Why does hypercalcemia cause neurological symptoms

Hypercalcemic emergencies are possible but uncommon. Most cases are caused either by primary hyperparathyroidism HPT or malignancy. The condition can affect almost every organ system in the body. Symptoms are nonspecific and are related to the severity and rate of change of the serum calcium level, although neurologic dysfunction is an uncommon feature with mild hypercalcemia—patients can experience slight difficulties in concentrating but also experience depression, confusion, and coma as the condition becomes more severe.

Treatment depends on the cause of the disorder. Hypercalcemia is usually detected initially as an elevation of total plasma calcium levels rather than ionized calcium levels. The total calcium level is low in patients with low levels of binding proteins hypoalbuminemia and higher in those with high levels of binding proteins.

Although rare, this can result in pseudohypercalcemia—for example, in patients with hyperalbuminemia secondary to dehydration and in some patients with multiple myeloma.

The total plasma calcium level, therefore, must be corrected for the albumin level. Normal calcium levels range from 8. The calcium concentration [Ca] usually changes by 0. Thus, this formula estimates the actual total plasma calcium level:. Acidosis decreases the amount of calcium bound to albumin whereas alkalosis increases the bound fraction of calcium. The remainder is ionized calcium that is biologically active.

Measuring ionized calcium avoids issues with binding proteins. These and other causes are summarized in Table 1. Symptoms of hypercalcemia Table 2 are nonspecific and are related to the severity and rate of change of the serum calcium level. Symptoms are more severe with acute changes than with chronic calcium level elevation.

Symptoms of underlying diseases—malignancy, sarcoidosis, and tuberculosis, for example—causing hypercalcemia may dominate the clinical picture. A normal extracellular calcium concentration is necessary for normal neuromuscular function. Thus, neurologic dysfunction is the major feature of hypercalcemic states.

Patients can experience slight difficulties in concentrating to depression, confusion, and coma. These symptoms may resolve or improve after the hypercalcemia is corrected.

Chronic hypercalcemia may result in the formation of renal calculi. Hypercalciuria is the main factor in stone formation, but increased calcitriol production in primary HPT also plays a role.

Mechanisms include downregulation of water channels aquaporin 2 and tubulointerstitial injury caused by calcium deposition. Renal tubular acidosis and renal insufficiency are rare. Chronic hypercalcemic nephropathy may continue to worsen after the hypercalcemia is corrected. Hypertension can develop in patients with hypercalcemia as a result of renal insufficiency, calcium-mediated vasoconstriction, or both.

Hypertension may or may not resolve after the hypercalcemia is corrected. Cardiac effects include short QT intervals, which may increase sensitivity to digitalis, and deposition of calcium in the heart valves, myocardium, or coronary arteries. Constipation, anorexia, nausea, and vomiting are often prominent symptoms whereas acute pancreatitis via activation of trypsinogen in pancreatic parenchyma and peptic ulcer disease via stimulation of gastrin secretion are unusual.

Fatigue, musculoskeletal weakness, and pain are the only symptoms that correlate with increasing levels of serum calcium. Primary HPT can occur at any age but is most common in the 6th decade of life. It is 3 to 4 times more common in women than in men. The incidence of primary HPT increases with age in both sexes but more so in women after menopause.

The incidence greatly increases again at ages 70 to 79 for women—to —but remains lower at 95 for men. The incidence of primary HPT is highest among blacks 92 women; 46 men followed by whites 81 women; 29 men while rates for Asians 52 women, 28 men and Hispanics 49 women, 17 men are lower.

The underlying pathophysiology of primary HPT is excessive secretion of parathyroid hormone PTH , which leads to increased bone resorption by osteoclasts, increased intestinal calcium absorption, and increased renal tubular calcium reabsorption. The resulting hypercalcemia is often also accompanied by low-normal or decreased serum phosphate levels because PTH inhibits proximal tubular phosphate reabsorption.

Patients with primary HPT can present with any of the clinical manifestations summarized in Table 2. This diagnosis should be considered in any patient presenting with kidney stones, bone disease, or hypercalcemic crisis. Some of these patients may have calcium levels in the upper range of normal. Most calculi are composed of calcium oxalate, and the main factor in their pathogenesis is hypercalciuria.

Although PTH stimulates calcium reabsorption in the distal tubule, the kidney is overwhelmed by the increased amount of filtered calcium resulting from increased serum calcium levels.

Patients with increased vitamin D levels are more likely to have hypercalciuria and nephrolithiasis. Although bone disease is rare in HPT, it can develop in severe, long-standing cases or those caused by parathyroid carcinoma and in secondary or tertiary HPT associated with chronic renal insufficiency. Some patients with HPT also have low bone mineral density, but it is unclear whether the incidence is higher in these patients than in healthy people.

Some studies have reported decreased bone mineral density in untreated cases 3 but others have not. In one cohort of 1, patients with primary HPT in Uppsala, Sweden, only the men had an increased risk for cervical hip fractures. Abdominal pain, pancreatitis, peptic ulcer disease, nausea, and vomiting are common in these patients. The mechanism whereby a crisis develops is not clear, but dehydration, intercurrent illness, and infarction of a parathyroid adenoma may play a role.

Several studies have found excessive mortality in patients with HPT, with most of the excess caused by cardiovascular disease. The largest study, which included 4, Swedish patients, showed risk ratios for death from cardiovascular disease of 1.

The phosphorus level may be low but is usually just in the low-normal range. A subgroup of individuals with normal calcium levels and permanently elevated PTH levels may be recognized as having primary HPT if all causes of secondary HPT have been ruled out.

Urinary calcium excretion is measured by a hour urine collection, which should also specify total volume and urine creatinine levels. A careful family history is paramount to recognizing familial forms of primary HPT. In these cases, screening for pheochromocytoma is important before considering surgical treatment.

In some cases, a less invasive surgical approach can be used in which the abnormal parathyroid glands are localized preoperatively using ultrasound, Tcm sestamibi scintigraphy, or magnetic resonance imaging. The accuracy of these radiologic modalities is variable. They are not required for the diagnosis of HPT but serve mainly as guides for surgical strategy.

For more severe hypercalcemia, your doctor might recommend medications or treatment of the underlying disease, including surgery. Problems associated with overactive parathyroid glands often can be cured by surgery to remove the tissue that's causing the problem.

In many cases, only one of a person's four parathyroid glands is affected. A special scanning test uses an injection of a small dose of radioactive material to pinpoint the gland or glands that aren't working properly.

You might start by seeing your primary care provider. However, you'll likely be referred to a doctor who specializes in treating hormonal disorders endocrinologist.

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Rheumatol Int ;36 7 Depending on your age, kidney function, and bone effects, you might need surgery to remove the abnormal parathyroid glands. This procedure cures most cases of hypercalcemia caused by hyperparathyroidism.

This lowers your calcium level by decreasing PTH production. If you have osteoporosis, your doctor might have you take bisphosphonates to lower your risk of fractures. If you have cancer, your doctor will discuss treatment options with you to help you determine the best ways to treat hypercalcemia. You might be able to get relief from symptoms through intravenous fluids and medications like bisphosphonates.

This might make it easier for you to deal with your cancer treatments. The medication cinacalcet can also be used to treat high calcium levels due to parathyroid cancer.

Research suggests it may also have a role in the treatment of hypercalcemia due to other cancers as well. Hypercalcemia can cause kidney problems, such as kidney stones and kidney failure. Other complications include irregular heartbeats and osteoporosis. Hypercalcemia can also cause confusion or dementia since calcium helps keep your nervous system functioning properly.

Serious cases can lead to a potentially life-threatening coma. Your long-term outlook will depend on the cause and how severe your condition is. Your doctor can determine the best treatment for you. Talk to your doctor regularly to stay informed and ask questions.

Be sure to keep up with any recommended follow-up tests and appointments. You can do your part to help protect your kidneys and bones from damage due to hypercalcemia by making healthy lifestyle choices. Make sure you drink plenty of water. This will keep you hydrated, keep blood levels of calcium down, and decrease your risk of developing kidney stones.

Smoking also causes many other health issues. Quitting smoking can only help your health. A combination of physical exercises and strength training can keep your bones strong and healthy. Talk to your doctor first to find out what types of exercises are safe for you.