ESPE Abstracts

Background: Monocarboxylate transporter 8 (MCT8) is a specific transporter of triiodothyronine (T3). MCT8 gene mutations cause a rare X-linked disorder known as Allan–Herndon–Dudley syndrome, characterized by thyroid dysfunction (high T3, low T4, and normal/high TSH) and psychomotor retardation.Case report: A 4-year- and 9-month-old boy, who was already having L-T4 treatment fo...

Introduction: Mutations in the thyroid hormone (TH) transporter MCT8 result in MCT8 deficiency, which is characterized by severe intellectual and motor disability and high serum T3 concentrations inducing thyrotoxicity in peripheral tissues. At present, no effective treatment is available, although preclinical studies suggest that the T3 analog Triac is a promising candidate to i) normalize serum T3 levels and thus alleviate the thyrotoxicosis and ii) restore TH signaling in t...

Background: Patients with a mutation in the thyroid hormone (TH) receptor TRα1 are characterized by growth retardation, delayed bone development, mild cognitive defects and constipation. They also have abnormal TH levels: low FT4, high T3, and low rT3 levels, suggesting an altered peripheral TH metabolism by deiodinases. The type 3 deiodinase (D3) inactivates TH by catalyzing the degradation of T3. D3 is importantly expressed in...

Background: Recently, the first patients with resistance to thyroid hormone (RTHα) due to inactivating mutations in TRα1 have been identified. These patients are characterized by growth retardation, delayed bone development, mild cognitive defects, delayed motor development and abnormal thyroid function tests.Objective and hypotheses: We hypothesized that the phenotype of a TRα mutation depends on its location, e.g. if it is present only i...

Background: Recently, T3 receptor alpha (TRα) mutations have been identified in a number of patients with varying degrees of growth impairment, delayed development, constipation, increases in serum T3 and decreases in T4 and rT3.Objective: To determine the spectrum of clinical and functional consequences of novel TRα mutations.Method: Clinical assessment and biochemical, imaging...

Background: The majority of children diagnosed with idiopathic isolated growth hormone deficiency (IIGHD) show a normal growth hormone (GH) secretion (assessed by GH stimulation tests) when retested at near adult height (NAH). It appears plausible that if normal stimulated GH secretion is observed in mid-puberty, continuing recombinant human GH (rhGH) treatment may only have a minor effect on NAH. The effect on NAH has never been investigated in a prospective ...

Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism in iodine sufficient regions. TD includes a broad spectrum of developmental anomalies varying from absence of thyroid (athyreosis) to an abnormally located thyroid (ectopy), small (hypoplasia) or asymmetric thyroid. Thyroid dysgenesis is usually sporadic, but up to 2% of cases is familial. Genetics of TD is complex and advances in developmental biology over the past two decades revealed monogenetic f...

Background: Congenital hypothyroidism is primarily due to thyroid dysgenesis (TD). The genes implicated in TD, account for a small number of patients with monogenic forms, less than 5%. Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis.Objective and hypotheses: To understand the role of Borealin mutations found in patients with TD.Method: We performed whole exome sequencing (WES) ...

Background: Traumatic brain injury (TBI) is common in childhood and can induce pituitary defects. Long-term endocrine consequences are missing.Objective and hypotheses: To determine in a prospective way if pediatric patients with a personal history of TBI developed long term pituitary deficiency independently of the results of the early hormonal investigation.Method: Prospective follow-up of an initial cohort of subjects (0–15...

Background: Multiple organ dysfunction occurs in mitochondrial diseases (MDs). MDs are sometimes difficult to diagnose, because patients have solitary and/or combination of various symptoms including short stature, diabetes, myopathy, and seizure. Since plasma levels of lactate and pyruvate are not always the perfect biomarker for MDs, there are many pseudo-mitochondrial patients who are suspect for MDs. Diagnosis for MDs often requires muscle biopsy, gene analysis, and measur...