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Hormones out of the reference range. If any of their hormones are out of range, then obviously I am going to treat those hormones, but if they are within range then often I'm going to take a wait-and-see approach. Rob reports that for those within the reference range, rather than using bio-identical hormones, he may work with adaptogenic herbs and supplements.
Tracking a single variable. If the patient has fatigue, I want to know that I have affected that fatigue with my antimicrobial approach. I don't want to wonder whether it was the tincture or the hormones that improved their fatigue. I want to know that I'm correct in my diagnosis. Does this patient have babesia or bartonella as the current dominant infection? The only way that I can be sure about that is by noting the patient's symptomatic response to just one treatment variable.
Optimizing Hormone Levels
Rob: What I learned with you and other Lyme-literate physicians around the country is that our primary goals are to support the immune, endocrine, and nervous systems. A good example is a patient that I just saw yesterday. He is 67 years old. His IGeneX Lyme test lit up like a Christmas tree with all the bands, an unequivocal positive test result. He also has a free testosterone of 35 and a total testosterone of 230. He meets the laboratory definition of androgen deficiency, and he marked nine out of ten positive responses on the ten-point questionnaire that I use from the St. Louis School of Medicine – a protocol that I use for objectifying andropause. In addition, he had adrenal insufficiency.
I found this gentleman to have severe babesia symptoms, which included heart palpitations, night sweats, chills, fevers, numbness, and tingling in his hands, as well as panic attacks, anxiety, brain fog, insomnia, air hunger, and migraine-like headaches with auras. I put him on the appropriate adrenal protocols (as many of these symptoms also overlap with those of adrenal insufficiency) and started him on a supplement of organic maca, a Peruvian herb that we use to help balance testosterone. He came back to see me this week, and he is 70% better with all of these symptoms. His headaches are nearly gone. Many of the babesia symptoms are nearly gone, but he still has anxiety, a little trouble sleeping, and brain fog, although his brain is much better. In my clinical experience with babesia, in particular, the anxiety response that men experience is much more pronounced than that of women, especially when testosterone is low. I put him on bio-identical testosterone this week, and on this protocol, he tapered down to a more normal anxiety level, comparable to that you would expect when testosterone is just starting to be replaced. I'll see him back in a month, and after that I'm going to start treating him for Lyme and babesia.
If you have been tracking the patient over time, I believe that you are not going to lose the clinical presenting features. I consider the addition of a hormone just one more factor whose effects I observe. This can be compared with how you would treat someone for babesiosis. I would put them on artemisinin and then see what changes with the babesia symptom pattern. In this case, we have put this patient on a testosterone adaptogenic herb and some adrenal support; the babesia symptoms are better, but the babesia is not gone. However, the patient is much more comfortable and as a result will be much more compliant in going through the treatment process. My experience is that the people for whom you can initially optimize hormones have fewer and less intense herx reactions when you treat them. I think that goes back to your poignant observation earlier, that inflammation is reduced when patients are on hormone replacement.
Clinically I worry less about confounding symptom patterns because I never see the neurologic exam appreciably improved by BHRT (and I do rely heavily on neurological evaluation with these patients). The neurological exam improves only with reducing the level of infectious pathogens and, in a subset of celiac patients, improvement with gluten-free diets. Also, I am inclined to agree with you about holding off on treating with BHRT in one regard and that is the gut. I will not treat with BHRT if the gallbladder or liver is tender on physical exam. Since most hormones are metabolized through the liver, compromised liver function is just a setup for failure. Generally speaking, these patients are the ones who will not tolerate BHRT.
Providing BHRT During Hormonal Transitions
Wayne: There are a few hormonal situations in which I am much more liberal with hormonal replacement or support. In particular, I want to track and support hormones when significant hormonal changes are occurring in the body: in puberty, during pregnancy or lactation, and in perimenopause, menopause, and andropause. We know that these neurotoxins compromise cellular function and make all cells less efficient. This can have an enormous impact on endocrine glands, in particular at times when they have to function at ultimate, peak performance.
Often people with Lyme are only mildly symptomatic due to their underlining inflammatory disorders, but when they go through one of these hormonal transitions, will have a significant aggravation of their symptoms. In patients who are unaware that they have Lyme, these symptoms are simply regarded as typical of menopause or puberty, assuming that there will be more mood disorder or more behavioral dysfunction or more problems during those times without any awareness of the presence of an underlying infection.
Non-responders. I will treat hormones more aggressively in my non-responding patient. If I'm not getting much traction from my antimicrobials, I will then fall back and treat hormones more aggressively.
Chronic pain patients. This is another group that I will treat with hormones more aggressively. I think they need the advantage of the anti-inflammatory effects of those hormones. And yes, if their hormones are out of range, then obviously I'm going to treat those hormones, but if they are within range then I'm going to take a wait-and-see approach.
Patterns of genetic vulnerability. As mentioned, we often run LabCorp HLA-DRB genetic test and when we see any of these patterns of potential vulnerability, we treat that patient more aggressively hormonally, and earlier in treatment.
Supporting the Adrenals and the Depleted System
Rob: When we see someone who is not having the expected response to BHRT it is usually due to one of three reasons: They may have an underlying infection due to Lyme, a coinfection, or a build-up of neurotoxins. Another potential pattern is that they did not recover because their adrenals were not addressed. That can be significant. Lastly, their detoxification systems may not be open, in particular the hepatic, renal/lymphatic, or integumentary system.
Minimizing suffering. My approach is to support the patient's depleted system as much as possible with the primary goal of alleviating suffering, the suffering that is present before me and in the future reducing herx reactions (die-off). The majority of my patients are people who get up and go to work even though they do not feel that they can. They do not have the desire to get out of bed, but they have to work, and most, frankly, cannot afford to stop, so I try to alleviate their suffering as quickly as possible.
The pre-treatment phase. My experience has been that if I put someone on antibiotics right away, or if I put them on any of the herbs right away, they're going to have very severe herx reactions. Clinically, they will suffer less if I support their immune and endocrine systems in advance. So when necessary, I spend a great deal of time initially doing basic ground-level support for the adrenals and the thyroid, at a minimum, while at the same time working on detoxification.
Restoring the adrenals as a priority. I might not necessarily put someone on a thyroid supplement until I am sure that the adrenals are corrected, because the thyroid cannot become fully functional unless the adrenals are supported adequately. I would agree that often it is premature to put someone on a thyroid supplement unless the adrenals have had a chance to recover. It can be a temptation to think, "Okay, we gave them herbs for the adrenals, and we gave them hormone replacement. Let's go right to the thyroid." But it can take six months or a year for the adrenals to come back into order. All of this is predicated on what the clinical and symptomatic picture looks like in the individual patient, as you so eloquently state. For instance, I will often use a botanical such as ashwaganda or a pure source adrenal supplement like neonatal bovine adrenal cortex, at the same time using an adaptogenic thyroid supplement. Then I reassess thyroid levels at regular intervals to see if the body has adequately recovered; people often do beautifully with concurrent Lyme treatment.
The Hypothalamus and Pituitary
Wayne: The hypothalamus sits just above the pituitary in the brain, the master gland that initiates much of the hormone activity in the body. The hypothalamus communicates with the pituitary and the pituitary then communicates with the thyroid, adrenals, pancreas, and sex hormones, striving for homeostasis. Given that neurotoxins disproportionally affect the brain, the hypothalamus is also disproportionally affected, and hypothalamic dysregulation affects all of the hormones downstream.
Hypothalamic regulation also affects a number of basic physiological functions, including sleep, temperature tolerance, weight gain or loss along with appetite, thirst, hydration, fluid balance, and pain. Just as the inflammatory processes of babesia, bartonella, and Lyme affect the brain, they also affect the regulatory systems of the hypothalamus. In some cases I intervene to try to regulate these effects on the hypothalamus, earlier rather than later if I think that patient needs support in that system. I focus on the downstream effects of hypothalamic dysregulation and thus support the thyroid, adrenals, and sex hormones when appropriate.
Rob: It's a well-known fact that the adrenals are associated with increased vulnerability in acute and especially chronic infectious states. Every cell in the body has a receptor for cortisol and without it we cannot live. Cortisol is also indirectly involved with sex steroid synthesis. High cortisol levels often relate to frequent colds, infections, and difficulty losing weight, particularly adipose tissue. In general, we see our patients come in with phase I, II, or III adrenal insufficiency; most of them are in phase II or phase III.
DHEA and cortisol. When patients have lower DHEA levels, they have problems with phase II detoxification in the liver, which affects proper flow from the gallbladder. If left unchecked long enough, this can severely hamper the immune system by causing the liver to develop congestion and the body to retain toxins. For instance there is a four- to five-fold decrease in breast cancer recurrence when DHEA levels are in the upper third of normal, with the correlary that low DHEA is associated with higher rates of breast cancer and its recurrence. We work on DHEA and cortisol levels, using various adaptogens and direct bio-identical hormone replacement. The supplements most often used in my practice are selenium, zinc, omega 3 (pure source) fish oil, B complex, vitamin C and D3, and DHEA with or without cortisol supplementation with Cortef or an extract from a pure animal source. Supplementation depends on how much reserve or depletion is present.
Pregnenolone and progesterone. It is also important to address pregnenolone and progesterone as they are also made in the adrenals through a complex and energy-consuming process. Supplementing these hormones exogenously saves the body from the taxing metabolism of cholesterol, and the adrenals do not have to work so hard to maintain adequate levels. This is important clinically in cases of bartonelosis, frequently associated with severe PMS in female patients. In these cases, one can try some pregnenolone, or bio-identical low-dose progesterone, at the same time addressing any magnesium deficiency. All sex hormones can be made from pregnenolone. In addition, pregnenolone makes cortisol, and in a chronic stress state (as we see with Lyme) nearly all the pregnenolone is going to cortisol instead of DHEA and the sex hormones. It makes sense to replace pregnenolone and DHEA in these chronic stress states.
Psychoneuroimmunology. When Lyme patients present, often they are in an altered psychological state, usually full of fear. Imagine the state of medicine today if cancer or hepatitis patients were tested with lab work that had up to a 92% false negative test result. How would people respond psychologically? Fear can become a chronic state that either drives cortisol upward or depletes it. Many of these patients are in phase II or phase III by the time they present. One of the most important things we can do from the very start is to give our patients hope, which will support the hypothalamic/pituitary axis, establishing better hormone levels and increasing endorphin production. It is well established that opioid compounds play a major role in immune modulation by enhancing the cell-mediated pathways, in contrast to the dysregulating effects of the fear response. As Wayne points out, the adrenals provide our primary anti-inflammatory, and they take a big hit in these illnesses both physically and psychologically.
Rob: In the Lyme patient, thyroid is such an important issue to address because inflammatory cytokines often suppress thyroid function. We usually see this pattern begin with the adrenals. As you may recall, adrenal function must be intact in order to support a well-functioning thyroid, among other hormones. This balance is further disrupted if an autoimmune process such as Hashimoto's is present. However, Lyme is not the only culprit in terms of autoimmunity. Given that 70% of the immune system is in the digestive system, gastroenteritis, gut dysbiosis, or heavy metal toxicity can drive the autoimmune process as well. There are many effective thyroid protocols including Wilson's, the Wiley protocol, thyroid hormone optimization (with or without total T3/reverse T3 ratio), using any or all of the combinations of animal thyroid (Armour), Synthroid, Cytomel, and/or Iodorol in conjunction with various nutrients, such as those used in the adrenal support protocol described earlier.
Thyroid optimization is a key ingredient in BHRT. For instance, T3 increases NK cell and immune modulation activity. Moreover, T3 and T4 repair DNA which acts as a free radical balancer. In clinical practice, I have observed Hashimoto's in approximately 25%-30% of my Lyme patients. When a low WBC (white blood cell count) is observed and no other apparent cause is found, the patient usually has Lyme. This is found in approximately 20% of my patients. Gilbert's syndrome, associated with elevated levels of bilirubin, correlates with the presence of Lyme in my patients approximately 92% of the time. When all three of these conditions are present in tandem (a low WBC count, Hashimoto's, and Gilbert's) in my patient population, that has been 100% predictive of the presence of Lyme disease. I am currently completing a retrospective study tracking this phenomenon (the Gitlin Triad). In my patient population, this triad is present in 5%-10% of cases. It provides a highly useful set of markers because it has a high predictive correlation and it saves patients health care dollars.
Wayne: This is fascinating! I know that my Lyme patients consistently have low WBCs , and many have Hashimoto's, but I had not associated those with Gilbert's syndrome. You are onto something here. What I like about your observation is putting together seemingly unrelated pieces of clinical information and creating a fascinating hypothesis. This is what we all need to be doing – tracking the patterns in the complex presentation of chronic inflammatory illness within the Lyme disease spectrum and seeing the connections. Great job.
Wayne Anderson, ND
Dr. Anderson holds a degree in naturopathic medicine from National College of Naturopathic Medicine in Portland, Oregon, and additional broad-based training in health and medicine. For the first two decades of his practice, Dr. Anderson worked in a busy community-based family medical center in a region in which Lyme was endemic. As he became aware of the prevalence of chronic Lyme disease and related conditions, he realized the important part they can play in chronic illness. In 2002, Dr. Anderson left family practice to work with Eric Gordon, MD, and focus on the treatment of Lyme disorders using leading-edge therapies from both conventional and integrative medicine.
Gordon Medical Associates
3471 Regional Parkway, Santa Rosa, California 95403
Office: 707-575-5180; Fax: 707-575-5509
Robert Gitlin, DO
Dr. Gitlin graduated from the Kirksville College of Osteopathic Medicine in 1992 after completing an undergraduate teaching fellowship in Osteopathic Manipulative Medicine. He then became board certified with the AOBFP and the AAFP on completing family medicine studies with the osteopathic and allopathic (AOA and AMA) certifying program at the Shasta-Cascade Family Medicine Program at Mercy Medical Center in Redding, CA. He is a Lyme-literate physician in Northern California practicing integrative family medicine and osteopathic manipulative medicine with his wife, Karla, who is also an osteopathic physician in rural Redwood Valley, California.
Redwood Valley Medical Clinic
8501 West Road, Redwood Valley, California 95470
Video on Genetic Testing (HLA-DRB)
A workshop video is available on genotype evaluation, presented by Wayne Anderson, ND, from the ILADS International Conference held in Boston, October 2012. To purchase a copy, go to ILADS.org, click on "Shop" then "Conference Videos. Click on the Boston Conference; Dr. Anderson's entry is the first on that page. The video is available for $15 and recommended to both physicians and patients.
If your patients have the desire to get additional testing beyond what is covered by their insurance, you can assess their metabolism with send-out test kits through Health Diagnostics Research, an institute that provides a Methylation Panel (email@example.com). Further information on genetic testing can be found in Genetic Bypass, a book by Amy Yasko and on her website, www.DrAmyYasko.com, which contains a wealth of information at no cost.
Nancy Faass, MSW, MPH, is a writer and editor in San Francisco who has worked on more than 45 books for publishers that include Elsevier, Harper, McGraw-Hill, Mosby, and others. Director of the Writers' Group, she also provides articles, white papers, and writing for the Web. For more information, contact info@HealthWritersGroup.com.