The degree of selenium deficiency needed to affect thyroid metabolism is
unusual in UK populations.

Barry

Barry Sampson

Consultant Clinical Scientist and Honorary Lecturer
Director, SAS Trace Element Laboratory
Clinical Biochemistry
Charing Cross Hospital (Imperial College Healthcare NHS Trust) & Imperial
College School of Medicine London W6 8RF UK
Phone +44-020-33133644
Fax +44-020-33117007
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On 11/03/2013 18:20, "Nick Miller" <[log in to unmask]> wrote:

>Well this panel thinks you are wasting your time worrying about
>circulating FT3 in patients on thyroid replacement.
>
>Nick Miller
>London
>
>On 11/03/2013, Bart Ballieux <[log in to unmask]> wrote:
>> 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
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