Beatrix Sármán

Ghrelin: A new peptide regulating the neurohormonal system, energy homeostasis and glucose metabolism

Identification of ghrelin started with the discovery of growth hormone secretagogues, continued with the description of ghrelin receptors and ended with the elucidation of the chemical structure of ghrelin. However, several issues concerning the role of ghrelin in physiological and pathophysiological processes are still under investigation. Most of the ghrelin produced in the body is secreted in the stomach, but it is also expressed in the hypothalamus, pituitary, pancreas, intestine, kidney, heart and gonads. Ghrelin stimulates growth hormone secretion via growth hormone secretagogue receptors. Ghrelin secretion in the stomach depends on both acute and chronic changes in nutritional status and energy balance. Current data support the hypothesis that the stomach, in addition to its important role in digestion, not only influences pituitary hormone secretion but, via ghrelin production, it also sends orexigenic (appetite increasing) signals to hypothalamic nuclei involved in the regulation of energy homeostasis. In addition to these main effects, ghrelin influences insulin secretion and glucose metabolism and it may exert potentially important effects on cardiovascular and gastrointestinal functions. Because of its effects on a large number of physiological functions, ghrelin may be involved in the pathomechanism of several human disorders, including disturbances of appetite, energy homeostasis and glucose metabolism. Further research might lead to a better understanding of the pathophysiology of ghrelin and might provide more effective therapy for the above disorders. Copyright

Role of endothelin-1 in diabetes mellitus.

Endothelin-1 is mainly synthesized by the vascular endothelial cells and acts on the vascular smooth muscle. Because of its vasoconstrictor and mitogenic effects it plays a role in the development of vascular diseases. In diabetes mellitus atherosclerosis is accelerated. The authors summarize the available data of the role of endothelin-1 in Type 1 and Type 2 diabetes mellitus and the development of diabetic complication.

MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.

Cord serum dipeptidyl-peptidase 4 activity in gestational diabetes

Tissue‐specific dipeptidyl‐peptidase 4 (DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 ‐incretin system has not been studied in foetal life. In this study, DPP4 activity and glucagon‐like peptide‐1 (GLP‐1) levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus (GDM) and nondiabetic controls.

Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma syndrome diagnosed during the past 20 years

Bevezetés: A phaeochromocytoma-paraganglioma szindróma laboratóriumi kórismézése jelentős fejlődésen ment keresztül az utóbbi két évtizedben. Célkitűzés: Jelen vizsgálat célja, hogy retrospektív elemzéssel bemutassa és értékelje a Semmelweis Egyetem, II. Belgyógyászati Klinikán 1993–2013 között diagnosztizált phaeochromocytomás/paragangliomás betegek klinikai és laboratóriumi adatait. Módszer: A vizeletkatecholaminokat és metabolitjaikat nagy felbontású folyadékkromatográfiát követő elektrokémiai detektálással mérték 155 phaeochromocytoma-paraganglioma szindrómás (28,4%-uk örökletes hátterű) betegben és 170 nem phaeochromocytomás egyénben. A szérum-chromogranin-A-t immunradiometriás módszerrel vizsgálták. Eredmények: A 24 órás gyűjtött vizeletben a frakcionált metanephrinek szenzitivitása (93,2%) és specificitása (87,0%) meghaladta a katecholaminok (90,9% és 85,7%) és a szérum-chromogranin-A-meghatározás (88,7%, illetve 77,5%) hasonló értékeit. A vizeletnormetanephrin, illetve a szérum-chromogranin-A pozitív összefüggést mutatott a daganatátmérővel (r = 0,552, p<0,0001, illetve r = 0,618, p<0,0001). Következtetések: Az eredmények a vizelettel ürülő katecholaminmetabolitok meghatározásának jelentőségét igazolják a phaeochromocytoma-paraganglioma diagnosztikájában. A vizeletnormetanephrin és a szérum-chromogranin-A segíthet a tumortömeg és a progresszió megítélésében. Orv. Hetil., 2015, 156(16), 626–635.INTRODUCTION Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. AIM Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. METHOD Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. RESULTS Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). CONCLUSIONS These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

Plasma ghrelin response to an oral glucose load in growth hormone-deficient adults treated with growth hormone

ZusammenfassungHINTERGRUND: Die Pathophysiologie der Ghrelin-Sekretion bei Wachstumshormon-defizienten Erwachsenen unter Therapie mit Wachstumshormon ist weitgehend unbekannt. Auch die Beziehung zwischen Plasma-Ghrelin-Spiegeln und einer durch eine orale Glukosebelastung induzierten Hyperinsulinämie wurde in solchen Patienten noch nicht erforscht. ZIEL DER STUDIE: In der vorliegenden Studie untersuchten wir die Beziehung zwischen Plasma-Ghrelin, Insulin, C-Peptid und Leptin nach einer oralen Glukosebelastung bei Wachstumshormon-defizienten Erwachsenen, die unter einer Therapie mit Wachstumshormon standen. METHODEN: Plasma-Ghrelin, Leptin, Insulin, C-Peptid und Blutzucker wurden vor sowie 30, 60, 90 und 120 Minuten nach der oralen Einnahme von 75 g Glukose bei 20 Wachstumshormon-defizienten Erwachsenen (12 Frauen, 8 Männer), die 7,2 ± 1,3 (MW ± SE) Jahre mit Wachstumshormon behandelt worden waren, gemessen. Plasma-Ghrelin wurde vor und nach einer Glukosebelastung bei 10 gesunden im Alter und Gewicht entsprechenden Personen (5 Männer, 5 Frauen) gemessen. ERGEBNISSE: Die orale Glukosebelastung bewirkte bei Wachstumshormon-defizienten Patienten und bei Gesunden eine prozentuell ähnliche Unterdrückung des Plasma-Ghrelins. In beiden Gruppen sank das Plasma-Ghrelin 30 Minuten nach der Glukosegabe signifikant und blieb von da ab bis zum Ende der Untersuchung unterdrückt. Bei den Wachstumshormon-defizienten Patienten zeigten Insulin (basal 15,9 ± 3,9 µIU/ml) und C-Peptid (basal (2,5 ± 0,3 ng/ml) gegenläufige Veränderungen mit Spitzenwerten 30 Minuten (Insulin: 109,5 ± 15,6 µIU/ml) bzw. 60 Minuten (C-Peptid: 10,3 ± 1,1 ng/ml) nach der Glukosegabe. Zum Unterschied vom basalen Ghrelin korrelierte bei diesen Patienten das post-Glukose Plasma-Ghrelin negativ mit dem Plasma-Insulin, dem C-Peptid und den Blutzuckerwerten. Das basale Ghrelin korrelierte invers mit dem basalen Plasma-Leptin. SCHLUSSFOLGERUNGEN: Die Unterdrückung von Plasma-Ghrelin nach einer oralen Glukosebelastung bei Wachstumshormon-defizienten Patienten unter Wachstumshormon-Therapie ist ähnlich der bei Gesunden beobachteten; dies spricht gegen eine gestörte Regulation der Ghrelin-Sekretion bei diesen Patienten. Die Korrelationen zwischen post-Glukose Plasma-Ghrelin, Insulin und Blutzucker machen einen schon früher vorgeschlagenen Zusammenhang zwischen einer Hyperinsulinämie (bzw. einem erhöhten Blutzucker) und der Suppression der Ghrelin Spiegel wahrscheinlich.SummaryBACKGROUND: Little is known about the pathophysiology of ghrelin secretion in growth hormone-deficient adults treated with growth hormone, and the relationship between plasma ghrelin and hyperinsulinemia induced by an oral glucose load has not been investigated in these patients. OBJECTIVE: In the present study we examined the relationship between plasma ghrelin, insulin, C-peptide and leptin after an oral glucose load in growth hormone-deficient adults receiving treatment with growth hormone. METHODS: Plasma ghrelin, leptin, insulin, C-peptide and blood glucose were measured before and then at 30, 60, 90 and 120 min after the ingestion of glucose (75 g orally) in 20 growth hormone-deficient adults (12 women and 8 men), who had been treated with growth hormone for 7.2 ± 1.3 years (mean ± SE). Plasma ghrelin was also determined before and after the glucose load in 10 age-and weight-matched healthy persons (5 women and 5 men). RESULTS: The oral glucose load induced a similar percent suppression of plasma ghrelin in the growth hormone-deficient patients and in the healthy persons. In both groups plasma ghrelin decreased significantly 30 min after the glucose load and remained suppressed throughout the test period. In the patients plasma insulin (baseline, 15.9 ± 3.9 µIU/ml) and C-peptide (baseline, 2.5 ± 0.3 ng/ml) showed opposite changes with peak responses at 30 min (insulin, 109.5 ± 15.6 µIU/ml) or 60 min (C-peptide, 10.3 ± 1.1 ng/ml). In these patients, post-glucose, but not baseline plasma ghrelin levels correlated negatively with plasma insulin, C-peptide and blood glucose levels, whereas baseline plasma ghrelin correlated inversely with baseline plasma leptin. CONCLUSIONS: The similar suppression of plasma ghrelin in growth hormone-deficient patients treated with growth hormone and in healthy persons after an oral glucose load argues against disturbed regulation of ghrelin secretion in these patients. The correlations between post-glucose plasma ghrelin, insulin and blood glucose support the existence of a previously proposed link between hyperinsulinemia (or increased blood glucose) and suppression of ghrelin levels.

A laboratóriumi diagnosztika eredményei az elmúlt 20 évben kórismézett 155 phaeochromocytoma/paraganglioma szindrómás beteg adatainak elemzése alapján@@@Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma syndrome diagnosed during the past 20 years

Bevezetés: A phaeochromocytoma-paraganglioma szindróma laboratóriumi kórismézése jelentős fejlődésen ment keresztül az utóbbi két évtizedben. Célkitűzés: Jelen vizsgálat célja, hogy retrospektív elemzéssel bemutassa és értékelje a Semmelweis Egyetem, II. Belgyógyászati Klinikán 1993–2013 között diagnosztizált phaeochromocytomás/paragangliomás betegek klinikai és laboratóriumi adatait. Módszer: A vizeletkatecholaminokat és metabolitjaikat nagy felbontású folyadékkromatográfiát követő elektrokémiai detektálással mérték 155 phaeochromocytoma-paraganglioma szindrómás (28,4%-uk örökletes hátterű) betegben és 170 nem phaeochromocytomás egyénben. A szérum-chromogranin-A-t immunradiometriás módszerrel vizsgálták. Eredmények: A 24 órás gyűjtött vizeletben a frakcionált metanephrinek szenzitivitása (93,2%) és specificitása (87,0%) meghaladta a katecholaminok (90,9% és 85,7%) és a szérum-chromogranin-A-meghatározás (88,7%, illetve 77,5%) hasonló értékeit. A vizeletnormetanephrin, illetve a szérum-chromogranin-A pozitív összefüggést mutatott a daganatátmérővel (r = 0,552, p<0,0001, illetve r = 0,618, p<0,0001). Következtetések: Az eredmények a vizelettel ürülő katecholaminmetabolitok meghatározásának jelentőségét igazolják a phaeochromocytoma-paraganglioma diagnosztikájában. A vizeletnormetanephrin és a szérum-chromogranin-A segíthet a tumortömeg és a progresszió megítélésében. Orv. Hetil., 2015, 156(16), 626–635.INTRODUCTION Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. AIM Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. METHOD Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. RESULTS Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). CONCLUSIONS These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

A laboratóriumi diagnosztika eredményei az elmúlt 20 évben kórismézett 155 phaeochromocytoma/paraganglioma szindrómás beteg adatainak elemzése alapján

Bevezetés: A phaeochromocytoma-paraganglioma szindróma laboratóriumi kórismézése jelentős fejlődésen ment keresztül az utóbbi két évtizedben. Célkitűzés: Jelen vizsgálat célja, hogy retrospektív elemzéssel bemutassa és értékelje a Semmelweis Egyetem, II. Belgyógyászati Klinikán 1993–2013 között diagnosztizált phaeochromocytomás/paragangliomás betegek klinikai és laboratóriumi adatait. Módszer: A vizeletkatecholaminokat és metabolitjaikat nagy felbontású folyadékkromatográfiát követő elektrokémiai detektálással mérték 155 phaeochromocytoma-paraganglioma szindrómás (28,4%-uk örökletes hátterű) betegben és 170 nem phaeochromocytomás egyénben. A szérum-chromogranin-A-t immunradiometriás módszerrel vizsgálták. Eredmények: A 24 órás gyűjtött vizeletben a frakcionált metanephrinek szenzitivitása (93,2%) és specificitása (87,0%) meghaladta a katecholaminok (90,9% és 85,7%) és a szérum-chromogranin-A-meghatározás (88,7%, illetve 77,5%) hasonló értékeit. A vizeletnormetanephrin, illetve a szérum-chromogranin-A pozitív összefüggést mutatott a daganatátmérővel (r = 0,552, p<0,0001, illetve r = 0,618, p<0,0001). Következtetések: Az eredmények a vizelettel ürülő katecholaminmetabolitok meghatározásának jelentőségét igazolják a phaeochromocytoma-paraganglioma diagnosztikájában. A vizeletnormetanephrin és a szérum-chromogranin-A segíthet a tumortömeg és a progresszió megítélésében. Orv. Hetil., 2015, 156(16), 626–635.INTRODUCTION Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. AIM Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. METHOD Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. RESULTS Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). CONCLUSIONS These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

Simultaneous presentation of Brugada syndrome and primary aldosteronism

The authors present a case of a 42-year-old male patient, who was referred for evaluation for tachycardia. Detailed studies revealed Brugada syndrome and hypokalaemia due to primary aldosteronism. With this case report the authors draw attention to the risk of malignant ventricular tachycardia in a patient with low potassium level, especially in case of coexisting Brugada syndrome.

Pathogenesis and treatment of pain in chronic pancreatitis

Chronic pancreatitis is an inflammatory, usually painful disease characterized by progressive fibrosis and the loss of exocrine and endocrine functions. Pain influences the quality of life of patients and may lead to inability to work and frequent hospitalisation. The pathogenesis of pain in chronic pancreatitis is still unclear. Several different mechanisms of pain have been proposed, but pain in chronic pancreatitis is most probably multifactorial. Pain management in chronic pancreatitis is difficult. This is due to the multifactorial origin, there are no standardized methods to quantify pain and patients are often addicted to alcohol in chronic pancreatitis. This review summarises the different hypotheses of pain and the possibilities of pain management in chronic pancreatitis.