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Wednesday, February 27, 2008


I have been searching high and low for a dvd version of Marilyn Waring's "Sex Lies and Economics" or "who's counting?"

This documentary changed my life some 10 years ago, please spend one hour of your life, download the audio version of this in two parts and listen carefully.

Maybe this will change your life like it changed mine

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Monday, February 25, 2008


Wish I'd thought of it...

Valentine's message in our local rag...


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Friday, February 22, 2008


You are in my power...



 

 


Cat's Life Tips 101

Assemble lasagne in the nude.

I find it useful to assemble lasagne in the nicky noo nah.

Yesterday I made my famous vego lasagne and while I don't actually cook the red sauce in the buff, who wants to be scalded by burning sauce rosa? I do find it helps with the cleaning up if assembling is done in the nakey, or at least topless.
Those red spots are so hard to get out otherwise!! The white sauce isn't an issue.
Here's one I prepared earlier:


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Never done this before, but, this post was so popular I'm repeating it...

Monday, February 11, 2008


Never treat hypoT on free T3 without taking symptoms into account

aka - never discount the T3 auto antibodies....

Ok we all know that using the TSH to dose thyroid meds is like trying to navigate a shopping mall using a soccer ball as a map - or maybe even less useful.

TSH only has a useful relationship to serum thyroid hormones when all systems are working properly, failing that, all bets are off.

As thyroid stimulating hormone is actually produced in the pituitary, and is released in response to the body perceiving a need for more thyroid hormone, a number of things can go wrong. The body may be in thyroid hormone conservation mode, this can happen after a number of years of being hypothyroid without treatment, or in the case of some, extreme dieting can bring it on, shock etc. The pituitary may not be unable to produce enough TSH to stimulate the thyroid gland, the body may not sense the lack and stimulate the pituitary to produce TSH, and you may have antibodies to the TSH itself, so the body attacks it's own hormone, and your thyroid doesn't get stimulated.

To get around this, most forward thinking people use the free t3 test to indicate how one should be replaced, correlating this to symptoms for "most" people has shown that with a freeT3 in the top 1/4 of the lab range, or just over, most hypothyroid people begin to feel well and regain some of the life they have lost to the illness.

But what if your free T3 is at the top of the range with no cessation of symptoms?

What if, like me, you can go for a week with no thyroid hormone supplement, and your symptoms worsen to the point of being bedridden, but your free T3 still shows on the top of range on a serum test while free T4 and TSH are both below range?

T3 has a half life of up to 10 hours, so after a week, it should be gone right?

Not neccesarily, what has been proven in case after case after case where an elevated T3 in the presence of hypothyroid symptoms has been evaluated, is the presence of antibodies to the T3 itself, which causes it to become bound in the serum, unavailable to the cells where it is needed for metabolism, causing high so called "free" T3 testing, and persistent hypothyroid symptoms.

Don't take my word for it, read the research, and DEMAND better treatment to the cessation of symptoms, rather than just to make some numbers on some paper look pretty.



http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=3224724&cmd=showdetailview&indexed=google

[Triiodothyronine(T3) autoantibodies in a woman with nonthyroidal disorder: a study on preparation of serum IgG fraction employing protein A column chromatography]
[Article in Japanese]
Mizuno E, Sugenoya A, Haniuda M, Sakai R, Kameko M, Kato M, Iida F.
Department of Surgery, Shinshu University School of Medicine.
A 48-year-old non-goitrous woman, who had undergone cardiac surgery for mitral stenosis under the extracorporeal circulation, showed high levels of serum T3 and free T3 in a recent follow-up study, employing antibody coated-bead RIA for T3 and -Amerlex M particle RIA for free T3. However, other thyroid function tests (T4, free T4, TSH and TBG) were normal. We suspected that thyroid hormone autoantibodies (THAA) in her serum interfered with T3 and free T3 analyses. The presence of THAA was demonstrated by the use of various procedures as follows. Firstly, the patient's serum was directly incubated with 125I-T3 or -T4 analog which did not bind to TBG, followed by B/F separation with polyethyleneglycol, counting the precipitates. Secondly, after the serum was treated with an acid-charcoal solution to remove circulating thyroid hormone, the measurement of THAA was made as stated above. Normal sera were used as controls. Both the non- and acid-charcoal-treated sera showed much higher percentages of 125I-T3 analog precipitation as compared with controls. In the case of 125I-T4 analog, there was no difference between them. In the third study, the presence of IgG antibodies that bound T3 but not T4 was investigated. The IgG fraction of the patient's serum was separated employing a Protein A-Sepharose CL-4B column chromatography. Then, the prepared IgG fraction was purified by a technique of gel filtration chromatography (Sephacryl S 200). Non-purified and purified-IgG fractions both revealed higher binding percentages of 125I-T3 analog than the control IgG fraction and non-IgG fraction of the patient. Furthermore, a good dose response was observed between the binding percentage of 125I-T3 analog and each dose of the patient's serum or IgG fraction. From these observations, it was clarified that this woman had anti-T3 IgG autoantibodies using a Protein A column chromatography with confirmation of gel filtration chromatography.
PMID: 3224724 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/8006324?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Thyroid hormone autoantibodies and their implications for free thyroid hormone measurement.
Vyas SK, Wilkin TJ.
Endocrine Section, University Medicine, Southampton General Hospital, UK.
Thyroid hormone autoantibodies (THAA) disrupt the equilibrium between thyroid hormones and their binding proteins. This may lead to spurious estimations of free thyroxine (FT4) and triiodothyronine (FT3) by radioimmunoassay (RIA). In the present study we highlight the importance of THAA by examining the frequency of THAA in consecutive sera sent to a routine district hospital laboratory. Over a period of six months, sera were collected from 200 consecutive hypothyroid, 200 hyperthyroid and seven patients whose clinical and biochemical thyroid status were contradictory. A further 200 patients with non-thyroid autoimmune conditions, 20 patients with insulin autoantibodies and 100 healthy blood transfusion donors were studied. In all sera, both effects of antigen removal on THAA detection and where THAA were found, the effect of their removal on FT4, were examined. The frequencies of THAA amongst hypothyroid, hyperthyroid and non-thyroid autoimmune conditions were 7%, 1.5% and 7.5% respectively, whilst no THAA were found in insulin autoantibody positive patients and 100 blood transfusion donors. However, THAA frequency was highest in those patients whose biochemical thyroid status was widely inappropriate to clinical state (5/7 = 64%). Sera stripped of thyroid hormones prior to THAA detection had significantly higher antibody activity than unstripped sera (p = 0.0027 and p = 0.0123 for T3 and T4 binding respectively). Free thyroxine levels measured by the Amerlex-M RIA kit after antibody removal fell in all 21 THAA positive sera tested. The correlation coefficient between antibody activity in serum with percentage fall in FT4 was 0.79 (Spearman's Rank Correlation Test).(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 8006324 [PubMed - indexed for MEDLINE]





http://www.clinchem.org/cgi/reprint/41/1/117

Spuriously High Concentration of Serum Free Thyroxine due to Anti-Trilodothyronine Antibodies ,
R#{233}S maypin, 1.3 Fran#{231}oiGseasser,' Andreas Boehn,2 and Muriel Rondeau2 ['Inst. de Phys. Biol. (Dir. Pr. J.
Chambron), Facultd de Med., F-67085 Strasbourg Cedex, France;2 Med. Interne A (Pr. D. Christmann), Clin. Med.
A, Hopital Central, CHRU, F-67091 Strasbourg Cedex, France; 3Author for correspondence: Fax Tnt + 33 88 3714 97, E-mail sapin@alsace.u-strasbg.frI
Free thyroxine (Fr4) is now frequently measured in serum by one-step labeled antibody assays based on a Solid-Phase Antigen-Linked Technique (SPALT) (1). In this assay the serum sample is incubated with a large excess of triiodothyronine (T3)-coupled solid phase and with a limited amount of labeled anti-T4 antibody. Because the solid phase acts as a ligand of low affinity for the anti-T4 antibody, interference from circulating anti-thyroid hormone (anti-T4 or anti-T3) autoantibodies (THAA) is theoretically possible.
However, until now, to our knowledge, this assay was considered to be only slightly affected by THAA (2-4).
The highest measured FT4 values (up to 35 pmol/L) could be related to therapy with T4 (4). Nevertheless, recently we observed a very high FT4 value (131 pmol/L) measured by a SPALT assay (Amerlex- MAB; Kodak Clinical Diagnostics, Amersham, UK) in the serum of a hospitalized patient with Crohn disease. This 33-year-old man was euthyroid by clinical evaluation and by his normal thyrotropin serum concentration (0.59 mIUIL, normal range 0.15-4.5 mIUfL) determined with BeriLux kit (Behring, Marburg, Germany). The biological evaluation showed a moderate hypergammaglobulinemia (17 g/L, normal range <14 g/L) with increased IgG concentration (21.8 g/L, normal range <17 g/L). The followed procedures were in accordance with the Helsinid Declaration of 1975 as revised in 1983.
This patient's serum contained anti-T3 but no anti-T4 antibodies, as identified with the technique of Allan et a!. (5) by using the analog T3 or T4 radioactive tracer of the Amerlex-M FT3 or FT4 kits, respectively (Kodak Clinical Diagnostics). The percentage of radioactive T3 analog tracer precipitated by polyethylene glycol, 12%, was above normal (5% in absence of THAA) but still quite low. The measurement of Amerlex-M FT3 remained normal ( 4.1 pmol/L, reference range 3.7-9.2 pmol/L). Fixation of a radioactive '251-labeled native T3 tracer on the fraction pre cipitated by polyethylene glycol was also not very high: 7.1% (vs normal of <5% in absence of THAA). That the free thyroidhormone concentrations were normal was confirmed by two-step RIAs known to be unaffected by the presence of THAA: FT4 24.8 pmol/L (normal range 9-25.7 pmol/L by Gammacoat"; Incstar, Stifiwater, MN); FT3 3.7 pmol/L (normal range 3.1-6.1 pmol/L by Ria-gnost; Behring). This very marked interference in the FT4 Amerlex-MAB assay shows an interaction of anti-T3 autoantibodies with the T3 immobilized on the solid phase. This interaction can occur in the presence of THAA of high affinity for the T3 fixed on the solid phase; perhaps the serum of this patient contains an antibody with a high affinity towards the T3- bridge that is used to link the solid phase to T3. This interaction can also occur with THAA of low affinity but of high capacity (i.e., the ligand is present in high concentration) (4).
The prevalence of THAA seems to be low (1/2360) (2) but the frequency of THAA is much higher in hypothyroid (7%), hyperthyroid (1.5%), and nonthyroid autoimmune ( 7.5%) patients (6). Compared with other one-step FT4 kits, the Amerlex-MAB assay is considered to be little affected by THAA (4), with only one of eight Amerlex-MAB FT4 results being higher than two-step values in the study by John et al. (2). However, users of this FT4 kit, and more generally of SPALT Fr4 kits with a T3-coupled solid phase, should be aware that such methods can give grossly misleading overestimates of FT., in presence of anti-T3 autoantibodies and produce a misclassification of thyroid sta tus. Therefore, not only anti-T4 but also anti-T3 antibodies should be suspected when a FT4 result does not correspond to the clinical state of the patient.

References
1. Christofides ND, Sheehan CP, Midgley JEM. One-step, labeledantibody assay for measuring free thyroxin. I. Assay development and validation. Cliii Chem 1992;38:11-8.
2. John R, Henley R, Shankland D. Concentrations of free thyroxunand free triiodothyronine in serum of patients with thyroxinand triiodothyronine-bindung autoantibodies. Clin Chem 1990;36: 470-3.
3. Sapin R, Gasser F, Schlienger JL, Chambron J. Analytical and clinical evaluation of a new one-step non-analogue radioimmuno assay for serum free thyroxin. Ear J Nucl Med 1990;17:111-5.
4. Sheehan CP, Christofides ND. One-step, labeled-antibody assay for measuring free thyroxine. II. Performance in a multicenter trial. Clin Chem 1992;38:19-25.
5. Allan DJ, Murphy F, Needham CA, Barron N, Wilkins TA, Midgley JEM. Sensitive test for thyroid hormone autoantibodies in serum [Letter!. Lancet 1982;ii:824.
6. Vyas SK, Wilkin TJ. Thyroid hormone autoantibodies and their implications for free thyroid hormone measurement. J Endocrino! Invest 1994;17:15-21.




http://www.clinchem.org/cgi/content/full/51/6/1071

Letters to the Editor

Falsely High Serum Free Triiodothyronine and Free Thyroxine Concentrations Attributable to Anti-Diiodothyronine and Anti-Triiodothyronine Antibodies
Kunihiro Iwahara1, Chizuko Tanabe1, Kozo Nishiyama2, Hiroyuki Ohashi 3 and Masato Maekawa1,a
1 Department of Laboratory Medicine
2 2nd Department of Internal Medicine and3 3rd Department of Internal Medicine, Hamamatsu University, School of Medicine, Hamamatsu, Japan
aAddress correspondence to this author at: Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192 Japan. Fax 81-53-435-2794; e-mail mmaekawa@hama-med.ac.jp

To the Editor:
We observed a patient with markedly increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations measured on a Vitros ECi analyzer (Ortho Clinical Diagnostics). The patient was a hospitalized 42-year-old woman with lupus erythematosus who appeared euthyroid and had normal thyroid-stimulating hormone (TSH) concentrations (Table 1 in the Data Supplement that accompanies the online version of this letter at http://www.clinchem.org/content/vol51/issue6/). Thyroid peroxidase antibody and thyroglobulin antibody were <0.3 kilounits/L, and rheumatoid factor was < 6.0 kilounits/L. We suspected interference from heterophilic antibodies (1 )(2), but our experiments suggested interference from antibodies to diiodothyronine (T2), T3, or their conjugates, as have been described (3 )(4)( 5). The procedures in this study were in accordance with the Helsinki Declaration of 1975 and the subsequent 1996 amendments.
In contrast to results of the Vitros ECi FT3 and FT4 assays, which use solid phases with T2 - and T3-gelatin, respectively, and labeled sheep antibodies, FT3 and FT4 were normal by the Elecsys assays (Roche Diagnostics), which use biotinylated antibodies in a one-step method.
To the Vitros FT3II and FT4 assay wells we added 0.05 mL of serum from the patient or from controls (n = 5) and 0.1 mL of diluent [phosphate-buffered saline (PBS) containing, per liter, 2 mL of Tween 20 (Sigma) and 10 g of bovine globulin (Sigma)], and incubated them at 37 °C for 18 min. After washing each well, we added 0.125 mL of horseradish peroxidase-labeled goat anti-human IgG antibody conjugate (Chemicon International. Inc.), diluted 50 000-fold in the same diluent, and incubated the mixtures at 37 °C for 18 min. After each well was washed, the Vitros Signal Reagent was added to the well, and the luminescence was measured (ALOKA luminometer). The IgG fraction of serum samples from the patient and from five control individuals was purified with a MAbTrapTM Kit (Amersham Biosciences), and the IgG concentration was adjusted to 4.0 g/L. The purified IgG (0.08 mL) was incubated at 4 °C for 24 h with 0.08 mL of PBS alone or with T2, T3, or T4 (Sigma; at 4570, 42, and 768 nmol/L, respectively) dissolved in PBS. Each sample was mixed vigorously with 1.2 mL of polyethylene glycol (PEG; 125 g/L), centrifuged at 2800g for 30 min, aspirated, and washed with 1.2 mL of PEG (125 g/L). After the precipitates were dissolved in 0.001 mol/L hydrochloric acid ( 0.04 mL) and neutralized by equal amounts of 0.001 mol/L sodium hydroxide, T2 and T3 were measured by the FT3 assay and T4 by the FT4 assay. The concentrations of T2 were expressed as T3 concentrations. Each sample was analyzed in duplicate. The ability of the purified IgG to bind T2, T3, or T 4 was defined as the difference between the FT3 or FT4 assay result and the respective blank value and is reported as the T2 , T3, or T4 value.
The ratios of FT3 and FT4 concentrations in PEG-treated samples ( 6) to those in untreated samples were significantly lower for the patient than for 37 other patients (Table 1 in the online Data Supplement); therefore, immunoglobulins in the patient's serum interfered with both the FT3 and FT4 assays. FT3 and FT4 values in the mixtures of serum with sheep IgG, bovine globulin, and gelatin did not differ significantly from those in the mixtures of serum and PBS only, suggesting that heterophilic antibodies and anti-gelatin antibodies did not cause the high FT3 and FT4 values.
When we examined the patient's IgG binding with Vitros FT3II and FT4 assay wells, the luminescence generated by the patient's serum was higher than that of the 5 control individuals (Table 1 in the online Data Supplement). This suggested that the patient's IgG bound to T2- and T3-gelatin.
The FT3 and FT4 concentrations in purified IgG and in treated samples of purified IgG ( 6) were below the lower detection limits of the Elecsys assays, suggesting an absence of T3 and T4 contamination in the IgG fractions. The patient's T2 and T3 values were higher than those of the 5 control individuals, but the T4 value was within 2 SD of the values for the 5 controls (Table 1 in the online Data Supplement). This finding implies that the patient's IgG interacted with T 2 and T3 but not with T4. The cross-reactivity of the anti-T3 antibody with T2 in the Vitros FT3II assay was very low, whereas the patient's T2 value was evidently higher than that of 5 control individuals. We conclude that T2 was bound to the patient's IgG.
Because anti-gelatin antibodies in the patient's serum were not recognized, we suggest that the interfering substance were antibodies to T2 and T3. As the interfering antibodies did not interfere with the Elecsys FT3 assay, the interfering antibody in the patient's serum may recognize T 2 and T3 conjugates used in the Vitros ECi FT3 and FT4 assays, as reported for a labeled-antibody assay ( 7). We suggest that this interference in the Vitros ECi FT3 and FT4 assays arose from antibodies to T2 , T3, or their conjugates.

References
1. Fiad TM, Duffy J, McKenna TJ. Multiple spuriously abnormal thyroid function indices due to heterophilic antibodies. Clin Endocrinol (Oxf) 1994;41:391-395. [Medline] [Order article via Infotrieve]
2. Kricka LJ. Human anti-animal antibody interferences in immunological assays. [Review]Clin Chem 1999;45:942-956. [Abstract/Free Full Text]
3. Lai LC, Day JA, Clark F, Peaston RT. Spuriously high free thyroxine with the Amerlite MAB FT4 assay. J Clin Pathol 1994;47:181-182. [Abstract/Free Full Text]
4. Sapin R, Gasser F, Boehn A, Rondeau M. Spuriously high concentration of serum free thyroxine due to anti-triiodothyronine antibodies. Clin Chem 1995;41:117-118. [Free Full Text]
5. John R, Henley R, Shankland D. Concentrations of free thyroxin and free triiodothyronine in serum of patients with thyroxin- and triiodothyronine-binding autoantibodies. Clin Chem 1990;36:470-473. [Abstract/Free Full Text]
6. Kuzuya H, Blix PM, Horwitz DL, Steiner DF, Rubenstein AH. Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes 1977;26:22-29. [Abstract]
7. Westerhuis LW, Venekamp WJ. Falsely high serum free thyroxine concentration measured with Amerlite-MAB FT4. Clin Chem 1995;41:633-634. [Free Full Text]





http://www.ncbi.nlm.nih.gov/pubmed/7535535?ordinalpos=15&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Autoimmunity against thyroid hormones.
Sakata S.
Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
The presence of thyroid hormone autoantibodies (THAA) is a common phenomenon. More than 270 cases have been reported by the end of 1993 involving not only thyroidal but also nonthyroidal disorders. Clinically, THAA in a patient's serum produces variation in thyroid hormone metabolism and, in particular, may interfere with the radioimmunoassay (RIA) results of total or free thyroid hormone measurements, which can cause unusually high or low values of the hormones depending on the B/F separation method used. This in vitro interference can give clinicians confusing information about the patient's thyroid state. As a result, the patient may receive inappropriate treatment from physicians who are unaware of this disorder. The presence of THAA has been reported not only in humans but also in dogs, chickens, and rats. In this review article, clinical features of THAA and the mechanism of autoantibody production are discussed.
PMID: 7535535 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/7958106?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[Studies on patients with a discrepancy between free thyroid hormones and thyrotropin values]
[Article in Japanese]
Hisaoka T, Iino S, Saitoh H, Yoshimura H, Ishikawa N, Momotani N, Ito K.
Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Thyroid function has been almost exactly evaluated by the measurement of serum free thyroxine (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) concentrations. However, we occasionally experience patients who show a discrepancy between free thyroid hormones and TSH values, and the assessment of thyroid function in such cases is extremely difficult. Thyroid hormone autoantibodies (THAA) interfere with radioimmunoassay (RIA) of FT4 and FT3 by giving inappropriate values. To investigate the incidence of THAA, immune precipitation of patients' sera after incubation with labelled T4 (125I-T4) or T3 (125I-T3) analog tracer was done in 394 patients with thyroid diseases. 9 patients ( 2.3%) showed an increased binding of 125I-T4 or 125I-T3 analog. Heterophilic antimouse antibodies in a patient's serum (human antimouse immunoglobulin antibodies: HAMA) can interfere in two-site immunometric assays (IMA) using mouse monoclonal antibodies and result in spuriously increased serum TSH concentrations. Manufacturers now customarily add nonspecific mouse immunoglobulins into their assay kits to absorb HAMA and prevent such interference. This approach may not always be enough to prevent HAMA interference in all samples. In 14 thyrotoxic patients with inappropriately high TSH measured by an IMA kit, we measured the levels of TSH by the further addition of mouse serum into this kit. Their serum TSH levels were fully suppressed except for 2 patients with a syndrome of inappropriate secretion of TSH (SITSH). The presence of abnormal albumin in the serum also interferes with RIA of FT4 and FT3. We experienced a female case of Graves' disease treated with methimazole who showed an inappropriately high serum FT3 measured by an analog tracer RIA kit, whose serum FT4, FT3 and TSH were 1.31 ng/dl, 19.3 pg/ml and 1.9 mu U/ml respectively. Although the anti-T3 autoantibody was considered to be present initially, immune precipitation of her serum with 125I-T3 analog tracer gave a negative result. In order to elucidate this finding, Sephadex-G200 chromatography of her serum after incubation with 125I-T3 analog tracer was done. Radioactivity of her serum in albumin fraction was significantly higher than that of normal control serum to indicate the presence of abnormal albumin in the serum. In conclusion, to assess the thyroid function of a patient with a discrepancy between free thyroid hormones and TSH values, it is important to consider the presence of THAA, HAMA, or rarely, an abnormal albumin.
PMID: 7958106 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/7556780?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[Three thyroid patients showing fluctuation of thyroid hormone autoantibody titers during long-term treatment]
[Article in Japanese]
Ikekubo K, Hino M, Saiki Y, Kajikawa M, Hattori N, Ishihara T, Moridera K, Kurahachi H.
Department of Nuclear Medicine, Kobe City General Hospital.
Development and fluctuation of thyroid hormone autoantibody (THAA) titers were observed during long-term treatment of thyroid diseases in three patients. The presence of THAA was noticed by spuriously high serum free thyroid hormone levels measured with an analog tracer RIA (Amerlex-M FT3, FT4) in all three patients. Amerlex-M FT3 or FT4 levels gradually decreased to appropriate values for the clinical status according to the decreasing titers of THAA. Free thyroid hormone levels with radiolabeled antibody radioassay (Amerlex-MAB FT3, FT4) were not affected by the THAA and always reflected actual thyroid function. Case 1 was a 46-year-old man with untreated primary hypothyroidism. Auti-T4 autoantibody was detected in his serum. The 125I-T4 analog binding to the autoantibody (125I-T4 analog binding ratio) gradually declined after L-T4 therapy and finally almost disappeared two years and four months later. Amerlex-MAB FT4 level rose to the normal range two months after T4 therapy, but TSH level remained slightly elevated ( 5.4-13 microU/ml) for five months during T4 therapy. The 125I-T4 analog binding ratio and anti-Tg autoantibody (TgAb) titer were inversely correlated. Case 2 was a 72-year-old woman had received desiccated thyroid for a long time. Sequential changes of 125I-T4 analog binding ratio were very similar to those of TgAb titer. Case 3 was a 74-year-old woman with Graves' disease. She had been treated with methimazole (MMI) and desiccated thyroid for three years and five months. Ten months after stopping both drugs, anti-T3 autoantibody was detected. The 125I-T3 analog binding ratio was transiently elevated and gradually declined to reference range for four years during L-T4 therapy. 125I-T3 analog binding ratio and TgAb titer changed in a similar way. These results suggest that desiccated thyroid hormone therapy and TgAb formation are related to the development of THAA and that L-T4 therapy reduces the THAA titer.
PMID: 7556780 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/8697622?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Autoantibodies to thyroid hormones: the role of thyroglobulin.
Erregragui K, Cheillan F, Defoort JP, Prato S, Fert V.
Immunotech, Marseille, France.
Autoantibodies against thyroid hormones (THAA) are frequently detected in the sera of patients with thyroid disorders together with autoantibodies against thyroglobulin (TGAA). THAA are considered to be a subset of TGAA, but alternative possibilities have not been excluded. We hypothesize that if THAA arise through an immune response to iodothyronines carried by circulating thyroglobulin (hTg), THAA should be found together with autoantibodies against the peptide backbone of hTg (TPAA) close to the hormone-forming sites. We measured TPAA in 178 serum samples, obtained from healthy subjects and patients with thyroid disorders, using two hormone-forming peptides isolated from hTg. The occurrence of TPAA was much lower than that of TGAA. Autoantibodies to the hormone-rich peptide, P3, were significantly more common than autoantibodies to the hormone-poor peptide, P1 (111/178 = 62.3% for TGAA versus 21/178 = 11.8% for anti-P3 TPAA and 7/178 = 3.9% for anti-P1 TPAA). The presence of autoantibodies to thyroid hormones was investigated in 25 TPAA+ and 26 TPAA- sera. THAA were found more frequently in TPAA+ sera (10/25 = 40% for TPAA+ and 4/26 = 15.3% for TPAA-). Correlation analysis shows that the anti-P3, but not the anti-P1 binding activity, correlates positively with the THAA-binding activity (P < 0.001 for anti-T4 THAA; P < 0.01 for anti-T3 THAA). Specificity of anti-P3 TPAA indicates that a subset of the anti-P3 antibodies is directed against the thyroid hormone moiety and another subset is directed against the peptide backbone near the hormone-forming peptide, according to our hypothesis. These results indicate that the THAA response is an anti-hTg response directed, in a significant number of cases, against the hormone-forming site included in the P3 peptide. This response seems to be elicited by either native hormone-rich hTg or by hTg fragments.
PMID: 8697622 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/9175389?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Antitriiodothyronine antibody in patient with Hashimoto's thyroiditis.
Plengvidhya N, Sunthornthepvarakul T, Vannasaeng S.
Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
We described a 44-year-old female patient with a history of goiter for 2 months. Physical examination revealed a diffusely enlarged thyroid gland weighing 40 g firm to hard in consistency. She was clinically euthyroid and had neither ophthalmopathy nor dermopathy. Serum thyroid hormone levels revealed total T4 (RIA) of 4.8 micrograms/dL (normal, 4-11 micrograms/dL), total T3 (RIA) of above 600 ng/dL (70-175 ng/dL), and TSH (IRMA) of 54 mU/L (0.3-6 mU/L). Antithyroglobulin and antiperoxidase antibody titers were 1:5,120 and 1:409,260, respectively. Because of the discrepancy between the patient's clinical status and laboratory values, assay for thyroid hormone autoantibodies (THAA) was done and subsequently demonstrated antitriiodothyronine antibody with percentage of precipitation by polyethylene of 98.4 per cent (normal range, 3.06 +/- 8.58%). In conclusion, THAA should be suspected in patients whose clinical status is incoherent with the thyroid function test.
PMID: 9175389 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/6896035?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus

[A study on anti-T3 and anti-T4 autoantibodies found in two sisters with juvenile hypothyroidism due to Hashimoto's thyroiditis (author's transl)]
[Article in Japanese]
Nakamura S, Fushimi K, Okuyama M, Miura K.
Anti-thyroid hormone autoantibodies were found in two sisters of short stature (case 1: 13 years old, case 2: 10 years old). Physical examination revealed clinical findings of hypothyroidism with diffuse goiter. A diagnosis of Hashimoto's thyroiditis was made by open biopsy of the thyroid gland in both patients. Serum levels of T3 and T4 were assayed by double antibody radioimmunoassay. In case 1, serum T3 level was 16 ng/dl and serum T4 level was 2.0 microgram/dl. In case 2, serum T3 levels were high (range, 375 approximately 1660 ng/dl), while serum T4 remained at a very low level (0.9 microgram/dl). On the other hand, the level of T3 in case 2 as well as the level of T4 in case 1 was not detectable by a single antibody radioimmunoassay using dextran-coated charcoal or polyethylene glycol separation. In each case, the serum TSH level measured by double antibody radioimmunoassay was extremely high (255 microunits/ml in case 1, 240 microunits/ml in case 2), which was compatible with the clinical features of primary hypothyroidism. Sera from both patients were incubated with 125I-T3 and 125I-T4, followed by precipitation with polyethylene glycol. The binding of 125I-T3 with serum from case 2 and the binding of 125I-T4 with serum from case 1 were markedly high, suggesting the presence of T3- and T4-binding substance(s) in the sera. IgG prepared from the sera of both cases showed marked and specific binding with T3 in case 2 and T4 in case 1. The association constant for T4-antibody in case 1 was 5.2 x 10(8) M-1 and for T3-antibody in case 2 was 5.0 x 10(9) M-1. The binding capacity for T4 was 1.2 ng/ml.IgG and for T3 was 0.3 ng/mg.IgG.
PMID: 6896035 [PubMed - indexed for MEDLINE]

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Monday, February 18, 2008


Absolute Must read...

http://www.geocities.com/organdonate/trustingyourhospital.html

The Nasty Side Of
Organ Transplanting
The Cannibalistic Nature of Transplant Medicine

Norm Barber

Third Edition 2007


“Transplant technology may be compared to an evil genie let out of a bottle and now won’t return.”
Nancy Scheper-Hughes, Organs Watch



Copyright 2007 Norm Barber, Adelaide, South Australia, Australia, standardoil@hotmail.com; gumflat88@hotmail.com . All Rights Reserved. This publication may not be reproduced, stored in a retrieval system or transmitted, in any form or by any means, without the author’s written prior permission. However, a single copy may be printed from an electronic database for the exclusive use of the person authorising or doing the printing. More generous copying and printing rights may be given upon application to the author, who encourages the wide reading of this text.

Acknowledgments

Dr David Wainwright Evans, Cardiologist, Queens' College, Cambridge, U.K.; Dr David Hill, Emeritus Consultant Anaesthetist, Cambridgeshire, U.K.; Dr R.G. Nilges, Emeritus Neurosurgeon, Swedish Covenant Hospital, Chicago, U.S.A.; Associate Professor Cicero Galli Coimbra, Head of the Neurology and Neurosurgery Department at the Federal University of Sao Paulo, Brazil; the late Dr Phillip Keep, former Consultant Anaesthetist, Norfolk and Norwich Hospital, U.K; Professor Nancy Scheper-Hughes, Director, Organs Watch, University of California; Associate Professor Mario C. Deng of Columbia University College of Physicians and Surgeons, New York; Dr Yoshio Watanabe, Consultant Cardiologist, Chiba Tokushu-kai Hospital, Funbashi, Japan; Duane Horton of OrganKeeper, Rhode Island, U.S.A.; Dr Peter Doyle of the British Department of Health; Berendina Schermers van Straalen, Kluwer Academic Publishers, PO Box 17, 3300AA Dordrecht, The Netherlands; David Brockschmidt and Vita Vitols of Skye, Australia, Anton Keijzer, Susan Mitchell, The Staff at the Port Adelaide Library; Karen Herbertt of the South Australia Organ Donation Agency; Bob Spieldenner of the United Network for Organ Sharing, U.S.A.; The Staff at the Disability Information and Resource Centre, Adelaide.


Contents

Foreword to the Third Edition
1. An Invented Death
2. Donors May Need Anaesthetic
3. The Apnoea "Brain Death" Test May Kill Patient
4. Organ Rejection
5. Battle for the Body
6. Aggressive Hospital Harvest Teams
7. Harvest Time
8. The Nurse’s Tale
9. Types of Donors
10. Donation after Cardiac Death
11. Futile transplants and flexible survival statistics
12. Body Parts and Business
13. Coercion, Live Donation and Slippery Ethics
14. Deception by Organ Donor Agencies
15. Australian Transplant Legislation
16. Avoiding Harvest Time
17. Societal Consensus and the Slippery Slope
18. Terminology and Gender Donor Rates
19. Getting A Transplant
20. Religion, Culture and Harvesting
21. The Politics of Suppressed Death Statistics
22. A Short History of Human and Xeno Transplanting
23. Trusting Your Hospital
24. Organ Selling, Organ Theft
25. Sociological Implications
Appendix One: Some Comments on Testing for Brain Death
Appendix Two: Some Comments on Treating Brain Injury
End Notes

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Thursday, February 14, 2008


Two Miracles

The legend of the Happy Plant says that when it flowers, a miracle happens.. My happy plant that I have been caring for for 23 years, since 1985, through 11 houses, is currently flowering for the first time...

I knew this was a time for miracles...
Please watch this video, please, it will continue to heal you as it heals all Australians

http://www.video.news.com.au/newsinteractive/videopage/videoplayer/?Channel=National+News&ClipId=1094_238199&bitrate=300&Format=wmp

The draceana fragrans massangiana, or I didn't know this but it is called a corn plant in the states, is known locally as a happy plant, or a chinese money tree, even though it is from Africa... the legend goes that you must never buy one for yourself, but only give them as gifts, or receive them as gifts, and when they flower, a miracle will occur... looks like we got ours :-)

The blooms have a deep frangipani like scent, which is interesting because it is dwarfed by my back neighbour's border of native frangipani (hymenosporum flavum) which also give off that scent, but they are not in flower currently.


It looks like this one:



I see these days the lucky bamboo and jade tree have taken over from the dracaena fragrans as the "Chinese Money Tree"

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Monday, February 11, 2008


Never treat hypoT on free T3 without taking symptoms into account

aka - never discount the T3 auto antibodies....

Ok we all know that using the TSH to dose thyroid meds is like trying to navigate a shopping mall using a soccer ball as a map - or maybe even less useful.

TSH only has a useful relationship to serum thyroid hormones when all systems are working properly, failing that, all bets are off.

As thyroid stimulating hormone is actually produced in the pituitary, and is released in response to the body perceiving a need for more thyroid hormone, a number of things can go wrong. The body may be in thyroid hormone conservation mode, this can happen after a number of years of being hypothyroid without treatment, or in the case of some, extreme dieting can bring it on, shock etc. The pituitary may not be unable to produce enough TSH to stimulate the thyroid gland, the body may not sense the lack and stimulate the pituitary to produce TSH, and you may have antibodies to the TSH itself, so the body attacks it's own hormone, and your thyroid doesn't get stimulated.

To get around this, most forward thinking people use the free t3 test to indicate how one should be replaced, correlating this to symptoms for "most" people has shown that with a freeT3 in the top 1/4 of the lab range, or just over, most hypothyroid people begin to feel well and regain some of the life they have lost to the illness.

But what if your free T3 is at the top of the range with no cessation of symptoms?

What if, like me, you can go for a week with no thyroid hormone supplement, and your symptoms worsen to the point of being bedridden, but your free T3 still shows on the top of range on a serum test while free T4 and TSH are both below range?

T3 has a half life of up to 10 hours, so after a week, it should be gone right?

Not neccesarily, what has been proven in case after case after case where an elevated T3 in the presence of hypothyroid symptoms has been evaluated, is the presence of antibodies to the T3 itself, which causes it to become bound in the serum, unavailable to the cells where it is needed for metabolism, causing high so called "free" T3 testing, and persistent hypothyroid symptoms.

Don't take my word for it, read the research, and DEMAND better treatment to the cessation of symptoms, rather than just to make some numbers on some paper look pretty.



http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=3224724&cmd=showdetailview&indexed=google

[Triiodothyronine(T3) autoantibodies in a woman with nonthyroidal disorder: a study on preparation of serum IgG fraction employing protein A column chromatography]
[Article in Japanese]
Mizuno E, Sugenoya A, Haniuda M, Sakai R, Kameko M, Kato M, Iida F.
Department of Surgery, Shinshu University School of Medicine.
A 48-year-old non-goitrous woman, who had undergone cardiac surgery for mitral stenosis under the extracorporeal circulation, showed high levels of serum T3 and free T3 in a recent follow-up study, employing antibody coated-bead RIA for T3 and -Amerlex M particle RIA for free T3. However, other thyroid function tests (T4, free T4, TSH and TBG) were normal. We suspected that thyroid hormone autoantibodies (THAA) in her serum interfered with T3 and free T3 analyses. The presence of THAA was demonstrated by the use of various procedures as follows. Firstly, the patient's serum was directly incubated with 125I-T3 or -T4 analog which did not bind to TBG, followed by B/F separation with polyethyleneglycol, counting the precipitates. Secondly, after the serum was treated with an acid-charcoal solution to remove circulating thyroid hormone, the measurement of THAA was made as stated above. Normal sera were used as controls. Both the non- and acid-charcoal-treated sera showed much higher percentages of 125I-T3 analog precipitation as compared with controls. In the case of 125I-T4 analog, there was no difference between them. In the third study, the presence of IgG antibodies that bound T3 but not T4 was investigated. The IgG fraction of the patient's serum was separated employing a Protein A-Sepharose CL-4B column chromatography. Then, the prepared IgG fraction was purified by a technique of gel filtration chromatography (Sephacryl S 200). Non-purified and purified-IgG fractions both revealed higher binding percentages of 125I-T3 analog than the control IgG fraction and non-IgG fraction of the patient. Furthermore, a good dose response was observed between the binding percentage of 125I-T3 analog and each dose of the patient's serum or IgG fraction. From these observations, it was clarified that this woman had anti-T3 IgG autoantibodies using a Protein A column chromatography with confirmation of gel filtration chromatography.
PMID: 3224724 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/8006324?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Thyroid hormone autoantibodies and their implications for free thyroid hormone measurement.
Vyas SK, Wilkin TJ.
Endocrine Section, University Medicine, Southampton General Hospital, UK.
Thyroid hormone autoantibodies (THAA) disrupt the equilibrium between thyroid hormones and their binding proteins. This may lead to spurious estimations of free thyroxine (FT4) and triiodothyronine (FT3) by radioimmunoassay (RIA). In the present study we highlight the importance of THAA by examining the frequency of THAA in consecutive sera sent to a routine district hospital laboratory. Over a period of six months, sera were collected from 200 consecutive hypothyroid, 200 hyperthyroid and seven patients whose clinical and biochemical thyroid status were contradictory. A further 200 patients with non-thyroid autoimmune conditions, 20 patients with insulin autoantibodies and 100 healthy blood transfusion donors were studied. In all sera, both effects of antigen removal on THAA detection and where THAA were found, the effect of their removal on FT4, were examined. The frequencies of THAA amongst hypothyroid, hyperthyroid and non-thyroid autoimmune conditions were 7%, 1.5% and 7.5% respectively, whilst no THAA were found in insulin autoantibody positive patients and 100 blood transfusion donors. However, THAA frequency was highest in those patients whose biochemical thyroid status was widely inappropriate to clinical state (5/7 = 64%). Sera stripped of thyroid hormones prior to THAA detection had significantly higher antibody activity than unstripped sera (p = 0.0027 and p = 0.0123 for T3 and T4 binding respectively). Free thyroxine levels measured by the Amerlex-M RIA kit after antibody removal fell in all 21 THAA positive sera tested. The correlation coefficient between antibody activity in serum with percentage fall in FT4 was 0.79 (Spearman's Rank Correlation Test).(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 8006324 [PubMed - indexed for MEDLINE]





http://www.clinchem.org/cgi/reprint/41/1/117

Spuriously High Concentration of Serum Free Thyroxine due to Anti-Trilodothyronine Antibodies ,
R#{233}S maypin, 1.3 Fran#{231}oiGseasser,' Andreas Boehn,2 and Muriel Rondeau2 ['Inst. de Phys. Biol. (Dir. Pr. J.
Chambron), Facultd de Med., F-67085 Strasbourg Cedex, France;2 Med. Interne A (Pr. D. Christmann), Clin. Med.
A, Hopital Central, CHRU, F-67091 Strasbourg Cedex, France; 3Author for correspondence: Fax Tnt + 33 88 3714 97, E-mail sapin@alsace.u-strasbg.frI
Free thyroxine (Fr4) is now frequently measured in serum by one-step labeled antibody assays based on a Solid-Phase Antigen-Linked Technique (SPALT) (1). In this assay the serum sample is incubated with a large excess of triiodothyronine (T3)-coupled solid phase and with a limited amount of labeled anti-T4 antibody. Because the solid phase acts as a ligand of low affinity for the anti-T4 antibody, interference from circulating anti-thyroid hormone (anti-T4 or anti-T3) autoantibodies (THAA) is theoretically possible.
However, until now, to our knowledge, this assay was considered to be only slightly affected by THAA (2-4).
The highest measured FT4 values (up to 35 pmol/L) could be related to therapy with T4 (4). Nevertheless, recently we observed a very high FT4 value (131 pmol/L) measured by a SPALT assay (Amerlex- MAB; Kodak Clinical Diagnostics, Amersham, UK) in the serum of a hospitalized patient with Crohn disease. This 33-year-old man was euthyroid by clinical evaluation and by his normal thyrotropin serum concentration (0.59 mIUIL, normal range 0.15-4.5 mIUfL) determined with BeriLux kit (Behring, Marburg, Germany). The biological evaluation showed a moderate hypergammaglobulinemia (17 g/L, normal range <14 g/L) with increased IgG concentration (21.8 g/L, normal range <17 g/L). The followed procedures were in accordance with the Helsinid Declaration of 1975 as revised in 1983.
This patient's serum contained anti-T3 but no anti-T4 antibodies, as identified with the technique of Allan et a!. (5) by using the analog T3 or T4 radioactive tracer of the Amerlex-M FT3 or FT4 kits, respectively (Kodak Clinical Diagnostics). The percentage of radioactive T3 analog tracer precipitated by polyethylene glycol, 12%, was above normal (5% in absence of THAA) but still quite low. The measurement of Amerlex-M FT3 remained normal ( 4.1 pmol/L, reference range 3.7-9.2 pmol/L). Fixation of a radioactive '251-labeled native T3 tracer on the fraction pre cipitated by polyethylene glycol was also not very high: 7.1% (vs normal of <5% in absence of THAA). That the free thyroidhormone concentrations were normal was confirmed by two-step RIAs known to be unaffected by the presence of THAA: FT4 24.8 pmol/L (normal range 9-25.7 pmol/L by Gammacoat"; Incstar, Stifiwater, MN); FT3 3.7 pmol/L (normal range 3.1-6.1 pmol/L by Ria-gnost; Behring). This very marked interference in the FT4 Amerlex-MAB assay shows an interaction of anti-T3 autoantibodies with the T3 immobilized on the solid phase. This interaction can occur in the presence of THAA of high affinity for the T3 fixed on the solid phase; perhaps the serum of this patient contains an antibody with a high affinity towards the T3- bridge that is used to link the solid phase to T3. This interaction can also occur with THAA of low affinity but of high capacity (i.e., the ligand is present in high concentration) (4).
The prevalence of THAA seems to be low (1/2360) (2) but the frequency of THAA is much higher in hypothyroid (7%), hyperthyroid (1.5%), and nonthyroid autoimmune ( 7.5%) patients (6). Compared with other one-step FT4 kits, the Amerlex-MAB assay is considered to be little affected by THAA (4), with only one of eight Amerlex-MAB FT4 results being higher than two-step values in the study by John et al. (2). However, users of this FT4 kit, and more generally of SPALT Fr4 kits with a T3-coupled solid phase, should be aware that such methods can give grossly misleading overestimates of FT., in presence of anti-T3 autoantibodies and produce a misclassification of thyroid sta tus. Therefore, not only anti-T4 but also anti-T3 antibodies should be suspected when a FT4 result does not correspond to the clinical state of the patient.

References
1. Christofides ND, Sheehan CP, Midgley JEM. One-step, labeledantibody assay for measuring free thyroxin. I. Assay development and validation. Cliii Chem 1992;38:11-8.
2. John R, Henley R, Shankland D. Concentrations of free thyroxunand free triiodothyronine in serum of patients with thyroxinand triiodothyronine-bindung autoantibodies. Clin Chem 1990;36: 470-3.
3. Sapin R, Gasser F, Schlienger JL, Chambron J. Analytical and clinical evaluation of a new one-step non-analogue radioimmuno assay for serum free thyroxin. Ear J Nucl Med 1990;17:111-5.
4. Sheehan CP, Christofides ND. One-step, labeled-antibody assay for measuring free thyroxine. II. Performance in a multicenter trial. Clin Chem 1992;38:19-25.
5. Allan DJ, Murphy F, Needham CA, Barron N, Wilkins TA, Midgley JEM. Sensitive test for thyroid hormone autoantibodies in serum [Letter!. Lancet 1982;ii:824.
6. Vyas SK, Wilkin TJ. Thyroid hormone autoantibodies and their implications for free thyroid hormone measurement. J Endocrino! Invest 1994;17:15-21.




http://www.clinchem.org/cgi/content/full/51/6/1071

Letters to the Editor

Falsely High Serum Free Triiodothyronine and Free Thyroxine Concentrations Attributable to Anti-Diiodothyronine and Anti-Triiodothyronine Antibodies
Kunihiro Iwahara1, Chizuko Tanabe1, Kozo Nishiyama2, Hiroyuki Ohashi 3 and Masato Maekawa1,a
1 Department of Laboratory Medicine
2 2nd Department of Internal Medicine and3 3rd Department of Internal Medicine, Hamamatsu University, School of Medicine, Hamamatsu, Japan
aAddress correspondence to this author at: Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192 Japan. Fax 81-53-435-2794; e-mail mmaekawa@hama-med.ac.jp

To the Editor:
We observed a patient with markedly increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations measured on a Vitros ECi analyzer (Ortho Clinical Diagnostics). The patient was a hospitalized 42-year-old woman with lupus erythematosus who appeared euthyroid and had normal thyroid-stimulating hormone (TSH) concentrations (Table 1 in the Data Supplement that accompanies the online version of this letter at http://www.clinchem.org/content/vol51/issue6/). Thyroid peroxidase antibody and thyroglobulin antibody were <0.3 kilounits/L, and rheumatoid factor was < 6.0 kilounits/L. We suspected interference from heterophilic antibodies (1 )(2), but our experiments suggested interference from antibodies to diiodothyronine (T2), T3, or their conjugates, as have been described (3 )(4)( 5). The procedures in this study were in accordance with the Helsinki Declaration of 1975 and the subsequent 1996 amendments.
In contrast to results of the Vitros ECi FT3 and FT4 assays, which use solid phases with T2 - and T3-gelatin, respectively, and labeled sheep antibodies, FT3 and FT4 were normal by the Elecsys assays (Roche Diagnostics), which use biotinylated antibodies in a one-step method.
To the Vitros FT3II and FT4 assay wells we added 0.05 mL of serum from the patient or from controls (n = 5) and 0.1 mL of diluent [phosphate-buffered saline (PBS) containing, per liter, 2 mL of Tween 20 (Sigma) and 10 g of bovine globulin (Sigma)], and incubated them at 37 °C for 18 min. After washing each well, we added 0.125 mL of horseradish peroxidase-labeled goat anti-human IgG antibody conjugate (Chemicon International. Inc.), diluted 50 000-fold in the same diluent, and incubated the mixtures at 37 °C for 18 min. After each well was washed, the Vitros Signal Reagent was added to the well, and the luminescence was measured (ALOKA luminometer). The IgG fraction of serum samples from the patient and from five control individuals was purified with a MAbTrapTM Kit (Amersham Biosciences), and the IgG concentration was adjusted to 4.0 g/L. The purified IgG (0.08 mL) was incubated at 4 °C for 24 h with 0.08 mL of PBS alone or with T2, T3, or T4 (Sigma; at 4570, 42, and 768 nmol/L, respectively) dissolved in PBS. Each sample was mixed vigorously with 1.2 mL of polyethylene glycol (PEG; 125 g/L), centrifuged at 2800g for 30 min, aspirated, and washed with 1.2 mL of PEG (125 g/L). After the precipitates were dissolved in 0.001 mol/L hydrochloric acid ( 0.04 mL) and neutralized by equal amounts of 0.001 mol/L sodium hydroxide, T2 and T3 were measured by the FT3 assay and T4 by the FT4 assay. The concentrations of T2 were expressed as T3 concentrations. Each sample was analyzed in duplicate. The ability of the purified IgG to bind T2, T3, or T 4 was defined as the difference between the FT3 or FT4 assay result and the respective blank value and is reported as the T2 , T3, or T4 value.
The ratios of FT3 and FT4 concentrations in PEG-treated samples ( 6) to those in untreated samples were significantly lower for the patient than for 37 other patients (Table 1 in the online Data Supplement); therefore, immunoglobulins in the patient's serum interfered with both the FT3 and FT4 assays. FT3 and FT4 values in the mixtures of serum with sheep IgG, bovine globulin, and gelatin did not differ significantly from those in the mixtures of serum and PBS only, suggesting that heterophilic antibodies and anti-gelatin antibodies did not cause the high FT3 and FT4 values.
When we examined the patient's IgG binding with Vitros FT3II and FT4 assay wells, the luminescence generated by the patient's serum was higher than that of the 5 control individuals (Table 1 in the online Data Supplement). This suggested that the patient's IgG bound to T2- and T3-gelatin.
The FT3 and FT4 concentrations in purified IgG and in treated samples of purified IgG ( 6) were below the lower detection limits of the Elecsys assays, suggesting an absence of T3 and T4 contamination in the IgG fractions. The patient's T2 and T3 values were higher than those of the 5 control individuals, but the T4 value was within 2 SD of the values for the 5 controls (Table 1 in the online Data Supplement). This finding implies that the patient's IgG interacted with T 2 and T3 but not with T4. The cross-reactivity of the anti-T3 antibody with T2 in the Vitros FT3II assay was very low, whereas the patient's T2 value was evidently higher than that of 5 control individuals. We conclude that T2 was bound to the patient's IgG.
Because anti-gelatin antibodies in the patient's serum were not recognized, we suggest that the interfering substance were antibodies to T2 and T3. As the interfering antibodies did not interfere with the Elecsys FT3 assay, the interfering antibody in the patient's serum may recognize T 2 and T3 conjugates used in the Vitros ECi FT3 and FT4 assays, as reported for a labeled-antibody assay ( 7). We suggest that this interference in the Vitros ECi FT3 and FT4 assays arose from antibodies to T2 , T3, or their conjugates.

References
1. Fiad TM, Duffy J, McKenna TJ. Multiple spuriously abnormal thyroid function indices due to heterophilic antibodies. Clin Endocrinol (Oxf) 1994;41:391-395. [Medline] [Order article via Infotrieve]
2. Kricka LJ. Human anti-animal antibody interferences in immunological assays. [Review]Clin Chem 1999;45:942-956. [Abstract/Free Full Text]
3. Lai LC, Day JA, Clark F, Peaston RT. Spuriously high free thyroxine with the Amerlite MAB FT4 assay. J Clin Pathol 1994;47:181-182. [Abstract/Free Full Text]
4. Sapin R, Gasser F, Boehn A, Rondeau M. Spuriously high concentration of serum free thyroxine due to anti-triiodothyronine antibodies. Clin Chem 1995;41:117-118. [Free Full Text]
5. John R, Henley R, Shankland D. Concentrations of free thyroxin and free triiodothyronine in serum of patients with thyroxin- and triiodothyronine-binding autoantibodies. Clin Chem 1990;36:470-473. [Abstract/Free Full Text]
6. Kuzuya H, Blix PM, Horwitz DL, Steiner DF, Rubenstein AH. Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes 1977;26:22-29. [Abstract]
7. Westerhuis LW, Venekamp WJ. Falsely high serum free thyroxine concentration measured with Amerlite-MAB FT4. Clin Chem 1995;41:633-634. [Free Full Text]





http://www.ncbi.nlm.nih.gov/pubmed/7535535?ordinalpos=15&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Autoimmunity against thyroid hormones.
Sakata S.
Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
The presence of thyroid hormone autoantibodies (THAA) is a common phenomenon. More than 270 cases have been reported by the end of 1993 involving not only thyroidal but also nonthyroidal disorders. Clinically, THAA in a patient's serum produces variation in thyroid hormone metabolism and, in particular, may interfere with the radioimmunoassay (RIA) results of total or free thyroid hormone measurements, which can cause unusually high or low values of the hormones depending on the B/F separation method used. This in vitro interference can give clinicians confusing information about the patient's thyroid state. As a result, the patient may receive inappropriate treatment from physicians who are unaware of this disorder. The presence of THAA has been reported not only in humans but also in dogs, chickens, and rats. In this review article, clinical features of THAA and the mechanism of autoantibody production are discussed.
PMID: 7535535 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/7958106?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[Studies on patients with a discrepancy between free thyroid hormones and thyrotropin values]
[Article in Japanese]
Hisaoka T, Iino S, Saitoh H, Yoshimura H, Ishikawa N, Momotani N, Ito K.
Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Thyroid function has been almost exactly evaluated by the measurement of serum free thyroxine (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) concentrations. However, we occasionally experience patients who show a discrepancy between free thyroid hormones and TSH values, and the assessment of thyroid function in such cases is extremely difficult. Thyroid hormone autoantibodies (THAA) interfere with radioimmunoassay (RIA) of FT4 and FT3 by giving inappropriate values. To investigate the incidence of THAA, immune precipitation of patients' sera after incubation with labelled T4 (125I-T4) or T3 (125I-T3) analog tracer was done in 394 patients with thyroid diseases. 9 patients ( 2.3%) showed an increased binding of 125I-T4 or 125I-T3 analog. Heterophilic antimouse antibodies in a patient's serum (human antimouse immunoglobulin antibodies: HAMA) can interfere in two-site immunometric assays (IMA) using mouse monoclonal antibodies and result in spuriously increased serum TSH concentrations. Manufacturers now customarily add nonspecific mouse immunoglobulins into their assay kits to absorb HAMA and prevent such interference. This approach may not always be enough to prevent HAMA interference in all samples. In 14 thyrotoxic patients with inappropriately high TSH measured by an IMA kit, we measured the levels of TSH by the further addition of mouse serum into this kit. Their serum TSH levels were fully suppressed except for 2 patients with a syndrome of inappropriate secretion of TSH (SITSH). The presence of abnormal albumin in the serum also interferes with RIA of FT4 and FT3. We experienced a female case of Graves' disease treated with methimazole who showed an inappropriately high serum FT3 measured by an analog tracer RIA kit, whose serum FT4, FT3 and TSH were 1.31 ng/dl, 19.3 pg/ml and 1.9 mu U/ml respectively. Although the anti-T3 autoantibody was considered to be present initially, immune precipitation of her serum with 125I-T3 analog tracer gave a negative result. In order to elucidate this finding, Sephadex-G200 chromatography of her serum after incubation with 125I-T3 analog tracer was done. Radioactivity of her serum in albumin fraction was significantly higher than that of normal control serum to indicate the presence of abnormal albumin in the serum. In conclusion, to assess the thyroid function of a patient with a discrepancy between free thyroid hormones and TSH values, it is important to consider the presence of THAA, HAMA, or rarely, an abnormal albumin.
PMID: 7958106 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/7556780?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[Three thyroid patients showing fluctuation of thyroid hormone autoantibody titers during long-term treatment]
[Article in Japanese]
Ikekubo K, Hino M, Saiki Y, Kajikawa M, Hattori N, Ishihara T, Moridera K, Kurahachi H.
Department of Nuclear Medicine, Kobe City General Hospital.
Development and fluctuation of thyroid hormone autoantibody (THAA) titers were observed during long-term treatment of thyroid diseases in three patients. The presence of THAA was noticed by spuriously high serum free thyroid hormone levels measured with an analog tracer RIA (Amerlex-M FT3, FT4) in all three patients. Amerlex-M FT3 or FT4 levels gradually decreased to appropriate values for the clinical status according to the decreasing titers of THAA. Free thyroid hormone levels with radiolabeled antibody radioassay (Amerlex-MAB FT3, FT4) were not affected by the THAA and always reflected actual thyroid function. Case 1 was a 46-year-old man with untreated primary hypothyroidism. Auti-T4 autoantibody was detected in his serum. The 125I-T4 analog binding to the autoantibody (125I-T4 analog binding ratio) gradually declined after L-T4 therapy and finally almost disappeared two years and four months later. Amerlex-MAB FT4 level rose to the normal range two months after T4 therapy, but TSH level remained slightly elevated ( 5.4-13 microU/ml) for five months during T4 therapy. The 125I-T4 analog binding ratio and anti-Tg autoantibody (TgAb) titer were inversely correlated. Case 2 was a 72-year-old woman had received desiccated thyroid for a long time. Sequential changes of 125I-T4 analog binding ratio were very similar to those of TgAb titer. Case 3 was a 74-year-old woman with Graves' disease. She had been treated with methimazole (MMI) and desiccated thyroid for three years and five months. Ten months after stopping both drugs, anti-T3 autoantibody was detected. The 125I-T3 analog binding ratio was transiently elevated and gradually declined to reference range for four years during L-T4 therapy. 125I-T3 analog binding ratio and TgAb titer changed in a similar way. These results suggest that desiccated thyroid hormone therapy and TgAb formation are related to the development of THAA and that L-T4 therapy reduces the THAA titer.
PMID: 7556780 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/8697622?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Autoantibodies to thyroid hormones: the role of thyroglobulin.
Erregragui K, Cheillan F, Defoort JP, Prato S, Fert V.
Immunotech, Marseille, France.
Autoantibodies against thyroid hormones (THAA) are frequently detected in the sera of patients with thyroid disorders together with autoantibodies against thyroglobulin (TGAA). THAA are considered to be a subset of TGAA, but alternative possibilities have not been excluded. We hypothesize that if THAA arise through an immune response to iodothyronines carried by circulating thyroglobulin (hTg), THAA should be found together with autoantibodies against the peptide backbone of hTg (TPAA) close to the hormone-forming sites. We measured TPAA in 178 serum samples, obtained from healthy subjects and patients with thyroid disorders, using two hormone-forming peptides isolated from hTg. The occurrence of TPAA was much lower than that of TGAA. Autoantibodies to the hormone-rich peptide, P3, were significantly more common than autoantibodies to the hormone-poor peptide, P1 (111/178 = 62.3% for TGAA versus 21/178 = 11.8% for anti-P3 TPAA and 7/178 = 3.9% for anti-P1 TPAA). The presence of autoantibodies to thyroid hormones was investigated in 25 TPAA+ and 26 TPAA- sera. THAA were found more frequently in TPAA+ sera (10/25 = 40% for TPAA+ and 4/26 = 15.3% for TPAA-). Correlation analysis shows that the anti-P3, but not the anti-P1 binding activity, correlates positively with the THAA-binding activity (P < 0.001 for anti-T4 THAA; P < 0.01 for anti-T3 THAA). Specificity of anti-P3 TPAA indicates that a subset of the anti-P3 antibodies is directed against the thyroid hormone moiety and another subset is directed against the peptide backbone near the hormone-forming peptide, according to our hypothesis. These results indicate that the THAA response is an anti-hTg response directed, in a significant number of cases, against the hormone-forming site included in the P3 peptide. This response seems to be elicited by either native hormone-rich hTg or by hTg fragments.
PMID: 8697622 [PubMed - indexed for MEDLINE]




http://www.ncbi.nlm.nih.gov/pubmed/9175389?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Antitriiodothyronine antibody in patient with Hashimoto's thyroiditis.
Plengvidhya N, Sunthornthepvarakul T, Vannasaeng S.
Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
We described a 44-year-old female patient with a history of goiter for 2 months. Physical examination revealed a diffusely enlarged thyroid gland weighing 40 g firm to hard in consistency. She was clinically euthyroid and had neither ophthalmopathy nor dermopathy. Serum thyroid hormone levels revealed total T4 (RIA) of 4.8 micrograms/dL (normal, 4-11 micrograms/dL), total T3 (RIA) of above 600 ng/dL (70-175 ng/dL), and TSH (IRMA) of 54 mU/L (0.3-6 mU/L). Antithyroglobulin and antiperoxidase antibody titers were 1:5,120 and 1:409,260, respectively. Because of the discrepancy between the patient's clinical status and laboratory values, assay for thyroid hormone autoantibodies (THAA) was done and subsequently demonstrated antitriiodothyronine antibody with percentage of precipitation by polyethylene of 98.4 per cent (normal range, 3.06 +/- 8.58%). In conclusion, THAA should be suspected in patients whose clinical status is incoherent with the thyroid function test.
PMID: 9175389 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/6896035?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus

[A study on anti-T3 and anti-T4 autoantibodies found in two sisters with juvenile hypothyroidism due to Hashimoto's thyroiditis (author's transl)]
[Article in Japanese]
Nakamura S, Fushimi K, Okuyama M, Miura K.
Anti-thyroid hormone autoantibodies were found in two sisters of short stature (case 1: 13 years old, case 2: 10 years old). Physical examination revealed clinical findings of hypothyroidism with diffuse goiter. A diagnosis of Hashimoto's thyroiditis was made by open biopsy of the thyroid gland in both patients. Serum levels of T3 and T4 were assayed by double antibody radioimmunoassay. In case 1, serum T3 level was 16 ng/dl and serum T4 level was 2.0 microgram/dl. In case 2, serum T3 levels were high (range, 375 approximately 1660 ng/dl), while serum T4 remained at a very low level (0.9 microgram/dl). On the other hand, the level of T3 in case 2 as well as the level of T4 in case 1 was not detectable by a single antibody radioimmunoassay using dextran-coated charcoal or polyethylene glycol separation. In each case, the serum TSH level measured by double antibody radioimmunoassay was extremely high (255 microunits/ml in case 1, 240 microunits/ml in case 2), which was compatible with the clinical features of primary hypothyroidism. Sera from both patients were incubated with 125I-T3 and 125I-T4, followed by precipitation with polyethylene glycol. The binding of 125I-T3 with serum from case 2 and the binding of 125I-T4 with serum from case 1 were markedly high, suggesting the presence of T3- and T4-binding substance(s) in the sera. IgG prepared from the sera of both cases showed marked and specific binding with T3 in case 2 and T4 in case 1. The association constant for T4-antibody in case 1 was 5.2 x 10(8) M-1 and for T3-antibody in case 2 was 5.0 x 10(9) M-1. The binding capacity for T4 was 1.2 ng/ml.IgG and for T3 was 0.3 ng/mg.IgG.
PMID: 6896035 [PubMed - indexed for MEDLINE]

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Thursday, February 07, 2008


Kung Hi Fat Chow!!!

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