Title page

TITLE PAGE
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 at Nyack Hospital, Nyack, New York
Senior Attending, Manhattan Eye Ear & Throat Hospital,
New York, New York

ABSTRACT

Low triiodo-L-thyronine 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 are difficult to control in spite of
standard therapies, and recurrent infections - stomatitis, sinusitis, bronchitis); and
dermatologic problems (hives, urticaria, eczema, dry skin, hair loss). When these
problems present with typical hypothyroid complaints (excessive tiredness,
excessive coldness, brittle nails) or there are also problems of autoimmune disease,
chronic fatigue/fibromyalgia, constipation or depression, low triiodo-L-thyronine
hypothyroidism is likely contributing or causing the disease.1 These patients do not
adequately convert tetraiodo-L-thyronine into triiodo –L-thyronine – the main
thyroid hormone, which is four times stronger than tetraiodo-L-thyronine in
elevating metabolism. Some of these patients are already on tetraiodo-L-thyronine
(Levothyroxine or Synthroid); however, they too continue to have a lowered
metabolism because of their inadequate conversion to triiodo-L-thyronine. Also,
supplementation with tetraiodo-L-thyronine is significantly converted to its
biologically inactive isomer - reverse triiodo-L-thyronine, which further dampens
metabolism. Therefore, analyzing metabolism by traditional methods in which
only thyroid stimulating hormone and tetraiodo-L-thyronine levels are considered
is insufficient and misleading. Emphasis should be placed more on triiodo-L-
thyronine analysis and treatment should be with triiodo-L-thyronine primarily,
since it cannot be converted into its inactive isomer.
INTRODUCTION
Although hypothyroidism is often in the differential diagnosis of many disease
entities, it is a diagnosis that is missed frequently because current screening
methods do not emphasize triiodo-L-thyronine (T3) levels. Typically thyroid panels
measure thyroid stimulating hormone (TSH), tetraiodo-L-thyronine (T4), and
triiodo-L-thyronine (T3) uptake (an indirect measure of empty receptor sites for T3
on the thyroglobulin molecule). Instead, I propose that testing must measure free
T3 (FT3), total T3 (TT3), and reverse T3 (RT3) as well as TSH and free T4 (FT4)
levels. The laboratory goals in treating these patients (in order of importance) are
as follows: obtaining a TT3/RT3 ratio between 10-15, a FT3 in the upper 25% of
the normal range (3.7-4.2), and maintaining the FT4 in the low end or slightly
below the low end of the range (0.7-0.8).2 The TSH may fall well below the low
normal value; however, it is the least important factor and, as I will show, these
parameters coincide with the least amount of disease.

Methods

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. At times these other metabolic
elevators will be needed 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 (TBII/TRA). 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
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
slow- magnesium or quinine can minimize muscle cramping. Heat intolerance may
require reducing the dosage or considering other causes such as low estrogen in
peri-menopausal women. Adrenal dysfunction may also need investigation and
treatment for maximum results. Less common side effects are loss of menstruation
and increase in fertility. A few patients will have headaches from Cytomel and will
need to start on Armour Thyroid instead. Side effects may prevent reaching the
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 case
reports will demonstrate the effects of T3 elevation in a variety of difficult ENT
disorders.

CASE PRESENTATIONS

J.K. is a 45-year-old female I have 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, intermittent treatments with 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 her
for inhalant and cyclic food allergies. I confirmed her severe pollen sensitivities
and Skin Endpoint Titration (S.E.T.) testing revealed severe food sensitivities to
soybean, chocolate, and tomato. 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 stated that 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 she was stationary. She denied vertigo. She had been diagnosed with auditory processing problems. She 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 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 autoimmune thyroiditis status with elevated antibodies to TPO and thyroglobulin. I diagnosed her with low T3 hypothyroidism with AIT. 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 – 10.45, FT3 – 3.3, FT4 – 0.76, TSH – 1.51. She’s currently on Synthroid 50mcg AM and Cytomel 10mcg. BID. I will continue to monitor her symptoms, for any side effects, and her thyroid profile 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), 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 FT4- 0.99. 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 25% 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 upper lip non-healing ulcer. For fifteen years she 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, 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, FT4-0.67, TSH-.415, which was closer to the ideal but still not perfect. She now had rare lesions of short duration. On Armour Thyroid 15mcg. BID plus 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. Her quality of life is significantly improved. 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 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, FT4-1.7, 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 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. His quality of life has significantly improved. 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, 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 and hypothyroidism with AIT for which she was on levothyroxine 112mcg a day. She also had a diagnosis of fibromyalgia, GERD, and hypertension. Additional medications included norvasc, Atenolol, Pepcid, and Ecotrin. I diagnosed her with low T3 hypothyroidism three years ago. Her thyroid profile at that time 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 problems with Raynauds, and less dry skin. She has had no side effects and uses Astelin and Nasalcort as needed and with greater efficacy at this point. D. I. is a 57-year-old female with complaints of severe cervical neuralgia (despite multiple negative workups and therapeutic modalities), headaches, seasonal and 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. 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 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 (total T3) is a measure of the bound T3 plus the FT3 (free T3). 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 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 no metabolic activity and dampens metabolism.4 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. 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. This is probably related to the metabolic enhancing effects of testosterone. When more than one symptom is present the odds that that patient is suffering from a lowered metabolic state is greatly increased and raising their metabolism may alleviate that symptom or disease. The trigger points for a patient’s symptoms can occur with relatively small decreases in their metabolism. 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 skin (hives, urticaria, dryness, hair loss), nervous system (brain fog, neuralgia), respiratory (allergy, airway obstruction) and GI tract (stomatitis, constipation), and constitution (coldness, lethargy, depression). Low TT3/RT3 and FT3 levels make allergy control much more difficult. Difficult ENT conditions including Meniere’s syndrome, recurring dizziness, and stomatitis, may result from or be aggravated by a lowered metabolism - even in patients who are already taking T4. Elevating 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. I would like to thank Alan McDaniel, MD for his keen insights into the endocrine/allergy connections, and for the establishment of the ENT/Endocrine Study Group. 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.

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