Hypothyroidism:Optimizing Medication withSiow-Reiease CompoundedThyroid Replacement

In observing patients taking either levothyroxine (L-thyroxine) USP (e.g., Synthroid, Levoxyl) or dessicatedthyroid USP (e.g., Armour Thyroid, Westhroid,Naturethroid). it has become apparent that a significantpercentage continue to suffer from thyroid-related.symptoms in spite of optimal blood levels of thyroidhormones. This became even more apparent whenthe American Association of Clinical Endocrinologists(AACE) changed its guidelines for optimal thyroid-

Signs and Symptoms of Hypothyroidism

The AACE names the following as the most commonsigns and symptoms of hypothyroidism:

AtaxiaBradycardiaCoarsening or loss of hairCold intoleranceConstipationDecreased concentrationDelay in the relaxation phase of deep tendon reflexesDepressionDry, yellow skinFatigueGoiter {thyroid gland enlargement)HoarsenessHyperlipidemiaHypothermiaInfertilityIrregular or heavy mensesMemory and mental impairmentMyalgias (muscle aches)Myxedema (fluid infiltration of tissues)Weight gain from fluid retentionWorsening hypercholesterolemia

by Martin Miiner, NDNational College of Naturopathic Medicine

stimulating hormone (TSH) values in patients receivingthyroid replacement. The old reference values, whilevarying somewhat depending on the laboratory test kitused, ranged from 0.5 to 5.0 pIU/mL. The new guidelinesfor TSH optimization, adopted in 2003, range from 0.3to3.0plU/mL.

This change required that many patients' doses ofthyroid replacement be raised so that their serum levelswould fall into the new range. Although this changewas intended to optimize treatment outcomes, manyhypothyroid patients have continued to suffer from avariety of hypothyroid symptoms, presumably becausetheir dose of thyroid replacement is suboptimal. Themost common lingering complaints include fatigue,impaired concentration, and persistent difficulty losingweight in spite of adequate exercise and reasonablecaloric restrictions.

In 1996, I began tracking patients who were takinglevothyroxine as their thyroid replacement medication,and closely monitoring their symptoms. Althoughtheir dosages seemed adequate on the basis of serumtesting, it became apparent that more than 75% of thepatients continued to suffer from common hypothyroidsymptoms. I asked these patients to track their basalbody temperature by keeping daily records of eitherfirst morning axillary (armpit) temperatures or serialoral temperatures three, six, and nine hours afterrising. Both niethods revealed temperatures almostalways below 98.0°F. Low temperature is commonlyreported as a sign of hypometabolism, as describedeloquently by Broda Barnes, MD, in the classic textHypothyroidism: The Unsuspected Illness (see SuggestedReading).

TOWNSEND LETTER - FEBRUARY'MARCH 2007

Incidence of HypothyroidismIt is estimated that approximately two percent of the

US population - 5.8 million people - are afflicted withhypothyroidism. Women are more likely to develophypothyroidism than men, and the incidence increaseswith age. (See the sidebar. "Signs and Symptoms ofHypothroidism," for a list of the most common signsand symptoms of hypothyroidism.)

Adequacy of Synthetic and Glandular ThyroidReplacement

If a patient is taking thyroid replacement andsymptoms persist, the condition is not being optimallymanaged. The medication most commonly prescribedfor hypothyroidism is synthetic thyroid hormone,or levothyroxine CT4). But it is the active form of thehormone, triiodothyronine (T3). that we use in our cellsand tissues. The conversion of T4 to T3 happens in theliver and in the cells themselves. T4 is converted intoboth T3 and reverse T3. Reverse T3 is a stereoisomer ofT3 and has no biological activity. T4 can be comparedto a key that has not yet been cut by a locksmith to fitin the lock (the thyroid receptor site). When it is cutproperly (as T3), it fits in the lock and opens the door.The reverse T3 stereoisomer of T3 is a mirror imageof the active T3 molecule - a key that is cut differentlyenough by the locksmith that it fits in the lock (receptorsite) yet doesn't open the door. When there is an excessof reverse T3, no thyroid metabolism is stimulated.

Reverse T3 is biologically essential to slow downmetabolism as a natural compensation mechanismduring times of starvation or famine. In fact, reverseT3 creates more powerful negative feedback on theproduction of T3 than vice versa. Under varyingstressors such as extreme caloric restrictions,pregnancy, and emotional stress, the conversionof T4 to T3 can become unbalanced as the bodyproduces excessive amounts of reverse T3. ReverseT3 exerts its negative feedback on T3 and ties upthyroid receptors. Reverse T3 must be displaced bythe proper biologically active T3 if metabolism is to

Table 1. Comparison of Triiodothyroxine (T3) andThroxine (T4) in Humans.

Production rate (nmol/day)Fraction from thyroidRelative metabolic potencySerum concentrations^• Total (nmol/L)

100.00• Free (pmol/L)

Fraction of total hormone in free form {x10-2)Distribution volume (L)Fraction intracellularHalf-life (days)" To convert T4from nmot/L to pg/dL (total) or pmol/L lo ng/dL (free), divideby 12.87. To convert T3from nmol/L to ng/cL (total) or pmol/L to pg/dL (free),multiply by 65.1.

T350.00

0.201.00

1.80

5.000.30

40.000.640.75

T4110.00

1.000.30

20.000.02

10.000.156.70

normalize. This is impossible, however, if a patient isbeing given synthetic T4 only. In these cases, thertis no replacement source of the T3 that is needed U>displace the excess accumulations of reverse T3 in thecirculation and receptors. In the absence of adequatebiologically active T3, symptoms of hypothyroidismremain, despite an adequate level of T4 in the serumand a normal TSH level. Since most of the conversionof T4 into T3 happens in the cells, serum levels of freeT3 and reverse T3 may be normal even when T3 and

Larynx

Cartilage

Trachea(windpipe)

ThyroidGland

reverse T3 levels are not in balance. It is as though thecells are starving for biologically active T3 in the midstof plenty. Unfortunately, the "plenty" is plenty of T4 andreverse T3 rather than the essential biologically activeT3.1 see many examples of this in my ciinical practice.Many patients continue to suffer with hypothyroidsymptoms even though they are taking T4100 pg (0.1mg) per day. Their blood levels of TSH and T4 arenormal, yet symptoms persist.

T3 is available as a manufactured drug in the formof liothyronine sodium (Cytomel). This syntheticT3 is released immediately, without delay, and ismanufactured only in 5 pg and 25 |ig doses. T3 isthree to four times more biologically active than T4and exerts its effects more rapidly and vigorouslythan T4. The half-life of T3 is 0.7,5 days, while that ofT4 is 6.7 days (Table 1). Patients are much more likelyto experience side effects from Cytomel than fromcompounded, slowly released T3. These side effectsinclude, yet are not limited to, tachycardia, arrhythmia,anxiety, nervousness, agitation, irritability, sweating.

I

OWNSENO LETTER - FEBRUARY/MARCH 2007

Hypothyroidism

headaches, increased bowel motility, and menstrualirregularities. Angina, congestive heart failure, andatrial fibrillation can be aggravated or induced byexcessive doses of T3. Other physiological distinctionsbetween T4 and T3 are worth noting. They are bestsummarized by Williams and Williams in their Textbookof Endocrinology (see Suggested Reading).

USP dessicated thyroid or Armour Thyroid is madewith a ratio of four parts of T4 for every one part ofT3. This ratio is comparable to those in the human andporcine thyroid glands, which produce 75% T4 and25% T3. One grain of Armour Thyroid contains 36 pgof T4and 9 pg of T3. The T3 is released all at once, notslowly.

Another manufactured drug, liotrix (Thyrolar),contains T3 in a similar ratio of 75% T4 to 25% T3. Again,the T3 in Thyrolar is not released slowly. Because T3 isgenerally considered to be four times more potent thanT4, a 25-pg dose of T3 is equivalent to a 100-pg dose ofT4.

The amount of slow-release T3 prescribed,whether formulated in combination with T4 or takenseparately from T4, should be about 25% more thanthe mathematical equivalencies would suggest. This isbecause T4 blunts the utilization of T3 to some extent.The compounded slow-release form seems to allow forless total drug absorption. This can vary considerablyfrom patient to patient. The best approach is to monitorserum levels of free T4, free T3, and TSH in patientstaking T4 and slow-release T3 replacement six to eightweeks after every dose adjustment. Further doseadjustments can then be made if necessary. Since T3has a short half-life and serum levels tend to peak threeto four hours after dosing of compounded slow-releaseT3, we instruct patients to not take their morning slow-release medication until after their blood draw. Thisallows measurement of their 24-hour lowest levels ofcirculating serum T4 and T3. (These equivalencies aresummarized in the accompanying sidebar, "T4 and T3Equivalencies.")

T4 and T3 Equivalencies

Armour Thyroid 1 grain = T4 36 pg, T39 pgT3 9 pg x4 = T4 equivalency of 36 ig

Armour Thyroid 1 grain = T4 total equivalency of 72 pg(36 pg directly from T4 and 36 pg from T3 9 pg x4)

Nutrients as Cofactors in Thyroid MetaboilsmSelenium is an essential cofactor in the conversion

of T4 Into T3. T4 is converted into T3 by the selenium-dependent enzyme 5'-deiodinase. Selenium depletion

of soil is common in many areas of the US, andmany individuals do not supplement adequately tocounteract this deficiency. Iodine is also essential inthe conversion of T4 into T3. While iodine depletionis common in US soils, many Americans use iodizedsalt to counteract this. Commercial farming methodsused in the last century, which fertilized soil only withnitrogen, phosphorus, and potassium, have allowedsoils formerly rich in selenium and iodine to becomefully depleted. Other nutrients essential to optimizingthyroid metabolism are tyrosine, zinc, copper, andessential fatty acids. In a sense, all the essentialnutrients play a role in optimizing the health of thethyroid gland (essential amino acids, essential fattyacids, vitamins, minerals, and trace minerals).

The SoiutionOver the years, I have developed several different

replacement strategies as alternatives to the use ofthe standard therapies (levothyroxine and dessicatedthyroid). These replacement strategies have in commonsome blend of T4 with slow-release T3. The exampleused in the first case is best suited to the patient whohas higher demands for energy during the day and/orsuffers from some type of sleep disorder at night. Theapproach used in Case 1 is also best for patients whohave a hard time taking more than one pill daily orthose who have financial constraints, since this is theleast expensive option.

Case ReportsIn each of these cases, we start with a patient who is

currently taking T4 100 pg as the starting dose. We willbe changing each patient's therapy to a blend of T4 andT3, slowly released.

Case 1This patient's starting TSH is 2.5 pIU/mL, and we

have a target of 1.0 pIU/mL to optimize quality of life andminimize hypothyroid symptoms. The patient's dose ofT4 should be increased to 125 pg or 150 \ig to drive theTSH level down from 2.5 to 1.0 pIU/ mL. For discussionpurposes, this final T4 dose is 150 lg. This dose of T4must be converted to an appropriate combination ofslow-release T4 and T3 at the correct ratio. As alreadydiscussed, the thyroid gland maintains a T4:T3 ratioof 4:1, but most patients who are symptomatic areconverting an excessive amount of T4 into reverseT3. They need a ratio of T4;T3 of perhaps 3:1 or 2:1 or.rarely, even more T3 relative to T4. This is especiallythe case at the beginning of therapy. If we decide on aT4:T3 ratio of 2:1, converting 150 pg of T4 to a blend ofslowly released T4 and T3 mathematically calculates to50 pg of T4 and 25 pg of T3. The 25 pg of T3 multipliedby 4 represents a T4 equivalency of 100 pg. Adding the50 pg of T4 brings the total T4 dose to 150 pg.

TOWNSEND LETTER FEBRUARYfMARCH 2007

Keep in mind, however, that doses of slow-releasecombinations need to be increased by approximately25% because of differences in absorption. Mathematicalequivalencies are just that, and often a deliveryform can increase or reduce absorption from what ismathematically assumed. If we increase this initial doseof 150 pg of T4 by 25% to accommodate this, the correctdose of T4 is 187.5 \ig. The equivalency of this dose ina T4:T3 ratio of 2:1 would be about 60 pg of T4 and 30pg of T3. The 30 pg of T3 multiplied by 4 equals 120 pgof T4 on an equivalency basis; with the 60 pg of T4, thisadds up to a finished equivalency of 180 pg, slightly shyof the 187.5 pg target.

A formula can be used to make the calculationseasier, as follows:

T4 dose divided by 3 = new T4 doseT4 dose divided by 6 = new T3 doseA 300 pg T4 dose would convert to (300/3 = 100

pg T4) plus (300/6 = 50 pg T3)The same mathematics apply to increasing

or decreasing the T4:T3 ratio in subsequentprescriptions. From a practical perspective, however,the levels of T4 and T3 in the patient's serum shouldguide the prescriber to the proper proportional ordisproportional dose adjustments needed to reachtargeted serum levels of free T4, free T3, and TSH.

If the degree of thyroid resistance and need foractive T3 is not as extreme, we might consider a T4:T3ratio of 3:1. An equivalency of 187.5 pg would convertto 81 pg of T4 and 27 pg of T3. Multiplication of 27pg T3 by 4 equals 108 pg; this added to the 81 pg T4equals approximately 190 pg of T4. The easiest way tocalculate this is to realize that the amount of T3 will beslightly less than that needed for the 2:1 ratio (i.e., T460 |Jg/T3 30 pg). Multiply the 27 pg T3 by 3 to preservethe 3:1 ratio and calculate the finished equivalency.These ratios are modified as indicated by remainingsymptoms, temperature log results, and balance of freeT4, free T3, and TSH in the blood.

Case 2In this case, the patient (who is initially taking 100 pg

of T4) also requires a dose increase to 150 pg to get herTSH level down to a target of 1.0 pIU/mL. The patientcould continue to take T4. yet at a lower dose of 50 pg.These medications come in doses of 25. 50. 75. 88, 100,112, 125, 137. 150, 175, 200, and 300 pg. Because it hasno food dyes or coloring added, 1 like to use the 50-pgtablet and divide the dose. If the target desired dose is60 pg as in Case 1, the closest we can get is 50 pg. The30 pg of T3 needed to make up the correct T4:T3 ratiois compounded as a slow-release tablet, either as 30 pgonce daily or 15 pg every 12 hours. I prefer the slow-release capsule to be taken first, upon rising; Ideally,the patient would then wait one hour before eatingbreakfast and take the T4 pill three hours after the T3.The patient would then take the second T3 capsule,

Hypothyroidismif appropriate, 12 hours after the first. Some patientsneed their T3 slowly released over 24 hours, especiallyas the doses are increased to avoid side effects or tooptimize distribution of energy throughout the day to ^be more even and to avoid fatigue in the late afternoon |or evening.

This dosage regime is more complicated for patients,Remember, these are hypothyroid patients who willtake medication daily for the rest of their life. Asking Msomeone to take a morning dose, another dose three ™hours later, and a third 12 hours after the first can be acompliance nightmare. Some patients feel best on thisprotocol, however, and are not significantly botheredby the routine. It can be simplified by taking the entireday's dose of T3 in the morning and the T4 three hourslater, or even further by taking the T4 and T3 togetherupon rising. (The T4 does not have to be releasedslowly, since its half-life is seven days.) Most convenientfor the patient is compounding the T4 together with theslow-release T3 in one capsule, so that the patient hasto take only one capsule in the morning.

Armour and USP ThyroidRecall that there is a good chance that a hypothyroid

patient with lingering chronic hypothyroid symptom.sis converting too much T4 into reverse T3, which is ibiologically inert. By replacing some of the prescribed HT4 with slow-release T3, the reverse T3 gets displaced "by the active T3, and metabolism returns to normal.

Glandular Thyroid USP (Armour Thyroid) deliversapproximately four parts T4 to one part T3. T3 is aboutfour times more potent than T4 but is metabolized threetimes faster. The T3 in Armour Thyroid is not releasedslowly and therefore gets delivered unevenly throughout Hthe day. This is not the way the thyroid gland and mtissues work. T3, owing to its high biological activity,should be delivered in even amounts. Compoundedslow-release T3 does just that. Furthermore, accuratelyadjusting the dose of Glandular Thyroid USP is difficult.Amounts of T4 and T3 can vary from batch to batch andfrom manufacturer to manufacturer. USP thyroid comesin limited strengths, including one-quarter grain, one-half grain, 1 grain, 2 grains, and 3 grains. Optimizingthe dose in sensitive and difficult cases may be verychallenging. •

Please note that I do not advocate treatinghypothyroidism with slow-release T3 alone, as theonly form of thyroid replacement. T3 works best when Hcombined with T4. Too much T3 without T4 can cause ^other problems. Including osteoporosis and heartarrhythmias. T4 also helps blunt the risk of side effectsfrom T3, which can occur even with slow-releaseT3. Finally, T4 offers a reservoir of thyroid hormonematerial with which to make more T3 as needed.

I

WNSEMD LETTER - FEBRUARY/MARCH 2007 BEST OF NATUROPATHIC MEDICINE

Hypothyroidism

Many patients suffering from years of lingeringhypothyroid symptoms while being treated withsynthetic T4 or Armour Thyroid will feel much betterif their treatment is changed. Appropriate changesinciude either a lowered dose of the current medicationcombined with slow-release T3 or a customizedcompounded blend of slow-release T4 and T3.

I urge patients to consult with their endocrinologistbefore making any change in thyroid medication. Theyshould be aware, though, that very few physiciansare knowledgeable about slow-release T3 and itsproper use. Although some available drugs deliverT3 (Cytomel, for example) or combine T4 with T3(Thyrolar), the T3 in these preparations is not releasedslowly. As a result, patients continue to suffer from thesymptoms that result from uneven T3 distribution.

Compounded Slow-Release T4 and T3In making the medication, a compounding

pharmacist uses properly aliquoted concentrations ofT4 and T3. The T4 and/or T3 are combined togetherwith cellulose derivatives that regulate their slowrelease. This mixture is then either tumbled for at leastsix hours or blended fully in a V mixer to assure evendistribution of the active ingredients. The finishedmaterial is then placed into capsules. Once swallowed,the capsule forms a bolus in the stomach and slowlyreleases T4 and T3. TheT4 and T3 used in compoundingare synthetic, yet they are biologically identical tothe T4 and T3 made by the human thyroid gland (T4 =levothyroxine sodium or 3,3',5,5'tetraiodothyroninesodium, and T3= L-triiodothyronine).

Monitoring Medication AdjustmentsThe T4:T3 ratio initially prescribed is arbitrary and

will most likely be adjusted up or down. Adjustmentsare based on ongoing symptoms, body temperatures,and the balance of serum levels of free T4, free T3, andTSH reported after six to eight weeks on a stable dose.In the most severe cases of thyroid resistance, whichrequire the highest doses of T3, the dose will need tobe adjusted until the serum TSH level is 0.2-1 plU/mL,with the free T4 level at the low end of normal or evenbelow normal, while the free T3 level is at the high endof normal or even above normal.

Since T3 is so biologically active, we like to instructour patients to take no thyroid medication the morningof the blood draw. We have them come in for this blooddraw as the first patient scheduled in the morning (8to 9 AM). This allows us to capture their lowest levelof circulating T3 in the 24-hour period. They areinstructed to take their medication immediately afterthe biood draw.

When changing from T4 to a slow-release blend of T4and T3, the initial dose is an estimate. The guidelinesalready described are only guidelines; actual dosevaries from patient to patient, depending upon thatpatient's intestinal heaith and absorption of thyroidhormone. In our initial change of prescription, weauthorize patients to return in three weeks for repeatblood work if they are feeling poorly and in two monthsif they are doing well. Within three weeks after a doseadjustment, the serum levels of T4 and T3 reach theirnew steady state. If an individual is feeling poorly fromeither underdosing or overdosing, we can check at thisearly juncture their circulating blood levels of free T4and free T3. TSH level will not stabilize for six to eightweeks after a dose change.

Dnig-Drng and Drng-Nutrient InteractionsThyroid hormone can potentiate the effects of

warfarin, requiring a lowering of blood warfarin level toavoid excessive anticoagulation. Digoxin level can bepotentiated by thyroid medication, requiring loweringthe dose of digoxin. Antidepressant drugs can be mildlypotentiated by thyroid hormone. Patients taking thyroidin excessive doses for weight loss can develop life-threatening symptoms of toxicity and/or arrhythmia,especially when the thyroid is given in association withsympathomimetic amines for their anorexic and weightloss effects. No interactions of thyroid with alcohol ortobacco have been documented. Estrogen replacementand estrogen dominance can increase the need forthyroid replacement. As hypothyroid women approachmenopause and accumulate more estrogen dominance,their thyroid replacement dose may need to increase.Similarly, estrogen replacement therapy can increasea woman's need for thyroid replacement. Insulinrequirements can increase as thyroid replacementdose increases. Thyroid medication can increase theadrenergic effects of epinephrine.

Calcium supplements can reduce utilization ofthyroid hormone, especially when taken in high doses.Thyroid hormone replacement is best taken in themorning, and calcium is best absorbed in the evening.Taking calcium with dinner minimizes any impairmentof utilization of thyroid taken in the morning. High levelsof soy in the diet can impair thyroid hormone utilization.Soy is best eaten in small amounts in the evening meal.Iodine and selenium potentiate the conversion of T4into T3, acting as cofactors in the conversion. Brassicavegetables (broccoli, cauliflower, Brussels sprouts) canreduce thyroid hormone utilization.

ConclusionHypothyroidism is a common condition. A large

percentage of patients remain significantly symptomaticin spite of apparently adequate replacement therapy.Symptoms may include intractable chronic fatigue,impaired concentration, and weight gain. These

BEST OF NATUROPATHIC MEDICINE TOWNSEND LETTER - FEBRUARY/MARCH

symptoms may have devastating consequences onquality of life. Changing medication to a blend of T4with slow-release T3 resolves many of these limitationsof patients' quality of life. The compounding of exactcustomized levels of T4 and T3 enables the clinicianto achieve optimal targeted serum levels of TSH, freeT4, and free T3 with precision. These levels can becarefully customized to optimize symptom resolutionwhile improving metabolic temperature status.Customized compounding allows dose adjustments toachieve whatever balance of T4 and T3 is necessary toachieve optimal health and resolution of symptoms.

Martin Miiner, NDMedical Director, Center for Natural Medicine, Inc.1330 S.E. 39th AvenuePortland, Oregon 97214drmilner@hotmail.com

Editor's note: This article was originally published in\.\\e.InternationalJournal of Pharmaceutical Compounding(July/August 2005; 9 [4]) .

Suggested ReadingBarnes B, Galton L. Hypothyroidism: The Unsuspected fUness.

New York. NY: Thorruss Y Crowell Co.; 1976.Bayliss RI, Tunbridge WM. Thyroid Disease: The Facts. Third

Edition. New York. NY; Oxford University Press; 1998.Bunevicius R, Kazanavicius G, Zaiinkevicius R, et al.

Effects of thyroxine as compared with thyroxine plustriiodothyronine in patients with hypothyroidism. N EngiJMed. 1999; 340(6); 424-429.

DeGroot LJ, Larsen PR, Refetoff S, et al. The Thyroid and ItsDisease.-i. Fifth Edition. New York, NY: .lohn Wiley; 1984.

De Rosa G, Testa A, Maussier ML, et al. A slightly suppressivedose of L-thyroxine does not affect bone turnover andbone mineral density in pre- and postmenopausal womenwith nontoxic goiter. Horm Metab Res. 1995; 27(11); 503-507.

Marcocci C, Golia F, Bruiio-Bossio G, et al. Carefully monitoredlevothyroxine suppressive therapy is not associated withbone loss In premenopausal women. J Clin EndocrinolMetab. 1994; 78(4); 818-823.

Marcocci C, Golia F, Vignali E, et al. Skeletal integrity in menchronically treated with suppressive doses of L-thyroxine.J Bone Miner Res. 1997;12(1); 72-77.

McDougall IR. Thyroid Disease in Clinical Practice. New York,NY: Oxford University Press; 1992.

Miiner M. Natural Medicine and Compounding Symposium.Presented [Audiotape, Videotape] at; A symposium ofProfessional Compounding Centers of America; February12-13, 1999; February 12-13, 1999; Houston, TX.

Miiner M. Wilson's syndrome and T3 therapy: A clinical guideto safe and effective patient management. UPC. 1999; 3(5):344-35L

Muller CG, Bayley TA. i-larrison JE, et al. Possible limitedbone loss with suppressive thyroxine therapy is unlikelyto have clinical relevance. Thyroid. 1995; 5(2); 81-87.

Hypothyroidism[No author listed.] Actual trends in thyroid physiopathology.

Horm Res. 1987; 26(1-4); 1-230.Nuzzo V, Lupoli G, Esposito Del Puente A. et al. Bone mineral

density in pre-menopausal women receiving levothyroxinesuppressive therapy. Gynecol Endocrinol. 1998; 12(5); 333-337.

Refetoff S. Resistance to thyroid hormone. In; BravermanLE, Utiger RE, eds. Werner and Ingbar's The Thyroid:A Fundamental and Clinical Text. Seventh Edition.Philadelphia, PA; Lippincott-Raven Publishers; 1996; 1032-1048.

Rosenthal MS. The Thyroid Sourcebook. Fourth Edition, NewYork, NY; McGraw-Hill; 2000.

Schneider DL, Barrett-Connor EL. Morton DJ. Thyroidhormone use and bone mineral density in elderly women.Effects of estrogen. JAMA. 1994; 271(16): 1245-1249.

Schoutens A, Laurent E, Markowicz E, et al. Serumtriiodothyronine, bone turnover, and bone mass changesin euthyroid pre- and post-menopausal women. CalcifTissue Int. 1991; 49(2): 95-100.

Williams AB, Williams RI. Textbook of Endocrifwlogy.Philadelphia, PA: Saunders: 2003: 342.

Wilson ED. Doctor's Manual for Wilson's Syndrome. ThirdEdition. Lady Lake, FL: Muskeegee Medical PublishingCo.; 1997.

Wilson ED. Wilson's Thyroid Syndrome: A Reversible ThyroidProblem. Orlando, PL; Cornerstone Publishing Co; 1991.

Martin Miiner, ND, receivedhisNDin 1983 from NCNM.He has remained at hisalma mater for the past20 years as Professorof Cardiovascular andPulmonary Medicine. Dr,Miiner is also the CEO andMedical Director of theCenter for Holistic Medicine(1983-1991) and Centerfor Natural Medicine, Inc.(1991-present). He is worldrenown for his naturaltreatment protocols for heartdisease, menopause andhypothyroidism.

IOWNSENO LETTER - FEBRUARY/MARCH 2007