Accepted Article
1
Received date: 06/18/2014 Accepted date: 11/09/2014 Revised date: 10/26/2014
Original Articles Gut hormones of preterm infants with abdominal symptoms and hypothyroxinemia1
Running title: Thyroid and gut hormones in prematurity
List of authors: Ryou Kawamata1, MD; Yume Suzuki1, MD; Yukari Yada1, MD, PhD; Yasunori Koike1, MD; Yumi Kono1, MD, PhD; and Naoto Takahashi2, MD, PhD Author institutional affiliations: 1Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan; 2Department of Pediatrics, The
University of Tokyo, Tokyo, Japan Corresponding author: Ryou Kawamata, MD, Department of Pediatrics, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Tel: +81-285-58-7366; Fax: +81-285-44-6123; E-mail: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the
copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ped.12556
This article is protected by copyright. All rights reserved.
Accepted Article
2
Number of text pages, 15; references pages, 5; tables, 5
Abstract
Background: The pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. Methods: In eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin were measured using a bead array system. Results: Serum GLP-1, GIP and PYY levels in the subjects before T4-Na supplementation were lower than in controls at age two weeks. After improvement of abdominal symptoms and free thyroxine levels, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. Conclusions: In preterm infants with abdominal symptoms, serum levels of GLP-1, GIP and PYY might be related to thyroid function.
This article is protected by copyright. All rights reserved.
Accepted Article
3
Keywords: thyroxine, GIP, GLP-1, PYY, premature infants
Introduction Abdominal distention, loss of appetite, constipation and poor weight gain are symptoms of congenital hypothyroidism in infants. Hypothyroidism is presumed to affect gastrointestinal motility;1 nevertheless, it has not been well understood why abdominal
symptoms occur in hypothyroidism. In preterm infants, a transient decrease in serum thyroxine (T4) may occur within a week after birth.2 Abdominal distention, feeding intolerance and poor weight gain are sometimes seen in premature infants with transient hypothyroxinemia.3
Earlier, we reported that thyroxine supplementation was effective in improving abdominal symptoms in very low birth weight infants whose serum free thyroxine (fT4) level was less than 1.31 ng/dL.3 However, the mechanism of thyroid hormone action on intestinal function has not been elucidated. We investigated postnatal changes in serum concentration of eight gut hormones and reported that each gut hormone had its own particular pattern of postnatal change in preterm infants.4 Although the number of reports about gut hormones in preterm and
This article is protected by copyright. All rights reserved.
Accepted Article
4
term infants has been increasing, no study has yet been reported on the relationship between gut hormones and thyroid hormones. In the present study, we investigated changes in serum concentration of eight gut hormones after thyroxine supplementation in preterm infants with abdominal symptoms and hypothyroidism. Methods Subjects
A total of 75 preterm infants born at 30 gestational weeks or less were admitted to the neonatal intensive care unit at Jichi Medical University Hospital between September 2009 and March 2011. Of these, eight infants who had abdominal distention and feeding intolerance with hypothyroxinemia during the first few months of life were enrolled in the present study (Disease group, Dg). Fourteen gestational age-matched infants without abdominal symptoms within the first few months after birth were selected as the control group (Cg). We could not choose preterm infants whose birth weights were well matched with Dg, because Dg contained many infants who were small for gestational age (SGA). Infants with severe perinatal asphyxia, congenital malformations, congenital hypothyroidism, hypopituitarism or any severe infections or abdominal diseases such as necrotizing enterocolitis or structural intestinal obstruction during the period of blood
This article is protected by copyright. All rights reserved.
Accepted Article
5
sampling were excluded from both groups. Approval from the Ethics Committee of Jichi Medical University School of Medicine was obtained prior to starting the study (No.A09-20, A11-10). Informed consent was obtained from the parents of all infants. Indications for T4-Na supplementation T4-Na was administered to the infants at an initial dose of 5 μg/kg/day if they had: 1) TSH>10 μU/mL and free T4
1
Received date: 06/18/2014 Accepted date: 11/09/2014 Revised date: 10/26/2014
Original Articles Gut hormones of preterm infants with abdominal symptoms and hypothyroxinemia1
Running title: Thyroid and gut hormones in prematurity
List of authors: Ryou Kawamata1, MD; Yume Suzuki1, MD; Yukari Yada1, MD, PhD; Yasunori Koike1, MD; Yumi Kono1, MD, PhD; and Naoto Takahashi2, MD, PhD Author institutional affiliations: 1Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan; 2Department of Pediatrics, The
University of Tokyo, Tokyo, Japan Corresponding author: Ryou Kawamata, MD, Department of Pediatrics, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Tel: +81-285-58-7366; Fax: +81-285-44-6123; E-mail: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the
copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ped.12556
This article is protected by copyright. All rights reserved.
Accepted Article
2
Number of text pages, 15; references pages, 5; tables, 5
Abstract
Background: The pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. Methods: In eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin were measured using a bead array system. Results: Serum GLP-1, GIP and PYY levels in the subjects before T4-Na supplementation were lower than in controls at age two weeks. After improvement of abdominal symptoms and free thyroxine levels, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. Conclusions: In preterm infants with abdominal symptoms, serum levels of GLP-1, GIP and PYY might be related to thyroid function.
This article is protected by copyright. All rights reserved.
Accepted Article
3
Keywords: thyroxine, GIP, GLP-1, PYY, premature infants
Introduction Abdominal distention, loss of appetite, constipation and poor weight gain are symptoms of congenital hypothyroidism in infants. Hypothyroidism is presumed to affect gastrointestinal motility;1 nevertheless, it has not been well understood why abdominal
symptoms occur in hypothyroidism. In preterm infants, a transient decrease in serum thyroxine (T4) may occur within a week after birth.2 Abdominal distention, feeding intolerance and poor weight gain are sometimes seen in premature infants with transient hypothyroxinemia.3
Earlier, we reported that thyroxine supplementation was effective in improving abdominal symptoms in very low birth weight infants whose serum free thyroxine (fT4) level was less than 1.31 ng/dL.3 However, the mechanism of thyroid hormone action on intestinal function has not been elucidated. We investigated postnatal changes in serum concentration of eight gut hormones and reported that each gut hormone had its own particular pattern of postnatal change in preterm infants.4 Although the number of reports about gut hormones in preterm and
This article is protected by copyright. All rights reserved.
Accepted Article
4
term infants has been increasing, no study has yet been reported on the relationship between gut hormones and thyroid hormones. In the present study, we investigated changes in serum concentration of eight gut hormones after thyroxine supplementation in preterm infants with abdominal symptoms and hypothyroidism. Methods Subjects
A total of 75 preterm infants born at 30 gestational weeks or less were admitted to the neonatal intensive care unit at Jichi Medical University Hospital between September 2009 and March 2011. Of these, eight infants who had abdominal distention and feeding intolerance with hypothyroxinemia during the first few months of life were enrolled in the present study (Disease group, Dg). Fourteen gestational age-matched infants without abdominal symptoms within the first few months after birth were selected as the control group (Cg). We could not choose preterm infants whose birth weights were well matched with Dg, because Dg contained many infants who were small for gestational age (SGA). Infants with severe perinatal asphyxia, congenital malformations, congenital hypothyroidism, hypopituitarism or any severe infections or abdominal diseases such as necrotizing enterocolitis or structural intestinal obstruction during the period of blood
This article is protected by copyright. All rights reserved.
Accepted Article
5
sampling were excluded from both groups. Approval from the Ethics Committee of Jichi Medical University School of Medicine was obtained prior to starting the study (No.A09-20, A11-10). Informed consent was obtained from the parents of all infants. Indications for T4-Na supplementation T4-Na was administered to the infants at an initial dose of 5 μg/kg/day if they had: 1) TSH>10 μU/mL and free T4
