Calcitriol - Kresser Institute Membership Site

Marker Name: Calcitriol

REFERENCE RANGES FOR SERUM CALCITRIOL:

Laboratory reference range: 19.9–79.3 pg/mL

Functional reference range: Same as conventional range

DESCRIPTION:

Calcitriol, also known as 1,25-dihydroxyvitamin D, is the most biologically active form of vitamin D.¹ It is tightly regulated by PTH and is directly responsible for increasing the intestinal absorption of calcium, increasing the resorption rate of bone, and decreasing the excretion of calcium and phosphate by the kidneys.¹ These three functions of calcitriol work to increase the level of calcium in the blood.² As such, vitamin D is important for the regulation of normal calcium levels. Normal calcium levels, regulated by the action of vitamin D, promote bone formation during development and prevent bone demineralization in older individuals.^1,2^,³ Adequate vitamin D is required for normal function of muscle tissue, nervous tissue, and cells of the immune system.⁴ Vitamin D deficiency, on the other hand, is associated with high blood pressure, heart attack, and cancer.⁴

Vitamin D may be ingested and absorbed from dietary sources and supplements. Generally, these forms of vitamin D, namely ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are biologically inactive. A third inactive form of vitamin D, 7-dehydrocholesterol, may be converted into vitamin D3 by UV light striking the skin.¹^,³ These forms of vitamin D must be metabolized by enzymes in the liver to produce the weakly active form of vitamin D, 25-hydroxyvitamin D (calcidiol).³ 25-hydroxyvitamin D may act directly in the body or be converted to 1,25-dihydroxyvitamin D (calcitriol) by enzymes in the kidney.^1,5 Calcitriol has a short half-life in the body, approximately four hours.³ Calcitriol is inactivated by the liver and excreted with the bile in the gastrointestinal tract.¹^,⁶

While 1,25-dihydroxyvitamin D (calcitriol) is the most biologically active form of vitamin D, it is not the routine test for vitamin D status. Serum 25-hydroxyvitamin D is the routine test and may be a good indicator of a person’s vitamin D status in many circumstances.^3,7 However, for the most complete picture of functional vitamin D status, it is best to test serum 25-hydroxyvitamin D along with serum calcitriol, serum PTH, serum calcium, and serum phosphorus. This will also help clarify vitamin D status in people with chronic renal failure, rickets, or those taking therapeutic calcitriol.⁸ Calcitriol measurements may also be useful in determining the cause of disorders of calcium or phosphorus metabolism.⁸

Abnormally high calcitriol levels usually reflect an elevated serum 25-hydroxyvitamin D level. Excess serum 25-hydroxyvitamin D is usually caused by excess intake of vitamin D.²It is possible that calcitriol levels could be increased due to deficient activity of degradative enzymes, particularly hepatic 24-hydroxylase; however, this is quite rare.⁹

Since vitamin D status is usually determined by measuring 25-hydroxyvitamin D levels, we know much more about what causes low 25-hydroxyvitamin D than calcitriol, specifically. Nonetheless, 25-hydroxyvitamin D levels are a useful surrogate in this case, given the well-characterized regulation of these vitamin D molecules. It is important to note, however, that calcitriol is more tightly regulated than calcidiol. Inadequate consumption, absorption, or synthesis of vitamin D may cause low calcitriol levels.^1,3,10,11 On the other hand, low serum calcitriol may result from increased liver metabolism and excretion, or, to a much lesser extent, excessive excretion from the kidneys.^1,3,10 Certain drugs can cause abnormally low calcitriol levels as well. The most well-known are anticonvulsant drugs, but certain antimicrobials and corticosteroids can cause low calcitriol levels.¹¹ The most common cause of low calcitriol levels, specifically, is chronic kidney disease.¹¹

If calcitriol is being measured, it usually means 25-hydroxyvitamin D levels are also being considered.^8,12 To clarify diagnosis, parathyroid hormone, serum calcium, and serum phosphorus should also be tested.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^2,10

Excessive intake
Hyperparathyroidism
Sarcoidosis
Hematological malignancy
Solid organ malignancy
Certain infections (mycobacterium, histoplasmosis)
Other granulomatous conditions

Low in:^2,11

Chronic kidney disease
Renal failure
Nephrotic syndrome
Normal pregnancy
Breastfeeding infants
Inadequate sunlight exposure
Obesity
Fat malabsorption
Hypoparathyroidism
Secondary hyperparathyroidism
Small bowel disease
Gastric bypass surgery
Pancreatic insufficiency
Advanced liver disease
Thermal burn injury with extensive skin damage
Hereditary vitamin D-resistant rickets (vitamin D-dependent rickets, type 2)
Cystic fibrosis
Drugs
- Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)
- Isoniazid
- Rifampin
- Corticosteroids
- Theophylline

FUNCTIONAL RANGE INDICATIONS:

High in:

Same as conventional indications

Low in:

Same as conventional indications

References: