Treatment Adherence and Compliance in Maintaining TSH Levels for Hypothyroidism

James Hennessey, MD, FACP: Tony, when it comes to factors that impact TSH [thyrotropin] levels, what kind of thought process have you put into this? And what are your observations?

Antonio Bianco, MD, PhD: If I see a patient who has been on a steady dose of levothyroxine, and suddenly that TSH is off target, I start asking, "Have you been taking your medication?” Most patients, after years of being diagnosed with hypothyroidism, they often take their medications. I don’t think there are many patients who are skipping, but yes, they could be skipping. I always tell them, “If you forget 1 day, take 2 tablets the next day. Don’t take them during the day because there’s the food effect.” In using that rule, most of the patients adapt, if you forget 1 day, just take 2 the next day. That’s my thought process. The first thing I think is, how are you taking it? Are you forgetting? When you forget, are you taking the additional tablet the next day?

James Hennessey, MD, FACP: That’s important to keep in mind. I get many referrals for, “I can’t control this patient’s TSH.” Then with open-ended questions like, “How many tablets do you miss per month?” They say, “Oh, 5 or 6, I don’t know.”

Antonio Bianco, MD, PhD: Correct.

James Hennessey, MD, FACP: That’s a lot of thyroid mess.

Antonio Bianco, MD, PhD: The other thing that I always struggle with is, what time do you take your tablets? And how far apart from your meals do you take your tablets? I always feel a little guilty telling my patients, “You must wait 1 hour for breakfast after you take your tablet,” because 1 hour sounds like a lot of time to me. I evolved over time, I used to say 45 minutes to an hour, then 30 to 45 minutes, and I hear our colleagues saying between 30 and 60 minutes before your meals. The important thing is to be consistent. If you can, keep 30 to 60 minutes before the first meal in the morning. Many of my patients tell me, “Doctor, I put a glass of water on my nightstand. I wake up early, I take the tablet, and then I wait in bed until I [fully] wake up, I stand up, and go do my business during the day.” I think that’s a good idea as well. How do your patients cope with this idea of having to wait for breakfast?

James Hennessey, MD, FACP: That’s an interesting question. I’ve recently been thinking quite a bit about that and looking at the data. But the bottom line is I agree with you, if they get up at 5 am or 4 am for any reason, take their tablet then. Then they’ve got at least 60 minutes prior to their breakfast; that should be the optimal way to do it. There’s a bit of controversy there because I know the guidelines that we’ve published have come up with this compromise of at least 30 minutes before breakfast. That was based upon the things you were talking about: I feel bad for my patient, they’re always complaining, so we compromise. But of course when I compromise that doesn’t change the data. The data clearly show that the most consistent way of doing this is 60 minutes prior to the breakfast. On the other hand, I can say to them, “Do you want optimal treatment, or are you willing to compromise the consistency with which we’ll get outcomes?” They’re like, “Fine, I’ll do it.”

There’s a meta-analysis that just came out looking at that question of pre breakfast versus with breakfast or bedtime dosing. The interesting thing in this meta-analysis was they chose only studies where the patients were instructed to take it 30 minutes prior to breakfast. Then they compared that to bedtime, where there was a lot of variability as to when the bedtime dosing was occurring. And they concluded that 30 minutes before breakfast was the same as bedtime dosing. There were so many different moving parts in this meta-analysis, that I looked at it and said, wait a minute, none of those studies included the 60 minutes before breakfast studies that were so carefully and skillfully done. Why is that? Well, if you want to conclude that 30 minutes is the same as bedtime, then you only choose studies that looked at 30 minutes.

Antonio Bianco, MD, PhD: I see.

James Hennessey, MD, FACP: They completely ignored the 60-minute studies. Far better consistency.

Antonio Bianco, MD, PhD: That’s correct. Bedtime dosing is a new concept for me. Every now and then a patient will ask, “What if I have a neighbor or a friend that takes it at night?” I was never a very good supporter of that because I’m from Brazil, and in Brazil dinner is very late. In my mind, it doesn’t make a lot of sense. Now, if you have dinner at 6 pm, then it could make sense to have a tablet before you go to bed.

James Hennessey, MD, FACP: Exactly, I agree with you. In many of the studies in that meta-analysis to look at the studies carefully, those were the inconsistencies that were in there. They were from all over the world, the spacing between having dinner or supper, whatever you want to call the evening meal, and then taking the thyroxin, it varied between 15 minutes and 2 hours.

Antonio Bianco, MD, PhD: Absolutely, yes.

James Hennessey, MD, FACP: Yes, it was statistically significant, but there were some issues.

Antonio Bianco, MD, PhD: The important thing to tell the patients is consistency and at least half an hour before breakfast in the morning. If you are not doing that, then you should expect variability in your TSH that shouldn’t be there.

Transcript edited for clarity