Overtreatment for GD?

Posted on October 4, 2011 by gravity

There was an article about overtreating patients in the New York Times today. It opened with the classic case of Graves’ Disease. The article looks (briefly) at the pros and cons of getting the aggressive treatment (radioactive iodine or surgery) versus just taking a pill. Indeed, RAI and surgery do “fix” the problem, but, according to the view of the article, this may be like amputating a finger for a hangnail.

How to Steer Toward the Path of Least Treatment

The first doctor Lynn Munroe consulted about her hyperactive thyroid gland recommended radioactive iodine treatment to destroy the gland, followed by a lifelong regimen of thyroid hormone replacement pills.

The second physician she consulted said that he could operate, removing the gland without radiation, but that she would still need to take the pills.

A third doctor suggested a more cautious approach, prescribing medication to depress the gland’s activity. It worked: Ms. Munroe, 49, a publicist in West Nyack, N.Y., no longer has symptoms of hyperthyroidism, even though she has been weaned off the medication.

“And I still have my thyroid intact,” she said. “Thank God for third opinions.”

[Read the rest of this article at NYT.com]

Posted in Anti-thyroid drugs, Radioactive iodine, Surgery, Treatment options | Leave a comment

The risks of PTU

Posted on March 1, 2011 by gravity

Summary

ResearchBlogging.orgThere are two main drugs used to treat Graves’ Disease medically – MMI (methimazole or it’s nearly identical relative carbimazole) and PTU (propylthiouracil).

As with all drugs, there are risks and side effects.  As a patient, I’ve often been frustrated when trying to understand exactly how risky these drugs are.  The listed risks (liver failure, loss of white blood cells) are terrifying, and yet, very few people ever experience these.  What do we know about the risks and what can we patients do to avoid them?  Dr. David Cooper at Johns Hopkins has published several papers about these risks and I’m going to review them over the next few weeks.

The paper today is a recent (2009) summary of two scientific meetings that were held to discuss the risks involved with the use of PTU.  Currently in the US, about 25% of Graves’ patients are on PTU.  Doctors prescribe PTU rather than MMI for several reasons.  PTU is considered better for pregnant women, especially during the first trimester, as MMI can sometimes cause birth defects.  Some people have an allergic reaction or other mild side effects from MMI and so take PTU instead.

Because of this, the general trend is to prescribe MMI first, and if that doesn’t work for some reason (pregnancy or adverse reaction), then switch to PTU.  MMI is also considered “better” than PTU in that in is more effective when people are severely hyperthyroid, people adhere to it better, and it causes less toxicity, especially at low doses.


So, how risky is PTU?

There are approximately 600,000 60,000 new cases of Graves’ diagnosed in the US each year.  Of these, 25% get put on PTU for one of the above reasons, so there are 15,000 people who start taking PTU each year.  Of these people, approximately 1 in 1000, or 15 people total, develop severe liver damage, and 1 or 2 die.

Various organizations keep different sorts of records on PTU-related liver failure.  For instance, there are 42 cases reported in the scientific literature since 1947, while the FDA knows of 47 cases.  UNOS (the organ transplant association) reported 23 liver transplants over a 17-year period related to PTU, but none related to MMI.  The FDA-AERS database lists 34 cases of liver failure in the last 20 years.

Who gets these nasty reactions?

The average dose of PTU in the people who had these reactions was 300 mg per day.  The victims had been taking PTU for 6-450 days.  About half had been taking PTU for less than 120 days, and half for more than that.  About a third of the victims were children, and there were two reports of fetal liver damage.  Because children make up only about 6% of Graves’ disease patients, but nearly 33% of the patients experiencing liver damage, PTU may affect children more negatively than it does adults.

Can you tell if you are having these reactions?

Because liver toxicity happens so rapidly, routine monitoring of liver values is not helpful.  Monitoring does not reduce the risk of liver injury because of the unpredictable nature of the drug reaction.  Signs of liver failure include:

  • jaundice (yellowish skin or eyes)
  • fatigue or malaise (tiredness)
  • nausea
  • anorexia (no appetite)
  • pharyngitis (sore throat)

If you have any of these signs, stop taking PTU and go get your liver enzymes checked immediately.

 

What about pregnancy?

I’ll quote here from the paper:

Considering the intricacies of care and risks involved for a woman with active [Graves' disease] during pregnancy, treatment with radioactive iodine or surgery before pregnancy should be strongly considered for those who desire future pregnancy. Doing so can avoid the dilemma of choosing between a drug associated with a small risk of fetal birth defects [MMI] and another drug associated with a similarly small but finite risk of serious liver injury in the mother [PTU].

For women who choose not to take the risks of surgery (anesthesia, mistakes) or radioactive iodine (radioactivity, hypothyroidism), the current recommendation is to take:

  • PTU for the first trimester (to prevent birth defects)
  • MMI (if needed) for the second two trimesters

The upshot?

Stick to MMI if possible.  If you choose PTU, you will more than likely be one of the 999/1000 people who has no problems whatsoever.  Hooray!

But, be aware of the symptoms mentioned above and seek help immediately if you experience them.

If you are thinking about getting pregnant, have a good look over the risks of all of these options and talk with your doctor.

Reference
Cooper, D., & Rivkees, S. (2009). Putting Propylthiouracil in Perspective Journal of Clinical Endocrinology & Metabolism, 94 (6), 1881-1882 DOI: 10.1210/jc.2009-0850

Abstract

This paper had no abstract

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Posted in Anti-thyroid drugs | 6 Comments

Taking methimazole for 10+ years

Posted on February 10, 2011 by gravity

ResearchBlogging.org

In the US, most Graves’ Disease patients get herded into either radioactive iodine treatment (RAI treatment) or surgical thyroid removal.  These are seen as “definitive” treatments, meaning permanent fixes.  There is some truth to this as it is impossible to be hyperthyroid if you don’t have a thyroid.  Taking anti-thyroid drugs, on the other hand, is seen as a temporary solution, usually for less than two years, before getting one of the “definitive” treatments.

Anti-thyroid drugs are, indeed, not definitive.  20-70% of Graves’ patients relapse after stopping medication.  In that sense, these drugs don’t “cure” the disease, while the “definitive” treatments do.
However, after surgery or RAI, people usually become hyp-O-thyroid (too little thyroid hormone) and have to take supplementary hormone.  The choice,  from the patient’s perspective, is then either a lifetime of taking an anti-thyroid drug (such as methimazole, tapazole, or polythiouracil), or a lifetime of taking a “pro”-thyroid drug, such as Synthroid, Levothyroxine, or Armour.

If you have to take a pill every day no matter what, what’s the difference?

The antithyroid drugs have some minor side effects (rashes, headaches) as well as some rare, but very scary ones, such as agranulocytosis (loss of your white blood cells), problems with blood clotting, and death of liver cells.  The “pro”-thyroid drugs have fewer serious side effects (possibly a slightly increased chance of osteoporosis, some digestive upsets).  However, the risks of the “definitive” treatments themselves are worth considering.  RAI is thought to strongly increase your risk of developing Graves’ Opthlamopathy, an eye disorder.  Surgery and anesthesia have numerous inherent risks.

One solution that is common in Europe, but less so in the US is just staying on the anti-thyroid drugs permanently.  This eliminates the risks of surgery or RAI, has the same impact on the daily life of patients (one or two pills a day), and, as long as you tolerate the drugs and don’t develop the nasty side effects from them can, presumably, be taken indefinitely.

The study I’m discussing today tests that last assumption – is taking methimazole as a long-term treatment safe and effective?

The authors started with 504 patients who were treated with methimazole for 18 months, after which treatment stopped but the patients were monitored.  104 patients’ hyperthyroidism returned within a year.  Of these, the authors randomly treated half with RAI and half with more methimazole.  They then followed these patients for 10 years and measured many indicators of their health, including liver enzymes, cholesterol, bone density, thyroid hormones, and cardiac tests (among others).

After 10 years, they found that the groups had similar thyroid levels, similar cost of treatment (from the perspective of the health care system) and many similar blood values. The RAI group had slightly higher LDL (“bad cholesterol”) levels, slightly lower bone densities, and similar cardiac tests.  However, the methimazole group had more goiter and higher anti-thyroid antibody levels.  The authors concluded that long-term use of methimazole was a good alternative to surgery or RAI.  They say:

“Except for mild side effects, serious reactions are rare, and the risks of occurrence of cardiac and bone complications are equal to or less than those of radioiodine therapy…[A] possible approach to the therapy of hyperthyroidism may be to control the disease, for a lifetime, with antithyroid drugs. The remarkable lack of MMI side effects and the apparent high treatment compliance in this study prompt the adoption of an alternative approach such as this.”

End result?  As long as you tolerate it (and most people do), long-term use of methimazole is a decent alternative to RAI or surgery.

Abstract

Objective: To investigate the long-term effects of continuous methimazole (MMI) therapy. Design and methods: Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continu- ous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained. Results: There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treat- ment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12–2.95, P,0.02) and 1.6 (1.09–2.34, P , 0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups. Conclusion: Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.


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Azizi, F. (2005). Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine European Journal of Endocrinology, 152 (5), 695-701 DOI: 10.1530/eje.1.01904

Posted in Anti-thyroid drugs, Radioactive iodine | 97 Comments