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.