Calcium concentration is regulated by plasma membrane calcium receptor, PTH and its receptor, calcitonin and

its receptor, and by the actions of vitamin D on kidneys, bone, and intestines. PTH mobilizes calcium directly
by enhancing bone resorption, and indirectly, by stimulating one alpha-hydroxylase which increases vitamin D3
production, in turn, leading to increased absorption of calcium from the gut and increased bone resorption.
Primary hyperparathyroidism is due to a solitary adenoma or diffuse hyperplasia of the gland. In this condition,
there is an abnormal set point in the relation between calcium and PTH levels and calcium-independent PTH
secretion.  Familial hypocalciuric hypercalcemia is inherited autosomal dominant pattern and is due to an
inactivating mutation in the calcium-sensing receptor gene. Granulomatous lesions cause ectopic vitamin D
production. Transient neonatal hypercalcemia can rarely be seen in infants born to mothers with
hypoparathyroidism.
Hypercalcemia from hyperparathyroidism is mild and could go one for years and be asymptomatic.
Hypercalcemia from malignancy is associated with rapidly increasing calcium levels

Treatment for hypercalcemia is required if the patient is symptomatic or if the calcium level is more than 15
mg/dL, even in asymptomatic patients. The goals of treating hypercalcemia include increased elimination from
the extracellular fluid, reducing gastrointestinal (GI) absorption and decreasing bone resorption. Immediate
therapy is directed at restoring intravascular volume and promoting calcium excretion in the urine with an
infusion of 0.9% saline at twice the maintenance rate until any fluid deficit is replaced and diuresis occurs
(urine output ≥ 200 mL/h to 300 mL/h). Hemodialysis is the treatment of choice to rapidly decrease serum
calcium in patients with heart failure or renal insufficiency. Loop diuretics should be used with caution as even
though they may enhance renal excretion, paradoxical hypercalcemia can occur due to bone resorption.
Patients with hyperparathyroidism require surgical exploration and removal of the source of increased PTH
secretion. Postoperatively, patients need to be monitored closely for the development of hypocalcemia and
tetany. Bisphosphonates such as etidronate, pamidronate, and alendronate are the drugs of choice for
hypercalcemia of malignancy as they inhibit osteoclastic activity.
Calcitonin can be administered subcutaneously but in most cases, the effects are mild and limited to a few days.
Mithramycin can block the function of osteoclasts and is often administered to patients with malignancy-
associated hypercalcemia. but the drug has significant renal, liver, and bone marrow toxicity.
Hypercalcemia associated with excess vitamin D can be treated with steroids as they inhibit one alpha-
hydroxylase activity. Ketoconazole, an antifungal agent, has also been used in hypervitaminosis D as it inhibits
1-alpha-hydroxylase activity. Hypercalcemia of immobilization can be prevented by encouraging activity as
tolerated and adequate hydration. The specific cause of hypercalcemia needs to be identified, and treatment
directed accordingly.

https://www.ncbi.nlm.nih.gov/books/NBK430714/

https://www.aafp.org/afp/2003/0501/p1959.html
 HYPERCALCEMIA

Calcium Concentration

PTH Receptor

PTH mobilizes calcium

Directly Indirectly

Enhancing bone resorption Stimulating one alpha-hydroxylase

Increases vitamin D3 production

Increased absorption of calcium Increased bone resorption