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

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. Orv. Hetil., 2015, 156(16), 626-635

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH

A szomatosztatinanalóg kezelés eredményei acromegaliában = Outcome of somatostatin analogue treatment in acromegaly

Az acromegalia kezelésére rendelkezésre álló lehetőségek közül a gyógyszeres, elsősorban szomatosztatinanalógokkal történő kezelés jelentősége az utóbbi évtizedben számottevően megnőtt. Célok: Jelen közlemény a Semmelweis Egyetem Általános Orvostudományi Karának, II. Sz. Belgyógyászati Klinikáján az elmúlt 10 évben acromegalia miatt szomatosztatinanalóg kezelésben részesült betegek kezelési eredményeit foglalja össze. Betegek és módszerek: A szerzők 1–7 éven keresztül (átlag±SE 3,1±0,3 év) szomatosztatinanalóg kezelésben részesülő 32 acromegaliás betegben (26 nő és 6 férfi) a szérum-növekedésihormon (GH) és az inzulinszerű növekedési faktor-1 (IGF-1) koncentrációját, valamint MR-vizsgálattal a hypophysisadenoma méretének változását elemezték. Primer szomatosztatinanalóg kezelést 10 beteg (7 nő és 3 férfi) kapott, előzetes műtét után 15 beteg (14 nő és 1 férfi), előzetes műtét és sugárkezelés után 7 beteg (5 nő és 2 férfi) részesült szomatosztatinanalóg kezelésben. Eredmények: A szomatosztatinanalóg kezelés bevezetése után 3 hónappal mind a szérum-GH-, mind a kor és nem szerinti referenciatartomány felső határához viszonyított relatív IGF-1-értékek szignifikánsan csökkentek, majd a kezelés további időtartama alatt kisebb átmeneti változásoktól eltekintve a 3 hónap után elért csökkent szinten maradtak. A szérum-GH 15,7±4,9 ng/ml szintről a kezelés végére 5,5±1,4 ng/ml értékre, a relatív IGF-1 204±14%-ról 135±12%-ra csökkent. A kezelés hatékonyságát nem befolyásolta a szomatosztatinanalóg alkalmazását megelőző műtéti vagy műtéti és sugárkezelés. A kezelés végén a betegek 36,7%-ában észleltek biztonságos (<2,5 ng/ml) szérum-GH-szintet, míg a relatív IGF-1-érték a betegek 41,4%-ában érte el a célértéket (<100%). Az MR-vizsgálat a betegek 46%-ában mutatott ki hypophysisdaganat-regressziót, progressziót egyetlen esetben sem észleltek. Következtetések: A szomatosztatinanalóg kezelés hatékony kezelési lehetőséget jelent azoknál az acromegaliás betegeknél, akiknél primer hypophysisműtét a társuló betegségek, illetve szövődmények miatt nem végezhető, vagy a műtét (és sugárkezelés) ellenére a betegség aktivitása fennmarad, vagy a betegség kiújul. | During the past decade the importance of medical therapy, especially treatment with somatostatin analogues has increased significantly in patients with active acromegaly. Aims: Authors analyzed the outcome of somatostatin analogue treatment in acromegalic patients evaluated and followed up at the 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, during the past 10 years. Patients and methods: Changes in serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentration, as well as morphologic changes of pituitary adenomas followed by MRI scans were evaluated and compared in 32 acromegalic patients (26 women, 6 men) during long-term somatostatin analogue treatment (mean±SE, 3.1±0.3 years, range, 1–7 years). Primary somatostatin analogue treatment was applied in 10 patients (7 women and 3 men), whereas 15 patients (14 women and 1 man) had pituitary surgery and 7 patients (5 women and 2 men) underwent both pituitary surgery and irradiation therapy prior to somatostatin analogue treatment. Results: After a 3-month treatment with somatostatin analogues, both serum GH and IGF-1 levels decreased significantly and they remained around the same decreased levels throughout the treatment period. Serum GH decreased from 15.7±4.9 to 5.5±1.4 ng/ml, and serum IGF-1, expressed as a percentage of the upper limit of age- and sex-adjusted reference value, decreased from 204±14% to 135±12% at the end of treatment. The efficacy of somatostatin analogue treatment was not influenced by surgical or surgical and irradiation therapies which were applied prior to medical treatment. At the end of treatment 36.7% of patients had safe serum GH (<2.5 ng/ml), while serum IGF-1 returned below the upper limit of age- and sex-adjusted reference range in 41.4% of patients. Pituitary MRI showed regression of the adenoma in 46% of patients, and none of the patients had progression of the pituitary adenoma. Conclusions: Somatostatin analogues are effective therapeutic options for acromegalic patients when primary surgical treatment cannot be performed due to complications and associated disorders, or in patients whose acromegaly remains active after pituitary surgery or after pituitary surgery and irradiation

Atherosclerotic risk factors and complications in patients with non-functioning adrenal adenomas treated with or without adrenalectomy: a long-term follow-up study

Objective: Despite the increased prevalences of hypertension. type 2 diabetes mellitus (T2DM). hyperlipidemy, and obesity in patients with non-functioning adrenal adenomas (NFAAs), there is a paucity of data on long-term atherosclerotic morbidity as well as the long-term cardiovascular effects of adrenalectomy in these patients. Design, patients, and methods: This retrospective study includes the results or baseline and follow-up investigations of 125 patients (29 males and 96 females: mean age 60.1 years) with NFAAs referred for endocrine evaluation between 1990 and 2001. Of the 125 patients, 47 underwent unilateral adrenalectomy, while 78 patients were followed conservatively. These patients were reinvestigated after a mean follow-up time of 9.1 (5-16) years in 2006, with special emphasis on laboratory and other atherosclerotic risk factors (ARF), vascular events, and interventions. Results: The prevalences of hypertension, impaired glucose tolerance or T2DM, hyperlipidemy, and obesity were 82, 43, 58, and 50%, and 89, 58, 82, and 50% at baseline and follow-up, respectively None of the investigated ARF prevalences were different between patients treated and not treated with adrenalectomy, and between patients with and without subclinical Cushing's syndrome. The prevalences of angina pectoris, acute myocardial infarction, coronary and peripheral arterial interventions or cerebrovascular stroke did not differ significantly between patients treated and not treated with adrenalectomy Conclusion: Our study confirms previous investigations reporting markedly increased prevalences of various ARF in patients with NFAAs. Adrenalectomy performed in these patients failed to decrease the prevalence of ARF and atherosclerotic morbidit

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Hungarian Scientific Research Fund (OTKA, PD100648 (AP)) Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010). AP is the recipient of a “Lendület” grant from the Hungarian Academy of Sciences

A iatrogén Cushing-szindróma kezelése: a glükokortikoid terápia leépítésének kérdései = Treatment of iatrogenic Cushing’s syndrome: questions of glucocorticoid withdrawal

A iatrogén Cushing-szindróma a hypercortisolismus leggyakoribb formája. Számos betegség kezelésében alkalmaznak sokszor nagy adagban glükokortikoidokat, ami nem ritkán súlyos klinikai képpel jellemzett hypercortisolismus kialakulásához vezet. A iatrogén Cushing-szindróma különlegességét az exogén glükokortikoidok okozta hypercortisolismus tüneteinek és az endogén hypothalamo-hypophysis-mellékvese rendszer gátlásának kettőssége adja. A kórkép kezelésének központi kérdése a glükokortikoid terápia leépítésének nehézsége. A hypothalamus-hypophysis-mellékvese rendszer gátlásában és regenerálódásában igen nagy fokú az egyének közötti variabilitás, emiatt a leépítés megtervezése csak fokozatosan, a klinikai kép és az endogén hormonaktivitás hatékonyságát jelző laboratóriumi paraméterek figyelembe vételével lehetséges. A leépítés során három fő szövődmény jelentkezhet: az alapbetegség reaktiválódása, másodlagos mellékvesekéreg-elégtelenség kialakulása, ill. az ún. szteroid megvonási tünetegyüttes. A szerzők saját klinikai tapasztalataik és a nemzetközi irodalom javaslatai alapján foglalják össze a témakör legfontosabb kérdéseit. Iatrogenic Cushing’s syndrome is the most common form of hypercortisolism. Glucocorticoids are widely used for the treatment of various diseases, often in high doses that may lead to the development of severe hypercortisolism. Iatrogenic hypercortisolism is unique, as the application of exogenous glucocorticoids leads to the simultaneous presence of symptoms specific for hypercortisolism and the suppression of the endogenous hypothalamic-pituitary-adrenal axis. The principal question of its therapy is related to the problem of glucocorticoid withdrawal. There is considerable interindividual variability in the suppression and recovery of the hypothalamic-pituitary-adrenal axis, therefore, glucocorticoid withdrawal and substitution can only be conducted in a stepwise manner with careful clinical follow-up and regular laboratory examinations regarding endogenous hypothalamic-pituitary-adrenal axis activity. Three major complications which can be associated with glucocorticoid withdrawal are: i. reactivation of the underlying disease, ii. secondary adrenal insufficiency, iii. steroid withdrawal syndrome. Here, the authors summarize the most important aspects of this area based on their clinical experience and the available literature data