Hakan Doneray

The relationship between breast milk leptin and neonatal weight gain

Aim: To investigate whether change in leptin content of breast milk during lactation acts on neonatal body weight gain.

Vitamin D intoxication and therapy with alendronate (case report and review of literature)

Dear editor, We read the article of Bereket and Ertogan [1], reporting a 3-month-old boy with vitamin D intoxication, who was treated with alendronate, with great interest. Here we present a 7-year-old male with acute vitamin D intoxication, who was treated with oral alendronate. A 7-year old male child was admitted to our Pediatric Emergency Unit with symptoms of anorexia, nausea, vomiting, polydipsia, polyuria and constipation. In history, he was administered 300,000 units of oral vitamin D (cholecalciferol) daily for 15 days by an internist, who suspected vitamin D deficiency. Above mentioned symptoms had occurred at the end of 15 days. The physical examination on admission revealed impaired turgor of the skin and dryness of the oral mucosa consistent with moderate dehydration. The rest of the examination was unremarkable. On admission, laboratory findings are shown in Table 1. The patient was admitted to the ward and emergency treatment was initiated with IV hydration (2,500 mL/m/d, additional 20 mEq/l potassium chloride), furosemide (1 mg/kg/dose, every 6 h). Dietary calcium and vitamin D intake were restricted. A repeat serum calcium level was 14.8 mg/dL on the following day. Urinary calcium/creatinine ratio was initially high. Renal ultrasonography was reported as normal. Alendronate sodium 5 mg/d given by mouth was added to treatment after obtaining informed consent from the father. Serum calcium was still 14.3 mg/dL on the 3rd day of admission, the dose of alendronate was increased to 10 mg/d. Calcium levels decreased gradually in the following days. Then serum calcium dropped to 10.3 mg/dL on the 16th day and treatment was discontinued without any relapse. No side effects were noted with this treatment. Serum calcium levels remained normal thereafter. Urinary calcium/creatinine ratio decreased gradually to normal levels on 2nd month. Renal ultrasound examination at 2nd month after the admission did not show any evidence of nephrocalcinosis or other abnormalities. A radiographs of the hand taken on the admission, at 1 and 2 months after the admission did not show metaphyseal sclerosis. Laboratory values and treatment during follow-up are shown in Table 1. It is known that rapid normalization of serum calcium level and maintaining of normocalcemia are necessary to prevent acute complications and prolonged hypercalciuria and nephrocalcinosis [6]. Relative potency of alendronate to inhibit bone resorption is 10–20 times higher than that of pamidronate [7]. Although pamidronate has been used in children with vitamin D intoxication [2, 4], studies examining the efficacy of oral alendronate in children are limited. In literature, we found one case report which represented efficacy of alendronate in hypervitaminosis D [1]. There is currently little information to guide clinicians as to duration of treatment and what criteria should be used to indicate termination of the treatment. In our study normalization of serum calcium level also took almost two weeks and hypercalcemia did not recur. Another condition is duration of treatment effect. It is currently unclear how long the effect of bisphosphonate treatment will last once discontinued. When administered, bisphosphonates are cleared rapidly from the circulation. Its half-life in serum is short, a few hours or less, whereas the half-life in the bone Z. Orbak . H. Doneray . F. Keskin . A. Turgut . H. Alp . C. Karakelleoglu Department of Pediatric Endocrinology, Ataturk University Faculty of Medicine, Erzurum, Turkey

Bone mineral density of children with Wilson disease: efficacy of penicillamine and zinc therapy.

Objectives Osteoporosis accompanying chronic liver disease is well known; however, the exact prevalence is unknown. No data on bone mineral density (BMD) of children with Wilson disease (WD) have been published so far. In this study, we aimed to investigate the prevalence of osteoporosis in childhood WD and to observe the probable positive effects of penicillamine and zinc therapy on osteoporosis. Methods Thirty-one children with newly diagnosed WD and sex and age-matched 16 healthy children were included. Mean age was 9.0±3.2 years (2 to 16 y). Bone mineral content (BMC) and BMD were measured on admission and in 13 cases they were reassessed after 1 year of treatment with penicillamine and zinc. Results Mean BMD, BMC, and Z scores of the patients were significantly lower than those of healthy children: 0.52±0.09 versus 0.72±0.09 (P=0.001), 19.27±13.01 versus 29.67±14.23 (P=0.009), and −2.33±1.28 versus −0.12±0.31 (P=0.001), respectively. The prevalence of osteopenia and osteoporosis in children with WD was found as 22.6% and 67.7%, respectively. BMD and BMC levels were higher in children with neurologic involvement. The severity of the disease had no effect on the mentioned parameters. One year under treatment with penicillamine and zinc did not significantly alter the mentioned parameters. Conclusions In this first study investigating the prevalence of osteoporosis in children with WD, we found an extremely high prevalence. Because of nonbeneficial effect of routine treatment of WD on osteoporosis, we emphasize the necessity of screening of bone mineralization and additional therapeutic approach for those children.

Circulating insulin-like growth factor binding protein-4 (IGFBP-4) is not regulated by parathyroid hormone and vitamin D in vivo: evidence from children with rickets.

Objective: Insulin-like growth factor binding protein-4 (IGFBP-4), inhibits IGF actions under a variety of experimental conditions. Parathyroid hormone (PTH), 1.25-hydroxy(OH)vitamin D, IGF-I, IGF-II and transforming growth factor (TGF)-b are the major regulators of IGFBP-4 production in vitro. However, little is known about the in vivo regulation of circulating IGFBP-4 in humans. Methods: We measured serum concentrations of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), PTH, vitamin D, IGF-I, IGFBP-3, and IGFBP-4 in infants (n=22) with nutritional rickets before and after treatment of rickets with vitamin D (300 000 U single dose po). Results: The mean±SD age of the patients was 1.3±1.6 years (range 0.2-3). Serum Ca and P increased, whereas ALP and PTH decreased after treatment (Ca from 6.6±1.4 to 9.5±1.6 mg/dL, P from 3.9±1.4 to 5.4±0.8 mg/dL, ALP from 2590±2630 to 1072±776 IU/mL and PTH from 407±248 to 27.4±20.8 ng/dL, respectively). Vitamin D levels were low (7.8±2.5 ng/mL) and increased after treatment (18.1±4.0 ng/mL, p<0.001). Serum IGF-I and IGFBP-3 levels both increased after treatment (IGF-I: 13.5±12.2 vs. 23.7±14.2 ng/mL, p<0.001 and IGFBP-3: 1108±544 vs. 1652±424 ng/mL, p<0.001). However, serum IGFBP-4 levels did not change significantly after treatment (18.8±8.0 vs. 21.5±4.8 ng/mL). No correlation between PTH and IGF-I, IGFBP-3 or IGFBP-4 was detected. Significant correlations were observed between PTH and ALP (r=0.53, p<0.05), and between IGF-I and IGFBP-3 (r=0.46, p<0.05). Conclusion: The results demonstrate that contrary to in vivo studies, circulating IGFBP-4 levels are not influenced by secondary hyperparathyroidism in vitamin D deficiency rickets since IGFBP-4 levels did not change after normalization of PTH with vitamin D treatment. Conflict of interest:None declared.

Effect of Smoking on Neonatal and Maternal Serum and Breast Milk Leptin Levels

Maternal smoking is considered to be a risk factor for low birth weight. It is hypothesized that alteration in leptin concentration may be associated with reduced fetal growth. In this study, we assess the effect of smoking during pregnancy on maternal and neonatal serum leptin concentrations, and also on breast milk leptin levels. When the infants were brought to routine physical examination at 7 days old, blood samples and breast milk specimens were taken for leptin measurement from mothers who smoked during pregnancy and their newborns. Nonsmoking mothers and their infants were recruited randomly over the same period as a control group. Maternal age, number of pregnancy, weight of the mothers, birth weight, and gestational age of the infants were similar in both groups (p > 0.05). There was no significant difference between groups in maternal serum and breast milk leptin levels (p = 0.14 and p = 0.96, respectively). However, serum leptin levels were found significantly lower in neonates born to smoking mothers compared with infants born to nonsmoking mothers (p = 0.02). Our findings suggest that maternal smoking dose not have an effect on maternal serum and breast milk leptin levels but decreases neonatal serum leptin concentration independent of birth weight.

Intragastric alendronate therapy in two infants with vitamin D intoxication: A new method

In recent years, alendronate, an oral biphosphonate, has been added to therapy of hypercalcemia secondary to vitamin D intoxication in children. Alendronate may cause mucosal ulcerations in the mouth and esophagus. We report our experience in two infants with vitamin D intoxication to whom alendronate therapy was administered through nasogastric tube, an alternate route for alendronate administration.

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. ΔlogCu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.

The Effect of Vitamin D Treatment on Serum Adiponectin Levels in Children with Vitamin D Deficiency Rickets

Objective: Adiponectin and its receptors are known to be expressed in osteoblasts and may have important functions in normal bone cells. The aim of this study was to investigate the effect of vitamin D therapy on serum adiponectin levels in children with vitamin D deficiency rickets (VDDR). Methods: 21 patients with VDDR were included in the study. Patients were treated with 300,000 U D3 (IM) and calcium lactate (50mg/kg/ day, PO, for 10 days). Anthropometric parameters and serum biochemical markers including calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), intact parathormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and adiponectin levels were measured before and after one month of therapy. Results: Weight and length, but not BMI, increased significantly after treatment. Serum 25(OH)D level increased significantly after treatment, while serum adiponectin level decreased (4.21±1.84 vs 52.73±17.63 ng/ml, p<0.000; 150.1±66.14 vs 84.29±9.06 mg/ml, p<0.000, respectively). No significant correlations were found between serum adiponectin and 25(OH)D levels before and after treatment or between delta adiponectin concentrations and delta 25(OH)D levels. Conclusion: Serum adiponectin levels are increased in patients with VDDR, a finding which is probably related to increased osteoblastic activity. Conflict of interest:None declared.

Clinical outcomes in children with hyoscyamus niger intoxication not receiving physostigmine therapy.

Objective Diagnosis of hyoscyamus niger intoxication is based on clinical symptomatology and history. Therapy includes stomach lavage, supportive therapy, and physostigmine as a specific antidote. Physostigmine is not available in Turkey. This retrospective study investigated the clinical outcomes in children with hyoscyamus niger intoxication who did not receive physostigmine therapy. Methods Twenty-three children whose history and medical records indicated hyoscyamus niger intoxication were included the study. Results None of the cases had any abnormal laboratory findings. All the patients were performed gastric lavage and provided with supportive therapy. None of the children had any complications, and none required mechanical ventilation or died. All the patients were discharged in good health within 48 h. Conclusion Our findings suggest that hyoscyamus niger intoxication in children is self-terminating and responds to supportive therapy and that routine use of physostigmine is unnecessary in every case with hyoscyamus niger intoxication.

Late vitamin K deficiency bleeding: 16 cases reviewed.

In this study, clinical and demographic features of 16 cases with late vitamin K deficiency bleeding are presented. Ages of infants were between 30 and 130 days. Their delivery histories were uneventful, and family histories for bleeding disorders were negative. All parents except one were unaware of whether their children received vitamin K at birth or not. All cases did not have any underlying illness to explain the abnormal coagulation profile. The common presenting finding was pallor (62.5%). Intracranial haemorrhage was the most common bleeding site (37.5%), and two patients (12.5%) died because of it. Late vitamin K deficiency bleeding is still an important handicap in infants. Parents and healthcare providers should be informed about the importance of vitamin K prophylaxis to prevent vitamin K deficiency in infants.