FP34-1 Steady state serum T3 concentrations for 48 hours following the oral administration of a single dose of T3 sulfate

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP34-Molecular Mechanisms in Thyroid Hormone Action & Cancer
Basic/Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 103 (Moscone Center)

Poster Board MON-415
Ferruccio Santini*1, Monica Giannetti1, Ilaria Ricco1, Giorgia Querci1, Giorgio Saponati2, Daniela Bokor3, Giovanni Rivolta3, Lewis E Braverman4, Paolo Vitti5 and Aldo Pinchera1
1University of Pisa, Pisa, Italy, 2Ispharm S.R.L., Lucca, Italy, 3Bracco S.p. A., Milan, Italy, 4Boston University School of Medicine, Boston, MA, 5University of Pisa, Italy
Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances inner ring deiodination, leading to the generation of inactive metabolites.  A de-sulfating pathway reverses this process and thyromimetic effects have been observed following the parental administration of 3,5,3’-triiodothyronine sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of 3,5,3’-triiodothyronine (T3). Twenty-eight hypothyroid patients (7 men and 21 women, mean age 44 ± 11 years [SD]) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (40 days for thyroxine, 14 days for T3) prior to radioiodine remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group) or 160 mcg (16 patients/group) T3S was administered. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased reaching a peak at 2-4 hours and progressively returned to basal levels 8 hours later. The T3S Cmax and area under the curve (AUC 0-48h) were directly and significantly related to the administered dose (expressed as mcg T3S/kg BW).

            An increase in serum TT3 concentration levels was observed, significant after 1 hour, further increased at 2 and 4 hours, and then remained steady up to 48 hours after T3S administration. In the 160 mcg group, the mean serum TT3 increase (ng/dl, minus baseline)  was: 10.5 (1 h), 17.7 (2 h), 23.6 (4 h), 17.7 (8 h), 19.7 (12 h), 28.2 (24 h), 22.7 (48 h). There was a significant direct correlation between the TT3 AUC 0-48h and the administered dose of T3S. No changes in serum free thyroxine concentrations during the entire study period were observed, while serum TSH levels increased slightly at 48 hours not related to the dose of administered T3S. No adverse events were reported.

            In conclusion: 1) T3S  is absorbed following oral administration in humans; 2) the oral administration of a single dose of T3S is converted to T3 in a dose-dependent manner and results in steady state serum T3 concentrations for 48 hours; 3) T3S may represent a new agent in combination with thyroxine in the therapy of hypothyroidism.

Disclosure: FS: Principal Investigator, Bracco S.p.A.. MG: Coinvestigator, Bracco S.p.A.. IR: Coinvestigator, Bracco S.p.A.. GS: Consultant, Bracco S.p.A.. DB: Employee, Bracco S.p.A.. GR: Employee, Bracco S.p.A.. PV: Coinvestigator, Bracco S.p.A.. Nothing to Disclose: GQ, LEB, AP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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