Least fillers/excipients?

A common request is know which product (typically levothyroxine, but could be almost any medicine) has the least fillers?

I find this very difficult to answer for several reasons.

Excipients is a word which covers all ingredients in a medicine except for the active pharmaceutical ingredients. Yes, some of these might be present as fillers (bulking agents), but they have many other functions like disintegrants, glidants, colourants, coatings, etc. That is why I prefer to use the term excipients.

But another issue is what is meant by "least"? The smallest number of individual excipients? Or the smallest quantity of excipients in total?

A couple of non-pharmaceutical examples to illustrate:

Ferrero Rocher has about 17 ingredients.

Milk Chocolate 30% (

Sugar, 
Cocoa Butter, 
Cocoa Mass, 
Skimmed Milk Powder, 
Concentrated Butter, 
Emulsifier: Lecithins (Soya), 
Vanillin), 

Hazelnuts (28.5%), 
Sugar, 
Palm Oil, 
Wheat Flour, 
Whey Powder (Milk), 
Fat-Reduced Cocoa, 
Emulsifier: Lecithins (Soya), 
Raising Agent (Sodium Bicarbonate), 
Salt, 
Vanillin.

Total weight of one: 12.5 grams

A loaf of bread has four ingredients.

Wholewheat flour,
Water,
Salt,
Yeast

Total weight of one: 800 grams 

The loaf weighs the same as 64 Ferrero Rocher sweets. But has a mere four ingredients. About a quarter the number.

And it is likely that there is more than 12.5 grams - the total weight of a Ferrero Rocher - of each and every ingredient in the loaf.

You might complain that of course a loaf is much bigger than a Ferrero Rocher. I fully accept that. But tablets also vary quite substantially, if not as extreme as these illustrations.

Trouble is, when comparing you might be much happier with four ingredients that are familiar, than 17 of which several are not things we are likely to have in our kitchens.

On the other hand, there will be less than a fraction of a gram of several of the Ferrero Rocher ingredients. Quite possibly little enough to cope with even if you could not take larger amounts.

For thyroid hormones, we often have to take more than one tablet to reach our required dose. Quite common to need 100 + 50 + 25. You must add all the individual tablets you need. Also, a higher dose tablet might well be the same size as a 25 microgram tablet or, in some cases, smaller, which makes this more awkward to calculate.

Think through what you really want to achieve.

My own view is that we need to identify excipients we know we need to avoid and exclude products that contain them. Then look through what options remain. You might be disappointed that there are only one or two.

Availability is also an issue. We often do not have the choice of all the products that could be available. 

A final comment: Always remember that only something like one thousandth of a thyroid hormone tablet is the actual hormone! So every tablet consists almost entirely of excipients.

 

 

 

 

Vitamin C and Levothyroxine

Discussion

A widely discussed issue is whether Vitamin C enhances absorption of levothyroxine. For example, these two papers:

The interplay between vitamin C and thyroid.

https://europepmc.org/article/MED/37246589

https://doi.org/10.1002/edm2.432

Levothyroxine treatment and gastric juice pH in humans: the proof of concept. 

https://europepmc.org/article/MED/35477833

https://doi.org/10.1007/s12020-022-03056-1

If you decide to try this approach, there are some important points.

Form of Vitamin C 

There are several forms of Vitamin C. But the forms which are not ascorbic acid will not help.

That is, sodium ascorbate and calcium ascorbate are unlikely to have any positive effect.

Other Ingredients

And many forms of Vitamin C are not just the active ingredient but other substances like those in the list below. Some are very pure ascorbic acid but some have numerous other ingredients. And each of those ingredients needs to be considered.

• microcrystalline cellulose
• magnesium stearate
• polyethylene glycol
• sodium starch glycolate
• silica colloidal anhydrous
• talc
• syrup (sucrose)
• potato starch
• hypromellose (derived from cellulose) capsule
• calcium laurate

 

https://helvella.blogspot.com/2025/06/vitamin-c-and-levothyroxine.html 

How do you test when alternate day dosing?

Many members do not take the same dose of levothyroxine every day.

A typical example is alternating 50 and 75 micrograms in order to average 67.5. Or 75 and 100 to get 87.5. Or 100 and 125 to get 112.5. Or even 50 and 100 to get 75.

We also see some patterns such as a higher (or lower) dose on Saturdays and Sundays, or three or four days a week. I consider all these regimes questionable. They often seem to have been chosen to make the life of the prescriber easier. Or because the prescriber thinks we are unable to cope with more even patterns or tablets splitting.

In particular, three or four days a week on a higher dose seem odd to me. You inevitably end up with two consecutive days on the lower, or higher, dose. It would probably make more sense to dose alternate day for 7 days in each fortnight - with hardly any difference in total dose.

Personally, having alternate day dosed for some considerable time, I realised it didn’t suit me. I used to split the 25 microgram tablets so as to take 112.5 every day. And would do so again, if needed, to end up taking the same dose every day.

To get to the point of this blog! The trouble I want to discuss is testing. Taking a simple 50/75 alternate day dosing regime as the example, do you get your blood tested on a day you took 50? Or 75?

And precisely what effect does that decision have on TSH, Free T4 and Free T3? The answers are not immediately obvious - though we can expect the Free T4 to be a bit higher if the last dose was a higher dose. Effects on TSH and Free T3 levels are somewhat more subtly affected by levothyroxine dosing.

And can you achieve that consistently into the future?

Of course, there are the usual issues of how many hours after your dose to do the blood draw, but if you are alternating, you now ALSO have to consider whether that dose was a low or high dose!

I don’t think there is a satisfactory answer to this conundrum.

Either ensure you take an even dose every day. (At least for several days before testing.) Or accept that the effects on your results could be somewhat unpredictable.

Beyond thyroid dysfunction: the systemic impact of iodine excess

Yet another paper which is highlighting the issues which can be caused by excess iodine intake.

In particular, read the Conclusion in the full paper.

Beyond thyroid dysfunction: the systemic impact of iodine excess
Aiman Khudair  1† Sara Anjum Niinuma 1† Haniya Habib 1† Butler 2*

    1 School of Medicine, Royal College of Surgeons in Ireland - Medical University of Bahrain, Busaiteen, Bahrain
    2 Research Department, Royal College of Surgeons in Ireland - Medical University of Bahrain, Busaiteen, Bahrain

As an essential micronutrient, iodine plays a crucial role in several physiological systems, particularly in the production of thyroid hormone. While deficiency is widely recognized, the consequences of iodine excess (IE) are less studied. IE, which may be caused by iodine-rich diets, supplements, iodinated contrast media and salt iodization, has been implicated in a range of adverse outcomes on thyroid and systemic health. Examples include autoimmune thyroid diseases like Graves’ disease and Hashimoto’s thyroiditis, driven by immune cell polarization and gut microbiota alterations. Furthermore, excessive iodine intake is associated with increased risks of cardiovascular diseases, including hypertension and atherosclerosis, due to oxidative stress, inflammation, and endothelial dysfunction. It contributes to the development of thyroid cancer, particularly papillary thyroid cancer, through genetic mutations such as BRAF mutations and enhanced cancer cell proliferation. Excess iodine intake has been implicated to have neurotoxic effects, significantly impairing learning and memory, negatively impacting neonatal brain development, and potentially contributing to the progression of neurodegenerative conditions. It also has a potential role in renal dysfunction in vulnerable populations, due to overload from povidone-iodine in sterile equipment. This mini-review aims to collate the adverse effects of IE, beyond its effect on thyroid health, through investigation of the cardiovascular, nervous, and renal systems. Through our consolidation of the current literature, we hope to raise awareness and contribute to the understanding of the multifaceted impact of excessive iodine intake.

Open access:

https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1568807/full

Advancing drug safety and mitigating health concerns: High-resolution mass spectrometry in the levothyroxine case study

This paper is a fascinating study which performed detailed chemical analysis on levothyroxine products in order to identify degradation products and unexpected substances. This was partly the result of the reformulation of Merck levothyroxine from lactose to mannitol - and the consequences in several countries - especially France which was the first to receive the new formulation.

The paper is extremely heavy going in parts with highly technical language. Nonetheless, it is actually quite easy to skip most of that and read the explanatory parts which are much easier. We don't need to know how to perform the analyses! Only what they found.

Next time a doctor, a nurse, a pharmacist or anyone else tells you all levothyroxine products are the same, offer a copy of this study... 

Advancing drug safety and mitigating health concerns: High-resolution mass spectrometry in the levothyroxine case study

 

Abstract

Levothyroxine is a drug with a narrow therapeutic index. Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability, which can result in major health problems. However, the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed. In this study, we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes. Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry (UHPLC-DIA-HRMS) was employed. UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products, but also the presence of non-expected components in the formulations. Among these, we identified compounds resulting from reactions between mannitol and other excipients, such as citric acid, stearate, and palmitate, or from reactions between an excipient and an active pharmaceutical ingredient, such as levothyroxine-lactose adduct. In addition to these compounds, undeclared phospholipids were also found in three formulations. This non-targeted approach is not common in pharmaceutical quality control analysis. Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.

And the first sentence of the conclusion:

This work was designed as an independent study with the aim to comprehensively investigate levothyroxine formulations and thus contribute to their quality and safety in response to previous significant health crises.

Full paper including PDF version are open access at link below.

https://www.sciencedirect.com/science/article/pii/S2095177924000674

And

https://europepmc.org/article/MED/39350965 

Manufacturers and Adverse Reactions/Side Effects

I couldn't tolerate Teva levothyroxine. (In common with many others.)

However, there is almost no reason to suggest that any other Teva product would be a problem.

Yet this has often been suggested.

Discussion

Products are often manufactured across many factories, across many countries. This is particularly likely for companies like Teva which grew by acquisition of existing companies. Each of which had their own formulations, supplier agreements, etc.

Excipients (inactive ingredients) are often very different in various medicines. Some occur quite frequently - maize starch, magnesium stearate, etc. However, you might well be able to find two products from the same company with not a single excipient in common.

These excipients can change sourcing from one batch to the next. The suppliers are expected to keep their excipients within tight specifications. And these will apply both to a single source and across multiple sources.

Tablet manufacturers might well switch excipient suppliers on the basis of cost, availability, time to deliver and other factors. On the basis that they are to the same specification and might well use them already.

The excipient suppliers could be supplying the same excipients, from the same batches, to many tablet manufacturers.

On the other hand...

An anonymous factory in a country with poor standards could see multiple poor quality products being produced. Indeed, it is to overcome such issues that USA (FDA) and EU (EMA) inspectors visit factories across the world.

If a factory receives a batch of an excipient which is used in several of their products, it is possible that multiple could be affected.

Widespread changes

Occasionally a single excipient might be found unacceptable.

Some animal-derived products might be avoided in order to make products more acceptable to those who wish to avoid such sources.

Some excipients might be avoided in order to conform to common religious tenets.

There has been a move away from lactose (often - but not always - towards mannitol) for many reasons including extending expiry dates. This is despite mannitol being more expensive than lactose.

However, pharmaceutical companies know it can cost a lot to change formulations. Especially if there are negative reactions from patients. They likely have more incentive not change change anything even when there are some potential advantages.

 

Machine learning-based exploration of the associations between multiple minerals' intake and thyroid dysfunction: data from the National Health and Nutrition Examination Survey

The importance of a reasonable balance of mineral intake has long been a core message among patients.

This paper picks up on nine minerals and identifies their importance collectively: calcium, iron, zinc, selenium, magnesium, phosphorus, potassium, copper, and iodine.

Machine learning-based exploration of the associations between multiple minerals' intake and thyroid dysfunction: data from the National Health and Nutrition Examination Survey

Shaojie Liu1, Weibin Huang, Yaming Lin, Yifei Wang, Hongjin Li, Xiaojuan Chen, Xiaojuan Chen, Yijia Zou, ChenBo Chen, Baochang He, Zhiping Yang, Jing Fan

Objectives: 

The associations between various minerals' intake and thyroid dysfunction (TD), including hyperthyroidism and hypothyroidism, are still inconclusive, which may be attributed to the potential synergistic effects among various minerals.

Methods: 

The data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001–2002 and 2007–2012 databases. Dietary interviews were conducted to collect the consumption of multiple minerals. Blood samples were collected to measure concentrations of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone. A total of 7,779 participants with aged over 20 years were effectively enrolled in this study and categorized into hyperthyroidism or hypothyroidism groups. Weighted multivariate logistic regression model along with three machine learning models WQS, qg-comp, and BKMR were employed to investigate the individual and joint effect of multiple minerals' consumption on TD.

Results: 

Among 7,779 subjects, 134 participants were diagnosed as hyperthyroidism and 184 participants were diagnosed as hypothyroidism, with prevalence of 1.6 and 2.4%, respectively. The results from logistic regression model showed that the higher the intakes of calcium, magnesium and potassium, the lower the prevalence of hyperthyroidism, with OR values of 0.591, 0.472, and 0.436, respectively (all P < 0.05); while the higher the intake of iodine, the higher the prevalence of hyperthyroidism, with OR and 95%CI values of 1.262 (1.028, 1.550). Three machine learning models were employed to evaluate the joint effect of nine minerals' consumption on TD, revealing a negative correlation with both hyperthyroidism and hypothyroidism. Of them, the potential minerals associated with TD were calcium, zinc, copper, and magnesium.

Conclusion: 

In short, the maintenance of a well-balanced consumption of multiple minerals is considered crucial in the prevention and treatment of TD, and the intakes of various minerals exhibit varying degrees of association with TD.

Open access:

https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1522232/full

Relationships between iodine nutrition status, and bone mineral density and bone metabolism: a cross-sectional study of 1207 thyroid disease-free adults in China

There is a history of those with thyroid issues being encouraged to take iodine supplementation. Indeed, at the level of iodised salt, this is often national policy. (Though not in the UK.)

However, some sources encourage consumption of iodine in quantities far greater than the highest levels found in diet. Japan is often quoted as having the highest population intake of iodine of any of the larger countries of the world - typically around 3 milligrams a day is quoted.

This paper claims to identify an association between higher iodine intake levels and bone mass density, osteopenia and osteoporosis.

Relationships between iodine nutrition status, and bone mineral density and bone metabolism: a cross-sectional study of 1207 thyroid disease-free adults in China

Published online by Cambridge University Press:  10 April 2025

Zheng Zhou, Jinjin Liu, Baoxiang Li, Yun Chen, Yanhong He, Bingxuan Ren, Qiuyang Wei, Meihui Jin, Yao Chen, Haiyan Gao, Siyuan Wan, Lixiang Liu and Hongmei Shen

Abstract

Little is known about the association between iodine nutrition status and bone health. The present study aimed to explore the connection between iodine nutrition status, bone metabolism parameters, and bone disease (osteopenia and osteoporosis). A cross-sectional survey was conducted involving 391, 395, and 421 adults from iodine fortification areas (IFA), iodine adequate areas (IAA), and iodine excess areas (IEA) of China. Iodine nutrition status, bone metabolism parameters and BMD were measured. Our results showed that, in IEA, the urine iodine concentrations (UIC) and serum iodine concentrations (SIC) were significantly higher than in IAA. BMD and Ca2+ levels were significantly different under different iodine nutrition levels and the BMD were negatively correlated with UIC and SIC. Univariate linear regression showed that gender, age, BMI, menopausal status, smoking status, alcohol consumption, UIC, SIC, free thyroxine, TSH, and alkaline phosphatase were associated with BMD. The prevalence of osteopenia was significantly increased in IEA, UIC ≥ 300µg/L and SIC > 90µg/L groups. UIC ≥ 300µg/L and SIC > 90µg/L were risk factors for BMD T value < -1.0 SD. In conclusion, excess iodine can not only lead to changes in bone metabolism parameters and BMD, but is also a risk factor for osteopenia and osteoporosis. 

Keywords
Water iodine concentrations, BMD, Iodine nutrition, Bone metabolism

Abstract and full paper (as PDF) open access:

DOI:  10.1017/S0007114525000790

https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/relationships-between-iodine-nutrition-status-and-bone-mineral-density-and-bone-metabolism-a-crosssectional-study-of-1207-thyroid-diseasefree-adults-in-china/B98904C377A39F1D7EBA2BE9485971DC

Dosing by weight

The UK's NICE NG145 thyroid guidance is often quoted as saying that, for levothyroxine, a dose of 1.6 micrograms per kilogram is recommended. This is a misinterpretation of the guidance.

What it actually says is:

1.3.6 Consider starting levothyroxine at a dosage of 1.6 micrograms per
kilogram of body weight per day (rounded to the nearest 25 micrograms)
for adults under 65 with primary hypothyroidism and no history of
cardiovascular disease.

https://www.nice.org.uk/guidance/NG145

It does NOT say that this is the right dose for anyone. It says to consider that as a starting dose.  It is a suggestion. Which might then need to be adjusted. The guidance goes on about persistent symptoms, checking TSH, "optimal wellbeing", even looking at Free T4. But it gives effectively no guidance on how to manage changes to dosing. And does not even hint at a maximum dose.

It does not say this is a typical, likely or desirable eventual stable dose.

The guidance doesn't even appear to consider that 1.6 micrograms per kilogram could be too much - whether as a starting dose or long-term. Some who are clearly hypothyroid without treatment simply do not ever need this high a dose and achieve quite good results and acceptable laboratory results for TSH, Free T4 and Free T3 tests.

There is plenty of historical evidence that doses in the range 1.6 to 2.3 micrograms of levothyroxine per kilogram are expected. With the advent of oral solutions (liquid) and gelcaps, these numbers would need reassessment because they are usually expected to be absorbed somewhat better. And there is also plenty of evidence that some people simply do not absorb levothyroxine as effectively as many others.

Therefore, you cannot look on 1.6 micrograms per kilogram as anything other than an estimate based on historic approaches to treatment which is unlikely to seriously overdose in people who do really need levothyroxine.

And the issue about age 65? Well, again this is a starting dose. Not long term. Older people in particular are more likely to have absorption issues which can end up needing very much higher doses. (Younger people can also have these issues, but I'm making the point that there really is no ceiling for doses and high doses can be required to achieve sufficient absorption, regardless age.)

My own take on dosing by weight finds many reasons to question the approach in its entirety. But even NG145 does not say that this starting dose is a target or some sort of universal dosing.

helvella - Estimation of Levothyroxine Dosing in Adults

https://helvella.blogspot.com/p/helvella-estimation-of-levothyroxine.html

Can consumption of traditional fermented foods protect against Hashimoto's thyroiditis?

Sometimes papers come out which appear to contradict recent ideas and trends. For example, avoidance of dairy has often been recommended, even advised. Yet this paper very clearly implies that at least fermented dairy produce might well be beneficial.

Obviously it is necessary to read fully and consider circumstances. And it is important to be clear about the mothers and the offspring and who is consuming the fermented produce!

Can consumption of traditional fermented foods protect against Hashimoto's thyroiditis?

Fatma Özgüç Çömlek  1 , Muslu Kazım Körez  2

    1   Department of Pediatric Endocrinology. Faculty of Medicine. Selçuk University.
    2   Department of Biostatistics. Faculty of Medicine. Selçuk University.

    PMID: 40195756 DOI: 10.20960/nh.05508

Abstract

Background: 

this study examined fermented food consumption habits and the relationship between other factors and Hashimoto's thyroiditis.

Methods: 

the study included 90 children and their mothers, 45 of whom had HT and 45 of whom did not. Participants answered a survey questioning about their fermented food consumption habits and the status of various environmental factors.

Results: 

mothers who consumed homemade pickles during pregnancy (OR: 0.341, [95 % CI: 0.117 to 0.990]) homemade yogurt (OR: 0.091, [95 % CI: 0.011 to 0.752]), tarhana (OR: 0.325 [95 % CI: 0.136 to 0.778)]) and olive oil (OR: 0.163 [95 % CI: 0.033 to 0.792]) were found to have a statistically significant lower risk of developing Hashimoto's disease in their children. The risk of HT in children who consumed homemade yogurt (OR: 0.091 [95 % CI: 0.011 to 0.752]), cheese (OR: 0.242 [95 % CI: 0.100 to 0.590]), and olive oil (OR: 0.042 [95 % CI: 0.002 to 0.750]) was found to be significantly lower than in children who did not consume it.

Conclusions: 

fermented food consumption habits can be protective against autoimmune diseases such as HT by affecting the immune system through the intestinal microbiota.

Open access via the links below - make sure you get the version in English!

https://pubmed.ncbi.nlm.nih.gov/40195756/

https://www.nutricionhospitalaria.org/articles/05508/show

Fecal glucocorticoid metabolite and T3 profiles of orphaned elephants differ from non-orphaned elephants in Zambia

Many times, members have mentioned issues in their early lives. In this paper, these are referred to as early-life adverse events (ELAEs).

I note that diogenes several times referred to issues such as stress in early life as being causative, or at least contributory, to thyroid issues.

It is, in my view, entirely reasonable to look for links between elephants and humans. We have a lot in common. 

Fecal glucocorticoid metabolite and T3 profiles of orphaned elephants differ from non-orphaned elephants in Zambia

Daniella E Chusyd  1 , Janine L Brown  2 , Steve Paris  2 , Nicole Boisseau  2 , Webster Mwaanga  3 , Moses Kasongo  3 , Lisa Olivier  3 , Stephanie L Dickinson  4 , Bailey Ortyl  4 , Tessa Steiniche  1 , Steven N Austad  5   6 , David B Allison  4   5 , Michael D Wasserman  7

    PMID: 40196305 PMCID: PMC11974515 DOI: 10.7717/peerj.19122

Abstract

Background: 

Elephants provide valuable insight into how early-life adverse events (ELAEs) associate with animal health and welfare because they can live to advanced ages, display extensive cognitive and memory capabilities, and rely heavily on social bonds. Although it is known that African savanna elephants that experienced ELAEs, such as being orphaned due to human activities, have altered behavioral outcomes, little is known regarding the physiological consequences associated with those stressors.

Methods: 

We compared fecal glucocorticoid (fGCM) and thyroid (fT3) metabolites as well as body condition scores (BCS) in rescued and rehabilitated orphaned (early-dry season: n = 20; late-dry season: n = 21 elephants) African savanna elephants in Kafue National Park, Zambia to age- and sex-matched wild non-orphaned controls groups (early-dry season: n = 57; late-dry season: n = 22 elephants) during the early- (May/June) and late- (September/October) dry seasons, respectively. Age and sex were known for orphans. For non-orphan controls, age was estimated based on dung diameter, and sex was determined based on external genitalia. Hormone concentrations were compared between groups by age class to account for developmental and nutritional transitions experienced in early life. Given that environmental stressors (e.g., availability of food and water sources) change over the course of the dry season, early- and late-dry seasons were separated in the analyses.

Results: 

fGCM concentrations were higher in orphans at younger ages than non-orphaned controls of any age. This may be due to the younger orphans being temporally closer to the traumatic event and thus not having had sufficient time to establish meaningful social bonds that could buffer the negative outcomes associated with ELAEs. Alternatively, orphans could have acclimated to living under human care, resulting in fGCM concentrations that were not different from wild controls at older ages. Orphans also had significantly higher mean fT3 concentrations than non-orphans, suggesting increased caloric intake during rehabilitation. There was no difference in BCS between orphan and non-orphan elephants at any age or time period, possibly reflecting the limitations associated with BCS assessments in younger elephants.

Conclusions: 

Together, these results provide insight into possible physiological responses underlying ELAEs and/or living under human care, including alterations in fGCM and fT3 concentrations, particularly in younger orphans. While these hormonal changes suggest a physiological response to trauma, the support of social bonds and acclimation to human care may mitigate long-term stress effects, highlighting the critical role of social integration in elephant rehabilitation and conservation efforts.

Keywords: African savanna elephants; Early life adversity; Stress; Thyroid hormone. 

https://pubmed.ncbi.nlm.nih.gov/40196305/

Open access here:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11974515/

The role of resistive index in the diagnosis of Hashimoto thyroiditis: A cross-sectional study

Unlike X-rays, Computerised Tomography (CT) and MRI, ultrasonography is relatively inexpensive in terms of equipment, and has no risks from radiation.  Further, some patients require an ultrasound anyway so adding this RI should not add much to the overall costs.

Positive diagnosis of Hashimoto's Thyroiditis (indeed, any form of autoimmune thyroid disease) tends to be poor. It is often based on a positive Thyroid Peroxidase antibodies test and little else. But the antibody test tends to be deferred until thyroid hormone levels are affected. 

The role of resistive index in the diagnosis of Hashimoto thyroiditis: A cross-sectional study.

Soltani K 1 , Keshavarz E 2 , Pouya EK 2 , Jamali R 3 ,  Langroudi TF 4 , Haseli S 5

Medicine, 01 Apr 2025, 104(14):e41933
https://doi.org/10.1097/md.0000000000041933 PMID: 40193673 

Abstract 

The diagnostic role of Doppler ultrasonography regarding Hashimoto thyroiditis (HT) is not fully established. We examined intraparenchymal resistive index (RI) as a Doppler parameter, thyroidal vascularity and other Gray-Scale findings in adults with HT in order to evaluate the clinical feasibility of RI in the diagnosis of this disease. The study included 48 women aged 20 to 50 years who had recently been diagnosed with HT. These participants, who were either euthyroid or sub-clinically hypothyroid during the study period, underwent sonographic examination. Thyroid glands were classified into 4 distinct patterns, using the Color Doppler Scale introduced by Schultz et al and also based on Sostre and Reyes Gray-Scale Grading System they were classified into 4 Grades. Intraparenchymal RIs were obtained in 2 locations within each lobe of the thyroid gland. Gray-Scale findings were compared to Doppler findings (RI). Also, intraparenchymal RIs were obtained in 45 healthy adults as a control group. The mean RI values were determined by calculating the mean of the RI measurements obtained from both lobes of each participant in the patient and control groups. The mean RI value was found to be 0.57 ± 0.05 (range 0.5-0.7) cm/s in patient group and 0.54 ± 0.05 (range 0.47-0.7) cm/s in control group. The results were distributed as follows: pattern 0 was observed in 22 cases, pattern I in 15 cases, pattern II in 6 cases, and pattern III in 5 cases. The mean RI values for patients with normal or nearly normal Gray-Scale findings (n = 13) and those with more pronounced Gray-Scale changes (n = 35) showed no significant difference. However, both groups exhibited higher mean RI values compared to the normal adults in the control group. The results highlight that the RI could be an effective and sensitive tool for diagnosing HT through Doppler ultrasonography.

Article linked from here:

https://europepmc.org/article/MED/40193673

The DOI link does not currently work (often happens with new papers) hence I cannot determine whether it is paywalled nor find the actual journal link.

https://doi.org/10.1097/md.0000000000041933

Increased risk of multisystem comorbidities and disease trajectories following hyperthyroidism: evidence from the 0.5 million UK Biobank population.

Many of those who have received radioactive iodine treatment report that they were not told that hypothyroidism is inevitable. But were led to believe that while it can happen, many don't have that problem. Hence interesting to read this sentence:

Long-term follow-up studies have shown that hypothyroidism was an inevitable consequence of radioiodine therapy in patients with hyperthyroidism of multiple etiologies.

The paper mentions 110 comorbidities. It is necessary to scroll past the end of the main text to view the diagrams and tables which provide more details.

Increased risk of multisystem comorbidities and disease trajectories following hyperthyroidism: evidence from the 0.5 million UK Biobank population.

Abstract 

Hyperthyroidism is a clinical syndrome caused by the excessive production of thyroid hormones, which can have a broad impact on overall health. We systematically investigated the subsequent multisystem comorbidities associated with hyperthyroidism and the progression of these conditions. After a 1:4 propensity score matching, a total of 5,832 hyperthyroidism patients and 22,579 controls from the UK Biobank were included in this study. Phenome-wide association study was conducted to explore the associations between hyperthyroidism and a broad range of subsequent diseases, supplemented by landmark analysis to depict the time-varying effects. Disease trajectory analysis was used to explore the sequential pattern of comorbidity progression of hyperthyroidism. Patients with prior diagnosed hyperthyroidism were observed to have an elevated risk of developing 110 subsequent diseases across multiple systems, as well as all-cause mortality and four causes of death, with particularly marked short-term adverse effects. Disease trajectory analysis demonstrated that the three disease clusters most affected by hyperthyroidism were cardiovascular disease cluster, gastrointestinal inflammation disease cluster, and diabetes-mediated disease cluster. Hyperthyroidism is associated with an elevated risk of subsequent multisystem diseases and mortality. Disease trajectory analysis has elucidated critical sequential patterns of disease progression, offering valuable insights for the management of comorbidities in patients with hyperthyroidism.

Paper is Open Access and may be reached via links below:

https://doi.org/10.1530/ec-25-0066

https://europepmc.org/article/MED/40193316

Currently the PDF is a double-spaced "manuscript" format which is not ideal for reading.

https://ec.bioscientifica.com/view/journals/ec/aop/ec-25-0066/ec-25-0066.xml

Lawrence Tallon begins role as new MHRA CEO

Posted without comment as I know nothing of Lawrence Tallon.

Lawrence Tallon begins role as new MHRA CEO

Lawrence Tallon today (1 April 2025) begins his role as Chief Executive Officer of the Medicines and Healthcare products Regulatory Agency (MHRA).

From:
    Medicines and Healthcare products Regulatory Agency
Published
    1 April 2025

Lawrence brings a strong focus on patient safety, innovation and partnership working, which have been central to his previous roles including as Deputy Chief Executive of Guy’s and St Thomas’ NHS Foundation Trust since March 2020.

Lawrence said: “I am delighted to be joining the MHRA, which plays a vital role in ensuring people across the UK and the NHS have access to safe and effective medicines and medical devices.

“My priorities are patient safety, improving patient access to new medicines and medical devices through risk-proportionate regulation, innovation and growth, and building partnerships in the UK and internationally.”

Lawrence has also been Managing Director of the Shelford Group, which represents some of England’s leading NHS teaching hospitals. This experience has given him valuable insight into the challenges and opportunities facing modern healthcare and life science systems.

Prior to this he served as Director of Strategy, Planning and Performance at University Hospitals Birmingham NHS Foundation Trust and worked within the Department of Health and Social Care alongside ministers and NHS leaders.

Lawrence succeeds Dr June Raine DBE, who is retiring after leading the MHRA since 2019, having steered the agency through the COVID-19 pandemic and the UK’s exit from the European Union.

Lawrence was announced as the new MHRA CEO in March 2025 by the Department of Health and Social Care.

https://www.gov.uk/government/news/lawrence-tallon-begins-role-as-new-mhra-ceo

Iron Deficiency in Adults - A Review

Quite pleased to see this paper actually lists Endocrine disease (hypothyroidism) as a possible cause of iron deficiency.

Other than that, it appears to be a fairly typical review but, by being new, might be more up to date (e.g. mentioning ferritin below 30 as indicating deficiency.

Review
March 30, 2025

Iron Deficiency in Adults - A Review

Michael Auerbach, MD 1, 2; Thomas G. DeLoughery, MD 3; Jennifer S. Tirnauer, MD 4
Author Affiliations Article Information
JAMA. Published online March 30, 2025. doi:10.1001/jama.2025.0452

Abstract

Importance  

Absolute iron deficiency, defined as low iron stores with or without anemia, affects approximately 2 billion people worldwide and 14% of adults in the US. Iron-deficiency anemia, defined as low hemoglobin due to low iron stores, affects approximately 1.2 billion people worldwide, including 10 million in the US.

Observations  

Absolute iron deficiency progresses from low iron stores to iron-deficiency anemia. Individuals with nonanemic iron deficiency or iron-deficiency anemia may be asymptomatic or experience fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32%-40%), pica (40%-50%), dyspnea, lightheadedness, exercise intolerance, and worsening heart failure (HF). Symptom prevalences vary depending on age, comorbidities (eg, chronic kidney disease [CKD], HF), and severity and rate of development of iron deficiency. The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy. In high-income countries, approximately 38% of nonpregnant, reproductive-age women have iron deficiency without anemia and about 13% have iron-deficiency anemia. During the third trimester of pregnancy, iron deficiency affects up to 84% of pregnant women, based on data from high-income countries. Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease (IBD [13%-90%]), and other chronic inflammatory conditions, such as CKD (24%-85%), HF (37%-61%), and cancer (18%-82%). Testing for iron deficiency is indicated for patients with anemia and/or symptoms of iron deficiency (fatigue, pica, or restless legs syndrome) and should be considered for those with risk factors such as heavy menstrual bleeding, pregnancy, or IBD. Iron deficiency is diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20%. Causes of iron deficiency should be identified and treated. Oral iron (ferrous sulfate 325 mg/d or on alternate days) is typically first-line therapy. Intravenous iron is indicated for patients with oral iron intolerance, poor absorption (celiac disease, post–bariatric surgical procedure), chronic inflammatory conditions (CKD, HF, IBD, cancer), ongoing blood loss, and during the second and third trimesters of pregnancy.

Conclusions and Relevance  

Iron deficiency and iron-deficiency anemia are common conditions that may cause symptoms such as fatigue, exercise intolerance, and difficulty concentrating. Ferritin and/or transferrin saturation are required for diagnosis and screening. Oral iron is first-line therapy for most patients. Intravenous iron is used for individuals who do not tolerate or have impaired absorption of oral iron, those with ongoing blood loss, certain chronic inflammatory conditions (IBD, CKD, HF, cancer), and during the second and third trimesters of pregnancy.

https://jamanetwork.com/journals/jama/fullarticle/2832131

TSH inhibits osteoclast differentiation through AMPK signaling pathway

There are many reasons to question this paper. Not least that the research is in specific strain of mice which have had genetic modification. Doesn't necessarily invalidate the paper but does require careful assessment - more than we can achieve with the limited access.

If TSH levels such as those without thyroid issues exhibit are sufficient to make such an impact as appears to be claimed, then we need to consider many issues beyond the usual insistence that we lower our doses of thyroid hormone to achieve a TSH in - let us suggest - a range like 0.5 to 2.0.

Of course, even if that range were agreed, we have to ask whether it is likely that having four times as much TSH (at 2.0) as the lower level (0.5) is entirely acceptable. And we need to investigate with urgency whether TSH levels of 5, 10 or more have their own negative effects. Remember, we are told that many who are hypothyroid should not be treated until TSH reaches 10. Or to look at that the other way round, twenty times as much TSH as is needed 

We also need to suggest that those who cannot secrete sufficient TSH should receive continuing dosing with TSH. For example, those who have pituitary issues. And question what to do in subclinical hyperthyroidism? The obvious inference being that if they are sufficiently hyperthyroid to have a low/suppressed TSH, then they would need to be treated without waiting for overt hyperthyroidism. (Though the question of which treatment is another matter.) With a similar issue arising in those who have had suppressed TSH due to overt hyperthyroidism, or relatively high doses of thyroid hormone as has long been prescribed post-cancer treatment.

Mention of the AMPK signaling pathway is also of interest because AMPK is influenced by thyroid hormone. Therefore we see that while AMPK is activated by TSH it is also increased by thyroid hormone treatment. You cannot look at the effect of TSH without also looking at the effects of thyroid hormone. Perhaps they balance out? Or it might be necessary to look at all twelve variants of AMPK?

I suggest that the worst of all worlds might occur when someone has low TSH in conjunction with low thyroid hormone levels. A state which occurs when patients are dosed by TSH alone when their TSH level, for whatever reason, fails to rise.

Also important to consider that there are numerous slightly different forms of TSH. Treating them as all having an identical effect is questionable.

TSH inhibits osteoclast differentiation through AMPK signaling pathway

Wenwen Zhang a b c d e 1, Yu Chen a b c d e 1, Yan Wang a b c d e, Yanman Zhou f, Honglin Guo a b c d e g, Jin Xu a b c d e

Received 8 January 2025, Revised 13 March 2025, Accepted 24 March 2025, Available online 27 March 2025, Version of Record 1 April 2025.

Abstract

Purpose

It is believed that osteoporosis (OP) is associated with hyperthyroidism as a result of the elevation in thyroxine levels. However, patients with subclinical hyperthyroidism, which is characterized by decreased levels of thyroid-stimulating hormone (TSH) alone, are at equal risk of osteoporosis. Research has shown that TSH receptor (TSHR) is expressed on osteoclasts, but whether TSH directly regulates osteoclasts and the underlying mechanisms remain unclear.

Methods

In this study, we used osteoclast precursor cell conditional TSHR-knockout (TSHR CKO) mouse to study the effects of TSHR knockout on bone metabolism in mice and the changes in osteoclast differentiation in vitro. Transcriptomics was used to identify differentially expressed genes and signaling pathways.

Results

In vitro, experiments confirmed that TSH inhibited osteoclast differentiation in mouse RAW264.7 monocyte/macrophage cell line and targeted the key signaling pathway AMPK by RNA-seq sequencing. We found TSHR CKO mice exhibited decreased femoral biomechanics and damaged bone microstructure. The serum levels of bone resorption marker were increased, accompanied by an increase in the number of osteoclasts.

Conclusion

TSH inhibits osteoclast differentiation by activating the AMPK signaling pathway, and exerts an osteoprotective effect. This study will provide guidance for the diagnosis and treatment of osteoporosis. TSH structural analogs or AMPK activators are expected to provide new ideas for the development of drugs to prevent and treat osteoporosis.

Limited access to abstract and a few key points:

https://www.sciencedirect.com/science/article/abs/pii/S0378111925002306

Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression

Much of the time we hear lots of negativity about T3 (liothyronine, triiodothyronine). We are told it will have horrendous effects on us - even in small doses.

While this study is on mice, it claims very significant benefits of T3 in relation to alcohol and liver disease.

Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression

Renli Luo  1   2 , Sanqiang Li  1   2 , Mengli Yang  1   2 , Junfei Wu  1   2 , Jiayang Feng  1   2 , Yue Sun  1   2 , Yadi Zhao  1   2 , Longfei Mao  1

    PMID: 40170552 DOI: 10.1177/09603271251332505

Abstract

Introduction

Alcoholic liver disease poses a severe threat to human health. The thyroid hormone Triiodothyronine (T3) is closely related to liver metabolism. This study investigated the effect and mechanism of T3 in alcoholic liver injury.

Methods

Acute alcoholic liver injury model was established in mice by alcohol administration. Alcoholic liver fibrosis models were established in vivo and in vitro using hepatic stellate cells (HSC)-T6 cells and mice. The role and regulatory mechanism of T3 in the occurrence and progression of alcoholic acute liver injury and fibrosis were analyzed by evaluating key factors involved in cell proliferation and apoptosis, inflammatory response, oxidative stress, and autophagy using histopathological staining.

Results

The results showed that T3 at low and medium concentrations reduced inflammation and oxidative damage in acute alcoholic liver injury and inhibited HSC activation and delayed the onset and progression of alcoholic liver fibrosis in mice. T3 inhibited the PI3K/AKT and NF-κB signal pathway, increased Nrf2 expression levels, and restored liver autophagy. However, high T3 concentrations had the opposite effect.

Discussion

Optimal T3 concentrations protects the liver from alcoholic liver injury by inhibiting inflammatory response and oxidative stress injury and by restoring hepatocyte proliferation, apoptosis, and autophagy.

Keywords: alcoholic liver disease; autophagy; hepatic stellate cells; liver fibrosis; oxidative stress; thyroid hormone.

Open access:

https://pubmed.ncbi.nlm.nih.gov/40170552/

https://doi.org/10.1177/09603271251332505

https://journals.sagepub.com/doi/10.1177/09603271251332505

Identification and Characterization of Highly Potent and Isoenzyme-Selective Inhibitors of Deiodinase Type I via a Nonradioactive High-Throughput Screening Method

One of the many problems of hyperthyroidism is the limited number of medicines which act as anti-thyroid agents. The two groups that exist both have the potential for severe side effects/adverse reactions.

Any new agents have the potential for improving hyperthyroidism treatment. This is most especially true given that the accepted alternatives to the existing agents are radioactive iodine and thyroidectomy. Both of which are known to have the potential for numerous side effects and unintended consequences (e.g. damage to parathyroid glands, affecting the voice, salivary glands, etc.)

Even if these agents are not regarded as definitive, they might well allow safe long-term use.

Identification and Characterization of Highly Potent and Isoenzyme-Selective Inhibitors of Deiodinase Type I via a Nonradioactive High-Throughput Screening Method

Rajas Sane  1 , Carola Seyffarth  2 , Sabrina Kleissle  3 , Martin Neuenschwander  2 , Jens Peter von Kries  2 , Caroline Frädrich  1 , Kostja Renko  4 , Eva K Wirth  5   6 , Josef Köhrle  1

PMID: 40170637 DOI: 10.1089/thy.2025.0036 

Abstract

Objective:

Deiodinase type I (DIO1) is crucial in maintaining thyroid hormone (TH) balance. It converts the prohormone thyroxine (T4) to the active triiodothyronine (T3) and degrades T3 to inactive 3,3'-diiodothyronine (3,3'-T2). It also acts on reverse T3 (rT3) and sulfated TH metabolites, thus contributing to TH elimination. Upregulation of DIO1 is linked to hyperthyroid conditions such as Graves' disease and autonomous thyroid adenoma, making it a promising target for pharmacological intervention. The adverse side effects of the antithyroid drug propylthiouracil (PTU), used in clinics to treat hyperthyroidism due to its thyroid peroxidase- and DIO1-blocking action, highlight the need for novel and potent DIO1-selective inhibitors. 

Methods: 

Using a semiautomatic high-throughput screening (HTS) assay based on the Sandell-Kolthoff (SK) reaction in 384-well plates, we screened 69,344 low-molecular-weight compounds for DIO1-inhibitory effects. Shortlisted hits underwent detailed manual characterization, where we evaluated the potency and isoenzyme specificity by assessing their DIO-inhibitory effects on enzyme preparations from all three DIO isoenzymes, over a wide concentration range (5 nM-20 µM). To evaluate the DIO1 inhibitory effects in intact cells, we applied a novel protocol based on the SK reaction to cell culture supernatants and assessed the intracellular deiodinase activity in DIO1 overexpressing HEK293 cells.

Results: 

The robust HTS assay flagged 436 (<1%) of the screened compounds as hits, also including known DIO1 inhibitors such as PTU and genistein. Based on a validation screen of 298 compounds, we prioritized 26 compounds to comprehensively characterize their DIO1-selective inhibition. We identified 15 DIO1-selective compounds (IC50 < 1 µM), more potent than the bonafide DIO1-selective inhibitor PTU. Additionally, 8 of the 13 tested compounds were found capable of inhibiting DIO1 in intact cells.

Conclusions: 

With a successful SK-reaction-based HTS application, we identified novel, potent, and selective inhibitors of DIO1 with nanomolar IC50 values. Furthermore, we successfully showed that some of these compounds were also capable of inhibiting intracellular DIO1 in intact cells. These novel compounds hold immense potential in studying TH modulation, deciphering DIO1 enzyme structure, and developing structure-activity relationships. Furthermore, our novel inhibitors act as lead compounds in developing strategies to combat hyperthyroidism.

Keywords: DIO1; DIO1-inhibitors; deiodinases; high-throughput screening; thyroid hormones.

Levodopa induces thyroid function regulation in a patient with thyroid hormone resistance and Parkinson's disease: a case report

This paper does not imply the use of dopamine/dopamine agonists in thyroid hormone resistance. Though, in time, we might get to understand the mechanisms by which dopamine agonists had the reported effects. Given the low profile of thyroid hormone resistance, and the low numbers of confirmed cases, any published research is to be welcomed.

Levodopa induces thyroid function regulation in a patient with thyroid hormone resistance and Parkinson's disease: a case report

Gabriela Rozo-Paz  1 , Clara Maria Ruiz-Forero  2 , José David Suárez-Mera  3 , Guillermo Monsalve Duarte  4 , William Kattah Calderón  5

PMID: 40171189 PMCID: PMC11958178 DOI: 10.3389/fendo.2025.1536372

Abstract

Introduction:

Thyroid hormone resistance (THR) is a rare genetic syndrome characterized by reduced sensitivity to thyroid hormones. Patients may be asymptomatic, although clinical manifestations depend on the THR subtype. This entity commonly has abnormal thyroid function tests and can be confirmed by molecular analyses.

Case presentation:

The present study describes a 55 year-old female diagnosed with surgically resected papillary thyroid carcinoma. During the endocrinology consults, elevated thyroid hormone levels were detected without an adequate TSH response, and THR was suspected. Moreover, Parkinson's disease was diagnosed, and treatment with levodopa/carbidopa was initiated. Following this regimen, her TSH and total T3 levels were subsequently normalized, which suggests a potential effect of this agent on the normalization of these hormone levels in the blood. In this case, the role of levodopa was crucial to regulate the TSH concentration which was required to carry out the resection of a tumoral remnant.

Conclusion:

The influence of dopamine in the endocrine system, specifically in the thyroid gland, is beneficial in conditions such as THR where abnormal TSH levels can be lowered, helping to balance the thyroid and hormones function.

Keywords: Parkinson’s disease; case report; dopamine; levodopa; thyroid hormone resistance.

Thankfully, a fully open access paper:

https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1536372/full

Variable hyperthyroidism outcomes related to different treatment regimens – an analysis of UK Biobank data

Posting for information. I have not read in detail.

Variable hyperthyroidism outcomes related to different treatment regimens – an analysis of UK Biobank data

Kris Elomaa 1†, Matt Spick 1†, Earn H Gan 2,3, Simon H Pearce 3‡* and Nophar Geifman 1‡*
1 School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
2 Translational and Clinical Research Institute, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK
3 Department of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
† ‡ Contributed equally
* Correspondence: n.geifman@surrey.ac.uk , simon.pearce@ncl.ac.uk
Keywords: hyperthyroidism, Graves’ disease, comorbidity, biomarkers, first-line, radiotherapy,
thionamides, thyroidectomy

Background

UK guidance on the assessment and management of thyroid disease was set out in NICE guideline NG145 in 2019 and is expected to result in an increase in radioactive iodine (RAI) being offered as a first-line definitive treatment for hyperthyroidism.

Methodology

In this work we analyse longitudinal UK Biobank data to assess all-cause mortality and comorbidity risks associated with the main treatment modalities for 793 participants with hyperthyroidism, specifically antithyroid drugs (ATDs), RAI and thyroidectomy.

Results

Participants treated with RAI showed reduced all-cause mortality compared with those treated with ATD alone (time to event ratio 1.8, 95% CI 0.9 – 3.6), albeit the result did not reach statistical significance, as did those treated by thyroidectomy (time ratio 2.0, 95% CI 1.1 – 3.9). For treated patients odds ratios were generally elevated for osteoporosis, cardiovascular events and atrial fibrillation, but again did not reach statistical significance except for those patients treated by ATDs with an odds ratio for atrial fibrillation of 2.2 (95% CI 1.2 – 4.1) versus controls.

Conclusion

Our findings were consistent with those previously reported in the literature, and do not reveal any evidence from the UK Biobank to contradict the safety of RAI being offered as a first-line treatment. The data are also suggestive, however, that treatments do not fully eliminate risks of complications related to hyperthyroidism. This reinforces the need for both clear communication where there may be risks of complications such as osteoporosis, as well as clinical support for patients, even after definitive treatment.

https://etj.bioscientifica.com/view/journals/etj/aop/etj-24-0393/etj-24-0393.xml