title: Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).
abstract: OBJECTIVE
  Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3.
  
  
  METHODS
  Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration.
  
  
  RESULTS
  At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported.
  
  
  CONCLUSIONS
  (1) T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours; (3) T3S may represent a new agent in combination with T4 in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Ferruccio
authors: F
authors: Santini
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Monica
authors: M
authors: Giannetti
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Ilaria
authors: I
authors: Ricco
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Giorgia
authors: G
authors: Querci
authors: Ispharm CRO, Lucca, Italy.
authors: Giorgio
authors: G
authors: Saponati
authors: Bracco S.p.A., Milan, Italy.
authors: Daniela
authors: D
authors: Bokor
authors: Bracco S.p.A., Milan, Italy.
authors: Giovanni
authors: G
authors: Rivolta
authors: Bracco S.p.A., Milan, Italy.
authors: Simona
authors: S
authors: Bussi
authors: Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts.
authors: Lewis E
authors: LE
authors: Braverman
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Paolo
authors: P
authors: Vitti
authors: Department of Clinical and Experimental Medicine, Endocrinology Unit 1, University Hospital of Pisa, Italy.
authors: Aldo
authors: A
authors: Pinchera
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014284:Triiodothyronine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*
chemical_list: D014284:Triiodothyronine; C037673:triiodothyronine sulfate