Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism in Williams Syndrome

Abstract

In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. However, the frequency of biochemical thyroid assessment, particularly in the first year of life, is being debated. In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5–4 mIU/l) with a low FT₄ concentration (10.21 pmol/l; normal range: 10.29–24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas ^99mTc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. Therefore, treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.

Congenital hypothyroidism as the initial presentation that led to the diagnosis of Williams syndrome

“…In all previous reports structural abnormalities of thyroid gland, including thyroid hemiagenesis (Cammareri et al, 1999), sublingual ectopic thyroid (Bini and Pela, 2004) and significant hypoplasia (Stagi et al, 2008), as in our case, have been found. However, in all three cases, neonatal TSH screening was normal and clinical signs and symptoms of hypothyroidism, confirmed by abnormal TSH and T 4 levels, were developed at an advanced age.…”

“…Even in pediatric patients with WS, subclinical hypothyroidism is a frequent finding, either with normal or hypoplastic thyroid gland (Cambiaso et al, 2007). Additionally, a few cases of congenital hypothyroidism due to thyroid hypoplasia or thyroid ectopia can be found in the literature (Bini and Pela, 2004;Cammareri et al, 1999;Stagi et al, 2008). In the majority of these cases, congenital hypothyroidism was not detected at screening test but the diagnosis was established at a more advanced age, preceding the diagnosis of WS by approximately 2 years.…”

A rare association of central hypothyroidism and adrenal insufficiency in a boy with Williams-Beuren syndrome

“…Primary hypothyroidism occurs in about one-third of all patients with WBS8910). About 70% of the patients with hypothyroidism show morphological or volumetric abnormalities of the thyroid gland8910). The major gland abnormality detected in these patients is hypoplasia8910).…”

“…About 70% of the patients with hypothyroidism show morphological or volumetric abnormalities of the thyroid gland8910). The major gland abnormality detected in these patients is hypoplasia8910). Unsurprisingly, therefore, most patients have subclinical hypothyroidism8910).…”

“…These reports point to a need for close monitoring of endocrine dysfunction in patients with WBS to detect and treat any known or new abnormalities in a timely fashion567). Thyroid dysfunction occurs in approximately 30% of patients with WBS and is characterized by the presence of thyroid gland abnormalities, particularly hypoplasia in a majority of the patients48910). All the patients reported till now had primary hypothyroidism.…”