Comment by Johannes W. Dietrich on this new paper:
@drjwdietrich.bsky.social
About 10% of hypothyroid patients have reduced quality of life despite normal TSH under therapy with levothyroxine (L-T4). A new randomised, double-blind trial demonstrated better QoL under L-T4 + L-T3 compared to L-T4 alone.
I can't help feeling a mixture of being pleased that even in far off places, in this case Iran, they are seeing issues and researching. Blended with despair that it seems to be a 100% worldwide problem.
All papers seem to end with "more research needed". None end with "because some patients do better, combination treatment should be offered to many more patients".
Early effects of LT3 + LT4 combination therapy on quality of life in hypothyroid patients: a randomized, double-blind, parallel-group comparison trial.
Hajtalebi F 1 , Alaei-Shahmiri F 2 , Golgiri F 2 , Shahini N 3 , Akbari H 1 , Assadian K 4 , Mosalamiaghili S 4
Abstract
Background
This study aimed to evaluate the impact of combined levothyroxine (LT4) and triiodothyronine (LT3) therapy on quality of life in patients with primary hypothyroidism.
Methods
In a randomized, double-blind, parallel-group trial, 151 Iranian patients diagnosed with primary hypothyroidism between 2020 and 2021 were enrolled. One group received LT4 alone (n = 80), while the other received LT4 and LT3 (n = 71) for a minimum of six months. The primary outcome was quality of life assessed using the SF-36V1 questionnaire, and the secondary endpoints included clinical and laboratory measurements.
Results
In the LT4 + LT3 group, a significant reduction in TSH levels (p < 0.05) was observed compared to baseline. While no significant differences emerged between the groups in terms of blood pressure, lipid profiles (except for low-density lipoprotein cholesterol), or body weight, there were notable improvements in physical functioning and bodily pain in the LT4 + LT3 group compared to the LT4 + placebo group. Compared with baseline, combination therapy significantly increased the physical component summary score after six months, but the difference was not significant.
Conclusion
Combination therapy may benefit patients with primary hypothyroidism, particularly those experiencing body pain or physical function issues. However, the overall impact on quality of life remains inconclusive, as evidenced by the scores for the mental component. Further research is needed to determine the broader implications of this therapy. This study provides valuable insights into the potential advantages of combining LT4 and LT3 in the management of primary hypothyroidism.
Trial registration
The study was registered with the Iranian Registry of Clinical Trials (IRCT) and assigned the registration number IRCT20200410047012N1 on 2022-08-07.
Trial registration number
IRCT20200410047012N1. Date of registration: 2020-06-12.
Agreed it's a shame that there is no emphatic endorsement of combined T3 & T4 therapy, but this will certainly be something I'll add to my file when discussing my lower than range TSH and self sourced T3 addition to T4 with my GP!! Thanks for posting.
Interesting that the lowered TSH of 0.05 is noted. Mine is usually around there on combined therapy, yet the endocrinologist constantly says we need to reduce my medication as the TSH is too low.
"Which can be significantly different to the rest of the body."
The pitutary does have peripheral conversion negative feedback loops, so it should have some awareness of the rest of the body, in the same way that it would for someone without Thyroid Disease. The only difference being the TSH-T3 shunt feeback loop is distorted, but this is a localised short feedback, and so isn't an issue in this regard.
My understanding is that the pituitary *should* be aware of everything that's required for necessary TSH production, otherwise why does the system work so well in normal healthy people?
I’m struggling with the fact it was a “double-blind study”! Surely those on the combination arm would know they were on the combination as they were taking extra pills and at different times of the day?
Secondly, They mention QOL , blood pressure, lipids and pain scores as an outcome but not one mention of thyroid hormone levels other than TSH. Surely that should have been the main focus because unless they are optimum then everything else won’t follow.
I’m struggling with the fact it was a “double-blind study”! Surely those on the combination arm would know they were on the combination as they were taking extra pills and at different times of the day?
People are given fake pills (i.e. placebo) that look identical to the real ones in research. So everyone will get Levo plus either real T3 or fake T3 but they shouldn't be able to tell the difference.
It is not that the researchers were unaware. They do mention T3 and T4:
Serum thyroid-stimulating hormone (TSH) levels were assessed using an immunocytometric assay (LIAISON TSH, Byk Gulden Italia, Milan, Italy). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were determined through enzymatic colorimetric methods (Pars Azmoon, Iran). Due to limitations, we could not assess triiodothyronine (T3) or T4 levels.
Wonder what limitations they were, possibly not done at all,since we know that FT4/FT3 rarely are in GP surgeries here at least - interesting they did the cholesterol levels though!😊❤️
They actually go into some detail about how they handled the blinding.
Interventions
Patients were randomized to either continue their usual LT4 dose (initially averaging 100 µg/day) in combination with a placebo (to ensure blinding) for six months (Group 1) or transition to combination therapy of LT4 (LT4 dose at the time of inclusion—50 µg) and LT3 (6.25 μg twice daily, administered in the morning and afternoon) (Group 2). The reduced LT4 dose was chosen because 100 μg of LT4 tablets are available in our country, preventing standard 14:1 T4:T3 ratio dosing from being feasible. The placebo was "liothyronine," which was labeled "approved for research purposes only." The placebo was placed into envelopes based on the allocation orders by another independent nurse who was unaware of the study. Patient IDs, visit dates, and other relevant information were recorded in each envelope. Neither the patients nor the evaluating physicians were aware of the treatment. After six months, another independent researcher not informed about the therapy assessed the patients' health-related quality of life scores.
One issue I have with thyroid research generally is that people do not usually have a free hand in how much Levo they are prescribed before the research is started. So the patients might feel anywhere from awful to wonderful before the research starts. This research was carried out on people who had been treated for only a few months. And a doctor will have determined how much Levo the patients are prescribed before the research, it won't have been the patient deciding for themselves. And in my experience if a doctor thinks I should feel fine on a particular regimen of drugs for any condition, then they won't pay attention if I tell them I feel awful, because I'm only a patient and I must be wrong.
The inclusion criteria for patients :
necessitated that participants be older than 16 years of age; possess proficiency in reading and understanding the Persian language;have a confirmed diagnosis of overt hypothyroidism established at least six months before inclusion; maintain a stable and consistent regimen of LT4 monotherapy for a minimum of three months before inclusion; and self-report signs and symptoms of hypothyroidism, including fatigue, mood changes, weight gain, lethargy, decreased psychomotor performance, cognitive issues, depression, and disturbances, despite having normal thyroid hormone levels.
The other thing I noted :
Patients were randomized to either continue their usual LT4 dose (initially averaging 100 μg/day) in combination with a placebo (to ensure blinding) for six months (Group 1) or transition to combination therapy of LT4 (LT4 dose at the time of inclusion—50 μg) and LT3 (6.25 μg twice daily, administered in the morning and afternoon) (Group 2). The reduced LT4 dose was chosen because 100 μg of LT4 tablets are available in our country, preventing standard 14:1 T4:T3 ratio dosing from being feasible.
I've read about the origin of the 14:1 T4:T3 ratio that many doctors think is perfect for patients, and how dodgy that is. (On the Thyroid Patients Canada website). This is just a couple of links where it is discussed :
I struggled for years to get a thyroid hormone dose that I could tolerate well (I ended up on T3 only for several years and only started to take a combo of T4 + T3 in my 8th or 9th year of treatment), and had to deal with high cortisol, and low nutrients that I struggled to increase. The patients in this research seem to have been included after a very short time on treatment with Levo only, so I don't feel that this research applies to me.
Just for info, my own current T4 : T3 ratio is 4.5 : 1. I suspect this would cause panic amongst doctors who think Pilo was absolutely right. But this research does at least explain why patients so often have their Levo reduced to 50mcg if they are going to be prescribed T3 at some point.
it’s always seemed to me that the only actually validnstudies of thyroid hormone should be on those of us who have had thyroidectomy. Otherwise it feels always compounded by existing T4/T3 production. And testing and addressing T3, serial testing throughout the day (after mels, exercise, etc). A normal healthy thyroid works on a response to need basis, supplying T4 and some T3 when needed. It does jot pump out 100 mcg of T4 every morning an hour before breakfast then go back to sleep for the rest of the day.
Thank you for sharing this study. I have recently experimented with adding Tiromel (accessed from Turkey) together with levothyroxine. Because my endocrinologist was unwilling to prescribe T3, I was wary of doing this particularly as I was unsure what mcg-age to take, and how much levo to reduce my dose by. I started with a quarter of a 25mcg tablet of T3 and reduced my levothyroxine to 100mcg (from 150). Every three days I increased t3 until I was taking 5mcg twice per day.Because of my age, the recent changes to TSH (last Monitor my Health blood test it was 7.86); t4 of 22.5 (range 12 - 22) and my t3 3.6) I was wary. Mostly because when my thyroid went out of synch (been stable since 1996 with no problems), I developed an irregular heartbeat on occasion. I was also taking BP medicine. The reason that I stopped this experiment was because I ran out of BP tablets (I get them sent online and the wrong dosage was sent and I didn't realise until I went to open the nw packet) this was a week last Friday, and ringing my surgery resulted in having to wait until Monday to have a telephone consultation with a GP!! I probably panicked. I was unaware as to whether T3 raised BP. I tested and it seemed Ok, but as I was quite worried about doing this test without medical supervision I stopped T3. I had intended to do a blood test in another couple of weeks.
Anyway, the important bit, and one that I would welcome comment on. Actually, I would welcome any advice! The advise re supplements has been useful. I didn't have arrhythmias on T3 but they started again when I upped the levo dose after stopping T3. I think that I had depression because I felt mentally positive to the extent of initiating house repairs and gardening; contacting friends again and taking up old hobbies. This was after about 3 days of taking T3. I have been very reclusive and worried about how my home environment has deteriorated since I was felt so exhausted and ill. Since stopping them, I am again struggling, and even awoke this morning wishing that that people weren't coming to do the garden work tomorrow. The difference in the way I feel mentally is incredible which goes against what the article suggested in that quality of life was not significantly different on combination therapy.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
)
U.S. Study Shows Combination Treatment Is Safe, Effective
