Thyroid Disease — Lab Tests & Hypothyroidism

Thyroid disorders are confusing, which makes them fun.  We’ll deal with:

• Hypothyroidism
• Hyperthyroidism (a.k.a. Thyrotoxicosis)
• Thyroid Nodules

If you’re unfamiliar with normal thyroid physiology and feedback loops, click here.  If unfamiliar with typical signs and symptoms of Hyperthyroidism vs. Hypothyroidism, click there.

A quick preliminary word about lab tests.  The most common ones ordered these days are:

• TSH  (Thyroid Stimulating Hormone)
• Free T4  (abbrev. “FT4”)  [a.k.a. Free Thyroxine]

Only order a T3 (the other hormone produced by the thyroid gland) in the context of Hyperthyroidism.

Then there’s “Total T4,” which includes FT4 plus bound-T4.  T4 binds to certain serum proteins called “Thyroid-Binding Globulins;” only the “Free” molecules are active.  In poor countries, Free T4 may be too expensive, so Total T4 might be test-of-choice.

No big deal, except that certain conditions may elevate the thyroid-binding globulins, so Total T4 winds up higher than usual, while the active-but-unable-to-measure FT4 is still the same .  There’s a way around this, by ordering a “Free Thyroxine Index” (FTI), a laboratory calculation from the Total T4 and the “T3-Resin Uptake.”

• T3-Resin Uptake is an indirect estimation of Thyroid Binding Globulins.
• It IS NOT a measurement of T3!!!!!  T3 is simply an ingredient used to perform the test.
• The calculated “Free Thyroxine Index” represents an approximation of Free T4.
• If you can order a Free T4, there’s no reason in the world to ever care about T3-Resin Uptake & the FTI.

Now, on to the diseases.

HYPOTHYROIDISM

• elevated TSH   [normal is usually 0.5 – 4.5 mU/L]

• low FT4   [normal is usually 0.8 – 1.8ng/dL]

s that!  No need to order any antibody tests, because whatever the etiology, treatment is the same (replacement with Levo-Thyroxine).

Ordering a TPO (Thyroid Peroxidase Antibody) seeks to identify Hashimoto’s Thyroiditis, but it doesn’t make any difference.  Besides, so many people who’ll never develop thyroid disease are TPO-positive, that the test would only serve to rule-out Hashimoto’s if it’s negative.  Outside of pregnancy [see below], this is irrelevant.  Other antibodies are even less useful.

Management of Hypothyroidism consists of picking a starting daily dose of replacement hormone (usually Levo-Thyroxine) based on weight, age, TSH level, and intuition, then adjusting by subsequent TSH & FT4 values.  Begin a little low in the elderly and anyone with cardiovascular risks or illness.

Easiest chronic disease in the world, if you have to get something.  Just two things to remember about follow-up:

• L-Thyroxine has a very long half-life.  Don’t repeat labs for at least a month; I prefer to wait a full 6 weeks.
• Question adherence before upping the dose (as with anything).  I’ve seen iatrogenic thyrotoxicosis from providers raising dosage without realizing the patient was missing half their pills.

Subclinical Hypothyroidism

Defined by an elevated TSH and normal (usually low-normal) FT4.  It’s debatable as to whether there are sequelae, and whether it needs treatment.  Consensus seems to be:

• TSH >15 mU/L should get Tx
• TSH <10 (with normal FT4) doesn’t need Tx
• TSH 10-15 leans toward Tx, especially if the FT4 is at lowest limits of normal

As mentioned in a prior post, don’t jump on subtle lab abnormalities as indicators of disease, even if they’re persistent.  By definition, 1 out of 40 people will have a high TSH, since lab “normal” is simply, by definition, outside the 2 standard deviations from the mean (viz. 5%; half of them high & half low).

Also, follow the TSH a while; no need to rush to treatment.  Maybe their hypothyroidism will go away…

Resolving Hypothyroidism

Viral Thyroiditis, not uncommon, begins Hyperthyroid, turns Hypothyroid, and eventually resolves Euthyroid.  I’ve picked up patients who transferred in on low doses of L-Thyroxine for years.  I had them stop it, and thyroid function remained perfectly normal.  Patients with frank Hypothyroidism have a fairly high TSH, like 100 mU/L (I’ve seen 250 with only subtle symptoms).  They require L-Thyroxine at daily doses of at least 0.10 mg (100 mcg), often 0.20 – 0.30 mg.  Not merely 0.025 – 0.050.

Hypothyroidism In Pregnancy

Real bad.  There’s a very high rate of spontaneous abortion (60%), and a host of other fetal & maternal complications.  The American College of Obstetrics & Gynecology promises to recommend routine TSH screening at pregnancy diagnosis any year now, but I don’t think they have as of yet.

Since the hCG molecule has thyroid-stimulating properties, less TSH is needed, so normals are lower in pregnancy.  Use the following values for the TSH:

• Non-Pregnant:    0.4 – 4.5 mU/L
• 1^st Trimester:      0.1 – 2.5
• 2^nd Trimester:      0.2 – 3.0
• 3^rd Trimester:      0.3 – 3.0

Then there’s the Free T4 problem  —  measurement may be unreliable in pregnancy.  Be sure to use whatever normal values are dictated by the specific kit the Lab has used.  If that’s not available (one lab could only quote me from their overall manual, not the actual kit’s manufacturer’s), it may be safer to rely on the FTI mentioned above.  Or just use the Total T4 test, but multiply by 1.5 to compensate for normal increase in thyroid binding globulins induced by pregnancy’s estrogens.

NOTE  —  If a preexisting Hypothyroid patient gets pregnant, quickly increase her L-Thyroxine dose by 30% and follow the TSH every month, using the above normals-for-pregnancy.

Subclinical Hypothyroidism is an issue in pregnancy, just because any progression to frank disease can be so catastrophic.  For pregnant women with an elevated TSH and a normal FT4, this may be the time to order the TPO Antibody.  Even though the TPO is so common within the general population, if high, it may warrant low-dose L-Thyroxine treatment for Subclinical Hypothyroidism in Pregnancy, with monthly TSH monitoring, to avoid development of overt disease.

Central Hypothyroidism

Most uncommon.  The etiology is hypothalamic or pituitary, resulting in insufficient TSH to stimulate the thyroid.  Count mostly on a low FT4.  The TSH may be also low or normal, occasionally even inappropriately high (slightly), due to biologically inactive TSH secretion.

Diseases includes masses, brain surgery or irradiation, strokes, infections, trauma.  Another cause is Sheehan’s Syndrome: pituitary infarction from [very] severe post-partum hemorrhage.

To work up Central Hypothyroidism, order other pituitary Hormones: Growth,  Luteinizing, Follicle-Stimulating, and ACTH; also Prolactin.  And an MRI.

Phenytoin & carbamazepine can cause a spuriously low FT4 with a normal TSH.

That’s it for Hypothyroidism.  Next time we’ll go on to Hyperthyroidism, and also touch on thyroid Nodules.