Kent Holtorf, MD: Taking a subcutaneous shot several times a day can be problematic, but when patients have great results it is worth it for most. A few tricks: First, some people are concerned that the medications require refrigeration, but it’s usually not necessary, as these medications are very stable at normal daytime temperatures. So it’s not a problem to keep it in your purse or in the desk drawer.
The biggest side effect is nausea, which occurs in about 25% of patients. Most of the time it is mild and diminishes with continued use, but a few patients will not be able to tolerate it. For Byetta, I recommend starting with a 5 mcg injection before meals. Some patients start with half a shot for the first few days (only pushing the plunger halfway). The nausea in some people can be due to an increased production of stomach acid, so Zantac (ranitidine) or a proton pump inhibitor drug -- like Prilosec (omeprazole), Prevacid (lansoprazole), or Nexium (esomeprazole) for example -- can be helpful. There is a once-a-week shot in the FDA approval process, which has been shown to have reduced side effects as well as the increased convenience.
Mary Shomon: You've mentioned that for some patients, you have them taking up to 10 mcg injection of Byetta three times daily, with meals. What's the optimal treatment level for Symlin?
Kent Holtorf, MD: Nausea is less commonly a side effect of Symlin, compared to Byetta, so it’s preferable for some patients. For Symlin, the optimal dose is 120 mcg, three times per day. Both Byetta and Symlin have very low risks for hypoglycemia unless you are on insulin or on a sulfonylurea medication for diabetes.
Mary Shomon: You also feel that reverse T3 is an issue. Can you tell us a little bit about reverse T3?
Kent Holtorf, MD: T4 can be either converted to T3, the active hormone that has a metabolic effect, or to reverse T3, which is the inactive form of T3, and actually blocks the effects of T3. Doctors -- including endocrinologists -- are taught that reverse T3 is just an inactive metabolite, but studies show that it has potent antithyroid effects. In fact, is has been shown to be a more potent inhibitor of thyroid effect than PTU, a medication used for hyperthyroidism. Reverse T3 inversely correlates with intracellular T3 levels, so it is also a marker for tissue hypothyroidism, with higher levels (or lower Free T3/RT3 ratio) indicating a more significant deficiency.
Mary Shomon: Why do you feel reverse T3 plays a role in making it difficult for some thyroid patients to lose weight?
Kent Holtorf, MD: The reverse T3 is produced in times of stress or starvation to reduce metabolism, and with chronic stress or dieting, RT3 can remain elevated, suppressing tissue thyroid activity and metabolism. People on chronic diets -- or those who lose significant amounts of weight -- will have a lower metabolism than a person with the same weight and muscle mass who had not had not lost significant weight or drastically dieted in the past. This was demonstrated in a study by Leibel published in the journal Metabolism, titled “Diminished Energy Requirements in Reduced-Obese Patients.” This study compared the basal metabolic rate in individuals who had lost significant weight to those of the same weight who had not lost significant weight in the past. The authors found that those who had dieted and lost weight in the past had, on average, a 25% lower metabolism than the control patients who had not lost significant weight.
All those trainers and health gurus that never had a weight problem who tell you to do just as they do don’t realize what a disadvantage it is for people who have had a long-term weight problem. Of course, even these trainers would not even be able to maintain their weight with a metabolism that is 20 to 40% below normal.
We test the resting metabolic rate in our thyroid patients and find it inversely correlates with the reverse T3. The higher the reverse T3, the lower the metabolism, with many such individuals having a metabolism that is 20 to 40% lower than expected for their body mass index (BMI). Nobody believes how little they eat, and they are made to feel like failures -- despite doing everything right. Until their metabolic abnormalities are addressed, diet and exercise will certainly fail to achieve long-term success.
Mary Shomon: At what point do you consider reverse T3 too high and requiring treatment?
Kent Holtorf, MD: Like everything else in medicine it is a continuum, but healthy individuals are usually below 250 pg/ml and should have a free T3/reverse T3 ratio greater than 1.8 if free T3 is in ng/dl or 0.018 if free T3 is in pg/ml.
Mary Shomon: How do you typically treat elevated reverse T3 levels?
Kent Holtorf, MD: The higher the reverse T3, the more ineffective T4 only preparations will be. T4/T3 combinations are significantly better than T4-only preparations, such as Levoxyl and Synthroid, but for the higher levels straight timed released T3 is optimal.
Mary Shomon: What dietary and lifestyle changes do you recommend along with these medical approaches?
Kent Holtorf, MD: Most patients who come in have been on numerous diets and lifestyle changes and they generally are very knowledgeable in that area. Low-carbohydrate diets will suppress thyroid function and increase reverse T3 more than comparable calorie reductions with adequate carbohydrates, so while a low-carbohydrate diet may result in initial weight loss, patients are prone to regaining weight unless the reverse T3 issue is addressed.