Calcium Excess (Hypercalcemia): Causes

Pathogenesis (development of disease)

Calcium is subject to calcium homeostasis, so calcium distribution is usually assured:

  • 98% of the total calcium is located in the skeleton.
  • 2% of the total calcium is located in the extracellular space (outside the body cells)
    • About 50% is free or ionized calcium.
    • About 45% of serum calcium is protein-bound (of which 90% is bound to albumin)
    • 5 % are present as complex-bound calcium

The biologically active portion is the free calcium! Causes of tumor hypercalcemia are:

  • Hypercalcemia in local osteolysis (bone loss; e.g., due to malignant neoplasms/malignant neoplasms).
  • Humoral hypercalcemia (PTHrP).
  • Hypercalcemia in malignant lymphoma (eg, Hodgkin’s disease).

The following factors are involved in tumor hypercalcemia:

  • Group E prostaglandins
  • PTH related peptides (PTHrP)
  • IL-1, IL-6, 1,25(OH)2vitamin D

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents
    • Genetic diseases
      • Familial benign hypocalciuric hypercalcemia (FBHH) – rare, autosomal-dominant inherited disorder of calcium balance caused by an inactivating mutation of the calcium-sensitive receptor in the parathyroid gland and kidneys; hypercalcemia in childhood; laboratory: normal PTH concentration, hypermagnesemia (magnesium excess), and low urine calcium/magnesium clearance.

Behavioral causes

  • Physical activity
    • Immobilization

Causes related to disease

Blood, blood-forming organs – immune system (D50-D90).

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • Calcium-alkali syndrome (CAS; synonym: Burnett syndrome) – calcium metabolic disorder resulting from an excess of readily absorbable alkalis (e.g., as bicarbonates) and calcium (e.g., via milk).
  • Hyperthyroidism (hyperthyroidism)
  • Hypomagnesemia
  • Idiopathic hypercalcemia in childhood (William’s syndrome, developmental disorder).
  • Metabolic alkalosis – metabolic alkalosis; metabolic disorder characterized by bicarbonate elevation or loss of hydrogen ions.
  • Addison’s disease (adrenocortical insufficiency).
  • Primary hyperparathyroidism (pHPT) – primary disease of the parathyroid glands with increased production of parathyroid hormone and resulting hypercalcemia (excess calcium) [25% of cases].

Cardiovascular system (I00-I99).

Musculoskeletal system and connective tissue (M00-M99).

  • Paget’s disease (synonyms: Paget’s disease of bone) – disease of the skeletal system with bone remodeling; hypercalcemia here exclusively in bedriddenness due to immobilization.

Liver, gallbladder and bile ducts – pancreas (pancreas) (K70-K77; K80-K87).

  • Constipation (constipation)

Neoplasms – tumor diseases (C00-D48) [tumor hypercalcemia; 65% of cases]

Psyche – nervous system (F00-F99; G00-G99)

  • Acute confusion
  • Delir

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99).

  • Abnormal weight loss
  • Anuria – lack of urine output (maximum 100 ml/24 h).
  • Fatigue
  • Nocturia – urination at night
  • Oliguria – decreased amount of urine with a daily maximum of 500 ml.

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

Medication

  • Calcium-containing antacids
  • Hormones
  • Lithium
  • Thiazides (reduce the excretion of calcium).
  • Vitamin D supplements/vitamin D analogues
  • Vitamin A supplements