Alev Ozön | Middle East Technical University / Hacettepe University (original) (raw)

Papers by Alev Ozön

American Journal of Infection Control, Sep 1, 2015

ABSTRACT The aim of this prospective study was to establish the methicillin-resistant Staphylococ... more ABSTRACT The aim of this prospective study was to establish the methicillin-resistant Staphylococcus aureus (MRSA) colonization rates in pediatric outpatients with type 1 diabetes mellitus, while also evaluating changes in colonization rates over time. There was no significant difference between 2005 and 2013 patients in terms of demographic and clinical findings. MRSA colonization rates were 0.7% (in 101 patients) and 0.9% (in 134 patients) (P = .84). Although increased MRSA colonization has become a significant problem worldwide, it does not seem to be a major issue in our diabetic outpatient population. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The Journal of Steroid Biochemistry and Molecular Biology, 2017

Pediatric endocrinology reviews : PER, 2003

Newborn screening for congenital hypothyroidism (CH) is one of the major achievements of preventi... more Newborn screening for congenital hypothyroidism (CH) is one of the major achievements of preventive medicine, as the condition occurs frequently (1/4000 newborns) and results in brain damage if not detected and treated in the first few days of life. Measurement of T4 and/or TSH in dried blood spots collected on the second through fifth days of life are the most widely used methods in screening programs for CH currently. Some children with the disease may be missd in any screening program, however, owing to factors related to the disease itself and the methods employed in its detection, as well as factors ascribed to the element of human error, ie screening errors. The methods employed in newborn screening programs for CH, their efficiency in disease detecetion, and biological factors as well as screening errors leading to missed cases are discussed.

Pediatric Neurosurgery, 2004

Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood... more Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood, caused either by the tumor itself or the consequences of treatment. Tumor management in terms of recurrence rate, quality of life and complications is still controversial. Sixty-six patients with craniopharyngioma at pediatric age were reviewed for symptoms, signs, types of treatment, recurrence rates, complications, and endocrinological outcome. The majority of symptoms was related to the neurological system. Complaints only affecting the endocrinological system were seen in 6% of patients. The most frequent complaints were headache and vomiting (74.2%). The main endocrinological complaints were polyuria and polydipsia (15%), and lassitude (10.6%). Although short stature was a symptom in 9.1% of patients, it was a finding in 39.7% of patients. Plain skull X-rays raised the suspicion of intracranial tumor in more than 90% of children with craniopharyngioma. Recurrence rates were indepe...

Journal of Pediatric Endocrinology and Metabolism, 2014

OBJective: To determine the demographic and clinical characteristics of type 1 diabetes (T1D) in ... more OBJective: To determine the demographic and clinical characteristics of type 1 diabetes (T1D) in the past two decades, and to analyze changing trends over the past 40 years. Patients with a diagnosis of T1D in 1990-2010 were included. Patients diagnosed in the first half of the period comprised Period I, and those from the second half comprised Period II. Age at onset, gender, seasonal distribution, infectious etiology, and clinical picture at onset are analyzed and compared in two periods. In addition, we compared these data with that of the preceding two decades (1969-1991), which was reported in a previous publication. A total of 354 children with T1D were included in the study. The median age at diagnosis of T1D was 7 years in the period 1990-2010 in comparison to 9.5 years during the period 1969-1991. Patients were diagnosed mostly in winter and autumn, and 32.3% of the children had an infection at the time of diagnosis. Frequency of diabetic ketoacidosis was 50.8% at diagnosis. The peak age at onset was 4 to 6 years. Our study provides substantial information about the clinical characteristics of Turkish children. The age of onset of T1D decreased in the past 20 years, as observed in other parts of the world. Our findings also suggest seasonality at onset of T1D. This study shows the changes of demographic and clinical characteristics of T1D in central and northeastern parts of our country over a 40 year period.

Journal of Pediatric Endocrinology and Metabolism, 2008

Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH... more Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH with the GH receptor (GHR) is necessary for systemic and local production of insulin-like growth factor-I (IGF-I) which mediates GH actions. Mutations in the GHR cause severe postnatal growth failure; the disorder is an autosomal recessive genetic disease resulting in GH insensitivity, called Laron syndrome. It is characterized by dwarfism with elevated serum GH and low levels of IGF-I. We analyzed the GHR gene for mutations and polymorphisms in eight patients with Laron-type dwarfism from six families. We found three missense mutations (S40L, V125A, I526L), one nonsense mutation (W157X), and one splice site mutation in the extracellular domain of GHR. Furthermore, G168G and exon 3 deletion polymorphisms were detected in patients with Laron syndrome. The splice site mutation, which is a novel mutation, was located at the donor splice site of exon 2/ intron 2 within GHR. Although this mutation changed the highly conserved donor splice site consensus sequence GT to GGT by insertion of a G residue, the intron splicing between exon 2 and exon 3 was detected in the patient. These results imply that the splicing occurs arthe GT site in intron 2, leaving the extra inserted G residue at the end of exon 2, thus changing the open reading frame of GHR resulting in a premature termination codon in exon 3.

Journal of Pediatric Endocrinology and Metabolism, 2008

Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH ... more Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH deficiency is still debatable. We analyzed the auxological data of boys with growth retardation who had normal GH responses to stimulation tests only after priming to establish the validity of priming in the diagnosis of GH deficiency. We also analyzed the effect of different protocols for priming and their efficiency in the diagnosis of GH deficiency. Fifty boys with growth retardation who failed to respond to unprimed GH stimulation tests but responded normally to primed tests were included in the study. Thirty-one of 50 boys responded to GH stimulation tests after single low dose testosterone, 11/50 boys after single conventional dose, and 8/50 boys with multiple-dose testosterone. The study group was followed till final height; height velocity, final height and height SDS were compared to parental and mid-parental heights to determine whether or not the children achieved their height potential. Mean final height SDS of the study group (-1.27 +/- 0.72 SDS) was similar to mid-parental (-1.38 +/- 0.72 SDS) (p = 0.249) and maternal height SDS (-1.26 +/- 1.05 SDS) (p = 0.941), whereas it was greater than the paternal height SDS (-1.7 +/- 0.86) (p = 0.001). The final height SDS of the study group was correlated to maternal, paternal and mid-parental height SDS. Height velocity after the test was greater than the previous height velocity. Final height SDS of the boys who responded to the GH stimulation tests with different priming protocols were compared and found to be similar. Normal responders in primed GH tests grow normally to their target height, suggesting that priming might be a valuable method in the assessment of GH status. Use of priming in the GH stimulation tests of peripubertal boys with decreased growth rate may help avoid unnecessary GH therapy. Multiple-dose testing might exclude GHD in a patient population who failed to respond to a single dose of testosterone. This finding suggests that multiple-dose testosterone might be a more valuable method for priming in the differentiation of normal from abnormal GH secretion.

Journal of Pediatric Endocrinology and Metabolism, 2007

Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects a... more Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects are less common compared to systemic use; however, newer potent preparations may have serious side effects. A potential danger is their inappropriate use. Three infants who developed iatrogenic Cushing's syndrome and prolonged adrenal suppression in the course of GC therapy for simple diaper dermatitis are described. One patient also developed steatohepatitis which is uncommon with local GCs.

Journal of Pediatric Endocrinology and Metabolism, 2011

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease... more Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL.

Journal of Diabetes and its Complications, 2006

Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also... more Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also possibly related to obesity and insulin resistance. There is little information, however, regarding the status of fibrinolytic system in Type 1 diabetes, in particular as reflected by thrombin-activatable fibrinolysis inhibitor (TAFI) activity and global fibrinolytic capacity (GFC). To provide information in this respect, 30 Type 1 diabetic patients (median age=16) and 28 healthy controls (median age=14) were enrolled in this study. The median duration of diabetes was 7 years, and median HbA(1c) was 8.85% (range: 5.5-11.9%) in the diabetic group. None of the patients had macrovascular complications. Microvascular complications were present in a total of eight patients (nephropathy: n=5; retinopathy: n=3). A comparison of the TAFI activity between the patient (median 84.9, range: 71.5-103.3%) and the control groups (median=83.3, range: 63.7-97.4%) yielded no statistically significant difference (P=.950). Similarly, GFC was comparable between the two groups (median=8.22, range: 0.72-22.38 microg/ml, and median=13.32, range: 3.0-23.22 microg/ml, respectively, in the diabetic and control groups, P=.086). TAFI activity did not significantly correlate with age, albumin excretion, fasting plasma glucose, HbA(1c), D-dimer, and fibrinogen by Spearman rank correlation test. There was as a significant inverse correlation between GFC and TAFI activity (r=-.414, P=.006). Contrary to the previous observations in Type 2 diabetes, our data suggest that fibrinolytic activity is not adversely affected by Type 1 diabetes, and it has no relationship with the degree of metabolic control.

Hormone Research in Paediatrics, 2007

Aims: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. ... more Aims: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). Methods: Fifty-one patients, mean age 10.8 ± 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 µg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0–10–20–30–40 min). Results: Mean basal serum cortisol level was 8.21 ± 4.10 µg/dl (mean ± SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 µg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 µg/dl defined A...

Clinical Endocrinology, 2011

Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of... more Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic-pituitary-gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time-consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90 min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut-off level for LH indicating adequate suppression. Prospective study. One hundred and forty-two patients with CPP were included in this study. Peak LH level during iv GnRH stimulation test after the third dose of GnRHa was compared with LH level 90 min after injection of the 3rd dose of GnRHa. There was a positive correlation between LH level following a GnRHa injection and peak LH during standard iv GnRH stimulation test (r = 0·83; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·0001). A LH value of 2·5 mIU/ml or less 90 min after GnRHa injection was considered to be the cut-off for the determination of pubertal suppression (sensitivity and specificity was 100% and 88%, respectively). In 117 patients, gonadotrophin suppression was existed according to both GnRHa and iv GnRH tests. In 25 patients, gonadotrophin suppression was not found in the GnRHa test. However, 16 of them were suppressed according to the iv GnRH test. Single LH determination 90 min after GnRHa administration using a cut-off level of 2·5 mIU/ml reflects pubertal suppression with a high sensitivity and specificity. However, this test may fail to show pubertal suppression in some cases. Those patients who appear to be inadequately suppressed should be reassessed using standard iv GnRH stimulation test for optimal dose adjustment.

Turkiye Klinikleri Journal of Pediatrical Sciences, 2006

The Turkish journal of pediatrics

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined... more Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with...

Proceedings of the National Academy of Sciences of the United States of America, Mar 22, 2017

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hy... more Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clini...

Turkish Journal of Pediatrics

In this study, we aimed to analyze early-onset atherosclerotic changes in adolescents with risk o... more In this study, we aimed to analyze early-onset atherosclerotic changes in adolescents with risk of cardiovascular disease in comparison to healthy controls using carotid intima media thickness (CIMT), homocysteine and markers of endothelial function as indicators. Children aged 10 years or older, all pubertal, with type 1 diabetes mellitus (T1DM), obesity, or obesity with glucose intolerance and age- and sex-matched healthy controls were included in the study. Endothelial markers (von Willebrand factor [vWF], tissue plasminogen activator [tPA], plasminogen activator inhibitor [PAI]-1), CIMT, homocysteine, folic acid, and vitamin B12 levels were measured in all subjects. Mean CIMT of the obese subjects were significantly higher than that of lean diabetic children and healthy controls (p=0.024). There was an independent relationship between CIMT and homocysteine level (b=0.76, p<0.0001). Further, homocysteine was negatively correlated with vitamin B12 (r=-0.20, p<0.001) and foli...

The Turkish journal of pediatrics, 2002

Iodine deficiency is an important public health problem worldwide. It is well known that it has s... more Iodine deficiency is an important public health problem worldwide. It is well known that it has severe consequences such as brain damage, developmental delay, deficits in hearing and learning and lower intellectual attainment. It also has a negative impact on growth. In this study, we aimed to address this issue and we assessed height standard deviation scores of children living in an area of severe iodine deficiency in comparison to those living in a mild iodine deficiency area. Serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also analyzed to investigate the mechanisms by which iodine depletion leads to growth failure. Pubertal children in a severe iodine deficient SID area had lower height standard deviation scores (HSDS), IGF-I and IGFBP-3 levels than those living in mild iodine deficient MID area. Similar findings could not be elucidated in the prepubertal age group. The major deter...

The Turkish journal of pediatrics, 2012

Vitamin D-deficient rickets (VDDR) remains an important health problem especially in developing c... more Vitamin D-deficient rickets (VDDR) remains an important health problem especially in developing countries. Insufficient dietary intake of vitamin D and inadequate sun exposure increase the risk of vitamin D deficiency. Since their vitamin D requirement is increased, children and adolescents are potentially at higher risk for vitamin D deficiency. In adolescents, vitamin D deficiency causes osteomalacia, osteoporosis and muscle weakness. While osteoporosis is not associated with bone pain, osteomalacia has been associated with isolated or generalized bone pain. The present case suffered from generalized bone pain for three years. She was misdiagnosed as ankylosing spondylitis, which is a seronegative arthropathy, and was treated with corticosteroids and methotrexate, which have potential side effects. Hypocalcemia, hypophosphatemia, elevated alkaline phosphatase level, secondary hyperparathyroidism, and extremely low vitamin D level were consistent with the diagnosis of severe vitami...

The Turkish journal of pediatrics, 2006

Cholestatic hepatitis is identified as one of the features of hypopituitarism in the newborn, but... more Cholestatic hepatitis is identified as one of the features of hypopituitarism in the newborn, but the exact etiology of cholestasis in these cases has not been well established yet. We report here two infants, one with isolated glucocorticoid deficiency and the other with multiple pituitary hormone deficiency, indicating primary and central adrenal insufficiency, respectively, who presented with recurrent hypoglycemic seizures and cholestatic hepatitis. Severe cortisol deficiency in these cases was suggested to be the cause of cholestatic hepatitis. Review of the literature and our cases showed that the cortisol deficiency in both primary and central adrenal insufficiency occurring only during neonatal and early infancy period cause cholestatic hepatitis. The severity and the age of onset of cortisol deficiency are suggested to be the important predictors of cholestatic hepatitis in childhood.

The Turkish journal of pediatrics, 2004

Iodine deficiency is an important public health problem worldwide. In addition to severe conseque... more Iodine deficiency is an important public health problem worldwide. In addition to severe consequences such as brain damage, developmental delay, deficits in hearing and learning, it also has a negative impact on growth. The negative impact of severe iodine deficiency (SID) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) was shown previously. In this study we aimed to analyze the impact of iodine supplementation on growth and growth factors of children with SID. One hundred and four children (63 boys and 41 girls) aged 5-15 years participated in the study. Height standard deviation scores (HSDS), and serum levels of IGF-I and IGFBP-3 were assessed both before and six months after a single dose of iodized oil. Serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were also analysed to investigate the mechanisms by which alterations of iodine status may influence growth. Pubertal children had lower HSDS six months ...

American Journal of Infection Control, Sep 1, 2015

ABSTRACT The aim of this prospective study was to establish the methicillin-resistant Staphylococ... more ABSTRACT The aim of this prospective study was to establish the methicillin-resistant Staphylococcus aureus (MRSA) colonization rates in pediatric outpatients with type 1 diabetes mellitus, while also evaluating changes in colonization rates over time. There was no significant difference between 2005 and 2013 patients in terms of demographic and clinical findings. MRSA colonization rates were 0.7% (in 101 patients) and 0.9% (in 134 patients) (P = .84). Although increased MRSA colonization has become a significant problem worldwide, it does not seem to be a major issue in our diabetic outpatient population. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The Journal of Steroid Biochemistry and Molecular Biology, 2017

Pediatric endocrinology reviews : PER, 2003

Newborn screening for congenital hypothyroidism (CH) is one of the major achievements of preventi... more Newborn screening for congenital hypothyroidism (CH) is one of the major achievements of preventive medicine, as the condition occurs frequently (1/4000 newborns) and results in brain damage if not detected and treated in the first few days of life. Measurement of T4 and/or TSH in dried blood spots collected on the second through fifth days of life are the most widely used methods in screening programs for CH currently. Some children with the disease may be missd in any screening program, however, owing to factors related to the disease itself and the methods employed in its detection, as well as factors ascribed to the element of human error, ie screening errors. The methods employed in newborn screening programs for CH, their efficiency in disease detecetion, and biological factors as well as screening errors leading to missed cases are discussed.

Pediatric Neurosurgery, 2004

Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood... more Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood, caused either by the tumor itself or the consequences of treatment. Tumor management in terms of recurrence rate, quality of life and complications is still controversial. Sixty-six patients with craniopharyngioma at pediatric age were reviewed for symptoms, signs, types of treatment, recurrence rates, complications, and endocrinological outcome. The majority of symptoms was related to the neurological system. Complaints only affecting the endocrinological system were seen in 6% of patients. The most frequent complaints were headache and vomiting (74.2%). The main endocrinological complaints were polyuria and polydipsia (15%), and lassitude (10.6%). Although short stature was a symptom in 9.1% of patients, it was a finding in 39.7% of patients. Plain skull X-rays raised the suspicion of intracranial tumor in more than 90% of children with craniopharyngioma. Recurrence rates were indepe...

Journal of Pediatric Endocrinology and Metabolism, 2014

OBJective: To determine the demographic and clinical characteristics of type 1 diabetes (T1D) in ... more OBJective: To determine the demographic and clinical characteristics of type 1 diabetes (T1D) in the past two decades, and to analyze changing trends over the past 40 years. Patients with a diagnosis of T1D in 1990-2010 were included. Patients diagnosed in the first half of the period comprised Period I, and those from the second half comprised Period II. Age at onset, gender, seasonal distribution, infectious etiology, and clinical picture at onset are analyzed and compared in two periods. In addition, we compared these data with that of the preceding two decades (1969-1991), which was reported in a previous publication. A total of 354 children with T1D were included in the study. The median age at diagnosis of T1D was 7 years in the period 1990-2010 in comparison to 9.5 years during the period 1969-1991. Patients were diagnosed mostly in winter and autumn, and 32.3% of the children had an infection at the time of diagnosis. Frequency of diabetic ketoacidosis was 50.8% at diagnosis. The peak age at onset was 4 to 6 years. Our study provides substantial information about the clinical characteristics of Turkish children. The age of onset of T1D decreased in the past 20 years, as observed in other parts of the world. Our findings also suggest seasonality at onset of T1D. This study shows the changes of demographic and clinical characteristics of T1D in central and northeastern parts of our country over a 40 year period.

Journal of Pediatric Endocrinology and Metabolism, 2008

Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH... more Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH with the GH receptor (GHR) is necessary for systemic and local production of insulin-like growth factor-I (IGF-I) which mediates GH actions. Mutations in the GHR cause severe postnatal growth failure; the disorder is an autosomal recessive genetic disease resulting in GH insensitivity, called Laron syndrome. It is characterized by dwarfism with elevated serum GH and low levels of IGF-I. We analyzed the GHR gene for mutations and polymorphisms in eight patients with Laron-type dwarfism from six families. We found three missense mutations (S40L, V125A, I526L), one nonsense mutation (W157X), and one splice site mutation in the extracellular domain of GHR. Furthermore, G168G and exon 3 deletion polymorphisms were detected in patients with Laron syndrome. The splice site mutation, which is a novel mutation, was located at the donor splice site of exon 2/ intron 2 within GHR. Although this mutation changed the highly conserved donor splice site consensus sequence GT to GGT by insertion of a G residue, the intron splicing between exon 2 and exon 3 was detected in the patient. These results imply that the splicing occurs arthe GT site in intron 2, leaving the extra inserted G residue at the end of exon 2, thus changing the open reading frame of GHR resulting in a premature termination codon in exon 3.

Journal of Pediatric Endocrinology and Metabolism, 2008

Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH ... more Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH deficiency is still debatable. We analyzed the auxological data of boys with growth retardation who had normal GH responses to stimulation tests only after priming to establish the validity of priming in the diagnosis of GH deficiency. We also analyzed the effect of different protocols for priming and their efficiency in the diagnosis of GH deficiency. Fifty boys with growth retardation who failed to respond to unprimed GH stimulation tests but responded normally to primed tests were included in the study. Thirty-one of 50 boys responded to GH stimulation tests after single low dose testosterone, 11/50 boys after single conventional dose, and 8/50 boys with multiple-dose testosterone. The study group was followed till final height; height velocity, final height and height SDS were compared to parental and mid-parental heights to determine whether or not the children achieved their height potential. Mean final height SDS of the study group (-1.27 +/- 0.72 SDS) was similar to mid-parental (-1.38 +/- 0.72 SDS) (p = 0.249) and maternal height SDS (-1.26 +/- 1.05 SDS) (p = 0.941), whereas it was greater than the paternal height SDS (-1.7 +/- 0.86) (p = 0.001). The final height SDS of the study group was correlated to maternal, paternal and mid-parental height SDS. Height velocity after the test was greater than the previous height velocity. Final height SDS of the boys who responded to the GH stimulation tests with different priming protocols were compared and found to be similar. Normal responders in primed GH tests grow normally to their target height, suggesting that priming might be a valuable method in the assessment of GH status. Use of priming in the GH stimulation tests of peripubertal boys with decreased growth rate may help avoid unnecessary GH therapy. Multiple-dose testing might exclude GHD in a patient population who failed to respond to a single dose of testosterone. This finding suggests that multiple-dose testosterone might be a more valuable method for priming in the differentiation of normal from abnormal GH secretion.

Journal of Pediatric Endocrinology and Metabolism, 2007

Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects a... more Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects are less common compared to systemic use; however, newer potent preparations may have serious side effects. A potential danger is their inappropriate use. Three infants who developed iatrogenic Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome and prolonged adrenal suppression in the course of GC therapy for simple diaper dermatitis are described. One patient also developed steatohepatitis which is uncommon with local GCs.

Journal of Pediatric Endocrinology and Metabolism, 2011

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease... more Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL.

Journal of Diabetes and its Complications, 2006

Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also... more Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also possibly related to obesity and insulin resistance. There is little information, however, regarding the status of fibrinolytic system in Type 1 diabetes, in particular as reflected by thrombin-activatable fibrinolysis inhibitor (TAFI) activity and global fibrinolytic capacity (GFC). To provide information in this respect, 30 Type 1 diabetic patients (median age=16) and 28 healthy controls (median age=14) were enrolled in this study. The median duration of diabetes was 7 years, and median HbA(1c) was 8.85% (range: 5.5-11.9%) in the diabetic group. None of the patients had macrovascular complications. Microvascular complications were present in a total of eight patients (nephropathy: n=5; retinopathy: n=3). A comparison of the TAFI activity between the patient (median 84.9, range: 71.5-103.3%) and the control groups (median=83.3, range: 63.7-97.4%) yielded no statistically significant difference (P=.950). Similarly, GFC was comparable between the two groups (median=8.22, range: 0.72-22.38 microg/ml, and median=13.32, range: 3.0-23.22 microg/ml, respectively, in the diabetic and control groups, P=.086). TAFI activity did not significantly correlate with age, albumin excretion, fasting plasma glucose, HbA(1c), D-dimer, and fibrinogen by Spearman rank correlation test. There was as a significant inverse correlation between GFC and TAFI activity (r=-.414, P=.006). Contrary to the previous observations in Type 2 diabetes, our data suggest that fibrinolytic activity is not adversely affected by Type 1 diabetes, and it has no relationship with the degree of metabolic control.

Hormone Research in Paediatrics, 2007

Aims: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. ... more Aims: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). Methods: Fifty-one patients, mean age 10.8 ± 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 µg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0–10–20–30–40 min). Results: Mean basal serum cortisol level was 8.21 ± 4.10 µg/dl (mean ± SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 µg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 µg/dl defined A...

Clinical Endocrinology, 2011

Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of... more Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic-pituitary-gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time-consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90 min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut-off level for LH indicating adequate suppression. Prospective study. One hundred and forty-two patients with CPP were included in this study. Peak LH level during iv GnRH stimulation test after the third dose of GnRHa was compared with LH level 90 min after injection of the 3rd dose of GnRHa. There was a positive correlation between LH level following a GnRHa injection and peak LH during standard iv GnRH stimulation test (r = 0·83; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·0001). A LH value of 2·5 mIU/ml or less 90 min after GnRHa injection was considered to be the cut-off for the determination of pubertal suppression (sensitivity and specificity was 100% and 88%, respectively). In 117 patients, gonadotrophin suppression was existed according to both GnRHa and iv GnRH tests. In 25 patients, gonadotrophin suppression was not found in the GnRHa test. However, 16 of them were suppressed according to the iv GnRH test. Single LH determination 90 min after GnRHa administration using a cut-off level of 2·5 mIU/ml reflects pubertal suppression with a high sensitivity and specificity. However, this test may fail to show pubertal suppression in some cases. Those patients who appear to be inadequately suppressed should be reassessed using standard iv GnRH stimulation test for optimal dose adjustment.

Turkiye Klinikleri Journal of Pediatrical Sciences, 2006

The Turkish journal of pediatrics

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined... more Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with...

Proceedings of the National Academy of Sciences of the United States of America, Mar 22, 2017

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hy... more Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clini...

Turkish Journal of Pediatrics

In this study, we aimed to analyze early-onset atherosclerotic changes in adolescents with risk o... more In this study, we aimed to analyze early-onset atherosclerotic changes in adolescents with risk of cardiovascular disease in comparison to healthy controls using carotid intima media thickness (CIMT), homocysteine and markers of endothelial function as indicators. Children aged 10 years or older, all pubertal, with type 1 diabetes mellitus (T1DM), obesity, or obesity with glucose intolerance and age- and sex-matched healthy controls were included in the study. Endothelial markers (von Willebrand factor [vWF], tissue plasminogen activator [tPA], plasminogen activator inhibitor [PAI]-1), CIMT, homocysteine, folic acid, and vitamin B12 levels were measured in all subjects. Mean CIMT of the obese subjects were significantly higher than that of lean diabetic children and healthy controls (p=0.024). There was an independent relationship between CIMT and homocysteine level (b=0.76, p<0.0001). Further, homocysteine was negatively correlated with vitamin B12 (r=-0.20, p<0.001) and foli...

The Turkish journal of pediatrics, 2002

Iodine deficiency is an important public health problem worldwide. It is well known that it has s... more Iodine deficiency is an important public health problem worldwide. It is well known that it has severe consequences such as brain damage, developmental delay, deficits in hearing and learning and lower intellectual attainment. It also has a negative impact on growth. In this study, we aimed to address this issue and we assessed height standard deviation scores of children living in an area of severe iodine deficiency in comparison to those living in a mild iodine deficiency area. Serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also analyzed to investigate the mechanisms by which iodine depletion leads to growth failure. Pubertal children in a severe iodine deficient SID area had lower height standard deviation scores (HSDS), IGF-I and IGFBP-3 levels than those living in mild iodine deficient MID area. Similar findings could not be elucidated in the prepubertal age group. The major deter...

The Turkish journal of pediatrics, 2012

Vitamin D-deficient rickets (VDDR) remains an important health problem especially in developing c... more Vitamin D-deficient rickets (VDDR) remains an important health problem especially in developing countries. Insufficient dietary intake of vitamin D and inadequate sun exposure increase the risk of vitamin D deficiency. Since their vitamin D requirement is increased, children and adolescents are potentially at higher risk for vitamin D deficiency. In adolescents, vitamin D deficiency causes osteomalacia, osteoporosis and muscle weakness. While osteoporosis is not associated with bone pain, osteomalacia has been associated with isolated or generalized bone pain. The present case suffered from generalized bone pain for three years. She was misdiagnosed as ankylosing spondylitis, which is a seronegative arthropathy, and was treated with corticosteroids and methotrexate, which have potential side effects. Hypocalcemia, hypophosphatemia, elevated alkaline phosphatase level, secondary hyperparathyroidism, and extremely low vitamin D level were consistent with the diagnosis of severe vitami...

The Turkish journal of pediatrics, 2006

Cholestatic hepatitis is identified as one of the features of hypopituitarism in the newborn, but... more Cholestatic hepatitis is identified as one of the features of hypopituitarism in the newborn, but the exact etiology of cholestasis in these cases has not been well established yet. We report here two infants, one with isolated glucocorticoid deficiency and the other with multiple pituitary hormone deficiency, indicating primary and central adrenal insufficiency, respectively, who presented with recurrent hypoglycemic seizures and cholestatic hepatitis. Severe cortisol deficiency in these cases was suggested to be the cause of cholestatic hepatitis. Review of the literature and our cases showed that the cortisol deficiency in both primary and central adrenal insufficiency occurring only during neonatal and early infancy period cause cholestatic hepatitis. The severity and the age of onset of cortisol deficiency are suggested to be the important predictors of cholestatic hepatitis in childhood.

The Turkish journal of pediatrics, 2004

Iodine deficiency is an important public health problem worldwide. In addition to severe conseque... more Iodine deficiency is an important public health problem worldwide. In addition to severe consequences such as brain damage, developmental delay, deficits in hearing and learning, it also has a negative impact on growth. The negative impact of severe iodine deficiency (SID) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) was shown previously. In this study we aimed to analyze the impact of iodine supplementation on growth and growth factors of children with SID. One hundred and four children (63 boys and 41 girls) aged 5-15 years participated in the study. Height standard deviation scores (HSDS), and serum levels of IGF-I and IGFBP-3 were assessed both before and six months after a single dose of iodized oil. Serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were also analysed to investigate the mechanisms by which alterations of iodine status may influence growth. Pubertal children had lower HSDS six months ...