Calcium - Kresser Institute Membership Site

REFERENCE RANGES FOR SERUM CALCIUM:

Laboratory reference range: 8.7–10.2 mg/dL

Functional reference range: 9.2–10.1 mg/dL

DESCRIPTION:

Calcium is a divalent ion that plays an important role in cell signaling, blood clotting, muscle contraction, and nerve function.^1,2 Virtually all calcium in the body is found within the bones and teeth.¹ A relatively small amount of calcium can be found extracellularly (i.e., within the serum) and within cells. Because of the potentially toxic effects of free intracellular calcium, calcium within cells is kept within membrane-bound organelles and released only under specific circumstances, such as muscle contraction or neurotransmitter release.³

Total body calcium levels are regulated by a complex interplay of factors that take place within the intestines, kidneys, and bone.⁴ Calcium homeostasis is regulated by parathyroid hormone (PTH), vitamin D, fibroblast growth factor 23 (FGF-23), calcitonin, and estrogen.^4,5 Calcium levels are chiefly governed by the parathyroid gland, which relies on calcium-sensing receptors to detect blood calcium levels and respond with appropriate changes in PTH secretion.⁵ Serum PTH and serum calcium are usually inversely correlated.⁶

PTH acts rapidly to increase blood calcium levels through multiple mechanisms, including increased bone resorption, increased reabsorption of calcium by the kidneys, increased vitamin D levels in the blood, and in turn, increased absorption of calcium in the small intestine. As serum calcium levels increase, PTH levels decrease.⁵ FGF-23 generally acts in opposition to PTH by lowering phosphate and vitamin D levels and by inhibiting PTH secretion itself.^4,5

Calcium in the serum exists in one of three forms: 40 percent is bound to albumin, 15 percent is bound to organic and inorganic anions (e.g., sulfate, phosphate, lactate, citrate), and the remaining 45 percent is ionized, or “free,” calcium.⁷ Total serum calcium concentration is generally a good reflection of total calcium, with exceptions of hypoalbuminemia, acid-base disorders, and chronic kidney disease.^4,7 In the presence of hypoalbuminemia, the true calcium level can be estimated by correcting for albumin using the following equation:⁷

Corrected [Ca] = Measured Total [Ca] + (0.8 (4.0 -[Alb]))

Hypercalcemia may be due to an abnormality in the action or regulation of PTH. For example, hypercalcemia and elevated PTH may co-occur in primary hyperparathyroidism due to impaired PTH negative feedback in the parathyroid gland. Hypercalcemia of malignancy may or may not be related to PTH.⁸ Calcium intake alone is rarely the cause of elevated serum calcium; however, excess vitamin D supplementation can give rise to hypercalcemia.⁹ Renal failure results in a state called tertiary hyperparathyroidism and, consequently, hypercalcemia.⁹

As with elevated serum calcium, hypocalcemia may or may not be related to abnormalities in PTH. Magnesium deficiency is a common cause of minor hypocalcemia; it can occur in the context of high, low, or normal PTH levels, since it can reduce PTH secretion or interfere with PTH function.¹⁰

Serum PTH is the most useful test for distinguishing among etiologies of hypocalcemia.¹¹ Serum magnesium, creatinine, phosphate, vitamin D metabolites (primarily 25-hydroxyvitamin D), and alkaline phosphatase can also provide helpful information.¹¹ An albumin level may be required to identify and correct for hypoalbuminemia.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^12-14

Nutrient imbalances
- Excessive vitamin D
- Excessive vitamin A
- Excessive calcium intake (rare)
Primary hyperparathyroidism
Hyperthyroidism
Adrenal insufficiency
Parenteral nutrition
Milk alkali syndrome
Familial hypocalciuric hypercalcemia
Familial isolated hyperparathyroidism
Acromegaly
Renal failure (tertiary hyperparathyroidism)
Multiple endocrine neoplasia
Pheochromocytoma
Malignancy
Chronic granulomatous disease
Immobility
Drugs
- Thiazide diuretics
- Lithium
- Theophylline

Low in:^10,11

States of low PTH (hypoparathyroidism)
- Hypomagnesemia with reduced PTH secretion
- Post-surgical (e.g., thyroidectomy, parathyroidectomy, radical neck dissection)
- Hungry bone syndrome (post-parathyroidectomy)
- Autoimmune (e.g., autoimmune polyglandular syndrome)
- Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)
- Isolated hypoparathyroidism due to activating antibodies to calcium-sensing receptor
- Radiation-induced destruction of parathyroid glands
- Various genetic disorders
- HIV infection
States of high PTH (secondary hyperparathyroidism in response to hypocalcemia)
- Vitamin D deficiency or resistance
- Parathyroid hormone resistance
- Hypomagnesemia with parathyroid hormone resistance
- Renal disease
- Loss of calcium from the circulation
  - Hyperphosphatemia
  - Tumor lysis
  - Acute pancreatitis
  - Osteoblastic metastases
  - Acute respiratory alkalosis
  - Sepsis or acute severe illness
- Drugs
  - Fluoride poisoning
  - Calcium chelators (EDTA, citrate, phosphate)
  - Inhibitors of bone resorption (e.g., bisphosphonates, calcitonin)
  - Cinacalcet
  - Foscarnet
  - Phenytoin

FUNCTIONAL RANGE INDICATIONS:

High in:¹³

Dehydration (causing mild or transient hypercalcemia)
Excessive vitamin D supplementation
Excessive calcium
Immobility
Drugs (e.g., lithium)

Low in:¹⁵

Dietary factors: caffeine, phosphates (found in soda), high intake of phytate
Vitamin D deficiency
Magnesium deficiency
Low stomach acid
Chronic renal failure
Alcoholism
Medications (bisphosphonates, diuretics, antibiotics, estrogen replacement therapies, insulin, excessive laxative use)

References: