39- How to optimize growth and development in children with juvenile
hypothyroidism?
Early diagnosis and optimal replacement therapy result in attainment of normal
final adult height in children with juvenile hypothyroidism. Children with long-
standing hypothyroidism will experience catch-up growth after initiation of
levothyroxine; however, catch-up growth is often incomplete in these patients
due to diminished chondrocyte reserve. Children in the peripubertal age and
those who are overzealously treated with levothyroxine may experience rapid
skeletal maturation and, hence, compromised final adult height. There are a few
reports of use of GnRH analogue with or without rhGH in peripubertal children
with juvenile hypothyroidism, who had incomplete catch-up growth. However,
the results were variable. Failure to have a catch-up growth despite optimal
levothyroxine replacement in children with juvenile hypothyroidism should
raise a suspicion of coexisting disorders like celiac disease, Turner syndrome,
or growth hormone deficiency. - What are the causes of short stature in children with T1DM?
Children with poorly controlled type 1 diabetes have impaired linear growth.
Uncontrolled diabetes is a catabolic state associated with elevated pro-
inflammatory cytokines (TNF-α, 1L-6). In addition, type 1 diabetes is associated
with low IGF1 despite high GH levels. This is because optimal concentration of
portal vein insulin is required for the expression of GH receptor at hepatocytes
and, consequently, GH-mediated IGF1 generation. Further, hypoinsulinemia
also results in increased levels of IGFBP1, leading to decreased “free” IGF1.
Early and intensive insulin therapy in children with T1DM can normalize these
abnormalities in GH–IGF1 axis and may even result in accelerated growth
velocity. The other causes of poor linear growth in children with T1DM include
associated celiac disease, hypothyroidism, and delayed puberty.- How to suspect growth hormone deficiency in a neonate?
The clinical clues that suggest the presence of congenital growth hormone defi-
ciency (GHD) in a neonate include midline defects, micropenis, neonatal hypo-
glycemia, prolonged physiological jaundice, and breech presentation. The birth
length is usually normal in neonates with congenital GHD as prenatal growth is
GH-independent.- Why is congenital growth hormone deficiency associated with prolonged physi-
ological jaundice?
Glucuronyl transferase is a key enzyme involved in bilirubin metabolism, and
its activity is regulated by thyroxine and growth hormone. Therefore, neonates
with congenital hypothyroidism or growth hormone deficiency present with
prolonged physiological jaundice (>2 weeks in term and >3 weeks in preterm
baby).
1 Disorders of Growth and Development: Clinical Perspectives