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; Greta Lyons; Laura Watson; Kevin Taylor; Sue Oddy; David Halsall; Krishna Chatterjee

doi:10.1530/endoabs.101.PS3-27-05

PS3-27-05

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Endocrine Abstracts (2024) 101 PS3-27-05 | DOI: 10.1530/endoabs.101.PS3-27-05

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

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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.

Table 1. Imaging characteristics of parathyroid adenoma (n = 17)
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.