Search

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Our 69-year-old female patient was investigated for a 20 kg weight gain over 2 years. The patient's medical history included hypertension, hyperuricemia, bilateral cataract surgery and musculosceletal complaints. Diabetes mellitus was not found. Physical examination revealed abdominal obesity, proximal myopathy and atrophic, vulnerable skin. The "overnight", low-dose and long, low-dose dexamethasone suppression tests indicated autonomous cortisol overproduction (plasma cortisol level: 172.6 and 153.2 nmol/L, cut-off: 50 nmol/L). The suppressed ACTH (<1.11 pmol/L, normal value: 1.12-10.75 pmol/L) suggested ACTH-independent hypercortisolism. Abdominal CT described macronodular enlargement of both adrenals. The size of the largest nodule was 23 × 20 mm in the right, and 24 × 30 mm on the left side (with -33 ± 37 HU density values on native scans). The 131I-cholesterol adrenal scintigraphy and SPECT/CT showed almost equally intensive radiopharmacon uptake on both sides. Based on the clinical results, bilateral macronodular adrenal hyperplasia associated with ACTH-independent hypercortisolism was diagnosed. Genomic DNA was obtained from the peripheral blood leukocytes. Targeted sequencing of 25 genes potentially involved in adrenal tumorigenesis revealed a new disease-causing armadillo repeat-containing 5 (ARMC5) gene mutation (c.1724del28 bp, g.31,476,067-31,476,094). Because of the autosomal dominant inheritance of this genetic alteration, the patient's two children underwent genetic screening for the ARMC5 mutation. The same mutation was found in the younger child of our patient. To the best of our knowledge, this is the first published Hungarian case of ARMC5 mutation with bilateral macronodular adrenal hyperplasia and ACTH-independent Cushing's syndrome. The genetic alteration is present in two generations of the family of the index patient. Orv Hetil. 2023; 164(32): 1271-1277.

Congenital adrenal hyperplasia is a group of genetic diseases due to the disablement of 7 genes; one of them is steroid 21-hydroxylase deficiency. The genes of congenital adrenal hyperplasia encode enzymes taking part in the steroidogenesis of adrenal gland. Steroid 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations of the steroid 21-hydroxylase gene. The mutations of steroid 21-hydroxylase gene cause 95% of the congenital adrenal hyperplasia cases. Although the non-classic steroid 21-hydroxylase deficiency with mild symptoms is seldom diagnosed, the classic steroid 21-hydroxylase deficiency may lead to life-threatening salt-wasting and adrenal crises due to the insufficient aldosterone and cortisol serum levels. The classic type requires life-long steroid replacement which may result in cushingoid side effects, and typical comorbidities may be also developed. The patients' quality of life is decreased, and their mortality is much higher than that of the population without steroid 21-hydroxylase deficiency. The diagnosis, consequences and the patients' life-long clinical care require a multidisciplinary approach: the specialists in pediatrics, internal medicine, endocrinology, laboratory medicine, genetic diagnostics, surgery, obstetrics-gynecology and psychology need to work together. Orv Hetil. 2018; 159(7): 269-277.

The common features of hereditary endocrine tumour syndromes or multiple endocrine neoplasias (MEN) are the association of various tumours of different endocrine organs in one patient or within the same family. Different types can be distinguished from among which type 1 and type 2 are the most common. The mode of inheritance is autosomal dominant, meaning that there is a 50% chance to inherit the pathogenic alteration. The pathogenic variants of genes responsible for MEN syndromes have also been identified in sporadic endocrine tumours and many cases initially referred to as sporadic have been later categorized as familiar based on genetic analysis. The main role of the molecular genetic analysis in these syndromes is to identify the pathogenic variant, then, after appropriate genetic counseling, to perform the genetic screening of first-degree relatives. Following molecular genetic analysis, the state-of-the-art clinical follow-up of the clinically healthy mutation carriers may decrease or even prevent the morbidity and mortality. Due to technological developments in recent years, the molecular genetic analysis of hereditary tumour syndromes has also been changed. Using next generation based sequencing methods in routine clinical diagnostics, the number of pathogenic genes in endocrine tumours has also increased. The present review focuses on the genetic background of hereditary endocrine tumour syndromes and the recently used molecular biological methods will also be presented. Orv Hetil. 2018; 159(7): 285-292.

Endogenous glucocorticoids exert a diverse array of physiological processes and play an important role in immune modulatory and anti-inflammatory responses. The secretion of cortisol by the adrenal gland is regulated through two mechanisms. Systemic regulation is substantiating by the hypothalamo-pituitary-adrenal axis. Furthermore, a tissue-specific local regulatory system, containing the 11β-hydroxysteroid dehydrogenase enzyme responsible for local glucocorticoid synthesis and the glucocorticoid receptor, has also been demonstrated. Based on the recent evidences, an extra-adrenal corticosteroid synthesis exists in various tissues. Steroidogenic enzymes necessary for this de novo corticosteroid synthesis have been observed in the skin, intestine, thymus and possibly in the brain, heart and lung. These locally synthesized steroids most likely act in an autocrine and paracrine manner and their regulation is mediated by local regulatory loops. The importance of this de novo corticosteroid synthesis seems to be important in the regulation of local homeostasis, immune processes and tissue-specific inflammatory reactions. Orv Hetil. 2018; 159(7): 260-268.

Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2-15% of patients with idiopathic short stature (ISS), in 50-90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome., Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency., Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods., Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients., Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351-1356.

Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929-937.

MicroRNAs (miRNA, miR) are short - 19-25 nucleotide long - single stranded (in their mature form), non-coding RNA molecules that regulate gene expression mostly at the posttranscriptional level. microRNAs are involved in the regulation of various physiological processes such as cell differentiation and proliferation, development, haematopoesis, cell death, while their aberrant expression is observed in numerous diseases, like autoimmune disorders, inflammations, vascular diseases or tumorigenesis. microRNAs are expressed in a tissue specific fashion. Beyond their appearance in tissues, they can be found in body fluids as well. microRNAs are present in blood, mother milk, semen, saliva, urine, etc. MicroRNAs in body fluids, especially the blood-borne circulating microRNAs can be exploited as minimally invasive biomarkers of tumor diagnosis. The number of endocrine tumor-associated circulating microRNA alterations is relatively low, mostly described for papillary thyroid cancer, adrenocortical cancer, ovarian and neuroendocrine tumors. As the histological diagnosis including the establishment of malignancy of some of these neoplasms is difficult, studies on circulating microRNAs might have great perspectives. Orv. Hetil., 2017, 158(13), 483-490.

Phaeochromocytoma is a tumor of the catecholamine-producing cells of the adrenal gland. Extraadrenal phaeochromocytomas are frequently called paragangliomas. The majority of phaeochromocytomas are sporadic, however, about 25-30% are caused by genetic mutation. These tumor are frequently referred as hereditary phaeochromocytomas/paragangliomas. Their incidence increases continuously which can be attributed to availability of genetic examination and to the discovery of novel genes. The 47-year-old female patient underwent abdominal computed tomography which revealed bilateral adrenal gland enlargement. Abdominal magnetic resonance imaging, the 131-I- metaiodobenzylguanidine scintigraphy, urinary catecholamines and serum chomogranin A measurements confirmed the diagnosis of bilateral phaeochromocytomas. The genetically identical twin sister of the patient was also diagnosed with hormonally active bilateral phaechromocytoma, suggesting the genetic origin of phaeochromocytoma. Mutation screening confirmed a germline mutation of the transmembrane protein 127 tumorsupressor gene in both patients. Both patients underwent cortical-sparing adrenalectomy. The adrenal gland with the larger tumor was totally resected, while in the opposite side only the tumor was resected and a small part of the cortex was saved. After the operation urinary catecholamines and serum chromogranin A returned to normal in both patients. Adrenocortical deficiency was absent in the first patient, but her sister developed adrenal insufficiency requiring glucocorticoid replacement. To the best of the authors' knowledge phaeochromocytoma affecting twins has never been described earlier. Genetic examination performed in siblings confirmed the presence of the mutant gene through four generations. Orv. Hetil., 2016, 157(33), 1326-1330.

The technical developments leading to revolution in clinical genetic testing offer new approaches for patients with cancer. From one mutation or one gene approach the scale of genetic testing moved to whole exome or whole genome scale. It is well known that many tumours are genetically determined and they are part of familial tumour syndromes. In addition, some mutations indicate specific molecular targeted therapies. Although sampling and sample preparation are different for testing germline and somatic mutations, the technical background of the analysis is the same. The aim of clinical genetic testing is to identify patients who are carriers of disease-causing mutations or to test tumour tissue for the presence of genetic alterations which may be targets for therapeutic approaches. In this review the authors summarize novel possibilities offered by next-generation sequencing in clinical genetic testing of patients with endocrine tumours. In addition, the authors review recent guidelines on technical and ethical issues related to these novel methods.

Estrogens modulate the immune response as well as the risk and progression of autoimmune disorders. Their effects are mediated by nuclear receptors (i.e. estrogen receptor alpha and beta), membrane receptors, and are influenced by their interactions with other hormones. Locally produced hormones and cytokines are the main factors in maintaining tissue homeostasis. The response of immune cells to estrogens is related to their developmental stage. The diverse effects of estrogens on various autoimmune disorders are the result of the versatility of their pathomechanism. In general, progression of B-cell mediated disorders is aggravated by estrogens. Their effects on T-cell mediated disorders, on the other hand, are driven by Th1 or Th2 dominance. As estrogens promote the escalation of the Th2 immune response, Th2-dominant disorders are aggravated, while Th1-dominant disorders are ameliorated upon high estrogen levels. Inflammation on its own also modulates the impact of estrogens. Inflammatory cytokines alter the expression of the alpha and beta estrogen receptors as well as the activity of estrogen metabolizing enzymes. Monitoring the local, tissue-wide interaction between hormones and immune cells would provide a better tool for identification and characterization of molecules involved in this system. To date, routinely used laboratory methods have a limited role in monitoring the local effects of estrogens. In this current paper the authors summarize the role of estrogens in immune system and overview those novel methods which are useful in the investigation of local endocrine milieu.

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.

Chromogranin-A is a member of the granine protein family. It is produced in neuroendocrine cells via secretory granules. Many cleavage proteins are formed from chromogranin-A, from which some have well known biological activity, while the function of others is not yet fully known. Serum chromogranin-A levels are used in neuroendocrine tumour diagnostics. Recent studies showed that one of its cleavage protein, WE-14 may also play a role in the development of type 1 diabetes. WE-14 may function as an autoantigen for T-cells involved in the destruction of β-cells. This mechanism was previously observed only in non-obese diabetic mice. Novel results show that WE-14 also serves as a target for autoreactive cells in newly diagnosed type 1 diabetic patients as well, which reaction can be increased with transglutaminase. In this paper the authors summarize the recent knowledge about chromogranin-A and its potential role in the pathomechanism of type 1 diabetes mellitus.

Circulating markers of neuroendocrine tumours are useful tools in the diagnosis of these tumours. Laboratory tests for general biomarkers have acceptable sensitivity for the recognition of neuroendocrine tumours as these biologically active proteins are typically synthesized by all types of neuroendocrine cells. Measurement of chromogranin A is widely used not only in the diagnosis of neuroendocrine tumours but it may predict the prognosis of the diseases and the effect of the antitumor therapy. It is also a useful tool for the detection of residual tumours. Neurendocrine tumours represent a heterogeneous group of tumours with the ability to secrete several hormones and, therefore, measurement of these hormones can also serve as neuroendocrine cell type-specific markers in routine clinical practice. In this review the authors summarize the significance of tumour markers in the diagnosis of neuroendocrine tumours as well as in the management and follow-up of patients with this disease.

The most important estrogen is estradiol in both men and women. In men elevated estradiol levels and associated metabolic disorders have been implicated in the development of common diseases including cardiovascular disorders, insulin resistance and type 2 diabetes mellitus, as increased estradiol associated with decreased testosterone levels increases the risk of these diseases. In this review the authors summarize the causes and consequences of androgen deficiency and estradiol excess, and they review recent studies on potential therapeutic strategies to correct increased estradiol levels in men.

Carcinoids are rare tumors originating from neuroendocrine cells. A large proportion of these tumors produce serotonin and other biologically active hormones which may produce carcinoid syndrome characterized by flushing, diarrhoea and bronchospasm. Carcinoid heart disease, a rare complication of carcinoid syndrome, may itself have a great impact on life expectancy of patients with carcinoid syndrome. The authors present a case history of a patients with carcinoid heart disease and they review the symptoms, diagnosis and therapeutic options of this rare complication of carcinoid syndrome.

Glucocorticoids play an important role in the regulation of carbohydrate and amino acid metabolism, they modulate the function of the immune system, and contribute to stress response. Increased and decreased production of glucocorticoids causes specific diseases. In addition to systemic hypo- or hypercortisolism, alteration of local synthesis and metabolism of cortisol may result in tissue-specific hypo- or hypercortisolism. One of the key enzymes participating in the local synthesis and metabolism of cortisol is the 11β-hydroxysteroid dehydrogenase enzyme. Two isoforms, type 1 and type 2 enzymes are located in the endoplasmic reticulum and catalyze the interconversion of hormonally active cortisol and inactive cortisone. The type 1 enzyme mainly works as an activator, and it is responsible for the generation of cortisol from cortisone in liver, adipose tissue, brain and bone. The gene encoding this enzyme is located on chromosome 1. The authors review the physiological and pathophysiological processes related to the function of the type 1 11β-hydroxysteroid dehydrogenase enzyme. They summarize the potential significance of polymorphic variants of the enzyme in clinical diseases as well as knowledge related to inhibitors of enzyme activity. Although further studies are still needed, inhibition of the enzyme activity may prove to be an effective tool for the treatment of several diseases such as obesity, osteoporosis and type 2 diabetes.

Transient or chronic hyperglycaemia increases the formation of intracellular reactive oxygen species and aldehydes. The accumulation of reactive aldehydes is implicated in the development of diabetic complications. Methylglyoxal, a glucose dependent α-dicarbonyl might be the most important reactive aldehyde in diabetes and its complications. Diabetes was the first disease in which evidence emerged for the increased formation of methylglyoxal in the cells and in the serum. Methylglyoxal has a toxic effect on insulin secretion from pancreatic beta-cells, and on modifications of proteins and nucleic acids. Moreover, methylglyoxal is one of the major precursors of advanced glycation end-products. The glyoxalase enzyme system that exists in all mammalian cells is catalyzing the detoxification of methylglyoxal. This review summarizes the methylglyoxal metabolism in normoglycaemic and hyperglycamic conditions and the role of methylglyoxal in the development of late diabetic microvascular complications.

Carney complex is a rare disease inherited in an autosomal dominant manner. It is mostly caused by inactivating mutations of the subunit of protein kinase A. Carney complex is associated with atrial myxoma, nevi or myxomas of the skin, breast tumors and endocrine overactivity. Primary pigmented nodular adrenocortical disease is the specific endocrine manifestation. The authors present the history of a 53-year-old female patient who had undergone surgery for atrial myxomas, thyroid tumor and breast cancer. She was also operated for an adrenal adenoma causing Cushing's syndrome. Genetic study revealed a mutation in the regulatory subunit of protein kinase A (ivs2-1G>A splice mutation in intron 2). Her heterozygous twins were also genetically screened and one of them carried the same mutation. The authors emphasize that despite the absence of specific treatment for patients with Carney complex, confirmation of the diagnosis by genetic studies is important for the close follow-up of the patient and early identification of novel manifestations.

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1.

Complete or partial gene deletions and copy number variations of disease-causing genes have pathophysiological significance in several monogenic hereditary diseases. Direct DNA sequencing is not suitable for the detection of these genetic abnormalities. In this work, authors review methods of large gene deletion testing and present their own results in two monogenic diseases to demonstrate the application of current methods in clinical practice. Classical methods (chromosome banding, Southern-hybridisation, fluorescent in situ hybridisation), polymerase chain reaction-based techniques (denaturing high performance liquid chromatography, quantitative real-time polymerase chain reaction, microsatellite marker analysis, multiple amplifiable probe hybridisation, multiple ligation probe amplification) as well as techniques based on recent advances in bioinformatics (comparative genome hybridisation, array-based analysis) are presented. Finally, authors present their own findings on large deletion testing of the VHL gene using quantitative real-time polymerase chain reaction and multiple ligation probe amplification in patients with von Hippel-Lindau disease and review a simple polymerase chain reaction method for the detection of large deletion of the CYP21A2 gene in patients with congenital adrenal hyperplasia.

Unlabelled: 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.

Ionic calcium has been known as an important intracellular second messenger for many decades. In addition, a whole series of experimental and clinical studies from the past fifteen years have provided evidence that extracellular ionic calcium itself is also a first messenger, since it is the ligand of a cell surface G-protein coupled receptor called calcium-sensing receptor. This review summarizes the current knowledge on the role of calcium-sensing receptor in the maintenance of calcium homeostasis, its functions in various tissues and some of the most important disorders characterized by defective calcium sensing. The inherited disorders of the calcium-sensing receptors may be classified as the results of loss-of-function and gain-of-function mutations of the calcium-sensing receptor gene. Loss-of-function heterozygous mutations lead to familial hypocalciuric hypercalcemia while homozygous mutations result in the frequently life-threatening disorder called neonatal severe hyperparathyroidism. Gain-of-function mutations of this receptor's gene cause the disorder called autosomal dominant hypocalcemia. The authors briefly highlight the clinical features, laboratory characteristics and therapeutic implications of these disorders. Also, they discuss briefly the molecular mechanisms resulting defective calcium-sensing in of patients with primary and secondary hyperparathyroidism, and summarize the results of some recent investigations on the functional consequences of genetic variants of the calcium-sensing receptor gene.

Unlabelled: Hereditary paraganglioma/pheochromocytoma syndrome is an autosomal dominantly inherited disease caused by germline mutation of the genes encoding subunits of the mitochondrial succinate dehydrogenase (SDH) enzyme involved in the mitochondrial respiratory chain. The pathogenetic role of SDH gene mutations was first recognized in 2000. Authors present the history of a patient with extra-adrenal pheochromocytoma who represents in Hungary the first genetically confirmed case of hereditary paraganglioma/pheochromocytoma syndrome due to disease-causing mutation of the SDHD gene. Also, the authors review the progress of our knowledge about this syndrome., Case Report: A 33 years-old man was observed with hypertension, increased perspiration and palpitation. Laboratory analysis showed increased urinary catecholamine metabolite excretion, abdominal radiologic imaging revealed a retroperitoneal tumor with 3.5 cm extension located close to the abdominal aorta. After tumor resection the clinical symptoms disappeared. Histological examination of the tumor proved extra-adrenal pheochromocytoma. Although family history was unremarkable, the young age of the patient raised the possibility of a hereditary syndrome. Mutation screening using peripheral blood DNA samples of the patient indicated the presence of c.148-149 insA frameshift mutation of the SDHD gene. Genetic analysis of family members revealed the presence of the same mutation in his asymptomatic father while the mutation was not present in his mother and brother., Conclusion: The presented patient represents the first case with hereditary paraganglioma/pheochromocytoma syndrome from Hungary, in whom genetic analysis identified a disease-causing mutation of the SDHD gene. Pedigree analysis was compatible with genomic imprinting which has been demonstrated in many families with this syndrome.

Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining glucocorticoid sensitivity. The physiologic response and sensitivity to glucocorticoids may significantly differ among species, individuals, tissues and cell types. The variability of the effect of endogenous and exogenous glucocorticoids is largely determined by genetic components, of which the authors review the knowledge on the glucocorticoid receptor gene. The authors describe the genomic and non-genomic pathways of receptor function, the significance of isoforms produced during receptor protein formation, the pathomechanism of glucocorticoid resistance syndrome and the results of clinical investigations related to receptor gene polymorphisms. Through subtle alteration of receptor function, the gene polymorphisms may increase or diminish sensitivity to glucocorticoids and may play a role in the pathogenesis of metabolic disorders. In their own studies the authors found, that the N363S polymorphism, which increases glucocorticoid sensitivity, may play a role in the pathogenesis of bilateral adrenal adenomas, it may modify the clinical phenotype of patients with congenital adrenal hyperplasia, and may have an impact on steroid-induced ocular hypertension. It is presumed that further research in other diseases will continue to complete our knowledge on the pathophysiology of glucocorticoid receptor gene polymorphisms.

Introduction: Primary aldosteronism is the most common form of mineralocorticoid hypertension. The disease has been described by Jerome W. Conn in 1955; since that time there has been a great progress in the knowledge concerning the prevalence, diagnostics and treatment of the disease., Aims: The authors retrospectively analyzed the efficacy of diagnostic procedures and the outcome of treatment by the analysis of data of 187 patients with primary aldosteronism examined between 1958 and 2004 at the 2nd Department of Medicine of Semmelweis University., Methods: The efficacy of different methods used for the diagnosis, the frequency of the different subtypes of primary aldosteronism, as well as the surgical outcomes in patients with surgically treated subtypes of primary aldosteronism were studied., Results: Aldosterone-producing adenoma was detected in more than two thirds of patients (n = 135), whereas idiopathic hyperaldosteronism was found in 46 patients. Other subtypes of primary hyperaldosteronism occurred less frequently (unilateral primary adrenocortical hyperplasia in 5 patients and adrenocortical carcinoma in one patient). For the diagnosis of familial hyperaldosteronism type I, molecular biological studies of the aldosterone-synthase/11beta-hydroxylase gene chimera were carried out in 30 patients but none of them showed the presence of the chimeric gene. When comparing the clinical parameters of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, no significant differences were found in the time period between the diagnosis of hypertension and the diagnosis of primary aldosteronism, or in the systolic and diastolic blood pressure values. The mean of the lowest documented serum potassium concentration was slightly lower in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l) compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l), but the difference was not significant. Normokalemic primary hyperaldosteronism was found in 7 cases. The ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h) was above 20 in all patients with aldosterone-producing adenoma and in all but 5 cases with idiopathic hyperaldosteronism. To confirm the diagnosis and to differentiate the subtypes of primary aldosteronism, the postural test combined with furosemide administration was performed in the majority of patients. When cases showing an elevation of plasma cortisol level during the test were excluded, this test differentiated patients with aldosterone-producing adenoma from those with idiopathic hyperaldosteronism with a sensitivity of 69% and a specificity of 92%. In cases of adrenocortical adenomas not or not clearly detectable by radiological imaging techniques, as well as in cases with bilateral adrenocortical adenomas, selective adrenal vein sampling was performed (n = 55). All but 4 patients with aldosterone-producing adenoma underwent adrenalectomy. Histology and postoperative hormone results confirmed the preoperative diagnosis in all operated patients. After surgery serum potassium concentration returned to normal in all patients showing low serum potassium levels before surgery. Also, the moderate to severe preoperative hypertension disappeared or improved after surgery., Conclusions: These observations are in contrast with the results of international studies which showed a high frequency of normokalemic primary aldosteronism and a more frequent occurrence of idiopathic hyperaldosteronism well treatable with aldosterone-antagonists. Therefore, it can be presumed that a significant number of primary aldosteronism cases that are not accompanied with severe hypokalemia remain undetected in Hungary.

Multiple endocrine neoplasia type 1 syndrome is an autosomal dominant disorder characterized by endocrinopathies involving the parathyroid glands, anterior pituitary gland, and pancreas. Also, it may be associated with foregut carcinoid, adrenocortical tumors and non-endocrine tumors. After reviewing the prevalence, genetic background, clinical symptoms, diagnosis and treatment of the disorder, the authors present their genetic screening method used for the detection of mutations of the MEN1 gene (prescreening of polymerase chain reaction amplified exons using temporal temperature gradient gel electrophoresis followed by direct DNA sequencing). Using this method, the authors identified disease-causing MEN1 gene mutations in 9 probands (small deletions in 2 cases, insertion in 2 cases, nonsense mutations in 2 cases and missense mutations in 3 cases). Of the 9 mutations, 4 proved to be novel mutation not reported in the literature. Family screening indicated de novo mutations in 2 probands. In addition to mutations, several sequence polymorphisms were also detected. The authors conclude that one of the major advantages of genetic screening in families with MEN1 syndrome was the identification of family members carrying the mutation who should be regularly screened for disease manifestations and those not carrying the mutation in whom clinical screening is unnecessary. Also, genetic screening may be useful in cases when MEN1 syndrome is suspected, but the clinical manifestations do not fully establish the diagnosis of MEN1 syndrome.

Introduction: Familial hypocalciuric hypercalcemia is often considered but rarely proved during evaluation for hypercalcemia. The disorder is characterized by lifelong persisting hypercalcemia and hypocalciuria., Case Report: In this study, the authors analyzed a 25-yr-old Hungarian woman with mild hypercalcemia detected by routine laboratory testing. Evaluation revealed hypercalcemia, relative hypocalciuria and non-suppressed serum intact parathormone level. The diagnosis of hypocalciuric hypercalcemia was confirmed by the low ratio of calcium clearance/creatinine clearance. Genetic studies for calcium-sensing receptor gene mutations were performed in blood DNA samples. After polymerase chain reaction amplification, DNA sequencing of exons 2-7 were performed. The proband and her father had the same mutation (CCG-->CTG) at codon 55 of exon 2, leading to a conversion of the proline to a leucine., Discussion: This case report presents the first case of familial hypocalciuric hypercalcemia, published in a Hungarian patient.

To study the usefulness of 6beta-hydroxycortisol (6betaOHF) measurements for assessing hepatic drug metabolizing enzyme activity, plasma 6betaOHF and cortisol were measured in 22 patients with alcoholic liver disease after at least 2 weeks of alcohol abstinence, in 5 patients with severe Cushing's syndrome and in 12 healthy non-drinker subjects. Blood samples were drawn under resting conditions during midnight, in the morning at 0800 h, after a 1-mg overnight dexamethasone test and after ACTH administration. Plasma cortisol and 6betaOHF were determined with radioimmunoassay. In patients with alcoholic liver disease, the plasma cortisol levels at midnight and 0800 h, as well as after the administration of dexamethasone and ACTH were not different from corresponding values measured in non-drinker controls. In addition, these patients with alcoholic liver disease had similar plasma 6betaOHF levels at midnight, 0800 h and after dexamethasone administration as compared to corresponding values in controls. By contrast, ACTH administration in patients with alcoholic liver disease resulted in a significantly (p<0.05) larger increase of plasma 6betaOHF (from 106 +/- 22 to 1102 +/- 106 ng/dl, mean +/- SE) as compared to that found in controls (from 74 +/- 3 to 337 +/- 76 ng/dl). The markedly increased 6betaOHF response to ACTH administration in patients with alcoholic liver disease was similar to that measured in patients with severe Cushing's syndrome, in whom increased and non-suppressible plasma cortisol levels were accompanied by markedly elevated plasma 6betaOHF levels. These results indicate that alcohol abstinence in patients with alcoholic liver disease is associated with an exaggerated 6betaOHF response to ACTH and that this abnormality may prove to be a clinically useful parameter for a sensitive detection of altered drug metabolism present in these patients.

The authors review the historical and epidemiological aspects, as well as the distinguishing clinical features and complications of acromegaly to emphasize the importance of early diagnosis and treatment of patients with this disorder. Acromegaly is a rare disorder with a prevalence of 55-69 cases per million population and an incidence of 3-4 newly detected cases per million per year. Recent estimates indicate, that its slow progression and insidious course leads to a considerable time lag of 7-12 years between the first symptoms and the diagnosis of the disease, although younger patients with more severe disease may be detected earlier. In addition to the disfigurement and disability which develop progressively from the onset of the disease, acromegaly is associated with a number of complications resulting in a two- or three-fold increase of mortality and a decrease of life expectancy by about 10 years. The major causes of death include cardiovascular and cerebrovascular events, respiratory disease and malignancy. Because the duration of the disease before effective therapy may be one of the major predictors of increased mortality, practicing doctors need to be particularly vigilant to recognize undiagnosed cases in order to avoid the serious complications of the disease.