Miklos Toth

Publications (138) View all

• Article: Glucocorticoid-induced osteoporosis: lessons from cushing's syndrome.

  Miklós Tóth, Ashley Grossman
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  ABSTRACT: Glucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary bone disorders. Most of our knowledge on its pathogenesis and treatment has been obtained by investigating patients treated with exogenous glucocorticoids. This review will focus on the bone disorder in endogenous Cushing's syndrome, updating recent advances in its pathophysiology, diagnostic aspects and the various predictors which are important in determining bone mineral density and fracture risk. We now know strong evidence that beside bone mineral density, bone microarchitecture, one of the most important elements of bone quality, is a key factor in determining fracture risk. Recently, two new methods (spinal deformity index, trabecular bone score) have been shown to be useful markers of bone microarchitecture in GIO. Investigations of GIO in endogenous Cushing's syndrome have also contributed to our understanding on its natural history and reversibility. Relying on recently published guidelines for management of exogenous GIO, a short list of suggestions is provided regarding the optimal diagnostic and therapeutic approach to patients with endogenous GIO. © 2013 Blackwell Publishing Ltd.
  Clinical Endocrinology 03/2013; · 3.17 Impact Factor
• Article: [Importance of the 11β-hydroxysteroid dehydrogenase enzyme in clinical disorders].

  Karolina Feldman, István Likó, Zsolt Nagy, Agnes Szappanos, Vince Kornél Grolmusz, Miklós Tóth, Károly Rácz, Attila Patócs
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  ABSTRACT: 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. Orv. Hetil., 2013, 154, 283-293.
  Orvosi Hetilap 02/2013; 154(8):283-93.
• Article: The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women.

  Karolina Feldman, Agnes Szappanos, Henriett Butz, Vince Grolmusz, Judit Majnik, István Likó, Balázs Kriszt, Péter Lakatos, Miklós Tóth, Károly Rácz, Attila Patócs
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  ABSTRACT: INTRODUCTION: The 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) plays an important role in the regulation of local glucocorticoid concentration in a tissue specific manner. Previous studies indicated associations between polymorphisms (SNPs) of the HSD11B1 gene and laboratory as well as osteodensitometric parameters of bone metabolism. In our present work we examined whether the tagging HSD11B1 gene polymorphisms could influence bone metabolism in healthy and postmenopausal osteoporotic women. EXPERIMENTAL: HapMap database was used for identification and selection of SNPs located in the 38kb range of the HSD11B1 gene. Twelve SNPs were selected and genotyped in 209 healthy control women using Taqman SNP assays on Real-Time PCR and direct DNA sequencing. Of these SNPs, the rs4844880 was genotyped in 154 women with postmenopausal osteoporosis. Functional characterization of the rs4844880 was performed by in vitro luciferase assay. RESULTS: One of the 12 HSD11B1 SNPs, the rs4844880 showed a significant association with higher bone mineral density and/or T- and Z-scores at lumbar spine in healthy women. When data from 154 postmenopausal osteoporotic women were compared to those obtained from 101 age-matched postmenopausal healthy women selected from our healthy control group this association was strongly significant at the femoral neck region. In vitro luciferase assay demonstrated that the polymorphic rs4844880 allele inhibited the luciferase activity more significantly than the major allele. CONCLUSIONS: The rs4844880 polymorphism in the promoter region of the HSD11B1 gene resulting in a reduced expression of the enzyme may exert a beneficial effect on bone in healthy and postmenopausal osteoporotic women.
  Steroids 09/2012; 77(13):1345-1351. · 2.83 Impact Factor
• Article: Cutoff values of midnight salivary cortisol for the diagnosis of overt hypercortisolism are highly influenced by methods.

  Gabriella Beko, Ibolya Varga, Edit Glaz, Marta Sereg, Karolina Feldman, Miklós Toth, Karoly Racz, Attila Patocs
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  ABSTRACT: Midnight salivary cortisol (MSC) concentration has been considered as a sensitive marker of overt hypercortisolism. Because no studies on commercially available automated, non-isotopic MSC assays have been reported, we determined and compared the diagnostic performance of an automated electrochemiluminescent immunoassay (ECLIA, Elecsys E170) and an in-house radioimmunoassay (RIA) for MSC measurement. The study involved 126 consecutive patients referred for evaluation because of symptoms of Cushing's syndrome, obesity, or the presence of incidentally discovered adrenal adenoma. Using detailed clinical, hormonal and radiological evaluation overt endogenous hypercortisolism was confirmed in 9 patients and was excluded in 117 patients. ROC analysis indicated that the best performance of MSC was obtained at cutoff value of 0.35 microg/dl using ECLIA (sensitivity, 100%; specificity, 88%) and 0.29 microg/dl (sensitivity, 100%; specificity, 71%) using RIA. When the findings were compared to those obtained from low dose dexamethasone test, both ECLIA and RIA of MSC showed a better diagnostic performance. MSC measurement is useful for the diagnosis of overt hypercortisolism but the cutoff value is highly dependent on the method used. We recommend the use of automated ECLIA for MSC assay, and we propose further studies on other automated immunoassay analyzers potentially suitable for MSC measurements.
  Clinica chimica acta; international journal of clinical chemistry 12/2009; 411(5-6):364-7. · 2.54 Impact Factor
• Article: [Editor's commentary].

  Miklós Tóth
  Orvosi Hetilap 08/2011; 152(33):1303.