Eur J Pediatr Surg 2011; 21(4): 246-249
DOI: 10.1055/s-0031-1273778
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Parafollicular C-Cells of the Thyroid are Decreased in Patients with Congenital Diaphragmatic Hernia

A. L. Luis1 , F. Pederiva1 , J. L. Encinas1 , E. Ruiz2 , J. I. Rodriguez2 , L. Martinez1 , J. A. Tovar1
  • 1Hospital Infantil La Paz, Pediatric Surgery, Madrid, Spain
  • 2Hospital La Paz, Pathology, Madrid, Spain
Further Information

Publication History

received January 19, 2011

accepted after revision February 21, 2011

Publication Date:
08 April 2011 (online)

Abstract

Background: Parathyroid and thymic anomalies related to embryonic neural crest dysfunction have been demonstrated in rats with congenital diaphragmatic hernia (CDH). These rats, like infants with CDH, have conotruncal, facial, and other neurocristal defects. The present study examines whether parafollicular C-cells (CC) of the thyroid, whose embryogenesis is related to that of the parathyroids and thymus, might also be abnormal in babies with CDH.

Material and methods: Autopsy sections of the thyroids of 12 babies dead from CDH and of 11 controls were stained with anti-calcitonin antibodies. Calcitonin-stained areas and the histological distribution of CC within the thyroid gland were assessed. Mann-Whitney tests were used for comparison, with p<0.05 considered significant.

Results: The proportion of stained surface to total thyroid surface was significantly smaller in CDH babies than in controls (0.035±0.030% vs. 0.072±0.052%, p<0.05). A normal central CC location was demonstrated in both groups.

Conclusions: Parafollicular thyroid C-cells are deficient in patients with CDH. These findings further support the involvement of neural crest dysregulation in the pathogenesis of CDH and the pertinence of using this experimental model to investigate the human condition. The clinical effects of this anomaly are unknown and probably irrelevant, but they are currently under scrutiny.

References

  • 1 Migliazza L, Otten C, Xia H. et al . Cardiovascular malformations in congenital diaphragmatic hernia: human and experimental studies.  J Pediatr Surg. 1999;  34 1352-1358
  • 2 Tovar JA, Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.  J Pediatr Surg. 2007;  42 915-926
  • 3 Martinez L, Pederiva F, Martinez-Calonge W. et al . The myenteric plexus of the esophagus is abnormal in an experimental congenital diaphragmatic hernia model.  Eur J Pediatr Surg. 2009;  19 163-167
  • 4 Pederiva F, Aras Lopez R, Martinez L. et al . Abnormal development of tracheal innervation in rats with experimental diaphragmatic hernia.  Pediatr Surg Int. 2008;  24 1341-1346
  • 5 Pederiva F, Lopez RA, Martinez L. et al . Tracheal innervation is abnormal in rats with experimental congenital diaphragmatic hernia.  J Pediatr Surg. 2009;  44 1159-1164
  • 6 Acosta JM, Chai Y, Meara JG. et al . Prenatal exposure to nitrofen induces Fryns phenotype in mice.  Ann Plast Surg. 2001;  46 635-640
  • 7 Pederiva F, Rodriguez JI, Ruiz-Bravo E. et al . Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction.  J Pediatr Surg. 2009;  44 496-499
  • 8 Yu J, Gonzalez S, Rodriguez JI. et al . Neural crest-derived defects in experimental congenital diaphragmatic hernia.  Pediatr Surg Int. 2001;  17 294-298
  • 9 Martinez L, De Ceano-Vivas M, Gonzalez-Reyes S. et al . Las células C tiroideas están disminuidas en la hernia diafragmática experimental.  Cir Pediatr. 2006;  19 101-105
  • 10 Gamallo C, Garcia M, Palacios J. et al . Decrease in calcitonin-containing cells in truncus arteriosus.  Am J Med Genet. 1993;  46 149-153
  • 11 Palacios J, Gamallo C, Garcia M. et al . Decrease in thyrocalcitonin-containing cells and analysis of other congenital anomalies in 11 patients with DiGeorge anomaly.  Am J Med Genet. 1993;  46 641-646
  • 12 Greer JJ, Babiuk RP, Thebaud B. Etiology of congenital diaphragmatic hernia: the retinoid hypothesis.  Pediatr Res. 2003;  53 726-730
  • 13 Kling DE, Schnitzer JJ. Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital diaphragmatic hernia (CDH).  Am J Med Genet C Semin Med Genet. 2007;  145C 139-157
  • 14 Andersen DH. Effect of diet during pregnancy upon the incidence of congenital hereditary diaphragmatic hernia in the rat; failure to produce cystic fibrosis of the pancreas by maternal vitamin A deficiency.  Am J Pathol. 1949;  25 163-185
  • 15 Warkany J. Disturbance of embryonic development by maternal vitamin deficiencies.  J Cell Physiol Suppl. 1954;  43 207-236
  • 16 Thebaud B, Tibboel D, Rambaud C. et al . Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats.  Am J Physiol. 1999;  277 L423-L429
  • 17 Lohnes D, Mark M, Mendelsohn C. et al . Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants.  Development. 1994;  120 2723-2748
  • 18 Mendelsohn C, Lohnes D, Decimo D. et al . Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants.  Development. 1994;  120 2749-2771
  • 19 Major D, Cadenas M, Fournier L. et al . Retinol status of newborn infants with congenital diaphragmatic hernia.  Pediatr Surg Int. 1998;  13 547-549
  • 20 Nakazawa N, Montedonico S, Takayasu H. et al . Disturbance of retinol transportation causes nitrofen-induced hypoplastic lung.  J Pediatr Surg. 2007;  42 345-349
  • 21 Nakazawa N, Takayasu H, Montedonico S. et al . Altered regulation of retinoic acid synthesis in nitrofen-induced hypoplastic lung.  Pediatr Surg Int. 2007;  23 391-396
  • 22 Chen MH, MacGowan A, Ward S. et al . The activation of the retinoic acid response element is inhibited in an animal model of congenital diaphragmatic hernia.  Biol Neonate. 2003;  83 157-161
  • 23 Mey J, Babiuk RP, Clugston R. et al . Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents.  Am J Pathol. 2003;  162 673-679
  • 24 Montedonico S, Nakazawa N, Puri P. Retinoic acid rescues lung hypoplasia in nitrofen-induced hypoplastic foetal rat lung explants.  Pediatr Surg Int. 2006;  22 2-8
  • 25 Noble BR, Babiuk RP, Clugston RD. et al . Mechanisms of action of the congenital diaphragmatic hernia-inducing teratogen nitrofen.  Am J Physiol Lung Cell Mol Physiol. 2007;  293 L1079-L1087
  • 26 Keijzer R, Liu J, Deimling J. et al . Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia.  Am J Pathol. 2000;  156 1299-1306
  • 27 Trainor PA, Krumlauf R. Hox genes, neural crest cells and branchial arch patterning.  Curr Opin Cell Biol. 2001;  13 698-705
  • 28 Manley NR, Capecchi MR. The role of Hoxa-3 in mouse thymus and thyroid development.  Development. 1995;  121 1989-2003
  • 29 Manley NR, Capecchi MR. Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands.  Dev Biol. 1998;  195 1-15
  • 30 Kim C, Nielsen HC. Hoxa-5 in mouse developing lung: cell-specific expression and retinoic acid regulation.  Am J Physiol Lung Cell Mol Physiol. 2000;  279 L863-L871
  • 31 Fu M, Chi Hang Lui V, Har Sham M. et al . HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts.  Dev Dyn. 2003;  228 1-10
  • 32 Chinoy MR, Nielsen HC, Volpe MV. Mesenchymal nuclear transcription factors in nitrofen-induced hypoplastic lung.  J Surg Res. 2002;  108 203-211
  • 33 Martinez L, Ceano-Vivas MD, Gonzalez-Reyes S. et al . Decrease of parafollicular thyroid C-cells in experimental esophageal atresia: further evidence of a neural crest pathogenic pathway.  Pediatr Surg Int. 2005;  21 175-179

Correspondence

Leopoldo MartinezMD 

Hospital Infantil La Paz

Pediatric Surgery

Paseo de la Castellana 261

28046 Madrid

Spain

Phone: +34 91 727 70 19

Fax: +34 91 727 74 78

Email: lmartinezm.hulp@salud.madrid.org

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