International Journal of Endocrinology and Metabolism International Journal of Endocrinology and Metabolism Int J Endocrinol Metab http://www.endometabol.com 1726-913X 1726-9148 10.5812/ijem en jalali 2017 5 27 gregorian 2017 5 27 10 2
en 10.5812/ijem.2920 Postprandial Effect of Orlistat on the Peaking of Lipid Level After Sequential High Fat Meals Postprandial Effect of Orlistat on the Peaking of Lipid Level After Sequential High Fat Meals research-article research-article Background

Postprandial lipemia has been found to be strongly associated with atherosclerosis due to its atherogenic and thrombogenic lipoprotein changes. This phenomenon occurs even in normal subjects especially after high fat meals. Orlistat, an anti- obesity drug, has been shown to address postprandial lipemia after a single high fat meal.

Objectives

To compare the effects of orlistat and placebo on the postprandial lipid levels after sequential high-fat meals in healthy individuals with normal fasting lipid levels.

Patients and Methods

Thirty-one healthy adult volunteers with normal fasting lipid levels were fed 50% fat meals (3 meals and 2 snacks of pre-weighted butter and bread). The subjects were blindly randomized to receive either placebo or orlistat 120 mg before each main meal. The outcome parameters were total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and very-low–density lipoprotein (VLDL) cholesterol levels measured at fasting (0 h) and every 2 h thereafter, until the sixteenth hour. Additionally, we estimated the lipid levels at the fifth and ninth hour.

Results

The non-orlistat group showed a significant postprandial rise in the levels of TG and VLDL, which began 4 h after breakfast (P < 0.05); this rise in levels was sustained until 9 h after breakfast for TG and up to 10 h after breakfast for VLDL. In contrast, only one significant rise in both TG and VLDL levels (at 4 h after breakfast) was noted in the orlistat group. The maximum mean difference from the baseline TG level for the orlistat group was lower than that for the non-orlistat group (0.22 mmol/L vs. 0.756 mmol/L, respectively). Similarly, the maximum mean difference from the baseline VLDL level from baseline in the orlistat group was only 0.099 mmol/L, which was lower than that in the non-orlistat group (0.588 mmol/L). LDL levels rose to a lesser extent in the orlistat group than in the non-orlistat group (0.268 vs. 0.362 mmol/L). The TC levels did not show a postprandial rise; instead, the levels reduced in both groups, with the orlistat group showing a higher reduction than the non-orlistat group (-0.288 vs. -0.188 mmol/L). The orlistat group did not show any significant differences in the HDL measurements.

Conclusions

Administration of orlistat abolished the significantly sustained postprandial rise of TG and VLDL levels in healthy individuals who were fed sequential 50% fat meals.

Background

Postprandial lipemia has been found to be strongly associated with atherosclerosis due to its atherogenic and thrombogenic lipoprotein changes. This phenomenon occurs even in normal subjects especially after high fat meals. Orlistat, an anti- obesity drug, has been shown to address postprandial lipemia after a single high fat meal.

Objectives

To compare the effects of orlistat and placebo on the postprandial lipid levels after sequential high-fat meals in healthy individuals with normal fasting lipid levels.

Patients and Methods

Thirty-one healthy adult volunteers with normal fasting lipid levels were fed 50% fat meals (3 meals and 2 snacks of pre-weighted butter and bread). The subjects were blindly randomized to receive either placebo or orlistat 120 mg before each main meal. The outcome parameters were total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and very-low–density lipoprotein (VLDL) cholesterol levels measured at fasting (0 h) and every 2 h thereafter, until the sixteenth hour. Additionally, we estimated the lipid levels at the fifth and ninth hour.

Results

The non-orlistat group showed a significant postprandial rise in the levels of TG and VLDL, which began 4 h after breakfast (P < 0.05); this rise in levels was sustained until 9 h after breakfast for TG and up to 10 h after breakfast for VLDL. In contrast, only one significant rise in both TG and VLDL levels (at 4 h after breakfast) was noted in the orlistat group. The maximum mean difference from the baseline TG level for the orlistat group was lower than that for the non-orlistat group (0.22 mmol/L vs. 0.756 mmol/L, respectively). Similarly, the maximum mean difference from the baseline VLDL level from baseline in the orlistat group was only 0.099 mmol/L, which was lower than that in the non-orlistat group (0.588 mmol/L). LDL levels rose to a lesser extent in the orlistat group than in the non-orlistat group (0.268 vs. 0.362 mmol/L). The TC levels did not show a postprandial rise; instead, the levels reduced in both groups, with the orlistat group showing a higher reduction than the non-orlistat group (-0.288 vs. -0.188 mmol/L). The orlistat group did not show any significant differences in the HDL measurements.

Conclusions

Administration of orlistat abolished the significantly sustained postprandial rise of TG and VLDL levels in healthy individuals who were fed sequential 50% fat meals.

Orlistat;Lipids;Postprandial Lipemia;Fatty Meal;Cardiovascular Disease Orlistat;Lipids;Postprandial Lipemia;Fatty Meal;Cardiovascular Disease 458 463 http://www.endometabol.com/index.php?page=article&article_id=2920 Frederick S. S. Gabriel Frederick S. S. Gabriel Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Clarissa E. E. Samson Clarissa E. E. Samson Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Zaynab R. R. Abejuela Zaynab R. R. Abejuela Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Paula R. R. Sicat-Gabriel Paula R. R. Sicat-Gabriel Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Joan P. P. Sumpio Joan P. P. Sumpio Dietary Services, University Of Santo Tomas Hospital, Espana Blvd, Philippines Dietary Services, University Of Santo Tomas Hospital, Espana Blvd, Philippines Manuel B. B. Zacarias Manuel B. B. Zacarias Section of Cardiology, University Of Santo Tomas Hospital, Espana Blvd, Philippines Section of Cardiology, University Of Santo Tomas Hospital, Espana Blvd, Philippines Leilani B. B. Mercado-Asis Leilani B. B. Mercado-Asis Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph; Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph; Sectionsoofeonoos{oooooyaondmmuucoom{m,uowws{}}yoofsso~otomssHospital, Espana Blvd, Philippines +63-27313046, leilanimercadoasis@endo-society.org.ph
en 10.5812/ijem.3794 Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients With Type 2 Diabetes Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients With Type 2 Diabetes research-article research-article Background

Osteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail.

Objectives

This study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan.

Patients and Methods

The subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period.

Results

There were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene.

Conclusions

Treatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.

Background

Osteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail.

Objectives

This study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan.

Patients and Methods

The subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period.

Results

There were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene.

Conclusions

Treatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.

Diabetes Mellitus, Type 2;Hemodialysis;Osteoporosis;Raloxifene Diabetes Mellitus, Type 2;Hemodialysis;Osteoporosis;Raloxifene 464 469 http://www.endometabol.com/index.php?page=article&article_id=3794 Osamu Saito Osamu Saito Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp; Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp; Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Takako Saito Takako Saito Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Shinji Asakura Shinji Asakura Oyama Suginoki Clinic, Japan Oyama Suginoki Clinic, Japan Tetsu Akimoto Tetsu Akimoto Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Makoto Inoue Makoto Inoue Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Yasuhiro Ando Yasuhiro Ando Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Shigeaki Muto Shigeaki Muto Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Eiji Kusano Eiji Kusano Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp Department of Nephrology, Jichi Medical University, Simotsuke, 329-0498, Japan +81-285587346, nephsait@jichi.ac.jp
en 10.5812/ijem.2459 Effects of Circuit Resistance Training Intensity on the Plasma Ghrelin to Obestatin Ratios in Healthy Young Women Effects of Circuit Resistance Training Intensity on the Plasma Ghrelin to Obestatin Ratios in Healthy Young Women research-article research-article Background

Ghrelin and obestatin are orexigenic and anorexigenic peptides, respectively. It appears that an accurate balance between theses peptides is important for regulating energy homeostasis and body weight.

Objectives

The aim of this study was to identify the possible mechanisms by which circuit resistance training influences energy homeostasis and weight control.

Patients and Methods

Twenty-seven female students with the mean age of 22 ± 1.54 years and mean body mass index (BMI) of 20.76 ± 1.86 kg/m2 were selected and randomly divided into experimental and control groups. Subjects performed circuit resistance training with 40% and 80% of 1 repetition maximum (1RM) for 4 weeks. Total plasma ghrelin, obestatin, and glucose levels and the ghrelin to obestatin ratio were measured for all subjects before and after training.

Results

One-way ANOVA tests showed that, the plasma ghrelin to obestatin ratio increased significantly in the 80% 1RM group (P < 0.05). Furthermore, a significant reduction of the plasma obestatin level was found in this group (P < 0.05).

Conclusions

It appears that an energy deficit caused by circuit resistance training in 80% of the 1RM group resulted in the ghrelin precursor being increasingly used for ghrelin production. Thus, obestatin secretion decreased and the ghrelin to obestatin ratio increased in order to stimulate food intake and lost energy resource consumption to eventually restore the energy balance in the body.

Background

Ghrelin and obestatin are orexigenic and anorexigenic peptides, respectively. It appears that an accurate balance between theses peptides is important for regulating energy homeostasis and body weight.

Objectives

The aim of this study was to identify the possible mechanisms by which circuit resistance training influences energy homeostasis and weight control.

Patients and Methods

Twenty-seven female students with the mean age of 22 ± 1.54 years and mean body mass index (BMI) of 20.76 ± 1.86 kg/m2 were selected and randomly divided into experimental and control groups. Subjects performed circuit resistance training with 40% and 80% of 1 repetition maximum (1RM) for 4 weeks. Total plasma ghrelin, obestatin, and glucose levels and the ghrelin to obestatin ratio were measured for all subjects before and after training.

Results

One-way ANOVA tests showed that, the plasma ghrelin to obestatin ratio increased significantly in the 80% 1RM group (P < 0.05). Furthermore, a significant reduction of the plasma obestatin level was found in this group (P < 0.05).

Conclusions

It appears that an energy deficit caused by circuit resistance training in 80% of the 1RM group resulted in the ghrelin precursor being increasingly used for ghrelin production. Thus, obestatin secretion decreased and the ghrelin to obestatin ratio increased in order to stimulate food intake and lost energy resource consumption to eventually restore the energy balance in the body.

Obestatin;Ghrelin;Plasma;Women Obestatin;Ghrelin;Plasma;Women 475 479 http://www.endometabol.com/index.php?page=article&article_id=2459 Mehdi Hedayati Mehdi Hedayati Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122432500, Hedayati@endocrine.ac.ir; Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122432500, Hedayati@endocrine.ac.ir Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122432500, Hedayati@endocrine.ac.ir; Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122432500, Hedayati@endocrine.ac.ir Marziyeh Saghebjoo Marziyeh Saghebjoo Faculty of Physical Education and Sports Sciences, University of Birjand, IR Iran Faculty of Physical Education and Sports Sciences, University of Birjand, IR Iran Abbass Ghanbari-Niaki Abbass Ghanbari-Niaki Faculty of Physical Education and Sports Sciences, Mazandaran University, IR Iran Faculty of Physical Education and Sports Sciences, Mazandaran University, IR Iran
en 10.5812/ijem.3442 Prevalence and Risk Factors for Non-Vertebral Fractures in Patients Receiving Oral Glucocorticoids Prevalence and Risk Factors for Non-Vertebral Fractures in Patients Receiving Oral Glucocorticoids research-article research-article Background

Glucocorticoids taken orally increase the risk of fractures. It has been noted that a dose as low as 2.5 mg/day increases the risk of vertebral fracture. What is less clear is the possible influence of other risk factors for osteoporosis on the presence of non-vertebral fractures in patients taking glucocorticoids.

Objectives

A cross-sectional study, performed on 513 men and women from Spain, who were taking at least 7.5 mg/day of oral prednisone for a minimum of 3 months. A questionnaire was developed, through which information on risk factors was collected.

Patients and Methods

A cross-sectional study, performed on 513 men and women from Spain, who were taking at least 7.5 mg/day of oral prednisone for a minimum of 3 months. A questionnaire was developed, through which information on risk factors was collected.

Results

28.3% of the patients who were taking glucocorticoids at a daily oral dose of 7.5 mg/day for a minimum of 3 months had suffered at least one non-vertebral fracture. The risk increased with age, the number of months the glucocorticoids had been taken, the presence of falls in the last year and, above all, with a maternal history of hip fracture.

Conclusions

In patients taking oral glucocorticoids for over 3 months at doses higher than 7.5 mg/day of prednisone or equivalent, the prevalence of non-vertebral fractures was 28.3%. Some risk factors associated with the presence of these fractures were identified. The duration of glucocorticoid use appears to be more strongly related to the presence of non-vertebral fractures than the daily dose.

Background

Glucocorticoids taken orally increase the risk of fractures. It has been noted that a dose as low as 2.5 mg/day increases the risk of vertebral fracture. What is less clear is the possible influence of other risk factors for osteoporosis on the presence of non-vertebral fractures in patients taking glucocorticoids.

Objectives

A cross-sectional study, performed on 513 men and women from Spain, who were taking at least 7.5 mg/day of oral prednisone for a minimum of 3 months. A questionnaire was developed, through which information on risk factors was collected.

Patients and Methods

A cross-sectional study, performed on 513 men and women from Spain, who were taking at least 7.5 mg/day of oral prednisone for a minimum of 3 months. A questionnaire was developed, through which information on risk factors was collected.

Results

28.3% of the patients who were taking glucocorticoids at a daily oral dose of 7.5 mg/day for a minimum of 3 months had suffered at least one non-vertebral fracture. The risk increased with age, the number of months the glucocorticoids had been taken, the presence of falls in the last year and, above all, with a maternal history of hip fracture.

Conclusions

In patients taking oral glucocorticoids for over 3 months at doses higher than 7.5 mg/day of prednisone or equivalent, the prevalence of non-vertebral fractures was 28.3%. Some risk factors associated with the presence of these fractures were identified. The duration of glucocorticoid use appears to be more strongly related to the presence of non-vertebral fractures than the daily dose.

480 485 http://www.endometabol.com/index.php?page=article&article_id=3442 Sosa-HenrIquez Manuel Sosa-HenrIquez Manuel Spanish Society for Investigation of Osteoporosis and Bone Metabolic Diseases (SEIOMM), Spain; Spanish Society for Investigation of Osteoporosis and Bone Metabolic Diseases (SEIOMM), Spain Spanish Society for Investigation of Osteoporosis and Bone Metabolic Diseases (SEIOMM), Spain; Spanish Society for Investigation of Osteoporosis and Bone Metabolic Diseases (SEIOMM), Spain Gomez de Tejada-Romero Maria Jesus Gomez de Tejada-Romero Maria Jesus Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Saavedra-Santana Pedro Saavedra-Santana Pedro Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Blazquez-Cabrera Jose Antonio Blazquez-Cabrera Jose Antonio Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Garcia-Vadillo Jesús Alberto Garcia-Vadillo Jesús Alberto Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Valdes-Llorca Carmen Valdes-Llorca Carmen Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Diaz-Curiel Manuel Diaz-Curiel Manuel Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Munoz-Torres Manuel Munoz-Torres Manuel Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Martinez-Rodriguez Maria Elena Martinez-Rodriguez Maria Elena Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Navarro-Ceballos Carmen Navarro-Ceballos Carmen Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Sanfelix-Genoves Jose Sanfelix-Genoves Jose Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Cancelo-Hidalgo Maria Jesus Cancelo-Hidalgo Maria Jesus Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Carpintero-Benitez Pedro Carpintero-Benitez Pedro Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Mesa-Ramos Manuel Mesa-Ramos Manuel Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Wsq~okewocoo~y2nos5y~wms|iwatiooafdoswwo~osoisiand Bone Metabolic Diseases (SEIOMM), Spain Palacios-Gil Antunano Palacios-Gil Antunano Santiago, Madrid Santiago, Madrid
en 10.5812/ijem.3505 Normality Tests for Statistical Analysis: A Guide for Non-Statisticians Normality Tests for Statistical Analysis: A Guide for Non-Statisticians article-commentary article-commentary

Statistical errors are common in scientific literature and about 50% of the published articles have at least one error. The assumption of normality needs to be checked for many statistical procedures, namely parametric tests, because their validity depends on it. The aim of this commentary is to overview checking for normality in statistical analysis using SPSS.

Statistical errors are common in scientific literature and about 50% of the published articles have at least one error. The assumption of normality needs to be checked for many statistical procedures, namely parametric tests, because their validity depends on it. The aim of this commentary is to overview checking for normality in statistical analysis using SPSS.

Normality;Statistical Analysis Normality;Statistical Analysis 486 489 http://www.endometabol.com/index.php?page=article&article_id=3505 Asghar Ghasemi Asghar Ghasemi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir Saleh Zahediasl Saleh Zahediasl Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, IR Iran +98-2122409309, zahedi@endocrine.ac.ir
en 10.5812/ijem.3447 Management of Subclinical Hyperthyroidism Management of Subclinical Hyperthyroidism review-article review-article

The ideal approach for adequate management of subclinical hyperthyroidism (low levels of thyroid-stimulating hormone [TSH] and normal thyroid hormone level) is a matter of intense debate among endocrinologists. The prevalence of low serum TSH levels ranges between 0.5% in children and 15% in the elderly population. Mild subclinical hyperthyroidism is more common than severe subclinical hyperthyroidism. Transient suppression of TSH secretion may occur because of several reasons; thus, corroboration of results from different assessments is essential in such cases. During differential diagnosis of hyperthyroidism, pituitary or hypothalamic disease, euthyroid sick syndrome, and drug-mediated suppression of TSH must be ruled out. A low plasma TSH value is also typically seen in the first trimester of gestation. Factitial or iatrogenic TSH inhibition caused by excessive intake of levothyroxine should be excluded by checking the patient’s medication history. If these nonthyroidal causes are ruled out during differential diagnosis, either transient or long-term endogenous thyroid hormone excess, usually caused by Graves’ disease or nodular goiter, should be considered as the cause of low circulating TSH levels. We recommend the following 6-step process for the assessment and treatment of this common hormonal disorder: 1) confirmation, 2) evaluation of severity, 3) investigation of the cause, 4) assessment of potential complications, 5) evaluation of the necessity of treatment, and 6) if necessary, selection of the most appropriate treatment. In conclusion, management of subclinical hyperthyroidism merits careful monitoring through regular assessment of thyroid function. Treatment is mandatory in older patients (> 65 years) or in presence of comorbidities (such as osteoporosis and atrial fibrillation).

The ideal approach for adequate management of subclinical hyperthyroidism (low levels of thyroid-stimulating hormone [TSH] and normal thyroid hormone level) is a matter of intense debate among endocrinologists. The prevalence of low serum TSH levels ranges between 0.5% in children and 15% in the elderly population. Mild subclinical hyperthyroidism is more common than severe subclinical hyperthyroidism. Transient suppression of TSH secretion may occur because of several reasons; thus, corroboration of results from different assessments is essential in such cases. During differential diagnosis of hyperthyroidism, pituitary or hypothalamic disease, euthyroid sick syndrome, and drug-mediated suppression of TSH must be ruled out. A low plasma TSH value is also typically seen in the first trimester of gestation. Factitial or iatrogenic TSH inhibition caused by excessive intake of levothyroxine should be excluded by checking the patient’s medication history. If these nonthyroidal causes are ruled out during differential diagnosis, either transient or long-term endogenous thyroid hormone excess, usually caused by Graves’ disease or nodular goiter, should be considered as the cause of low circulating TSH levels. We recommend the following 6-step process for the assessment and treatment of this common hormonal disorder: 1) confirmation, 2) evaluation of severity, 3) investigation of the cause, 4) assessment of potential complications, 5) evaluation of the necessity of treatment, and 6) if necessary, selection of the most appropriate treatment. In conclusion, management of subclinical hyperthyroidism merits careful monitoring through regular assessment of thyroid function. Treatment is mandatory in older patients (> 65 years) or in presence of comorbidities (such as osteoporosis and atrial fibrillation).

Hyperthyroidism;Disease Management;Therapeutics;Graves’ Disease Hyperthyroidism;Disease Management;Therapeutics;Graves’ Disease 490 496 http://www.endometabol.com/index.php?page=article&article_id=3447 Silvia Santos Palacios Silvia Santos Palacios Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es Eider Pascual-Corrales Eider Pascual-Corrales Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es Juan Carlos Galofre Juan Carlos Galofre Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es; Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es; Department of Endocrinology and Nutrition, University Clinic of Navarra, Uoov}{{mt{6of3qvyrra, Spain +94-8255400, jcgalofre@unav.es
en 10.5812/ijem.3644 An Update on Plant Derived Anti-Androgens An Update on Plant Derived Anti-Androgens review-article review-article

Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials.

Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials.

Androgens;Anti-Androgens;Prostate Cancer;Prostatic Hyperplasia;Spearmint Androgens;Anti-Androgens;Prostate Cancer;Prostatic Hyperplasia;Spearmint 497 502 http://www.endometabol.com/index.php?page=article&article_id=3644 Paul Grant Paul Grant Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk; Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk; Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk Shamin Ramasamy Shamin Ramasamy Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk Department of Endocrinology, Kings College Hospital, Denmark Hill, UK +44-23099999, drpaul.grant@doctors.org.uk
en 10.5812/ijem.3769 Tetralogy of Fallot Associated With Invasive Adrenocortical Tumor in an Adult Woman Tetralogy of Fallot Associated With Invasive Adrenocortical Tumor in an Adult Woman case-report case-report

Migration of cardiac neural crest cells into the pharyngeal arches and the pharyngeal and splanchnic mesoderm contributes to the development of the cardiac outflow tract. The adrenal cortex is derived from the splanchnic mesoderm. Neuroblastoma is more prevalent in patients with congenital heart disease than in the general population, because both originate from embryonal neural crest-derived cells. Similarly, and in light of recent embryological findings, abnormal development or migration of splanchnic mesoderm, possibly due to an underlying genetic defect, could contribute to the association of adrenocortical carcinoma and tetralogy of Fallot. We present the case of a cardiologically asymptomatic 49-year-old woman with total correction of tetralogy of Fallot in the first year of life.

Migration of cardiac neural crest cells into the pharyngeal arches and the pharyngeal and splanchnic mesoderm contributes to the development of the cardiac outflow tract. The adrenal cortex is derived from the splanchnic mesoderm. Neuroblastoma is more prevalent in patients with congenital heart disease than in the general population, because both originate from embryonal neural crest-derived cells. Similarly, and in light of recent embryological findings, abnormal development or migration of splanchnic mesoderm, possibly due to an underlying genetic defect, could contribute to the association of adrenocortical carcinoma and tetralogy of Fallot. We present the case of a cardiologically asymptomatic 49-year-old woman with total correction of tetralogy of Fallot in the first year of life.

Tetralogy of Fallot;Adernal Cortex Neoplasms;Woman Tetralogy of Fallot;Adernal Cortex Neoplasms;Woman 503 505 http://www.endometabol.com/index.php?page=article&article_id=3769 Efren Martinez-Quintana Efren Martinez-Quintana Cmsemomowym{ww~ice~hmns}sv-mqtmroamwq~wil University Hospital, Spain +34-928373050, efrenmartinezquintana@yahoo.es; Cmsemomowym{ww~ice~hmns}sv-mqtmroamwq~wil University Hospital, Spain +34-928373050, efrenmartinezquintana@yahoo.es Cmsemomowym{ww~ice~hmns}sv-mqtmroamwq~wil University Hospital, Spain +34-928373050, efrenmartinezquintana@yahoo.es; Cmsemomowym{ww~ice~hmns}sv-mqtmroamwq~wil University Hospital, Spain +34-928373050, efrenmartinezquintana@yahoo.es Fayna Rodriguez-Gonzalez Fayna Rodriguez-Gonzalez Ophthalmology Service. Dr. Negrín University Hospital, Spain Ophthalmology Service. Dr. Negrín University Hospital, Spain Maria Pino Pino Alberiche-Ruano Maria Pino Pino Alberiche-Ruano Endocrinology Service. Insular-Materno Infantil University Hospital, Spain Endocrinology Service. Insular-Materno Infantil University Hospital, Spain Maria Soledad Soledad Martinez-Martin Maria Soledad Soledad Martinez-Martin Anatomopathology Service. Insular-Materno Infantil University Hospital, Spain Anatomopathology Service. Insular-Materno Infantil University Hospital, Spain
en 10.5812/ijem.4174 Hashimoto Encephalopathy: A Rare Intricate Syndrome Hashimoto Encephalopathy: A Rare Intricate Syndrome case-report case-report

Recently, several patients have been reported with various signs of encephalopathy and high thyroid antibody levels together with good responsiveness to glucocorticoid therapy. Despite the various clinical presentations, these cases have been termed “Hashimoto encephalopathy” (HE). Although all of the pathogenic components have not yet been clearly elucidated, it is believed that brain vasculitis and autoimmunity directed against common brain-thyroid antigens represent the most likely etiologic pathway. The most common clinical signs include unexplained or epilepsy-like seizures resistant to anti-convulsive treatment, confusion, headaches, hallucinations, stroke-like episodes, coma, impairment of cognitive function, behavioral and mood disturbance, focal neurological deficits, disturbance of consciousness, ataxia, and presenile dementia, together with the presence of high thyroid antibody levels, especially against thyroperoxidase (TPOab). In most cases, the thyroid function is normal or decreased; the thyroid function is rarely increased. The examination of the cerebrospinal fluid, EEG, MRI, SPECT, and neuropsychological examinations are primarily used as diagnostic tools. Most cases showed neural symptoms for months before the acute onset; in some cases, a dramatic acute onset was described. Once the diagnosis is made, corticosteroid treatment usually provides a dramatic recovery. The authors also present a short review of literary cases reported in last decade.

Recently, several patients have been reported with various signs of encephalopathy and high thyroid antibody levels together with good responsiveness to glucocorticoid therapy. Despite the various clinical presentations, these cases have been termed “Hashimoto encephalopathy” (HE). Although all of the pathogenic components have not yet been clearly elucidated, it is believed that brain vasculitis and autoimmunity directed against common brain-thyroid antigens represent the most likely etiologic pathway. The most common clinical signs include unexplained or epilepsy-like seizures resistant to anti-convulsive treatment, confusion, headaches, hallucinations, stroke-like episodes, coma, impairment of cognitive function, behavioral and mood disturbance, focal neurological deficits, disturbance of consciousness, ataxia, and presenile dementia, together with the presence of high thyroid antibody levels, especially against thyroperoxidase (TPOab). In most cases, the thyroid function is normal or decreased; the thyroid function is rarely increased. The examination of the cerebrospinal fluid, EEG, MRI, SPECT, and neuropsychological examinations are primarily used as diagnostic tools. Most cases showed neural symptoms for months before the acute onset; in some cases, a dramatic acute onset was described. Once the diagnosis is made, corticosteroid treatment usually provides a dramatic recovery. The authors also present a short review of literary cases reported in last decade.

Hashimoto’s Encephalitis;Vasculitis;Glucocorticoids Hashimoto’s Encephalitis;Vasculitis;Glucocorticoids 506 514 http://www.endometabol.com/index.php?page=article&article_id=4174 Juraj Payer Juraj Payer Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk; Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk; Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk Tomas Petrovic Tomas Petrovic Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk Clinic of Internal Medicine, Faculty of Medicine, Comenius University, Faculty Hospital Ruzinov, Slovakia +421-248234108, payer@ru.unb.sk Lubomir Lisy Lubomir Lisy Clinic of Neurology, Slovak Medical University, Slovakia Clinic of Neurology, Slovak Medical University, Slovakia Pavel Langer Pavel Langer Institute of Experimental Endocrinology, Slovak Acadeamy of Sciences, Slovakia Institute of Experimental Endocrinology, Slovak Acadeamy of Sciences, Slovakia
en 10.5812/ijem.3826 Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children research-article research-article Background

The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone–insulin-like growth factor (GH–IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate.

Objectives

To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children.

Patients and Methods

Ten GHD (male/female [M/F], 6/4; age [mean ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min.

Results

Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion.

Conclusions

Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action.

Background

The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone–insulin-like growth factor (GH–IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate.

Objectives

To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children.

Patients and Methods

Ten GHD (male/female [M/F], 6/4; age [mean ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min.

Results

Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion.

Conclusions

Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action.

Acylated Ghrelin;Growth Hormone;Growth Hormone Deficiency Acylated Ghrelin;Growth Hormone;Growth Hormone Deficiency 470 474 http://www.endometabol.com/index.php?page=article&article_id=3826 Flavia Prodam Flavia Prodam Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Italy Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Italy Giulia Genoni Giulia Genoni Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Simonetta Bellone Simonetta Bellone Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Silvia Longhi Silvia Longhi Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it Valentina Agarla Valentina Agarla Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Gianni Bona Gianni Bona Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Italy Giorgio Radetti Giorgio Radetti Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it; Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it; Department of Pediatrics, Regional Hospital of Bolzano, via L. Boehler 5, 39100, Italy +39-0471908651, giorgio.radetti@asbz.it