Thyroid Disease in Down’s Syndrome

Abstract & Commentary

Synopsis: Thyroid dysfunction was found in more than 30% of children with Down’s syndrome and frequently occurred before the age of 8 years.

Source: Karlsson B, et al. Thyroid dysfunction in Down’s syndrome: Relation to age and thyroid autoimmunity. Arch Dis Child 1998;79:242-245.

Down’s syndrome, one of the most common chromosomal disorders, is often associated with autoimmune diseases, especially those involving the thyroid gland. Karlsson and associates from the Uppsala Children’s Hospital in Sweden longitudinally followed 85 patients, 1-25 years of age, with Down’s syndrome. Studies of thyroid function and tests for thyroid antibodies were annually performed. Hypothyroidism, diagnosed by finding a low serum concentration of free thyroxine (T4), combined with a high level of serum thyroid stimulating hormone (TSH), was found in 30/85 children. Two children developed hyperthyroidism, and there was no sex difference. Half of the patients with hypothyroidism acquired the condition before the age of 8 years, but only one of these had thyroid antibodies at the time of diagnosis. Most of the 14 patients who developed hypothyroidism after age 6 had thyroid antibodies. In prepubertal patients with hypothyroidism, growth velocity was lower in the year before starting thyroxine replacement than during the year after treatment began. Thyroid dysfunction is common in children with Down’s syndrome. Therefore, annual screening, beginning in early life, is important.

Comment by Myron Genel, MD, FAAP

An association of thyroid dysfunction with Down’s syndrome has long been recognized. Indeed, prior to recognition of the classic cytogenetic abnormality and the development of highly sensitive assays for circulating thyroid hormones and TSH, a popular theory was that there was a causal relationship between hypothyroidism and Down’s syndrome. In part, this association reflected the superficial similarity of symptoms of hypothyroidism, especially congenital hypothyroidism, and some signs of Down’s syndrome. In its extreme, this theory led some practitioners to treat Down’s syndrome with thyroid preparations, on occasion with positive, beneficial results. With the benefit of hindsight and the advent of highly sensitive diagnostic tests, both for Down’s syndrome and for thyroid disease, it is apparent that the disorders are entirely distinct but that there is a high frequency of thyroid autoimmunity and thyroid dysfunction, hypothyroidism in particular, in children with Down’s syndrome.

The Swedish study is of interest, not only for the frequency, which was more than 30% in a longitudinal study, but also because half or 14 of the patients developed hypothyroidism by age 8 and 10 of these before age 2. None had congenital hypothyroidism. Only one of these younger patients had positive thyroid antibodies, thus, leading the Swedish investigators to speculate that some patients with Down’s syndrome have relative thyroid hypoplasia, which decompensates during a period of rapid growth. Thyroid antibodies were detected in the vast majority of children who developed hypothyroidism after age 8 as well as in some patients who remained euthyroid.

From the clinician’s perspective, however, the major "take home" message is that thyroid dysfunction, in particular hypothyroidism, occurs commonly in Down’s syndrome and not infrequently at an early age. Thus, any signs of thyroid dysfunction, in particular an unexplained deceleration in growth, should call for routine thyroid indices and, in particular, measurement of TSH. Thyroid replacement will reverse these common signs of thyroid deficiency, although they will not, as was once thought, correct the underlying disorder.