DARRYL CHUTKA: This is Mayo Clinic Talks, a curated weekly podcast for physicians and health care providers. I'm your host, Darryl Chutka, a general internist at Mayo Clinic in Rochester, Minnesota.

It's estimated that up to 20 million Americans have some type of thyroid disorder. And over half are unaware of the disorder.

Hypothyroidism and thyroid nodules are two of the most common thyroid disorders we see in the primary care practice. They had both conditions are commonly detected on routine physical exams, or screen laboratory testing.

In most cases, the problems are benign and easily managed. But in some cases, if the diagnosis or treatment is delayed, serious complications can develop.

Today's topic of discussion is hypothyroidism and thyroid nodules. And here to discuss these topics, is Dr. Regina Castro, an endocrinologist at Mayo Clinic in Rochester, Minnesota. Regina, welcome.

REGINA CASTRO: Thank you, Darryl.

DARRYL CHUTKA: Let's talk about hypothyroidism, first. It's quite common, I see this, probably the most common endocrine disorder that I see in my practice. What's the most common cause of hypothyroidism?

REGINA CASTRO: So yes. As you say, Darryl, hypothyroidism is very, very common. In fact, it's one of the probably most common diseases of human kind, and certainly one of the most common disorders in endocrinology.

By far, the most common cause of hypothyroidism, is a condition known as Hashimoto's thyroiditis. This is a benign autoimmune condition of the thyroid, by which, for reasons that we don't clearly understand, our body develop antibodies that are directed against certain proteins in the thyroid gland, causing some chronic inflammation, which, over time, can lead to thyroid dysfunction and hypothyroidism.

DARRYL CHUTKA: So who is at risk for developing hypothyroidism?

REGINA CASTRO: So like I said before, hypothyroidism is very common. Generally, people who are considered to be at risk, are people who have a strong family history of autoimmune thyroid disease. And it's not just people with other members in the family, who have Hashimoto's, or hypothyroidism. Even people who have other family members with hypothyroidism, or Grave's disease, are certainly at risk.

People, for example, who have had radiation to their neck area, are at increased risk of developing hypothyroidism. People who live in countries where there is iodine deficiency, they're at risk of becoming hypothyroid and developing, sometimes, goiters.

People who have had previous neck surgery, particularly those who may have had part of the thyroid removed for a benign condition, like, say, a large benign thyroid nodule, and only have part of the thyroid. Some of them can do fine, and just not need any thyroid trauma, but other people will develop hypothyroidism and need treatment.

So those are probably, I would say, the people with the highest risk to have hypothyroidism.

DARRYL CHUTKA: We've got a variety of thyroid function tests, that are sometimes often ordered as a group. So how do we use these tests? Sensitive TSH, the total T4, or free T4, TPO or antibodies. How should we look at these and decide what's going on?

REGINA CASTRO: OK, that's a great question. So generally speaking, we tend to, when we're trying to look for a condition in patients who may have some vague symptoms of possible hypothyroidism, the best screening tests that we have to, kind of, detect hypothyroidism early on, is a test called TSH, or a sensitive TSH test.

If that test is normal in a patient, otherwise doesn't have any history of, for example, brain tumors, or surgery in their brains, or conditions affecting the pituitary.

That test is usually pretty good to tell us that hypothyroidism is probably not a problem, or hypothyroidism, for that matter.

However, if the TSH is elevated, and that may be mildly elevated, or more significantly elevated, then we would typically get additional tests. And those tests will, typically, be measuring the actual thyroid hormones. A T4, in general, is the test that we tend to do. And in many cases we also do measurement of TPO antibodies.

These are the antibodies that are the most common cause of Hashimoto's thyroiditis, which, as I said before, is, by far, the most common cause of hypothyroidism.

So measuring TSH, if it's normal we, generally, stop there. If it's abnormal, we do additional testing that will, typically, include a total or a free T4, and typical antibodies.

That kind of helps us determine if the patient has hypothyroidism, how severe it is, and what the underlying condition causing it could be.

DARRYL CHUTKA: I don't think in my career I have seen florid hypothyroidism. We always seem to pick it up early, but what does that look like? What can happen if a patient is, either not diagnosed, or doesn't start treatment? What can the complications look like?

REGINA CASTRO: So generally speaking, patients who develop severe hypothyroidism, and we do see, I agree, a lot less of severe hypothyroidism nowadays, because the majority of patients get tested and get screened with TSH.

But every now and then, we see people who don't go to the doctor very often, and present with more severe hypothyroidism. And those patients usually will have a lot of symptoms.

And probably some of the more common symptoms is that they will be very tired, they will complain of feeling cold all the time, they have difficulty losing weight, sometimes they have memory problems, they can come with depression, sometimes. If you measure their cholesterol levels, and they're severely hypothermic, they will be elevated.

They will complain of problems with brittle hair, brittle nails, a variety of symptoms. Constipation is a common symptom of patients with hypothyroidism.

The problem is that many of these symptoms are very pervasive and very prevalent in people who don't have thyroid disease. And so it is very important, when patients present with a constellation of symptoms, to check the thyroid hormone levels, to see, could this be caused by the thyroid? Because if it is, bingo, we have a good treatment for that.

DARRYL CHUTKA: Yeah I get a lot of patients who say, I must have hypothyroidism. I'm tired, I'm gaining weight, constipated, and in Minnesota we're cold nine months of the year, anyway.

But their symptoms are very vague, and we really need the blood test to help confirm what we're dealing with.

REGINA CASTRO: Absolutely. It is very important that we confirm with a test, because, like I said, the symptoms are very pervasive, they are commonly associated with many, many different conditions, of which hypothyroidism is one of them. And we should never be making the diagnosis of hypothyroidism without laboratory confirmation.

DARRYL CHUTKA: One of the issues I come across frequently, is the patient who is clinically euthyroid, but we get their sensitive TSH back, and it's slightly elevated. You know, five, six, seven. What do we do with those patients?

REGINA CASTRO: This is a situation where we talk about subclinical hypothyroidism. And let's define what it means to have subclinical hypothyroidism. This is a patient who typically we'll have very mild elevations in one of the tests, the TSH, and it could be, typically, above the upper limit of normal. Sometimes it can be as high as 15, or so.

But if you measure the thyroid hormone levels, the T4, the T3, they're typically going to be normal.

These patients have, basically, what we describe as subclinical hypothyroidism. Many of these patients are completely asymptomatic, meaning they have absolutely no symptoms of hypothyroidism.

The decision of when do you treat, or what do you do with a patient with subclinical hypothyroidism, is one that is very interesting, and when do we start treatment, is an area where even the experts sometimes don't agree.

There is consensus, generally, even among the experts, that if somebody presents with subclinical hypothyroidism, but their TSH, meaning that sensitive test, is above 10, the majority of people would agree that this patient needs to be treated. Why? Because we know that most of his patients will have some mild symptoms, but even if you leave untreated, it's likely to progress.

And also, there's some data suggesting that there might be some increased risk of cardiovascular issues, including high cholesterol, et cetera.

So for the patient with mild hypothyroidism, with TSH above 10, there's little controversy. In the gray zone is that in which there is a very subtle elevation, like the patient that you just described. And in there, the decision is a little bit harder.

And that's where the experts don't agree. Some say you should treat, some other experts say you don't treat. And the decision to treat or not to treat, will depend on a variety of factors.

On the one hand, you may, one thing that is very important, is to talk to the patient, assess their symptoms, and assess a preference.

Also the age of the patient is very important, and what the other tests show. For example, if you have a patient with mild elevation of a TSH, that is a young woman, and in addition to having a TSH of six or seven, they may or may not report a lot of symptoms, but they have markedly positive TPO antibodies.

Well, we know this patient is more likely to progress. It's young, and so I'm more inclined to treat this patient, particularly if the patient wishes to try treatment.

On the other hand, we have patients who are older, in whom the benefit of treatment of this very mild subclinical hypothyroidism is much less certain, and there's actually data that suggested that. You know, studies that have been well done and controlled, looking at people with mild subclinical hypothyroidism, especially elderly people, and some were treated, and some were not.

And what they found is that the majority of those patients didn't find any difference with being treated, or not treated. That they didn't have any difference in the quality of life.

And so for those patients, there may not be a benefit of treatment early on. And you may be better off waiting to see, whether the elevation or the abnormality progresses, or not, before you decide on treatment.

Sometimes patients prefer to tell you, I'd rather not be on one more medicine, unless I absolutely have to take it. And if they have little, in terms of symptoms, and their TSH does only mildly elevated, this is the kind of patient that you may want to follow and, just check through TSH. You know, in a few weeks, or in a few months, and see if they're progressing. And then definitely decide on treatment.

But if they're stable, then you may just want to hold off. We do know that, in up to 50% of patients who have this very mild subclinical hypothyroidism, if we recheck the test, they maybe just normalize, without doing anything.

DARRYL CHUTKA: And I've seen that many times. This may have been going on for five, six, seven years. And sometimes it's normal, sometimes it's a bit elevated.

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A common condition that I see, is this subclinical hypothyroidism, and hypolipodimia. Is it worth starting those patients on thyroid supplement?

REGINA CASTRO: You know, that's again one of those areas of debate. There is some data to suggest that if you have even subclinical hypothyroidism, that correction of that may lead to some improvement in LDL levels, for example.

The effect is very, very mild in general. It is more pronounced in patients with overt or severe hypothyroidism. Very subtle and minimal in patients with very mild subclinical hypothyroidism.

And you have to weigh that versus the risk associated with potential overtreatment, when the hypothyroidism is very mild. And those risks are certainly increased in elderly patients, because then, you know, these patients can have underlying cardiovascular disease, they can develop tacky arrhythmias, which could be more problematic.

Overtreatment of hypothyroidism can lead to hypothyroidism, which is very easy to happen when the defect is very, very mild. And those patients are at increased risk of bone loss and osteoporosis, problems that are already very prevalent and very common in elderly people.

So there's all these things that we have to weigh, when trying to decide, whether or not to treat a patient with very mild abnormality. And a lot of it will depend on patient preference. So you have to have that conversation, discuss the risk discuss the benefits, and many times is what the patient prefers to do, that you can just, basically, guide them a little bit, and then, basically, follow up with tests.

DARRYL CHUTKA: Let's talk about treatment. So how should we start patients who are, either symptomatic with hypothyroidism, or their symptoms TSH is elevated enough, that we feel that warrants treatment. How do we start the thyroid supplement?

REGINA CASTRO: That's a great question. So it depends on the severity, you know, and the age of the patient, the severity of the hypothyroidism.

So if you have an elderly patient with mild, or even moderate hypothyroidism, typically, we tend to start slower with smaller doses, and gradually increase the dose over time, because we're trying to make sure that we're not going to uncover some underlying heart disease, or we're not going to create problems with chest pain, if they have severe coronary disease.

So generally, we tend to start with a smaller dose. And if the abnormality is very mild, we may start with the doses, as little as 25 micrograms. Sometimes we may start, I tend to start most people on around 50 micrograms, except the very old people. And every few weeks you can increase the dosage, until you get to that level, where you get the TSH levels where you want them to be.

If it's an older patient, we tend to aim for the upper half of the normal range. If it's a younger patient, we tend to aim for the lower half of the normal range.

If you, on the other hand, have a young woman who has moderate or overt hypothyroidism, many times we choose to start them on a full replacement dose.

And how do we decide what a full replacement dose? Well, we estimate the dose based on their weight, and so we calculate about 1.6 to 1.7 micrograms per kilogram.

And then, what we do is we will check a thyroid function test, about six to eight weeks later, after they've started the treatment, to decide whether we need to make any adjustments. So the fine tuning comes six to eight weeks later.

DARRYL CHUTKA: OK. I've had a few patients coming in on thyroid extract. Let's talk about that.

REGINA CASTRO: So yes. That's something that happens very frequently, and it's a common question that we, endocrinologists, face.

Generally, it is not recommended that people go into thyroid extracts. What is the issue? And so what are these thyroid extracts? And what are the problem, what is the problem we see with those?

So thyroid extracts, they come in many forms and many names. But basically, they're made from desiccated thyroid gland from pigs, from animals.

And one of the issues with this extracts, is that they contain, of course, a combination of T4 and T3, which is part of the thyroid gland, and pressing in the thyroid gland.

The problem is we, humans, are not pigs, and, obviously, our levels of the combination are the proportion of thyroid hormone T4 and T3 that we produce, is very different from what animals have.

And the majority of these preparations contain a disproportionately larger amount of T3, than what is physiologic in humans.

So when people are started on this preparations, particularly, when they tend to go on the higher doses, they very often will be found to have evidence of hypothyroidism. And that is driven by the high levels of T3 that are contained in this preparations.

And so, generally, we try to stay away from them. Some patients may prefer to be on combination of T4, T3, for a variety of reasons. In those cases we can do combination treatment. It's not the preferred treatment of choice, but we do, sometimes, have patients on combination treatment of T4 and T3.

But we do them separately, and we try to keep the proportions of T4 and T3 more physiologic.

DARRYL CHUTKA: OK. Well, let's turn to thyroid nodules now. A common finding on physical exam. So if we find a nodule, what's the next step in the evaluation of that patient?

REGINA CASTRO: So like you said, thyroid nodules are very, very common. Just to give you a sense of how common these things are, it is estimated that about 60% of the population have thyroid nodules. That's more than half of the population have thyroid nodules, if we go looking for them.

Many times, we find them on exam, but more often nowadays, we discover them incidentally. Patients who go for a CT of the head, a CT of a neck, a CT Of the chest for things that are totally unrelated to the thyroid, and we find that, oh by the way, there is a nodule in your thyroid, and we need to look at it.

So what do we do when we find a thyroid nodule? Well, if the patient hasn't already had a TSH, or a thyroid test, we should do that the very first thing.

In the majority of patients with thyroid nodules, we're going to find that the TSH is generally normal. And if that is the case, the second best, the second step that we should follow, is to get an ultrasound.

The ultrasound is the best test to look at thyroid nodules, because it gives you a very good idea of all the characteristics of the nodules. An ultrasound can tell you how big it is, whether it's cystic or solid, whether it has features that raise concern for cancer, or whether it looks completely benign.

Once you have the ultrasound, depending on the features, and we tend to grade the thyroid nodules nowadays, as being very low suspicion, or low suspicion, or high suspicion.

And so depending on these sonographic features, that we find on the ultrasound, we need to decide when to do a biopsy.

And the threshold for doing a biopsy, which is the next step, a fine needle aspiration biopsy, depends on what the nodule looks like is it high suspicion, or is it low suspicion. The higher the level of suspicion, the lower the threshold to stick a needle.

So generally, we try to stay away from putting needles in very tiny thyroid nodules that are less than 10 millimeters, because we know that the majority of these nodules do not pose a risk.

But when the nodule is greater than 10 millimeters, if they have high suspicion, we do recommend a biopsy. If they're very low suspicion, we may not need a biopsy, until the nodule is greater say, 15 or 20 millimeters in size.

So the ultrasound will guide us to how soon, or which patients need to have a biopsy, and which patients don't.

DARRYL CHUTKA: So if a patient has a nodule, we do an FNA, and it's benign, do they need any future follow-up, or can we just put that aside?

REGINA CASTRO: OK. So if the patient has a nodule, and you do a biopsy, and you've done an ultrasound, you know how big it is, generally the final aspiration is very accurate, in terms of telling you what nodules are benign.

It is said, in general, that a negative biopsy carries a very good negative predictive value, meaning the rate of false negatives is very low. It's about 5%, 7% depending on where you're looking at, but it's not zero.

And so generally, what we tell our patients who have had a biopsy, is that, if this is the first time that we discover the nodule, and we have the ultrasound, we recommend that they have a follow-up ultrasound sometime within the next 18 months. For convenience, we generally say, in about a year.

And what that does is, it gives you a sense of, is this nodule growing? And if so, how fast? Many nodules we know, just sit there for a long period of time, and they experience very little growth, whereas others may grow a lot faster.

And so if you see that the nodule has a changed in a year, and you already have a biopsy that tells you that it is benign, we can space out, or we can defer the next ultrasound to 3 to 5 years.

And depending on the age of the patient, and what else is going on, sometimes we just stop altogether. So it depends on the individual patient.

DARRYL CHUTKA: When do we decide that surgery resection of these nodules is needed?

REGINA CASTRO: OK. So there are certain indications for surgery. The most compelling one, to get a patient to surgery, is, obviously, when you do a biopsy, and there is concern for cancer. Either the biopsy is positive for cancer, or is, what we call, suspicious for cancer.

When a biopsy says it is suspicious, even though it's not definitive, we know that the risk of that nodule being cancer, is about 70%. So because of very high risk, those patients should have surgery.

You know, in the case of patients who have had a biopsy, and we know the nodule is benign, when should we consider excision or surgery? Mostly it depends on whether the patient has symptoms.

So if the nodule is benign, and the patient's completely asymptomatic, and doesn't have any, what we call, compressive symptoms, meaning difficulty swallowing, that may happen because a nodule even though it's benign, it's located in a position close to the esophagus, and therefore, is going to affect their swallowing. Those patients may need to have surgery to relieve the symptoms.

Patients will may have breathing problems, sometimes they may have a very large goiter, a very large nodule that is putting pressure on the trachea, on the windpipe. Those patients may require surgery.

Sometimes it may not be compressive in that sense, but if you have a young woman, for example, who has a very large nodule, that is very visible, and patient is bothered by it, or everybody is looking constantly at their neck, that might be another very good reason to have surgery.

So when the nodule is benign, the reasons to have surgery are less clear, and a lot more dependent or elected by the patient.

DARRYL CHUTKA: And I've had some patients who had quite large nodules that do compress the esophagus, and they actually had dysphagia because of the thyroid nodule, and required surgery to have that resected.

REGINA CASTRO: Yeah

DARRYL CHUTKA: So what percent of thyroid nodules are, actually, malignant?

REGINA CASTRO: Like we said before, nodules are very, very common, 60% of people have them. So when do we worry about it? We know that about 5% to 7% of all the nodules in the thyroid are malignant, are cancerous. So only a small minority, and that's where the ultrasound and the biopsy come in very handy, to try to figure out that.

But in the majority of cases, we know that nodules, not only are very common, but most of them are benign.

DARRYL CHUTKA: We've been discussing hypothyroidism and thyroid nodules with Dr. Regina Castro, an endocrinologist at the Mayo Clinic in Rochester, Minnesota.

Regina, thank you for sharing your expertise with us.

REGINA CASTRO: Thank you, Darryl. My pleasure.

DARRYL CHUTKA: If you've enjoyed Mayo Clinic talks podcasts, please subscribe. Stay healthy, and see you next week.

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