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26300 Intact Fibroblast Growth Factor 23, Serum (IFG23)

Intact Fibroblast Growth Factor 23, Serum (IFG23)
Test Code: IFG23SO
Synonyms/Keywords

​FGF23
Intact-FGF23
Autosomal Dominant Hypophosphatemic Rickets
Familial Tumoral Calcinosis with Hyperphosphatemia
Fibroblast Growth Factor 23
Oncogenic Osteomalacia
Phosphatonin
X-linked Hypophosphatemia

Useful For

​Diagnosing and monitoring tumor induced osteomalacia

Diagnosing X-linked hypophosphatemia or autosomal dominant hypophosphatemic rickets

Diagnosing familial tumoral calcinosis with hyperphosphatemia

Specimen Requirements
Fasting RequiredSpecimen TypePreferred Container/TubeAcceptable Container/TubeSpecimen VolumeSpecimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum​Serum Separator Tube (SST)​Red Top Tube (RTT)​0.5 mL​0.25 mL
Collection Processing Instructions

​Centrifuge and aliquot serum into plastic vial.

Specimen Stability Information
Specimen TypeTemperatureTime
Serum​ ​Refrigerated (preferred)​14 days
​Frozen​90 days
Rejection Criteria
Gross hemolysis

Reject

​Gross lipemia​OK
Interference

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.

Performing Laboratory Information
Performing LocationDay(s) Test PerformedAnalytical TimeMethodology/Instrumentation
Mayo Clinic Laboratories​​Wednesdays​1 day​Chemiluminescence Based Quantitative Sandwich Immunoassay
Reference Lab
Test Information

​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 Range Information
Reference Values

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

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

Interpretation

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.

Outreach CPTs
CPTModifier
(if needed)
QuantityDescriptionComments
​83520​1
Synonyms/Keywords

​FGF23
Intact-FGF23
Autosomal Dominant Hypophosphatemic Rickets
Familial Tumoral Calcinosis with Hyperphosphatemia
Fibroblast Growth Factor 23
Oncogenic Osteomalacia
Phosphatonin
X-linked Hypophosphatemia

Ordering Applications
Ordering ApplicationDescription
​COM​Int Fibroblast Growth Factor23
​Cerner​Fibroblast G-Factor23,S(IFG23)
​Portal​Fibroblast G-Factor23,S(IFG23)
​Centricity​Fibroblast G-Factor23,S(IFG23)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Fasting RequiredSpecimen TypePreferred Container/TubeAcceptable Container/TubeSpecimen VolumeSpecimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum​Serum Separator Tube (SST)​Red Top Tube (RTT)​0.5 mL​0.25 mL
Collection Processing

​Centrifuge and aliquot serum into plastic vial.

Specimen Stability Information
Specimen TypeTemperatureTime
Serum​ ​Refrigerated (preferred)​14 days
​Frozen​90 days
Rejection Criteria
Gross hemolysis

Reject

​Gross lipemia​OK
Interference

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.

Useful For

​Diagnosing and monitoring tumor induced osteomalacia

Diagnosing X-linked hypophosphatemia or autosomal dominant hypophosphatemic rickets

Diagnosing familial tumoral calcinosis with hyperphosphatemia

Reference Range Information
Reference Values

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

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

Interpretation

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.

For more information visit:
Performing Laboratory Information
Performing LocationDay(s) Test PerformedAnalytical TimeMethodology/Instrumentation
Mayo Clinic Laboratories​​Wednesdays​1 day​Chemiluminescence Based Quantitative Sandwich Immunoassay
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPTModifier
(if needed)
QuantityDescriptionComments
​83520​1
For most current information refer to the Marshfield Laboratory online reference manual.