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Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

ABSTRACT: Resistance to thyroid hormone beta (RTH?) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor ? gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone.The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis.In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

SUBMITTER: Maruo Y

PROVIDER: S-EPMC4709977 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

Maruo Yoshihiro Y Mori Asami A Morioka Yoriko Y Sawai Chihiro C Mimura Yu Y Matui Katsuyuki K Takeuchi Yoshihiro Y

BMC endocrine disorders 20160112

<h4>Background</h4>Resistance to thyroid hormone beta (RTHβ) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor β gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone.<h4>Case presentation</h4>The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), c ...[more]

PMID: 26754848

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Project description:Abstract Background Liothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer patients during the preparation for nuclear medicine procedures, and there is renewed interest in its use in combination with LT4 in patients who do not respond to the standard treatment. This therapy is commonly done on fixed doses potentially resulting in supraphysiologic levels of T3. A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes able to maintain serum T3 levels within normal range, but data on the PK of LT3 are conflicting. Here we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, not receiving LT4. Methods We performed an open label PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived thyroid cancer (Clinicaltrials.gov ID NCT01441154). LT3 was substituted for LT4 at 1:3 mcg/mcg dosage ratio thrice daily for at least thirty days. PK of single dose LT3 and terminal elimination were assessed over eleven days and first dose PK was offered following the nuclear medicine procedures. Results Fourteen patients (7 males, 7 females) age 48.5±16.0 years completed the study. The LT3 daily dose was 53.7±12.3 (0.74±0.1 mcg/Kg). PK studies performed with the morning dose (18.8±4.4 mcg), indicate a Cmax of 320±60 ng/dl, significantly above the upper limit (90-215). Tmax was 1.8±0.5 hours and two distinct phases of linear elimination with a fast distribution phase and slow elimination phases with half-lives of 1.2 hours and 29.9 hours were identified, supporting a two-compartment model. PK modeling for a 50 mcg LT3 total dose predicted that while the mean T3 levels would not significantly differ among single, twice, or thrice daily administration regimens, the variance would differ dramatically, 213.5±126 vs. 214.5±61 vs. 214.5±35 ng/dl, single, twice and thrice daily administration, respectively. We next performed a PK modeling for LT3/LT4 combination therapy, twice daily administration. The results indicate that low dose LT3 (up to 0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the normal range. Conclusions The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapy directed to maintain stable T3 serum levels. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Project description:BackgroundTo summarize the clinical characteristics, genetics and follow-up data of four children with thyroid hormone resistance (RTH) syndrome and review the related literatures.MethodsThe clinical data of the four children diagnosed with RTH syndrome in our hospital from 2018 to 2020 were retrospectively analyzed. Next-generation sequencing of the candidate genes related to thyroid diseases was performed using the blood collected from all the children and their parents who signed an informed consent. Then, relevant cases were retrieved on medical literature databases for analysis and summary.ResultsAmong the four cases, three cases of goiter; two cases of tachycardia, palpitations, personality change, hyperactivity, weight loss; one case of academic performance decline, and no hearing and vision loss were observed. Laboratory thyroid function tests indicated a mild increase in free triiodothyronine and with or without increased free thyroxine levels. Thyroid-stimulating hormone (TSH) levels were normal or slightly elevated, but thyrotropin receptor autoantibodies were negative. Octreotide inhibition test showed that the TSH levels of all the children decreased by more than 50% compared with the basal value (the genes of four cases were positive). However, magnetic resonance imaging of the pituitary gland showed no abnormalities. Related gene detection in the children and their families showed that four cases had THRB mutations: two proband mutations were from their fathers, and two cases had de novo mutations.ConclusionsThe clinical manifestations of pediatric RTH syndrome vary, and the diagnosis mainly depends on thyroid function tests. Heterozygous mutations in THRB are overall rare, even if with the advanced development of next-generation sequencing, not all the children with RTH syndrome have mutations. Furthermore, octreotide inhibition tests cannot be used as a diagnostic criterion to distinguish RTH syndrome from pituitary tumors in children.

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Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

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Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

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