ETA2024 Poster Presentations Thyroid and Genetics (9 abstracts)
1Endocrine Department, Endocrine, Ucd School of Medicine, Dublin, Ireland; 2Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrookes 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.