Another interesting paper (and letters), supporting use of T3 - both synthetic and as desiccated thyroid.
J Clin Endocrinol Metab.2021 Nov; 106(11): e4400–e4413.
Published online 2021 Jun 29. doi: 10.1210/clinem/dgab478
PMCID: PMC8530721
PMID: 34185829
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 L Fonseca,4 Vinh Q Mai,1,2 Antonio C Bianco,4 and Thanh D Hoang1,2
Author information Article notes Copyright and License information Disclaimer
Associated Data
Data Availability Statement
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Abstract
Introduction
Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients.
Methodology
Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect.
Results
Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).
Conclusions
As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
Paper freely accessible here:
ncbi.nlm.nih.gov/labs/pmc/a...
The paper then received a letter as response. Unfortunately, I have no access to the letter - if you follow the link, it offers it as a PDF but I am denied access. If anyone does have access, even just to read, please let us know what the letter said.
“Letter to the editor from Steen Joop Bonnema et al: (Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism)”
Steen Joop Bonnema, Kamilla Ryom Riis, Christian Zinck Jensen, Marianne Thvilum, Birte Nygaard
The Journal of Clinical Endocrinology & Metabolism, dgab778, doi.org/10.1210/clinem/dgab778
academic.oup.com/jcem/advan...
That letter then received a response from the authors of the paper! And this response letter is accessible - you can download a PDF.
Unfortunately, that rather leaves us guessing what the first letter said.
Response to Letter to the Editor from Steen Joop Bonnema: (Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism)”
Mohamed K M Shakir, Daniel I Brooks, Elizabeth A McAninch, Tatiana De Lourdes Fonseca, Vinh Q Mai, Antonio C Bianco, Thanh D Hoang
The Journal of Clinical Endocrinology & Metabolism, dgab779, doi.org/10.1210/clinem/dgab779
Dear Editor,
We thank Bonnema et al1 for giving us the opportunity to provide further details on our recent publication2 while addressing their insightful questions.
1. In reference to the consequences of long-term treatment with LT3, we respectfully point out that there is now solid data that LT3 does not increase the frequency of adverse reactions if serum TSH levels are maintained within the normal range. For example, an observational study during 1997-20143 that compared nearly 34,000 patients taking only 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 1,000 patients observed for up to 1 year indicated that peaks of serum T3 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 LT44. Bone turnover markers were studied in two trials, and they remained within normal range. This was confirmed in a recent meta-analysis by Millan-Alanis et al5 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.
2. 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. 7 patients received LT4 on Arm-1 and 9 patients received LT4 on Arm-2. Thus, it is unlikely that a placebo effect played a role.
3. Baseline values were considered in the analyses. As stated under 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 sub-analysis we also considered the baseline values but were not able to detect differences between baseline and LT4-treated arm.
4. In reference to a subgroup analysis of patients on DTE or LT4+LT3 prior to 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 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 study6. It has been our experience that most patients taking DTE show strong preference for continuing on DTE rather than switching to LT4.
academic.oup.com/jcem/advan...
There was another relevant recent thread:
healthunlocked.com/thyroidu...
And this post about a highly relevant paper from some of the same people nine years ago:
Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study.