Hypercalcemia
| Classification according to ICD-10 | |
|---|---|
| E83.59 | Calcium metabolism disorders, unspecified |
| ICD-10 online (WHO version 2019) | |
Hypercalcemia (also called hypercalcemia ) is a disorder of the calcium and phosphate balance in which there is an increased calcium level in the blood serum . The limit value is (depending on the laboratory) a concentration of ionized (unbound) calcium> 1.3 m mol / l or a total calcium concentration> 2.7 mmol / l. The free calcium is the physiologically relevant parameter; when interpreting the total calcium concentration, deviations from the normal plasma protein concentration or from the normal pH value must be taken into account, as these parameters influence the proportion of free calcium. The prevalence of hypercalcaemia among hospitalized patients is approximately 1%. From a total serum calcium of> 3.5 mmol / l, one speaks of a hypercalcemic crisis, where polyuria , vomiting , desiccosis with fever , psychosis and finally coma occur.
causes
Hypercalcemia can develop in the body in three different ways. By shifting the bone metabolism towards bone resorption, osteoclasts release more calcium, which passes into the bloodstream. Increased calcium uptake through the intestine and decreased excretion of calcium in the urine are less common mechanisms in the development of hypercalcaemia.
One possible cause of hypercalcemia is bone loss and calcium release from a malignant tumor disease. Calcium can be released through the direct invasion of bone metastases . Many tumors also produce factors that can increase calcium absorption from the bone. The parathyroid hormone-related protein (PTHrP) produced by tumor cells is similar to the body's own parathyroid hormone and activates the parathyroid hormone receptor on osteoclasts. Myeloma cells and lymphoblasts from lymphomas can increase osteoclast activity by producing interleukin-1-alpha, interleukin-1-beta and interleukin-6, as well as tumor necrosis factor . In the context of Hodgkin's disease or T-cell lymphoma, tumor cells can produce calcitriol and thus an increased calcium intake.
The most common cause of hypercalcaemia is primary hyperparathyroidism (overactive parathyroid glands). Here, a benign parathyroid nodule, a diffuse cell proliferation of one of four parathyroid glands due to an overproduction of parathyroid hormone, increases the calcium level in the blood. Another common cause is the onset of vitamin D substitution. Secondary hyperparathyroidism, which occurs almost exclusively in chronic kidney failure , only rarely leads to manifest hypercalcemia, since the calcium absorption in the body is reduced due to the mostly simultaneous calcium deficiency.
An overactive thyroid , acromegaly, or pheochromocytoma can also lead to hypercalcemia. Granulomatous diseases can also increase the calcium level in the blood through overproduction of calcitriol in the macrophages that form the granulomas. This is common with sarcoid . Cases of tuberculosis , leprosy and beryllias have also been described.
Rare genetic diseases can be associated with hypercalcaemia. In metaphyseal chondrodysplasia type Jansen , a mutation in the parathyroid hormone receptor leads to a disturbed bone and calcium metabolism. In familial benign hypocalciuric hypercalcemia , a mutation of the G-protein-coupled calcium receptor, which is used in the body to determine the blood calcium level, leads to hypercalcemia, but this does not cause any threatening symptoms.
Sudden immobilization can lead to hypercalcaemia, especially in previously active patients with active bone metabolism. Hypercalcemia also occurs in around a quarter of patients who suffer acute kidney failure as part of rhabdomyolysis . This is returned by mobilizing calcium from the damaged muscle cells.
Overloading the body with vitamin A or vitamin D can lead to hypercalcaemia via the increase in calcium absorption. Thiazide diuretics inhibit calcium excretion from the kidneys. The same applies to the psychotropic drug lithium . When taking high doses of calcium and antacids, increased calcium intake can lead to milk-alkali syndrome .
complaints
The development of symptoms is variable and depends primarily on the speed at which the hypercalcemia develops. Metabolic disorders that develop quickly lead to complaints even with slightly elevated laboratory values, while disorders that develop slowly can remain asymptomatic. The early symptoms show increased fatigue, muscle weakness, concentration disorders , nervousness or even depression . Subsequently, digestive tract complaints develop. This leads to nausea, constipation , vomiting and, rarely, stomach ulcers or inflammation of the pancreas . In the kidneys, the increased calcium level leads to an increase in the amount of urine , which leads to tubulointerstitial kidney damage in the sense of nephrocalcinosis due to fluid loss and the deposition of calcium crystals . Calcium stones can also appear on the kidneys or the urinary tract. As the blood salt disorder progresses, the neuropsychiatric symptoms can develop into a coma . The build-up of calcium crystals can cause conjunctivitis or keratititis in the eye . In the heart, hypercalcemia leads to an increase in contractility and can lead to increased toxicity of digitalis glycosides .
diagnosis
The laboratory diagnosis is based on increased serum calcium. To clarify the cause of hypercalcaemia, a tumor search (e.g. abdominal sonography, chest X-ray, mammography in women) must be initiated and the following parameters must also be determined: parathyroid hormone (PTH intact), parathyroid hormone-related peptide (PTHrP), 1.25- (OH) 2 -Vitamin D 3 , 25-OH-Vitamin D 3 .
therapy
Primary (benign) hyperparathyroidism (overactive parathyroid gland) is finally cured by a simple endoscopic procedure after prior scintigraphy of the polar bodies. The hypercalcemia disappears for a short time. Possibly. temporary anxiolytics are useful. The treatment of malignant hypercalcaemia should be adapted to the severity of the symptoms. The best therapy is the treatment of the underlying disorder of calcium metabolism. However, due to the clinical picture or the fact that the underlying disease cannot be treated, it is often necessary to lower the calcium level in the blood temporarily or permanently. There is consensus that a total calcium of 3.5 mmol / l with corresponding symptoms represents a potentially life-threatening emergency in the sense of a hypercalcemic crisis and requires an immediate lowering of the calcium level under intensive medical conditions.
The intravenous administration of fluids can lower the calcium in the blood. Since most patients with hypercalcemia are dehydrated, this is the most important measure to protect kidney function. The administration of loop diuretics increases the excretion of calcium and fluid via the kidneys. Treatment with fluids and diuretics can be made difficult by pre-existing cardiovascular disease or renal insufficiency.
The hormone calcitonin , which lowers the calcium level within hours, can be administered for acute lowering of the calcium level . The use of the hormone as monotherapy does not make sense, as a complete loss of effectiveness of the hormone can be expected within two days due to downregulation of the calcitonin receptor on the target cells. In severely affected patients, calcitonin should be administered together with a slower-acting drug and ensures a short-term drop in calcium levels until other drugs or measures take effect.
Bisphosphonates , which inhibit the breakdown of bone by osteoclasts and the formation of calcitriol, are the agents of choice for permanently lowering the calcium level . Active substances of this class can be administered intravenously or orally depending on the severity of the clinical picture. Many manufacturers advise against use in patients with kidney damage due to a lack of data, but due to their efficiency, the drugs are often used anyway. Bisphosphonates induce a drop in calcium levels within 48 hours. The maximum effect of this drug class occurs after around six days and a measurable effect lasts for up to thirty days. Current active ingredients are pamidronate and zoledronate , with zoledronate reducing the calcium level more than pamidronate. The dose of the medication must be adjusted to the calcium level and, in the case of zoledronate, also to the kidney function. In order to avoid the risk of kidney damage, the infusion rate of the active ingredient should be increased in patients with kidney failure. The dose of pamidronate does not need to be reduced if the kidneys are weak. Zoledronate has been tested in this indication up to creatinine values of 4.5 mg / dl. In this case, the dosage should be based on the risk-benefit assessment; according to the specialist information, full dosage can also be used in tumor hypercalcaemia.
Corticosteroids antagonize the action of calcitriol and are particularly effective in patients with granulomatous diseases or a vitamin D overload. The antifungal ketoconazole also inhibits the formation of calcitriol and can be used off-label in the treatment of hypercalcaemia .
In the case of increased calcium levels with minor symptoms, Cinacalcet can be used in the presence of hyperparathyroidism , which increases the sensitivity of the body's own calcium receptor.
In the case of life-threatening, therapy-refractory hypercalcaemia, emergency hemodialysis is indicated, in which calcium is removed from the patient's blood by using a calcium-free or low-calcium dialysate.
forecast
The lethality of a hypercalcemic crisis is up to 50%.
Pseudohypercalcemia
About half of the serum calcium is bound to albumin and other serum proteins. However, only the free protein-unbound calcium is decisive for the physiological effect, but it is in dynamic equilibrium with the protein-bound calcium. If the protein level in the blood is high, pseudohypercalcemia can occur. Apparently the calcium level in the blood is increased, but in fact only the protein-bound portion is increased and the free serum calcium is normal.
See also
Individual evidence
- ↑ a b c d e f g h i j k l m Bryan Kestenbaum, Tilman B. Drüeke: Disorders of Calcium, Phosphate, and Magnesium Metabolism. In: Jürgen Floege, Richard J. Johnson, John Feehally: Comprehensive Clinical Nephrology. 4th edition. St. Louis 2010, pp. 130-148.
- ↑ a b p Minisola, J. Pepe, S. Piemonte, C. Cipriani: The diagnosis and management of hypercalcaemia. In: BMJ. 350, Jun 2, 2015, p. H2723. PMID 26037642
- ↑ O. Hopfer, A. Gawliczek, MG Kiehl: Tumor-induced hypercalcemia. In: Internist. 54, 2013, pp. 1043-1050. PMID 23934479
- ↑ S. Ahmad, G. Kuraganti, D. Steenkamp: Hypercalcemic crisis: a clinical review. In: Am J Med. 128 (3), Mar 2015, pp. 239–245. PMID 25447624
- ↑ Zometa
