ETA2024 Poster Presentations Thyroid and Genetics (9 abstracts)
Thyroid hormone analogue (TRIAC) therapy in resistance to thyroid hormone beta, reduces hyperthyroid symptoms, lowers circulating thyroid hormones and metabolic rate effectively, without adverse effects
Carla Moran 1 , Greta Lyons 2 , Laura Watson 2 , Kevin Taylor 3 , Sue Oddy 4 , David Halsall 4 & Krishna Chatterjee 5
1Endocrine Department, Endocrine, Ucd School of Medicine, Dublin, Ireland; 2Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom; 3Cambridge University Hospitals NHS Foundation Trust, Clinical Biochemistry; 4Cambridge University Hospitals NHS Foundation Trust; 5University of Cambridge, Wellcome-Mrc Institute of Metabolic Science, Cambridge, United Kingdom
Background: The treatment of Resistance to Thyroid Hormone beta (RTHb) is challenging because no therapy restores the euthyroid state in all tissues. Triac (triiodothyroacetic acid), a centrally-acting thyroid hormone analogue that preferentially activates thyroid hormone receptor beta, is reported to be beneficial in case reports or small case series.
Methods: We have treated a cohort of adult RTHb patients with hyperthyroid symptoms with Triac for upto a decade. Here, we describe the clinical, biochemical, metabolic and cardiac responses to therapy. (Patients in whom the HPT axis was altered (due to ATDs, thyroid surgery or radioiodine) were excluded.
Results: A total of eight adult patients were treated with Triac and their characteristics and responses (HSS: Hyperthyroid Symptoms Score, SHR: sleeping heart rate, REE: resting energy expenditure) to therapy are tabulated below.
| Subject No. | Gender, Age | THRB Mutation | Triac Dose(/24 hrs)/Duration of treatment (yrs) | Baseline FT4, Nadir FT4 | Baseline TT3, Nadir TT3 | Baseline HSS, Nadir HSS | Baseline SHR, Nadir SHR | Baseline REE, Nadir REE |
| A1 | M, 39 | R243Q | 3.5 mg/2.5 | 31.6, 20.9 | 2,72, 1.46 | 16, 11 | 62, 56 | 2.5, 1.4 |
| A2 | M, 25 | R429Q | 1.4 mg/3 | 28.4, 19.1 | 2.36-1.43 | 14, 5 | 54, 52 | 1.2, 0.5 |
| A3 | F, 54 | P452L | 1.4 mg/12 | 22.1, 13 | N/A | 17, 1 | 53, 61 | 1.2, 0.8 |
| A4 | M, 18 | S314Y | 2.1 mg/1 | 48.6, 25.8 | 2.93, 1.91 | 18, 14 | 58, 53 | 1.7, 1.1 |
| A5 | M, 29 | R316H | 2.1 mg/3.5 | 26.4, 15.9 | 2.09, 1.1 | 9, 5 | 48, 48 | -1.2, -0.8 |
| A6 | F, 19 | R483C | 1.75 mg/1 | 30.7, 18.8 | N/A | 21, 19 | 65, 59 | 0.9, -0.3 |
| A7 | F, 37 | R483C | 1.4 mg/0.7 | 28.7, 17.9 | 2.84, 2.3 | N/A | 65, 60 | 3.1, 1.2 |
| A8 | F, 34 | R483H | 2.8 mg/4.5 | 31.6, 12 | 4.41, 0.97 | 22, 9 | 72, 59 | 1.6, 1.4 |
| 7 of 8 patients achieved normal circulating FT4 (measured by immunoassay; mean FT4 fell from 31.2 pmol/l to 18.3 pmol/l, RR 10.5-21) and 5 of 6 achieved normal total T3 concentrations (measured by LC-TMS; mean TT3 fell from 2.89 to 1.52nmol/l, RR 1.09-2.24). Mean reductions in other parameters: HSS from 17/40 to 9/40, SHR from 60 to 56bpm, REE Z score from +1.375 to +0.66. No reported side effects. No patients discontinued therapy. | ||||||||
Conclusions: Triac therapy in RTHbeta reduces hyperthyroid symptoms, lowers circulating FT4 and TT3 concentrations and reduces basal metabolic and heart rate effectively, without adverse effects. Whether longer-term Triac treatment alters adverse cardiovascular outcomes recently associated with RTHbeta, remains to be determined.
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Endocrine Abstracts
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