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.
- Genetic diseases
Behavioral causes
- Physical activity
- Immobilization
Causes related to disease
Blood, blood-forming organs – immune system (D50-D90).
- Sarcoidosis (Boeck, M.)
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).
- Cardiac arrhythmias (arrhythmias; bradycardia (heartbeat too slow: < 60 beats per minute)).
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]
- Bronchial carcinoma (lung cancer).
- Lymphoma – e.g. Hodgkin’s disease
- Mammary carcinoma (breast cancer)
- Monoclonal gammopathy – disease associated with an increase in monoclonal immunoglobulins or their parts (light or heavy chains) within the gamma fraction of serum proteins.
- Plasmocytoma (multiple myeloma).
- Prostate carcinoma (prostate cancer)
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).
- Acute renal failure (ANV) or recovery period after acute renal failure (ANV).
Medication
- Calcium-containing antacids
- Hormones
- Antiestrogens (tamoxifen)
- Parathyroid hormone analogue (teriparatide).
- Lithium
- Thiazides (reduce the excretion of calcium).
- Vitamin D supplements/vitamin D analogues
- Vitamin A supplements