Table 7.
Characteristics of Randomized Controlled Trials Comparing Health and Psychological Effects in Hypothyroid Patients Treated with Synthetic Combination LT4/LT3 Therapy Compared to LT4 Alone
| Reference | Treatment dosinga | Etiology primary hypothyroidism | Design | No. of patients randomized (completed follow-up) | Treatment duration | End of study TSH differences between groups |
|---|---|---|---|---|---|---|
| 386 | T4: usual dose LT4/LT3: 10:1 or 5:1 ratio of T4 to T3 ratio, respectively Dosing: twice daily |
Autoimmune | Parallel, blinded | 141 (130) | 15 weeks | LT4/LT3<LT4 (TSH significantly lower only in the 5:1 LT4/LT3 dose group) |
| 387 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 12.5 μg/d Dosing: once daily |
Mixed: autoimmune, thyroid cancer | Cross-over, blinded | 35 (33) | 5 weeks | NS |
| 517 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 10 μg/d Dosing: once daily |
All Graves' disease, history of subtotal thyroidectomy | Cross-over, blinded | 13 (10) | 5 weeks | NS |
| 518 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 15 μg/d Dosing: twice daily |
Mixed: autoimmune, post-RAI, thyroid surgery, post-EBRT, 1 patient thyroid cancer | Parallel, blinded | 46 (44) | 4 months | NS |
| 519 | T4: 100 μg/d LT4/LT3: LT4 75 μg/d and T3 5 μg/d Dosing: once daily |
Mixed: autoimmune, post-RAI | Cross-over, blinded | 28 (26) | 8 weeks | LT4/LT3>LT4 |
| 520 | T4: 1.6 μg/kg/d LT4/LT3: estimated T4 dose minus 25 μg/d with T3 12.5 μg/d Dosing: once dailyb |
Untreated overt hypothyroidism, etiology not reported | Parallel, unblinded | 36 (36) | 6 months | NS |
| 521 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 20 or 50 μg/d, respectively Dosing: once daily |
Autoimmune | Cross-over, blinded | 68 (59) | 12 weeks | NS |
| 384 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 10 μg/d Dosing: once dailyb |
Mixed: autoimmune, post-RAI, thyroid surgery | Cross-over, blinded | 30 (27) | 6 weeks | NS |
| 522 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 10 μg/d Dosing: once daily |
Primary hypothyroidism, no thyroid cancer | Parallel, blinded | 697 (573) | 12 Months (outcomes assessed 3 and 12 months) | LT4/LT3>LT4 |
| 388 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 total 25 μg/d Dosing: Twice daily T3, once daily T4 |
Primary hypothyroidism, no thyroid cancer, no thyroidectomy, no history of hyperthyroidism | Parallel, blinded | 40 (33) | 15 weeks | NS |
| 523 | T4: usual LT4/LT3: usual T4 dose minus 5% with T3 5% (aim 14:1 ratio LT4 to T3) Dosing: once dailyb |
Mixed: autoimmune, post-RAI, thyroid surgery, no thyroid cancer | Cross-over, blinded | 26 (23) | 12 weeks | LT4/LT3<LT4 |
| 524 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 total 12.5 μg/d Dosing: twice daily T3, T4 once daily |
Mixed: autoimmune, post-RAI, thyroid surgery, but no one on TSH-suppressive therapy | Parallel, blinded | 71 (60) | 4 months | NS |
| 385 | T4: usual LT4/LT3: usual T4 dose minus 50 μg/d with T3 10 μg/d Dosing: once dailyb |
Mixed: autoimmune, post-RAI, thyroid surgery, but no thyroid cancer on TSH-suppressive therapy | Cross-over, blinded | 110 (101) | 10 weeks | LT4/LT3>LT4 |
a
Starting treatment doses are shown (prior to adjustments within trials according to thyroid function tests).
b
Dosing not reported, assume once daily.
NS, not significantly different; RAI, radioactive iodine treatment; EBRT, external beam radiation treatment.