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

In vitro efficacy of aqueous PVP-iodine solution below 5% as alternative to preoperative antisepsis in ophthalmology as the basis for an in vivo study

Good to see people questioning standard practice. Also good to see recognition of the potential for a thyroid issue - though they do not seem to see any thyroid issues with the 5% solution.

In vitro efficacy of aqueous PVP-iodine solution below 5% as alternative to preoperative antisepsis in ophthalmology as the basis for an in vivo study

Paula Zwicker, Nevin Opitz, Julia Harris, Andreas Stahl, Ulrich Kellner, Ruth Koelb-Keerl, Philipp S. Muether, Anne Hunold & Axel Kramer 

Abstract

Purpose

Pre-operative antisepsis of the conjunctiva is indicated prior to intraocular surgery to prevent post-interventional endophthalmitis. In Germany, antisepsis with 5% povidone-iodine (PI) aqueous solution is explicitly required prior to intravitreal injections (IVI), and also generally recommended for intraocular surgery. However, this concentration often leads to a foreign body sensation and an unpleasant burning in combination with dry eye symptoms. Postoperative eye pain, persistent corneal epithelial defects, and a risk of keratitis are further side effects. Due to the repetitive nature of IVI, these symptoms are particularly present in IVI patients. A reduced concentration may be favorable to decrease patient discomfort. A 1.25% PI solution does not increase the iodine concentration in the aqueous humor and is also used for prophylaxis of ophthalmia neonatorum and for preoperative antisepsis; in both cases the renal iodine excretion stays in a physiological range thus thyroid diseases are no contraindication for its use. Thus, the efficacy of reduced concentrations of PI should be evaluated in vitro.

Methods

PI with dilutions below 5% (0.625 − 2.5% serial 1:2 dilution) was tested in vitro in a quantitative suspension assay and in a quantitative carrier test without and with addition of matrices to identify their antimicrobial effect against Staphylococcus epidermidis, Pseudomonas aeruginosa, Cutibacterium acnes and Candida albicans.

Results

No differences in the antimicrobial effect was seen due to reduced concentrations of PI in comparison to a 5% solution. However, a trend was seen regarding the required contact time of the antiseptic solution.

Conclusion

The in-vitro tests have shown adequate antisepsis of 1.25% PI prior to intraocular surgery. However, it is important to pay attention to a sufficient contact time of the antiseptic of about 1 min before ophthalmologic intervention. In order to give final recommendations, in vivo testing is needed to build a robust data foundation.

Highlights

5% PVP-Iodine solution prior IVI leads to unpleasant side effects.

In vitro, antimicrobial effect of 5% PI is comparable to that of 1.25% PI.

Addition of matrices had no visible effects on antimicrobial activity.

Contact time of 1 min is necessary.

Unusually, an Open Access paper:

https://joii-journal.springeropen.com/articles/10.1186/s12348-025-00489-3

Hashimoto's thyroiditis- What's in a name?

This paper is ultimately confusing.

I agree with abandoning the eponym Hashimoto's thyroiditis. (Though, at least in the abstract of the paper, the eponym Ord's thyroiditis isn't even recognised.)

But I strongly disagree with the assertion that we should not test for thyroid autoantibodies, and we should avoid imaging. Another case of ensuring that by not looking, you won't find?

In common with many other diseases/disorders, it might be useful to subdivide "autoimmune thyroiditis" and/or "autoimmune thyroid disease" into those with various antibodies or other features. And you also need to include those who are hypothyroid despite not having been diagnosed with either of the classic antibodies.

I very much question how many asymptomatic people are ever diagnosed and treated. Rather, I suspect that numerous signs and symptoms are missed/ignored as they are not recognised as the classic indicators of autoimmune thyroid disease - or, indeed, non-autoimmune thyroid disease. After all, we see multiple posts by HealthUnlocked forum members who have what appear euthyroid results for the TSH test (often the only test), and Free T4, and (if ever done) Free T3. This is part of the course of the disease for many. A variation of thyroid hormone levels, with possibly unclear other symptoms, and potentially over years.

And it bizarrely tells us not to use the word "disease", then discourages the use of the word when only tests and imaging show the issues, but gives no replacement word? How about "autoimmune thyroid not yet recognised as disease"?

Hashimoto's thyroiditis- What's in a name?

Mikhail Khachaturov  1 , Dimitrios G Goulis  2 , Petros Perros  3

    PMID: 40172784 DOI: 10.1007/s42000-025-00646-2

Abstract

Hashimoto's thyroiditis (HT) is the most common autoimmune endocrine disease worldwide with an annual incidence of 0.3-1.5 per 1000 people and a prevalence of 8% of the general population. At least nine terms appear in the literature denoting HT, which are used as synonyms or are terms describing disorders closely related to HT. Moreover, the definitions of HT vary, and the role of several parameters in making a diagnosis remains unclear. Furthermore, the term "thyroiditis" is often used among experts to describe the triphasic evolution in thyroid status (thyrotoxicosis, hypothyroidism, and euthyroidism) that can occur not only after some forms of HT but also in other causes of thyroid inflammation. The present work proposes novel approaches for the nomenclature problems. Firstly, we should abandon the eponym "Hashimoto" in keeping with recent trends. The void left can be replaced by the terms "autoimmune thyroiditis" or "autoimmune thyroid disease", which are already in use. In communicating among ourselves and with patients, it is imperative and good practice to provide, whenever possible, context to these terms by specifying whether they apply to thyroid status, presence or absence of goiter, thyroid autoantibodies, imaging, cytology/histology, epidemiology, or etiology. Secondly, the considerable potential harm associated with treating euthyroid people with thyroid hormones could be curtailed by avoiding testing for thyroid autoantibodies or performing thyroid imaging in asymptomatic euthyroid patients following the current guidelines and by discouraging the use of the word "disease" when the evidence is based only on results of investigations, such as positive antibodies, or imaging.

Keywords: Definition; Endocrinology; ICD-11; Immunology; Nomenclature; Pathology; Radiology.

https://link.springer.com/article/10.1007/s42000-025-00646-2

Mendelian randomization reveals causal effect of Hashimoto's thyroiditis on immune thrombocytopenic purpura

There are towards a dozen or so posts on the HealthUnlocked Thyroid UK forum ( https://healthunlocked.com/thyroiduk/ ) which mention "purpura", "immune thrombocytopenic purpura", "idiopathic thrombocytopenic purpura" or "immune thrombocytopenia". And I suspect numerous other which do not use these formal terms - or mention petechiae, etc.

Hence this paper on the association/relationship of Hashimoto's Thyroiditis and purpura seems potentially of interest and relevance.

DermNet NZ, as so often, provides a good description of and introduction to Purpura, if you need it:

https://dermnetnz.org/topics/purpura

Mendelian randomization reveals causal effect of Hashimoto's thyroiditis on immune thrombocytopenic purpura

ABSTRACT
Introduction

Patients with immune thrombocytopenic purpura (ITP) usually express thyroid antigen-specific antibodies. The purpose of this study was to explore the causal relationship between Hashimoto's thyroiditis (HT) and ITP.
Methods

A two-sample Mendelian randomization (TSMR) analysis was applied to investigate the potential causal relationship between HT and ITP in European population. Five complementary methods including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode were performed in our study. Risk genes of HT and ITP were selected through Mendelian randomization (MR), and the common risk genes were further analysed by bioinformatics methods to explore the common pathogenesis of the two diseases.
Results

The MR analysis revealed a potential causal relationship between HT and risk of ITP [odds ratio (OR) = 1.22; 95% confidence interval (CI) 1.01, 1.49; P = 0.046]. Gene eQTL data were obtained from the IEU database. HT and ITP were respectively treated as outcome variables for MR analysis, and a total of 32 common risk genes were selected, including 12 high-risk genes and 20 low-risk genes. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that risk genes were closely related to antigen processing and presentation, and played a crucial role in the process of various viral and bacterial infections.
Conclusion

Our study demonstrated that HT may increase the risk of ITP, and revealed the role of their common risk genes in the development of the two diseases.

Full paper currently accessible here:

https://www.tandfonline.com/doi/10.1080/16078454.2025.2484959

(The PDF is not currently accessible.)

Does Higher Dairy Intake Reduce CRC [colorectal cancer] Risk?

A Medscape article. (You might need to sign-up to read it. It is free.) 

It does question whether dairy-free diets are always a good choice.

Maybe it is worth considering that Ötzi the Iceman had dairy food in his stomach despite being lactose-intolerant? It could be that what he ate was fermented in some way resulting in low lactose content.

Yogurt, kefir, cheese, sour cream, and many others. Here's a link to Wiki's list of such foods which demonstrates how widespread they are:

https://en.wikipedia.org/wiki/List_of_fermented_milk_products

Does Higher Dairy Intake Reduce CRC Risk?

Tara Haelle

March 28, 2025

Two recent studies have added to the growing body of research suggesting consuming more dairy reduces a person’s risk of getting colorectal cancer.

A prospective cohort study in Nature Communications published in January looked at the incidence of colorectal cancer (CRC) in more than 540,000 UK women over 16 years and found a 14% reduced risk for the cancer for every 200 g of dairy milk consumed per day. It also found an 8% reduced risk per 50 g of yogurt per day.

Article continues here:

https://www.medscape.com/viewarticle/does-higher-dairy-intake-reduce-crc-risk-2025a10007fn?form=fpf

 

What happens to T3?

If you are familiar with thyroid hormones, you will probably be aware that the interaction of the T3 hormone (tri-iodo-thyronine) with the T3 receptor is how it has its effects on cells.

We need enough T3 - much of which will be transported into our cells from the bloodstream. (Some might be formed by de-iodinating T4 within cells. But I'm desperately trying to simplify this to the extreme!)

The diagram below illustrates T3 (whether supplied to the cell as T3 or converted within the cell) to the T3 receptors in the nucleus. 

We often see descriptions of T3 (and many other substances) reaching their receptors as if a key is being put into a lock. And that makes it very clear that only the specific substance can actually properly activate the receptor. Other substances could potentially block a receptor, or act rather like the the proper substance - but often with less (or more) stimulation of the receptor.

For example:

• Blocking TSH-receptor antibodies prevent the usual TSH stimulating the thyroid gland to produce and release thyroid hormone.
• Stimulating TSH-receptor antibodies act more powerfully than the usual TSH thus stimulating the thyroid gland to produce and release excess thyroid hormone. Which is the fundamental issue in Graves disease.

But what is almost never discussed is what happens to the T3 when it has locked into the receptor. How long does it remain there? What eventually makes the receptor releasee it? Why doesn't that T3 molecule immediately re-attach to that same receptor? Or, if that receptor has become exhausted, why does it not attach to another T3 receptor?

Or does the T3 attach to several T3 receptors in succession?

I find it difficult to see how to combine the processes that would appear obvious with the extremely tight requirement for T3.

If one T3 molecule can attach to multiple receptors, what controls the total number?

Does the T3 molecule released by the T3 receptor get expelled from the cell?

Does the T3 molecule get degraded in some way? Or converted into T2? In which case we need to go through the same questions regarding T2 and T2 receptors!

 

Intramuscular and Subcutaneous Levothyroxine: Success in Treating Refractory Hypothyroidism

An interesting case. Not least that it ends up with self-administration of subcutaneous injections. After all, we see B12 patients being told they cannot self-administer because the B12 products are only licensed for intramuscular administration. And the current Serb injectable levothyroxine says intramuscular or intravenous. But not subcutaneous.

If you at all interested, it is strongly recommended that you read the full paper - which is well-written and easy to follow.

Intramuscular and Subcutaneous Levothyroxine: Success in Treating Refractory Hypothyroidism

Eur Thyroid J. 2025 Mar 1:ETJ-25-0012. doi: 10.1530/ETJ-25-0012. Online ahead of print.
Authors

Nadia Chaudhury  1 , Winston Crasto  2 , Ponnusamy Saravanan  3 , Vinod Patel  4

1 N Chaudhury, Department of Diabetes and Endocrinology, George Eliot Hospital NHS Trust, Nuneaton, CV10 7DJ, United Kingdom of Great Britain and Northern Ireland.
2 W Crasto, George Eliot Hospital NHS Trust, Nuneaton, United Kingdom of Great Britain and Northern Ireland.
3 P Saravanan, University of Warwick Medical School, Coventry, United Kingdom of Great Britain and Northern Ireland.
4 V Patel, University of Warwick Medical School, Coventry, United Kingdom of Great Britain and Northern Ireland.
PMID: 40163437
DOI: 10.1530/ETJ-25-0012

Abstract

Introduction: 

Refractory hypothyroidism often poses a clinical problem as treatment regimens are difficult to individualise to the patient and feasibility of its delivery is difficult to organise within a health care system. We present a patient who became intolerant of intramuscular (IM) levothyroxine (LT4) after 18 years of treatment, thus subcutaneous (SC) LT4 was initiated.

Case presentation: 

13-year-old female with newly-diagnosed hypothyroidism, remained hypothyroid despite escalating doses of oral LT4 and LT3. Thyroxine malabsorption was further suggested by nasogastric administration of LT4, whereby high dose thyroxine administration resulted in only 2.8 pmol/L increase in free T4 level (normal >5.14pmol/L). She eventually achieved long-term euthyroid status at age of 18 with fortnightly IM LT4, alongside oral LT4 and LT3. This was maintained for 18 years. Unfortunately, scar tissue developed around injection sites, resulting in increased pain and difficulty of administration. SC LT4 was trialled with success, and she has remained euthyroid for the last six years with self-administration and minimal side effects.

Conclusion: 

Refractory hypothyroidism often presents a challenge for clinicians, both for diagnosis and management. We discuss a patient with longest follow-up to-date within the published literature for both IM and SC LT4 for patient-administered treatment of refractory hypothyroidism and review the literature on alternative formulations available.

PubMed index link here:

https://pubmed.ncbi.nlm.nih.gov/40163437/

Full paper accessible here:

https://etj.bioscientifica.com/view/journals/etj/aop/etj-25-0012/etj-25-0012.xml

Prevalence and characteristics of adults avoiding gluten without celiac disease: a long-term population-based follow-up study

This paper is not directly a thyroid issue but the number of those with thyroid issues who choose to avoid gluten seems to be significant. Hence it could be relevant.

The paper doesn't explain the issues. Rather it reports on the prevalence and makes a few observations. Of course, until an issue is reported, there is unlikely to be research which explains them. That makes it potentially important.

Prevalence and characteristics of adults avoiding gluten without celiac disease: a long-term population-based follow-up study.

Tiainen M 1 , Kurppa K 1 , Jääskeläinen T 2 , Kaartinen N 2 , Huhtala H 3 , Kaukinen K 1 , Taavela J 1

BMC Gastroenterology, 25 Mar 2025, 25(1):199
https://doi.org/10.1186/s12876-025-03799-x PMID: 40133823 PMCID: PMC11938570

Abstract

Objective

Nationwide prevalence studies on people avoiding gluten without celiac disease (PWAG) are lacking, and in particular, long-term follow-up studies are unavailable. We aimed to evaluate the prevalence, incidence, and characteristics of PWAG in a population-based cohort in 2000 and 2011.

Methods

Health and diet-related data were collected in nationwide Health 2000 and 2011 surveys, which comprised 5,777 and 3,866 individuals, respectively, representing 2,682,733 and 1,967,876 Finnish adults. Serum samples were taken for the measurement of transglutaminase autoantibodies. In total 3,296 individuals participated in both surveys, forming a prospective cohort. PWAG refers to subjects avoiding gluten without celiac disease or positive autoantibodies. Psychological health was assessed with General Health Questionnaire and the Beck Depression Inventory.

Results

The prevalence of PWAG increased significantly from 0.2% (2000) to 0.7% (2011) (p < 0.001), with the highest prevalence (1.3%) detected in individuals > 70 years old. An annual incidence rate of 42 (95% confidence interval 25-71) per 100,000 persons was noted. The PWAG group was more likely to maintain additional special diets than those not avoiding gluten, including e.g. lactose-free diet (41.7% vs. 12.0% in 2011, p < 0.001) and food restriction for allergy (12.5% vs. 3.0%, p = 0.007). Beck Depression Inventory indicated more depression (p = 0.023) among PWAG in 2000, while no difference was seen in 2011 or in General Health Questionnaire. Celiac disease-related risk factors, including female gender, anemia, autoimmune diseases or antibody levels near the upper limit of normal in 2000, did not predict later gluten avoidance.

Conclusions

The prevalence of PWAG multiplied over a decade, reaching 0.7% in 2011 in Finland. The PWAG group maintained more likely additional dietary restrictions than those not avoiding gluten and had signs of psychosocial burden. No predicting factors for the condition were identified.

Full text open access from both links:

https://europepmc.org/article/MED/40133823

https://doi.org/10.1186/s12876-025-03799-x

The role of the hypothalamic–pituitary–thyroid axis in thyroid cancer

Use of TSH-suppressing doses of thyroid hormone after thyroidectomy or radioactive iodine treatment for thyroid cancers has long been a common practice.

In more recent years, opinion appears to have moved to using a TSH-suppressing dose to begin with, then reducing it to a more standard dosing level (e.g. one which sees TSH rise towards the reference interval).

While this paper continues down this route, without access to the full paper it is difficult to properly and fully appreciate their rationale.

ReviewVolume 13, Issue 4p 333-346 April 2025

The role of the hypothalamic–pituitary–thyroid axis in thyroid cancer

Laura Abaandou, PhD† ∙ Raisa Ghosh, MD† ∙ Joanna Klubo-Gwiezdzinska, MD PhD joanna.klubo-gwiezdzinska@nih.gov

DOI: 10.1016/S2213-8587(24)00364-4

Summary

The hypothalamic–pituitary–thyroid axis plays a crucial role in the pathogenesis, diagnosis, risk stratification, effectiveness of radioiodine therapy, and treatment response evaluation in epithelial thyroid cancer. Supraphysiological doses of levothyroxine are used in patients with intermediate-risk and high-risk thyroid cancer to suppress thyroid-stimulating hormone (TSH) to prevent tumour progression. However, free thyroxine and tri-iodothyronine have also been found to promote tumour growth in thyroid cancer preclinical models. Moreover, current evidence remains inconclusive about the role of TSH suppression in improving survival outcomes and reveals an increased risk of cardiovascular and skeletal adverse events after long-term exposure to excess levothyroxine. Stimulation of the axis with either recombinant human TSH or thyroid hormone withdrawal has been proven equally effective for diagnostic purposes and for facilitating radioiodine uptake for thyroid remnant ablation, but evidence is insufficient for non-inferiority of recombinant human TSH-based vs thyroid hormone withdrawal-based stimulation before radioiodine therapy of distant metastases.

This paper is, as so many papers are, behind a paywall:

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00364-4/abstract

This is also available on link below - which includes  few extra snippets:

https://www.sciencedirect.com/science/article/abs/pii/S2213858724003644

We keep hearing of doctors who deny that cholesterol levels are linked to hypothyroidism. The comments on forum often say something like “they used to use cholesterol as an indicator of thyroid levels”. However, rarely has this actually been complemented by a link, a quote, of an actual example.

I found this case report, one of nine in the paper, when I was looking for something else. It was published in the British Medical Journal in 1950.

In addition to the specific cholesterol issue, some may find interest in what was happening around the time thyroxine started to become available.

ORAL THYROXINE IN TREATMENT OF
MYXOEDEMA
BY
F. DUDLEY HART, M.D., F.R.C.P.
Assistant Physician, Westminster Hospital; Lecturer in
Applied Pharmacology, Westminster Medical School
AND
N. F. MACLAGAN, D.Sc., M.D., M.R.C.P.
Professor of Chemical Pathology in University of London
at Westminster Medical School; Chemical Pathologist to
Westminster Hospital

Case 2 (See Fig. 2)

A married woman aged 63 was diagnosed as a case of myxoedema in 1936, and treated with dried thyroid extract.

1946, after ten years' treatment, she ceased to attend. After eighteen months there was a gradual return of symptoms.

On examination typical myxoedema was noted. Her blood pressure was 170/100. Renal function was 64% of normal.

The initial B.M.R. was -21%, and serum cholesterol 437 mg. per 100 ml.

Treatment.-

DL-thyroxine 1 mg. daily was given. Within a week she began to feel better and lost weight. In a fortnight her voice had almost returned to normal. Serum cholesterol dropped to 205 mg., and urea clearance rose to 81% of normal.

Improvement was in every way satisfactory. Thyroxine was increased to 1.4 mg. a day. Her only disability was that the hair continued to fall out. Her energy was still slightly sub-
normal. Thyroxine was increased to 1.8 mg. a day. One month later she stated that she had stopped "falling about” and was now entirely steady on her feet, although her gait had always been unsteady since the onset of myxoedema. Her hair was now falling out much less. Treatment was changed to DL-sodium thyroxine 1 mg. a day, then reduced to 0.6 mg. after two months. Two months later treatment was changed to L-sodium thyroxine (0.3 mg. a day).

Comment.-

Improvement was entirely satisfactory when on 1 mg. of DL-thyroxine sodium. Her B.M.R. rose to +22% and serum cholesterol dropped to 206 mg. On the reduced dosage she continues to be well. She appears to be at her best when [u]the cholesterol reading is slightly raised[/u] and the B.M.R. is within the normal range. The only time the cholesterol figure has been within normal limits was when other symptoms suggested that dosage was excessive. She has been on L-thyroxine sodium for four months. Her present dose is 0.2 mg. a day. The observation period was one year five months.

https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2037331&blobtype=pdf

Explanatory notes:

B.M.R. - Basal Metabolic Rate 

DL-thyroxine-sodium - a mixture of L-thyroxine (which we widely call levothyroxine) and D-thyroxine which is no longer used. D-thyroxine is not the form found in our bodies. It required much higher doses and was eventually recognised as causing heart issues. Which is why we now only see L-thyroxine. It also partly the doses quoted appearing much higher than we see today. It is also possible that the less exacting purity of the product, and issues about how it was delivered, also affected requirements.

Application of Thyroid Hormones in Women's Hair for the Non-Invasive Prediction of Graves' Disease

An interesting development in the realm of FT4 and FT3 testing.

Application of Thyroid Hormones in Women's Hair for the Non-Invasive Prediction of Graves' Disease
Kouhei Igarashi  1   2 , Chie Takita  1   2 , Masako Matsumoto  3 , Wataru Kitagawa  4 , Atsuko Ota  2 , Naoko Miyazaki  5 , Koichi Ito  4 , Kazutaka Ikeda  1   6
Affiliations

    PMID: 40149889 DOI: 10.3390/biom15030353

Abstract

Graves' disease (GD) is an autoimmune disorder that can be difficult to distinguish from other diseases due to symptom similarity. The exacerbation of GD owing to delayed diagnosis is a serious issue, and a novel accessible health screening system is needed. Therefore, this study investigated the association between GD and thyroid hormone levels in women's hair and evaluated the prediction accuracy of this non-invasive type of sample. By optimizing pretreatment and analysis techniques using liquid chromatography-mass spectrometry (LC-MS), free triiodothyronine (FT3) and thyroxine (FT4) could be detected in only 2 mg of hair with high sensitivity. Compared with healthy controls, the thyroid hormone levels in the hair of GD patients were significantly higher in correlation with blood levels. The predictive ability of hair thyroid hormones was analyzed using a receiver operating characteristic (ROC) curve, and the optimal cut-off value was determined via the Youden index. As a result, the area under the curve (AUC) was 0.974 (95% confidence interval (CI): 0.935-1.000) for FT3 and 0.900 (95% CI: 0.807-0.993) for FT4. The cut-off value was 0.133 pg/mg (sensitivity: 91.2%; specificity: 100%; positive predictive value (PPV): 100%; negative predictive value (NPV): 76.9%) for FT3 and 0.067 pg/mg (sensitivity: 70.6%; specificity: 100%; PPV: 100%; NPV: 50.0%) for FT4. Collectively, our new approach offers the possibility of accurately and non-invasively detecting GD using hair samples. Since hair can be stored and transported at room temperature, this system facilitates large-scale screening at locations including hair salons and homes, potentially enabling the early determination of GD outside of medical facilities.

Keywords: Graves’ disease; health check; lipidomics; mass spectrometry; non-invasive hair screening; thyroid hormone.

Igarashi, K., Takita, C., Matsumoto, M., Kitagawa, W., Ota, A., Miyazaki, N., Ito, K., & Ikeda, K. (2025). Application of Thyroid Hormones in Women's Hair for the Non-Invasive Prediction of Graves' Disease. Biomolecules, 15(3), 353. https://doi.org/10.3390/biom15030353

https://pubmed.ncbi.nlm.nih.gov/40149889/

29/03/2025

Thyroid Hormones and Metabolism Regulation: Which Role on Brown Adipose Tissue and Browning Process?

We have two types of adipose tissue (fat cells) - white and brown.

White adipose tissue is primarily fat storage.

Brown adipose tissue is capable of generating heat directly by metabolic processes. Not by shivering. Not by any muscle actions.

White fat cells, adipocytes, can convert to brown adipocytes. 

This conversion is controlled, at least in part, by thyroid hormones.

(You might occasionally see discussion of beige adipocytes.)

Thyroid Hormones and Metabolism Regulation: Which Role on Brown Adipose Tissue and Browning Process?
Laura Sabatino  1 , Cristina Vassalle  2
Affiliations

    PMID: 40149897 DOI: 10.3390/biom15030361

Abstract

Thyroid hormones (THs) are important modulators of many metabolic processes, being strictly associated with the control of energy balance, mainly through activities on the brain, white and brown adipose tissue, skeletal muscle, liver, and pancreas. In this review, the principal mechanisms of TH regulation on metabolic processes will be discussed and THs' relevance in metabolic disease progression will be evaluated, especially in the cardiovascular context and correlated diseases. Moreover, we will discuss THs' regulatory role on metabolic events in white and brown adipose tissue, with a special focus on the process of "browning", which consists of the gradual acquisition by white adipocytes of the physical and functional characteristics of brown adipocytes. The advancements in research on molecular mechanisms and proposed physiopathological relevance of this process will be discussed.

Keywords: brown adipose tissue; browning; metabolism; thyroid hormones.

Sabatino, L., & Vassalle, C. (2025). Thyroid Hormones and Metabolism Regulation: Which Role on Brown Adipose Tissue and Browning Process? Biomolecules, 15(3), 361. https://doi.org/10.3390/biom15030361

https://www.mdpi.com/2218-273X/15/3/361

29/03/2025

helvella - Fasting for blood tests

My view is this: Always fast for blood tests.

My logic is this:

For most tests, most of the time, fasting might make no difference. Sometimes fasting might make a modest difference. But there are some tests which must be done fasting.

Say we don’t usually fast. Then we are scheduled to have a test which definitely requires fasting.

If that is the only test we are having, fine.

If we have that test in combination with other tests, ones which do not need fasting, this time they are done in a fasting state. Though previously the same tests might have been done without fasting.

Any effects due to fasting (or not), even if small, make comparison with previous tests just a bit more questionable. Was that a real and potentially important difference? Or was it due solely to fasting?

Always fast and the question disappears.

helvella - Testing Companies

This links to Lola Health who have possibly the best range of testing offers which include visiting phlebotomists. For some people, this option makes the difference between being able to get a test done - and not.

Personal experience showed that they are efficient and the doctors' interpretations were properly considered and helpful. Obviously this is on a very small number of tests.

Link to Lola Health

(You can avoid using the referral link above, if you wish: Lola Health without referral.)

Thyroid UK lists several private testing labs. However, there are other private testing labs which are NOT listed but might be particularly helpful to some people.