Screening of Parents and Siblings of Patients with Thyroid Dysgenesis by Thyroid Function Tests and Ultrasound

Abstract

Aims: To investigate the frequency of thyroid dysgenesis (TD) in first-degree relatives of TD cases. Methods: 244 first-degree relatives of 82 TD cases were screened by thyroid ultrasound (USG), T₄, fT₄ and TSH. USG was also performed in 220 unrelated, age- and sex-matched healthy controls to obtain normative data for thyroid volumes. Results: Specific diagnoses of indexes were 35 ectopia, 22 athyreosis, 14 severe hypoplasia, 8 hypoplasia, and 3 hemiagenesis/asymmetric hypoplasia. In 5 of 77 families (6.5%), there were 2 cases with known symptomatic TD. A total of 10 cases made familial symptomatic TD ratio 12% (10/82) in our cohort. Screening of 244 asymptomatic family members did not reveal new cases with overt hypothyroidism. However, low thyroid volume in 15 and slightly elevated TSH in 6 family members and both in 1 family member were detected (7.4% for low thyroid volume, 3.2% for high TSH). Thus, the ratio of affected (symptomatic and asymptomatic) family members among families of TD cases was found to be 8.7%. Conclusions: 12% of TD cases are familial in our cohort. Screening of asymptomatic family members of TD revealed an additional 7.4% mild hypoplasia and 3.2% hyperthyrotropinemia without overt hypothyroidism which points out the importance of genetic factors in pathogenesis.

Morphogenetics of early thyroid development

“…Although TD in humans is sporadic in the absolute majority of cases, a familial occurrence has been demonstrated in 2% of the cases, which is 15 times higher than expected by chance alone, in a large French cohort (Castanet et al 2000(Castanet et al , 2001(Castanet et al , 2010. Similar findings were recently found in a less extensive Turkish study (Karakoc et al 2008). Interestingly, both athyreosis and thyroid ectopia can be found among affected family members, implicating that heterogeneous manifestations of the disease may have a common genetic basis (Castanet et al 2010).…”

“…A hereditary component is further suggested by observations of an increased prevalence of occult developmental anomalies of the thyroid in asymptomatic first-degree relatives (Leger et al 2002, Adibi et al 2008, Karakoc et al 2008). However, it should be firmly kept in mind that monozygotic twins are generally discordant for TD (Perry et al 2002), arguing against simple Mendelian transmission (Deladoey et al 2007b, Castanet et al 2010.…”

Pitfalls in the diagnosis of thyroid dysgenesis by thyroid ultrasonography and scintigraphy

“…3). Subjects diagnosed with hypoplasia by thyroid scintigraphy (nZ10, 12%) (7 males and 3 females) were shown to have hypoplastic thyroid gland by US when thyroid volume was compared with the age-matched normative values (4). No hyperechogenic structures were detected in this group, however, one patient with hypoplasia showed a cystic structure with diameters of 3.2 and 5.2 mm on US in the left thyroid lobe.…”

“…Although, some studies reported age-adjusted K2S.D. cut-offs for thyroid gland volume in newborns and children, these data show great variability, indicating the necessity of a population-specific data (4,(14)(15)(16)(17)(18). Furthermore, these cut-offs are rarely used and interpreted in reports by radiologists since they usually report presence or absence of ectopic thyroid tissue, and give the dimensions of the gland.…”

Thyroid developmental anomalies among first-degree relatives of children with thyroid dysgenesis and congenital hypothyroidism

“…The study focused on patients selected in mass screening for CH in the years 1980 -1998 and demonstrated that 2 % of cases (48 of 2472) with TD-caused CH were familial. In turn, prospective studies carried out by Turkish investigators indicated a higher -as much as 12 % -prevalence rate of CH resulting from TD (10 of 82 cases) (29) . In the present material, the prevalence of TD-caused familial CH was 6 % and the condition was seen in one family, where thyroid hypoplasia affected two of three siblings.…”