Cases & Commentaries

Coming Up Short

Commentary By Ze'ev Hochberg, MD, PhD

The Case

A 12-year-old Hispanic female was seen for a
well-child check. The child was delivered 2 months prematurely
(likely due to domestic violence) in Puerto Rico. She had an
intracerebral hemorrhage and was in the neonatal intensive care
unit (NICU) for 6 months. The child moved to the United States with
her family 5 years ago. The child is currently 22.7 kg and 107 cm
(very small according to the growth chart [Figure] for her age),
with a normal-sized head. The patient's mother, who speaks only
Spanish, says the child developed and grew normally until age 7,
when she stopped growing and began to lose ground developmentally.
A few years ago, a school evaluation found that she was mentally
retarded.

At the time of the
present evaluation, the mother stated that the child had been seen
twice in a family practice office for "well checks" over the past
few years but had not had blood tests or a thorough evaluation for
her growth and developmental problems. On this visit, the family
physician ordered routine labs and referred her to pediatric
endocrinology. The thyroid-stimulating hormone (TSH) test result
was 834 (a near record high), and she was diagnosed as likely
having Hashimoto's disease. Thyroglobulin antibodies of 701 and
anti-thyroid peroxidase (TPO) antibodies of 576 confirmed this
diagnosis. The patient has since begun thyroid replacement therapy
and is likely to grow and develop with thyroid replacement.
However, according to the endocrinologist, the child's mental
function is unlikely to recover.

The Commentary

This case represents a colossal failure to
diagnose hypothyroidism in a juvenile with extreme short stature,
relative overweight, and developmental delay. It raises several
issues of management, but mostly the inadequacy of this type of
well-child check. After all, such checks are mostly meant to
identify the unwell child.

Whereas most symptoms of hypothyroidism are
nonspecific (i.e., lethargy, cold intolerance, constipation, and
delayed intellectual development), the pediatric age group
demonstrates the most sensitive symptom of them all, one that
adults do not show: growth retardation. Thyroid hormones are
required for every step of the growth process: growth hormone (GH)
generation and secretion, GH-receptor function, growth of
longitudinal bones at the growth plate, and osteogenesis of the
growth plate cartilage.(1)
Thus, any child with hypothyroidism is by definition also
GH-deficient, and endocrinologists know never to measure GH before
they verify that the child is euthyroid, or to begin treatment for
GH deficiency in case the child is hypothyroid.

The age at onset of hypothyroidism in this
child is unknown. It might have started at age 7, when her parents
noticed growth failure, but the extreme short stature suggests that
it started earlier—much earlier. Most parents and
pediatricians do not identify growth failure until it is quite
severe—unless they measure the children routinely. The age at
onset is crucial in terms of the mental prognosis in untreated
hypothyroidism: the earlier, the worse. In fact, if the onset
indeed occurred at age 7, this child has a fairly good chance to
recover mentally and regain age-appropriate intellectual
development. However, I fear that the onset was much earlier, in
which case mental retardation may not respond to therapy.

The same holds true for her growth prognosis.
The completeness of catch-up after growth insult depends on the age
and duration of the insult: the longer and earlier, the worse. With
the severe and prolonged growth failure of this child, she is
unlikely to have a complete catch-up in growth.

The symptom to notice is child growth, not
height. As growth is a process over time, it requires at least two
measurements, separated in time, and the calculation of growth
velocity (the units are cm/year) to identify growth insufficiency.
The key to the initial evaluation is a careful history and
determination of the growth-related parameters. On physical
examination, I look for evidence of systemic disease and abnormal
body proportions. The laboratory workup starts with surveillance of
all body systems, as chronic dysfunction of almost every organ and
tissue may result in growth failure. My own lab surveillance list
for growth insufficiency includes: complete blood count (CBC),
erythrocyte sedimentation rate (ESR), electrolyte panel, TSH and
FT4 (TSH alone will miss cases of central hypothyroidism),
antigluten antibodies, and others as indicated.(2) In girls, I add a chromosome panel to rule out Turner
syndrome. Bone maturation assessed by X-ray ("bone age") can
provide a helpful hint (3); in
hypothyroidism as severe and prolonged as this child had, bone
maturation would have been much delayed, and hypothyroidism should
be first in the differential diagnosis of much-delayed bone
age.

This girl's height was –7 standard
deviation scores (SDS) below the mean for her age (the third
percentile is –1.81 SDS), and her weight was high for her
stature (–3.5 SDS)—she is obese. We see so many
overweight children these days that we may forget the essentials:
the association of growth stunting with obesity has a fairly short
differential diagnosis list. Hypothyroidism is first on this list,
but the rare GH deficiency and the very rare Cushing syndrome have
to be entertained as well.

It has long been appreciated that growth is a
valuable marker of the socioeconomic conditions for a given
population. Thus, on a population basis, the so-called secular
trend toward taller stature in many societies parallels
improvements in health and nutrition. This has become one of the
major measures used by UNICEF in worldwide surveys of the state of
child development, and for socioeconomic status on the whole. At
the individual level, the growth chart is an excellent "log book"
of a child's health both in physical and psychological terms. Even
short periods of undernutrition, infection, or psychosocial
deprivation are mirrored by a decreased growth rate, followed by
catch-up growth when conditions improve. In recent years, we tend
to search for GH deficiency, but chronic illness is by far the most
common cause of stunted growth, and hypothyroidism is an important
example of a growth-stunting chronic disease.

Take-Home Points

  • Measuring a child and plotting his or
    her height and weight are essential routine tests that can help
    determine whether the child is well or not. Even in a busy clinic,
    this measurement must be done annually.
  • Providers should use widely available
    tools to calculate the child's growth velocity, then compare it to
    age-related references.
  • Growth retardation with excessive weight
    gain is pathological, and hypothyroidism is at the top of the
    list.
  • Insult to growth in the first year of
    life is not associated with catch-up growth.(4)
  • Severely delayed bone maturation ("bone
    age") is strongly suggestive of thyroid insufficiency.

Ze'ev Hochberg, MD,
PhD
Division Chief, Pediatric Endocrinology

Meyer
Children's Hospital, Rambam Medical Center
Faculty of Medicine, Technion

Haifa,
Israel

References

1. Hochberg Z. Clinical physiology and pathology
of the growth plate. Best Pract Res Clin Endocrinol Metab.
2002;16:399-419. [go to
PubMed]

2. Hochberg Z, ed. Practical Algorithms in
Pediatric Endocrinology. Basel, Switzerland: S Karger AG;2007.
ISBN: 380558220X.

3. Hochberg Z. Endocrine Control of Bone
Maturation. Basel, Switzerland: S Karger AG;2002. ISBN:
3805573138.

4. Hochberg Z, Albertsson-Wikland K. Evo-devo of
infantile and childhood growth. Pediatr Res. 2008;64:2-7.
[go to
PubMed]

Figure

Figure. Stature for age and weight for age
percentiles.


Click to enlarge.