Thursday, March 17, 2011

Metformin and Thyroid Tests

Every drug we take has many effects. The main effects are usually known by patients as well as physicians. For example, most people know that the drug metformin often causes gastric distress, which can be reduced by starting with a small dose and gradually working up to a therapeutic dose.

But most drugs also have minor effects. Sometimes your doctor is aware of these but doesn't tell you because the incidence of these effects is low and the doctor doesn't want to worry you. This is often true of the muscle weakness and memory problems that statins can cause.

Sometimes even your doctor isn't aware of the minor side effects.

Sometimes no one has yet discovered some side effects. This can be because you have to be on a drug for a certain amount of time before these side effects show up. It can be because no one has noticed the link between a particular drug and some side effect.

Or it can be because drugs can interact with other drugs, and when you're taking a lot of different drugs -- say a diabetes drug, a blood pressure drug, a lipid-lowering drug, an anti-reflux drug, an antidepressant, a beta blocker, an antihistamine, an osteoporosis drug, and an asthma drug -- and you complain of fatigue, it's not immediately clear which one of these drugs or which combination is causing that problem.

One relatively unknown drug-hormone interaction was first reported in 2006.

It seems that metformin suppresses thyroid-stimulating hormone (TSH; also called thyrotropin), the hormone that is generally tested to ascertain your thyroid function.

When your thyroid hormones (called T4 and T3) are too low, your pituitary gland secretes TSH. The TSH then tells the thyroid gland to secrete more T4 and T3.

Thus a high TSH level suggests low thyroid, and a low TSH level suggests high thyroid.

Your doctor often tests the T4 and T3 levels too, but often not. If the TSH is in the normal range, your doctor may assume your thyroid levels are fine and refuse to do more testing.

The normal ranges are controversial. The usual range is said to be about 0.4 to 5 microunits per milliliter. But some people say the cutoff on the high end should be lower, about 2.5. And graphs in endocrinology books show that the average TSH level in people considered to have healthy thyroid control is only 1.1, with very few in the upper ranges.

The new research shows that metformin therapy suppresses TSH levels. Two studies showed that it did this without affecting T4 and T3 levels. A third found that free T4 levels increased as TSH went down.

Most of the T4 and T3 in your blood is bound to proteins. The free (unbound) levels of the hormones are the active hormones, and that's what the free T4 (fT4) and free T3 (fT3) measure.

No one yet understands the mechanism of the TSH reduction by metformin. It's especially puzzling because it doesn't seem to be linked with the thyroid hormone level. And the metformin has no effect on TSH in people who have no thyroid problems.

But what it does mean for you is that if you're on metformin you should be aware of this link. Let's say you're on thyroid medication and then you start taking metformin. Your TSH goes down, and your doctor may worry that your thyroid is now too high and might reduce your dose.

But what if it's just a result of the metformin? Then you'd end up with a thyroid level that was too low.

So if you're on metformin and your TSH test doesn't seem to agree with how you're feeling, discuss this interaction with your doctor and have your T4 and T3 levels tested as well as the TSH. It could be that the lower TSH is caused by the metformin and notw higher thyroid levels.

Does this mean that metformin could interact with other lab tests? It's possible. The metformin-TSH interaction was only noticed in 2006, more than 10 years after the drug first became available.

Does this mean that other drugs could interact with the TSH test? It's possible.

We need to be vigilant about all the drugs we take, and if something seems wrong, we need to try to figure it out. Sometimes the published science reports can't tell us.

Trust your body. You know it better than anyone else. And don't let some doctor tell you that your symptoms are all in your head because there's no evidence for what you're saying. Maybe you're right and the current literature is wrong.