Publications

ORIGINAL MANUSCRIPTS (reverse chronological order)

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2019 European Thyroid Association guidelines on the management of thyroid dysfunction following immune reconstitution therapy. I Muller, C Moran, B Lecumberri, B Decallone, N Robertson, J Jones, CM Dayan. European Thyroid Journal 2019 Jul;8:173–185. DOI: 10.1159/000500881

Link to the paper: https://www.karger.com/Article/FullText/500881
Allegato: Screenshot 8.9.19 but Cambridge paid open access


ENGLISH summary: 2019 Guidelines of the European thyroid association for the clinical management of thyroid disorders induced by immune reconstitution. This commonly happens in three settings: 1) following alemtuzumab (Lemtrada®) treatment for multiple sclerosis; 2) after treatment of HIV infected patients with HAART; 3) following allogeneic bone marrow transplantation or hematopoietic stem cell transplantation.
ITALIAN summary: Linee guida 2019 dell' Associazione Europea della Tiroide sulla gestione clinica delle patologie tiroidee indotte da ricostituzione immunitaria. Questa complicanza si verifica comunemente in 3 condizioni: 1) dopo trattamento con alemtuzumab (Lemtrada®) in pazienti con sclerosi multipla; 2) dopo trattamento con HAART in pazienti HIV positivi; 3) dopo trapianto di midollo osseo o cellule staminali ematopoietiche


Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase 1 study. SHS Pearce, CM Dayan, DC Wraith, K Barrell, N Olive, L Jansson, T Walker-Smith, C Carnegie, KF Martin, K Boelaert, J Gilbert, CE Higham, I Muller, RD Murray, P Perros, S Razvi, B Vaidya, F Wernig, GJ Kahaly. Thyroid 2019 Jul;29(7):1003-1011.

Link to the paper: https://www.liebertpub.com/doi/full/10.1089/thy.2019.0036
Allegato: Scaricabile direttamente dal sito (Open Access)
ENGLISH summary: Encouraging results for a totally new approach for the treatment of Graves' disease (autoimmune hyperthyroidism). We tried "to educate" the immune system avoiding immunosuppression and aiming to spare the thyroid gland (the most popular target of current treatments, even if "not the culprit"). Always remember that good research takes time: years of future larger studies are needed to validate this potential new drug ... stay tuned! PS: Thanks a lot to all patients and people involved in this innovative UK multi-centre clinical trial!
Riassunto ITALIANO: Risultati incoraggianti ottenuti da un approccio totalmente nuovo per il trattamento del morbo di Basedow/Graves’ (ipertiroidismo autoimmune). Abbiamo tentato "di rieducare" il sistema immune senza ricorrere all'immunosoppressione e allo scopo di risparmiare la ghiandola tiroidea (il bersaglio più comune delle terapie in uso oggi, anche se "innocente"). Ricordate sempre che la ricerca ben condotta richiede tempo: sono necessari anni di futuri studi su un maggior numero di pazienti per poter confermare questo potenziale nuovo trattamento ... restate sintonizzati! PS: Infinite grazie a tutti i pazienti e alle persone coinvolte in questo innovativo studio clinico multicentrico condotto nel Regno Unito!


Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies. N Wilson, RS Steadman, I Muller, MS Draman, A Rees, P Taylor, CM Dayan, ME Ludgate, L Zhang. International Journal of Molecular Sciences 2019, 20, 2675.

Link to the paper: https://www.mdpi.com/1422-0067/20/11/2675
Allegato: Open Access Screenshot 8.9.19


ENGLISH summary: The molecule hyaluronan is a key regulator (inhibitor) of human adipose tissue production (“adipogenesis”).
ITALIAN summary: La molecola “acido ialuronico” è un regolatore chiave (inibitore) della produzione di tessuto adiposo umano (“adipogenesi”).


The antigenic link between thyroid autoimmunity and breast cancer. I Muller, PJ Barrett-Lee. Seminars in cancer biology 2019 May 22. DOI: 10.1016/j.semcancer.2019.05.013. [Epub ahead of print].

Link to the paper: https://www.sciencedirect.com/science/article/pii/S1044579X19300434?via%3Dihub
Allegato: Screenshot 8.9.19


ENGLISH SUMMARY: This review summarises what is currently known about the relationship between thyroid autoimmunity and breast cancer. The two diseases are connected and the target organs (thyroid, breast) have several biological similarities.
Riassunto in ITALIANO: Questo lavoro riassume cosa è noto al momento sull’associazione tra autoimmunità tiroidea e carcinoma della mammella. Le due malattie sono connesse, e gli organi coinvolti (tiroide, mammella) presentano varie similarità biologiche.


Prostaglandin F2-alpha eye drops (Bimatoprost) in Graves’ orbitopathy: a randomized controlled double-masked crossover trial (BIMA trial). MS Draman, D Morris, S Evans, A Haridas, J Pell, R Greenwood, C Foy, P Taylor, P Pooprasert, I Muller, L Zhang, C Lane, O Okosieme, M Ludgate, C Dayan. Thyroid 2019 Apr;29(4):563-572.

Link to the paper: https://www.liebertpub.com/doi/abs/10.1089/thy.2018.0506?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=thy
Allegato: NON DISPONIBILE.
ENGLISH summary: Bimatoprost is a drug known to reduce adipose tissue formation in laboratory experiments; in this study we tested whether it was able to induce the same effect in patients with Graves’ orbitopathy, thus expecting a reduction in their eyes protrusion. Bimatoprost treatment did not benefit Graves’ orbitopathy in its late inactive phase. Future studies are needed to test such therapeutic option in the early active phase.
ITALIAN summary: Il trattamento con Bimatoprost non è risultato efficace nell’ oftalmopatia di Basedow/Graves in fase tardiva ed inattiva. Nuovi studi sono necessari per esplorare tale opzione terapeutica in fase precoce ed attiva di malattia.


Liothyronine cost and prescriptions in England. PN Taylor, S Razvi, I Muller, J Wass, CM Dayan, K Chatterjee and K Boelaert. Lancet D&E 2019 Jan; 7(1):11-12.

Link to the website: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30334-6/fulltext
Allegato: NON DISPONIBILE.
ENGLISH summary: Levothyroxine (LT4) is the principal drug prescribed for hypothyroidism (insufficient levels of thyroid hormones), however in some patients T3 can be also prescribed in combination with LT4, or alone. In England the cost of liothyronine (T3) drug have had a huge rise (>5000%) in the recent years (2013-2018). We discovered that this caused a drop of prescriptions especially in the most economically deprived areas, where patients lost access to the drug. Urgent measures are needed to reduce the price of T3 drug in England, and ensure its availability to all patients.
Riassunto ITALIANO: Il forte incremento di prezzo del farmaco per l'ipotiroidismo "liotironina" (T3) nel Regno Unito (>5000%!) ha causato la perdita di accesso al farmaco soprattutto per i ceti sociali meno abbienti


Longitudinal characterization of autoantibodies to the thyrotropin receptor (TRAb) during alemtuzumab therapy: evidence that TRAb may precede thyroid dysfunction by many years. I Muller, M Willis, S Healy, T Nasser, S Loveless, S Butterworth, L Zhang, MS Draman, PN Taylor, N Robertson, CM Dayan and ME Ludgate. Thyroid 2018 Dec;28(12):1682-1693.

Link to the paper: https://www.liebertpub.com/doi/abs/10.1089/thy.2018.0232?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=thy
Allegato: Screenshot 8.9.19


ENGLISH summary: We discovered that autoantibodies to the thyrotropin receptor (TRAb), the key player of a thyroid autoimmune disease named “Graves’ disease”, represent a biomarker helping to predict which patients will develop thyroid dysfunction after receiving alemtuzumab treatment for multiple sclerosis. Alemtuzumab is an effective treatment for multiple sclerosis, however it triggers the development of thyroid autoimmunity and dysfunction in more than one third of treated patients. So far only limited predictors of such adverse event are available. Future studies are needed to develop a comprehensive model including several predictors allowing to individuate from baseline (before receiving alemtuzumab treatment) which patients are at risk to develop subsequent thyroid dysfunction.
ITALIANO: Abbiamo scoperto un nuovo marcatore che aiuta a predire quali pazienti svilupperanno disfunzioni tiroidee dopo terapia con alemtuzumab per la sclerosi multipla: gli autoanticorpi anti-recettore del TSH (TRAb), dosati tramite specifici saggi di laboratorio.


Thyroid function in pregnancy. I Muller, PN Taylor, JH Lazarus. Ann Thyroid 2018 Nov doi: 10.21037/aot.2018.10.05.

Link to the paper: http://aot.amegroups.com/article/view/4567/5508
Allegato: Open Access See conversation Copyright in the paper’s folder


ENGLISH SUMMARY: To keep normal levels of thyroid hormones during pregnancy is crucial for a positive pregnancy outcome and a correct foetal development, especially in the first trimester. Here we summarise how to monitor maternal thyroid function during pregnancy and how to diagnose and manage gestational thyroid dysfunctions.
Riassunto in ITALIANO: Il mantenimento di normali valori di ormoni tiroidei durante la gestazione è fondamentale sia per un esito favorevole della gravidanza, sia per un corretto sviluppo del feto. Qui riassumiamo come monitorare la funzione tiroidea durante la gestazione e come diagnosticare e gestire la disfunzione tiroidea in gravidanza.


Hypercalcaemia with undetectable parathormone levels. I Muller, LD Premawardhana. BMJ-British Medical Journal 2018 Nov 8;363:k4074.

Link to the paper: https://www.bmj.com/content/363/bmj.k4074
Allegato:


ENGLISH summary: A 54-year old woman presented with nausea and vomit, unintentional weight loss, constipation, low blood pressure, hypercalcaemia, a long history of smoking. Several different diseases can induce these clinical signs and symptoms: what was the correct diagnosis in this case? This woman was affected with an unusual clinical presentation of severe hyperthyroidism (excessive production of thyroid hormones) due to Graves' disease (an autoimmune disease inducing a persistent over-function of the thyroid gland).
Riassunto in ITALIANO: Una donna di 54 anni forte fumatrice da molti anni veniva ricoverata per nausea, vomito, perdita di peso non intenzionale, stitichezza, bassa pressione sanguigna, ipercalcemia. Varie malattie diverse possono causare questi sintomi e segni: qual è la diagnosi corretta in questo caso? Questa donna era affetta da una presentazione atipica di ipertiroidismo severo (eccessiva produzione di ormoni tiroidei) dovuto al morbo di Basedow/Graves’.


Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features. N Pariani, M Willis, I Muller, S Healy, T Nasser, A McGowan, G Lyons, J Jones, K Chatterjee, C Dayan, N Robertson, A Coles and C Moran. Journal of Clinical Endocrinology and Metabolism 2018 Aug 1;103(8):3010-3018. doi: 10.1210/jc.2018-00359

Link to the paper: https://academic.oup.com/jcem/article/103/8/3010/5033322
Allegato: Open Access


ENGLISH summary: Alemtuzumab is an effective treatment for multiple sclerosis, however it triggers the development of thyroid autoimmunity and dysfunction in more than one third of treated patients. Here we summarise the clinical course of patients with thyroid disorders induced by alemtuzumab, and the differences with the spontaneous forms.
Riassunto in ITALIANO: L’Alemtuzumab è un trattamento efficace per la sclerosi multipla, tuttavia provoca l’insorgenza di autoimmunità e disfunzione tiroidea in circa un terzo dei pazienti trattati. Qui riassumiamo l’andamento clinico di pazienti affetti da disfunzioni tiroidee indotte dall’alemtuzumab, e le differenze presenti con le forme spontanee.


Combining microRNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy. L Zhang, G Masetti, G Colucci, M Salvi, D Covelli, A Eckstein, U Kaiser, MS Draman, I Muller, M Ludgate, L Lucini, and F Biscarini. Scientific Reports 2018 May 30;8(1):8386. doi: 10.1038/s41598-018-26700-1

Link to the paper: https://www.nature.com/articles/s41598-018-26700-1
Allegato: Open Access


ENGLISH summary: We used proteomic and miRNA analyses, combined with robust bioinformatics, to identify circulating biomarkers to diagnose Graves’ disease, predict the disease status of Graves’ orbitopathy and optimize patient management.
Riassunto in ITALIANO: Abbiamo usato analisi proteomica e dei miRNA, combinate con bioinformatica robusta, al fine di identificare bio-marcatori ematici per diagnosticare il morbo di Basedow/Graves’, predire l’andamento dell’Oftalmopatia Basedowiana e ottimizzare la gestione dei pazienti.


Controlled Antenatal Thyroid Screening II: effect of treating maternal sub-optimal thyroid function on child cognition. C Hales, PN Taylor, S Channon, R Paradice, K McEwan, L Zhang, M Gyedu, A Bakhsh, O Okosieme, I Muller, M S Draman, JW Gregory, C Dayan, JH Lazarus, A Rees, M Ludgate. Journal of Clinical Endocrinology and Metabolism 2018 Apr 1;103(4):1583-1591. doi: 10.1210/jc.2017-02378

Link to the paper: https://academic.oup.com/jcem/article/103/4/1583/4802113
Allegato: Download available from site (Free Access).
ENGLISH SUMMARY: To keep normal levels of thyroid hormones during pregnancy is crucial for the foetal neurodevelopment, especially in the first trimester. Here we evaluated the impact of maternal suboptimal gestational thyroid function, and correction with levothyroxine treatment, on children’s cognitive function evaluated at age 9. Children of women with normal gestational thyroid function were also evaluated.
Riassunto in ITALIANO: Il mantenimento di normali valori di ormoni tiroidei durante la gestazione è fondamentale per un corretto sviluppo neurologico del feto. Qui abbiamo valutato l’impatto della funzione tiroidea materna subottimale, e del relativo trattamento con levotiroxina, sulla funzione cognitiva della prole valutata a 9 anni di età. Anche i figli di donne con funzione tiroidea normale durante la gravidanza sono stati inclusi nello studio.


TPOAb and thyroid function are not associated with breast cancer outcome: evidence from a large-scale study using data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Muller I, Kilburn LS, Taylor PN, Barrett-Lee P, Bliss JM, Ellis P, Ludgate ME and Dayan CM. European Thyroid Journal Jul 2017;6:197–207. DOI: 10.1159/000460246. 

Link to the paper: https://www.karger.com/Article/Abstract/460246?id=pmid:w.ncbi.nlm.nih.gov/pubmed/27367582
Allegato: Screenshot 8.9.19


ENGLISH SUMMARY: Earlier small studies suggested that the positivity of serum autoantibodies to thyroid peroxidase (TPOAb) was correlated to a better prognosis of breast cancer. Such observation was not confirmed in the present study, the largest to date.
Riassunto in ITALIANO: Precedenti studi su piccola scala avevano suggerito la possibilità che la presenza sierica di autoanticorpi anti perossidasi tiroidea (AbTPO) fosse associata ad una migliore prognosi di carcinoma mammario. Tale osservazione non è stata confermata in questo studio, ad oggi è il più esteso del settore.


The sodium iodide symporter is unlikely to be a thyroid/breast shared antigen. Muller I, Zhang L, Giani C, Dayan CM, Ludgate ME and Grennan-Jones F. Journal of Endocrinological Investigation 2016 Mar; 39(3):323-31. Epub 2015 Aug 8

Link to the paper: https://link.springer.com/article/10.1007/s40618-015-0368-6
Allegato: Screenshot 8.9.19


ENGLISH SUMMARY: The sodium iodide symporter (NIS) is expressed in both thyroid and neoplastic breast cells, thus it would represent an ideal shared antigen between the two, possibly contributing to explain the existing association between thyroid autoimmunity and breast cancer. In this study we discovered that autoantibodies to NIS (NISAb) are rare in both diseases, thus such hypothesis is unlikely.
Riassunto in ITALIANO: Il co-trasportatore sodio-iodio (NIS) è espresso sia dalla tiroide che dal carcinoma mammario, pertanto rappresenta un potenziale antigene comune tra i due, e quindi possibile co-responsabile della nota associazione tra autoimmunità tiroidea e carcinoma mammario. In questo studio abbiamo dimostrato che gli autoanticorpi anti NIS (AbNIS) sono rari in entrambe le malattie, pertanto tale ipotesi è improbabile.


The second wave of the Controlled Antenatal Thyroid Screening (CATS II) study: the cognitive assessment protocol. Hales C, Channon S, Taylor PN, Draman MS, Muller I, Lazarus J, Paradice R, Rees A, Shillabeer D, Gregory JW, Dayan CM, Ludgate M. BMC Endocrine Disorders. 2014 Dec 12;14:95. doi:10.1186/1472-6823-14-95

Link to the paper: https://bmcendocrdisord.biomedcentral.com/articles/10.1186/1472-6823-14-95
Allegato: Open Access


ENGLISH SUMMARY: We present the protocol to assess the cognitive function of age-9 children of women enrolled in the CATSII study, including mothers affected with suboptimal gestational thyroid function, corrected or not with levothyroxine treatment during pregnancy. Children of women with normal gestational thyroid function were also evaluated.
Riassunto in ITALIANO: Nel presente lavoro illustriamo il protocollo per valutare la funzione cognitiva dei figli di madri arruolate nello studio CATSII, il quale includeva donne con funzione tiroidea subottimale durante la gestazione, alcune delle quali trattate con levotiroxina. Anche i figli di donne con funzione tiroidea normale durante la gravidanza sono stati inclusi nello studio.


Melasma and endocrine disorders. Muller I and Rees AD. Pigmentary Disorders 2014 Oct S1:001. DOI: http://dx.doi.org/10.4172/2376-0427.1000S1001

Link to the paper: https://www.omicsonline.org/open-access/melasma-and-endocrine-disorders-2376-0427.1000s1001.php?aid=37159
Allegato: Open Access


ENGLISH SUMMARY: Brief overview about the association between melasma and endocrine disorders.
Riassunto in ITALIANO: Breve panoramica sull’associazione tra melasma e malattie endocrine.


Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer? Muller I, Giani C, Zhang L, Grennan-Jones FA, Fiore E, Belardi V, Rosellini V, Funel N, Campani D, Giustarini E, Lewis MD, Bakhsh AD, Roncella M, Ghilli M, Vitti P, Dayan CM, Ludgate ME. International Journal of Cancer. 2014 Apr 1;134(7):1706-14. Epub 2013 Oct 15

Link to the paper: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.28493
Allegato: Screenshot 28.9.19


ENGLISH SUMMARY: In this study we discovered that thyroid peroxidase (TPO), one of the main thyroid autoantigens, is also expressed by breast cancer (both mRNA and protein). Thus TPO is the most likely candidate as shared antigen between the two, possibly explaining the existing association between thyroid autoimmunity and breast cancer.
Riassunto in ITALIANO: In questo studio abbiamo scoperto che la tireoperossidasi (TPO), uno dei maggiori autoantigeni tiroidei, è espressa anche nel carcinoma mammario (sia mRNA che proteina). Quindi la TPO è il candidato ideale come antigene comune tra i due, potenzialmente responsabile della nota associazione tra autoimmunità tiroidea e carcinoma mammario.


Is the risk of primary hyperparathyroidism increased in patients with untreated breast cancer? Belardi V, Fiore E, Giustarini E, Muller I, Sabatini S, Rosellini V, Seregni E, Agresti R, Marcocci C, Vitti P, Giani C. Journal of Endocrinological Investigation. 2013 May; 36(5):321-5

Link to the paper: https://link.springer.com/article/10.3275/8580
Allegato:  Screenshot 28.9.19
ENGLISH SUMMARY: We found no apparent association between breast cancer and primary hyperparathyroidism.
Riassunto in ITALIANO: In questo studio non è stata riscontrata un’associazione tra carcinoma mammario e iperparatiroidismo primario.


High prevalence of breast cancer in patients with benign thyroid diseases. Muller I, Pinchera A, Fiore E, Belardi V, Rosellini V, Giustarini E, Giani C. Journal of Endocrinological Investigation. 2011 May; 34(5):349-52 DOI: 10.3275/7141

Link to the paper: https://link.springer.com/article/10.1007%2FBF03347458
Allegato:  Screenshot 28.9.19


ENGLISH SUMMARY: In this study population of patients with benign thyroid disorders, the prevalence of breast cancer was around 3 times more frequent compared with the general population.
Riassunto in ITALIANO: La popolazione oggetto di questo studio (pazienti affette da patologia tiroidea benigna) aveva una prevalenza di carcinoma mammario circa 3 volte superiore a quella attesa nella popolazione generale.


IGF-II mRNA expression in breast cancer: predictive value and relationship to other prognostic factors. Fiore E, Campani D, Muller I, Belardi V, Giustarini E, Rossi G, Pinchera A, Giani C. International Journal of Biological Markers. 2010 Jul-Sep; 25(3):150-6

Link to the paper: https://journals.sagepub.com/doi/abs/10.1177/172460081002500305
Allegato: Screenshot 28.9.19
ENGLISH SUMMARY: IGF-II mRNA expression per se is not an independent predictive factor in breast cancer but may be a marker of poor prognosis when associated with other prognostic factors such as Ki-67 index and p53 expression.
Riassunto in ITALIANO: L’espressione dell’ mRNA di IGF-II di per sé non rappresenta un fattore prognostico indipendente nel carcinoma mammario, tuttavia può essere associata ad una prognosi negativa se associata ad altri fattori prognostici come il Ki-67 e l’espressione di p53.


Favourable predictive value of thyroid autoimmunity in high aggressive breast cancer. Fiore E, Giustarini E, Mammoli C, Fragomeni F, Campani D, Muller I, Pinchera A, Giani C. Journal of Endocrinological Investigation. 2007 Oct; 30(9):734-8 http://dx.doi.org/10.1007/BF03350810

Link to the paper: https://link.springer.com/article/10.1007%2FBF03350810
Allegato: not available
ENGLISH SUMMARY: In this small-scale study of women with highly malignant breast cancer, the presence of positive serum thyroid autoantibodies was associated with a better survival, compared with women with negative autoantibodies.
Riassunto in ITALIANO: In questo studio basato su un piccolo numero di donne affette da carcinoma mammario ad alta malignità, la presenza sierica di autoanticorpi tiroidei è risultata associata ad una maggiore sopravvivenza, rispetto a donne con autoanticorpi negativi.

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