Unexplained Weight Gain

In America and Western Society in general, excessive weight is endemic. Sometimes it is clearly do to too much food and too little exercise. This is correctible with the above diet and a good exercise plan (see my book, the Antidepressant Survival Program).

But, what if you are eating well and exercising, and still not losing weight? There are a number of possibilities:

  • Medication-certainly many medications can cause weight gain, sometimes very rapidly (e.g., olanzapine, mirtazepine), and sometimes gradually (e.g. Prozac). In fact, virtually all psychiatric medications (with one or two exceptions such as buproprion and stimulants) can cause weight gain. How they do this is still somewhat of a mystery, but probably has something to do with interfering with the very complex appetite control system. By following the above food plan, with a good exercise plan, this type of weight gain can be slowly reduced. If you can do this, you will create a virtuous cycle, that may enable you to start to reduce the dosage of the offending medication, (always under your doctors supervision).
  • Infection-chronic infections such as Lyme, infected root canals, chronic gum disease, chronic sinusitis, chronic viral syndromes can (via many different) mechanisms cause weight gain. One way they do this is to change how the hypothalamus works, changing your hormonal set points, for example, changing your set point for thyroid hormone so you are chronically running at a lower metabolic rate, feeling colder (germs like you to be cold, they live better, fevers are rough on them). The best intervention here is to determine the infection type if possible, and to strengthen your immune system. Support the thyroid and adrenal glands if needed. All of this must be done in the context of a healthy diet and light exercise, and personalized nutrient and hormonal supplementation program.
  • Hypothyroidism – An under-active thyroid, also called hypothyroidism, is endemic in this society.

Whether it is due to medications, all the new to nature chemicals we are exposed to (called hormone interrupters), poor diet (e.g. inadequate minerals, vitamins, essential fatty acids, amino acids, excess carbohydrates), an immune reaction, genetic susceptibility, or radiation treatments for an overactive thyroid, this problem is very widespread. Regardless of the cause, hypothyroidism can lead to numerous problems including, but not limited to, weight gain, excessive tiredness, decreased sexual function, fibromyalgia, and brain fog—all of which can mimic depression. The condition can also render antidepressants ineffective. So you may think your medication isn’t working when the problem is actually due to an inadequate level of thyroid hormones.

Many people on antidepressants who have symptoms of hypothyroidism may not have the full blown condition that can be diagnosed using a standard blood test, which measures the level of thyroid stimulating hormone (TSH). Instead they have a milder form of the condition called subclinical hypothyroidism, which is frequently not detected on the standard test. In the early 1990s, I became frustrated after the test results of many of my patients with symptoms of hypothyroidism kept coming back normal. “This can’t be right,” I thought. I decided to perform a test called a thyroid releasing hormone stimulation test, a much more sensitive test that can detect subtle abnormalities in one part of the thyroid system — the pituitary gland’s responsiveness to the hypothalamus.

I hired an independent statistician to review the records of 100 patients who initially had normal results based on the standard thyroid tests. I was astounded when the statistician called me with the results. Fifty percent of the patients I tested turned out to have subclinical hypothyroidism! My findings were also confirmed clinically, after my patients noticed a clear improvement in their mental sluggishness, weight and energy levels, as well as numerous other symptoms (one patients periodontal surgery was cancelled when her gums were restored to normal after the initiation of Synthroid), after they were treated with a thyroid hormone medication called Synthroid. What concerns me most is that doctors, who rely on the results of the routine blood test, are missing many cases of hypothyroidism in patients on antidepressants.

The classic signs of hypothyroidism include sluggishness, muscle fatigue, cold sensitivity, constipation, irregular menstrual periods, dry skin, mental fuzziness, and weight gain—which can be upwards of 20 pounds. These symptoms are vague and can be indicative of a host of other medical conditions. For this reason, about half of the 11 million Americans who have hypothyroidism go undiagnosed because they mistakenly attribute their symptoms to normal aging, stress or menopause. I’d estimate that missed diagnoses are even more common in people who take antidepressants since their doctors may attribute their hypothyroid symptoms to antidepressant side effects.

Unfortunately, many doctors still aren’t aware of the connection between antidepressant use and hypothyroidism. If you are experiencing thyroid symptoms, you may need to be persistent to get your doctor to order the appropriate tests. If your request for testing is denied, make sure your doctor supplies a reason beyond “It isn’t necessary”. If you’re not satisfied with your doctor’s answer, find a doctor who will give you the test you need.

Getting Tested for Hypothyroidism

If you answered “yes” to two or more questions in the Thyroid quiz, I recommend a blood test to measure levels of three hormones: thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3). As I explained above, the standard test, which measures just TSH, is not always sufficient since TSH levels can be normal even when the thyroid is underactive. This is why I strongly recommend that your doctor perform the more comprehensive testing that measures all three hormones.

Four days before you see your doctor to have your blood drawn, you need to take your temperature three times a day and continue to do this for each of the next four days. You need to make a written record of your temperatures (include the date and time) and give this record to your doctor when you come in for the blood test. Take your oral temperature with a standard or digital mercury thermometer, and record the reading to one-tenth of a degree. Take the first reading three hours after waking, the second three hours later, and the third three hours later. If you wake up at, say, 7:00 a.m., you would take your temperature at 10:00 a.m., 1:00 p.m., and 4: 00 p.m.

The purpose of these temperature recordings is to determine the overall effectiveness of your of your thyroid system in controlling your metabolism. Since most of us — with the exception of some lawyers are warm-blooded creatures, our bodies function best in a narrow temperature range. (When we get a fever of even 1/2 degree above normal, we may feel a change in our sense of well being.)

If you have an overactive thyroid system, it will produce too much hormone and increase your body’s metabolism, raising your body temperature above the normal 98.6 degrees. If too little hormone is available, your metabolism will decrease, causing your temperature to drop below normal.

Note: Your temperature can be affected by various factors, such as having a cold, being premenstrual, exercising or eating hot or cold foods within 15 to 30 minutes before taking your temperature. Try to record your temperature before mealtimes and exercise, and (if you’re a woman) during the first half of your cycle.

Treatment for Hypothyroidism

If you are diagnosed with an underactive thyroid, your doctor will probably prescribe levothyroxine (Synthroid or Levoxil), a synthetic version of T4 or thyroxine. Synthroid is one of the five most commonly prescribed medications in the U.S. Other medications such as triiodothyronine (Cytomel) contain just T3. Your doctor can also prescribe T4 and T3 pills in combination. I explain the pros and cons of the various treatment options in the Note to Your Doctor below. Realize that your doctor may feel it is best if an endocrinologist manages your treatment. If this happens, I strongly advise you to find someone who specializes in thyroid problems.

Beyond medicinal treatments, you should be vigilant about following the Fundamentals, especially the nutrition and exercise components. Having a diet that’s too high in carbohydrates or depleted of certain micronutrients can reduce your body’s ability to manufacture T3. Exercise can help improve your energy levels and help you maintain a healthy weight.

  • Excessive calorie restriction: In some cases patients who are clearly overweight, insist that they take in a low caloric intake (e.g., 1200 calories). It is possible (I have seen one case) that the low caloric intake trains the body to have an inordinately efficient metabolism. The body learns that it is in starvation mode, and so lowers the metabolic rate. Paradoxically, the cure here, is to slowly increase caloric intake with moderate exercise. Slowly the body learns, over 1-2 years, that the starvation, the famine, is over. Weight starts to reduce. If you think this might apply to you, find a specialist in metabolism (a subspecialty in endocrinology) who guide you through this process.
  • Leptin is a hormone that is involved in controlling appetite. There is one well-done double blind, placebo controlled study that has shown that an herb (irvingia gabonensis) can, if taken twice per day, reduce weight and other manifestations of the metabolic syndrome, in those with high leptin levels.

Note to Your Doctors: Adequate Assessment of the Thyroid Axis

Studying the physiology of the thyroid axis makes it clear that a simple TSH level—even the most sophisticated kind—is not a fully adequate test of the thyroid system, unless one is only screening for advanced cases of thyroid dysfunction. As an example, if you suspect subclinical hypothyroidism, a well-established entity, a TSH is not sufficient as it only indicates the output of the pituitary gland. For example, if the pituitary or hypothalamus are suboptimally responsive to a low normal free t4 or free t3, then the TSH can be normal or, high normal, and the patient can still be subclinically hypothyroid. Thus, I recommend that every patient with signs and/or symptoms of hypothyroidism be tested with body temperatures (see above paragraphs) as well as a TSH, free T4 and free T3 (use the ‘free’ tests to eliminate protein binding distortions of test results). These results need to be looked at along with baseline temperature recordings.

A patient with suggestive signs and symptoms may have subclinical hypothyroidism if any of the three hormones mentioned above are near the limits of normal, abnormal or if temperature recordings are consistently averaging less than one-half degree below normal. In addition, after observing thyroid hormone lab results for several years, it has become clear that the relationship of the hormones to each other must be taken into account. For example, a low normal free t4 with a low normal TSH, indicates either a low set point, or a relative failure of positive feedback to the pituitary and/or hypothalamus. A mid range to high normal free t4 and a low normal TSH indicates a tendency to an overactive gland, which the hypothalamic/pituitary portions of the system are compensating for. A free t4 and TSH in the 50th percentile of normal, in the presence of a free T3 in the 10th percentile of the normal range indicates the possibility of a relativel poor conversion of t4 to t3 in the periphery. In this case, even though all the more central parts of the thyroid axis are intact, there is some peripheral disturbance in conversion which may be accounting for your patients sluggishness, failure to respond to antidepressants, presumed side effects of the medication, etc.

If test results indicate hypothyroidism, I recommend testing for thyroid peroxidase antibodies to rule out Hashimoto’s thyroiditis. In addition, the patient should be tested for an adrenal axis abnormality since adrenal axis malfunctions often go hand-in-hand with hypothyroidism. For instance, increased cortisol is associated with a lower body temperature set point and lower levels of free T3, two of the indicators used in assessing thyroid function. (Bartalena, et al, J. Clinical Endocrinology and Metabolism, 70:293, 1990.)

Subclinical hypothyroidism (low to low-normal levels of free T3 or T4) is common in patients exhibiting depressive symptoms or other symptoms of hypothyroidism and requires treatment even if TSH levels are within the normal range. One study found that 56% of people with subclinical hypothyroidism suffered from depression compared to a rate of 20% in the average population. (Am J Psychiatry 150:3, March 1993.) Many of these patients go on to develop full-blown hypothyroidism.

If your patient has signs of subclinical hypothyroidism (thyroid signs and symptoms, normal TSH, low range free T3 or low range free T4, and perhaps basal body temperature more than a half-degree below normal on average), I recommend referring your patient to an endocrinologist to perform a thyroid releasing hormone (TRH) stimulation test to the pituitary and hypothalamic aspects of thyroid axis function.

One study found that 19% of patients who had subclinical hypothyroidism, diagnosed using a TRH stimulation test, had had an episode of major depression within the past year, compared to none of the subjects with a normal TRH stimulation test. (American Journal of Psychiatry 150:3, March, 1993 pp. 508-510). Through my own experience, I’ve found that nearly all of my patients who have a normal TSH, and low normal free T4 and free t3 but an abnormal result on the TRH stimulation test had clinically significant improvement in their sluggishness, weight, depressed moods and other signs and symptoms after being treated with synthetic thyroid hormone.

Once you have ascertained that your patient has hypothyroidism, and have assessed the possible causes, you must now decide the best course of treatment–and this is not always easy. Your patient can either be treated with T4 (levothyroxine) or T3 (triiodothyronine) or with a combination of both. There is good clinical evidence that using a combination of T3 and T4 can help alleviate symptoms of depression in patients with hypothyroidism who have had only a partial response to antidepressants (Journal of Clinical Psychiatry 53:1, January 1992, pp. 16-18).

If you elect to begin the standard treatment of levothyroxine, you should periodically take blood samples to monitor levels of free T4 and TSH; the TSH level should not drop below .05, due to the increased risk of osteoporosis and, of course, the possibility of inducing iatrogenic hyperthyroidism.

With time, you may note that the thyroid symptoms or the depression may recur, which means you’ll need to recheck the thyroid axis, and possibly raise the dosage of levothyroxine. In these situations, I advise you to monitor your patient’s body temperature (as discussed above on page TK) and check levels of TSH, free t4, and free T3 again. If the levels of t3 are low to low-normal, while TSH and free t4 are clearly normal, you should start supplementing with T3, or substitute t3 for the t4 preparation you are prescribing, since the conversion of t4 to t3 is suboptimal. Despite the fact that Cytomel is reported to have a long half-life, only requiring once daily dosing, I have found that trough levels of free t3 are often low within 12 hours of taking the Cytomel, even with b.i.d. dosing. For this reason, when finances allow, I use a form of T3 compounded in a slow release base by a compounding pharmacy (see appendix [X] on page TK). This is taken every twelve hours in 7.5 mcg increments, and dosage is determined by following the body temperatures as well as the peak (six hours after dose) and trough (12 hours after dose) free t3. As always, one must be sure that the TSH is not overly suppressed to avoid increased risk of osteoporosis. This approach seems to keep the blood levels of T3 more steady and frequently improves sleep, energy, other symptoms and response to the antidepressant.

Researchers have also found thyroid intervention to be helpful in managing attention deficit disorder associated with depression. This is not surprising given the importance of T3 in catecholamine signaling pathways.

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