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TITLE: ELEVATING METABOLISM WITH TRIIODO-L-THYRONINE CAN SUCCESSFULLY TREAT DIFFICULT OTOLARYNGIC DISEASES AUTHOR: Donald T. Levine, MD, FACS 75 North Broadway Nyack, New York 10960 AFFILIATIONS: ENT Section Chief/Senior Attending at Nyack Hospital, Nyack, New York Assistant Attending, Manhattan Eye Ear & Throat Hospital, New York, New York 1 ABSTRACT OBJECTIVE: This study demonstrates the effectiveness of metabolic elevation as a tool to treat a wide variety of ENT disorders that would have otherwise been incompletely resolved with standard medical therapies. STUDY DESIGN: A retrospective review of over 500 private practice patients, selecting 6 representative cases with persistent, difficult, and varied ENT disorders that were significantly helped or cured utilizing this technique of Triiodo-Lthyronine (T3) metabolic elevation. METHODS: Institutional Review Board approval for this study was not required. Patients from my private practice with difficult ENT problems and hypothyroid symptoms were considered for T3 metabolic elevation. A detailed baseline thyroid profile is then ordered and gradual metabolic elevation utilizing T3 begins. Patients are reassessed monthly checking for improvements, side effects, and the attainment of blood test goals. 2 RESULTS: As the blood testing goals are reached, the patient’s medical problems are significantly diminished or cured. CONCLUSION: This specific format of metabolic elevation where the emphasis is on T3 evaluation and T3 treatment is very effective in treating difficult otolaryngic diseases. INTRODUCTION Low T3 hypothyroidism can cause or aggravate a number of otolaryngic disorders including otoneurologic diseases (meniere’s syndrome, vertigo); neurologic problems (neuralgias, headaches, migraine), immune problems (allergies especially to multiple foods or that are difficult to control in spite of standard therapies; and recurrent infections - stomatitis, sinusitis, bronchitis); and 3 dermatologic problems (hives, urticaria, eczema, dry skin). When these problems present with typical hypothyroid complaints (excessive tiredness, excessive coldness, weight gain, hair loss, brittle nails) or there are also problems of autoimmune disease, chronic fatigue/fibromyalgia, constipation or depression, low T3 hypothyroidism is likely contributing to or causing the disease.1 These patients do not adequately convert tetraiodo-L-thyronine (T4) into T3 – the main thyroid hormone, which is four times stronger than T4 in elevating metabolism. Some of these patients are already on T4; however, they too, continue in a lowered metabolic state because of poor peripheral conversion to T3 and the elevation of reverse triiodo-L-thyronine (RT3), a biologically inactive isomer which dampens metabolism further. Therefore, traditional analysis which looks only at the pituitary – thyroid axis, and which analyzes only the thyroid stimulating hormone (TSH), T4, and T3 uptake is insufficient. Emphasis should be placed more on T3 analysis; and treatment should begin with T3 primarily, since it cannot be converted into RT3. Testing must measure free T3 (FT3), total T3 (TT3), RT3 as well as free T4 (FT4), and TSH levels. The laboratory goals corresponding to maximum wellness in order of importance are: TT3/RT3 ratio between 10-15, FT3 in the upper 20% of the normal range (3.7-4.2), and FT4 in the low end or slightly below the low end of the range (0.7-0.8).2 TSH is least important since it wasn’t adequately setting the metabolism anyway. 4 METHOD When a patient has two or more of the above problems, metabolic elevation as described is often helpful. Once the above thyroid profile is obtained, the benefits and side effects are discussed. Cytomel, which is T3 is the preferred treatment choice because it is the most potent metabolic elevator (T3 is 4 times stronger than T4); it cannot be metabolized to RT3, which would dampen metabolism; and the above laboratory goals are most likely to be obtained using Cytomel. Other treatment choices include Armour Thyroid, which is a combination of T4 and T3. A 15mg.Tab of Armour Thyroid contains 9mcg. of T4 and 2.25mcg. of T3. Synthroid or Levoxyl (T4) would be the least desirable choices since they would produce RT3 elevations when metabolized. These other metabolic elevators may be needed later to maintain the FT4 in the low normal range. An autoimmune Thyroiditis (AIT) work up is ordered initially as well and includes: Thyroglobulin antibody (TG-ab), Thyroid Peroxidase antibody (TPO), and Thyrotropin Binding Inhibitory Globulin antibody (TBII/TRAb). AIT is very common and contributes to thyroid dysfunction including hyperthyroidism, hypothyroidism, and to nodule formation. To start, Cytomel 5mcg. is given twice a day (because of its six hour half-life) and 5 on an empty stomach – preferably one hour before breakfast and two hours after lunch. The second dosage should not be taken before bed or sleep may be disturbed. Some sensitive patients may need to start on a half of a 5mcg Cytomel twice a day and eliminate caffeine from their diets. Re-evaluating the thyroid profile in 3-4 weeks (to allow for equilibration) and 6hrs. after the morning dose is most important and will provide an average value of FT3 – a better reflection of the patient’s metabolic state. Heart palpitations, muscle cramping, and heat intolerance are the main side effects that must be considered before treatment and with each treatment escalation. Heart palpitations can be managed by reducing the dosages of Cytomel, eliminating caffeine and other stimulants from the diet, and elevating the dosages more gradually allowing extra time for equilibration. Supplementing with O.T.C potassium, slow- magnesium, or quinine can minimize muscle cramping. Shifting more dosage to the morning and less in the afternoon, if the muscle cramping occurs mostly at night, may also minimize this side effect. Heat intolerance may require reducing the dosage or considering other causes such as low estrogen in menopausal women. Adrenal dysfunction may also need investigation and treatment for maximum results. Less common side effects are loss of menstruation, increase in fertility, and headaches (switch to other generic may be necessary). Escalations of Cytomel advance by a half of a pill (2.5mcg.) morning first afternoon next. Patients will need a pill cutter. As long as no side 6 effects occur, a new thyroid profile is ordered about a month later and always 6hrs. after the morning dose. The patient then returns to the office one week after the blood testing at which time symptom relief, side effects, and blood test results are reviewed. Side effects may prevent reaching the therapeutic and laboratory goals. Side effects may also diminish or increase over time on the same dosage. That is why gradual elevation with monitoring is important. The following cases will demonstrate the effects of T3 elevation in a variety of difficult ENT disorders. CASE PRESENTATIONS J.K. is a 45-year-old female treated over the last 10 years. Originally, she presented with facial swelling and a history of inhalant allergies (trees, molds, dust), chemical sensitivities to fragrances and soaps, previous allergy immunotherapy for four years, courses of prednisone, food sensitivities (was on a yeast/wheat free diet with some reduction of her urticaria), constipation and bloating, and 2 previous septoplasties. She also was diagnosed with Hashimoto’s Thyroiditis with hypothyroidism and was on Synthroid 112mcg. At that time I treated her with various antihistamines and subsequently re-tested for inhalant and cyclic food 7 allergies. Severe pollen sensitivities and severe food sensitivities to soybean, chocolate, and tomato were obtained. Wheat and yeast testing were negative! Upon eliminating these foods and treatments with antihistamines, steroid sprays, and steroid cream she improved. She declined further immunotherapy. She then returned to my office 4 years later complaining of dizziness, decreased hearing, stuttering, aural fullness in her right ear, right forehead pain, and mental confusion. She was diagnosed with a learning disability; was seeing a speech and language pathologist; and had 3 separate head injuries as a child. The first was nasal trauma causing her deviated nasal septum. The second trauma to her right forehead resulted from her running into the edge of a door. The third occurred to her right eye and orbit from a baseball (no fracture). Audiometry revealed a mild high frequency hearing loss in her right ear at 8K Hz. and minimal Eustachian tube dysfunction in her right ear. CT scans, MRI’s, and neurologic work up were normal. She again was treated with antihistamines, steroid nasal sprays, and decongestants with some lessening of her symptoms. She declined immunotherapy. She returned to my office 2 years later complaining of dizziness of various intensities even when stationary. She denied vertigo. She had been diagnosed with auditory processing problems; still had mental confusion; a very poor memory, and took very detailed notes during our consultation. She worked as a computer consultant! Repeat MRI was normal and repeat audiogram revealed 8 only a mild hearing loss at 8K Hz. Discrimination scores were 100% bilaterally and impedance testing revealed no middle ear congestion. She then returned to my office one year ago because of allergic congestion despite antihistamines and decongestants. Though she was on Synthroid 100 mcg, she was still cold, had dry skin, and stated she had some unexplained weight gain. I ordered a thyroid profile, which revealed a TT3/RT3 - 3.32, FT3 – 2.9, TT3 – 80, TSH - .912, FT4 – 1.47 and confirmed her AIT. I diagnosed her with low T3 hypothyroidism. Over the next year I elevated her free and total T3 and reduced her reverse T3 by decreasing her Synthroid dosage and by giving her increasing amounts of Cytomel. Her symptoms improved dramatically. Her mental confusion abated by “75%!” Her energy level remains high. She is no longer dizzy. Her allergies have improved by “80%” with improved tolerance to inhalants and foods. She has no further neuralgias, and is no longer cold. Her latest thyroid profile demonstrated TT3/RT3 ratio – 12.3, FT3 – 3.2, FT4 – 0.75, TSH – 0.49. She’s currently on Synthroid 50mcg AM and Cytomel 10mcg. BID. I will monitor her every four months for now. We may recheck her food allergy end points and adrenal hormone status in the future. Her quality-of-life is significantly improved. J. M. is a 48-year-old female who I saw for the first time 6 years ago. At that time she complained of hives (worse pre-menstrual, with weather changes, and stress), 9 frequent headaches, and nasal congestion. She was cold sensitive, had difficulty losing weight, some tiredness, and some hair loss. Zyrtec helped to treat the hives but not completely. Inhalant testing revealed only mild sensitivities to dust, cats (she had 2), short ragweed, and delayed reaction to candida (the other 19 molds were negative). Skin endpoint titration food allergy testing demonstrated mild sensitivities to chicken, egg, rice, wheat and a pronounced sensitivity to strawberry. She subsequently avoided these foods and treated outbreaks with Fexofenedine 180 or Cetirizine. Thyroid testing at that time revealed FT3-294, TSH- 2.37, and FT40.99. Over the next 6 years I have transitioned her from Synthroid to Armour Thyroid and finally to Cytomel. She is now on Fexofenedine 180, Cytomel 17.5mcg. BID. Her current thyroid profile reveals TT3/RT3 ratio – 8.88, FT3 – 336, FT4 – 0.8, TSH-0.43. She has rare hives now, no nasal congestion, no headaches or hair loss. She states her energy level is excellent but has some coldness still. She has no side effects. I plan to try to get her TT3/RT3 ratio between 10 and 15 and the FT3 into the upper 20% of the normal range. She will need additional Cytomel, some T4 if her FT4 drops below 0.7, adrenal work-up, and further monitoring. D. D. is a 48-year-old woman first seen 3 years ago. She was referred for a lip biopsy because of a persistent lower lip non-healing ulcer. For fifteen years she 10 10 had suffered from lip, tongue, and cheek sores which would appear, stay for a very long time, and heal while new ones would appear in previously healed spots and in new areas. She had been to many physicians, oral surgeons, and chiropractors and was on many supplements. She had a previous biopsy, which diagnosed these lesions as pemphigoid and had been on topical and systemic steroids – all of which helped somewhat. She also had low body temperature, low energy, and some hair loss. Instead of biopsing this particular lesion (which I doubted would have made any difference) I ordered a thyroid profile and upon its review decided to raise her metabolism with Armour Thyroid. This did help to reduce the severity and the frequency of the lesions, but they weren’t eliminated and we hadn’t reached her lab goals. On Cytomel 7.5mcg BID; her lab values wereTT3/RT3-9.5, FT3-4.2, FT40.67, TSH-.415, which was closer to the ideal but still not perfect. She now had rare lesions of short duration. On Cytomel 7.5mcg. BID plus Armour Thyroid 15mcg. BID, she has no lesions and no side effects. Her blood values reflecting this are TT3/RT3 – 11.43, FT3 – 4.5, TSH - .141, FT4 - .65, TT3 – 144, RT3 .126. We will follow up in two months to check for symptoms, side effects, and her new blood values. W. N. is a 74-year-old male who came to me because of a right head pain centered in the right orbit and radiating posteriorly made worse by straining or bending. No 11 11 previous treatments with antibiotics or pain medications helped. CT scans of the sinuses and brain were negative. He had a history of cluster headaches 40 years ago and tried these medications again without success. He was on Synthroid 125mcg. a day for hypothyroidism but was still excessively cold. He denied any tiredness. His initial thyroid profile demonstrated TT3/RT3-6.25, FT3-299, FT41.7, TSH-0.31, and elevated Thyroid peroxidase and thyroglobulin antibodies. I continued his Synthroid dose and started him on Cytomel 5mcg BID. He developed nervousness, heart palpitations, headaches, and muscle spasms 2 days later. I halved the dose of Synthroid and Cytomel and then increased his Cytomel back up to 5 mcg BID once his side effects stopped. With a gradual transition to Synthroid 75mcg AM, Cytomel 10mcg AM/7.5mcg PM and Synthroid 75mcg.AM his blood work is as follows: TT3/RT3-9.67, FT3-351, FT4-1.0, TSH-0.17. He states that his head neuralgia (and even his sciatica) is “90% improved”; he is no longer cold, has great energy (which has been noticed by his family and friends); he’s back to gardening and his constipation is gone. He is being tested for allergies and uses Azelastin and Mometasone for intermittent congestion and will continued to be followed and treated metabolically and for allergies. S. B. is 72-year-old female who has been treated in my office over the last four years for recurrent and chronic sinusitis. She has been on many antibiotics, 12 12 sometimes for long durations and courses of prednisone especially when her infections were complicated by bronchitis. She’s had sinus CT scans which demonstrated only clearing of acute congestion and slight mucosal thickening. Other medications have included Montelukast, Azelastin, Advair Diskus 250/50, and guaifenesin. She’s been tested for inhalants (positives only for ragweed, aspergillus and Johnson grass smut mold in delayed reactions only). Nasal cultures showed different pathogens and were sometimes negative. She has a history of Raynauds as part of CREST Syndrome, hypothyroidism with AIT, fibromyalgia, GERD, and hypertension. Medications included norvasc, Atenolol, Pepcid, and Ecotrin. Low T3 hypothyroidism was suspected. Her thyroid profile three years ago on 112mcg. levothyroxine demonstrated TT3/RT3-5.2, FT3 – 267, FT4 – 1.4, TSH-1.99. Over the next 18 months I transitioned her to Synthroid 50mcg. and Cytomel 10mcg. BID. On this dosage her thyroid profile demonstrates the following: TT3/RT3-12, FT3 – 370, FT4-.8, TSH-0.53, TT3-156, and RT3-13. She has not had any further infections now for 2 years, has more energy, less coldness, less allergy, less Raynauds, and less dry skin. She has had no side effects and rarely needs her allergy and asthma medications. D. I. is a 57-year-old female with complaints of severe cervical neuralgia (despite multiple negative workups and therapeutic modalities), headaches, seasonal and 13 13 perennial allergies, and recurrent eustachian tube dysfunction despite treatment with Loratadine-D24, Mometasone spray, and analgesics with only some transient help. Symptoms of excessive tiredness and excessive coldness were elicited, so a thyroid profile was obtained which revealed TT3/RT3 - 7.88, FT3 – 299, FT4 – 1.2, TSH – 3.93, TT3 – 126. She is now on Cytomel 10mcg. AM, 7.5mcg. PM, Synthroid 25mcg. AM. She has minimal neuralgia, minimal allergies, and is no longer tired or cold. Her latest T – profile is TT3/RT3 – 11.93, FT3 – 381, FT4 – 0.9, TSH – 0.59, TT3 – 179. She is extremely happy and working full time again teaching singing and dance lessons. DISCUSSION Low T3 hypothyroidism is the primary cause for lowered metabolism. T3 is the major elevator of metabolism and is 4 times more potent than T4. It acts by binding to the nuclear membrane, DNA, mitochondria, and endoplasmic reticulum inside all cells.3 T3 is also stored as it is bound to thyroglobulin in the blood. TT3 is a measure of the bound T3 plus the FT3. Intracellular T3 is in equilibrium with extra cellular T3 both free and bound forms. T4, which is stored in the thyroid gland follicle and bound to thyroglobulin, can be considered a pre-hormone. It must be converted to T3 in order to significantly elevate metabolism. This occurs 14 14 peripherally in all tissues of the body. The 5’deiodinase enzyme cleaves off one of the iodines on the 4-iodinated thyronine molecule to activate it. In many individuals whether it be from stress, aging, illness, or cortisol, there is insufficient conversion (inhibition of 5’deiodinase enzyme) and the T3 levels fall below a level needed to sustain adequate function of that particular system. The 5- deiodinase enzyme activity is increased causing T4 conversion to RT3 (reverse T3), which has 4 no metabolic activity and dampens metabolism. In these individuals disease processes begin and healing processes are compromised. The well known hypothyroid symptoms of coldness, tiredness, hair loss, brittle nails, weight gain, recurrent infections are often present when elicited. Many patients have been in a lowered metabolic state for such a long time that they do not think of their coldness or tiredness as something out of the ordinary. Some of these patients are depressed because of their inability to function and are on antidepressants as a result. Sometimes the typical hypothyroid symptom may be masked by other disease states. For instance coldness may be masked by menopausal symptoms of hot flashes. Tiredness might be attributed to aging, poor sleeping, OSAS, chronic sinusitis, or anemia. Women seem to be effected more than men. Probably this is related to the metabolic enhancing effects of testosterone of which are ten times greater in men than women. The trigger points for a patient’s symptoms can occur with relatively small decreases in their metabolism. 15 15 CONCLUSION All of these 6 patients had significant improvements in their quality of life after T3 elevation. All 6 exhibited problems with their immune system. Each patient had different manifestations – some affecting their ears (dizziness), skin (hives, urticaria, dryness, hair loss), nervous system (brain fog, neuralgia), respiratory (allergy, airway obstruction), GI tract (stomatitis, constipation), and constitution (coldness, lethargy, depression). Low TT3/RT3 and FT3 levels make allergy control much more difficult. Difficult ENT conditions can persist even in patients on T4 supplementation. Optimizing a patient’s metabolism with T3 using the above criteria is a powerful tool, which can successfully treat difficult ENT problems. Other medical problems often resolve along the way resulting in a superior quality of life and excellent patient compliance. This technique will greatly enhance your ENT practice, as you turn difficult patients into grateful ones. 16 16 REFERENCES 1 . Wilson, E. Dennis. Wilson’s Syndrome The Miracle of Feeling Well, 3rd ed., Orlando: Cornerstone Publishing Company, 1996. p. 20-21. 2. McDaniel, Alan. Personal communication. 3. Werner and Ingbar’s The Thyroid: A Fundamental and Clinical Text, 6th.ed., edited by Braverman, Utiger, J. B. Lippincott Co.; 1991, p.145. 4. Ibid, pp. 358-360. 17 17 1 . Wilson, E. Dennis. Wilson’s Syndrome The Miracle of Feeling Well, 3rd ed., Orlando: Cornerstone Publishing Company, 1996. p. 20-21. 2 . McDaniel, Alan. Personal communication. 3 . Werner and Ingbar’s The Thyroid: A Fundamental and Clinical Text, 6th.ed., edited by Braverman, Utiger, J. B. Lippincott Co.; 1991, p.145. 4 . Ibid, pp. 358-360. 18 18