T4/T3 kombinasjonsbehandlingI Norge er det egentlig greit å få kombinasjonsbehandling. I gamle dager, når man bare hadde skjoldkjertelekstrakt, fikk pasientene faktisk kombinasjonsbehandling.. Thyroxin
ble registrert her i 1950 (kilde: www.legemiddelverket.no,
www.legemiddelsiden.no , preparatomtaler) |
||
| tilbake | til historien til Armour og thyroxin | |
| Artikkel
i legetidsskriftet nr 9/2002 av Haug
flere studier: A.M.Sawka et.al Kanada 2003pdf høyreklikk og velg last med |
Her har mange pasienter med suksess brukt
kombinasjonsbehandling, uten at det er stor debatt om det nå.
Stoffskifteforeningen (nå: thyreoideadoebundet) stod på for
å gjøre det kjent. Riktig dose å prøve er 10µg, som er en halv tablett, og den må man brekke i halv igjen og ta 5 µg i to omganger med fire-fem timers mellomrom. Per Egil Haug har nevnt dosen liothyronin ved kombinasjonsbehandling i en av artiklene i serien om thyreoidea som kom i 2002 . Det står i nummer 9 og 10, og ligger ute på internett. Det antydes 100µg levaxin pluss 10 µg liothyronin som et mulig sted å starte. Pasienter melder også om at man etterpå må sjekke hvordan ft4 og
ft3 oppfører seg, siden ft4 ofte går ganske mye ned og mange trenger
den opp igjen ved en liten økning av levaxin-dosen (i samråd med
legen, selvsagt). Mange beskriver virkningen av liothyronin som dramatisk, at tåken lettet innen noen timer og at de kunne konsentrere seg igjen. De som pga. legens uvitenhet prøvde hele tabletter, til og med flere tabletter om dagen, opplevde hjertebank og overdose-symptomer. I det store og hele er kombinasjonsbehandling her i Norge ganske greit, bare man vet at man må følge opp med blodprøver fordi ft4 kan synke, samt at man ikke skal ta hele tabletter på 20 µg.
Utlandet:Det ser ut som om de må gjøre forsøk i utlandet før de kan gå god for en type behandling. Dette er nok veldig vanskelig angående thyreoideasykdommer, siden dosene er så individuelle. Hvis man tenker etter, så er dosene hos de aller fleste andre medisiner like for alle voksne, med egne tabeller for barn. I konklusjonene til noen medisinske forsøk skylder de på at liothyronin må være upålitelig. Jeg har lest et par av artiklene (Noen må man betale for å få lest) og jeg synes at de har underbehandlet pasientene, siden TSH gikk opp, og at forsøkene var dårlig planlagte siden de ikke kunne øke thyroxindosen slik som forsøket var planlagt. Jeg mener at man må innrømme at forsøket avdekket at planleggingen må forandres, istedenfor å konkludere med at "placeboeffekten holdt ikke lenge" eller at liothyronin er ustabil. Utenlandske leger (fra land hvor andre preparater brukes) siteres ang. påstått upålitelighet i doser på t3 i Armour og påstått pålitelighet av levothyroxin. Amerikanske leger vet at det står i Federal Register at levothyroxin (og ikke Thyroid USP) er upålitelig. Derfor må man referere til skribenter utenfor USA. Det har vært trykket flere artikler om forsøk med t4/t3 kombinasjonsbehandlig i JCEM.Det tar en stund til jcem artiklene er gratis. Her er en australsk studie. Legg merke til at de tok vekk mer t4 enn som ville tilsvart dosen liothyronin, 10µg t3 er mer lik 36µg thyroxin. Da er det en stor risiko for at pasientene blir underbehandlet. Jeg så etter denne når jeg fant en medscape-artikkel som sa at man foretrekker t4 alene fordi den er mer stabil og er kjent for å være mer stabil enn t4. I medscape-artikkelen sies det at t3-behandlign og desiccated Thyroid gir svingninger i t3- nivåene med referanse til denne artikkelen her. Det menes formodentlig serum t3-nivåer siden levothyroxin er kjent for å være ustabil slik som dokumentert i Federal register i USA, og alle levothyroxinpreparater måtte gjennomgå en ny NDA New Drug Application. Mer om dette på en annen side her. Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary HypothyroidismJohn P. Walsh, Lauren Shiels, Ee Mun Lim, Chotoo I. Bhagat, Lynley C. Ward, Bronwyn G. A. Stuckey, Satvinder S. Dhaliwal, Gerard T. Chew, Minoti C. Bhagat and Andrea J. Cussons http://intl-jcem.endojournals.org/cgi/content/full/88/10/4543 Kommentar: Pasientene på thyroid.about.com forumet vil angripe temaet fra en helt annen synsvinkel, ikke så fokusert på TSH, de går etter ft4 og ft3. Hvis man er ok med t4 alene, og man kan følge en viss TSH, altså hvis man vt hvilken TSH man er helt ok på, da gjør man ikke noen forandringer. Hvis man er fremdeles dårlig, og ikke har lavt Ferritn, B-12 eller D-vitamininnhold i blodet, så ser men på ft4 og ft3. de fleste må ha ft4 i øvre halvdel av laboratoriets referanseområde, og mange veldig høyt. Så er neste trinn å se på ft3. Veldig mange har blitt mye bedre når de tok tilskudd av t3 (Liothyronin, i amerika heter det cytomel) som hever ft3-nivået. da er man på stadiet av de kliniske forsøk, de tar vekk 50µg t4 og
tilfører 10 eller 12,5 µg t3. Neste skritt er altså å måle ft4 og ft3 igjen og øke t4-dosen til man har en bra ft4 igjen, vanligvis i øvre halvdel. Noen få har det ok med en lav ft4 så lenge som ft3 er ganske høy, noen ganger litegrann over referanseområdet. Det samme gjør man med kombinasjonen Armour og levaxin, man går etter ft4 og ft3. Veldig mange pasienter har da en veldig lav TSH, fordi t3 senker TSH veldig mye. Dette andre trinnet er alltid utelatt i studiene jeg har lest, å øke t4-dosen tilbake. Her er beviset på at pasientene var underdosert i denne studien:
During combined T4/T3 treatment, serum free T4
was significantly (P < 0.001) lower than during T4
treatment (Table 5 TSH gikk altså
opp til 3 og ft4 ned. Vi kunne fortalt dem dette hvis de hadde lest på
forumene og lest hvordan pasienten må øke t4 tilbake igjen. Og
hvor står det noe om at t3 og desiccated thyroid er ustabilt, eller gir
ustabile blodverdier? "ustabile
blodverdier" er også sitert av BTA i sitt Statement
on Armour Thyroid . De gir ingen referanser, men det jeg antar er at
de lener seg til de diverse Medscape artikler som henviser til artiklene ovenfor av Walsh et al som igjen gir en referanse til
Wiersinga artikkelen. "Abstract Thyroid hormone replacement has been used for more than 100 years in
the treatment of hypothyroidism, and there is no doubt about its overall
efficacy. Desiccated thyroid contains both thyroxine (T4) and
triiodothyronine (T3); serum T3 frequently rises
to supranormal values in the absorption phase, associated with
palpitations. Liothyronine (T3) has the same drawback and
requires twice-daily administration in view of its short half-life.
Synthetic levothyroxine (L-T4) has many advantages: in view
of its long half-life, once-daily administration suffices, the
occasional missing of a tablet causes no harm, and the extrathyroidal
conversion of T4 into T3 (normally providing 80%
of the daily T3 production rate) remains fully operative,
which may have some protective value during illness. Consequently, L-T4
is nowadays preferred, and its long-term use is not associated with
excess mortality. The mean T4 dose required to normalize
serum thyroid stimulating hormone (TSH) is 1.6 µg/kg per day, giving
rise to serum free T4 (fT4) concentrations that
are slightly elevated or in the upper half of the normal reference
range. The higher fT4 values are probably due to the need to
generate from T4 the 20% of the daily T3
production rate that otherwise is derived from the thyroid gland itself.
The daily maintenance dose of T4 varies widely between 75 and
250 µg. Assessment of the appropriate T4 dose is by assay of
TSH and fT4, preferably in a blood sample taken before
ingestion of the subsequent T4 tablet. Dose adjustments can
be necessary in pregnancy and when medications are used that are known
to interfere with the absorption or metabolism of T4. A new
equilibrium is reached after approximately 6 weeks, implying that
laboratory tests should not be done earlier. With a stable maintenance
dose, an annual check-up usually suffices. Accumulated experience with
L-T4 replacement has identified some areas of concern. First,
the bioequivalence sometimes differs among generics and brand names.
Second, many patients on T4 replacement have a subnormal TSH.
TSH values of Copyright © 2001 S. Karger AG, Basel" Merk at man i holland bruker Thyreoïdum, et preparat av tørket
svinekjertel fra Danmark, med varierende innhold av T4 og T4, og det
inneholder en del mindre t4 enn Thyroid USP per 60 mg, nemlig ca 24µg
mot Thyroid USP som har 38µg. Til gjengjeld er hver batch nøye
analysert og varer i ett helt år. Det er dette som kan kalles
varierende styrke på tørket-kjertel-preparater, men det varierer ikke
fra tablett til tablett, men fra ett år til det neste året. Pasientene
merker forresten ikke noe fordkjell når man spør på det hollandske
forumet. Dr. Lowe benekter at hjerteklapp er et problem ved behandling med
Armour Thyroid. Derimot har de som har lavt ferritin, under 50-70, en generell
intoleranse mot stoffskiftemedisiner, altså at de reagerer med
hypersymptomer ved økning mens TSH ennå er høy og ft4 ennå er lav og
de har hyposymptomer.
Det gjelder ikke bare Armour eller liothyronin , det gjelder generelt
for alle, og de fleste klager over at de ikke tåler thyroxin. Grunnen
er en hyperadrenerg reaksjon hvis man har lavt ferritin. En som har lest referansene som det refereres til når man
fraråder desiccated Thyroid er Gaby. Pdf
her Her er utdrag fra artikkelen hans om bruken av Armour Thyroid: " Objections to the Use of
Armour Thyroid The main objections voiced in
textbooks and editorials 1,73
regarding the use of
desiccated thyroid are: (1) its potency
varies from batch to batch, and (2) the use of
T3-containing preparations causes the serum T3
concentration to rise to supraphysiological levels.
Regarding between-batch variability, there may have
been some problems with quality control a
half-century or more ago, and in a 1980 study a
number of generic versions of desiccated thyroid were
still found to be unreliable in their potency.
The amounts of T4 and T3 in Armour thyroid, on the
other hand, were found to be constant.74
Moreover, two-year old tablets of Armour thyroid
contained similar amounts of T4 and T3 as did
fresh tablets. Three studies are typically
cited to support the contention that
T3-containing preparations should not be used. Smith et
al reported a levothyroxine-plus-T3 product
caused adverse side effects in 46 percent of
patients; whereas, side effects occurred in only 10
percent of those receiving levothyroxine alone.75
In that study, however, the combination product and
the levothyroxine product
differed substantially in potency. For the combination
treatment, each 100 mcg of levothyroxine was
replaced by 80 mcg of levothyroxine plus 20 mcg of
T3. Considering 20 mcg of T3 is equivalent to 80
mcg of levothyroxine, the total
hormone dose in the combination product was 60-percent
greater than that in the levothyroxine
preparation. Therefore, the high incidence of adverse
side effects may not have been due to the T3, but to
the higher total dose of thyroid hormones. In the second study, by Surks
et al, the administration of
T3-containing preparations to hypothyroid patients caused
the plasma T3 concentration to become markedly elevated
for sev-eral hours after ingestion of the
medication.76 In most cases, however, the
amount of T3 administered (50-75 mcg) was considerably
greater than that contained in a typical
dose of desiccated thyroid (9 mcg T3 per 60 mg),77
and/or the total dose of thyroid hormones given was
excessive (180 mcg of levothyroxine plus 45
mcg of T3). By contrast, in a patient given 60 mg of
desiccated thy-roid, the plasma T3 concentration
increased from a hypothyroid level to a
euthyroid level. Of two hypothyroid patients treated
with 120 mg per day of desiccated thyroid, one
showed a relatively constant plasma concentration
of T3. In the other patient, the T3 level
increased by a maximum of 80 percent, to the bottom of
the range seen in hyperthyroid patients, and returned to the
baseline value within 24 hours. In
that patient, the pre-dose plasma T3 concentration was
near the top of the normal range, suggesting that
this patient may have been receiving too high
a dose of desiccated thyroid. Finally, Jackson and Cobb
reported that the serum T3 concentration (measured
2-5 hours after a dose) was above
normal in most patients receiving desiccated thyroid.2
They concluded there is little use for
desiccated thyroid in clinical medicine. Most of the
patients (87.5%) in that study, however, were taking a
relatively large dose of desiccated thyroid
(120-180 mg daily). Moreover, 57.5 percent of the patients
were not being treated for hypothyroidism,
but rather to suppress the thyroid gland. Nearly
half of the patients continued to have an elevated serum T3
concentration after they were switched to
levothyroxine, even though the equivalent
dose was reduced in 62.5 percent of patients.
Thus, the elevated serum T3 concentrations found in
this study can be explained in large part by the high
doses used and by the selection of patients,
the majority of whom were not hypothyroid. What
this study does suggest is that desiccated thyroid
should not be used for thyroid-suppression
therapy. Although the oral
administration of T3 causes a transient increase
in serum T3 concentrations, that fact does not appear to
be of significance for hypothyroid patients
receiving usual replacement doses of Armour
thyroid. In this author’s experience,
reports of post-dose symptoms of hyperthyroidism are
extremely rare, even among patients taking larger
doses of desiccated thyroid. An occasional
patient reports feeling better when he or she takes Armour
thyroid in two divided doses daily. The
nature of that improvement, however, is usually an
increase in effectiveness, rather than a reduction in
side effects. For patients taking relatively
large amounts of desiccated thyroid (such as 120 mg daily
or more), splitting the daily dose would obviate
any potential concern about transient
elevations of T3 levels. In practice, however,
splitting the daily dose is rarely necessary. " Så konklusjonen må være at man alltid skal sjekke referansene og
ikke umiddelbart ta dem for god fisk, spesielt når det ikke stemmer med
hva man har erfart og hva pasientene har erfart. For ordens skyld, her er hva BTF skriver: " Armour thyroid is a brand of natural desiccated thyroid extract made
by Forest Laboratories in the United States. Natural desiccated thyroid tablets are made from raw pork thyroid
glands collected at slaughterhouses, which are tested for absence of
Salmonella and E. Coli, then held in a frozen state until they are
delivered to the processing laboratory where they are minced, placed in
a vacuum dryer, defatted, then milled to a fine powder before being
packaged. Samples are tested for chemical and microbiological
characteristics. The manufacturers state that the following are the ingredients of
Armour: Active ingredients: T3 and T4 We have written on several occasions to the manufacturers to ask for
confirmation of their ingredients and for details of their quality
control procedures but have received no reply to date. Desiccated thyroid extract is not currently licensed in the UK and
was withdrawn from use in the UK in the 1970s after synthetic thyroxine
had been developed. At that time there was perceived to be a problem
with the quality control of thyroid extract with large variations from
batch to batch, due to the variation in T4 (thyroxine) and T3 (triiodothyronine)
that it contained. There is concern amongst some doctors over the substantial
fluctuations in T3 levels in blood of patients treated with Armour and
the potentially harmful effects on the heart (rapid irregular heart beat
which predisposes to clots forming inside the heart and then causing
strokes) and bones (osteoporosis). It is difficult to monitor treatment containing a combination of
T3/T4 because of peaks and troughs in T3. The long-term effects of T3,
Armour, or combinations of T3 and T4 are not known. T3 has a short
half-life of a few hours. Patients on T3 have fluctuating T3 levels and
at times these may go beyond the upper limit of normal. By contrast T3
levels in patients on thyroxine are stable. Monitoring thyroid hormone
replacement in patients on T4 is easy biochemically because of the
stable levels. In someone on T3 or Armour it will depend on the time
since the last dose. The Medicine and Healthcare Products Regulatory Agency (MHRA), the
licensing authority for pharmaceuticals in the UK and executive agency
of the Department of Health, states that natural thyroid products
including Armour are not currently licensed in the UK. Any hormone
preparation would be classed as a medicine in the UK. As a result they
can only be marketed if they have been fully assessed for safety,
quality and efficacy by the MHRA and granted a marketing authorisation
or product licence. The MHRA does not object to importation of
desiccated thyroid extract products provided that they are approved by
the United States' Food and Drugs Administration (FDA), standardised to
the specification of the United States Pharmacopoeia (USP), and that
they are authorised, prescription-only medicine for the treatment of
patients with thyroid diseases for whom the UK-licensed synthetic
thyroid hormones are not suitable. The MHRA says that it is the decision
of each individual PCT as to whether an unlicensed product, in this case
Armour, be available on NHS prescription or private prescription (MHRA,
Jan 2005). If it is prescribed on an NHS prescription, the patient
qualifies for medical exemption because the treatment is for
hypothyroidism. Being unlicensed in this country, the doctor would be
required to take full responsibility for any adverse effects of the
treatment. The Medicines Act makes provision for doctors to prescribe an
unlicensed medicine to meet the needs of an individual patient, on their
own responsibility, where they judge the benefit to the patient is
justified and outweighs the risk of the unlicensed product. Therefore,
the prescription of Armour is a question of clinical judgement on the
part of each patient's GP. It is the responsibility of NHS Primary Care
Trusts to fund supplies of medicines in their area, whether on a trial
or permanent basis. Therefore the decision to provide Armour free from
prescription charges would be taken by the GP in consultation with the
local PCT. The BTF sees synthetic thyroxine as the current first-line treatment
of hypothyroidism. Current medical practice is governed by evidence.
There is no known research showing that porcine thyroid extract is
superior to synthetic thyroxine. On the contrary, there are good data
that life-long treatment with synthetic thyroxine is safe. The BTF understands that there are concerns about the use of Armour
thyroid because of the rapid fluctuations in T3 levels, the difficulties
in monitoring such treatment, uncertainties about the long-term health
consequences and the considerably higher costs of such treatment. The major professional thyroid organisations and published
peer-reviewed guidelines on treatment of hypothyroidism recommend
thyroxine as the treatment of choice for hypothyroidism and our position
is in keeping with this view. We believe that patients who feel unwell on thyroid hormone treatment
merit assessment by a qualified, accredited endocrinologist. Such a
management pathway will ensure that thyroid hormone replacement is
optimal, other causes of symptoms are considered and a meaningful
exploration of the potential risks and benefits of unproven therapies
such as Armour can be explored. We do not consider natural thyroid extract to be suitable for
everyone but acknowledge that patients for whom synthetic thyroxine is
judged not to be suitable on clinical grounds may, together with their
doctor, wish to explore treatment with Armour. We acknowledge that some doctors, acting out of the best possible
interests in the well-being of their patients, and basing their
judgement on current research evidence, may be reluctant to prescribe
Armour. Much of the debate about the use of Armour relates to individual
accounts of patients who are convinced that switching from thyroxine to
Armour has transformed their lives. Doctors are equally aware of
patients who have found this treatment unhelpful and some have felt
worse than on thyroxine. We feel that it is important to keep an open
mind about alternative thyroid hormone replacement regimens to thyroxine,
but these issues can only be addressed by a properly conducted
prospective randomised controlled trial. " ------------------------------------ Dette er en privat hjemmeside. og ingen må ta dette som medisinske
råd. |
|
0.1
mU/l carry a risk of development of atrial fibrillation and are
associated with bone loss although not with a higher fracture rate. It
is thus advisable not to allow TSH to fall below - arbitrarily - 0.2 mU/l.
Third, recent animal experiments indicate that only the combination of T4
and T3 replacement, and not T4 alone, ensures
euthyroidism in all tissues of thyroidectomized rats. It is indeed the
experience of many physicians that there exists a small subset of
hypothyroid patients who, despite biochemical euthyroidism, continue to
complain of tiredness, lack of energy, discrete cognitive disorders and
mood disturbances. As organs vary in the extent to which their T3
content is derived from serum T3 or locally produced T3
from T4, these complaints may have a biologic substrate; for
example, brain T3 content is largely determined by local
deiodinase type II activity. Against this background it is of interest
that a number of psychometric scores improved significantly in
hypothyroid patients upon substitution of 50 µg of their T4
replacement dose by 12.5 µg T3. Confirmatory studies on this
issue are urgently awaited. It could well be that a slow-release
preparation containing both T4 and T3 might
improve the quality of life, compared with T4 replacement
alone, in some hypothyroid patients.