Many patients – particularly those who are newly diagnosed – wonder what the treatment options are. The following is a summary based on recent scientific articles.
The most frequently used initial treatment for the newly diagnosed is High Pulse IV Steroid Treatment with Solu-Medrol (methylprednisolone sodium succinate). Patients are generally given between 3 and 7 days of IV treatment. Treatment usually consists of receiving two infusions per day, for a total of 1000 mg (1 gram) of Solu-Medrol each day. Thereafter, patients are given oral prednisone and taper down the dosage over time. Most commonly, patients start with 60 mg per day at the conclusion of the IV treatment, and they taper the dosage slowly down over many months. In some patients, it will take up to a year to completely wean off steroids. Other patients, in whom symptoms re-emerge, require a maintenance dose of between 2 and 10 mg per day of prednisone indefinitely. More recently, physicians have found success in using so-called steroid-sparing agents as a form of ongoing maintenance for HE/SREAT. There are a number of different medications used for ongoing treatment. Research indicates that the most commonly used alternatives for maintenance are Imuran, Cellcept, or Methotrexate. A future post will focus on and discuss these maintenance therapies.
For those who do not respond sufficiently well to steroid therapy, there is the option of Intravenous Immunoglobulin treatment (IVIG). In this treatment protocol, the patient’s own antibodies are replaced with an infusion of antibodies from donors. Treatment is usually given as an outpatient, although the first session is often done inpatient to monitor for side effects. Typically, a patient will begin by receiving twice weekly infusions (intraveonusly), with each infusion taking 3 to 4 hours. Over time, treatment will go from the initial twice weekly treatments for the first month, to treatments once a week each month, and then ultimately to infusions given once each month. The goal is for the patient to, over time, go as long as possible between infusions. It should be noted that many insurance companies balk at this treatment because it is quite expensive. But research shows (see Case Studies link above) that IVIG can be a very effective way to treat patients who do not respond sufficiently well to steroid treatment.
The other treatment that has been found effective for many patients is Plasmapheresis, sometimes called Plasma Exchange or Plasma Transfer. In Plasmapheresis, a patient’s blood is filtered through a machine that separates the plasma from actual blood cells. The patient’s plasma may then be replaced with saline, albumin, or donor plasma. The reconstituted solution is then returned to the patient.
These are the most commonly used treatment options as of the date of this posting (October 2012). Future posts will discuss some of the maintenance therapies currently being used with good results.
How much of HE is related to thyroid dysfunction? Will treating a patient with “normal” thyroid hormone levels help with the HE symptoms? How much of all this is related? We really don’t know.
This post addresses the link between Levothyroxine, used to treat hypothyroidism, and its benefit on HE.
Mary Shomon, well known thyroid patient advocate, wrote an article “Do You Need Preventative Thyroid Treatment: Treating Antibodies When TSH is Normal“. A lot of us HE patients fall into the category of having high anti-TPO antibodies but “normal” TSH, T3 and T4 thyroid levels. A lot of us later develop hypothyroid symptoms, then it takes even longer to be diagnosed with hypothyroidism and finally receive treatment.
Recent studies show, preventative treatment could slow or even stop the development of hypothyroidism, and reduce the antibodies. However, at this point, most endocrinologists will dismiss you if you talk about preventative treatment. I have been dismissed many times by many endos, and now have developed almost all of the classic symptoms of hypothyroidism. This possibly could have been prevented.
She notes a recent study (that I currently can’t find a link to):
En-Ting Chang, Du-An Wu, Dee Pei, Shi-Wen Kuo, Ming-Chen Hsieh. [P2-552] Influence of L-Thyroxine Administration in Patients with Euthyroid Hashimoto’s Thyroiditis. Endocrine Society Endo 2005 Abstracts
In this study on HT patients with normal range TSH, but high antibodies, half were given levothyroxine and half were not treated. “Those receiving levothyroxine had substantially decreased auto-antibody levels; levels actually increased in some among the untreated group. TSH levels also decreased in the treated group, averaging 0.5 vs 2.5 in the untreated group. The researchers concluded that early prophylactic (preventative) levothyroxine treatment might be useful to help slow down the progression of the autoimmunity of Hashimoto’s Thyroiditis.”
Euthyroidism (patients having normal TSH levels):
In the study “One-Year Prophylactic Treatment of Euthyroid Hashimoto’s Thyroiditis Patients with Levothyroxine: Is There a Benefit?“, euthyroid HT patients were given levothyroxine as a prophylactic to see if it would benefit the autoimmune process. Half of the patients were treated with levothyroxine, the other half were not treated. The study states, “After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05). In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT.”
The study also states, “Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease.”
The purpose of the 2008 study, “Long-Term Follow-Up of Antithyroid Peroxidase Antibodies in Patients with Chronic Autoimmune Thyroiditis (Hashimoto’s Thyroiditis) Treated with Levothyroxine” was to see if patients treated with levothyroxine for HT reached the point where their TPO-Ab levels became within normal range (negative).
In the study, 92% of patients had a decrease in their TPO-Ab levels. “The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 ± 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%.”
The conclusion of the study was “Serum TPO-Ab levels decline in most patients with Hashimoto’s thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.”
The aim of the 2008 study “Effects of Prophylactic Thyroid Hormone Replacement in Euthyroid Hashimoto’s Thyroiditis” was “to evaluate the effects of prophylactic L-thyroxine treatment on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis.” The study states, “After 15 months of L-thyroxine treatment, there was a significant increase in free T4 and a significant decrease in TSH and anti-thyroglobulin antibody anti-thyroid peroxidase antibody levels.” “In conclusion, prophylactic thyroid hormone therapy can be used in patients with Hashimoto’s thyroiditis even if they are euthyroid.”
The study goes on to conclude, “Early treatment of Hashimoto’s Thyroiditis with L-thyroxine may slow down not only the disease process itself but through its immune modulating events it may also affect the course of other autoimmune diseases which accompany.”
This would relate to HE and the HE patient would benefit from the lowering of the antibodies as well, with less side effects from levothyroxine than steroids.
Subclinical Hypothyroidism (borderline levels):
A 2008 study, “Diagnostic strategies for subclinical hypothyroidism” notes “45 of the 61 subclinical hypothyroid patients had elevated anti-TPO levels (73%). This is an important finding suggesting an autoimmune etiology for subclinical thyroid dysfunction with a higher risk of developing overt hypothyroidism.” This study states that the antibodies should be considered in order to treat subclinical hypothyroidism.
A 2006 study “Subclinical Hypothyroidism“, notes “the titer of anti-thyroid peroxidase (TPO) antibodies is proportional to the degree of lymphocytic infiltration and inflammation within the gland. Thus, hypothyroidism in patients with high titers of anti-TPO antibodies is more likely to progress from subclinical to overt disease.” “Without treatment, progression to overt hypothyroidism is likely”. He also states, “Endocrinologists also disagree about the normal range for serum TSH levels. Although many laboratories have traditionally used 4 to 6 mIU/L as the upper limit of normal, the data used to calculate reference ranges have frequently included measurements in patients who had positive results on anti-TPO antibody tests or other evidence of early thyroid dysfunction. Careful analysis suggests that the true upper limit of normal for serum TSH concentration is closer to 2.5 mIU/L.”
Spontaneous Remission or Levothyroxine?
One patient in the case study “An 85-year-old Case with Hashimoto’s Encephalopathy, Showing Spontaneous Complete Remission” was taking thyroxine treatment at the time of his remission.
The case study, “Long-Term Treatment of Hashimoto’s Encephalopathy” states “35% of cases had subclinical hypothyroidism; 22% were euthyroid not on levothyroxine; 20% had overt hypothyroidism; and 8% were euthyroid on levothyroxine (as were our two cases); 7% had hyperthyroidism (5% overt, 2% subclinical); 6% had unknown thyroid status; and 1% did not have thyroid disease. A goiter was present in 62% of cases (see Table 2). Of the above cases with subclinical or overt hypothyroidism, 17% improved following treatment with levothyroxine alone, while 40% improved following combined treatment with levothyroxine and steroids.2 It is somewhat surprising that some cases improved with levothyroxine treatment alone. However, it may be that those cases were destined to improve spontaneously.”
The study summarized the treatment efficacy of reviewed literature, reporting “improvement in 98% of cases treated with steroids, 92% treated with steroids and levothyroxine, and 67% treated with levothyroxine, while 9% of cases did not improve with any of the above combinations.”
The study notes that it is interesting that some cases responded with levothyroxine treatment alone, and they hypothesize that these patients may have been destined to improve spontaneously. Perhaps the levothyroxine reduced the antibody levels enough to improve the HE symptoms. After all, we still don’t know the exact pathology of the link between the antibodies and the encephalopathy. But we do know there is a link.
My ending thoughts on this post:
Considering most HE patients eventually develop hypothyroidism, those with hypothyroid symptoms (regardless of the “normal” level of their TSH) should be treated with levothyroxine and monitored regularly for further thyroid problems. The side effects of levothyroxine are minimal and it has been shown to improve HE symptoms in some case studies, even leading to remission.
Rather than just steroids, perhaps a combination of steroids and levothyroxine should be considered as a primary treatment for HE.
I keep hearing debates about what actually causes HE. Thinking about it from another angle, why does the Prednisone work to suppress HE?
**After reading this post over, I realized this post is truly a stream of consciousness. I’m not sure it will make sense to anyone but me. So, sorry if this makes no sense.
Prednisone works from 2 possible directions: it suppresses the production of antibodies, and it reduces inflammation.
There is a lot of debate about what the antibodies are doing to cause the neurological problems. Are the antibodies themselves causing the HE or is the body’s response to the existing antibodies causing the HE?
In my case, I showed no signs of inflammation even in the most acute stages of my illness (in blood and scans). I find this to be strange. Swelling is the body’s natural response to damage after all. However, most people diagnosed with HE do not show signs of inflammation. Maybe the body doesn’t realize it is being damaged in a way that it would normally respond with inflammation.
So if there is no sign of an inflammatory process in most people, then is it really that reasonable to conclude that the neurological symptoms are a result of the body’s inflammatory response to the existence of the antibodies?
Wouldn’t it seem more likely that the antibodies themselves are actually attacking the brain, causing the neurological problems?
In the study, Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes, states “In immunofluorescence assays on monkey brain cerebellum sections, both HE patients’ sera and anti-TPO monoclonal antibodies (mAb) were able to bind cerebellar cells expressing glial fibrillary acid protein. Normal human astrocytes from primary cultures also reacted with anti-TPO mAb. Specific astrocyte binding of anti-TPO aAb suggests a role of these aAb in the HE pathogenesis.”
The glial fibrillary acid protein (GFAP) has a role in the functioning of the blood brain barrier. Disease related to GFAP is thought to interfere in astrocyte interactions with other cells as well as a possible inability to maintain the blood brain barrier.
So if the anti-TPO antibodies are binding to the cerebellar cells expressing GFAP, those cells might be interacting unusually with other cells and compromising the BBB.
HT -> results in overproduction of anti-thyroid antibodies -> intrathecal synthesis of autoantibodies into CSF -> anti-TPO antibodies bind to cerebellar cells -> possibly causing neurological symptoms
It appears that the antibodies are possibly directly responsible for neurological symptoms of HE. If true, this would serve to confirm that HE is a specific disease.
The question is what is allowing the antibodies through the BBB into the CSF so they can wreak havoc on our brains? In recent research it seems that although there is high prevalence of anti-thyroid antibodies in the serum of the normal population, those antibodies do not normally appear in the CSF of the normal population.
It appears that the process could be cyclic, that once the anti-TPO antibodies bind to the cells expressing GFAP it compromises the BBB. So the more antibodies that are binding would further compromise the BBB, possibly allowing more antibodies through the BBB. This would indicate that there should be a link between the level of the antibodies in the CSF and the severity of the symptoms.
If the antibodies are causing the problems, the Prednisone (or other steroids) would be working to suppress the production of these antibodies. This would be the primary benefit of the treatment.
Ending thoughts on this post:
This post was really a stream of consciousness. I made a lot of assumptions in order to make my conclusions. To me, this possible pathogenesis makes sense (and is based on a small number of recent studies). For someone with HE, the body’s autoimmune response creates an abundance of anti-thyroid antibodies (HT). These antibodies migrate into the CSF where they get to the brain and bind to the cells that regulate the BBB. Once these cells are compromised, they interfere with other cells, likely causing unusual neurological symptoms.
At this point, none of that is proven to be true. However, considering the efficacy of steroids in reducing the antibodies and thereby reducing symptoms, we should continue to search for a link between antibody levels in the CSF and the severity of the symptoms. This would be helpful in monitoring the treatment (for example when it would be safe to taper down the steroids). We should continue to develop safer treatments for reducing antibody levels in the CSF.