The Thyroid, Part Trois

The Thyroid, Partie Trois

Hello, people- welcome back to the thyroid blog! Last week, we took a deep dive into all of the causes and symptoms of hypothyroidism and hyperthyroidism, and today I’ll get into diagnosis and testing. Before I do, I just want to highlight some key points from last week and squeeze in a couple of other little facts, or “factlets” if you will. As I mentioned last week, hypothyroidism- underactive thyroid causing low hormone levels- is far more common than hyperthyroidism, with its overactivity and elevated hormone levels, but about 60 percent of people are unaware of their diagnosis at all. Thyroid disease can occur in anyone at any time, but it’s more common in women, and risk increases with age. In the United States, prevalence is generally highest in Caucasians, followed by Mexican Americans, then African Americans.

About 95 percent of cases of hypothyroidism are due to a problem in the thyroid gland itself, so they’re called primary hypothyroidism. However, certain medications and diseases can also decrease thyroid function, and this is called secondary hypothyroidism. An example of this may be when there’s a problem with the pituitary gland- the endocrine gland that controls the thyroid- and that results in decreased production of TSH, thyroid stimulating hormone, and as a result, the thyroid produces less hormone. Another example of secondary hypothyroidism that’s important to note actually involves hyperthyroidism- specifically after medical treatment for hyperthyroidism. When you have treatment for hyperthyroidism that includes surgical removal of the thyroid, called thyroidectomy, or even radioactive iodine treatment to destroy thyroid tissue and reduce hormone levels, you can then develop a secondary issue related to these decreased thyroid hormones, and this would be considered secondary hypothyroidism. And sometimes, a condition of tertiary hypothyroidism can occur. This happens when an underactive thyroid results from a problem with the hypothalamus. The hypothalamus is the endocrine gland responsible for stimulating the pituitary, which in turn is responsible for stimulating the thyroid. In cases of tertiary hypothyroidism, the problem with the hypothalamus stops up the works- the pituitary isn’t properly stimulated, so the thyroid isn’t properly stimulated, and as a result, it doesn’t produce enough thyroid hormone. Hence tertiary hypothyroidism.

Thyroid Regulation

The system by which the thyroid gland is regulated is what’s called a negative feedback loop. The thyroid regulation loop includes the two aforementioned endocrine glands- the hypothalamus and pituitary- in addition to the thyroid. Here’s how thyroid regulation works: the hypothalamus secretes its hormone called TRH, thyrotropin-releasing hormone. TRH stimulates the pituitary gland to produce TSH, thyroid-stimulating hormone. TSH, in turn, stimulates the thyroid gland to secrete its hormones T3 and T4. When the level of these thyroid hormones is high enough, the hormones holler back to stop the hypothalamus from secreting TRH, and that stops the pituitary from secreting TSH, which then prevents the thyroid from secreting more hormones. So when T3/ T4 get high enough, they holler back ‘No! Stop!’ – that’s the negative bit- and that stops the loop. Clearly they don’t actually holler back, they “feedback” to stop the loop, which is why it’s called a negative feedback loop. When that feedback happens, without the stimulation of TSH, the thyroid gland stops secreting its hormones T3 and T4, and the level of thyroid hormone starts to fall. 

When all three glands are functioning normally, thyroid production is regulated to maintain relatively stable levels of thyroid hormones in the blood. But if the thyroid gland is underactive- doesn’t produce sufficient T4/ T3- either due to thyroid issues or to pituitary issues/ insufficient TSH, then the affected person experiences symptoms of hypothyroidism, such as weight gain, dry skin, cold intolerance, irregular menstruation, and fatigue, etc. If the thyroid gland is overactive- produces too much T4/ T3- the affected person experiences symptoms associated with hyperthyroidism, such as rapid heart rate, anxiety, weight loss, difficulty sleeping, tremors, and eye issues, etc. I gave a much more complete list of symptoms last week so check that out if you need to refresh your memory.  

Thyroid Disease: Diagnosis and Testing 

Thyroid disease can be difficult to diagnose, because the symptoms are easily confused with those of other conditions. Fortunately, there are specific tests that can determine if your symptoms are being caused by a thyroid issue. These include lab tests, imaging, and physical exams.

Thyroid Lab Tests

One of the most definitive ways to diagnose a thyroid problem is through blood tests. These give an indication of how your thyroid gland is functioning, by measuring the amount of thyroid hormones in your blood. I imagine some of you have seen ads on the interwebs for home thyroid screening kits. You get it, lance your finger, send it in, and five days later, you get the results. I’m sure they’re pretty limited, and it’s probably better just to see your primary, but if you have symptoms and you can’t do that for some reason- say a no insurance sitch- and you don’t want to spend a small fortune on bloodwork to satisfy a hunch, then a home kit probably wouldn’t be the worst idea- definitely better than ignoring it. 

No matter how you get labs, measuring hormone levels sounds pretty straightforward, but this is the endocrine system we’re talking about here people, so it’s not that simple… There are multiple tests to measure function, but I’m going to simplify it as much as possible and only talk about three: TSH, T4 and T3. During thyroid diagnostics, there are so many tests that can be done, but these three, singly or in combination, are always among them. They offer the best snapshot of thyroid function, even post diagnosis, for monitoring treatment efficacy.

TSH Test

Arguably the most useful thyroid test, a TSH test measures the levels of thyroid stimulating hormone made by the pituitary gland. Looking at TSH is often the best way to initially test thyroid function, and changes can even serve as an early warning system, because they often occur before the actual level of thyroid hormone in the body becomes too high or too low and starts causing major symptoms.

Doctors generally consider TSH levels to be within a normal range if they are between 0.4 and 4.0 milliunits per liter (mU/l). I should note that this normal range can vary based on a person’s age, as ranges tend to increase as a person gets older. It can also vary in pregnant women. That said, research hasn’t shown a consistent difference in TSH levels between males and females. Some studies suggest higher levels in males, while others suggest the same in females, but any such difference appears quite small, and it’s unlikely to be clinically relevant.

Most labs use the following reference values for TSH levels for what is considered normal vs low, indicating hyperthyroidism vs high, indicating hypothyroidism:

Low TSH: 0 to 0.4 = Hyperthyroidism

Normal TSH: 0.4 to 4 = Normal

Elevated (mild) TSH: 4 to 10 = Mild hypo

High TSH: >10 = Hypothyroidism

These are the commonly accepted values, but there is some debate about the ranges- some studies suggest that normal levels are more likely to fall between 0.5 and 2.5 milliunits per liter (mU/l) so I suspect far more people would qualify as hypothyroid. 

A low TSH level indicates that the thyroid is producing too much thyroid hormone, meaning hyperthyroidism. It may seem counterintuitive at first glance, how a low level of one thing could cause overactivity of another, but low TSH levels being indicative of overactive thyroid makes sense in terms of the negative feedback mechanism: when the thyroid gland is secreting high levels of hormones, the pituitary gland is told to stop producing TSH, so TSH would be expected to be low.

On the flip side, a high TSH level indicates that the thyroid is not secreting enough thyroid hormone, meaning hypothyroidism. In this case, not only won’t the pituitary gland be told to stop making TSH, it will actually produce more TSH to try to compensate, to make the thyroid secrete more hormone. 

T4

A T4 test measures the blood level of thyroxine, the main hormone that accounts for about 95% of all thyroid hormone circulating in the blood at any given time. A typical normal range is generally about 4.5 to 11.2 mcg/dL, micrograms per deciliter, though I’ve also seen 5.0 to 12, it varies among different laboratories. Just so you’re aware, T4 exists in the body in two forms- bound and free- and there are a few different types of T4 tests, but I’m applying the KISS principle, and that’s too complex for our purposes today. But check it out if you’re interested. 

High levels in any T4 test generally indicate an overactive thyroid, or hyperthyroidism, while low levels in any T4 test generally indicate an underactive thyroid, or hypothyroidism.

It’s important to note that T4 levels are affected by several medications and medical conditions. Estrogen, oral contraceptives, methadone, amiodarone, pregnancy, liver disease, and hepatitis C can cause a high T4 level. Testosterone or androgens, anabolic steroids, lithium, phenytoin, propranolol, interferon alpha, and interleukin-2 can cause a low T4 level. 

The T4 test and the TSH test are the two most common thyroid function tests, and they’re usually ordered together. When their results are looked at together, they can offer a snapshot of overall function, as well as potentially suggest a cause for an abnormality. In fact, these are the tests I mentioned last week that are routinely performed on newborn babies to identify a low-functioning thyroid gland- a condition called congenital hypothyroidism- which, if left untreated, can lead to those severe developmental disabilities.

As a practical example of how looking at T4 and TSH together can give you an idea of the cause of an abnormality, consider this hypothetical: say lab results show low T4, indicating hypothyroidism. If TSH testing shows an elevated or high TSH, this would indicate that the problem is with the thyroid gland itself, because the pituitary is doing its job properly- you’d expect TSH to be high when hormones are low. So this would be like 95% of cases, primary hypothyroidism. Contrast that same low T4 with a TSH test that shows low TSH. That would indicate that the pituitary gland is the likely cause, because TSH should be high, and it’s not, so this would be considered a case of secondary hypothyroidism. 

T3 Test

A T3 test measures the level of the thyroid hormone triiodothyronine, which normally accounts for about 5% of thyroid hormone circulating in the blood at any given time. Like T4, T3 also exists in two forms. If T4 tests and TSH tests suggest hyperthyroidism, a T3 test is usually ordered to support the diagnosis, and T3 testing is especially useful in helping determine the severity of the hyperthyroidism present. It may also be ordered if you’re showing symptoms of an overactive thyroid gland, but your T4 and TSH aren’t elevated. In hypothyroidism, T3 testing is rarely helpful, because it’s generally the last hormone to become abnormal. Many factors influence T3 levels, including age, sex, and some health conditions, such as liver disease, and of course pregnancy. As such, an abnormal T3 level doesn’t always mean that a person has a thyroid condition.

A normal T3 level might be somewhere between 100 to 200 nanograms per deciliter. A high T3 level is indicative of overactive thyroid, or hyperthyroidism, and a low T3 level is indicative of underactive thyroid, or hypothyroidism. That said, patients can be severely hypothyroid- with a low T4 and high TSH- but still have a normal T3 level. That’s why it’s not super helpful in many hypothyroid patients.

T4 vs T3

In some individuals with hyperthyroidism and low TSH, only the T3 is elevated and the T4 is normal, and vice versa. In some specific types of thyroid diseases, the levels and proportions of T3 and T4 in the blood change, and in doing so can actually provide diagnostic information. For example, a pattern of increased T3 vs T4 is characteristic of the autoimmune condition called Graves’ disease, the most common cause of hyperthyroidism in the US. On the other hand, severe illness and medications- like steroids and amiodarone- can decrease the amount of thyroid hormone the body converts from T4 to T3, resulting in a lower proportion of T3. As a result, depending on the individual and the type of disease, generally the best way to get an accurate depiction of thyroid function is to look at blood levels of all three of these hormones: TSH, T4, and T3.

In addition to these most common hormone level tests, there are several thyroid antibody tests that can be run, especially during an initial diagnostic workup, to help identify and confirm different types of autoimmune thyroid conditions, such as Hashimoto’s Thyroiditis and Graves’ Disease. There’s also antibody testing; microsomal antibodies called TPO, thyroglobulin antibodies, aka TG abs, and stimulating immunoglobulins and blocking immunoglobulins. So many other components that can be part of thyroid disease. As part of a diagnostic workup, a physician may also look at calcitonin and thyroglobulins to look for potential hyperplastic, or cancerous and/ or inflammatory processes. 

One last note on thyroid labs, triglyceride levels may also be tested, because these can be an indicator of metabolic rate, and that’s what the thyroid controls. For instance, having very low triglycerides can be a sign of an elevated metabolic rate, so could support or suggest a diagnosis of hyperthyroidism.

Imaging Tests

If your blood work suggests that your thyroid gland is overactive or underactive, your doctor may order imaging tests to assist in diagnosis. Ultrasound can be used to examine and measure the size of the entire thyroid gland- as well as any masses that may be present within it- and then determine if a mass is solid or cystic. A thyroid uptake scan can be used to see if the thyroid is overactive; specifically, it can reveal whether the entire thyroid or just a single area of the gland is causing the overactivity. Based on these findings, a physician may want to sample tissue from the thyroid to check for cancer. Other imaging tests like CT or MRI can be used to look for things like pituitary tumor that could be causing the condition.

Physical Exam

Another way to quickly check the thyroid is with a physical exam in your healthcare provider’s office. This is a very simple and painless test where your provider feels your neck for any growths or enlargement of the thyroid. There are plenty of resources on the great interwebs that claim to make you an expert in self exam to determine thyroid health, but I think that’s a pretty dubious claim. If you think you might have a thyroid issue, see your primary. Or at the very least, order a home screening kit, lance your finger, and send it in. 

Next week, I’ll start with treatment for hyper and hypothyroidism; I’ll cover meds and modalities, as well as how diet and nutrition can be used to help manage or possibly prevent thyroid dysfunction. 

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Thank you and be well people!

MGA