This study found TSH lower when taking T4 at night instead of morning
http://www.blackwell-synergy.com/action/showPdf?submitPDF=Full+Text+PDF+%28230+KB%29&doi=10.1111%2Fj.1365-2265.2006.02681.x
new TSH, T4, TT4, sulfation etc paper .. measures every hr for 24 hrs
Link
About Three years ago Leslie (US Forum) did a switch from morning dose to evening dose of Thyroid meds.....along with other members of her family, for a number of sensible reasons.
Now, a Dutch team:- Bolk, Visser et al, from Erasmus Medical Centre in Rotterdam have taken that a step further and carried out a preliminary study to show that a larger investigation would not lead to faulty assumptions on the methods adopted.
Their preliminary findings are somewhat more astonishing than they thought they might have been (even from a small sample)
On shifting the time at which the meds were taken,
a) it was better absorbed,
b) it didn't change the circadian pattern of overnight TSH production
c) it greatly improved the resulting TSH (lower) from the same dose of meds
d) it unexpectedly demonstrated that FT4 was elevated and has a circadian rhythm
and work carried out by Visser with Saravanan and Dayan from Bristol University also added to the data, as elevated FT4 showed improved psychological well-being.
Bob
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I think the increase in is not just the absorption/digestion of T4 o'nite compared to in the day.. although that's way up there in the possibilities..
but I also think it has to do with a couple of undiscussed factors
1. "When T4 is released from the thyroid, it is primarily in a bound form with thyroid binding globulin (TBG), with lesser amounts bound to thyroxine-binding prealbumin (TBPA). It is estimated that only 0.03-0.05 percent of T4 within the circulatory system is in a free or unbound form; this unbound T4 is called free-T4 (fT4). "
so when we take t4 meds .. what are they bound to when absorbed??.. main question I'd like answered..and surely must be known?..????
If all free,T4.. that would increase the FT4 in blood a lot more than endogenous?.. or is the amount of T4 taken usually only sufficient to raise FT4 to ''normal" levels and not allow for thryoid binding.. I , at least, can see why FT4 may have to be above "normal for endogenously produced FT4 levels".. if we don't get a raise in total T4 somehow as well...then again,maybe it binds readily as absorbed???
If not the higher T4 would probably result in some quick "getting rid of this high FT4 "that can't be handled by the deioinases.. like via sulfation (see 2.)
2. "Evidence also indicates the sulfation pathway for T4 increases substantially following exogenous T4 therapy in premenopausal women. Although only low T4S levels are detectable in serum both pre- and post-T4 treatment, urinary T4S values increase significantly.[49] However, unlike T4, significant increases in both serum and urine T3S levels are observed following T4 therapy.[50] "
http://www.encyclopedia.com/doc/1G1-65068470.html
Perhaps as well as absorbing more, maybe during the night some of the T4 can bind better to become total T4 instead of being converted to T4S and T3S?
If you look at this a little more closely.. look at the graph for TBG (which binds most of the T4 released from the thryoid gland if one is "normal")... note how there is more TBG available from mid afternoon with the night time dosing.
This could be because estradiol has a peak (according to Larrian, an ) at noon.. and estradiol rising maybe would raise TBG.. I know estradiol rising can raise TBG levels in blood.. (from studies i think).. but why more when T4 was taken only at night??
The extra TBG available in the graphs, no matter how it WAS higher, could bind the T4 absorbed (with luck) and you'd have more TT4 (as observed).. now this increase in TT4 is probably more of big thing than the incr in FT4..as the amount of TT4 is way bigger (see in nmol not pmol for starters.. hundreds of times more in other words).. and this TT4 can keep the FT4 and FT3 higher thru the days following.. There is No great rush to lower it to a "normal ":amount of FT4 and possibly not as much T4S and T3S in urine?
Pity they didn't check that?.. will have to look at in more detail though to be sure
rough ideas here.. not finished post
Also I've found with iodine that it helps a lot with night sweats.. which are definitely estradiol related.. so maybe this TBG is to do with the iodine released from the T4 being available to help with estradiol metabolism at night somehow..I think its to do with conversion to estriol, unsure though (apparently the iodine from thryoid hormones may get reused by body either in formation of new thyoid hormones or as iodine in breasts etc)? .. all too confusing for me... But if more is converted to estriol in correct pathways with the extra iodine available.. then maybe somehow there's more TBG available to be used by the T4... really over my head though..and surely mroe complicated than my brain can get around at present..
There are other known pathways besides sulfation.. like carboxylation,glucuronidation, ,even I think hydoxylation? (not sure there's a effect of alcohol too somewhere but I've forgotten) and other metabolites.
eg. thyroid hormones can undergo deamination and decarboxylase reactions in the liver resulting in the formation of so-called acetic acid analogues of thyroid hormones ..In human liver, both triac and tetraiodothyroacetic acid are conjugated by glucuronidated reactions about 1500 and 200 times faster than T3 and T4, respectively. This preference of conjugation reactions for the acetic acid analogues might partially explain their short half-life in the body.[56]
Then there's bromide replacing iodide (if it does),
but sulfation, at least for starters, ought to have been looked at(I don't think much is known about the other paths ).. yes there re all minor pathways compared to the deiodinases
thing is..
"It is estimated that more than 70 percent of T4 produced in the thyroid is eventually deiodinated in peripheral tissues, either at the outer phenolic ring to form T3 or at the inner tyrosyl ring to form rT3.[2] "
so the other 30% is..??.. but will have to look at original studies to be sure of percentages. the way this other 30% is converted in the body must have a significant impact on the free levels when you consider that it is "estimated that only 0.03-0.05 percent of T4 within the circulatory system is in a free", (FT4)
All quotes from
http://www.encyclopedia.com/doc/1G1-65068470.html (above)
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It is a good study, however instead of suggestion absorption is defferent during the night than in the day, perhaps they should have looked at the excretion in thryoid hormones (and metabolites?) in the faeces first?.. and it would have been great to have urine metabolites tested as well.(like the T4S, T3S etc and see if these were different in those taken at night and day..considering it was known that there is a difference in those taking exogenous thyroid meds and those who are "normal".. own thryoid producing endogenous thryoid hormones). Perhaps this should be looked at in any future studies .. cheeky grins.
yep, good study!
If the difference was being excreted in faeces, the yes, the absorption rate would be cause?.. if not.. then no?
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, aged 34.7 +/- 8.0 years. Serum Ct was measured by IRMA. The Ct secretory response was related to thyroid size and cytological data, when available. RESULTS: Basal Ct concentrations in groups GH (0.08 ng/l, median) and AH (0.07 ng/l, median) were significantly lower than those of female controls (0.58 ng/l, median). Stimulated Ct peak values in groups GH (0.08 ng/l, median) and AH (0.19 ng/l, median) were significantly lower than those of female controls (13.61 ng/l, median). Also, both basal (2.72 ng/l, median) and stimulated Ct levels (35.73 ng/l, median) in male controls were significantly higher than in female controls given already. A positive correlation between the Ct secretory reserve and thyroid dimensions, evaluated by ultrasound scan, was found only in patients with thyroid atrophy (AH; rs = 0.61, P < 0.05). CONCLUSIONS: We have found low basal and stimulated calcitonin values in patients with chronic autoimmune thyroiditis and thyroid enlargement, which represents an early phase of chronic autoimmune thyroiditis. Our data have also confirmed previous findings of deficient calcitonin secretion in advanced stages of chronic autoimmune thyroiditis in which thyroid atrophy is usually found. These findings may be associated with C-cell destruction following progressive, nonspecific follicular cell damage caused by lymphocytic infiltration and fibrosis of the gland.