Hypercalcaemia

Vital mineral – calcium
For bodies to work efficiently, they need to be supplied with the right balance of vitamins and minerals. Calcium is vital for the development of healthy bones and teeth – 99% of the calcium in our bodies is found here. It is also needed for muscle contraction, regulation of the heartbeat and is involved in the formation of blood clots. To help the body absorb calcium is needed Vitamin D.
Good natural sources of calcium are – dairy products, cheese, yoghurt, canned fish, leafy green vegetables, fortified bread and cereals.

Calcium control
The 4 pea-sized parathyroid glands are responsible for regulating the body's calcium levels. These small glands, which are embedded in the tissue of the thyroid gland, detect fluctuations in the level of calcium in the blood. When the levels drop, they secrete parathyroid hormone. This causes calcium to be released from the bones, more to be reabsorbed through the kidneys and more to be absorbed from food in the intestines. If levels rise too much, parathyroid hormone secretion is decreased and calcium levels return to normal again. Both increased and decreased levels of serum calcium can have a serious effect on the way the body functions.

There are three forms of calcium in serum:

• ionised (physiological form)
• protein-bound (50%), mainly to albumin
• complexed to citrate and phosphate (1-2%)

Hypercalcaemia means too much calcium (serum calcium level higher than 2.6 mmol/L). It is a disorder that most commonly results from malignancy or primary hyperparathyroidism. Other causes of elevated calcium are less common and usually are not considered until malignancy and parathyroid disease are ruled out.

The normal range for serum calcium is 2.25 – 2.5 mmol/litre, however, just over half of the circulating calcium is protein bound, and therefore the level of circulating protein, principally albumin, must also be taken into consideration in making this measurement. The level for serum calcium is therefore frequently given as the „corrected level“ which has allowed for changes in albumin levels. In corrected level add 0.1 mmol/l to calcium concentration for every 4g/l that albumin is below 40g/l, and a similar substraction for raised albumin.

A rise in the level of calcium can produce a diverse collection of symptoms:

• at levels < 2.58 mmol/l – polyuria and polydipsia, dyspepsia, depression, mild cognitive impairment
• at levels < 3.5 mmol/l – all of the previous plus muscle weakness, constipation, anorexia and nausea, fatigue
• at levels > 3.5 mmol/l – all of the previous plus abdominal pain, vomiting, dehydration, lethargy, cardiac arrhythmias, shortened QT interval, coma, pancreatitis

Hypercalacemia is observed most often in chronic intoxications (aluminum), hyperparathyroidism, some neoplasms, bone metastases, and occasionally in theophylline and thiazide diuretics.
Untreated hypercalcaemia poses the risk of progressive mineralization of bone, hypercalciuria, nephrocalcinosis and deterioration to renal failure.

Hypercalcaemia is divided into PTH-mediated hypercalcaemia (primary hyperparathyroidism) and non-PTH-mediated hypercalcaemia.

Causes of hypercalcaemia

1. hyperparathyroidism and malignancy account for cca 90% of cases
2. abnormal parathyroid gland function
3. primary parathyroid hyperplasia
4. parathyroid carcinoma
5. multiple endocrine neoplasia
6. familial isolated hyperparathyroidism
7. familial hypocalciuric hypercalcaemia/familial benign hypercalcaemia
8. malignancy
9. solid tumor with humoral mediation of hypercalcaemia
10. hematologic malignancy
11. vitamin-D metabolic disorders
12. idiopathic hypercalcaemia of infancy
13. rebound hypercalcaemia after rhabdomyolysis
14. disorders related to high bone-turnover rates
15. prolonged immobilization
16. thiazide use
17. vitamin A intoxication
18. Paget's disease of the bone
19. renal failure
20. aluminum intoxication
21. milk-alkali syndrome

Treatment
When hypercalcaemia is mild and caused by primary hyperparathyroidism, patients may be followed closely by their doctor over time.
Severe hypercalcaemia causing symptoms and requiring hospitalization is treated aggressively with the intravenous fluids, bisphosphates, calcitonin, glucocorticoids, hemodialysis.

Prognosis
The prognosis of hypercalcaemia depends upon the cause of increased calcium levels. When the underlying cause is treatable and the treatment is initiated promptly, hypercalcaemia can have a good prognosis. However, when associated with malignancy that has progressed into development of hypercalcaemia, prognosis is poor.
Hypercalcaemia is potentially fatal. Early diagnosis is important, as the cause of high blood calcium is usally identified and treated to avoid long-term complications.
Signs and symptoms may be confused with those of end stage disease in terminal patients. In some patients, symptoms may be non-specific and have a slow onset. Some examples are anorexia, weakness, nausea, vomiting, and constipation.
In other cases, symptoms develop very quickly resulting from very rapidly rising calcium levels. This may result in a life threatening situation.