The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross-over study in thyroidectomized patients.
BACKGROUND
The substitution of liothyronine (L-T3) for levothyroxine (L-T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L-T3 for L-T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of L-T3 and L-T4.


METHODS
Randomized, double-blind, cross-over intervention study.


METHODS
NIH clinical center.


METHODS
Ten thyroidectomized patients.


METHODS
Study participants were treated with L-T3 or L-T4 with a target TSH >or= 0.5 <or= 1.5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed-over according to the same scheme.


METHODS
Area under the serum concentration-time curve of TSH from 0 to 60 min (AUC(0-60)) and peak TSH serum concentration (C(max)) following thyrotropin-releasing hormone (TRH) stimulation test, total L-T4 and L-T3 dose (mcg/kg), and L-T4/L-T3 ratio.


RESULTS
No difference was observed for time 0 TSH values between L-T3 and L-T4 replacement phases (1.48 +/- 0.77 vs. 1.21 +/- 0.62 mU/l, P = 0.293) at average daily doses of 40.3 +/- 11.3 mcg L-T3 and 115.2 +/- 38.5 mcg L-T4, L-T3: L-T4 ratio 0.36 +/- 0.06. TRH stimulation test resulted in similar L-T3 vs. L-T4 TSH responses with AUC(0-60) of 326.1 (95% CI 232.6-457.1) and 247.1 (95% CI 153.8-397.1) mU* min/l (P = 0.285); and C(max) of 6.83 (95% CI 4.88-9.55) and 5.23 (95% CI 3.31-8.3) mU/l (P = 0.383).


CONCLUSIONS
This is the first study addressing the equivalency between L-T3 and L-T4 therapy measured by baseline and TRH-stimulated TSH. The therapeutic substitution of L-T3 for L-T4 was achieved at approximately 1:3 ratio.
Celi
Francesco S
FS
Clinical Endocrinology Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Building 10, CRC, RM 6-3940, 10 Center Drive, MSC 1613, Bethesda, MD 20892-1613, USA. fc93a@nih.gov
Zemskova
Marina
M
Linderman
Joyce D
JD
Babar
Nabeel I
NI
Skarulis
Monica C
MC
Csako
Gyorgy
G
Wesley
Robert
R
Costello
Rene
R
Penzak
Scott R
SR
Pucino
Frank
F
D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013810:Therapeutic Equivalency; D013960:Thyroid Function Tests; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
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