Understanding Thyroid Diagnostics and Treatment Protocols

# The thyroid system: how it works, common problems, hypothyroidism, T3, T4, TSH, & more | Peter Attia
# https://www.youtube.com/watch/DHM5X9Tqjuw

00:00:00.960 foreign
00:00:05.100 okay so let’s start with the thyroid
00:00:07.319 system
00:00:08.820 um I’ve drawn a little bit of a
00:00:10.200 schematic here it’s a bit oversimplified
00:00:12.300 and it’s also at the same time a little
00:00:13.559 bit messy so I’m going to try to explain
00:00:14.820 it and hopefully it makes sense
00:00:16.859 you have the thyroid gland this is the
00:00:19.980 thing that sits in front of uh your
00:00:22.980 larynx you can actually feel the thyroid
00:00:26.039 gland and it’s shaped as a shield which
00:00:29.220 is how it gets its name and the thyroid
00:00:31.380 gland is regulated directly via a
00:00:34.079 hormone called TSH so TSH is stimulated
00:00:37.559 from the anterior portion of the
00:00:39.360 pituitary gland and it tells the thyroid
00:00:42.480 gland to make T4 and T3 and the
00:00:45.840 pituitary gland is regulated Upstream by
00:00:48.539 the hypothalamus which stimulates it via
00:00:51.420 a hormone called trh now I’ll come back
00:00:53.760 to the regulation of these in a moment
00:00:55.260 but let’s just go back to the thyroid
00:00:56.640 gland so the thyroid gland makes mostly
00:00:59.699 T4 and a little bit of T3 now where do
00:01:03.420 the three and the four come from what
00:01:04.619 are they referring to well they’re
00:01:05.700 referring to the number of iodines that
00:01:08.520 are in the molecule so not surprisingly
00:01:10.500 T4 has four iodines T3 has three iodines
00:01:15.180 what’s the difference between them the
00:01:17.340 difference has to do with their biologic
00:01:19.020 activity when you think of all the
00:01:21.360 things that the thyroid hormone does for
00:01:23.820 example how it keeps you warm AIDS in
00:01:26.100 metabolism
00:01:27.259 controls things like the brittleness of
00:01:29.640 your nails your hair a bowel function
00:01:32.159 all sorts of things all of the thyroid
00:01:34.439 promoting functions are controlled by
00:01:36.780 the active version which is T3 T4
00:01:39.960 conversely is the inactive version of
00:01:43.020 the hormone so if you’re paying
00:01:45.900 attention to what I just said you’ll
00:01:46.920 note I just said that basically most of
00:01:48.720 what comes out of the thyroid is T4
00:01:50.939 which is inactive now it’s not entirely
00:01:54.540 clear what the ratio is between these
00:01:56.159 but it’s directionally about four or
00:01:58.740 five to one I think it’s almost just as
00:02:00.960 easy to imagine that virtually
00:02:02.220 everything the thyroid is producing is
00:02:04.320 T4 so if the thyroid is producing T4
00:02:07.740 which is inactive it needs to be
00:02:10.258 converted into an active hormone in the
00:02:13.560 body and that’s where these enzymes
00:02:16.200 called diodenases come in and as their
00:02:19.500 name suggests D iodinases remove one of
00:02:23.340 the iodines from T4 to create T3 which
00:02:27.420 is the active hormone
00:02:29.640 now the story gets a little bit more
00:02:31.379 complicated because there are different
00:02:33.120 types of diode nases but the three most
00:02:36.180 relevant are D1 D2 and D3 so let’s talk
00:02:41.519 for a moment about these three
00:02:42.680 diogenases D1 and D2 are quite similar
00:02:45.720 in that they both convert T4 into T3
00:02:48.959 more about that in a moment it’s just
00:02:51.000 where they do it that’s slightly
00:02:52.080 different D1 is extracellular it’s on
00:02:54.900 the cell membrane facing outward whereas
00:02:57.599 D2 is on the membrane of the endoplasmic
00:03:00.420 reticulum and it’s facing internal to
00:03:02.580 the cytosol but put that aside for a
00:03:04.680 moment and just keep in mind that D1 and
00:03:06.420 D2 both convert T4 into the active
00:03:10.620 hormone T3 this is the one that has all
00:03:13.260 of the you know positive effects of
00:03:15.300 thyroid hormone
00:03:16.620 now D3 is different in that D3 takes T4
00:03:19.860 and makes something called reverse T3
00:03:21.780 reverse T3 is very similar to T3 except
00:03:25.739 for a very important difference which is
00:03:27.959 it doesn’t activate the receptor that T3
00:03:31.019 activates so it occupies the receptor
00:03:33.360 without activating it so in effect you
00:03:37.140 can think of reverse T3 as anti-t3 it
00:03:40.620 basically blocks the effects of T3
00:03:43.379 now it sounds like a very bad idea to
00:03:45.659 have reverse T3 floating around and
00:03:47.640 unfortunately in the modern world it
00:03:49.620 often is it usually is a sign of
00:03:51.659 inflammation illness or things of that
00:03:53.940 nature but I think that the reason it
00:03:56.700 probably exists is to cope with shortage
00:04:00.180 of nutrients in other words when
00:04:02.280 nutrients are scarce when you need to
00:04:03.840 slow down metabolism one of the first
00:04:06.000 things that the body does is it
00:04:08.040 increases the production of reverse T3
00:04:10.140 to block the effects of T3 in fact one
00:04:13.260 of the things I used to notice when I
00:04:14.700 did frequent fasting because I would
00:04:16.858 fast for say a week at a time and I
00:04:19.019 would always check my blood pre and post
00:04:20.760 is how much my thyroid function
00:04:23.160 deteriorated during that period of time
00:04:25.440 and it wasn’t just a deterioration in
00:04:28.800 the usual metrics such as TSH and T4 it
00:04:32.820 was how much my free T3 and reverse T3
00:04:35.580 changed in fact the ratio of my free T3
00:04:38.639 to reverse T3 might go from 0.25
00:04:43.440 which is pretty normal to
00:04:46.639 0.05 or less in just a five to seven day
00:04:50.639 fast and you know I would say about half
00:04:53.160 of that was due to the reduction in T3
00:04:55.320 and the majority of that was due to the
00:04:57.540 increase in Reverse T3 so the body is
00:05:00.240 going to regulate these three enzymes in
00:05:03.180 response to various physiologic
00:05:05.160 circumstances and that’s effectively at
00:05:08.100 the cellular level how the body is
00:05:09.720 controlling thyroid function now this
00:05:12.360 creates a bit of a problem when you want
00:05:14.100 to evaluate a patient for their thyroid
00:05:16.259 status because the traditional way to
00:05:19.020 think about a patient’s thyroid status
00:05:20.759 is actually just to look at their TSH
00:05:23.820 and on the surface this kind of makes
00:05:25.560 sense because if everything is working
00:05:27.720 perfectly the TSH should give you the
00:05:30.840 answer if the TSH is very high what must
00:05:34.560 be true well there must not be much T3
00:05:37.860 around because
00:05:40.020 it would be inhibiting TSH
00:05:43.380 if TSH is very very low you would be
00:05:46.680 getting a lot of inhibition from these
00:05:48.780 things you would be in a hyperthyroid
00:05:50.759 state
00:05:52.680 but the reality of it is you can
00:05:55.380 sometimes have a normal TSH and still
00:05:58.680 have the symptoms of hypothyroidism if
00:06:02.039 for example you have very high amounts
00:06:04.979 of reverse T3 and very low amounts of T3
00:06:08.580 in other words if your T4 is being
00:06:11.160 preferentially shunted into reverse T3
00:06:13.380 instead of T3 you might feel like you
00:06:16.860 have the symptoms of hypothyroidism you
00:06:18.960 could be cold your metabolism might be
00:06:21.060 slow you’d have difficulty sleeping if
00:06:23.280 it were really extreme your nails might
00:06:24.960 even get brittle you’d be constipated
00:06:26.639 these sorts of unfortunately
00:06:28.639 non-specific symptoms which make it
00:06:31.259 difficult to make such a diagnosis at
00:06:33.360 times so where does this matter when it
00:06:36.419 comes to how we treat hypothyroidism and
00:06:39.360 to be clear
00:06:40.460 hypothyroidism is far more common than
00:06:42.960 hype or thyroidism I’m not going to talk
00:06:44.759 about hyper thyroidism I’m going to talk
00:06:46.680 about hypo
00:06:48.419 the standard treatment for
00:06:50.900 hypothyroidism is to give T4 we give a
00:06:55.139 synthetic version of this hormone the
00:06:57.600 inactive thyroid hormone and we do that
00:06:59.819 with the knowledge that most patients
00:07:02.759 will convert that T4 via D1 and D2 into
00:07:07.800 T3 the T3 will go on to have all the
00:07:10.560 biologic effects and it will also
00:07:12.780 suppress trh and TSH and the body will
00:07:16.259 come back into line so for example if a
00:07:17.940 patient shows up to see you and they
00:07:19.740 have the classic symptoms of
00:07:21.139 hypothyroidism and their TSH is elevated
00:07:23.819 for example it’s six or seven
00:07:26.400 you might give them say 75 micrograms of
00:07:29.340 T4 and you might expect to come back and
00:07:32.220 see that TSH at two or three and them
00:07:35.220 feeling better and many times it works
00:07:37.440 out that way but unfortunately it
00:07:38.819 doesn’t always work out that way
00:07:40.560 and in fact what you see sometimes is
00:07:43.860 that you give a patient T4 and they
00:07:45.539 start to feel worse and sometimes their
00:07:48.180 TSH actually improves and the reason it
00:07:50.759 improves is T4 does have some inhibition
00:07:53.460 of TSH not as much as T3 but some
00:07:56.880 but what if
00:07:58.560 for physiologic reasons their D1 and D2
00:08:01.680 are being down regulated while their D3
00:08:03.900 is being upregulated and they’re taking
00:08:06.300 that T4 that you’re giving them and
00:08:07.680 they’re just making more and more
00:08:09.180 reverse T3 now again a person who’s
00:08:12.720 insulin resistant a person who has low
00:08:15.360 grade inflammation
00:08:17.160 these are typically things that we we
00:08:18.960 might see drive that state and that
00:08:21.660 patient even though their TSH improves
00:08:23.460 doesn’t necessarily feel better and for
00:08:26.220 those patients it might make more sense
00:08:28.379 to actually give them T3 because if you
00:08:30.900 give T3 you’re basically bypassing this
00:08:33.419 system all together you’re still getting
00:08:35.099 the feedback that’s appropriate but you
00:08:37.440 bypass the step where the body might
00:08:39.419 erroneously turn the T4 into reverse T3
00:08:42.179 now there’s a bit of a problem in giving
00:08:44.279 T3 because the regular version of T3 a
00:08:48.779 drug called cytomel is a very difficult
00:08:51.600 drug for patients to tolerate when I was
00:08:53.399 in training we would give T3 to patients
00:08:56.220 after we did thyroidectomies on them for
00:08:58.440 thyroid cancer and patients could rarely
00:09:00.899 tolerate it we had to give it to them
00:09:03.720 because we would immediately take all of
00:09:05.940 their thyroid out in one moment and they
00:09:08.640 needed a big dose of T4 but a hefty dose
00:09:10.920 of T3 to get them over the hump and
00:09:12.720 oftentimes they would feel pretty lousy
00:09:14.700 from that now since that time uh I think
00:09:18.480 T3 has largely fallen out of favor not
00:09:21.060 many doctors use cytomel which is the
00:09:24.240 trade name for T3 because it is so rapid
00:09:27.720 in its onset instead people are
00:09:31.380 typically using two other formulations
00:09:33.380 the first is a compounded control
00:09:36.540 release T3 so it’s the exact same
00:09:39.300 hormone T3 but it’s just compounded in a
00:09:42.660 way to be slowly released this seems to
00:09:45.360 be much more well tolerated and the
00:09:47.580 doses can be pushed a little bit higher
00:09:49.440 a typical dose might be anywhere from 10
00:09:51.839 to 25 or even 30 micrograms of control
00:09:54.480 release T3 and that seems to last a
00:09:56.820 patient throughout the day of course
00:09:57.779 they have to take this generally in the
00:09:59.580 morning to make sure that it’s out of
00:10:01.080 their system by evening or at least it’s
00:10:03.360 reduced in potency
00:10:05.399 there’s another way that patients often
00:10:07.860 receive T3 and that’s in combination
00:10:10.860 with T4 vis-a-vis a formulation known as
00:10:14.640 desiccated thyroid now desiccated
00:10:17.279 thyroid is basically whole thyroid gland
00:10:20.640 and therefore it contains T4 T3 and even
00:10:23.820 some T2 but we’re not going to talk
00:10:25.200 about that so the two most common
00:10:27.240 versions of desiccated thyroid are a
00:10:29.820 formulation called naturethroid and
00:10:31.680 armor thyroid so if you’re watching this
00:10:33.240 video and you’re interested in this
00:10:34.140 topic you’ve undoubtedly heard of these
00:10:36.180 things now I’m not going to get into the
00:10:37.860 religious debates about this stuff there
00:10:39.480 are really competing schools of thought
00:10:41.220 and there are some people that believe
00:10:42.540 that the only thing that should ever be
00:10:44.399 given to any patient with hypothyroidism
00:10:46.440 is a desiccated formulation similarly
00:10:49.079 there are other people who think all of
00:10:50.519 that desiccated stuff is total crap and
00:10:52.560 it should never be given and we should
00:10:54.000 only be giving T4 or we should only be
00:10:55.860 giving T4 with a little bit of T3 or you
00:10:58.560 should only be given control release T3
00:11:00.200 I interacted with people from all of
00:11:03.060 these schools and all I can say is if
00:11:05.519 you’re really interested in treating
00:11:06.600 hypothyroidism you better know all of
00:11:08.880 them because there are some patients in
00:11:10.980 whom one way works and another way
00:11:12.839 doesn’t I’ve had patients who came to me
00:11:15.120 on desiccated formulations and I thought
00:11:17.640 you know I don’t really like these
00:11:18.959 desiccated formulations I’m going to
00:11:20.399 switch switch them over to T4 plus
00:11:22.560 control release T3 and I could never get
00:11:25.140 them right and I ultimately end up
00:11:26.519 putting them on desiccated and getting
00:11:28.079 them right similarly I get patients that
00:11:30.000 show up undesicated and they sort of
00:11:31.980 feel okay but they’re not quite right
00:11:33.180 and we get them feeling right in other
00:11:34.860 ways now keep in mind if you’re giving
00:11:37.079 desiccated thyroid and this is kind of
00:11:39.300 the reason why I don’t generally like to
00:11:41.339 use it except when it works you’re
00:11:43.740 giving a fixed amount of T4 and T3 you
00:11:46.079 don’t get to control it the ratio is set
00:11:48.060 and it’s something like 1 to 4.2 or
00:11:51.420 something like that meaning for every
00:11:53.220 unit of T3 you’re giving you’re giving
00:11:56.720 4.2 units or micrograms of T4 and again
00:12:00.480 for some patients that’s just right but
00:12:02.760 there are other patients who need more
00:12:04.500 or less of one or the other and that’s
00:12:06.480 why I tend to use T4 and T3 separately
00:12:11.040 but again you’re here to fix the
00:12:13.380 symptoms more than you’re here to fix
00:12:15.000 the numbers and you’ll ultimately end up
00:12:17.579 using whatever works finally a word
00:12:20.579 third on half-life
00:12:22.380 T4 has a very long Half-Life it’s a
00:12:26.940 matter of days and for that reason a
00:12:30.180 patient shouldn’t Panic if they miss a
00:12:32.880 day of T4 so if they forget their dose
00:12:35.220 of T4 it’s okay just take it the next
00:12:38.040 day and don’t double up conversely T3
00:12:41.399 has a much shorter Half-Life and
00:12:43.980 therefore you do need to stay on top of
00:12:46.500 your T3 when you give it now of course
00:12:48.899 remember the control release in the
00:12:50.820 immediate release T3 also have very
00:12:52.740 different half-lives but what I’m
00:12:54.120 referring to is endogenous T3 as well so
00:12:58.200 there you have it a pretty hopefully
00:13:00.480 simple overview of the thyroid system I
00:13:04.440 guess one of the takeaways from this is
00:13:06.660 that it’s a little more complicated than
00:13:08.459 you might be led to believe if your
00:13:10.620 doctor is only looking at your TSH and
00:13:13.320 unfortunately when you go to the
00:13:15.180 doctor’s office a lot of the times
00:13:16.920 that’s the only lab they’ve ordered I
00:13:19.920 prefer to order not just the TSH but the
00:13:22.800 free T4 the free T3 and the reverse T3
00:13:26.339 if I have any concerns about
00:13:28.760 hypothyroidism I don’t always order this
00:13:31.139 blood test so if the TSH is normal the
00:13:34.320 T3 T4 are normal and the patient is
00:13:36.420 asymptomatic I’m not looking at their
00:13:37.920 reverse T3 but if a patient has symptoms
00:13:40.260 and you need to investigate them I think
00:13:42.120 you have to understand all of these and
00:13:43.680 what you’re basically doing is using the
00:13:46.320 amounts of T4 or free T4 T3 or free T3
00:13:50.040 reverse T3 to impute what the action is
00:13:54.779 of these diodonases and their for what
00:13:58.200 your treatment strategy needs to be