Calcitriol (1,25 di-OH Vit D)

Optimal Result: 24.8 - 81.5 pg/mL.

Calcitriol: The Active Form of Vitamin D

Calcitriol, also known as 1,25-dihydroxyvitamin D [1,25(OH)2D], is the biologically active form of Vitamin D. It plays a crucial role in maintaining calcium and phosphorus levels in the body, supporting bone health through the process of mineralization.

Key Functions of Calcitriol:

  • Calcium Absorption and Homeostasis: Calcitriol enhances the absorption of calcium in the intestines, helping regulate calcium levels and ensuring proper mineral balance in the body.
  • Bone Health: It promotes the release of calcium from bones when levels in the blood are low, ensuring a steady supply for vital functions like muscle contraction and nerve signaling.
  • Renal Calcium Reabsorption: In the kidneys, calcitriol increases the reabsorption of calcium, reducing the loss of this essential mineral through urine.
  • Immune Regulation: Emerging research highlights calcitriol’s role in modulating the immune system, helping in the differentiation of immune cells and promoting an appropriate immune response.

Vitamin D Metabolism & Function:

Vitamin D enters the body primarily in two ways:

  1. Skin Production: Exposure to ultraviolet B (UVB) rays from sunlight triggers the synthesis of vitamin D in the skin.
  2. Dietary Intake: Vitamin D is consumed in the form of cholecalciferol (vitamin D3) from animal-based foods, ergocalciferol (vitamin D2) from plant-based sources, or as dietary supplements.

Once in the body, vitamin D undergoes two critical transformations:

  • Conversion to Calcidiol: In the liver, vitamin D is converted into 25-hydroxyvitamin D (calcidiol), the main circulating form. This form is commonly used in blood tests to assess vitamin D levels.
  • Conversion to Calcitriol: The kidneys then convert calcidiol into the active hormone calcitriol (1,25-dihydroxyvitamin D), through an enzyme called 1a-hydroxylase. The production of calcitriol is tightly regulated by parathyroid hormone (PTH) and is influenced by serum calcium and phosphate levels.

Importance of Testing Calcitriol Levels:

  • Chronic Kidney Disease (CKD): Patients with CKD often have reduced levels of calcitriol due to impaired kidney function. Testing for calcitriol is valuable in managing their calcium and bone health.
  • Parathyroid Disorders: Abnormal calcitriol levels can help diagnose conditions related to parathyroid function, including hyperparathyroidism and hypoparathyroidism.

References:

  1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357(3):266-281. PMID: 17634462
  2. Holick MF, et al. Evaluation, treatment, and prevention of vitamin D deficiency: Endocrine Society guideline. J Clin Endocrinol Metab. 2011; 96(7):1911-1930. PMID: 21646368
  3. Norman AW. From vitamin D to hormone D: Vitamin D endocrine system. Am J Clin Nutr. 2008; 88(2):491S-499S. PMID: 18689389
  4. Llach F, Velasquez Forero F. Secondary hyperparathyroidism in CKD. Am J Kidney Dis. 2001; 38(5 Suppl 5). PMID: 11689384
  5. Malloy PJ, Feldman D. Genetic disorders in vitamin D action. Endocrinol Metab Clin North Am. 2010; 39(2):333-346. PMID: 20511055
  6. Bikle DD. Vitamin D metabolism and clinical applications. Chem Biol. 2014; 21(3):319-329. PMID: 24529992

What does it mean if your Calcitriol (1,25 di-OH Vit D) result is too high?

Elevated levels of calcitriol (1,25-dihydroxyvitamin D) can signify a variety of conditions, as calcitriol is involved in regulating calcium and phosphate metabolism. High levels may indicate an abnormal regulation of calcium in the body. Here are some possible implications of elevated calcitriol levels:

1. Primary Hyperparathyroidism:

→ Cause: In this condition, the parathyroid glands produce excess parathyroid hormone (PTH), which stimulates the kidneys to produce more calcitriol.

→ Effect: Elevated calcitriol increases intestinal absorption of calcium, leading to hypercalcemia (high blood calcium levels). This can result in symptoms like kidney stones, bone pain, and fatigue.

2. Granulomatous Diseases:

→ Examples: Conditions such as sarcoidosis, tuberculosis, or certain fungal infections.

→ Cause: In granulomatous diseases, immune cells (macrophages) in granulomas can produce calcitriol independent of normal regulatory control by PTH.

→ Effect: This leads to increased calcitriol and elevated calcium absorption, potentially resulting in hypercalcemia.

3. Lymphomas:

→ Cause: Some types of lymphoma can cause unregulated production of calcitriol by the tumor cells.

→ Effect: This increases calcium levels in the blood, leading to hypercalcemia, which may manifest as fatigue, nausea, confusion, and other systemic symptoms.

4. Vitamin D Intoxication:

→ Cause: Excessive intake of vitamin D supplements can lead to elevated levels of calcidiol (25-hydroxyvitamin D), which the kidneys convert to calcitriol.

→ Effect: Increased calcitriol enhances calcium absorption from the intestines, causing hypercalcemia and its associated symptoms.

5. Idiopathic Hypercalciuria:

→ Cause: In some individuals, elevated calcitriol leads to excessive calcium reabsorption in the kidneys and intestines.

→ Effect: This condition can result in elevated urinary calcium excretion (hypercalciuria), which increases the risk of kidney stones.

6. Chronic Kidney Disease (CKD) with Activated Renin-Angiotensin System:

→ Cause: In some cases of CKD, dysregulation of the renin-angiotensin system can enhance calcitriol production.

→ Effect: This can exacerbate calcium imbalances, though it is less common compared to calcitriol deficiency in CKD.

Conclusion:

Elevated calcitriol levels usually point to a disturbance in calcium and phosphate metabolism. This can be due to hormonal imbalances (such as in hyperparathyroidism), disease conditions that bypass normal regulatory controls (such as granulomatous diseases or lymphomas), or excessive vitamin D intake. Testing for calcitriol levels, alongside other markers like calcium, phosphate, and PTH, is crucial for diagnosing the underlying cause.

What does it mean if your Calcitriol (1,25 di-OH Vit D) result is too low?

Low calcitriol levels is one of the earliest changes to occur in persons with early kidney failure.

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