This is a reply to a group querying the validity of Bianco et al's paper on T4/T3 prefrence by some patients. I thought it nteresting to read the various arguments so I put it in full here, as it's behind a paywall.
Response to Letter to the Editor From Bonnema et al: “Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine + Liothyronine in Hypothyroidism”
Mohamed K. M. Shakir, 1,2 Daniel I. Brooks, 1 Elizabeth A. McAninch,3 Tatiana De Lourdes Fonseca, 3 Vinh Q. Mai, 1,2 Antonio C. Bianco, 4 and Thanh D. Hoang1,2
1 Walter Reed National Military Medical Center, Bethesda, Maryland 20889-5600, USA; 2 Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA; 3 Divsion of Endocrinology and Metabolism, Rush University Medical Center, Chicago, Illinois 60612, USA; and 4 Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637, USA
Dear Editor,
We thank Bonnema et al (1) for giving us the opportunity to provide further details on our recent publication (2) while addressing their insightful questions.
In reference to the consequences of long-term treatment with liothyronine (LT3), we respectfully point out that there is now solid data that LT3 does not increase the frequency of adverse reactions if serum thyrotropin (TSH) levels are maintained within the normal range. For example, an observational study during 1997 to 2014 (3) compared nearly 34 000 patients taking only levothyroxine (LT4) with those using LT4 + LT3 (n = 327) or LT3 alone (n = 73) during a mean follow-up of 9.3 years (SD 5.6) and a maximum follow-up of 17.3 years. The study did not reveal higher mortality or morbidity risk due to cardiovascular disease, atrial fibrillation, or fractures. In addition, an analysis of 20 clinical trials that included almost 1000 patients observed for up to 1 year indicated that peaks of serum 3,5,3′-triiodothyronine observed after the LT3 tablets only minimally affected serum TSH, heart rate, and blood pressure; the frequency of adverse reactions was similar to patients taking LT4 (4). Bone turnover markers were studied in 2 trials, and they remained within normal range. This was confirmed in a recent meta-analysis by Millan-Alanis et al (5) in which 18 clinical trials comparing LT4 vs LT4 + LT3 therapy were evaluated found no differences in adverse events. In fact, we are unaware that combination therapy containing LT3 has ever been associated with increased occurrence of adverse reactions in patients maintaining normal TSH levels.
In reference to a potential placebo effect associated with “entering a trial,” we found that 20 patients comprised the subgroup with the worst outcomes while on LT4 therapy and these patients were randomly distributed across the 3 treatment arms. Seven patients received LT4 in arm 1 and 9 patients received LT4 in arm 2. Thus, it is unlikely that a placebo effect played a role.
Baseline values were considered in the analyses. As stated under “Materials and Methods,” differences between treatments were evaluated using mixed-effects models. The primary outcome model included a fixed effect for treatment and a random effect of subject. Models were run with and without the inclusion of baseline scores to isolate between treatment differences. In the subanalysis we also considered the baseline values but were not able to detect differences between baseline and the LT4-treated arm.
In reference to a subgroup analysis of patients on desiccated thyroid extract (DTE) or LT4 + LT3 before the trial, we found that there were 8 patients on DTE and 3 patients on LT4/LT3 at baseline. At the end of the study, out of these 11 patients, 6 preferred DTE and 5 preferred the LT4 + LT3 combination. This suggests that a placebo effect could not explain our findings. An appropriately powered study could address this point further. Of note, a preference for DTE had already been identified in our previous study(6). It has been our experience that most patients taking DTE show a strong preference for continuing on DTE rather than switching to LT4.
