|
Gibson and colleagues reported a longitudinal study of thyroid function in
a population based cohort of 180 children with Down’s syndrome in Manchester,
England. Blood specimens were collected from 122 of these children aged 6 -14
years (median 9.8 years), and analyzed for thyroid stimulating hormone (TSH),
thyroid binding globulin (TBG), total thyroxine (T4), and thyroglobulin and
microsomal antibodies. In addition, at the time of initial sampling, data were
collected on hair, appetite, bowel function, height, weight, and family history
of autoimmune disease. Hypothyroidism was defined as low T4 and a TSH > 6
mU/mL. Isolated raised TSH (IR-TSH) was defined as normal T4 and TSH > 6
mU/mL. Euthyroid was defined as normal T4 and TSH < 6 mU/mL. Positive antibodies
were those with titers greater than 1:64. The authors assessed whether testing
of thyroid function in the first decade was predictive of hypothyroidism in
the second decade. Repeat studies were performed on 98 of the subjects in the
second decade (ages 10-20 years).
Initially one of the 122 children had been placed on thyroxine because of
an elevation in TSH. Of the remaining 121 children, 98 had normal thyroid function,
while 23 had IR-TSH. Over the decade 18 cases were lost to follow-up. Of the
remaining 103 subjects, 91 had normal thyroid function, 10 had IR-TSH, and
2 had definite hypothyroidism at re-testing.
At second testing, 14 of those with initial IR-TSH who were untreated showed
normal results. Of the 8 children who were initially positive for microsomal
antibodies, 3 became negative, 5 remained positive, 3 retained IR-TSH, and
1 developed hypothyroidism. There was a significant association between positive
autoantibody levels on first and second test. There was no significant sex
difference in antibody status. Symptoms related to hair, skin, appetite, bowel
function, height, weight, or family history of autoimmune disease were not
related to thyroid dysfunction or antibody status. One of the 2 children with
IR-TSH who started on thyroixine had no symptoms, but the other subject was
described as tired with a husky voice and her height was below the 3rd percentile
for Down’s syndrome. One of the cases of hypothyroidism was asymptomatic
while the other subject was overweight and had dry skin. Neither person had
growth failure. Association between IR-TSH on first testing and second testing
was significant. However, 70% of those with IR-TSH on first testing were normal
on second testing. Four with normal function on the first test had IR-TSH on
the second testing.
The authors stated that these studies confirm that there is a high
prevalence of thyroid dysfunction in Down’s syndrome. Of the 103 subjects,
12 showed abnormal results on second testing. They further stated that the
cause of IR-TSH had not been defined and may represent a predisposition to
a self-limiting autoimmune process resulting in IR-TSH without clinical symptoms.
They noted that to justify the introduction of a screening program a condition
needs to be relatively common, cause a significant health risk, and be defined
by a test that is relatively specific, reliable, acceptable, and cheap and
have satisfactory treatment. Indeed thyroid testing in Down’s syndrome
meets these criteria. There are however other considerations, including whether
or not there is a latent or early stage and whether or not the natural history
is understood. The findings in this study suggest that thyroid functions may
change during a relatively short period of time. Eight of the 17 children with
IR-TSH on initial testing had normal testing within 3 months and 14 of the
20 were normal on testing in the second decade, indicating that the natural
history may be one of recovery. The authors stated that there is “no
clear health gain from treating the group with IR-TSH”. The second consideration
of the researchers was whether or not there was a cost-benefit advantage; this
remains unclear.
Other important points included recognizing that IR-TSH in Down’s syndrome
is frequently self-limiting without the need for treatment. The physician should
pay particular attention to symptoms explainable on the basis of hypothyroidism
when parents or young people with Down’s syndrome report these, but remember
that some of these symptoms can be features of Down’s syndrome. In addition,
the authors point out the positive likelihood for combined abnormal antibody
status and IR-TSH on first testing. After testing positive for antibodies,
the probability for hypothyroidism in the second decade was 28%, which increased
to 34% when IR-TSH was also present. On the other side, testing negative for
antibodies with normal TSH in the first decade caused the probability of hypothyroidism
in the second decade to be exceedingly small. Therefore they proposed that
a decision on retesting be based on initial test results. Early positive results
for autobodies or IR-TSH could be used as a basis for selecting a subgroup
for further testing at perhaps 5 year intervals unless symptoms intervene.
They concluded that the yearly screening recommended by the American Academy
of Pediatrics is probably not justified in the first 20 years of life.
Gibson PA, Newton RW, Selby K, Price DA, Leyland K, Addison GM. Longitudinal study of thyroid function in Down’s syndrome in the first two decades. Arch Dis Child. 2005;90:574-578.
Editor’s Comment: This is an important
manuscript, which reports a longitudinally followed cohort of children with
Down’s syndrome evaluated for thyroid dysfunction at two points in
time. The authors use a logical and statistically relevant process to come
to the conclusion that yearly screening in all children with Down’s
syndrome is probably not justified in the first 20 years of life, but that
those children with positive autoantibodies and IR-TSH probably require more
frequent follow-up. Recent literature suggests that IR-TSH, especially in
adults, may be a reflection of subtle hypothyroidism and justify treatment
with thyroxine. Admittedly most of those adults also have some symptoms suggestive
of mild hypothyroidism. While the set point for TSH may be different in children
with Down’s syndrome, one should also be aware of the difficulty in
identifying symptoms associated with subtle or mild hypothyroidism in this
group of children. It would be interesting to review other longitudinal cohorts
to see if conclusions of Gibson and colleagues can be affirmed.
William L. Clarke, MD
|
Current GGH - Vol. 24 No. 1
Printer Friendly
Email Paper