Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non‐Insulinoma Pancreatogenic Hypoglycemia Syndrome

Starke, A.; Saddig, Christiane; Kirch, Barbara; Tschahargane, C; Goretzki, P. E.

doi:10.1007/s00268-005-0543-6

Cited by 42 publications

(41 citation statements)

References 58 publications

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“…In addition, it has already been observed that patients with nesidioblastosis can present a lower secretion of C-peptide and insulin than insulinoma patients (14,15), so that the diagnosis of nesidioblastosis is often more difficult than that of insulinomas. Moreover, it has been shown that patients with nesidioblastosis and even some rare glucose-sensitive insulinoma patients can undergo a 72-h fast test without hypoglycaemia (15), such patients being detected only with an oral glucose tolerance test (OGTT) or a meal test. In our study, proinsulin levels above 5 pmol/l during the fast test at the time of hypoglycaemia below 2.5 mmol/l appears to be the best criterion to make the diagnosis of endogenous hyperinsulinism with both 100% sensitivity and specificity.…”

Section: C-peptide Levels (Nmol/l)mentioning

confidence: 99%

Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Vezzosi¹,

Bennet²,

Fauvel³

et al. 2007

eur j endocrinol

123

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Objective: We evaluated the respective value of insulin, C-peptide and proinsulin levels in 33 patients with endogenous hyperinsulinism and in 67 controls to determine the best parameters and thresholds to make or to rule out the diagnosis of endogenous hyperinsulinism. Results: When blood glucose levels were below 2.5 mmol/l, insulin was !21 pmol/l in 8-35% of the patients and in all controls; C-peptide was O0.2 nmol/l in all insulinomas but not in the nesidioblastosis or in the controls; proinsulin was O5 pmol/l in all patients but not in the controls. When fasting blood glucose levels reached 2.5-3.3 mmol/l, proinsulin was !22 pmol/l in all the controls and O22 pmol/l in 74% of the patients. Proinsulin after an overnight fast was below 22 pmol/l in all non-obese controls and above 22 pmol/l in 73% of non-obese patients. Conclusion: Proinsulin levels above 5 pmol/l with blood glucose levels below 2.5 mmol/l during a 72 h fast test represent the best criterion for the diagnosis of endogenous hyperinsulinism, reaching 100% diagnostic specificity and sensitivity. Concomitant C-peptide levels above 0.2 nmol/l also make the diagnosis of all our insulinoma patients, not the diagnosis of nesidioblastosis, while insulin levels have much less diagnostic accuracy. Whether proinsulin levels above 22 pmol/l could also make the diagnosis of endogenous hyperinsulinism in part of the patients at the time of fasting blood glucose levels between 2.5 and 3.3 mmol/l or after an overnight fast in non-obese subjects needs further study. European Journal of Endocrinology 157 75-83

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Section: C-peptide Levels (Nmol/l)mentioning

confidence: 99%

Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Vezzosi¹,

Bennet²,

Fauvel³

et al. 2007

eur j endocrinol

123

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“…Reluctance to routinely combine a glucose load or a test meal with the fasting test may be due to the notion that postprandial hypoglycemia may not be a real disease per se except for reactive adaptations as found in insulin-resistant obesity, early type-2 diabetes, or after gastric surgery [24]. Since description of the first patients with NIPHS [6][7][8] and the characteristic postprandial neuroglycopenia, the diagnostic workup of patients with a suspected hypoglycemic disorder has changed. We recently reported [8] that these patients also may demonstrate late fasting hypoglycemia, typically associated with detectable insulin levels that are inappropriately elevated in the presence of true biochemical hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…Only a subgroup of patients with insulinoma demonstrates grossly elevated insulin levels as well as insulin secretion totally uncoupled to the ambient blood glucose concentration [4,5]. Furthermore, patients with non-insulinoma pancreatogenic hypoglycemia syndrome (NIPHS) present predominantly postprandial neuroglycopenia rather than fasting hypoglycemia associated with low insulin levels [6][7][8]. Diagnostic limits for insulin, C-peptide, proinsulin, and insulin surrogate parameters [9] according to the plasma glucose concentration have been thoroughly defined for the standard 72-h supervised fasting test.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Insulin Secretion Patterns in Insulinoma

2008

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Background In patients with insulinoma, biochemical proof of inappropriately elevated insulin secretion during hypoglycemia is required prior to surgery. Because circulating insulin levels usually vary widely, we have used the combined OGTT-fasting test to define new normative criteria for a retrospective systematic analysis. Methods We retrospectively analyzed insulin concentrations from OGTT-fasting tests of 64 patients with surgically removed insulinomas. In addition, the response to intravenous somatostatin infusions was estimated. Normative criteria were defined to obtain comparable estimates of insulin concentrations: basal, glucose-stimulated maximum, postglucose plateau, and secretory bursts. Results Three types of insulin secretion patterns were identified: (1) the autonomous secretion pattern (type 1, N = 17) with basal and post-OGTT plateau insulin concentrations of approximately 50 mU/L, suppression after OGTT by 41%, virtual absence of distinctive secretory bursts, and resistance to somatostatin-mediated suppression (25 %); (2) the inadequate suppression pattern (type 2, N = 28) with moderately elevated basal and post-OGTT insulin concentrations of approximately 20 mU/L, suppression after OGTT by 73%, absence of secretory bursts, and incomplete somatostatin-induced suppression (56 %); (3) the late-burst secretion pattern (type 3, N = 19) with similar basal and post-OGTT insulin concentrations of 17 mU/L, suppression after OGTT by 76%, true insulin bursts of D 13 ± 11 mU/L (184%), and nearly complete somatostatininduced suppression by 64%. Conclusions By means of a new normative analysis of the combined OGTT-fasting test, three different patterns of insulin secretion can be described in patients with insulinoma: the autonomous secretion type, the inadequate suppression type, and the late-burst secretion type.

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“…Já foi demonstrado que pacientes com nesidioblastose podem apresentar teste de jejum prolongado de 72h negativo e que o diagnóstico dessa desordem é mais difícil em relação ao insulinoma, sendo necessá-ria, muitas vezes, a realização do TOTG de 5h (27). Raros são os casos de falso-negativo em pacientes com insulinoma relatados na literatura e cuja demonstração do estado hiperinsulinêmico e da hipoglicemia foi realizada mediante o TOTG de 5h (28,29) ou do teste pós-refeição mista (3).…”

Section: Em Nosso Estudo Foram Avaliados Os Aspectos Diagnós-ticos (Cunclassified

Hiperinsulinismo endógeno: revisão e seguimento de 24 casos

Felício

Martins

Semer

et al. 2012

Arq Bras Endocrinol Metab

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SUMÁRIOEm decorrência do hiperinsulinismo endógeno (HHE), a hipoglicemia é diagnosticada em um indivíduo sintomático com níveis baixos de glicose plasmática, concomitante a valores elevados de insulina plasmática e peptídeo-C. Entre as causas de HHE, estão as doenças das células-b das ilhotas pancreáticas, o uso de secretagogos e a hipoglicemia autoimune. Neste artigo de revisão, estudamos 24 pacientes com hipoglicemia decorrente de hiperinsulinismo endógeno com a finalidade de descrever os aspectos de diagnóstico e tratamento. Nosso estudo mostrou que, após a realização do teste de jejum de 12h (minijejum) em três dias diferentes, todos os pacientes preencheram os critérios diagnósticos de HHE. Adicionalmente, encontramos que 11 dos 12 pacientes (91,7%) que realizaram o teste do glucagon apresentaram níveis de glicose no tempo 120 minutos menores que 50 mg/dL e inferiores ao valor basal. O teste do minijejum (3 amostras) e o teste do glucagon poderiam ser úteis para evitar a realização do jejum prolongado no diagnóstico do hiperinsulinismo endógeno. Arq Bras Endocrinol Metab. 2012;56(2):83-95 Descritores Hiperinsulinismo; insulinoma; hipoglicemia; pâncreas SUMMARY Hypoglycemia due to endogenous hyperinsulinism (EH) is diagnosed in a symptomatic patient with low levels of plasma glucose concomitant with elevated plasma insulin and C-peptide. Causes of EH are pancreatic islet-cells disease, use of insulin secretagogues, and autoimmune hypoglycemia. In this review, the authors studied 24 patients with hypoglycemia due to endogenous hyperinsulinism in order to describe aspects of diagnosis and treatment. Our study demonstrated that after 12 hours of fasting (mini-fasting test; at least three samples), all patients presented the diagnostic criteria for EH. Additionally, we found that 11 of 12 patients (91.7%) who underwent glucagon test achieved glucose levels less than 50 mg/dL and below baseline after 120 minutes. Mini-fasting (3 samples) and glucagon test may be useful to prevent prolonged fasting test to clarify the diagnosis of endogenous hyperinsulinism. Arq Bras Endocrinol Metab. 2012;56 (2) INTRODUÇÃOA glicose é um substrato metabólico fundamental para o cérebro, sendo a prevenção e a correção da hipoglicemia fundamentais para a manutenção da vida (1). A hipoglicemia pode ser dividida em pós-prandial (até 5h após a refeição) e de jejum e seu diagnóstico se baseia na presença da tríade de Whipple (glicose plasmática baixa, sintomas compatíveis com hipoglicemia e melhora dos sintomas após o aumento nas concentrações de glicose), cuja presença deve impelir à análise de suas potenciais causas, sendo essa investigação fortemente recomendada (2,3). Entretanto, o diagnóstico é praticamente inequívoco mesmo na ausên cia de sintomas se os valores de glicose plasmática estiverem abaixo de: 50 mg/dL na idade adulta e na adolescência (4,5), 40 mg/dL na criança pré-púbere (6), 30 mg/dL no neonato a termo e 20 mg/dL no neonato prematuro e/ou pequeno para a idade gestacional (7). EnCorrespondência para:

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Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non‐Insulinoma Pancreatogenic Hypoglycemia Syndrome

Abstract: In patients with postprandial and/or fasting neuroglycopenia NIPHS may be suspected when insulin levels are low but inadequately suppressed and localization studies failed to show a distinct pancreatic tumor.

Cited by 42 publications

References 58 publications

Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Differentiation of Insulin Secretion Patterns in Insulinoma

Hiperinsulinismo endógeno: revisão e seguimento de 24 casos

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