hypercalcaemia is due to a single disease when as stated above, malignancy will be a strong possibility. After taking a history (to include drug history, diuretics, lithium, vitamin D and calcium containing medications) and a full clinical examination, a blood sample should be taken and if necessary stored for measurement of serum calcium and PTH. This must be done before any attempt is made to lower the serum calcium. Note should be taken of any recent sunny holiday since hypercalcaemic sarcoid is much commoner after a period of hot sunshine. A chest radiograph may show changes of sarcoid, lymphoma, lung cancer or rib metastases.
If PTH is raised or in the upper 1/3 of the normal range primary hyperparathyroidism is likely but if a 24 hour urine calcium excretion is below 5mmol in the absence of renal insufficiency, lithium or diuretic therapy then familial hypocalciuric hypercalcaemia should be considered and family members assessed. FHH is not helped by parathyroid surgery. In deciding about surgical correction of hyperparathyroidism guidelines exist to help, but investigations should include documentation of the degree of calciuria evidence of renal tract calcification and reduction in bone mineral density. Localisation studies are only performed if a surgeon requires help in locating abnormal parathyroid tissue. It is not a diagnostic procedure.
When hypercalcaemia is present with low serum PTH, a non-parathyroid cause should be sought such as carcinoma of the lung, pancreas, breast, ovary, prostate, myeloma, lymphoma, sarcoid. Rarer causes include severe untreated thyrotoxicosis, Addisons disease, vipoma. The last perplexing case I saw was due to taking an inadequate history missing the self medication with Rennies in a lady with “Milk Alkali Sydrome”.
When PTH is suppressed measurement of vitamin D levels may reveal high calcitriol levels in sarcoid and lymphoma, or high PTH related peptide in squamous neoplasia. Steroids will control hypercalcaemia from excess extra renal synthesis of calcitriol as seen in granulomatous disease. Addisons disease and chemotherapy may help malignant hypercalcaemia although Pamidronate infusions will alleviate most cases of malignant hypercalcaemia in a few days.
In severe life threatening hypercalcaemia from primary hyperparathyroidism preoperative management includes fluid replacement and Pamidronate will control hypercalcaemia for 7-14 days.
The opinions expressed in this paper are those of the speaker and do not
necessarily reflect the views of the Society
Revised:
04-Sep-2003