Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3

Arosio, M.

doi:10.1210/jc.86.3.1091

Cited by 25 publications

(40 citation statements)

References 24 publications

(36 reference statements)

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“…Como exemplo, apresentamos a seguir as faixas de normalidade do IGF-1 para diferentes faixas etárias do ensaio IRMA pós-extração, utilizado em muitos laboratórios no Brasil: 20 a 200ng/mL (<6 anos), 88 a 450ng/mL (7-12 anos), 200 a 900ng/mL (13-16 anos), 180 a 780ng/mL (17-24 anos), 114 a 400ng/mL (25-39 anos), 90 a 360ng/mL (40-54 anos) e 70 a 290ng/mL (>54 anos). Levando-se em consideração a faixa etária do paciente, as concentrações de IGF-1 encontram-se aumentadas em 100% dos pacientes com acromegalia não tratada (48,49).…”

Section: Dosagem Do Igf-1unclassified

“…A IGFBP-1 é regulada pela insulina e sua concentração plasmática guarda uma relação inversa com a do GH (7,46). Em conseqüência, os níveis de IGFBP-1 são significativamente mais baixos em pacientes com acromegalia quando comparados a indivíduos controles, elevando-se após tratamento com octreotide (51) e após adenomectomia (49). Entretanto, os níveis plasmáticos muito baixos e variáveis durante o dia, associados a uma meia-vida plasmática muito curta, fazem com que a dosagem de IGFBP-1 seja de pouca utilidade na rotina diagnóstica da acromegalia (49).…”

Section: Dosagem Das Igfbpsunclassified

“…Similarmente à IGFBP-1, há evidên -cias de que a síntese de IGFBP-2 seja também inibida pelo GH (46). Entretanto, as dosagens de IGFBP-2 em acromegálicos têm produzido resultados conflitantes, com alguns estudos mostrando que os níveis estão diminuídos em relação ao grupo controle (52,53) e outros não encontrando diferença (49,54). Após cirurgia, Arosio e cols.…”

Section: Dosagem Das Igfbpsunclassified

“…Entre todas as IGFBPs, a mais extensivamente investigada na acromegalia é a IGFBP-3, uma vez que sua produção é influenciada pelo GH e IGF-1 (7,46). Entretanto, quando comparada a outros parâmetros bioquímicos, a dosagem de IGFBP-3 mostra-se muito pouco sensível no diagnóstico da acromegalia, estando normal em cerca de 25% dos pacientes (48,49). Do mesmo modo, a dosagem de IGFBP-3 é inferior a outros parâmetros para monitorar a atividade da doença durante o seguimento (9,48,49).…”

Section: Dosagem Das Igfbpsunclassified

“…Entretanto, quando comparada a outros parâmetros bioquímicos, a dosagem de IGFBP-3 mostra-se muito pouco sensível no diagnóstico da acromegalia, estando normal em cerca de 25% dos pacientes (48,49). Do mesmo modo, a dosagem de IGFBP-3 é inferior a outros parâmetros para monitorar a atividade da doença durante o seguimento (9,48,49). As dosagens de IGFBP-4, 5 e 6 não apresentam no presente momento qualquer relevância clínica na abordagem laboratorial da acromegalia (9,46,55).…”

Section: Dosagem Das Igfbpsunclassified

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O Laboratório no Diagnóstico e Seguimento da Acromegalia

Boguszewski

2002

Arq Bras Endocrinol Metab

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RESUMOAcromegalia é uma síndrome clínica característica, que na maior parte das vezes resulta de um macroadenoma hipofisário produtor de hormônio de crescimento (GH, growth hormone). A hipersecreção tumoral crônica de GH provoca deformidades esqueléticas, distúrbios metabólicos, complicações em vários órgãos e sistemas, e acaba reduzindo a expectativa de vida do paciente. O diagnóstico presuntivo baseia-se nos achados clínicos característicos da doença, com a confirmação vindo através de exames laboratoriais e da avaliação radiológica. Do ponto de vista laboratorial, a abordagem diagnóstica inclui dosagens basais e testes endócrinos que comprovem o excesso de GH, através de dosagens diretas do GH e/ou de fatores circulantes GH-dependentes, cujo melhor exemplo é o fator de crescimento insulina-símile-1 (IGF-1, insulin-like growth factor-1). A adenomectomia transesfenoidal permanece como o tratamento inicial de escolha na acromegalia, mas infelizmente a cura cirúrgi-ca ocorre em menos da metade dos pacientes portadores de macroadenomas. Conseqüentemente, os exames laboratoriais têm um papel muito importante no seguimento dos pacientes após a cirurgia, para definir os critérios de cura e monitorar a atividade da doença durante tratamento complementar com radioterapia ou medicamentos. Neste artigo, revisaremos os exames laboratoriais mais freqüentemente utilizados no diagnóstico da acromegalia e alguns métodos experimentais que vêm sendo testados na sua abordagem. Na parte final, apresentaremos as principais recomendações de dois workshops internacionais realizados nos últimos anos com o objetivo de padronizar a avaliação diagnóstica e a conduta terapêutica na acromegalia. ABSTRACTThe Laboratory in the Diagnosis and Follow-up of Acromegaly. Acromegaly is a characteristic clinical syndrome caused in most cases by a GH-producing pituitary macroadenoma. Tumoral GH hypersecretion results in skeletal changes, metabolic abnormalities, multi-systemic complications and a significant increase in the overall mortality. The diagnosis is suspected on clinical grounds, and it is normally confirmed by biochemical and radiological examinations. From the biochemical standpoint, the diagnostic approach for demonstration of GH excess involves either basal hormone measurements, mainly GH and insulin-like growth factor-1 (IGF-1), and endocrine tests, such as the oral glucose load. Transphenoidal adenomectomy remains the primary therapy of choice for most patients but, unfortunately, post-surgical remission is observed in less than half of the patients with macroadenomas. Consequently, hormone measurements have an important role in the follow-up of acromegalic patients, not only to define criteria for remission ("cure"), both also to evaluate the outcome of other therapeutic approaches such as radiotherapy and medical treatment. In this article, the most common biochemical measurements used in the management of acromegaly and some novel experimental assays are reviewed. In addirevisão O Laboratório no Diagnóstico e Seguimento da Acrome...

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Section: Dosagem Do Igf-1unclassified

Section: Dosagem Das Igfbpsunclassified

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O Laboratório no Diagnóstico e Seguimento da Acromegalia

Boguszewski

2002

Arq Bras Endocrinol Metab

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The development of composite circulating biomarker models for use in anticancer drug clinical development

Lancashire

Roberts

Renehan

2011

Intl Journal of Cancer

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The development of informative composite circulating biomarkers predicting cancer presence or therapy response is clinically attractive but optimal approaches to modeling are as yet unclear. This study investigated multidimensional relationships within an example panel of serum insulin-like growth factor (IGF) peptides using logistic regression (LR), fractional polynomial (FP), regression, artificial neural networks (ANNs) and support vector machines (SVMs) to derive predictive models for colorectal cancer (CRC). Two phase 2 biomarker validation analyses were performed: controls were ambulant adults (n 5 722); cases were: (i) CRC patients (n 5 100) and (ii) patients with acromegaly (n 5 52), the latter as ''positive'' discriminators. Serum IGF-I, IGF-II, IGF binding protein (IGFBP)-2 and -3 were measured. Discriminatory characteristics were compared within and between models. For the LR, FP and ANN models, and to a lesser extent SVMs, the addition of covariates at several steps improved discrimination characteristics. The optimum biomarker combination discriminating CRC vs. controls was achieved using ANN models [sensitivity, 94%; specificity, 90%; accuracy, 0.975 (95% CIs: 0.948 1.000)]. ANN modeling significantly outperformed LR, FP and SVM in terms of discrimination (p < 0.0001) and calibration. The acromegaly analysis demonstrated expected high performance characteristics in the ANN model [accuracy, 0.993 (95% CIs: 0.977, 1.000)]. Curved decision surfaces generated from the ANNs revealed the potential clinical utility. This example demonstrated improved discriminatory characteristics within the composite biomarker ANN model and a final model that outperformed the three other models. This modeling approach forms the basis to evaluate composite biomarkers as pharmacological and predictive biomarkers in future clinical trials.Biomarkers are increasingly important tools in oncology, and in particular to facilitate drug development.

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Hormone‐related diseases and prostate cancer: An English national record linkage study

Watts

Goldacre

Key

et al. 2019

Intl Journal of Cancer

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Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadalassociated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37-0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35-0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.Additional Supporting Information may be found in the online version of this article.

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Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3

Cited by 25 publications

References 24 publications

O Laboratório no Diagnóstico e Seguimento da Acromegalia

O Laboratório no Diagnóstico e Seguimento da Acromegalia

The development of composite circulating biomarker models for use in anticancer drug clinical development

Hormone‐related diseases and prostate cancer: An English national record linkage study

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