Primary hyperparathyroidism and malignancy account for about 90% of cases of hypercalcaemia.[8][9]
Parathyroid function[edit] => Primary hyperparathyroidism Solitary parathyroid adenoma Primary parathyroid hyperplasia Parathyroid carcinoma Multiple endocrine neoplasia (MEN1 & MEN2A) Familial isolated hyperparathyroidism[10]&Solitary parathyroid adenoma&Primary parathyroid hyperplasia&Parathyroid carcinoma&Multiple endocrine neoplasia (MEN1 & MEN2A)&Familial isolated hyperparathyroidism[10]&Lithium use&Familial hypocalciuric hypercalcemia/familial benign hypercalcemia[11][12][13
Solid tumour with metastasis (e.g. breast cancer or classically squamous cell carcinoma, which can be PTHrP-mediated)&Solid tumour with humoral mediation of hypercalcaemia (e.g. lung cancer, most commonly non-small cell lung cancer[14] or kidney cancer, phaeochromocytoma)&Haematologic cancers (multiple myeloma, lymphoma, leukaemia)&Ovarian small cell carcinoma of the hypercalcemic typ
Vitamin-D disorders[edit] => Hypervitaminosis D (vitamin D intoxication)&Elevated 1,25(OH)2D (see calcitriol under Vitamin D) levels (e.g. sarcoidosis and other granulomatous diseases such as tuberculosis)&Idiopathic hypercalcaemia of infancy[15]&rebound hypercalcaemia after rhabdomyolysi
High bone-turnover rates[edit] => Hyperthyroidism&Multiple myeloma&Prolonged immobilization&Paget's disease&Thiazide use&Vitamin A intoxicatio
Kidney failure[edit] => Severe secondary hyperparathyroidism&Tertiary hyperparathyroidism&Aluminium intoxication&Milk-alkali syndrom
Other[edit] => Adrenal insufficiency&Zollinger Ellison syndrom
Abnormal heart rhythms can also result, and ECG findings of a short QT interval[16] suggest hypercalcaemia. Significant hypercalcaemia can cause ECG changes mimicking an acute myocardial infarction.[17] Hypercalcaemia has also been known to cause an ECG finding mimicking hypothermia, known as an Osborn wave.[18]
The neuromuscular symptoms of hypercalcemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization.[5] This results in diminished deep tendon reflexes (hyporeflexia), and skeletal muscle weakness.[6] There is a general mnemonic for remembering the effects of hypercalcaemia: "Stones, Bones, Groans, Thrones and Psychiatric Overtones"
Stones (renal or biliary) (see calculus)&Bones (bone pain)&Groans (abdominal pain, nausea and vomiting)&Thrones (polyuria) resulting in dehydration&Psychiatric overtones (Depression 30–40%, anxiety, cognitive dysfunction, insomnia, coma
Other symptoms include cardiac arrhythmias (especially in those taking digoxin), fatigue, nausea, vomiting (emesis), anorexia, abdominal pain, constipation, & paralytic ileus. If renal impairment occurs as a result, manifestations can include polyuria, nocturia, and polydipsia.[6] Psychiatric manifestation can include emotional instability, confusion, delirium, psychosis, & stupor.[6] Limbus sign seen in eye due to hypercalcemia.[citation needed]
Hypercalcemia can result in an increase in heart rate[7] and a positive inotropic effect (increase in contractility).
Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l).[6] Severe hypercalcaemia (above 15–16 mg/dL or 3.75–4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result. The high levels of calcium ions decrease the neuron membrane permeability to sodium ions, thus decreasing excitability, which leads to hypotonicity of smooth and striated muscle. This explains the fatigue, muscle weakness, low tone and sluggish reflexes in muscle groups. The sluggish nerves also explain drowsiness, confusion, hallucinations, stupor and / or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.[citation needed]