Endocrine Webinar Part 6: Abnormal TFTs
Summary
This on-demand teaching session will focus on interpreting direct hormone function tests and their importance in clinical contexts. Discussion of regulatory mechanisms and clinical observations associated with hypo- and hyperthyroidism will be addressed. Attendees will get a chance to interact with a few cases and ask any questions they may have. It will provide GPs and medical professionals with the important questions to consider in patients’ histories and physical examinations, as well as discussing tests to assess the thyroid and their respective interpretations.
Learning objectives
Learning objectives:
- Describe the normal regulation of direct hormones.
- Identify clues in a patient's history and physical examination to aid in interpreting direct function test results.
- Identify key questions to ascertain when interpreting direct function test results.
- List the tests typically used to assess direct function.
- Explain how to interpret and act on direct function test results.
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The following transcript was generated automatically from the content and has not been checked or corrected manually.
Okay. Um So what I am, what I was thinking I'm going to do today is I will briefly cover the briefly make the revision for the H B T X s and we'll talk about clinical importance of the clinical contest in interpreting the direct functions. And, and uh we'll also cover the basic inter partitions for the direct function test. And also lastly, we'll discuss about a few cases and it would be good if we can interact throughout. Um We haven't got many viewers. I think it is a good opportunity to chat through uh either with a microphone or profit chat box. Um I wonder whether I can ask, is there any specific sort of like aims upset that you want to achieve after these sessions? And can people type a few things if you don't mind? So that I, I want to make sure that I covered. Okay. I, I think I'll just continue. Um I would like to revise briefly about the normal regulation of the direct hormones so that we understand which hormones we are actually testing in the direct functions and how they regulate each other. Um So as you all remember, um we've got T R H which is in from the hypothalamus coming down from the uh towards the interior pituitary to stimulate the TSH from the interior pituitary. And then the TSH will stimulate the direct land, which will then produce the uh direct hormone by using I odin's. And the direct low billions. And majority of the production will be T four, about 80% and 20% will be T three. And that majority of the T four will be utilizing peripherally by using the D O D Biotin ASIS to type of diagnosis enzymes to convert to T three and robust T three and T three is the active and the useful form of the direct hormone. Um These are the four positive feedbacks and there are some negative feedbacks. So obviously, T four, if the, if the T four level is high, they give the negative feedback to the TSH. Um and also T three will give the negative feedback to the TSH and uh trh productions. That's the usual sort of like feedback loop. And there are some feedback or regulatory mechanism um with a few different things as well. So for example, uh physiologic or emotional stress um will give the negative feedback to the trh and uh T S A stimulation. And this is particularly important when we are talking about the, the acute uh syndrome, for example. And apparently the cold temperature can inhibit the trh as well. And the other thing is the IUD in load which can give uh stimulatory as well as inhibitory effect. So initially, I think particularly this mechanism is important to understand because in our day to day life, we are giving a lot of patient's uh ordinated contrast from the scanning. And and also it is important to understand this mechanism for the amiodarone induced arthritis function. So there is two mechanism um that ech around um the thyroid hormone production will check off the fat and George base to affect. So we will check out um if people and um uh I wonder whether people heard about that before. So basically, when the sudden I ordinated um load was given the direct gland switch off the production um to make sure that um there is no overactivity of the direct hormones. So the auto regulation and sudden switching off we'll stay in uh will be for about 3 to 7 days. So it will switch off the productions to make sure that it has not become overactive. And then after 3 to 7 days, uh the the effect will wear off and, and become escape. And if and in people with a background baseline problem, uh such as great disease or toxic. No Jews, they become hyper hypothyroid and become toxic. So, uh these are the very basic uh sort of like regulatory mechanism and the feedback loops uh that we need to understand for us to be able to um interpret the direct functions properly. Um The important thing in interpreting the direct function is the clinical contest. I cannot stress that stress that enough. Um Without the clinical contest, everything is meaningless. So he's retaken and physical examination as usual, our keys. And um also we need to understand why the thyroid function was checked. And in what setting? Um as a background as usual, um we've got symptoms of hypothyroid and hypothyroid that we need to explore. Um I think you all know the symptoms of hypothyroid palpitations and intentional weight loss, um, diarrhea and excessive sweats and the tremor and anxiety and main symptoms of hypothyroid weight gain, lethargy, tiredness, constitution, cool intolerance. These are the base symptoms that you can explore around to see whether they are actually functionally feeling something of the abnormal thyroid hormone. And then you have some clues in your histories. You can get some clues in your histories. This is by no means I'm talking about the Carafate history and physical examination for the assessment. I will, I will be highlighting to what the, the important questions that you can, you can include in your, in your usual history and physical examination. So I think it is, it'll be good if we understand why the thyroid function was done. Uh Do they have the same terms? Um Was it intentionally to uh intentionally done to find out or to rule out whether they've got hyper or hypothyroidism at the time of the test whether the, the patient's are sick or whether they are well, are they known to have direct problems? Are the symptoms new? If the same times are new together with deride hypo hypothyroid symptoms. Do they have any other associated symptoms? For example, fever and pain to see whether uh they have got direct itis, etcetera. If the direct problem is known, then what's the diagnosis? Is it the primary direct issues or secondary or I tra genic? Um I think the these sort of questions um if you can include that in your history, um these are the important clue for you to be able to interpret uh better. Alright, function better. Other questions. Are they taking DeRozan if they are taking the oath arrows in? Um are they taking it with the compliance or they, whether you can rely on their history etcetera? And are they taking anti direct drugs? And if they are taking anti direct drugs, how long they have been taken? And, and are they taking any other medications? And are they on hydrocortisone, testosterone, growth hormone? These are the clue if they are taking hydrocortisone, testosterone, growth hormone, etcetera. These are the clues for the secondary hypothyroidism. Are they taking a Medrol? And this is a clue that uh this is the effect of the direct function could be the effect of the amiodarone, uh whether they are taking lithium bio ting. Um And uh the other thing is whether they are pregnant if they are pregnant? How many weeks are they in? Do, do they have hyper Emmis? Is because um this is not uncommon for us to see the abnormal thyroid function in a pregnant lady, especially in the first trimester of pregnancy. And most of the time this is quite harmless, abnormal biochemical hypothyroidism, um similar to the history on examination. These are the very focused signs that uh that can give you the clue of the underlying reason for the direct abnormalities, direct function abnormalities. So for example, if you see um exhaust demos, um lick, lick, lick retraction, optimal plasia. Um as I signs, then you're pretty much and, and if they combined with the uh the biochemical hypothyroidism, they are pretty much pointing to what's um uh the uh graves' disease and you look at the direct land, whether they've got the quietest, whether they've got the bruise. Again, the bruise bruise is the, the signs of the grave disease. Are they tender and inflaming the direct land? Um And then in that case, you may be thinking about, you need to be thinking about um subacute thyroiditis. Do they have the direct ectomy scar if they have got directed me scar, uh probably that they had a, they had a daughter thyroidectomy and requiring to take the uh replacement tablet and they may not be taken it regularly and you may be seeing direct functions, um results of noncompliant, etcetera. And also there may be some other similar evidence of other endocrine problems. Um Do they look cushion wide? Do they have signs of acromegaly if you see those signs, then um looking at the thyroid function, your interpretation maybe pointing towards the secondary hypothyroidism. So these are the important clues, an important sort of like the, the questions that you should probably include trying to include in your history and physical examination. So what are the tests that we will be doing? So the feedback feedback loop again. So we've got trh TSH T four T three. And what we measure is usually TSH and free T three and 3 to 4. And there are some other tools that we can use to help us to identify the underlying diagnosis. Those will be the antibody levels. So usually we use um TPO antibody levels when we think about the hypothyroidism or the risks of hypothyroidism. You know, people with a subclinical uh type of uh uh direct fashion test results. Um And the other one is the TSH receptor anybody uh which we use to diagnose the grave disease or allgen, you the hypothyroidism. And um and uh sometimes we probably need to use the ultrasound deride. Um I got this light from, from the internet. I think it is, it is a good uh summary. How should, how we should approach and how we should be ordering the uh vary function test. So if you have got low suspicions for the direct disease um on your left hand side. And I guess you will be requesting the direct function mainly because you wanted to rule out just in case. So you have to think about whether the patient is accurately ill or unwell. Um If they are accurately ill, then probably we should consider deferring the thorough function test because that will show us the sick, most likely show us a secure thyroidism. And we can't really interpret that result and we can't rely so, unless absolutely necessary at that stage, unless you are really thinking of whether this patient has got um uh myxedema coma or something, you should not be testing for the direct function in the acuity and well, patient. Um if they are not accurately and well, and if you have got low suspicion for the thyroid disease, then you just check the TSH. And if the TSH is normal, then you don't really need to do anything else. Um If the TSH is high, then you should check the free T four level. If the TSH is low, then you should check both, probably both three T three and 3 to 4. And if you have got high suspicion for the hypo directors, um thinking about the same times of your patient's, then uh you can check TSH and free T four in one goal. And if you have got high suspicion for the hypothyroidism, then you can check TSH FT three and F T four all in one go then how do you interpret them? So you, you can check TSH free T three and three T four. So, primary hypothyroidism very common uh to see in, in community in the G P surgeries or in a any or in on ecumenical take on the wards. Uh in primary hypothyroidism. TSH level is very likely to be undetectable. 323 can be high or very high and 3 to 4 can be high. So this is basically hypothyroidism and T three toxic osis is similar to the primary hypothyroidism. Again, this is the type of toxic osis. So usually the uh three T three level actually is the uh the entry is wrong and the free T three level will be high or very high. Three T four could be normal TSH level can be fully suppressed, undetectable, be suppressed because of the feedback loop. And subclinical hypothyroidism is um where you see suppressed TSH, suppressed to a certain degree, not necessarily fully suppressed an undetectable level. Um but 3 to 3 and three T four levels are normal. Um secondary hypothyroidism. This is very rare. Um This is the pituitary driven hypothyroidism, meaning that the pituitary gland is producing too much of a TSH stimulating to the direct land constantly um causing everything high. And the thyroid hormone resistance is similar to uh the finding uh to the secondary hypothyroidism. Um even though there is enough thyroid hormone in the body TSH remains high and there is no negative feedback mechanism. Uh means that the pituitary is not really sensing the high direct hormone levels in the body. Um Primary hypothyroidism is in the reverse for the primary hypothyroidism. Uh 3 to 4 and three T three levels are low. So that TSH need to uh increase the production, to stimulate the direct land to produce more. So you will, you'll be seeing low three T three T four and high TSH level. Subclinical hypothyroid is um again, also the reverse order for the subclinical hypothyroid. TSH is high, but three T three and T four levels can be normal and secondary hypothyroidism is um uh the pituitary problem or the very, very rarely hypothalamus problem. Uh So TSH will be low or normal with low 3 to 4 and three T three levels and then you sometimes see very weird and atypical direct functions. Um So I think these are covered in the previous slides. Um suppressed TSH and normal F T four is um out of your usual um finding of primary hypothyroidism in primary hypothyroidism and uh subclinical hypo and hypothyroidism. So this, this can be T three toxic osis in which you can see in 5% of thyrotoxicosis patient. Um I talked about that earlier suppressed TSH and, and normal F G four and F D three. It could be recovery from the director psychosis somewhere in the recovery or it could be uh settling to get hypothyroid, right? Or it could be excessive direct hormone replacement. It could be non directed illness. Um detective TSH and elevated um F T four and F T three. Um It could be because of the T S a secret in pituitary tumor because there is no um negative feedback mechanism there. And uh it could be direct hormone resistance like we discussed earlier and it could be due to the direct hormone replacement therapy uh and, and poor compliance and it could be a lab interactions, interactions, heterophile antibodies and, and boating can give you a very weird uh sort of like direct function test results. Elevator F D four F T three and separate TSH. That's the reason why it is always um important to find out what medication they are taking. Amiodarone will give elevated F T four, um low normal F T three and normal TSH. And it, it can give uh the other uh and the other way around as well. It can be low, it can be high uh dependent on the duration um uh of the medications. Um Heparin can give elevated F T four and T three and, and if everything is suppressed or normal uh or lu lu normal F T four and T three with the normal TSH, then it could be not directed illness like acute illness or it could be central hypothyroidism or it could be um isolated TSH deficiency. Um I actually, I set up this presentation to interact quite a lot So if I am talking once I did, I have to warn you that it will be finishing very quickly. Um This fast case. So 34 year old lady with a TSH, fully suppressed TSH and F T four of 68 pick a mobile liter. What would be your thought when you see these results? What I'll quickly do is I just invite everyone to the stage so that you can um mute as well if you feel like talking. Uh But please, do you use the chat function? Thank you. Anything. Nope. So, um so this is this lady who has got very high three to fully three t four level and fully suppressed TSH. And usually we see that in people with a hypothyroidism. So sometimes you, you were just looking at the blood test results and doesn't really mean anything to you and it could be uh other different shells can be there as well. So you go back to your history taking and physical examination and these are the focus um findings in the history and, and their clinical examination. So she was having tremors, she looks anxious. She's got competitions, she's got unintentional weight loss. Um and she has got frequent loose stools and she has not been um tolerant to the hot weather. Um And um on examination, she's got uh except demos lit, lack licked, retractions, diffuse quieter and the direct movies and TSH receptor anybody which is a marker for the grave disease is positive. And so this lady has got the grave disease and what she needs is the anti direct medications or, um, or radioactive iodine or the, or the salary. Um, the next case is a 27 year old lady with a fully suppressed TSH and elevated 3 to 4. And looking at that, um, the history is looking at that, the result is very similar to the fast lady, But when you take the proper history, she hasn't got any previous star ride problems. There are no same times of hypothyroidism. She has been significantly vomiting. How LMP was about two weeks ago, pregnancy test was positive on examination is slightly dehydrated. There is no quieter and no evidence of grapes Optim over the and uh no evidence of diarrhea toxic osis. Looking at this history before testing the TSH receptor anybody. Um we'll be thinking about this is the A C G media to direct dysfunction in the pregnancy. So, in the early phase, in the first trimester of pregnancy, a CT production, um significantly elevated and the the cross react with the TSH receptors and they stimulate the direct land very temporarily until the level go back down to um within range after about 14 to 18 weeks of pregnancy. And uh this is quite harmless unless they, they were developing the hypothyroid symptoms. And at this point, if they don't, if they looks relatively well, they don't need any treatment from the direct point of view. And we usually make a plan to repeat the direct functions. And at the same time, we'll be testing the TSH receptor. Anybody's. So what I'm trying to say in this two cases, two cases is that the history taking and physical examination and the clinical contest is very important to interpret the direct functions. So you've got two different diagnosis um from the very similar direct function test results. Um So this is another case, 45 year old lady with a TSH of 12.4, so higher than normal level and three T four level of eight um lower than reference range. So that means that she has got low F T four, so likely hypothyroid because TSH is elevated, it means that she has got probably has got primary hypothyroidism that what you will be thinking, but you still need to take the full history and um physical examinations. And um in the history, she, she said that she has got weight gain. She has not been feeling well tired and lethargic. Um she has got cool intolerance and experiencing constipations and history of um total thyroidectomy for PTC. When you ask her on examination, you notice car in the neck. She has got positive TP or anybody though. So, um if you did not get the history of um uh do that iridectomy, this could well be primary hypothyroidism requiring the treatment. But actually she has got to the direct ectomy. And um she was just not taking the direct hormone replacement and the, your consultation and your focus will be shifted towards the, the counseling about um the importance of the compliance with the direct hormone replacement. And also you probably need to discuss how she is taking. So usually they're a hormone replacement, need to take it on the empty stomach in early morning, um, when they wake up and they need to split out or separate with their breakfast or other with or with the other tablet for about half an hour to an hour, at least uh to get the full uh absorption. So um similar direct function test results to the primary hypothyroidism. Um but it is a bit different sort of like consultation that you need to make because of this history and your interpretation will be a bit different as well. Um Next case is 67 year old man with a TSH of 1.2. So that means that is the lower limit of normal reference range. Three T four level is 7.9, which is on the low side, um uh lower than normal range. So even though this patient has got low free T four level TSH is not stimulating and remained um at the lower end of normal. Ideally, what should have happened is the TSH, it should come up to stimulate the direct land. So then looking at this, you will be thinking about the possibility of secondary hypothyroidism, the obituary driven hypothyroidism. Um, so you, you take the history, he's experiencing some headaches, feeling tired, his vision is not quite right. He's got confusion and, and uh, there was a personality change. Um, this was the actual patient actually. So he on clinical examination that there was no quite, er, no obvious signs to comment. And because we are thinking about the central hypothyroidism, the commonest causes of the central hypothyroidism will be the vegetarian, enormous. Um And if they are large enough, they can compress the opt enough and optic as um so we need to test their field of vision and the peripheral feel a visions on the confrontation test um shows there is some slight constriction um of the uh of the peripheral fields. And because he is feeling tired and the vision uh and um and thinking because we are thinking about the central hypo that we, we continue to test his nine AM Cortisol, which was low. So this is the TSH deficiency likely from the pituitary adenoma. As you can, you can even say that even before uh during the uh imaging, um he may have size of cushions or the acromegaly if that adenoma was see creating or functioning. Um This is 75 year old man. Um TSH very low three T four on the low side, three t 3.9 on the low side as well. So everything is low. Um So you may be thinking whether this is the central um hypothyroidism, it is very common. Uh So the thyroid function test, um we, we can be asked to advise and in our, in our hospital uh in our day to day um hospital uh and you cry. Yeah. Actually, when, when you look at the whole history, uh the patient is in I T U intubated, very unwell on inotropes. Like we discussed earlier. This is the sick, you thyroidism, everything is slow because of the physiological stress. Uh TSH is suppress and trh is suppress. Um should not be testing that are function in this situation unless absolutely necessary. And unless we are thinking about the Myxedema coma. The next case, 64 year old women with a fully suppressed TSH and F T four or 55 looking at that fully suppressed TSH and elevated at FT four. So again, there is similar to the primary hypothyroidism. The history taken. Uh There are two, there can be two different scenario. One is, has got a symptom feeling unwell, swollen and painful neck and, and they cannot eat and drink well because of the pain. And uh there there was a viral illness about a week or so ago and on examination before diffuse quieter and tend not to charge. So this could be subacute thyroiditis. The management will be uh steroids or the painkiller supportive management rather than anti direct drugs. Um The second scenario is they've got no grave disease have been on the anti direct drug for about 16 months. Usually they need to take for about 18 months to cover the phone calls and to suppress their immunity properly. Um This patient has taken for 16 months so far doing very well. Thyroid function tests have been stable before. But recent investigation for the unexplained abdominal pain, new weight loss and anemia and, and the thyroid function after that suddenly go off. So this is this is in keeping with the acute iteration of thyroid function secondary to coordinate, I wouldn't make a contrast agent. Uh This is due to the underlying mechanism that I explained in the very first slides. Uh shakeout effect and job based oh phenomena. So when she was given the ordinated agent, the direct hormone production will temporarily switch off because of the sudden increase in the ordinated load. So the right we'll try to protect um itself and then after that, they cannot contain or maintain this protection for a long time. So after uh from 3 to 7 to 10 days, uh the the the effect we're wear off and they cannot protect themselves anymore and suddenly uh the direct and will be utilizing all the I odin's um as a source for the thyroid hormone production and they become hypothyroid. So this can happen especially in the people with the prior direct problem. Um uh for example, previous history of toxin, no Jews um uh partially treated all the people with the great disease. Uh This is, I think it can be relatively common finding in our day to day practice as well because we are requesting quite a lot of uh contra scans for the investigations and you may be seeing this type of results. So just to be aware of um this type of results and 46 year old lady TSH, 15 F T 4, 25. So both of them are elevated. Um This could be noncompliant with the uh with the replacement in a person with the primary hypothyroidism. Very rarely, it could be due to the direct hormone resistant, it could be to the TSH uh secreting tumor. So this is my last light. So summary, when you check the thyroid functions, TSH F G four and F E three are the keys history taking and physical examinations are important and um we have to put clinical contest into the interpretations. The similar sort of results can be due to the different things and the management can be different. Um Any questions which anything to add? No, I'm just wondering if anyone had any questions at all. Please do write them and chat have given people the option to um meet themselves, but the chat option might be the better option for now and please do filling the feedback forms if, if so, what was he trying to improve this? Um Okay. If there is no questions, I think uh this is the end of my session. Um um Perfect. So I just sent the feedback form in the chat as well. Um What we'll do is we'll put the recording up. So I think there'll be plenty of other people want to see this session line and um just to let you know the next talk is in two weeks time, Gina doctor strikes the next week. So be at the same time and I'll be on low cortisol. Um If there are any questions, we'll stick around for a minute or two. But um thank you so much for winner. Have for his excellent talk and thyroid function test. Thank you.