In search of thyroid hormone receptor alpha-1 mutations in adolescents with delayed puberty

Thyroid hormone receptor (TR) alpha and beta are nuclear receptors that mediate
the transcriptional effects of triiodothyronine (T3). Many different mutations
in TR beta are known to cause the syndrome of *resistance to thyroid
hormone* (RTH). Surprisingly, no patients with germline mutations in TR alpha-1
have been identified. Recently the phenotype of mice with a TR alpha-1 mutation
has been described. These mice are biochemically euthyroid but show severely
delayed development and seem to catch up during adult life.
Our research aims to identify TR alpha-1 mutations in biochemically euthyroid
patients who have a phenotype compatible with that of the TR alpha-1 mutant
mice. We will identify candidate patients with delayed puberty, for which no
other underlying cause has been found. Since these patients show a delayed
puberty of unknown cause, but catch up during adult life they are good
candidates for harbouring a mutation in the TR alpha-1 gene.

To identify patients with TRalpha-1 mutations among adolescents with delayed
puberty.

Patients with a previous diagnosis of delayed puberty will be asked to visit
the outpatient clinic of the department of Pediatric Endocrinology at Emma
Children*s Hospital AMC. The visit will consist of a short (structured)
interview and a venous blood collection.
The blood will be analyzed for thyroid function determinants and possible
TRalpha-1 mutations.

The study could provide knowledge into a cause of delayed puberty. The burden
to the subjects is minimal and consists of a one-time visit to the hospital,
answering a questionnaire and undergoing one venous punction.