Tag: Calcium Disorders

  • Tests in Calcium Disorders: Hypercalcemia

    Symptoms referable to hypercalcemia itself are very nonspecific; they include vomiting, constipation, polydipsia and polyuria, and mental confusion. Coma may develop in severe cases. There may be renal stones or soft tissue calcification. Hypercalcemia is most often detected on routine multitest biochemical screening panels, either in asymptomatic persons or incidental to symptoms from some disease associated with hypercalcemia (see the box on this page). In asymptomatic persons, primary hyperparathyroidism (PHPT) accounts for about 60% of cases. In hospital admissions, however, malignancy is the etiology for 40%-50% of cases and PHPT accounts for about 15%.

    Regulation of Serum Calcium Levels

    Regulation of serum calcium levels is somewhat complex. The major control mechanism is parathyroid hormone (PTH). Normally, parathyroid secretion of PTH is regulated by a feedback mechanism involving the blood calcium level. A decreased serum calcium level induces increased secretion of PTH, whereas an acute increase of the

    Selected Etiologies of Hypercalcemia

    Relatively common

    Neoplasia (noncutaneous)
    Bone primary
    Myeloma
    Acute leukemia
    Nonbone solid tumors
    Breast
    Lung
    Squamous nonpulmonary
    Kidney
    Neoplasm secretion of parathyroid hormone-related protein (PTHrP, “ectopic PTH”)
    Primary hyperparathyroidism (PHPT)
    Thiazide diuretics
    Tertiary (renal) hyperparathyroidism
    Idiopathic
    Spurious (artifactual) hypercalcemia
    Dehydration
    Serum protein elevation
    Lab technical problem

    Relatively uncommon

    Neoplasia (less common tumors)
    Sarcoidosis
    Hyperthyroidism
    Immobilization (mostly seen in children and adolescents)
    Diuretic phase of acute renal tubular necrosis
    Vitamin D intoxication
    Milk-alkali syndrome
    Addison’s disease
    Lithium therapy
    Idiopathic hypercalcemia of infancy
    Acromegaly
    Theophylline toxicity

    serum calcium level decreases secretion of PTH. PTH has a direct action on bone, increasing bone resorption and release of bone calcium and phosphorus. In addition, PTH increases the activity of the activating enzyme cyclic adenosine monophosphate (AMP) in the proximal tubules of the kidney, which increases conversion of calcidiol (25-hydroxyvitamin D) to calcitriol (1,25-dihydroxy-vitamin D). Calcitriol has metabolic effects that help to increase serum calcium levels, such as increased renal reabsorption of calcium, increased GI tract absorption of calcium, and the drawing out of some calcium from bone. On the other hand, an increased calcitriol level also initiates a compensatory series of events that prevents the calcium-elevating system from overreacting. An increased calcitriol level inhibits renal tubule phosphate reabsorption, which results in loss of phosphorus into the urine. This leads to a decreased serum phosphate level, which, in turn, inhibits production of calcitriol. The actions of PTH, phosphate, and calcitriol produce a roughly reciprocal relationship between serum calcium and phosphate levels, with elevation of one corresponding to a decrease of the other. Both PTH (through cyclic AMP) and phosphate act on the same enzyme (25-OH-D 1 a-hydroxylase), which converts calcidiol to calcitriol.

    Besides PTH, a hormone called “calcitonin” has important, although subsidiary, effects on calcium metabolism. Calcitonin is produced in the thyroid gland, and secretion is at least partially regulated by serum calcium levels. Acute elevation of serum calcium leads to increased calcitonin secretion. Calcitonin inhibits bone resorption, which decreases withdrawal of calcium and phosphorus and produces a hypocalcemic and hypophosphatemic effect that opposes calcium-elevating mechanisms.