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  1. Article: Interpreting growth hormone and IGF-I results using modern assays and reference ranges for the monitoring of treatment effectiveness in acromegaly.

    Clemmons, David R / Bidlingmaier, Martin

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1266339

    Abstract: Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This ... ...

    Abstract Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This paper reviews biochemical status assessed using methods available at the time and associated clinical outcomes. GH measurements were shown to provide an indication of changes in tumor size, and failure of GH suppression after glucose stimulation is associated with tumor recurrence. IGF-I levels were more closely associated with changes in symptoms and signs. Reduced GH and IGF-I concentrations were shown to be associated with increased longevity, although the degree of increase has only been analyzed for GH. Lowering of GH and IGF-I has consistently been associated with improved outcomes; however, absolute levels reported in previous studies were based on results from methods and reference ranges that are now obsolete. Applying previously described absolute thresholds as targets (e.g. "normal" IGF-I level) when using current methods is best applied to those with active acromegaly symptoms who could benefit from further lowering of biochemical markers. In asymptomatic individuals with mild IGF-I or GH elevations, targeting biochemical "normalization" would result in the need for combination pharmacotherapy in many patients without proven benefit. Measurement of both GH and IGF-I remains an essential component of diagnosis and monitoring the effectiveness of treatment in acromegaly; however, treatment goals based only on previously identified absolute thresholds are not appropriate without taking into account the assay and reference ranges being employed. Treatment goals should be individualized considering biochemical improvement from an untreated baseline, symptoms of disease, risks, burdens and costs of complex treatment regimens, comorbidities, and quality of life.
    MeSH term(s) Humans ; Acromegaly/diagnosis ; Acromegaly/therapy ; Growth Hormone ; Insulin-Like Growth Factor I/metabolism ; Reference Values ; Quality of Life ; Human Growth Hormone/therapeutic use ; Human Growth Hormone/metabolism ; Treatment Outcome
    Chemical Substances Growth Hormone (9002-72-6) ; Insulin-Like Growth Factor I (67763-96-6) ; Human Growth Hormone (12629-01-5)
    Language English
    Publishing date 2023-10-25
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1266339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book: IGFs: Local repair and survival factors throughout life span

    Clemmons, David

    (Research and perspectives in endocrine interactions)

    2010  

    Author's details David Clemmons ... (ed.)
    Series title Research and perspectives in endocrine interactions
    Keywords Insulin-like Growth Factor
    Subject IGF ; ILGF ; Insulinähnlicher Wachstumsfaktor
    Language English
    Size XIII, 157 S. : Ill., graph. Darst., 235 mm x 155 mm
    Publisher Springer
    Publishing place Heidelberg u.a.
    Publishing country Germany
    Document type Book
    HBZ-ID HT016162017
    ISBN 978-3-642-04301-7 ; 9783642043024 ; 3-642-04301-1 ; 364204302X
    Database Catalogue ZB MED Medicine, Health

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  3. Article ; Online: Role of IGF-binding proteins in regulating IGF responses to changes in metabolism.

    Clemmons, David R

    Journal of molecular endocrinology

    2018  Volume 61, Issue 1, Page(s) T139–T169

    Abstract: The IGF-binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF1 and IGF2. These proteins are present in plasma and extracellular fluids and regulate access of ... ...

    Abstract The IGF-binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF1 and IGF2. These proteins are present in plasma and extracellular fluids and regulate access of both IGF1 and II to the type I IGF receptor. Additionally, they have functions that are independent of their ability to bind IGFs. Each protein is regulated independently of IGF1 and IGF2, and this provides an important mechanism by which other hormones and physiologic variables can regulate IGF actions indirectly. Several members of the family are sensitive to changes in intermediary metabolism. Specifically the presence of obesity/insulin resistance can significantly alter the expression of these proteins. Similarly changes in nutrition or catabolism can alter their synthesis and degradation. Multiple hormones such as glucocorticoids, androgens, estrogen and insulin regulate IGFBP synthesis and bioavailability. In addition to their ability to regulate IGF access to receptors these proteins can bind to distinct cell surface proteins or proteins in extracellular matrix and several cellular functions are influenced by these interactions. IGFBPs can be transported intracellularly and interact with nuclear proteins to alter cellular physiology. In pathophysiologic states, there is significant dysregulation between the changes in IGFBP synthesis and bioavailability and changes in IGF1 and IGF2. These discordant changes can lead to marked alterations in IGF action. Although binding protein physiology and pathophysiology are complex, experimental results have provided an important avenue for understanding how IGF actions are regulated in a variety of physiologic and pathophysiologic conditions.
    MeSH term(s) Animals ; Humans ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor II/metabolism ; Receptors, Growth Factor/metabolism
    Chemical Substances Insulin-Like Growth Factor Binding Proteins ; Receptors, Growth Factor ; Insulin-Like Growth Factor I (67763-96-6) ; Insulin-Like Growth Factor II (67763-97-7)
    Language English
    Publishing date 2018-03-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 645012-x
    ISSN 1479-6813 ; 0952-5041
    ISSN (online) 1479-6813
    ISSN 0952-5041
    DOI 10.1530/JME-18-0016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Conference proceedings: Proceedings of the 34th International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism

    Clemmons, David

    October 2002, Budapest, Hungary

    (Growth hormone & IGF research ; 13, Suppl. A)

    2003  

    Institution International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism
    Author's details ed. by D. Clemmons
    Series title Growth hormone & IGF research ; 13, Suppl. A
    Collection
    Language English
    Size S170 S. : Ill., graph. Darst.
    Publisher Churchill Livingstone
    Publishing place Edinburgh u.a.
    Publishing country Great Britain
    Document type Book ; Conference proceedings
    HBZ-ID HT013820767
    Database Catalogue ZB MED Medicine, Health

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  5. Article: ACCURATE DIAGNOSIS OF GROWTH HORMONE DEFICIENCY IN ADULTS: THE ONGOING CHALLENGE.

    Clemmons, David R

    Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

    2016  Volume 22, Issue 12, Page(s) 1462–1464

    MeSH term(s) Adult ; Growth Hormone/deficiency ; Human Growth Hormone/deficiency ; Humans
    Chemical Substances Human Growth Hormone (12629-01-5) ; Growth Hormone (9002-72-6)
    Language English
    Publishing date 2016-11-16
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1473503-9
    ISSN 1530-891X
    ISSN 1530-891X
    DOI 10.4158/EP161486.CO
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Role of IGF Binding Proteins in Regulating Metabolism.

    Clemmons, David R

    Trends in endocrinology and metabolism: TEM

    2016  Volume 27, Issue 6, Page(s) 375–391

    Abstract: Insulin-like growth factors (IGFs) circulate in extracellular fluids bound to a family of binding proteins. Although they function in a classical manner to limit the access of the IGFs to their receptors they also have a multiplicity of actions that are ... ...

    Abstract Insulin-like growth factors (IGFs) circulate in extracellular fluids bound to a family of binding proteins. Although they function in a classical manner to limit the access of the IGFs to their receptors they also have a multiplicity of actions that are independent of this property; they bind to their own receptors or are transported to intracellular and intranuclear sites to influence cellular functions that may directly or indirectly modify IGF actions. The availability of genetically modified animals has helped to determine their functions in a physiological context. These results show that many of their actions are cell type- and context-specific, and have led to a broader understanding of how these proteins function coordinately with IGF-I and -II to regulate growth and metabolism.
    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2016.03.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Medical Costs Associated with High/Moderate/Low Likelihood of Adult Growth Hormone Deficiency: A Healthcare Claims Database Analysis.

    Yuen, Kevin C J / Blevins, Lewis S / Clemmons, David R / Faurby, Mads / Hoffman, Andrew R / Kelepouris, Nicky / Kerr, Janice M / Tarp, Jens Magelund / Fleseriu, Maria

    ClinicoEconomics and outcomes research : CEOR

    2024  Volume 16, Page(s) 133–147

    Abstract: Purpose: Adult growth hormone deficiency (AGHD) is often underdiagnosed and undertreated, leading to costly comorbidities. Previously, we developed an algorithm to identify individuals in a commercially insured US population with high, moderate, or low ... ...

    Abstract Purpose: Adult growth hormone deficiency (AGHD) is often underdiagnosed and undertreated, leading to costly comorbidities. Previously, we developed an algorithm to identify individuals in a commercially insured US population with high, moderate, or low likelihood of having AGHD. Here, we estimate and compare direct medical costs by likelihood level.
    Patients and methods: Retrospective, observational analysis using the Truven Health MarketScan database to analyze direct medical costs relating to inpatient and outpatient claims, outpatient prescription claims, medication usage, clinical utilization records, and healthcare expenditures. Patients were categorized into groups based on algorithmically determined likelihoods of AGHD. Likelihood groups were further stratified by age and sex. Trajectories of annual costs (USD) by likelihood level were also investigated.
    Results: The study cohort comprised 135 million US adults (aged ≥18 years). Individuals ranked as high-likelihood AGHD had a greater burden of comorbid illness, including cardiovascular disease and diabetes, than those ranked moderate- or low-likelihood. Those in the high-likelihood group had greater mean total direct medical monthly costs ($1844.51 [95% confidence interval (CI): 1841.24;1847.78]) than those in the moderate- ($945.65 [95% CI: 945.26;946.04]) and low-likelihood groups ($459.10 [95% CI: 458.95;459.25]). Outpatient visits accounted for the majority of costs overall, although cost per visit was substantially lower than for inpatient services. Costs tended to increase with age and peaked around the time that individuals were assigned a level of AGHD likelihood. Total direct medical costs in individuals with a high likelihood of AGHD exceeded those for individuals with moderate or low likelihood.
    Conclusion: Understanding the trajectory of healthcare costs in AGHD may help rationalize allocation of healthcare resources.
    Language English
    Publishing date 2024-03-08
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2520698-9
    ISSN 1178-6981
    ISSN 1178-6981
    DOI 10.2147/CEOR.S445495
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes.

    Clemmons, David R

    Endocrinology and metabolism clinics of North America

    2012  Volume 41, Issue 2, Page(s) 425–43, vii–viii

    Abstract: Insulin-like growth factor-I (IGF-I) is closely related to insulin but has distinct metabolic actions. IGF-I is an important stimulant of protein synthesis in muscle, but it also stimulates free fatty acid use. The administration of IGF-I to patients ... ...

    Abstract Insulin-like growth factor-I (IGF-I) is closely related to insulin but has distinct metabolic actions. IGF-I is an important stimulant of protein synthesis in muscle, but it also stimulates free fatty acid use. The administration of IGF-I to patients with extreme insulin resistance results in improvement in glycemic control, and IGF-I is associated with lowering glucose and enhancing insulin sensitivity in Type 1 and Type 2 diabetes. However, patients with diabetes are also sensitive to stimulation of side effects in response to IGF-I. IGF-I coordinately links growth hormone and insulin actions and has direct effects on intermediary metabolism.
    MeSH term(s) Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Dietary Carbohydrates/metabolism ; Dietary Fats/metabolism ; Dietary Proteins/metabolism ; Female ; Humans ; Hyperglycemia/drug therapy ; Hypoglycemic Agents/therapeutic use ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor I/therapeutic use ; Male ; Metabolic Syndrome/drug therapy ; Metabolic Syndrome/metabolism ; Mice ; Polymorphism, Genetic ; Rats ; Severity of Illness Index
    Chemical Substances Blood Glucose ; Dietary Carbohydrates ; Dietary Fats ; Dietary Proteins ; Hypoglycemic Agents ; Insulin-Like Growth Factor I (67763-96-6)
    Language English
    Publishing date 2012-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2012.04.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: AMP kinase signals the insulin-like growth factor system whether adequate nutrient is present to support an anabolic response.

    Clemmons, David R

    Cell cycle (Georgetown, Tex.)

    2011  Volume 10, Issue 7, Page(s) 1017–1018

    Language English
    Publishing date 2011-04-01
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.10.7.15088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays.

    Clemmons, David R

    Clinical chemistry

    2011  Volume 57, Issue 4, Page(s) 555–559

    Abstract: Growth hormone (GH) and insulin-like growth factor I (IGF-I) measurements are widely used in the diagnosis of disorders of GH secretion, evaluation of children with short stature from multiple causes, management of disorders that lead to nutritional ... ...

    Abstract Growth hormone (GH) and insulin-like growth factor I (IGF-I) measurements are widely used in the diagnosis of disorders of GH secretion, evaluation of children with short stature from multiple causes, management of disorders that lead to nutritional insufficiency or catabolism, and monitoring both GH and IGF-I replacement therapy. Therefore, there is an ongoing need for accurate and precise measurements of these 2 peptide hormones. Representatives of the Growth Hormone Research Society, the IGF Society, and the IFCC convened an international workshop to review assay standardization, requirements for improving assay comparability, variables that affect assay interpretation, technical factors affecting assay performance, assay validation criteria, and the development and use of normative data. Special attention was given to preanalytical conditions, the use of international commutable reference standards, antibody specificity, matrix requirements, QC analysis, and interference by binding proteins. Recommendations for each of these variables were made for measurements of each peptide. Additionally, specific criteria for IGF-I were recommended for age ranges of normative data, consideration of Tanner staging, and consideration of the effect of body mass index. The consensus statement concludes that major improvements are necessary in the areas of assay performance and comparability. This group recommends that a commutable standard for each assay be implemented for worldwide use and that its recommendations be applied to accomplish the task of providing reliable and clinically useful results.
    MeSH term(s) Antibody Specificity ; Clinical Chemistry Tests/standards ; Growth Hormone/standards ; Humans ; Reference Standards ; Somatomedins/standards
    Chemical Substances Somatomedins ; Growth Hormone (9002-72-6)
    Language English
    Publishing date 2011-02-01
    Publishing country England
    Document type Consensus Development Conference ; Journal Article ; Validation Studies
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
    DOI 10.1373/clinchem.2010.150631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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