High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients.

PURPOSE: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH. METHODS: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by "National Newborn Screening Program" (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET). RESULTS: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34-38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750. CONCLUSION: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

The Evaluation of The Effects of Paternal And Maternal Silent Coeliac Disease on Birthweight and Gestational Age in Newborns.

OBJECTIVE: Coeliac disease is a chronic disease and is common all over the world. It has many other associated systemic side effects. This study investigated the effect of paternal and maternal silent coeliac disease on birthweight and gestational age in newborns. METHODS: The study group consisted of 81 newborns who were hospitalized for prematurity or term-intrauterine growth retardation. The parents of premature and/or small for gestational age babies born with coeliac disease-specific antigens were investigated. RESULTS: The differences were not statistically significant in fathers' tissue transglutaminase levels between premature appropriate gestational age, premature small gestational age and term small gestational age infants (p > 0.05), but statistically significant in mothers (p < 0.05). CONCLUSIONS: Silent coeliac disease may occur in parents, especially in mothers of preterm and small for gestational age infants, even in the absence of apparent clinical indications.

Anophthalmia-plus syndrome with unusual findings. A clinical report and review of the literature.

We present a male child at 3 years old with Anophthalmia-Plus Syndrome (APS). He has asymmetry of the face and head, left choanal atresia, a sunken facial appearance, microphthalmia in the right eye, severe microphthalmia in the left eye, bilateral low-set ears, scarring from cleft palate surgery. Magnetic resonance imaging (MRI) sections revealed decreased right globe volume, an undeveloped left globe, decreased left optical nerve thickness, Chiari type 2 malformation, left choanal atresia and cleft palate. Echocardiography and abdominal ultrasonography were normal. The patient has a 45 dB conductive hearing loss in the left ear. Repeated thyroid function tests were evaluated as compatible with central hypothyroidism. We report a Fryns Anophthalmia-Plus Syndrome in a child with unusual findings including central hypothyroidism, chiari type 2 malformation, conductive hearing loss and developmental regression. Summary of the features reported in the present case and all 14 previous cases that might be defined as APS.

The effect of serum magnesium levels and serum endothelin-1 levels on bone mineral density in protein energy malnutrition.

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

Effects of steroid treatment on bone mineral metabolism in children with glucocorticoid-sensitive nephrotic syndrome.

Glucocorticoids have been used in nephrotic syndrome (NS) treatment for many years. In this study, we aimed to evaluate the effect of steroids on bone mineralization in children with glucocorticoid-sensitive nephrotic syndrome (GSNS). Twenty children who were first diagnosed as GSNS received glucocorticoid therapy for four months. Before treatment, at the 4th and 12th week of initial therapy, bone mineral density (BMD) and levels of the markers for bone turnover were evaluated. At the 4th and 12th week of treatment, mean serum calcium (Ca) and osteocalcin levels were found to be significantly lower than those at the beginning of the therapy. Mean serum total alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and urine calcium creatinine ratio (Ca/Cr), urinary deoxypyridinoline levels were significantly increased in comparison to the beginning of therapy There was no significant relationship between serum levels of phosphate and parathyroid hormone (PTH) at the beginning of treatment and at the 4th and 12th week of treatment. Mean value of BMD was significantly lower at the 4th and 12th week of treatment than that at the beginning of the therapy In conclusion, bone mineralization was negatively affected by steroid treatment in children with NS. These children should undergo regular BMD evaluation, and an appropriate therapeutic approach should be planned.

Adverse reaction of topical etofenamate: petechial eruption.

Etofenamate is a non-steroidal anti-inflammatory drug (NSAID). Clinical findings caused by etofenamate are uncommon. Allergic contact dermatitis is the most common cutaneous reaction reported. But petechial eruption due to etofenamate had not been reported yet. This report concerns an 11-year old male with petechial eruption after application of topical etofenamate. Physicians need to be aware that patients can develop an asymptomatic purpuric eruption when etofenamate is ordered.

Recurrent parotitis as a first manifestation in a child with primary Sjogren's syndrome.

Recurrent parotitis is an acute, severe inflammation of one or both parotid glands, the major salivary glands in young children. We report the case of a seven-year old boy with Primary Sjogrens syndrome (PSS) who presented with 15 episodes of painful recurrent bilateral swellings of the parotid glands over a four-year period.

Association between anthropometric hormonal measurements and bone mineral density in puberty and constitutional delay of growth and puberty.

The aim of this study is to evaluate the acquisition of bone mineral in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP), and to relate changes in bone mass to age, weight, height, sitting height, body mass index and sex hormones in healthy boys. A total of 90 boys: 15 boys with CDGP and 75 healthy boys in different pubertal stages were examined. The number of children assigned to each Tanner stages was 15. Although bone age, weight and Body Mass Index (BMI) were significantly higher in stages II, III, IV V compared to stage I and CDGI mean height and sitting height values were higher in stages III, IV V compared to stage I and CDGP Also, serum FSH, LH, oestradiol, total and free testosterone levels progressively increased, although serum sex hormone binding globulin (SHBG) levels decreased, in healthy children with progression of sexual development. Significant increase was observed for serum oestradiol levels at stage II and above (p < 0.001), for serum total and free testosterone levels at stage III and above (p < 0.001), for serum FSH and LH levels at stage IV and above (p < 0.01 and p < 0.001) respectively. Also, it was shown that bone mineral content (BMC) and bone mineral density (BMD) measurements were significantly higher for pubertal stage III and above groups according to both the CDGP group and stage I group. When BMD and BMC measurements of children with CDGP (0.62 +/- 0.05 gr/cm2 and 23.4 +/- 2.8 gr) were compared with bone age, age, BMI and height-matched controls, there was no significant difference between children with CDGP and controls, except for age. Bone mineral density and BMC measurements in children with CDGP were significantly lower than those of age-matched controls (for pubertal stage III: p < 0.05, for pubertal stage IV: p < 0.01). The strongest correlation coefficients were found between BMD and height among auxological parameters (r = 0.63, p < 0.001) and serum oestradiol levels among hormones (r = 0.55, p < 0.001). The most important findings of this investigation was the determination of body composition and hormonal measurement changes during puberty in boys; oestradiol was the most potent determinant of BMD among pubertal boys. We suggested that there is a critical age period for accumulation of bone mass according to the results. Longitudinal studies will elucidate why sufficient mineralization does take place after puberty starts in CDGP

Penicillin V-induced drug rash with eosinophilia and systemic symptoms.

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), previously named "drug hypersensitivity syndrome", is a severe adverse drug reaction characterized by skin rash, fever lymph node enlargement and internal organ involvement. We report on a 7-year old girl who developed DRESS syndrome caused by penicillin V treatment.

A case of Bonneau syndrome associated with multiple renal cortical cysts.

We describe a 2-month-old girl with congenital anomalies including facial anomalies, complex cardiac anomalies, polysyndactyly, dysgenesis of distal extremities and bilateral multiple renal cysts. The proband was the child of first-cousin parents. Clinical synopsis in Bonneau syndrome (OMIM: 263630) is polysyndactyly and cardiac malformation. In addition, liver anomalies were reported in two patients. We discuss polysyndactyly and cardiac malformation with bilateral multiple renal cysts, a combination not reported previously.

Association between bone turnover markers and bone mineral density in puberty and constitutional delay of growth and puberty.

The aim of this study was to evaluate associations between the markers of bone formation and resorption and bone mineral density in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP). For this reason, 15 boys with CDGP and 75 other boys in different pubertal stages were included in this study. Although mean serum phosphorus level was higher in stages II, III, IV, V compared to stage I and CDGP, mean bone specific akaline phosphatase (b-AP), parathyroid hormone (PTH), bone mineral density (BMD), bone mineral content (BMC) levels were higher in stages III, IV, V compared to stage I and CDGP Mean serum calcium (Ca) levels were lower in stages III, IV, V compared to stage I and CDGP. During puberty, urine DPry/Cr levels were not significant. The peak level of b-AP occurred at stage IV. Serum PTH, Ca, b-AP levels, urine Ca/Cr ratio, BMC and BMD measurements significantly changed during puberty in healthy children. While serum Ca levels progressively decreased, serum b-AP, PTH levels, urine Ca/Cr ratio and bone mineralization increased in healthy children with the level of sexual development. The only significant correlation is found between serum PTH levels and bone mineral density (p < 0.05). In our opinion, PTH may be a potent stimulator of skeletal dynamics in boys and may be associated with substantial increases in lumbar spine. We conclude that PTH behaved as a valuable marker in bone mineralization during puberty. Accelerated bone mineralization is reflected by high levels of serum PTH during puberty. All values of the markers of bone formation and bone resorption in children with CDGP were similar to those of prepubertal children. Children with CDGP had prepubertal properties. We suggest that there is a critical age period for accumulation of bone mass according to the results in this study.

Congenital rickets presenting with hypocalcaemic seizures.

At Ataturk University Hospital, eight infants who presented with hypocalcaemic seizures were subsequently found to have rickets. Their mothers had osteomalacia. Neither mothers nor infants received vitamin D supplementation. Maternal vitamin D deficiency and non-supplementation in the infants were causes of rickets in these patients. It is recommended that neonatal hypocalcaemia may be due to maternal vitamin D deficiency and all unsupplemented vitamin D infants presenting with seizures should be investigated for rickets.

Splenic lobulations in Bardet-Biedl syndrome: a first case report.

Bardet-Biedl Syndrome (BBS) is a rare genetic disorder. It is considered to develop as a result of ciliary dysfunction. There are some clues about splenic expression of ciliary dysfunction. Therefore, splenic anomalies may be expected in BBS. We, here, describe a first case of BBS associated with splenic lobulations.

Serum paraoxonase and arylesterase values as antioxidants in healthy premature infants at fasting and posprandial times.

OBJECTIVE: Newborn infants, particularly preterm infants, are at greater risk of oxidative stress because of an imbalance between high oxidant loads and immature antioxidant defenses. In several studies, the activities of serum paraoxonase (PON) and arylesterase (ARE) have been found to decline in patients under increased oxidative stress. We investigated the relationships between PON-1 and ARE with fasting and postprandial in premature newborns in this study. PATIENTS AND METHODS: Serum paraoxonase-1 and arylesterase levels were investigated in premature infants less than 37 weeks, after birth while they were fasting and postprandial. RESULTS: The paraoxonase-1 and arylesterase values of infants in fasting were significantly lower than the values in postprandial (for paraoxonase-1, p = 0.034, 0.002, and 0.002, respectively; for arylesterase, p < 0.001, 0.002, and p < 0.001, respectively). CONCLUSIONS: In premature infants, paraoxonase-1 and arylesterase values are increased in postprandial and reduced in fasting, showing that these neonates are subjected to oxidative stress. Thus, starting feeding as soon as possible in premature newborns is vital to protect them from oxidative damage.

Puberty and mineralization of the skeleton in girls.

We studied the acquisition of bone mineral and related changes in body mass, pubertal status, and sex hormones in 75 healthy prepubertal and pubertal girls aged 7.5-16 years. Bone mineral density of the lumbar spine (L-1, L-2, L-3, L-4) was measured in children by quantitative computerized tomography. Skeletal mineralization accelerated markedly at puberty. Age, weight, height, and body mass index (BMI) were highly correlated with bone mineral density.

Association between serum leptin and anthropometric parameters at birth and at 15th day of life in infants born asymmetrically small for gestational age.

The aim of this study was to investigate changes in skinfold measurements taken at three sites, mid-arm circumference and umbilical circumference during the first 15 days of life; and to evaluate relationships between anthropometric measurements and umbilical cord blood serum leptin levels in infants born small for gestational age (SGA) and appropriate for gestational age (AGA) infants. Of 50 newborn infants, 25 were SGA and 25 were AGA. Neonates' weight, mid-arm circumference (MAC), umbilical circumference (UC), and triceps, subscapular and periumbilical skinfold thicknesses were measured (Holtain callipers) immediately after delivery. Anthropometric parameters were measured again at 15th days of age. At birth, mean birth weight, mean skinfold thickness, MAC and UC measurements in the AGA group were significantly higher than those of the SGA group. These differences were also found on the 15th day. Birth weight correlated with all skinfold thicknesses, MAC and UC at birth. Weight at 15th day of life correlated with skinfold thicknesses, MAC and UC at 15th day of life. Cord blood leptin level was significantly lower in the SGA than in the AGA infants. This difference continued on the 15th day. When cord blood leptin level was compared with that of the 15th day, we found that leptin levels in the cord blood were significantly higher. There were significantly positive correlations between leptin levels and birth weight and skinfold thicknesses when the infants were all grouped together. When the newborns were grouped according to birth weight, there were positive correlations between cord blood serum leptin levels and these parameters in the AGA group, but no correlation in the SGA group. At the 15th day of life serum leptin levels correlated with weight, subscapular and triceps skinfold thickness in the AGA group, but only with triceps skinfold thickness in the SGA group.

Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3), leptin levels and early postnatal growth in infants born asymmetrically small for gestational age.

This study was planned to investigate the relationship between birth weight and insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and leptin levels in neonates with normal growth (appropriate for gestational age: AGA) and retarded growth (small for gestational age: SGA); and to evaluate these growth factors' effects in early postnatal growth. All newborns were full-term: gestational age 3,841 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and leptin levels were measured in maternal serum and venous cord blood at birth and at 15 days of life of neonates using specific RIAs. Maternal serum leptin concentrations were significantly higher than cord blood leptin concentrations (p < 0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show correlations with birth weight. In contrast, there were significantly positive correlations between birth weight and venous cord blood IGF-I, IGFBP-3 and leptin levels (p < 0.001). In the SGA group, the newborns with a slow postnatal growth pattern had lower umbilical cord serum IGF-I levels compared with newborns with a normal growth pattern. A similar result was also found in the AGA group. Similar results were not found for serum leptin and IGFBP-3. In conclusion, cord blood IGF-I, IGFBP-3 and leptin levels play an important role in the regulation of fetal and neonatal growth. It is likely that IGF-I has a more important role than the other factors in early postnatal growth.

Serum thyroid hormone and thyroid gland weight measurements in protein-energy malnutrition.

Protein-energy malnutrition (PEM) is a problem which concerns about half the world's children. We investigated the effects of malnutrition on thyroid gland weight and thyroid hormone levels. 22 children suffering from malnutrition (14 children suffering from marasmus and 8 children suffering from kwashiorkor) and 7 healthy controls were studied. Malnutrition was confirmed clinically and according to the Wellcome classification definition of malnutrition. Serum thyroid hormone concentrations were measured by radioimmunoassay and the weights of the thyroid gland were evaluated scintigraphically. In the groups with marasmus and kwashiorkor the mean TT4, TT3 and FT3 levels were significantly lower, and TSH levels were significantly higher, compared to controls. FT4 was not influenced by PEM. The mean thyroid gland weights of the groups with marasmus and kwashiorkor were higher than that of the control group. We found no significant differences in all these parameters between groups with marasmus and kwashiorkor. In each of the three groups, the most marked positive correlation was between thyroid gland weight and ratio of thyroid gland weight to body surface area.