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Hirschsprung’s disease (HD)
as well as congenital hypothyroidism can present with functional
intestinal obstruction and abdominal distension in neonates [1].
Hirschsprung’s disease results from a colonization defect of neural
crest cells through the colon and the aganglionic segment presents
with obstruction [2]. Thyroid hormone is necessary for neuronal
migration and lamination during brain development. Although
hypothyroidism impairs colonic motility resulting in
pseudo-obstruction, which may be reversed by thyroxine
supplementation, the effects of hypothyroidism on neuronal migration
through bowel have not been adequately studied. We report a child
with co-existence of the two conditions.
Case Report
A 21-day old female infant, product of a
consanguineous marriage, presented with vomiting, abdominal
distension and passage of small quantity of stool, liquid in
consistency, for the previous two weeks. There was an associated
history of poor feeding and excessive cry. There was no history of
convulsion, feeding abnormality or any other neonatal illness. The
baby had been delivered uneventfully with a birth weight of 2.5 kg
and a length of 48 cm. There was no history suggestive of any
significant maternal illness during pregnancy or in the past.
Examination revealed facial puffiness, open anterior and posterior
fontanelles, rough dry skin and cold peripheries. There was no neck
swelling or umbilical hernia. On abdominal examination, there were
prominent veins, visible intestinal peristalsis and mild
hepatosplenomegaly. The rest of the systemic examination was normal.
The hemogram, serum electrolytes, kidney and liver function tests
were normal. Plain abdominal radiograph revealed dilated gas filled
bowel loops. Barium enema revealed dilated proximal colon, empty
rectum, delayed emptying time, funnel like transition zone between
proximal dilated and distal constricted bowel. Her thyroid showed
low T3 (36.4 ng/ml), low T4 (1.4 µg/dL) and high TSH (>150 µIU/mL).
The maternal thyroid profile was normal. Thyroid scintigraphy (99mTc)
revealed athyrosis. After hemodynamic stabilization, a colonoscopic
biopsy and colostomy were done. Histopathology of the biopsy
specimen revealed aganglionic segment, confirming the diagnosis of
Hirschsprung’s disease. The patient’s genetic analysis revealed 46XX
karyotype without any chromosomal abnormality or any mutations. She
was discharged on oral thyroxine replacement. Five months later, the
infant weighed 6.3 kg and her length was 108 cm, and underwent a
transanal endorectal pull-through operation followed by colostomy
closure.
Discussion
Association of HD along with congenital
hypothyroidism is rare [3]. Our patient presented with vomiting,
abdominal distension with passage of small quantity of liquid stool
which are classically seen in HD. Hirschsprung’s disease results
from the failure of neural crest cell precursors to colonize the gut
resulting in absence of myenteric (Auerbach) and submucosal (Meissner)
plexuses [4]. The aganglionic segment is limited to the rectosigmoid
in 75% of patients; in 10% the entire colon lacks ganglion cells.
Total bowel aganglionosis is rare. HD occurs as an isolated trait in
70% of patients; in association with a chromosomal abnormality it
exists in 12% of cases [5]. There are eight genomes associated with
this disorder, the most common association being RET proto-oncogene
[6]. Our patient’s genetic analysis revealed a normalwithout any
mutations, hence the other associated abnormalities of MEN2 linked
with RET mutation were not searched for and no genetic counseling
was offered to family members.
Elevated TSH values with athyrosis observed on
thyroid scintigraphy (99mTc)
confirmed the diagnosis of congenital primary hypothyroidism. There
are 3 theories linking congenital hypothyroidism with HD. The most
commonly accepted theory is that there is a defective cranio-caudal
migration of neuroblasts due to thyroid hormone deficiency which is
necessary for appropriate neuronal migration and lamination during
brain development [7]. However, Cranio-caudal migration of
neuroblasts originating from the neural crest occurs much
earlier(5-12 wk gestation) than the recreation of thyroid hormones
in the fetus (12 wk gestation). Thyroid hormone in the early
gestational period is maternally originated, the mother’s thyroid
hormone status seems more important than that of the fetus in early
pregnancy [9]. The other two theories include: defects in the
differentiation of neuroblasts into ganglion cells [8] and
accelerated ganglion cell destruction within the intestine;
situations in which fetal thyroid hormone levels seem more
important.
Although hypothyroidism impairs the colonic
motility and function [10], the effect of thyroid hormone on neural
crest cell migration through the bowel have not been studied yet.
Our case highlights the possible role of thyroid hormones in the
development of HD. Further studies are needed to establish this.
Contributors: All the authors
contributed to the case management, reviewing the literature and
drafting the manuscript. All authors approved the final manuscript.
Funding: None; Competing interests:
None stated.
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