IGF-1, LC/MS
IGF-1, LC/MS
This test is used to assess growth disorders in symptomatic children and adults and to monitor response to therapy.
Test Summary
IGF-1, LC/MS
Test code: 16293
Clinical use
- Assess growth disorders
- Monitor response to therapy
Clinical background
Measuring IGF-1 is useful in assessing and managing growth-related disorders. For example, guidelines recommend IGF-1 measurements to help with diagnosis, monitoring, and/or therapy of acromegaly (growth hormone [GH] excess) and GH deficiency (GHD).1-3 In addition to growth-related disorders, evidence is emerging that IGF-1 measurement may have utility as a biomarker for symptom severity after traumatic brain injury.4 Serum-based testing is typically used to assess IGF-1 levels because concentrations are 100- to 1,000-fold higher than in urine5; IGF-1 is degraded during renal clearance.6
Immunoassays used to assess IGF-1, while simple to perform, have several shortcomings. IGF-1 binding proteins (IGFBPs), if not completely dissociated from IGF-1, may mask IGF-1 binding sites from antibodies used in immunoassays.7 This interference leads to artificially low IGF-1 values8 and the potential for misdiagnosis. In addition, inconsistency between laboratories has been reported; contributing factors include lack of standardization of the different immunochemical methods, protocols, reference materials, and reference ranges used to establish normal and abnormal values.8
Quest Diagnostics offers an advanced liquid chromatography/mass spectrometry (LC/MS)–based test that circumvents many of these shortcomings. The LC/MS method has demonstrated assay equivalence with radioimmunoassay (RIA) but has the advantage of not involving the handling and disposal of radioactive materials.9 RIA has a diagnostic sensitivity of 70%, specificity of 99%, and positive and negative predictive values of 95% for differentiating individuals with GHD from apparently healthy individuals matched for age, sex, and body-mass index (BMI).10
Clinicians should be aware of assay differences when considering switching between assay platforms; changes in IGF-1 values when measured using different technologies should not be used to guide patient management decisions.8,12 IGF1-levels determined using the LC/MS assay are highly correlated with some other types of immunoassays (eg, electrochemiluminescence [ECL]). However, when the methods are compared, the LC/MS method yields generally lower IGF-1 values.8,9,11 Widely disparate results in some specimens can be explained by the presence of IGF-1 variants, indistinguishable from the wild type by immunoassay and, until recently, not routinely measured by LC/MS.8,11,13 However, the variants are relatively rare (<0.5% in the clinical population14) and cannot explain the overall trend toward lower values by LC/MS.8,11 Instead, technical differences have been proposed as major contributors to the discordance between LC/MS- and ECL-based assays.8
The Acromegaly Consensus Group has recommended that assays used to monitor IGF-1 levels over time adhere to accepted performance standards.12 LC/MS methodology achieves these standards by combining molecular specificity, quantitative performance, well-characterized reference materials, and detailed age-/sex-specific reference intervals. Importantly, the recommendation specifies that the same assay should be consistently used for IGF-1 measurements over time.12
Individuals suitable for testing
- Individuals exhibiting signs of growth disorders, including
- Children with short stature and slow growth rate15
- Children showing signs of gigantism
- Adults with acral and facial features indicative of acromegaly1 (for a full list of signs and symptoms see reference 16)
- Adults lacking typical features of acromegaly but with several associated conditions (eg, sleep apnea syndrome, type 2 diabetes, debilitating arthritis, carpal tunnel syndrome, hyperhidrosis, and hypertension)1
- Patients with a pituitary mass and those who have undergone transsphenoidal surgery1
- Patients with suspected adult GHD who are affected by panhypopituitarism
- Individuals undergoing GH or IGF-1 replacement3,15
Method
- High-resolution LC/MS
- Selectivity and specificity for intact wild type IGF-1 achieved by a narrow-mass–based, high-resolution MS method8,9,17
- Robustness and a high degree of intra- and interday precision (coefficient of variation ≤5%)17 achieved through the use of (1) automation,8,9,17 and (2) stable isotope-labeled internal standard (15N-human IGF-1) to correct for any IGF-1 losses during sample manipulation8
- Adapted to detect the presence of rare hetero- and homozygous IGF-1 variants and estimate their levels13,18
- Sample preparation by acidified ethanol-based extraction of IGF-1 from serum
- Dissociates IGFBPs (no interference)
- Recoveries close to 100% total IGF-1 (free and bound)8,9,17
- Standardized8 to the current World Health Organization international reference preparation 02/254
- Compared to immunoassays
- Assay equivalence with RIA (slope=1.03, R2 =0.98)9
- Highly correlated with bias to lower values with ECL (slope=0.63 to 0.84, R2 =0.95 to 0.98)8,9,11
- Analytical measurement range: 10 ng/mL to 2,000 ng/mL
- Reference ranges derived from >2,000 individuals aged 3 to 85 years9 (for children <3 years, reference ranges were taken from published literature,19 modified to mid-year point)
Interpretive information
For an individual, relative to the sex- and age-adjusted means for a healthy population (in the absence of IGF-1 variants)
- A Z-score (number of standard deviations from the mean) >2.0 is compatible with GH excess (eg, suggestive of acromegaly or consistent with overtreatment with GH).
- A Z-score within ±2.0 indicates normal levels of IGF-1. This result suggests that acromegaly is less likely. However, patients with a small GH-secreting pituitary tumor may have normal IGF-1 levels. Consequently, dynamic testing (eg, GH glucose suppression) may be necessary to identify patients with mild acromegaly or to assess residual tumor burden in patients following surgery to remove a GH-secreting tumor.1 In addition, individuals with GHD may have normal IGF-1 levels (such as those with an increased BMI).3,15
- A Z-score <-2.0 indicates a low level of IGF-1 and may suggest GHD. Follow-up GH stimulation tests, usually using glucagon, may be considered, although such confirmation may not be necessary for some individuals (such as those with multiple hormone deficiencies or proven genetic causes of GHD).2,3,15
In managing GH disorders, age-normalized serum IGF-1 values signify that
- Acromegaly is controlled,1 whereas elevated values indicate that acromegaly is not controlled. According to the Pituitary Society guidelines, postoperative remission can be assessed by measuring IGF-1 levels after 6 weeks, but levels may remain mildly elevated for 3 to 6 months.20
- GH or IGF-1 deficiency has been successfully dosed (if other clinical GH parameters are also favorably assessed in the absence of adverse effects),3,15 whereas elevated values could indicate overdosing and low values could indicate underdosing.
The presence of rare IGF-1 variants and their estimated levels are reported; their presence may indicate that
- The wild-type concentration only represents half the circulating IGF-1 for heterozygous individuals.
- The absence of wild type IGF-1 can be explained by the individual’s being homozygous for the variant or heterozygous for 2 different variants.
In either case, these variants have unclear clinical significance.18
References
- Katznelson L, Laws ER, Jr Melmed S, et al. Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi:10.1210/jc.2014-2700
- Yuen KCJ, Biller BMK, Radovick S, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract. 2019;25(11):1191-1232. doi:10.4158/GL-2019-0405
- Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609. doi:10.1210/jc.2011-0179
- Weppner J, Rosenthal K, Bath J, et al. IGF-1 as a biomarker for symptom severity in adult traumatic brain injury: evidence from an observational study. Neurotrauma Rep. 2025;6(1):345-354. doi:10.1089/neur.2025.0009
- Sinha M, Tripathi T, Rai P, et al. Serum and urine insulin-like growth factor-1 as biochemical growth maturity indicators. Am J Orthod Dentofacial Orthop. 2016;150(6):1020-1027. doi:10.1016/j.ajodo.2016.04.028
- Thomas A, Kohler M, Schänzer W, et al. Determination of IGF-1 and IGF-2, their degradation products and synthetic analogues in urine by LC-MS/MS. Analyst. 2011;136(5):1003-1012. doi:10.1039/c0an00632g
- Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57(4):555-559. doi:10.1373/clinchem.2010.150631
- Bonert V, Carmichael J, Wu Z, et al. Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary disease: a prospective study. Pituitary. 2018;21(1):65-75. doi:10.1007/s11102-017-0849-z
- Bystrom C, Sheng S, Zhang K, et al. Clinical utility of insulin-like growth factor 1 and 2; determination by high resolution mass spectrometry. PLoS One. 2012;7(9):e43457. doi:10.1371/journal.pone.0043457
- Granada ML, Murillo J, Lucas A, et al. Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol. 2000;142(3):243-253. doi:10.1530/eje.0.1420243
- Hines J, Milosevic D, Ketha H, et al. Detection of IGF-1 protein variants by use of LC-MS with high-resolution accurate mass in routine clinical analysis. Clin Chem. 2015;61(7):990-991. doi:10.1373/clinchem.2014.234799
- Melmed S, Bronstein MD, Chanson P, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. doi:10.1038/s41574-018-0058-5
- Wu Z, Sanders H, Motorykin I, et al. Detection of insulin-like growth factor 1 variants by mass spectrometry: results from a clinical reference laboratory. Clin Chem. 2019;65(8):1060-1061. doi:10.1373/clinchem.2019.302539
- Motorykin I, Mu J, Miller BS, et al. Detection rate of IGF-1 variants and their implication to protein binding: study of over 240,000 patients. Clin Chem Lab Med. 2024;62(3):484-492. doi:10.1515/cclm-2023-0709
- Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi:10.1159/000452150
- What are the symptoms of acromegaly? National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Updated January 2020. Accessed January 23, 2026. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly#symptoms
- Bystrom CE, Sheng S, Clarke NJ. Narrow mass extraction of time-of-flight data for quantitative analysis of proteins: determination of insulin-like growth factor-1. Anal Chem. 2011;83(23):9005-9010. doi:10.1021/ac201800g
- Motorykin I, Li A, Wu Z. Monitoring and identifying insulin-like growth factor 1 variants by liquid chromatography-high-resolution mass spectrometry in a clinical laboratory. Methods Mol Biol. 2022;2546:239-251. doi:10.1007/978-1-0716-2565-1_22
- Brabant G, von zur Mühlen A, Wüster C, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003;60(2):53-60. doi:10.1159/000071871
- Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24(1):1-13. doi:10.1007/s11102-020-01091-7
Content reviewed 2/2026
This test is used to assess growth disorders in symptomatic children and adults and to monitor response to therapy.
Test Summary
IGF-1, LC/MS
Test code: 16293
Clinical use
- Assess growth disorders
- Monitor response to therapy
Clinical background
Measuring IGF-1 is useful in assessing and managing growth-related disorders. For example, guidelines recommend IGF-1 measurements to help with diagnosis, monitoring, and/or therapy of acromegaly (growth hormone [GH] excess) and GH deficiency (GHD).1-3 In addition to growth-related disorders, evidence is emerging that IGF-1 measurement may have utility as a biomarker for symptom severity after traumatic brain injury.4 Serum-based testing is typically used to assess IGF-1 levels because concentrations are 100- to 1,000-fold higher than in urine5; IGF-1 is degraded during renal clearance.6
Immunoassays used to assess IGF-1, while simple to perform, have several shortcomings. IGF-1 binding proteins (IGFBPs), if not completely dissociated from IGF-1, may mask IGF-1 binding sites from antibodies used in immunoassays.7 This interference leads to artificially low IGF-1 values8 and the potential for misdiagnosis. In addition, inconsistency between laboratories has been reported; contributing factors include lack of standardization of the different immunochemical methods, protocols, reference materials, and reference ranges used to establish normal and abnormal values.8
Quest Diagnostics offers an advanced liquid chromatography/mass spectrometry (LC/MS)–based test that circumvents many of these shortcomings. The LC/MS method has demonstrated assay equivalence with radioimmunoassay (RIA) but has the advantage of not involving the handling and disposal of radioactive materials.9 RIA has a diagnostic sensitivity of 70%, specificity of 99%, and positive and negative predictive values of 95% for differentiating individuals with GHD from apparently healthy individuals matched for age, sex, and body-mass index (BMI).10
Clinicians should be aware of assay differences when considering switching between assay platforms; changes in IGF-1 values when measured using different technologies should not be used to guide patient management decisions.8,12 IGF1-levels determined using the LC/MS assay are highly correlated with some other types of immunoassays (eg, electrochemiluminescence [ECL]). However, when the methods are compared, the LC/MS method yields generally lower IGF-1 values.8,9,11 Widely disparate results in some specimens can be explained by the presence of IGF-1 variants, indistinguishable from the wild type by immunoassay and, until recently, not routinely measured by LC/MS.8,11,13 However, the variants are relatively rare (<0.5% in the clinical population14) and cannot explain the overall trend toward lower values by LC/MS.8,11 Instead, technical differences have been proposed as major contributors to the discordance between LC/MS- and ECL-based assays.8
The Acromegaly Consensus Group has recommended that assays used to monitor IGF-1 levels over time adhere to accepted performance standards.12 LC/MS methodology achieves these standards by combining molecular specificity, quantitative performance, well-characterized reference materials, and detailed age-/sex-specific reference intervals. Importantly, the recommendation specifies that the same assay should be consistently used for IGF-1 measurements over time.12
Individuals suitable for testing
- Individuals exhibiting signs of growth disorders, including
- Children with short stature and slow growth rate15
- Children showing signs of gigantism
- Adults with acral and facial features indicative of acromegaly1 (for a full list of signs and symptoms see reference 16)
- Adults lacking typical features of acromegaly but with several associated conditions (eg, sleep apnea syndrome, type 2 diabetes, debilitating arthritis, carpal tunnel syndrome, hyperhidrosis, and hypertension)1
- Patients with a pituitary mass and those who have undergone transsphenoidal surgery1
- Patients with suspected adult GHD who are affected by panhypopituitarism
- Individuals undergoing GH or IGF-1 replacement3,15
Method
- High-resolution LC/MS
- Selectivity and specificity for intact wild type IGF-1 achieved by a narrow-mass–based, high-resolution MS method8,9,17
- Robustness and a high degree of intra- and interday precision (coefficient of variation ≤5%)17 achieved through the use of (1) automation,8,9,17 and (2) stable isotope-labeled internal standard (15N-human IGF-1) to correct for any IGF-1 losses during sample manipulation8
- Adapted to detect the presence of rare hetero- and homozygous IGF-1 variants and estimate their levels13,18
- Sample preparation by acidified ethanol-based extraction of IGF-1 from serum
- Dissociates IGFBPs (no interference)
- Recoveries close to 100% total IGF-1 (free and bound)8,9,17
- Standardized8 to the current World Health Organization international reference preparation 02/254
- Compared to immunoassays
- Assay equivalence with RIA (slope=1.03, R2 =0.98)9
- Highly correlated with bias to lower values with ECL (slope=0.63 to 0.84, R2 =0.95 to 0.98)8,9,11
- Analytical measurement range: 10 ng/mL to 2,000 ng/mL
- Reference ranges derived from >2,000 individuals aged 3 to 85 years9 (for children <3 years, reference ranges were taken from published literature,19 modified to mid-year point)
Interpretive information
For an individual, relative to the sex- and age-adjusted means for a healthy population (in the absence of IGF-1 variants)
- A Z-score (number of standard deviations from the mean) >2.0 is compatible with GH excess (eg, suggestive of acromegaly or consistent with overtreatment with GH).
- A Z-score within ±2.0 indicates normal levels of IGF-1. This result suggests that acromegaly is less likely. However, patients with a small GH-secreting pituitary tumor may have normal IGF-1 levels. Consequently, dynamic testing (eg, GH glucose suppression) may be necessary to identify patients with mild acromegaly or to assess residual tumor burden in patients following surgery to remove a GH-secreting tumor.1 In addition, individuals with GHD may have normal IGF-1 levels (such as those with an increased BMI).3,15
- A Z-score <-2.0 indicates a low level of IGF-1 and may suggest GHD. Follow-up GH stimulation tests, usually using glucagon, may be considered, although such confirmation may not be necessary for some individuals (such as those with multiple hormone deficiencies or proven genetic causes of GHD).2,3,15
In managing GH disorders, age-normalized serum IGF-1 values signify that
- Acromegaly is controlled,1 whereas elevated values indicate that acromegaly is not controlled. According to the Pituitary Society guidelines, postoperative remission can be assessed by measuring IGF-1 levels after 6 weeks, but levels may remain mildly elevated for 3 to 6 months.20
- GH or IGF-1 deficiency has been successfully dosed (if other clinical GH parameters are also favorably assessed in the absence of adverse effects),3,15 whereas elevated values could indicate overdosing and low values could indicate underdosing.
The presence of rare IGF-1 variants and their estimated levels are reported; their presence may indicate that
- The wild-type concentration only represents half the circulating IGF-1 for heterozygous individuals.
- The absence of wild type IGF-1 can be explained by the individual’s being homozygous for the variant or heterozygous for 2 different variants.
In either case, these variants have unclear clinical significance.18
References
- Katznelson L, Laws ER, Jr Melmed S, et al. Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi:10.1210/jc.2014-2700
- Yuen KCJ, Biller BMK, Radovick S, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract. 2019;25(11):1191-1232. doi:10.4158/GL-2019-0405
- Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609. doi:10.1210/jc.2011-0179
- Weppner J, Rosenthal K, Bath J, et al. IGF-1 as a biomarker for symptom severity in adult traumatic brain injury: evidence from an observational study. Neurotrauma Rep. 2025;6(1):345-354. doi:10.1089/neur.2025.0009
- Sinha M, Tripathi T, Rai P, et al. Serum and urine insulin-like growth factor-1 as biochemical growth maturity indicators. Am J Orthod Dentofacial Orthop. 2016;150(6):1020-1027. doi:10.1016/j.ajodo.2016.04.028
- Thomas A, Kohler M, Schänzer W, et al. Determination of IGF-1 and IGF-2, their degradation products and synthetic analogues in urine by LC-MS/MS. Analyst. 2011;136(5):1003-1012. doi:10.1039/c0an00632g
- Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57(4):555-559. doi:10.1373/clinchem.2010.150631
- Bonert V, Carmichael J, Wu Z, et al. Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary disease: a prospective study. Pituitary. 2018;21(1):65-75. doi:10.1007/s11102-017-0849-z
- Bystrom C, Sheng S, Zhang K, et al. Clinical utility of insulin-like growth factor 1 and 2; determination by high resolution mass spectrometry. PLoS One. 2012;7(9):e43457. doi:10.1371/journal.pone.0043457
- Granada ML, Murillo J, Lucas A, et al. Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol. 2000;142(3):243-253. doi:10.1530/eje.0.1420243
- Hines J, Milosevic D, Ketha H, et al. Detection of IGF-1 protein variants by use of LC-MS with high-resolution accurate mass in routine clinical analysis. Clin Chem. 2015;61(7):990-991. doi:10.1373/clinchem.2014.234799
- Melmed S, Bronstein MD, Chanson P, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. doi:10.1038/s41574-018-0058-5
- Wu Z, Sanders H, Motorykin I, et al. Detection of insulin-like growth factor 1 variants by mass spectrometry: results from a clinical reference laboratory. Clin Chem. 2019;65(8):1060-1061. doi:10.1373/clinchem.2019.302539
- Motorykin I, Mu J, Miller BS, et al. Detection rate of IGF-1 variants and their implication to protein binding: study of over 240,000 patients. Clin Chem Lab Med. 2024;62(3):484-492. doi:10.1515/cclm-2023-0709
- Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi:10.1159/000452150
- What are the symptoms of acromegaly? National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Updated January 2020. Accessed January 23, 2026. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly#symptoms
- Bystrom CE, Sheng S, Clarke NJ. Narrow mass extraction of time-of-flight data for quantitative analysis of proteins: determination of insulin-like growth factor-1. Anal Chem. 2011;83(23):9005-9010. doi:10.1021/ac201800g
- Motorykin I, Li A, Wu Z. Monitoring and identifying insulin-like growth factor 1 variants by liquid chromatography-high-resolution mass spectrometry in a clinical laboratory. Methods Mol Biol. 2022;2546:239-251. doi:10.1007/978-1-0716-2565-1_22
- Brabant G, von zur Mühlen A, Wüster C, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003;60(2):53-60. doi:10.1159/000071871
- Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24(1):1-13. doi:10.1007/s11102-020-01091-7
Content reviewed 2/2026