Test Catalog

Test Id : IFG23

Intact Fibroblast Growth Factor 23, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosing and monitoring tumor induced osteomalacia

 

Diagnosing X-linked hypophosphatemia or autosomal dominant hypophosphatemic rickets

 

Diagnosing familial tumoral calcinosis with hyperphosphatemia

Highlights

Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate homeostasis.

 

FGF23 measurements are useful in the differential diagnosis of hypophosphatemic diseases.

 

Intact FGF23 is elevated in patients with tumor induced osteomalacia (TIO) or X-linked hypophosphatemia (XLH).

Method Name
A short description of the method used to perform the test

Chemiluminescence Based Quantitative Sandwich Immunoassay.

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Intact Fibroblast Growth Factor 23

Aliases
Lists additional common names for a test, as an aid in searching

FGF23

Intact-FGF23

Autosomal Dominant Hypophosphatemic Rickets

Familial Tumoral Calcinosis with Hyperphosphatemia

Fibroblast Growth Factor 23

Oncogenic Osteomalacia

Phosphatonin

X-linked Hypophosphatemia

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial.

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

Renal Diagnostics Test Request (T830)

Oncology Test Request (T729)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.25 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
Frozen 90 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosing and monitoring tumor induced osteomalacia

 

Diagnosing X-linked hypophosphatemia or autosomal dominant hypophosphatemic rickets

 

Diagnosing familial tumoral calcinosis with hyperphosphatemia

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate (phosphorus) homeostasis. FGF23 is secreted primarily by bone, followed by thymus, heart, brain and, in low levels, by several other tissues. High serum phosphate (phosphorus) concentrations stimulate FGF23 expression and secretion through a yet poorly understood mechanism. Only intact FGF23 is considered bioactive. Intact FGF23 interacts with a specific receptor on renal tubular cells, decreasing expression of type IIa sodium/phosphate cotransporters, resulting in decreased phosphate reabsorption. In addition, gene transcription of 1-alpha-hydroxylase is downregulated, reducing bioactive 1,25-dihydroxy vitamin D, thereby further decreasing phosphate reabsorption. Eventually, falling serum phosphate concentrations lead to diminished FGF23 secretion, closing the feedback loop.

 

Measurement of FGF23 can assist in diagnosis and management of disorders of phosphate and bone metabolism in patients with either normal or impaired renal function. When FGF23 levels are pathologically elevated in individuals with normal renal function, hypophosphatemia, with or without osteomalacia, ensues. This can occur in rare, usually benign, mixed connective tissue tumors that contain characteristic complex vascular structures, osteoclast-like giant cells, cartilaginous elements, and dystrophic calcifications. These neoplasms secrete FGF23 ectopically and autonomously (tumor-induced osteomalacia; TIO). In less than one-fourth of cases, a different benign or malignant soft tissue tumor type or, extremely rarely, a carcinoma, may be the cause of paraneoplastic FGF23 secretion. In either scenario, complete removal of the tumor cures the TIO.

 

Hypophosphatemia and skeletal abnormalities are also observed in X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR). In XLH, variants in the PHEX (phosphate-regulating neutral endopeptidase) gene, which encodes a cell-surface-bound protein-cleavage enzyme, affect bioactive FGF23 secretion. Although the pathogenesis of XLH is not fully understood, animal studies indicate that loss of PHEX function results in enhanced secretion of FGF23.

 

In ADHR, FGF23 variants render the protein resistant to proteolytic cleavage, thereby increasing FGF23 levels. However, not all FGF23 variants increase renal phosphate secretions. Variants that impair FGF23 signaling, rather than increase its protease resistance, are associated with the syndrome of familial tumoral calcinosis (ectopic calcifications) with hyperphosphatemia.

 

In patients with renal failure, FGF23 contributes to renal osteodystrophy. The patient's kidneys can no longer excrete sufficient amounts of phosphate. This leads to marked increases in FGF23 secretion as a compensatory response, aggravating the 1,25-dihydroxy vitamin D deficiency of renal failure and the consequent secondary hyperparathyroidism.

 

In circulation, intact FGF-23 is cleaved to generate two biologically inactive fragments, a N-terminal fragment and a C-terminal fragment. FGF23 has a rapid clearance and short half-life which ranges between 46 and 58 min for intact and C-terminal fragments, respectively. Different types of FGF-23 immunoassays are available, those targeting the intact form (iFGF23), and those detecting C-terminal fragments (cFGF23). Various studies have suggested that iFGF23 assays are more sensitive than cFGF23for the detection of FGF23 concentrations in patients with TIO and patients with XLH. In addition, iFGF23 concentrations are not affected by iron deficiency which may lead to false positive results when using cFGF23 assays.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Pediatric (<18 yrs): < or =52 pg/mL

Adults (> or =18 yrs): < or = 59 pg/mL

Interpretation
Provides information to assist in interpretation of the test results

Increased fibroblast growth factor 23 (FGF23) concentrations are present in individuals with renal phosphate-wasting diseases such as autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), X-linked hypophosphatemia rickets (XLH) and tumor induced osteomalacia (TIO). Clinically, FGF23 measurement is useful in the differential diagnosis of these hypophosphatemic diseases since the patient presents with high FGF23 levels along with hypophosphatemia. In other causes of hypophosphatemia, such as vitamin D deficiency, FGF23 levels are low. In FGF23-producing tumors, a decrease in FGF23 concentrations following surgery is a reliable indication of complete tumor resection.

 

Intact FGF23 concentrations are elevated in patients with TIO or XLH. A study detected elevations of intact FGF23 in 19 of 22 TIO cases (86%).(1) In XLH, elevations of intact FGF23 were observed in 88% of patients (9 of10 children and 13 of 15 adults).(2) While levels of intact FGF23 in XLH are usually elevated, FGF23 concentrations within the reference interval do not exclude the disease and should be interpreted in the setting of phosphate concentrations (ie, an FGF23 concentration in the upper level of the reference interval in the context of hypophosphatemia might be indicative of XLH). In ADHR, FGF23 concentrations are not consistently elevated, and the severity of renal phosphate-wasting may wax and wane; FGF23 concentrations are normal during quiescent periods when serum phosphate levels are normal, and they are elevated during active, hypophosphatemic phases of the disease.(3) FGF23 concentrations are influenced by factors such as phosphate intake and vitamin D therapy. Therefore, intact FGF23 levels are most informative in untreated patients.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Fibroblast growth factor 23 (FGF23) concentrations must be interpreted in conjunction with serum phosphate (phosphorus) measurements, as FGF23 will be elevated in other conditions that cause hyperphosphatemia in vivo. These include: renal failure, severe catabolic states (eg, severe systemic illness, uncontrolled type I diabetes mellitus, and severe starvation) vitamin D toxicity, intravenous phosphate treatment and very high phosphate diets, advanced malignancy in particular with tumor lysis, crush or other significant muscle injury or destruction, fractures, and some endocrine disorders, in particular hypoparathyroidism and acromegaly. With the exception of renal failure, FGF23 measurements will not contribute to diagnosis or patient management in these situations.

 

Do not interpret FGF23 concentrations as absolute evidence of the presence or the absence of tumor induced osteomalacia (TIO). Some patients with TIO may have FGF23 levels within the reference interval. It is thought that tumors in these individuals may be secreting different, and yet unidentified, phosphatonins. Therefore, if the clinical picture and general osteomalacia laboratory workup suggest strongly that the patient has TIO; a normal intact FGF23 level should not discourage tumor search or removal.

 

Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results. Whenever the test results do not fit the clinical picture, the laboratory should be consulted regarding possible assay interference.

 

In vitro studies indicate that the presence of burosumab falsely decreases IFG23 results in a dose-dependent manner.

 

Patients receiving burosumab should not be monitored using the IFG23 assay. Serum phosphate, alkaline phosphatase, and 1,25(OH)2D measurements should be considered for monitoring response to therapy.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Imel EA, Peacock M, Pitukcheewanont P, et al: Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. J Clin Endocrinol Metab. 2006 Jun;91(6):2055-2061

2. Imel EA, Gray AK, Padgett LR, Econs MJ: Iron and fibroblast growth factor 23 in X-linked hypophosphatemia. Bone. 2014 Mar;60:87-92

3. Imel EA, Hui SL, Econs MJ: FGF23 concentrations vary with disease status in autosomal dominant hypophosphatemic rickets. J Bone Miner Res. 2007 Apr;22(4):520-526

4. Haffner D, Emma F, Eastwood DM, et al: Clinical practice recommendations for the diagnosis and management of X-linked hypophosphatemia. Nat Rev Nephrol. 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5

5. Fauconnier C, Roy T, Gillerot G, et al: FGF23: Clinical usefulness and analytical evolution. Clin Biochem. 2019 Apr;66:1-12. doi: 10.1016/j.clinbiochem.2019.03.002

Method Description
Describes how the test is performed and provides a method-specific reference

The intact fibroblast growth factor 23 (FGF23) assay is a 2-site immunoenzymatic assay using two anti-human FGF23 mouse monoclonal antibodies. One antibody is coated onto microtiter wells and the other is alkaline phosphatase labeled. The signal generated is proportional to the concentration of intact FGF23 in the serum sample. The amount of intact FGF23 is determined by means of multipoint calibrator curve. Cross-reactivity of the assay with C-terminal FGF23 was evaluated in-house and determined to be no cross-reactivity with C-terminal FGF23 concentrations up to 230,680 pmol/L.(Package insert: MedFrontier FGF23 Intact. Hitachi Chemical Diagnostics Systems Co, Ltd; 08/2019)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 7 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

90 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83520

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports