Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement

Maghnie, Mohamad; Aimaretti, Gianluca; Bellone, Simonetta; Bona, Gianni; Bellone, J.; Baldelli, Roberto; Sanctis, C. De; Gargantini, L; Gastaldi, Roberto; Ghizzoni, Lucia; Secco, Andrea; Tinelli, Carmine; Ghigo, Ezio

doi:10.1530/eje.1.01873

Cited by 94 publications

(67 citation statements)

References 38 publications

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“…More recently, normative values for the ITT in the transition adolescents have been defined (28). In fact, the diagnostic accuracy of a peak GH response of 6.1 mg/l showed 96% Se with 100% Sp (Fig.…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

“…The arrow indicates the location on the ROC curve of the diagnostic cut-off point that minimizes misclassification of panhypopituitary patients and control subjects. The cut-off point, sensitivity and specificity, with their confidence intervals (CI) at 95%, ROC AUC and accuracy are shown in the box (adapted from (28) and (29) with the permission of the European Journal of Endocrinology).…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

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Retesting the childhood-onset GH-deficient patient

Gasco¹,

Corneli

Beccuti³

et al. 2008

European Journal of Endocrinology

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GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as 'golden' standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 mg/l while that to GHRHCARG test is 19.0 mg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRHCARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect. European Journal of Endocrinology 159 S45-S52

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Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

Retesting the childhood-onset GH-deficient patient

Gasco¹,

Corneli

Beccuti³

et al. 2008

European Journal of Endocrinology

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“…anos, e com alta probabilidade de realmente terem DGH pelo fato de a maioria deles ter mais do que uma deficiência de hormônio hipofisário, ou por apresentarem alteração anatômica da região hipotalâmica-hipofisária, os níveis de resposta foram superiores a 3 µg/L em 23% desta amostra estudada e maiores que 5 µg/L em 11%, sugerindo realmente que deve-se ter um nível de corte mais elevado para pacientes no final da adolescência e mesmo nos primeiros anos da idade adulta (37). Por conseguinte, aplicar em adolescentes no final do seu crescimento estatural, ou em adultos jovens, a mesma interpretação da resposta do GH aos testes de estímulo, que é utilizada em adultos após a quarta década de vida, talvez não seja o mais adequado.…”

Section: Risco Cardiovascularunclassified

“…A sua dosagem não mostrou sensibilidade e especificidade maior que o teste de estímulo com GH em uma população de adultos jovens (37). Níveis normais de IGF-1 não excluem DGH (2,31).…”

Section: Risco Cardiovascularunclassified

Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto

Portes

Barbosa

2008

Arq Bras Endocrinol Metab

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Além de estimular o crescimento estatural, o hormônio de crescimento (GH) promove outros efeitos benéficos nos pacientes com deficiência de GH (DGH). A suspensão do GH em pacientes com DGH, durante o período de transição da criança para a vida adulta, induz a alterações metabólicas desfavoráveis na composição corporal, na integridade óssea, na capacidade para desempenhar atividade física, e também aumenta fatores de risco cardiovasculares. Estes parâmetros melhoram quando a reposição do GH é reiniciada em adultos com DGH. Com base nestas evidências, a reposição do GH não deveria ser suspensa quando o paciente atingisse sua altura final e, sim, mantida durante a vida adulta. Entretanto, considerando que muitos pacientes com diagnóstico de DGH, quando criança, não tem este diagnóstico confirmado no início da vida adulta, é necessário reavaliar a secreção de GH quando o paciente atingir a altura final. A história clínica do paciente, a resposta ao tratamento com GH, a ressonância magnética da região hipotalâmica-hipofisária e a concentração de IGF-1 podem ajudar nesta reavaliação. A realização de testes de estímulo para liberação do GH é necessária, a menos que o paciente apresente lesão estrutural ou genética que justifiquem a deficiência deste hormônio.

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“…These findings have important clinical implications in the diagnosis and prognosis of GHD after adult height achievement. Recent data, however, clearly show that when the criterion of a peak GH value of Ͻ3 or Ͻ5 g/l after ITT is applied, several misdiagnosed GHD subjects would be wrongly excluded from a potentially beneficial continuation of rhGH replacement treatment [6]. On the other hand, the diagnostic cut-off value of peak GH that should be adopted in young adults after combined arginine insulin or propanolol glucagon (used by the authors) has yet to be established; the role of sex hormones following the onset of puberty should not be underestimated.…”

Section: J Clin Endocrinol Metab 2004;89:5030-5034mentioning

confidence: 99%

Pituitary

Maghnie¹,

Secco²,

Loche³

2005

Yearbook of Pediatric Endocrinology 2005

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In the last decade, a number of regulatory proteins have been shown to be important in the development and function of the pituitary gland. These transcription factors act at different stages of development to trigger the expression of specific genes that regulate the development of specific cell lineages, as well as the expression of hormone genes. Indeed, over the last year, several interesting articles in this challenging new area have been extremely helpful for understanding pituitary gland genetics and pathology, as well as the physiology of anterior pituitary hormonal regulation. Other selections should have important clinical implications for practicing physicians. The resulting summary will hopefully provide valuable help for updating busy pediatric endocrinologists on the most interesting and relevant work recently published in the field of pituitary studies and will furnish insights into future directions. Mechanism of the year PROP-1 mutations: transition from hyperplasia to hypoplasia Role of PROP-1 in pituitary gland growthWard RD, Raetzman LT, Suh H, Stone BM, Nasonkin IO, Camper SA Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Mich., USA Mol Endocrinol 2005;19:698-710 Background: The PROP-1 gene is a tissue-specific, paired-like, homeodomain transcription factor expressed early in the anterior pituitary. The Prop-1 gene plays an essential role in the evolution of pituitary cells secreting GH, PRL, TSH and gonadotropins, as shown by hormone deficiencies in subjects with PROP-1 mutations. ACTH deficiency seems to be more common than was formerly thought. Pituitary morphology in patients carrying PROP-1 mutation varies considerably between small, normal and up to an extremely enlarged pituitary gland size, with no abnormalities among pituitary stalk and posterior pituitary. Spontaneous mutant Ames dwarf mice, however, display pituitary hypoplasia. The mechanism whereby PROP-1 regulates anterior pituitary growth from pituitary hyperplasia to hypoplasia is still largely unclear. Methods: Longitudinal studies in normal and Prop-1-deficient generated mice were carried out from early embryogenesis to adulthood. The volume of Rathke's pouch and its derivatives, the position and number of dividing cells and the rate of apoptosis and cell migration were evaluated. Results: Prop-1 deficiency results in early abnormal expansion of both Rathke's pouch and of the lumen with late pituitary dysmorphology and severe hypoplasia. Volumetric analysis by three-dimensional reconstruction confirms pituitary growth pattern with tenfold pituitary volume reduction after birth. The volumetric measurements suggest that proliferating cells progressively fail to populate the anterior pituitary, while pulse chase labeling shows impairment of the migration pattern of progenitors from the perilumenal region to the anterior lobe. After birth, mutant pituitaries displayed increased apoptosis. Conclusion: Mutations in the transcription factor Prop-1 causes dysmorphic pituitary primordium, ...

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Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement

Cited by 94 publications

References 38 publications

Retesting the childhood-onset GH-deficient patient

Retesting the childhood-onset GH-deficient patient

Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto

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