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Updated December 16, 2014.

Kent Holtorf, MD has a long history of working with patients who have hormone imbalances -- including thyroid, adrenal, and reproductive hormones. He runs the Holtorf Medical Group in California, where he specializes in complex endocrine dysfunction, including hypothyroidism, adrenal insufficiency, and insulin resistance.
Dr. Holtorf has been working with a number of his patients -- many of whom have an underactive thyroid -- who have found it difficult or seemingly impossible to lose weight.


What he discovered is that while there are many factors involved in the inability to lose weight, almost all the overweight and obese patients he treats have demonstrable metabolic and endocrinological dysfunctions that are major contributors to the weight challenges of these patients. In particular, Dr. Holtorf has, based on some of the latest research, focused on evaluating two key hormones -- leptin and reverse T3 (rT3)-- and treating any identified irregularities to help his patients lose weight.

I'm pleased to be able to bring you this interview with Dr. Kent Holtorf, discussing his approaches to help thyroid patients achieve long-term weight loss.

Mary Shomon: You have said that you feel that two key hormones -- leptin and reverse T3 -- are playing a key role in regulating weight and metabolism. Can you tell us a bit about leptin, first, and what it has to do with weight loss challenges?

Kent Holtorf, MD: The hormone leptin has been found to be a major regulator of body weight and metabolism.

Leptin is secreted by fat cells and the levels of leptin increase with the accumulation of fat. The increased leptin secretion that occurs with increased weight normally feeds-back to the hypothalamus as a signal that there are adequate energy (fat) stores. This stimulates the body to burn fat rather than continue to store excess fat, and stimulates thyroid releasing hormone (TRH) to increase thyroid stimulating hormone (TSH) and thyroid production.

Studies are finding, however, that the majority of overweight individuals who are having difficulty losing weight have varying degrees of leptin resistance, where leptin has a diminished ability to affect the hypothalamus and regulate metabolism. This leptin resistance results in the hypothalamus sensing starvation, so multiple mechanisms are activated to increase fat stores, as the body tries to reverse the perceived state of starvation.

The mechanisms that are activated include diminished TSH secretion, a suppressed T4 to T3 conversion, an increase in reverse T3, an increase in appetite, an increase in insulin resistance and an inhibition of lipolysis (fat breakdown).

These mechanisms may be in part due to a down-regulation of leptin receptors that occurs with a prolonged increase in leptin.

The result? Once you are overweight for an extended period of time, it becomes increasingly difficult to lose weight.

Mary Shomon: You've said that you feel that leptin levels above 10 may warrant treatment. Can you explain a bit more about leptin levels?

Kent Holtorf, MD: Most underweight or normal weight individuals will have leptin levels below 10, although most major labs will use a reference range of 1 to 9.5 for men and 4 to 25 for women. (It must be remembered that this range includes 95% of so-called normal people and includes many who are overweight.) Almost all patients who are of healthy weight will have a leptin less than 10.

Mary Shomon: How do you treat leptin resistance in your practice?

Kent Holtorf, MD: Treatment can be focus on treating the elevated leptin -- leptin resistance. An elevated leptin also indicates, however, that the TSH is an unreliable marker for tissue thyroid levels, as the TSH is often suppressed, along with significantly reduced T4-to-T3 conversion. In short, if your leptin is elevated, you have reduced tissue thyroid levels. Also, almost all diabetics are leptin resistant, which has been shown to reduce T4-to-T3 conversion in diabetics by as much as 50% without an increase in TSH, making it very difficult for type II diabetics to lose weight.

Because there is poor T4-to-T3 conversion, timed-released T3 is the optimal treatment -- although T4/T3 combination medications such as natural desiccated thyroid (NDT) can be used.

We check the resting metabolic rate (RMR) in our patients, and interestingly, those with elevated leptin levels indicative of leptin resistance have RMRs that are consistently below normal. These patients are often burning 500 to 600 calories less each day than someone of equal body mass.

Thus, to have a reasonable chance of losing weight, these patients can either try and reduce calories by 500 to 600 calories a day (just to keep from gaining weight), exercise for an hour or two a day (just to keep from gaining weight) or normalize the thyroid and metabolism.

Humans are a very successful species because we can store energy (fat) very well. There are many mechanisms to gain weight and leptin resistance is just one of them, so we use a multisystem approach; there is no one magic bullet, although any one treatment can have a dramatic effect on a particular patient.

In addition to optimizing the thyroid (remember, giving thyroid hormone to lose weight is not appropriate, but that’s not what we are doing, here we are correcting a deficiency), Symlin (pramlintide) and/or Byetta (exenatide) can be very effective for many. Human Chorionic Gonadrotropin (HCG) is another potential option that works for some. While I’ve found that the antidepressant Wellbutin (bupropion) does not work well for weight loss, a combination of Wellbutrin and low-dose naltrexone (LDN) is having some surprisingly good results. Topamax (topiramate) is an option for some but is not always well tolerated. Standard appetite suppressants, which boost metabolism, can be used, especially if the RMR is low.