Thyroid Disease

Thyroid disease is more common than you might think, and it pays to keep it in mind when working up patients with confusing presentations. Rather than re-invent the wheel, we've located some excellent primary source material from the American Asociation of Clinical Endocrinologists.

If you just want the basics, read below - otherwise, click here for excellent Overviews of Hypothyroid, Hyperthyroid, Nodules, and Thyroid Carcinoma.



Quick Review of Normal: The hypothalamus looks for Free T4. If it thinks there's not enough, it releases Thyroid Releasing Hormone (TRH).

TRH is received in the anterior pituitary. The pituitary, in addition to looking for TRH, is also looking for Free T4 - just like the hypotahalamus was. The pituitary reponds to these two inputs, and if it feels there's not enough "thyroid hormone" (the generic term for T4 and T3), it releases Thyroid Stimulating Hormone (TSH).

TSH is taken up by the thyroid, which responds by making thyroglobulin, which is in turn converted to T4 and T3. You'll remember that T3 is the more active form, which is made in much lower quantities.

T4 and T3 are picked up in the bloodstream by Thyroid Binding Proteins, which tend to make the T4 and T3 fairly useless, but a small fraction remains "free" in the bloodstream (not bound). By deiodination, T4 is converted to the more active T3 in the periphery.

Remember that for whatever reason, it's Free T4 that acts as feedback to both the hypothalamus and the pituitary - if there's too much Free T4, they slow down the production of TRH and TSH, and if there's too little Free T4, they make more.

The thyroid hormone the does its job - it regulates protein synthesis (and protein metabolism) - the driving force behind "basal metabolic rate."

That's normal. Things should generally stay within a fairly well-controlled range by the use of this feedback system.

Abnormal: When things get out of balance, the problem is usually with the thyroid itself. When this is true, we've got a 1o thyroid disease.

The most common cause of hypothyroidism is probably Hashimoto's Thyroiditis. (Remember the "o" at the end of both Hashimoto and at the end of hypo.) It's an autoimmune condition that attacks the thyroid gland and stops it from making thyroid hormone.

Similarly, the most common cause of hyperthyroidism is probably Grave's Disease. (No good mnemonic there - just remember that neither ends in "o.") This is also autoimmune, but this time instead of attacking the gland itself, the antibodies just bind to the TSH receptor site, and stimulate the thyroid to produce way too much thyroid hormone.

So how do we detect this? We check a TSH as our first screening tool. Remember that in 1o thyroid disease, everything is working fine except the thyroid itself. And also remember that the vast majority of thyroid disease is 1o. So we check to see how the other organs in the thyroid axis (the hypothalamus and the pituitary) are responding.

Surprisingly, even small shifts in thyroid hormone can lead to large responses by the pituitary. The pituitary is very good at maintaining the thyroid hormone levels to very tight tolerances - much tighter tolerances than we look for when we check labs for T4 or T3. In other words, the pituitary detects that something is wrong long before we would.

And, of course, it compensates for what it perceives as incorrect levels of thyroid hormone by increasing or decreasing TSH output - usually pretty drastically. Drastically enough that we can easily detect it with laboratory analysis.

There are 2o (pituitary-based) and 3o (hypothalamically-based) causes for thyroid disease, as well, but they're fairly rare, and tend to show up as other endocrine or brain disorders long before they affect the thyroid. Don't rule them out, but start off by assuming that the problem is in the thyroid. 

If you assume a 1o  disorder in your hyperthyroid patients, you'll be right >99% of the time. You'll also be right >90% of the time with your hypothyroid patients - hypothyroidism can be caused by pituitary disease (but again, you'll probably have figured out the pituitary disease before you notice the hypothyroidism).

Also, there are many more reasons for 1o thyroid disease than just Hashimoto's and Grave's Disease. There's thyroid cancer, Thyrotoxicosis, Euthyroid-sick syndrome, subclinical hypothyroidism, iodine deficiency or over-replacement, and on and on. Read the articles for this stuff.

Tidbits: An important point to keep in mind - thyroid hormone is an important regulator of cholesterol. If someone's cholesterol changes for no reason, check a TSH.

Also important but easier to remember - hypothyroidism is a treatable but often undiagnosed cause of depression. Check TSH in your depressed patients.

Pregnancy can mess with the thyroid. It's common for a slight hyperthyroid state at the beginning of pregnancy and a slight hypothyroid at the end. Hypothyroid at the beginning of pregnancy is not normal - and needs replacement and monitoring.

Total T4 and T3 are less accurate than the free varieties because lots of things (particularly hormones) like birth control, hormonal changes, and many many drugs can all effect the quantity of binding protein that's made. So use free T4 and free T3 instead of total.



The Thyroid Cascade

If you're in the outpatient setting and you suspect your patient may have thyroid disease, order the thyroid cascade instead of individual tests. It starts with a TSH and automatically follows-up abnormal results. You can also use it inpatient for basically healthy patients.

For most inpatients (particularly those in the ICU), you'll want to not use the cascade - instead, start with TSH and Free T4, particularly for hypothyroid diseases. If you suspect hyperthyroidism and those both come back normal, you may decide to add a Free T3 to rule out thyrotoxicosis.

The Cascade: