 |
 |
Just been updating our selenium SOP - review in JPMI 2012 vol 26, no 2 Riaz and Mehmood - http://www.jpmi.org.pk/index.php/jpmi/article/view/1262, brief paragraph on thyroid function, cites a 2009 paper which demonstrates selenomethionine supplementation does not result in clinically significant changes in thyroid hormone concentration. Of course that means more questions than answers - in what form are people taking selenium supplements - is going from deficient to "normal" selenium level going to change thyroid hormones whereas normal to higher levels doesn't - is this reference typical of the literature in this area or out of concensus - does it depend which method you use to measure thyroid hormones. I think I'm going to have to do some more reading! Regards, Fiona Dr Fiona Ivison FRCPath Prinicipal Clinical Biochemist Department of Clinical Biochemistry Central Manchester University Hospitals NHS Foundation Trust CSB 3, Oxford Rd, Manchester, M13 9WL Tel: 0161 701 1728 or 07806 883960 Fax: 0161 276 4773 E-mail: [log in to unmask] www.cmft.nhs.uk<http://www.cmft.nhs.uk/> Central Manchester University Hospitals NHS Foundation Trust includes: Manchester Royal Infirmary, Manchester Royal Eye Hospital, Royal Manchester Children's Hospital, Saint Mary's Hospital, University Dental Hospital of Manchester, Trafford Hospitals and Community Services. [cid:image001.jpg@01CE1E77.A93FDF40][cid:image002.jpg@01CE1E77.A93FDF40][cid:image002.jpg@01CE1E77.A93FDF40][cid:image002.jpg@01CE1E77.A93FDF40][cid:image002.jpg@01CE1E77.A93FDF40][cid:image002.jpg@01CE1E77.A93FDF40] ________________________________ From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Bart Ballieux Sent: 11 March 2013 16:25 To: [log in to unmask] Subject: Re: Thyroxine over-replacement You might think of the selenium status. Selenium is a cofactor for deiodinases and if selenium intake is low, selenium is preferentially stored in the thyroid, brain and gonades. Therefore T4 -> T3 conversion in the hypothalamus might be intact, adequately supporting feedback to TSH production, while in other tissues T3 supply might be suboptimal requiering suprafysiological T4 replacement. Beste regards, Bart Ballieux ________________________________ From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Mohammad Al-Jubouri Sent: maandag 11 maart 2013 13:17 To: [log in to unmask] Subject: Re: Thyroxine over-replacement Another set of results this morning on a patient receiving thyroxine replacement: FT3 4.5 pmol/L FT4 27.4 pmol/L TSH 0.14 mU/L So according to FT3, the patient is adequately replaced but according to FT4 & TSH, the patient is over-replaced. For long, we took it that TSH is a reliable indicator of adequacy of thyroxine replacement, but according to some references kindly provided by Rita Horvath, we need to rethink about our position regarding TSH monitoring in such patients. So what does the panel think? thanks Mohammad ________________________________ From: Mohammad Al-Jubouri <[log in to unmask]> To: [log in to unmask] Sent: Thursday, March 7, 2013 12:06 PM Subject: Re: Thyroxine over-replacement Thanks Ali, I am sure some of these patients would be on other medications, however the majority of patients on thyroxine who showed suppressed TSH and high FT4 would also show disproportionately normal or low FT3. You could check for this easily in your lab by measuring FT3 in some of the patients on thyroxine replacement and this is reported in the literature any way. I am not advocating combined T3 & T4 replacement but anecdotally some of GP colleagues are using such combination with some success in a selected number of their patients. Regards Mohammad ________________________________ From: Al-Bahrani Ali <[log in to unmask]> To: [log in to unmask] Sent: Thursday, March 7, 2013 10:35 AM Subject: Re: Thyroxine over-replacement Dear Mohammed Indeed, evidence is lacked on this front, however,we need to bare in mind that some of these patients are on other medications than thyroxine that could influence peripheral T4 to T3 conversion that could result in negative or positive TSH feedback surge, hence, give rise to such misleading levels!! Any of your patients are on such medicines? Kind Regards Ali Dr Ali Al-bahrani MBCh.B MSc.Chem Path. CSci. FRCPath. Director of Pathology Consultant Chemical Pathologist and HOD of Chemical Pathology St Mary's Hospital Newport Isle of Wight PO30 5TG United Kingdom Te: 01983 534859/534917 Fax. 01983 825437 ________________________________ From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Mohammad Al-Jubouri Sent: 07 March 2013 09:08 To: [log in to unmask] Subject: Re: Thyroxine over-replacement Many thanks Rita for your helpful and educational reply as ever. Thanks also to David Wright who gave a similar perspective. Yes these patients are primary hypothyroid patient on long term thyroxine replacement. We use TSH as frontline test and if it is below or above the reference range, then free T4 is automatically added and if TSH < 0.2 mU/L then a FT3 is added also. This rule is used for all patients including those on thyroxine replacement hence I see this phenomenon of relatively low FT3 compared to FT4 very frequently. Rita raised an interesting point that TSH responds differently to exogenous thyroxine compared to endogenous thyroxine, but I thought that T4 has to change to T3 at tissue level to exert its effect i.e T4 is a pro-hormone, hence any suppression of TSH is due to excessive T3 effect but its normal to low serum level in such patients doesn't reflect this explanation, unless tissue FT3 concentration at hypothalamic-pituitary level is completely different from serum FT3. David also mentioned the fact that the intact thyroid gland secrete up to 30% of the peripheral T3 poole and this is lacking in primary hypothyroid patients. I would welcome further debate on this interesting issue. Mohammad ________________________________ From: Rita Horvath <[log in to unmask]> To: [log in to unmask] Sent: Thursday, March 7, 2013 2:45 AM Subject: Re: Thyroxine over-replacement Mohammad, I copy here the relevant extract from a book chapter that I wrote in 2008 in the book Evidence-based Medical Monitoring (Eds: Paul Glasziou, Les Irwig, Jeffrey Aronson). It might help in explaining the below phenomenon. If interested, happy to send to you the whole book chapter with the below quoted ref-s. Assuming that these are primary hypothyroid patients on T4 for some time, the real Qs are - are these patients with these values clinically euthyroid and well? - Why were all these tests requested (if these are simple primary hypothyr. patients)? Or are these patients who were recently started on T4? NB: Due to the logarithmic relationship between TSH and fT4 we all think that TSH is the best and most sensitive marker of thyroid status, and thus TSH is the first line recommended test for monitoring patients on levothyroxine. I believe the picture is more complex than we think as TSH reacts somewhat differently to exogenous T4 replacement than to endogenous T4-T3 conversion. We use TSH as the best marker as we simply do not have a better one so far to assess the tissue effects of thyroid hormones. Hope the below helps rather than confuses many...J Suggest also see this link for the most recent guideline on the topic: http://aace.metapress.com/content/b67v7mk73g3233n2/fulltext.pdf Extract from the book chapter: In the absence of a true and reliable reference standard for the assessment of thyroid status at the tissue or organ level, it has become challenging to prove whether TSH is an equally good marker of exogenous as well as of endogenous T4 metabolism. When considering this point, it has to be remembered that exogenous thyroxine has a different effect on thyroid status, and patients taking levothyroxine commonly have supranormal free T4 (the key regulator of TSH feedback), while free T3 (the key regulator of tissue effects) is normal [35, 36, 37, 41]. Therefore, logic may dictate that T3 or free T3 would be a better marker of thyroid status at the tissue and end-organ levels. In practice, many clinicians use a combination of peripheral hormone and TSH assays, particularly when poor patient adherence to therapy is suspected [23, 26, 38, 53, 54]. Several pre-analytical, biological, and analytical problems need to be considered when using free T4 or free T3 measurements during levothyroxine replacement. Free T4 concentrations remain raised by about 13%for up to 6-9 hours after administration of a dose of levothyroxine and thus fluctuate more, owing to variations in sampling times during clinic visits [13, 14]. Therefore, if free T4 values are to be measured, the daily dose should be withheld before phlebotomy. Even though free hormones have lower intra-individual biological variation than TSH, interpretation of values is hampered by the fact that each patient has an individual set-point for maintaining euthyroidism and a normal TSH feedback response. Therefore, the wide population reference ranges cannot be used when individuals are monitored and free hormone concentrations are not informative without another marker of thyroid status (for example, TSH). In summary: Peripheral thyroid hormone measurements in isolation are unhelpful, as the individual set-point of patients for maintaining the euthyroid state is unknown. Furthermore, these tests are prone to pre-analytical variations which could grossly mislead therapeutic decisions. The TSH assay in isolation is not the most ideal test for monitoring, as it has large biological variation and thus a relatively small signal-to-noise ratio. In addition, it reflects the effect of exogenous T4 on the pituitary secretion of TSH rather than its effects on tissues and end-organ function. In the absence of appropriate evidence, further studies are needed on the diagnostic usefulness of TSH alone or in combination with free T4 or T3/free T3 measurements in monitoring patients taking levothyroxinereplacement and in predicting treatment outcomes. Kind regards, Rita Prof. Andrea Rita Horvath, MD, PhD, EurClinChem, FRCPath, FRCPA Past President of the European Federation of Clinical Chemistry and Laboratory Medicine Clinical Director, SEALS North, Department of Clinical Chemistry Level 4, Campus Centre, Prince of Wales Hospital Barker Street, Randwick, NSW 2031, Sydney, Australia Tel: (+612)-9382 9078 Fax: (+612)-9382 9099 Mobile No: (+61)-404 027 843 From:Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Mohammad Al-Jubouri Sent: Thursday, 7 March 2013 4:06 AM To: [log in to unmask] Subject: Thyroxine over-replacement We may have discussed this in the past in more than one occasion, but here we go again: exogenous T4 replacement is associated with relatively lower serum FT3 compared to FT4, these are three set of results for 3 patients on thyroxine replacement as examples: 1st patient: TSH < 0.05 mU/L, FT4 23.3 pmol/L and FT3 3.0 pmol/L 2nd patient: TSH 0.17 mU/L, FT4 25.1 pmol/L and FT3 4.4 pmol/L 3rd patient: TSH < 0.05 mU/L, FT4 25.1 pmol/L and FT3 5.7 pmol/L In all 3 patients, Free T4 is higher than the reference range of (10 - 20) and TSH is suppressed, but FT3 is within the reference range of (3.5 - 6.5) in two patients and less in one patient. So is this thyroxine over-replacement even though the active thyroid hormone FT3 is not raised? thanks Mohammad Dr. M A Al-Jubouri, MB ChB, MSc, FRCP Edin, FRCPath Consultant Chemical Pathologist ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk<http://www.acb.org.uk/> Green Laboratories Work http://www.laboratorymedicine.nhs.uk<http://www.laboratorymedicine.nhs.uk/> List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ --------------------------------------------------------------------------------------------- Illawarra Shoalhaven Local Health District, South East Sydney Local Health District and Sydney Children's Hospital Network (Randwick Campus) Confidentiality Notice This email, and the files transmitted with it, are confidential and intended solely for the use of the individual or entity to whom they are addressed. If you are not the intended recipient, you are not permitted to distribute or use this email or any of its attachments in any way. We also request that you advise the sender of the incorrect addressing. This email message has been virus-scanned. Although no computer viruses were detected, Illawarra Shoalhaven Local Health District, South East Sydney Local Health District and Sydney Children's Hospital Network (Randwick Campus) accept no liability for any consequential damage resulting from email containing any computer viruses. ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk<http://www.acb.org.uk/> Green Laboratories Work http://www.laboratorymedicine.nhs.uk<http://www.laboratorymedicine.nhs.uk/> List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ 1. ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk<http://www.acb.org.uk/> Green Laboratories Work http://www.laboratorymedicine.nhs.uk<http://www.laboratorymedicine.nhs.uk/> List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk<http://www.acb.org.uk/> Green Laboratories Work http://www.laboratorymedicine.nhs.uk<http://www.laboratorymedicine.nhs.uk/> List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk<http://www.acb.org.uk/> Green Laboratories Work http://www.laboratorymedicine.nhs.uk<http://www.laboratorymedicine.nhs.uk/> List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk Green Laboratories Work http://www.laboratorymedicine.nhs.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk Green Laboratories Work http://www.laboratorymedicine.nhs.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ Privacy and Confidentiality Notice: The information contained in this e-mail is intended for the named recipient(s) only. It may contain privileged and confidential information. If you are not an intended recipient, you must not copy, distribute or take any action in reliance on it. If you have received this e-mail in error, we would be grateful if you would notify us immediately. Thank you for your assistance. Please note that e-mails sent or received by our staff may be disclosed under the Freedom of Information Act (unless exempt). ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk Green Laboratories Work http://www.laboratorymedicine.nhs.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/