ESPE Abstracts (2016) 86 P-P1-917

Hypercholesterolemia in Two Siblings with THRB Mutation

Maja Jakica, Urh Groselja, Magdalena Avbelj Stefanijaa, Mojca Zerjav Tanseka, Katarina Trebusak Podkrajseka,b & Tadej Battelinoa,b


aUniversity Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia; bFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia


Background: Resistance to thyroid hormones (RTH) is a rare disease, characterized by reduced sensitivity of target tissues to thyroid hormones. Pathognomonically, thyroid hormones are moderately elevated, whereas TSH levels are inappropriately normal or elevated. Over 100 thyroid hormone receptor beta (THRB) mutations have been reported, which are found in around 85% of RTH cases. Hypercholesterolemia was not previously reported in RTH patients.

Objective and method: To assess the lipid levels in a Slovenian family (mother, two daughters and a son) with a previously reported causative THRB mutation p.Arg243Trp (c.727C>T).

Results: Index case was referred to our outpatient clinic due to suspicion of thyroid malfunction at the age of 13.5 years. She had a history of weight loss (3–4 kg over previous month). She had borderline tachycardia and slightly enlarged thyroid gland. Her TSH levels were normal, whereas her free T4 and free T3 levels were moderately elevated; thyroid antibodies were negative. Her total cholesterol levels were slightly elevated (5.5 mmol/l), but her LDL-C levels remained in upper-normal range. Genetic analysis revealed the THRB mutation, which was later confirmed in her mother, younger sister and brother. All of them also had moderately elevated free T4 and free T3, whereas the younger sister was also the only one in the family with elevation of TSH (over 10 mE/l). Hypercholesterolemia with elevated total cholesterol (6.6 mmol/l) and LDL-C (4.2 mmol/l) levels was also detected in her younger sister, but not in her brother (parents were not tested). Genetic causes of familial hypercholesterolemia were excluded in younger sister.

Conclusion: Mild hypercholesterolemia was present in 2 out of 3 tested family members with confirmed THRB mutation. Since the severity of hormonal resistance varies among different tissues, hypercholesterolemia in patients with THRB mutation might indicate the relatively hypothyroid state in the liver.

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