“Sub-laboratory” Hypothyroidism and the Empirical use of ... Hypothyroidism .pdf · treatment with desiccated thyroid has produced better clinical results than levothyroxine

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Alternative Medicine Review ◆ Volume 9, Number 2 ◆ 2004 Page 157

Review Hypothyroidism

AbstractEvidence is presented that many people havehypothyroidism undetected by conventionallaboratory thyroid-function tests, and cases arereported to support the empirical use ofArmour® thyroid. Clinical evaluation canidentify individuals with “sub-laboratory”hypothyroidism who are likely to benefit fromthyroid-replacement therapy. In a significantproportion of cases, treatment with thyroidhormone has resulted in marked improvementin chronic symptoms that had failed to respondto a wide array of conventional and“alternative” treatments. In some cases,treatment with desiccated thyroid hasproduced better clinical results thanlevothyroxine. Research supporting theexistence of sub-laboratory hypothyroidism isreviewed, and the author’s clinical approachto the diagnosis and treatment of this conditionis described.(Altern Med Rev 2004;9(2):157-179)

IntroductionHypothyroidism is a common disorder in

which the amount of hormone secreted by the thy-roid gland is inadequate to meet the body’s needs.As the main function of thyroid hormone is tostimulate metabolism, hypothyroidism results ina slower rate of metabolism and its associatedmanifestations. The symptoms of hypothyroidismcan vary considerably from person to person. Table1 includes a comprehensive list of symptoms,while Table 2 lists signs of hypothyroidism seenon physical exam.

“Sub-laboratory” Hypothyroidismand the Empirical useof Armour ® Thyroid

Alan R. Gaby, MD

Alan R. Gaby, MD – Private practice 17 years, specializingin nutritional medicine; past-president, American HolisticMedical Association; author Preventing and ReversingOsteoporosis (Prima, 1994), and The Doctor’s Guide toVitamin B6 (Rodale Press, 1984); coauthor The Patient’sBook of Natural Healing (Prima, 1999); has writtennumerous scientific papers in the field of nutritionalmedicine; contributing medical editor for The TownsendLetter for Doctors and Patients since 1985.Correspondence address: 301 Dorwood Drive, Carlisle, PA,17013

If not diagnosed and treated, hypothyroid-ism can in some cases become severely debilitat-ing or even fatal. Appropriate hormone-replace-ment therapy, on the other hand, will amelioratethe clinical manifestations of the disease, allow-ing most affected individuals to have a normal orclose-to-normal quality of life.

In cases of overt hypothyroidism, the se-rum concentrations of total and free thyroxine (T4)and triiodothyronine (T3) are below normal, andthe concentration of thyroid-stimulating hormone(TSH) is increased. The magnitude of the increasein TSH level is roughly proportional to the sever-ity of the hypothyroidism. TSH is released fromthe pituitary gland, which helps regulate the ac-tivity of the thyroid gland through a feedbackmechanism. The pituitary secretes more TSH inresponse to a hypothyroid state, less TSH in theeuthyroid state, and even less in the face of hy-perthyroidism. The secretion of TSH from the pi-tuitary gland is further regulated by the hypotha-lamic hormone thyrotropin-releasing hormone(TRH), which helps control the set-point of thepituitary.

Page 158 Alternative Medicine Review ◆ Volume 9, Number 2 ◆ 2004

Hypothyroidism Review


In milder cases of hypothyroidism, serumlevels of T4 and T3 are often normal (althoughtypically in the low-normal range), while the TSHlevel is above normal. This pattern of laboratoryvalues, which is frequently called “subclinicalhypothyroidism,” suggests the thyroid gland,while being stimulated to work harder, is only justkeeping up with the body’s needs. Most physi-cians recommend thyroid-replacement therapy forpatients with grossly elevated TSH levels (sug-gesting more pronounced hypothyroidism);whereas, the risk/benefit ratio in treating patientswith only slightly increased TSH values has beena topic of considerable debate. In the opinion ofmost authorities, a normal TSH level essentiallyrules out hypothyroidism.

Medical texts and review articles arealmost unanimous in recommendinglevothyroxine (T4) as the only appropriatetreatment for hypothyroidism.1,2 These sourcesacknowledge the human thyroid gland secretesboth T4 and T3, in a ratio of approximately 9to 1. Their reason for recommending only T4is that peripheral (i.e., extrathyroidal) tissuesare capable of converting T4, which is reallya prohormone, into its biologically active form,T3. Thus, administration of T4 provides a con-stant reservoir from which the body can meetits needs for T3. Most authorities discouragethe use of T3-containing preparations for thy-roid-replacement therapy. They point out thatT3 is rapidly absorbed and has a relativelyshort half-life, resulting in wide between-dosefluctuations in serum T3 levels that are notphysiologic. Thus, it is argued, a person tak-ing a T3-containing preparation might have asupraphysiological serum T3 concentration forseveral hours after each dose, followed by anexcessive decline in T3 level. The fact thatcommercially available preparations (such asdesiccated thyroid and synthetic T4/T3 com-binations) contain 20-percent T3 (comparedwith 10 percent in human thyroid secretions)further exacerbates the problem, according tothe prevailing point of view.

Another View of HypothyroidismThe conventional approach to diagnosing

and treating hypothyroidism has been of benefitto millions of patients. However, in the experi-ence of this author and a number of other practi-tioners (perhaps between several hundred and afew thousand in the United States), reliance solelyon this approach causes an unusually large num-ber of patients to be misdiagnosed and deprivedof effective treatment.

With regard to diagnosis, it appears manypeople have clinical hypothyroidism that is notdetectable by standard laboratory tests. Thissyndrome of hypothyroidism with normal bloodtests might reasonably be called “sub-laboratoryhypothyroidism.” In addition to the apparent lackof sensitivity of current diagnostic methods, the

Table 1. Common Symptoms Associatedwith Hypothyroidism

GeneralFatigueWeaknessConstipationWeight gainSluggishnessCold extremities, intolerance to coldEdemaMuscle achesHeadachesDecreased libido

PsychiatricDepressionPoor mental concentrationMemory loss

MiscellaneousHoarsenessDry, rough skinCoarse, dry, or thinning hair




conventional treatment for hypothyroidism(both the laboratory-documented and sub-laboratory types) can yield less-than-idealresults. This author has observed a significantnumber of hypothyroid patients treated withappropriate doses of levothyroxine fail toexperience adequate symptom relief, and somepatients do not improve at all. Many, althoughnot all, of these levothyroxine nonrespondersfare significantly better with Armour® thyroid(a brand of desiccated thyroid derived fromporcine thyroid gland).

During 19 years of clinical practice,this author has recommended a therapeutic trialof thyroid hormone for approximately 1,500patients who displayed signs and symptomssuggestive of hypothyroidism (often accom-panied by a low basal axillary temperature;e.g., 97.4 degrees F or lower), but who hadnormal laboratory tests for thyroid function.The laboratory assessment usually consistedof measurements of TSH plus either free T4or free-T4 index. In some cases, free- or total-T3 levels were also measured.

The empirical use of thyroid hormonewas based initially on the work of BrodaBarnes, MD, who pioneered and popularizedthe use of the basal body temperature test(which he considered a surrogate for the basalmetabolic rate) as a tool for diagnosing hypothy-roidism.3

With additional clinical experience, thisauthor came to rely more on medical history andphysical examination, and less on body tempera-ture, for assessing thyroid function and monitor-ing treatment. In approximately 60 percent of pa-tients so treated, one or more chronic symptomsimproved to the extent that both doctor and pa-tient considered the treatment worth continuing.Many patients reported dramatic relief of symp-toms that had plagued them for years and inter-fered with their quality of life and ability to func-tion – symptoms that frequently had failed to re-spond to a wide array of conventional and uncon-ventional treatments. In the other patients the treat-ment was discontinued, either because it was notbeneficial or because it caused side effects suchas nervousness, insomnia, rapid pulse, or (rarely)

tightness in the chest. Side effects requiring dis-continuation of treatment occurred in approxi-mately 15 percent of patients who underwent atherapeutic trial of thyroid hormone.

Most patients were treated with Armourthyroid; some received levothyroxine (Synthroid®,Levoxyl®); and a few were treated with a combi-nation of levothyroxine and T3 (Euthroid®). Inaddition, approximately 50 patients were seen overa 19-year period who had been diagnosed else-where with hypothyroidism and who had remainedsymptomatic despite appropriate replacementtherapy with levothyroxine. When these patientswere switched to Armour thyroid, marked im-provement occurred, often within 24-48 hours.Occasionally, the opposite was observed: patientswho failed to respond to Armour thyroid did welleither with levothyroxine or levothyroxine-plus-T3.

Table 2. Signs of Hypothyroidism Notedon Physical Exam

Myxedema – a non-pitting edema due to thedeposition of mucin in the skin around the ankles,below the eyes, and elsewhere

Carotenodermia – an accumulation of beta-carotene in the skin because of impairedconversion of beta-carotene to vitamin A

Follicular hyperkeratosis – presumably due tovitamin A deficiency

Dry rough skin

Dry, coarse, thinning hair

Pallor

Observation of delayed return on the Achilles’tendon reflex (ATR) test




The Broad-Ranging Potential ofThyroid Hormone

Many disorders may respond to thyroidhormone (Table 3). Several conditions associatedwith hypothyroidism are discussed in detail be-low, some illustrated with cases from this author’spractice. These disorders were selected for dis-cussion because either the association with hy-pothyroidism is not generally appreciated or be-cause there are data indicating the TSH level issometimes normal in hypothyroid patients withthose particular ailments. In cases in which TSHwas normal, the diagnosis was established bymeans of a TRH-stimulation test. This test involves

the intravenous injection of the hypothalamic hor-mone TRH, followed by serial measurements ofthe serum TSH concentration. An abnormally largeincrease in TSH level following injection of TRHindicates hypothyroidism. Although the TRH-stimulation test is considered more sensitive thana TSH measurement for identifying hypothyroid-ism, it is rarely used in clinical practice because itis expensive, time consuming, and invasive, andthe mainstream medical community believes mea-suring TSH is sufficient.

Case 1.

A 57-year-old woman presentedwith a lifelong history of depression. Herparents had been killed in the Holocaustand she had lived in orphanages during herearly years. During 38 years in the UnitedStates she had worked with at least eightphysicians, psychologists, and counselors.Although she had gradually learned to dealwith issues related to post-traumatic stresssyndrome, her depression had not im-proved over the years. She also experi-enced hot and cold sensations, which hadoccurred repeatedly for many years. Physi-cal examination was unremarkable and thefree-T4 index was 7.2 mcg/dL (normalrange, 5-12 mcg/dL). Her basal axillarytemperature was consistently below 96.4degrees F.

She was advised to take 30 mgArmour thyroid daily for 10 days and thenincrease to 60 mg daily. Clear improve-ment was evident within two weeks, andat her three-month follow-up visit she re-ported a “remarkable improvement” in de-pression and energy. The hot and cold sen-sations also disappeared. She was seen atleast annually for the next 10 years, dur-ing which time the improvement was main-tained with a dose of 60 mg Armour thy-roid daily, with an increase to 90 mg dailyduring the winter.

Table 3. Conditions Associatedwith Hypothyroidism

CardiovascularHypertensionAngina pectorisAtherosclerosisHypercholesterolemiaHyperhomocysteinemia

Gynecological/EndocrineMenstrual irregularities(amenorrhea,oligomenorrhea,menorrhagia)InfertilityPremenstrual syndromeFibrocystic breast diseasePolycystic ovary syndromeReactive hypoglycemia

DermatologicalPsoriasisUrticaria

Ear, nose, and throatVasomotor rhinitisAllergic rhinitis




DepressionDepression is a common manifestation of

hypothyroidism, often ameliorated after correctionof hypothyroidism (Case 1). In a study of 250 con-secutive patients referred to a psychiatric hospital forevaluation of depression, anergia, or both, 20 (8%)were found to have some degree of hypothyroidism.4

Of those, half had a normal TSH level, and their hy-pothyroidism would not have been detected withoutthe TRH-stimulation test. The results of this studydemonstrate sub-laboratory hypothyroidism ispresent in some patients with depression. As there isno reason to assume the TRH-stimulation test iden-tifies all cases of hypothyroidism, the prevalence ofsub-laboratory hypothyroidism among patients withdepression may actually be higher than the four per-cent suggested by this study. In the experience ofthis author, the prevalence is closer to 50 percent,which may be explained in part by selection bias(many patients come to the clinic specifically seek-ing a trial of thyroid hormone).

Chronic FatigueFine-needle aspiration of the thyroid gland

was performed on 219 patients complaining ofchronic fatigue of more than one year’s duration.5

Eighty-seven patients (40%) were found to havedefinite histological evidence of chronic lympho-cytic (Hashimoto’s) thyroiditis. In those patientsTSH levels were widely scattered (range, < 0.9 to> 15 mU/L); one-third had a TSH level of lessthan 3.0 mU/L and 58.6 percent had a level of lessthan 5.0 mU/L. The clinical response tolevothyroxine therapy was “equally favorable”(details not provided) among patients with lym-phocytic thyroiditis, irrespective of the initial TSHlevel. Thyroid autoantibodies (peroxidase, thyro-globulin, or both) were present in only half of thosewith definite histological evidence of lymphocyticthyroiditis.6 These results indicate chronic lym-phocytic thyroiditis is common among patientswith chronic fatigue, that measuring thyroid au-toantibodies in the blood may fail to detect thy-roiditis in half of these individuals, and that treat-ment with thyroid hormone can relieve fatigue inpatients with chronic lymphocytic thyroiditis,whether or not the TSH level is elevated.

Reactive Hypoglycemia/Dysinsulinism

Barnes reported that the common, thoughcontroversial, disorder of blood-glucose regula-tion referred to as “reactive hypoglycemia,”“hypoglycemia,” or “dysinsulinism” often im-proves after empirical treatment with desiccatedthyroid.7 Case 2 is an extreme example of the manypatients seen by this author in whom treatmentwith thyroid hormone improved the symptoms ofreactive hypoglycemia.

Although thyroid hormone has not beensystematically studied as a treatment for hypogly-cemia, circumstantial evidence suggests it is in-volved in glucose homeostasis. In a study ofhealthy volunteers made hypoglycemic by admin-istration of insulin, the mean serum concentration

Case 2.

A 23-year-old woman presentedwith the chief complaint of fainting whenshe did not eat every 2-3 hours. She soughtmedical treatment after being stopped bya policeman for speeding, while racing tothe nearest store to purchase food. Shecollapsed while waiting for the ticket tobe issued, and had to pay not only forspeeding, but also for the ambulance andhospital evaluation. The review of systemswas positive for intolerance to the cold.Physical examination revealed a delayedreturn on the Achilles’ tendon reflex (ATR)test and mild dryness and coarseness of theskin. Thyroid-function tests were normal.Based on her history, a presumptive diag-nosis of reactive hypoglycemia was made.The patient was treated with 30 mg Armourthyroid daily and within two weeks she wasable to fast for up to eight hours withoutexperiencing any significant problems.




of T3 increased significantly within 45 minutesafter the insulin injection.8 Other research hasshown thyroid hormone stimulates the synthesisof glucose through the process of gluconeogen-esis.9,10 Taken together, these findings suggest thatthyroid hormone plays a role in the metabolic ad-aptation to hypoglycemia.

Ear, Nose, and Throat DisordersForman observed in 1934 that vasomotor

rhinitis and, to a lesser extent, allergic rhinitis areoften associated with clinical evidence of hypothy-roidism, and that treatment with thyroid hormonerelieves the symptoms in some cases.11 He com-mented that the nasal mucosa of patients with va-somotor rhinitis frequently has a myxedematousappearance. In 1956, Hollender reported on 126patients seen in his otolaryngology practice whohad a low basal metabolic rate and were treatedwith levothyroxine. The response rates were asfollows: vasomotor rhinitis (68%), postnasal dis-charge (68%), hearing loss and/or tinnitus (69%),lymphoid hyperplasia of the pharynx (51%), andheadache (57%).12 Others have also reported treat-ment with thyroid hormone can ameliorate vari-ous otolaryngological problems;13,14 however,some investigators have failed to observe any ben-efit from this treatment.15 Withers reported in 1974that treatment with thyroid hormone frequentlyenhances the response to allergy-desensitizationtherapy.16

Menstrual Disorders and InfertilityConventional texts mention infertility,

menorrhagia, and oligomenorrhea as commondisorders associated with hypothyroidism. Thereis evidence these problems also may occur inassociation with sub-laboratory hypothyroidism(Case 3). In a study of 150 women withlongstanding (> 2 years) infertility due toanovulation or luteal insufficiency, 13.3 percentwere found to have hypothyroidism.17 In most ofthe cases of hypothyroidism, standard tests ofthyroid function were normal, and the TRH-stimulation test was needed to establish thediagnosis. After treatment with levothyroxine (50mcg daily), luteal function improved and two of

the 20 women became pregnant. This authorknows of several women with longstandinginfertility and normal thyroid-function tests whohave become pregnant after treatment withdesiccated thyroid.

In another study of three women withmenstrual disorders (hypermenorrhea, polymen-orrhea, and oligomenorrhea, respectively) theproblem resolved in each case after treatment withthyroid hormone.18 Each woman had a normalfree-T4 index and TSH level, although TSH lev-els were near the upper limit of normal. In eachcase, a TRH-stimulation test was needed to dem-onstrate hypothyroidism.

Premenstrual Syndrome (PMS)Of 54 women with PMS who were evalu-

ated in one study, 94 percent had laboratory evi-dence of hypothyroidism, compared with none of12 women without PMS.19 Of those with hypothy-roidism, 31 percent could be diagnosed by stan-dard laboratory tests; whereas, in 69 percent anabnormal TRH-stimulation test was the only labo-ratory evidence of hypothyroidism. Administra-tion of levothyroxine to 34 women with PMS re-sulted in complete relief of symptoms in all cases.

Fibrocystic Breast DiseaseNineteen women (ages 21-44) with mas-

talgia associated with fibrocystic breast diseasewere treated with 100 mcg levothyroxine daily forat least two months, and then as needed for cycli-cal recurrences of pain.20 Nine patients (47%) ex-perienced complete relief of pain and 73 percentobtained either complete or partial pain relief. In11 of 19 women a softening of the breast noduleswas observed. Only one woman had laboratoryevidence of hypothyroidism prior to being treated;the others had normal levels of T4, T3, and TSH.Improvements in fibrocystic breast disease werereported in another series of 286 patients with“clinical or subclinical hypothyroidism” aftertreatment with desiccated thyroid.21




Polycystic Ovary Syndrome (PCOS)Of 12 girls (ages 9-16) with severe and

longstanding hypothyroidism, nine were diag-nosed by pelvic ultrasound with PCOS. The cystsresolved rapidly after treatment with thyroid hor-mone.22 In another study of hypothyroid patientswith PCOS, administration of thyroid hormonewas associated with normalization of ovulation.23

These observations raise the possibility that sub-laboratory hypothyroidism is a contributing fac-tor in some cases of PCOS.

Dermatological ConditionsBarnes administered desiccated thyroid

empirically to 214 patients with various skin con-ditions associated with a low basal body tempera-ture.24 One hundred ninety-eight patients (92.5%)showed marked improvement, 12 (5.6%) showedsome improvement, and four (1.9%) did not im-prove. Conditions successfully treated includedacne (n=88), boils (n=20), dry skin (n=14), ec-zema (n=57), ichthyosis (n=21), psoriasis (n=11),and ulcers (n=3). In those responding to therapy,treatment had to be continued for years, sincesymptoms recurred within a few months whentreatment was discontinued.

Pelkowitz treated 200 patients with pso-riasis using large doses of levothyroxine and anunspecified amount of “essential phospholipids.”25

The initial dose was 100 mcg daily, increased pro-gressively to a maximum daily dose of 400-500mcg. Propranolol was used as needed to controlincreases in blood pressure and heart rate result-ing from supraphysiological doses of thyroid hor-mone. Typically, a marked improvement was seenafter 5-6 weeks on the maximum dose oflevothyroxine, although some patients respondedto lower daily doses, such as 100-300 mcg. Pa-tients with stable psoriasis and large plaques re-sponded more slowly. After a few months of con-trol, the dose of levothyroxine was reduced to amaintenance dose. Psoriatic arthritis also improvedmarkedly with this treatment, even in patientswhose arthritis had been refractory to other treat-ments. High-dose levothyroxine would not be con-sidered a first-line treatment for psoriasis, becauseof its potential to cause adverse side effects and

Case 3.

A 39-year-old woman presentedwith depression, hair loss, constipation,irritable bowel syndrome (manifesting asintestinal spasms), short-term memoryloss, acne vulgaris, and irregular menstrualperiods. Most of these symptoms had be-gun nine years previously, after the birthof her only child. At that time, her physi-cian diagnosed her with hypothyroidism,and her symptoms were relieved by 120mg Armour thyroid daily. Approximately18 months before her first visit to thisauthor’s clinic, the patient changed physi-cians, was switched to levothyroxine, andpromptly experienced a recurrence ofsymptoms. Despite this, her doctor reducedthe levothyroxine dose progressively untilher suppressed TSH level returned to thenormal range. These dosage reductions, toa final level of 0.125 mg daily, resulted ina worsening of most of her symptoms, al-though she did experience a lessening ofanxiety. Physical examination at the timeof her first visit revealed a delayed ATRreturn bilaterally and a subtle myxedema-tous appearance around the ankles.

She was switched fromlevothyroxine to 90 mg Armour thyroiddaily and rapidly experienced significantimprovement in her symptoms, includingnormalization of her menstrual irregulari-ties, with no exacerbation of anxiety. Ather follow-up visit seven weeks later, theATR return was almost normal and theankle myxedema was reduced. She con-tinued on 90 mg Armour thyroid daily andremained symptom-free for the next threeyears, after which she was lost to follow-up.




the availability of other effective treatments. Thisauthor, however, has observed an improvement inpsoriasis in several apparently hypothyroid pa-tients during treatment with physiological dosesof desiccated thyroid.

Thyroid hormone has also been found tobe of value for individuals with chronic urticariawho have laboratory evidence of thyroid autoim-munity. In one study, 10 euthyroid patients withrefractory urticaria were treated withlevothyroxine.26 The initial dose was 25-100 mcgdaily, depending on the patient’s age and medicalcondition; dosage was increased if a satisfactoryresponse was not obtained. Of seven patients withelevated anti-thyroglobulin and/or anti-microso-mal antibodies at baseline, all seven had a com-plete elimination of hives or marked improvementwithin four weeks. Two patients required an in-crease in the levothyroxine dose before a com-plete resolution was seen. In two others, alreadyon levothyroxine therapy for hypothyroidism, anincrease in the dose resulted in a resolution of theurticaria. The highest dose used was 250 mcg daily.The three patients without elevated anti-thyroidantibodies did not improve. Five patients had arecurrence after treatment was stopped, but thesymptoms resolved again when treatment was re-started.

AsthmaTwelve “clinically euthyroid” patients

(ages 20-38) with chronic asthma of more thanfive years’ duration were treated with 40 mcg T3daily for 60 days.27 Seven patients reported obvi-ous subjective improvement, three had no change,and two felt worse. The mean FEV

1 increased by

17.6 percent (p < 0.0025) and the maximal venti-latory volume increased by 13 percent (p < 0.025).The improvement in pulmonary function corre-lated well with subjective improvement and a re-duction in use of bronchodilators. The markedimprovement in asthma seen in Case 4 is supportedby the findings of this study.

Other reports, however, suggest treatmentwith thyroid hormone can worsen asthma.28 Be-cause of these conflicting reports, lung functionshould be monitored in patients with asthma inwhom treatment with thyroid hormone is initiated.

In asthmatics particular attention should also begiven to the type of thyroid hormone preparationused. Commonly used levothyroxine products(e.g., Synthroid, Levothroid®, Levoxyl), containartificial colorings (coal tar dyes) that have thepotential to trigger asthma attacks.29,30 Such col-oring agents are present in all dosages of each ofthese products, with the exception of the 50-mcgdose of each.

HypertensionHypertension is relatively common

among patients with laboratory evidence of hy-pothyroidism, occurring in 14.8 percent of patientsin one study, compared with 5.5 percent of euthy-roid controls.31 In that study, adequate thyroidhormone-replacement therapy for an average of15 months significantly reduced blood pressure;whereas, blood pressure did not improve in pa-tients who received inadequate replacementtherapy. Barnes observed that, among patients withhypertension who had some clinical evidence ofhypothyroidism, treatment with desiccated thyroidalone normalized blood pressure in 80 percent ofcases.32 Menof reported a similar response rate ina group of 44 patients with essential hypertensiontreated with desiccated thyroid.33 Dernellis et aladministered levothyroxine to 30 patients withhypertension and laboratory evidence of hypothy-roidism.34 Fifteen of the 30 patients became nor-motensive, while the others showed only a smalldecrease in blood pressure. Failure to exhibit anadequate blood pressure response was associatedwith increased aortic stiffness, a concomitant ofhypothyroidism. Because the increase in aorticstiffness was at least partially reversed during thetreatment period, it is possible that some of thenonresponders would have had a greater reduc-tion in blood pressure with a longer duration oftreatment. Case 5 illustrates alleviation of border-line hypertension by treating for hypothyroidism.




Case 4.

A 34-year-old female presented with a history of fatigue, low energy, and sensitivityto cold throughout most of her life. Other symptoms included waves of nausea, with no rela-tion to meals or time of day, difficulty with mental concentration, a general tendency to edema,waking up nightly at 2-4 a.m., with difficulty falling asleep again, and recurrent palpitations.When she did not eat every 2-3 hours she would develop a feeling of agitation, followed bysevere fatigue. She had developed asthma during childhood, which began to increase in sever-ity in her late teens, and which required frequent use of inhaled glucocorticoids andbronchodilators. She suffered from ocular allergies and perennial allergic rhinitis with sea-sonal exacerbations, and had been treated with various oral, intranasal, and ophthalmic anti-histamines and glucocorticoids. She had an eight-year history of irregular menstrual periods,with cycles occurring approximately every 40-50 days. Numerous medications, nutritionalsupplements, and herbs had been presecribed for her various symptoms, but the results hadbeen for the most part unsatisfactory.

Two weeks prior to her first visit she had undergone extensive testing by an endocri-nologist, who had concluded that her endocrine system was normal. At that time her TSHlevel was 2.34 mU/L (normal, 0.3-5.50 mU/L), and the calculated free T4 was 2.24 units(normal, 1.53-3.85 units).

On physical examination her ATR return was delayed and her ankles and lower legshad an appearance of subtle myxedema. Her basal axillary temperature had been taken on sixoccasions prior to her first visit and ranged from 95.8-97.2 degrees F, with three of the sixreadings below 97.0 degrees F.

On the basis of her symptoms, physical findings, and sub-normal body temperature, aprovisional diagnosis of hypothyroidism was made. She was advised to take 15 mg Armourthyroid daily, increasing to 30 mg daily after five days, with a further increase to be consid-ered, depending on her response and tolerance to the treatment. During the first two weeks,she experienced dramatic improvement in all symptoms except cold extremities. Two monthsafter the start of treatment, there was a recurrence of nausea and a decrease in energy level.The dose of Armour thyroid was increased to 60 mg daily and those symptoms again re-solved. One month later, a further increase in dosage to 90 mg daily was necessary in order tocontrol her fatigue and nausea.

Of note, the patient’s asthma and rhinitis improved rapidly after the start of treatment,to the extent she rarely needed medication for either condition. At her most recent follow-up,ten months after the start of treatment, she rated the degree of improvement in her varioussymptoms as follows (0% indicates no improvement, 100% indicates complete relief): fatigueand low energy (90%), nausea (90%), difficulty concentrating (95%), irregular menses (99%),asthma (85%), ocular allergies (80%; only seasonal exacerbations remained), palpitations(99%), edema (45%), and waking at night (70%). Her need to eat every 2-3 hours had beenextended to every 3-4 hours; however, there was no improvement in her sensitivity to thecold. No adverse side effects occurred and pulse rate and blood pressure did not change.




Cardiovascular DiseaseLongstanding hypothyroidism is

associated with an increased risk of cardiovasculardisease, presumably due in part to thehypercholesterolemia that often accompanieshypothyroidism. An elevated plasma concentrationof homocysteine, which is an independent risk

factor for cardiovascular disease, also occursfrequently in people with hypothyroidism. In onestudy, treatment of hypothyroid patients withlevothyroxine reduced the mean plasmahomocysteine concentration by 38 percent;35 inanother study, thyroid-replacement therapyreduced the median plasma homocysteine level by44 percent.36 As mentioned previously,hypothyroidism is associated with hypertension(another cardiac risk factor), and the correction ofhypothyroidism often reduces elevated bloodpressure.

While the relationship between subclini-cal or subtle hypothyroidism and cardiovasculardisease has been debated extensively, recent evi-dence supports the concept that mild hypothyroid-ism increases the risk of heart disease. In a popu-lation-based, cross-sectional study of 1,149women (mean age 69) participating in theRotterdam Study, subclinical hypothyroidism (de-fined as a TSH level greater than 4.0 mU/L, witha normal serum free-T4 concentration) was asso-ciated with an increased age-adjusted risk of aor-tic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1-2.6]) and myocardial infarction (odds ratio, 2.3[95% CI, 1.3-4.0]).37 Further adjustment for bodymass index, cholesterol level, blood pressure, andsmoking status did not affect the results.

Anecdotal evidence suggests that the car-diovascular benefits of thyroid hormone also ex-tend to those with sub-laboratory hypothyroidism.In a study of 1,569 patients treated empiricallywith desiccated thyroid and followed for a totalof 8,824 patient-years, Barnes observed only fournew cases of coronary heart disease, although 72new cases would have been expected in a similargroup of patients, according to data from theFramingham Study.38

Angina pectoris can result from hypothy-roidism and sometimes responds to thyroid hor-mone,39 as in Case 6. However, treatment withthyroid hormone may also exacerbate pre-exist-ing angina, or trigger its appearance in patientswith established coronary heart disease (CHD).40

Furthermore, the use of excessive doses of thy-roid hormone can trigger atrial fibrillation in sus-ceptible individuals, particularly in the elderly. For

Case 5.

A 41-year-old woman had a his-tory of borderline hypertension, hyper-cholesterolemia, a tendency to depressionand fatigue, dry skin, diffuse hair loss onthe head, and diffuse edema. Thyroid-function tests were normal. On physicalexamination, carotenodermia was noted onthe feet and hands, follicular hyperkera-tosis was present on the arms, and the ATRreturn was moderately delayed. Becauseshe had a history of extreme sensitivity tovarious medications, she was started on 7.5mg (one-eighth grain) Armour thyroiddaily, equivalent to approximately fourpercent of the daily secretion from a nor-mal thyroid gland. On that dose she expe-rienced a rapid and marked improvementin mood, energy level, exercise tolerance,sluggishness, edema, and hair loss; dryskin was moderately improved. Bloodpressure became normal within severaldays and remained normal thereafter. Thedose was increased to 15 mg daily after20 days, resulting in a sensation of exces-sive heat for two weeks, which then re-solved. As there was no additional im-provement at the higher dose, the originaldose of 7.5 mg daily was resumed and shewas doing well 14 months later, at the timeof this writing. Her serum cholesterol levelwas 270 mg/dL prior to starting thyroidhormone; after 12 months of treatment,with no change in diet, the cholesterol levelwas 223 mg/dL.




these reasons, administration of thyroid hormoneto people with CHD should be undertaken withextreme caution, starting with low doses. In somecases, full correction of hypothyroidism is notpossible, as the diseased cardiovascular system isnot able to tolerate the increased metabolic de-mand created by the administration of thyroid hor-mone.

On the other hand, Wren administereddesiccated thyroid for five years to 132 patientswith symptomatic atherosclerosis, of whom thegreat majority had no laboratory evidence of hy-pothyroidism.41 The initial dose was 15-30 mgdaily, which was increased gradually over a six-month period, based on clinical judgment and in-dividual tolerance. In the majority of cases, thefinal daily dose was 120 or 180 mg. Of 41 pa-tients who had angina at the start of the study, 29(71%) reported benefit, such as increased exer-cise tolerance and decreased frequency and sever-ity of attacks. No patient reported increased an-gina as a result of thyroid therapy, and the mortal-ity rate was lower than the expected rate for a simi-lar population, according to actuarial tables.

Case 7.

A 34-year-old male complained ofa two-year history of greatly diminishedlibido and intolerance to cold. Physical ex-amination and thyroid-function tests werenormal, but basal axillary temperaturesaveraged 95.8 degrees F (two degrees be-low normal). A therapeutic trial was insti-tuted of 30 mg Armour thyroid daily, in-creasing to 60 mg daily after 10 days. Bothsymptoms improved moderately on thelower dose and markedly within severaldays after increasing the dose. These im-provements persisted with continued treat-ment.

Case 6.

A 57-year-old woman complainedof fatigue, nonexertional chest pain, and pal-pitations, beginning nine years previously.At that time another physician treated herwith 0.1 mg levothyroxine daily (it was notclear whether thyroid-function tests wereperformed), which resulted in an improve-ment in her symptoms. Seven years later (twoyears prior to her first visit with this author),she was taken off levothyroxine, which re-sulted in a return of her previous symptoms.She underwent a stress thallium test, whichrevealed coronary artery disease with 80-90percent probability, and her chest pain wasdiagnosed as angina pectoris. Treatment witha calcium-channel blocker (diltiazem) re-duced the frequency of anginal episodes. Theaddition of coenzyme Q

10 and L-carnitine

three months prior to her first visit resultedin some additional improvement, but hersymptoms persisted. Past medical historywas significant for a partial thyroidectomyat age 14. Recent thyroid-function tests werenormal.

Based on her history, a therapeutictrial was begun with 15 mg Armour thyroiddaily, increasing to 30 mg daily after twoweeks. The patient was advised to reducethe dose or to discontinue treatment if theangina became worse. Instead, there was arapid improvement in symptoms and at herfollow-up visit two months later she reportedher angina, fatigue, and palpitations had dis-appeared. Although it was not possible to ruleout a delayed response to coenzyme Q

10 and

L-carnitine as the reason for her improve-ment, the patient was convinced the benefitwas attributable primarily to the desiccatedthyroid. She did experience a recurrence ofangina when she tried to discontinuediltiazem; therefore, she was maintained ondiltiazem plus 30 mg Armour thyroid dailyand continued to do well the next two years,after which she was lost to follow-up.




Resistance from the MedicalMainstream

The reaction of the conventional medicalcommunity to the empirical use of thyroid hor-mone has ranged from skepticism to derision andoutright hostility. One editorial described this ap-proach as “bizarre” and talked about practitionerswho “dish out” (rather than prescribe) thyroidhormone.42 A letter printed in a major medical jour-nal referred to the “notorious work of Barnes.”43

Others cite the “indiscriminate” use of thyroidhormone by some practitioners, often in exces-sive doses, to treat obesity or as a general tonicfor tiredness. Several physicians have been ac-cused by state medical boards of practicing sub-standard medicine, merely because they diagnosedhypothyroidism on clinical grounds or prescribeddesiccated thyroid instead of levothyroxine.

The emotional negativity that surroundsthis controversy is reminiscent of academicmedicine’s resistance to the concept that supple-mentation with vitamins and minerals might havehealth benefits. Goodwin and Tangum noted in aneditorial in Archives of Internal Medicine that themedical mainstream has a history of uncriticallyaccepting reports of micronutrient toxicity, usingan angry and scornful tone in discussions of mi-cronutrient supplementation, and ignoring evi-dence of possible efficacy.44 The debate surround-ing micronutrient supplementation and that regard-ing the empirical use of thyroid hormone sharetwo characteristics that, according to Goodwin andTangum, tend to raise the ire of the medical estab-lishment: (1) the ideas originated primarily fromoutside of the academic medical community, and(2) proponents often bypassed conventional medi-cal channels and took their ideas directly to thepublic. Whatever the reason, it appears that con-ventional medicine has not made a serious attemptto evaluate the evidence regarding the empiricaluse of thyroid hormone, and that its wholesale dis-missal of the concept represents, at least in part, abiased attitude.

A typical response to the anecdotalevidence is, “Of course, tired people are going tofeel better if you crank up their metabolism withthyroid hormone; but, that doesn’t mean they are

hypothyroid.” That argument overlooks twoimportant points. First, tired people who are notclinically hypothyroid often feel worse, not better,when they take thyroid hormone. Second, a veryspecific set of symptoms, not just fatigue ordepression, usually improves when clinicalhypothyroidism is treated.

The firmness with which most physiciansassert that a normal TSH level proves euthyroid-ism is surprising, considering such a notion isbased largely on circular reasoning. Ever since thediscovery in 1892 that an extract of animal thy-roid tissue could cure myxedema, hypothyroid-ism has been defined as a clinical syndrome thatresponds to treatment with thyroid hormone. Whilevarious laboratory tests have been developed thatcorrelate with thyroid status, hypothyroidism re-mains a clinical syndrome, and no clear reasonhas emerged to redefine it in terms of its labora-tory correlates.

That laboratory testing provides a less-than-perfect picture is suggested by the number of differ-ent thyroid-function tests that have been abandonedover the years after being hailed initially as the newdiagnostic “gold standard.” One of the earliest suchtests, the basal metabolic rate, was potentially one ofthe best, since it measured the effect of thyroid hor-mone in the body. This test, however, was subject toerror, because metabolic rate is influenced by theemotional state of the person being tested. Later camethe protein-bound iodine test, then the serum T4 andfree-T4 index, and most recently the TSH.

There is no question that TSH levels go upwhen thyroid hormone levels go down, and viceversa. There is also no question that extremely highand extremely low TSH values correlate well withhypothyroidism and hyperthyroidism, respectively.However, there is no a priori reason to assume aTSH value within or just outside the normal rangealways (or even usually) gives an exact indication ofthyroid hormone status. Computer-software-like pre-cision is probably more the exception than the rulein biological systems, particularly in systems that aresubjected to the disruptive influences of emotionalstress, environmental pollution, chronic illness, sub-optimal nutrition, genetic polymorphisms, and au-toantibodies.




It has been reported, for example, that ina series of 45 hypothyroid patients given thyroid-replacement therapy the TSH level remained per-sistently elevated in 44 percent of cases, eventhough the patients became clinically euthyroid,with normal serum T3 levels and normal or el-evated T4 levels. Increasing the dose oflevothyroxine to an amount that normalized theTSH level caused some of these patients to be-come clinically and biochemically hyperthyroid.45

Since, as this study shows, TSH levels are some-times “inappropriately” elevated, one might ex-pect to find other instances in which the TSH levelis “inappropriately” normal, as in cases of sub-laboratory hypothyroidism.

Potential Explanations for theDisconnect between Clinic andLaboratory

The coexistence of clinical hypothyroid-ism and normal laboratory values may be explain-able in some cases by tissue resistance to thyroidhormone (TRTH). A syndrome of TRTH is knownto occur, although it is believed to be rare (only250 cases had been reported as of 1992).46 TRTHis frequently characterized by an elevated free thy-roid hormone concentration in a clinically euthy-roid person, and is typically associated with a ge-netic mutation of one of the two thyroid hormonebeta-receptors.47 Almost every family with TRTHthat has been studied has been found to have adifferent mutation. That observation suggests theremay be other, as yet undiscovered and possiblymore prevalent, mutations that result in subtle thy-roid-receptor dysfunction. Mild TRTH couldmanifest as clinical hypothyroidism with low-nor-mal, normal, or even high-normal serum concen-trations of T4 and T3.

Hypothyroidism could also result from adefect in the conversion of T4 to its biologicallyactive metabolite T3, a phenomenon reported spo-radically in the medical literature.48,49 A mild de-fect in this metabolic pathway might reduce se-rum T3 to a level that, while still within the popu-lation range of normal, is below normal for a par-ticular individual.50 The conversion of T4 to T3depends on the action of deiodinase, an enzyme

that catalyzes the removal of one iodine atom fromT4. Two such enzymes, deiodinases I and II, oc-cur in humans. Common variants of the genes foreach of these enzymes have been identified,51,52

and some of these genes might code for the pro-duction of a functionally defective enzyme. Onevariant of the deiodinase II gene (Thr92Ala) oc-curs with an allele frequency of approximately 35percent. Its presence is associated with insulin re-sistance,51 which could be a consequence of re-duced availability of T3 to the peripheral tis-sues.53,54 A common variant of the beta-3-adrener-gic-receptor gene (Trp64Arg), which plays a rolein the transcription of deiodinase II, has also beenidentified and is associated with abdominal obe-sity, insulin resistance,55 and a tendency to a lowermetabolic rate.56

Whether the pituitary would recognize,and respond effectively to, small but clinicallyimportant changes in thyroid hormone status coulddepend on many factors. In cases of TRTH, thepituitary would presumably respond appropriatelyif the abnormal receptors in peripheral tissues werealso present in the pituitary. Thyroid hormone re-ceptors in the brain differ, however, from those inthe periphery. While the receptors in the braincontain a beta-1 and a beta-2 subunit, the periph-eral receptors contain only the beta-1 subunit.57

Consequently, some mutations of the thyroid hor-mone receptor might be experienced differentlyin the periphery than in the pituitary, resulting ina distortion of the feedback mechanism. Geneticvariations in the activity of deiodinase I or II mightalso be experienced differently in these respec-tive tissues. In rats, for example, 50 percent of theT3 in the pituitary gland is derived from thedeiodination of T4 within the gland itself; whereas,in other tissues only 20 percent of the T3 is de-rived from intracellular deiodination of T4.58 Inaddition, deiodinase I does not appear to be presentin pituitary tissues, so genetic variations in its ac-tivity would likely affect peripheral tissues differ-ently than the pituitary. Another possible scenariothat could disrupt the feedback mechanism is theinhibition of peripheral thyroid hormone recep-tors by various environmental toxins, metabolites,or byproducts of intestinal flora. Although thesesubstances would cause manifestations of hy-




pothyroidism in the periphery, they might be in-capable of crossing the blood-brain barrier. Con-sequently, the pituitary receptors would be pre-served, and the pituitary would erroneously sensethat the thyroid status in the periphery is normal.

Even if the pituitary accurately sensedhypothyroidism in the peripheral tissues, its ca-pacity to mount a TSH response might vary fromperson to person. In the extreme, the failure of thepituitary to manufacture and release adequateamounts of TSH results in the syndrome knownas secondary hypothyroidism. While secondaryhypothyroidism is uncommon, it is likely thatmilder gradations of pituitary weakness occurmore frequently. If they do occur, they would pre-sumably manifest as clinical hypothyroidism witha normal TSH level.

The extent to which any of these sug-gested malfunctions in the feedback mechanismactually occur is unknown. All are plausible, how-ever, and each could explain how a person mightbe both clinically hypothyroid and biochemicallyeuthyroid.

The recent recommendation by the Ameri-can Association of Clinical Endocrinologists59 thatthe upper limit of normal for TSH be changed from5.0 to 3.04 mU/L should, if nothing else, raise fur-ther questions about the validity of the TSH test.If this proposed change in the reference range isaccepted into the mainstream, then more than fourtimes as many people as before will be classifiedas hypothyroid (20.0% versus 4.64% of the popu-lation),60 indicating the current TSH test may bemissing more than 75 percent of cases of hypothy-roidism. After having been promoted for years asa nearly perfect test for thyroid function, the ac-knowledgment that the TSH test may be misdiag-nosing so many patients is not encouraging. To besure, lowering the upper limit of normal wouldincrease the sensitivity of the test. On the otherhand, it would likely decrease its specificity, too,resulting in some euthyroid patients incorrectlybeing classified as hypothyroid. Furthermore, doc-tors who relied solely on the new TSH referencerange would continue to overlook many cases ofhypothyroidism. In this author’s experience, asmany as half of clinically hypothyroid patientshave a TSH level below 3.04 mU/L.

Why the Preference for ArmourThyroid?

The reason Armour thyroid is the pre-ferred preparation for thyroid-replacement therapyis simple: as Barnes pointed out it sometimesachieves better results for a wider range of symp-toms than levothyroxine. Most patients who tryboth preparations find them to be equally effec-tive. Of those who can tell a difference betweenthe two, probably five or more patients preferArmour thyroid for every one that preferslevothyroxine. In many cases, the therapeutic ad-vantage of Armour thyroid is pronounced.

For example, one woman rated her energylevel a 2 on a scale of 10 while takinglevothyroxine. Within a few days after switchingto an equivalent dose of Armour thyroid her en-ergy level improved to 9 and remained at that levelthereafter. As is the case with many other patients,this woman had taken Armour thyroid in the dis-tant past. When her doctor retired, she was in-formed by her new physician that desiccated thy-roid is obsolete, and she was switched tolevothyroxine. Although this change was followedby an obvious deterioration in her health, she wasunable to find a doctor who would switch her back.After having resigned herself to a lesser state ofhealth, she was pleasantly surprised when the is-sue of Armour thyroid was raised during a visit tothe author’s clinic.

Levothyroxine consists solely of T4,whereas desiccated thyroid contains approxi-mately 80 percent T4 and 20 percent T3, as wellas other iodinated compounds (diiodotyrosine andmonoiodotyrosine). Each compound present indesiccated thyroid is secreted by the human thy-roid gland, although the concentration of T3 inporcine thyroid tissue (from which Armour thy-roid is derived) is approximately twice that ofhuman thyroid secretions. While peripheral tissuesare capable of converting T4 to T3, the use of T4-only preparations might alter the normal ratio ofT4 to T3 in these tissues, especially in people whohave variants in one of the deiodinase genes or inthe beta-3-adrenergic-receptor gene.




In a study of thyroidectomized rats treatedwith levothyroxine alone, no single dose was ableto restore normal concentrations of TSH, T4, andT3 in plasma and normalize T4 and T3 levels inall 10 tissues and organs analyzed.61 In most tis-sues, the dose of levothyroxine necessary to pro-duce normal T3 levels resulted insupraphysiological T4 concentrations. Only thecombined administration of levothyroxine and T3(in proportions similar to those secreted by thenormal rat thyroid) completely normalized all val-ues in both plasma and tissues.62

It was observed in humans as early as1958 that the combination of levothyroxine andT3 is more effective for some patients thanlevothyroxine alone.63 In a more recent crossoverstudy of 33 hypothyroid patients, substitution of50 mcg of the usual dose of levothyroxine with anequivalent amount of T3 (12.5 mcg) significantlyimproved measures of mood and cognitive func-tion, compared to treatment with levothyroxinealone.64 While three other studies have failed todemonstrate any advantage of the levothyroxine/T3 combination over levothyroxine alone,65-67 theresults of those studies do not negate the possibil-ity that combination therapy is preferable for asubset of the hypothyroid population. Some pa-tients in these negative studies (those with weakdeiodination mechanisms) may have felt betterwith combination therapy, while others (those withrobust deiodination mechanisms) may have feltworse while receiving additional T3. That possi-bility is consistent with this author’s observationthat occasional patients feel worse on desiccatedthyroid than on levothyroxine. If that is the case,then averaging the results of those who improvedand those who became worse would lead to theerroneous conclusion that combination therapy isof no benefit. Measuring the ratio of free T4 tofree T3 in serum might aid the clinician in choos-ing the best treatment for each particular patient;however, that approach has not been systemati-cally investigated.

Diiodotyrosine: The Third ThyroidHormone?

While the issue of levothyroxine-plus-T3versus levothyroxine-alone is far from settled,there may be advantages to using desiccated thy-roid unrelated to its T3 content. Barnes observedsome patients treated with the combination oflevothyroxine and T3 continued to experience re-sidual symptoms, particularly dry skin and edema.Both symptoms disappeared in 1-2 months whenthe treatment was changed to Armour thyroid.68

That observation suggests a third active substanceis secreted by the thyroid gland. The most likelycandidate is diiodotyrosine. Although little isknown about the function of this compound inhumans, the widely held assumption that it is meta-bolically inert may be incorrect. In a study ofguinea pigs, oral administration of diiodotyrosineprevented alterations in thyroid and pituitary func-tion induced by ovariectomy.69 Administration ofdiiodotyrosine also accelerated the metamorpho-sis of tadpoles70 and enhanced the growth of Tet-rahymena (a protozoan).71 It would be prematureto conclude diiodotyrosine has no function in hu-mans, merely because its function has not yet beenelucidated. For many decades it was believed theadrenal hormone dehydroepiandrosterone(DHEA) had no function; now it is recognized ashaving a wide range of therapeutic applications.72

Objections to the Use of ArmourThyroid

The main objections voiced in textbooksand editorials1,73 regarding the use of desiccatedthyroid are: (1) its potency varies from batch tobatch, and (2) the use of T3-containing prepara-tions causes the serum T3 concentration to rise tosupraphysiological levels. Regarding between-batch variability, there may have been some prob-lems with quality control a half-century or moreago, and in a 1980 study a number of generic ver-sions of desiccated thyroid were still found to beunreliable in their potency. The amounts of T4 andT3 in Armour thyroid, on the other hand, werefound to be constant.74 Moreover, two-year oldtablets of Armour thyroid contained similaramounts of T4 and T3 as did fresh tablets.




Three studies are typically cited to sup-port the contention that T3-containing preparationsshould not be used. Smith et al reported alevothyroxine-plus-T3 product caused adverseside effects in 46 percent of patients; whereas, sideeffects occurred in only 10 percent of those re-ceiving levothyroxine alone.75 In that study, how-ever, the combination product and thelevothyroxine product differed substantially inpotency. For the combination treatment, each 100mcg of levothyroxine was replaced by 80 mcg oflevothyroxine plus 20 mcg of T3. Considering 20mcg of T3 is equivalent to 80 mcg oflevothyroxine, the total hormone dose in the com-bination product was 60-percent greater than thatin the levothyroxine preparation. Therefore, thehigh incidence of adverse side effects may not havebeen due to the T3, but to the higher total dose ofthyroid hormones.

In the second study, by Surks et al, theadministration of T3-containing preparations tohypothyroid patients caused the plasma T3 con-centration to become markedly elevated for sev-eral hours after ingestion of the medication.76 Inmost cases, however, the amount of T3 adminis-tered (50-75 mcg) was considerably greater thanthat contained in a typical dose of desiccated thy-roid (9 mcg T3 per 60 mg),77 and/or the total doseof thyroid hormones given was excessive (180mcg of levothyroxine plus 45 mcg of T3). By con-trast, in a patient given 60 mg of desiccated thy-roid, the plasma T3 concentration increased froma hypothyroid level to a euthyroid level. Of twohypothyroid patients treated with 120 mg per dayof desiccated thyroid, one showed a relativelyconstant plasma concentration of T3. In the otherpatient, the T3 level increased by a maximum of80 percent, to the bottom of the range seen in hy-perthyroid patients, and returned to the baselinevalue within 24 hours. In that patient, the pre-doseplasma T3 concentration was near the top of thenormal range, suggesting that this patient mayhave been receiving too high a dose of desiccatedthyroid.

Finally, Jackson and Cobb reported thatthe serum T3 concentration (measured 2-5 hoursafter a dose) was above normal in most patientsreceiving desiccated thyroid.2 They concluded

there is little use for desiccated thyroid in clinicalmedicine. Most of the patients (87.5%) in thatstudy, however, were taking a relatively large doseof desiccated thyroid (120-180 mg daily). More-over, 57.5 percent of the patients were not beingtreated for hypothyroidism, but rather to suppressthe thyroid gland. Nearly half of the patients con-tinued to have an elevated serum T3 concentra-tion after they were switched to levothyroxine,even though the equivalent dose was reduced in62.5 percent of patients. Thus, the elevated serumT3 concentrations found in this study can be ex-plained in large part by the high doses used andby the selection of patients, the majority of whomwere not hypothyroid. What this study does sug-gest is that desiccated thyroid should not be usedfor thyroid-suppression therapy.

Although the oral administration of T3causes a transient increase in serum T3 concen-trations, that fact does not appear to be of signifi-cance for hypothyroid patients receiving usualreplacement doses of Armour thyroid. In thisauthor’s experience, reports of post-dose symp-toms of hyperthyroidism are extremely rare, evenamong patients taking larger doses of desiccatedthyroid. An occasional patient reports feeling bet-ter when he or she takes Armour thyroid in twodivided doses daily. The nature of that improve-ment, however, is usually an increase in effective-ness, rather than a reduction in side effects. Forpatients taking relatively large amounts of desic-cated thyroid (such as 120 mg daily or more), split-ting the daily dose would obviate any potentialconcern about transient elevations of T3 levels.In practice, however, splitting the daily dose israrely necessary.

A Clinical Approach to Sub-laboratory HypothyroidismDiagnosis

The decision to initiate a trial of thyroidhormone in a patient with normal laboratory testsis based on the clinical history, physical examina-tion, and basal body temperature. Many symptomsof hypothyroidism are nonspecific and overlapconsiderably with those of reactive hypoglycemia,food allergy, hypoadrenalism, Candida-related




complex, iron deficiency, depression, and anxi-ety. In the typical patient complaining of fatigueor depression, the presence of additional symp-toms such as cold extremities, dry skin, hair loss,decreased mental concentration, poor memory,constipation, or menstrual irregularities increasesthe index of suspicion for hypothyroidism. Manypatients do not volunteer these symptoms; indeed,some are not even aware they have them. For thisreason, patients should be carefully questionedabout the various symptoms associated with hy-pothyroidism. One patient, for example, deniedhaving fatigue, dry skin, and constipation. Fur-ther questioning revealed that she slept 10 hoursper night to avoid suffering from fatigue, put skincream on her legs every day to control dryness,and consumed bran and other high-fiber foods toprevent constipation.

Additional questioning might help distin-guish hypothyroidism from other conditions. Fa-tigue caused by hypothyroidism is often, althoughnot always, most pronounced in the morning. Fa-tigue or poor concentration caused by food allergyis frequently relieved by fasting and may becomeworse after meals. Fatigue caused by hypoadren-alism may be accompanied by hypotension, hy-poglycemia, and poor tolerance to stress and ex-ercise. The combination of fatigue, hair loss, emo-tional lability, poor mental concentration, and coldextremities may be caused by iron deficiency.Patients experiencing those symptoms should beasked about menstrual blood loss, use of non-ste-roidal anti-inflammatory drugs (which can causegastrointestinal bleeding), dietary iron intake, andconsumption of foods and beverages that inhibitiron absorption (such as coffee, tea, and soy);blood tests for iron status should also be consid-ered. A family history of hypothyroidism increasesthe likelihood that a patient is hypothyroid.

On physical examination, hypothyroidpatients often have a general appearance of pal-lor, with dry, coarse skin, particularly on the lowerlegs. A small amount of non-pitting edema is fre-quently present around the ankles or below theeyes. Follicular hyperkeratosis may be observed,particularly on the posterior aspect of the upperarms or the lateral portion of the thighs. A slight

orange tinge to the skin (carotenodermia), espe-cially on the palms of the hands and soles of thefeet, may be apparent. If carotenodermia is notassociated with excessive intake of carrots, otherorange or yellow vegetables, or beta-carotenesupplements, then hypothyroidism should be con-sidered. In this author’s experience, a delayed ATRreturn is the most reliable physical sign of hypothy-roidism, and other investigators have made thesame observation.78 While a slow ATR return isstrongly suggestive of hypothyroidism, a normalreflex does not necessarily rule it out. A delayedATR return on one side but not the other may in-dicate a radiculopathy, rather than hypothyroid-ism. An absent ATR provides no information aboutthyroid status.

Patients with suspected hypothyroidismare usually asked to take their basal axillary tem-perature, which provides a crude estimate of basalmetabolic rate. The test is performed by placing athermometer deep in the axilla for 10 minutes,immediately upon awakening in the morning, be-fore getting out of bed. Women should begin tak-ing their temperature on the second day of men-struation, which is the time of the cycle that thetemperature is the lowest. Typically the tempera-ture is taken for five consecutive days and the re-sults averaged. If the temperature is consistentlybelow 97.0 degrees F, then taking it for three daysis sufficient. The underarm temperature is pre-ferred because taking it orally has a greater po-tential for error (due to chronic sinusitis or “mouthbreathing”). Barnes recommended a trial of thy-roid hormone if the average axillary temperatureis below 97.8 degrees F. This author uses a lowercut-off point (97.4 degrees F) and views body tem-perature as only one data point in the context ofthe entire clinical picture. For example, some pa-tients are prescribed thyroid hormone on the ba-sis of symptoms and a delayed ATR return, eventhough their temperature is normal. In other casesthe use of thyroid hormone is not considered ap-propriate, even though body temperature is belownormal.




TreatmentIn most cases, the initial daily dose of

Armour thyroid is 30 mg (one-half grain) (equiva-lent to 50 mcg levothyroxine) in the morning. Thepatient is instructed to increase to 60 mg (1 grain)in the morning if, after 10 days on the lower dose,no marked improvement and no side effects haveoccurred. Further increases in the dose may beconsidered at six-week intervals. Patients with ahistory of sensitivity to medications, and thosewho are neurasthenic or have clinical evidence ofhypoadrenalism, are often started on 15 mg (one-fourth grain) daily, increasing stepwise over a pe-riod of 4-6 weeks to a maximum of 60 mg daily,depending on response and tolerance. Patients areadvised to watch for side effects, including anxi-ety, nervousness, insomnia, palpitations, rapidpulse, and pain or tightness in the chest. If any ofthese symptoms occur without some other obvi-ous explanation (such as drinking too much cof-fee or experiencing a major stressful event), thedose should be reduced or the treatment stopped,and the practitioner should be contacted. Patientsshould be advised that side effects sometimes oc-cur only on the day the treatment is started, or onthe day the dose is increased. If adverse effectsthat appear on the first day are tolerable, then thepatient may continue treatment to see if they di-minish or disappear. If side effects do not decreaseon the second day, or if they become more severe,then the dose should be reduced or the treatmentstopped. It is not uncommon for side effects toappear gradually, so patients should be cautionedto remain vigilant.

A follow-up visit is scheduledapproximately six weeks after the start oftreatment. At that time changes in symptoms, pulserate, blood pressure, appearance of the skin, andATR return (if initially delayed) are assessed. Ifadequate symptom relief has been obtained withno adverse side effects, then the patient continueson the same dose and is reassessed at progressivelyincreasing intervals (three months, six months, andannually thereafter). The dose should be reduced,however, if untoward physical findings such astachycardia or a fine hand tremor are observed. ATSH level below the normal range, unless

markedly suppressed, would not necessarily leadto a reduction in the dosage. If symptoms havenot been relieved sufficiently, then an increase inthe dose may be considered; however, this authortends not to increase the dose if a previouslydelayed ATR return has become normal, or if thepulse rate has increased by more than 10 beats perminute over the pretreatment rate. If there has beenno clear benefit after 6-8 weeks on the maximumdose considered safe, then treatment is usuallydiscontinued. Occasionally, however, patients takelonger than two months to respond to treatment,so the treatment period may be extended, ifdesired. In some cases, an initially favorableresponse diminishes after a month or two oftreatment. In most of these instances, an increasein the daily dose (typically by 30 mg) relieves thesymptoms that have recurred, and further increasesare usually unnecessary.

In the author’s practice, the final dailydose of Armour thyroid has been 15 mg or less inapproximately 10 percent of patients, 30 mg in20-25 percent of patients, 60 mg in about 40 per-cent of patients, 90 mg in 15-20 percent of pa-tients, and 120 mg or more in 10 percent of pa-tients. Some patients appear to need a slightlyhigher dose during the winter than during the restof the year.79 The doses used by this author aresomewhat lower than those used by Barnes andother proponents of the empirical use of thyroidhormone. This author uses a comprehensive ap-proach to patient care that often includes a bloodsugar-stabilizing diet, identification and avoidanceof allergenic foods, treatment of Candida albicanswhen indicated, and supplementation with vari-ous nutritional supplements. It is possible thatsome of these treatments help “unblock” thyroidreceptors, thereby allowing lower doses of thy-roid hormone to be effective. These interventionsare usually not begun at the same time as thyroid-replacement therapy, so as to avoid potential con-fusion about which treatment is working.

Most patients take the entire daily doseof desiccated thyroid in the morning. A few pa-tients, however, find they feel better (either greaterefficacy or prevention of side effects) if they takeone-half or two-thirds of the daily dose in themorning and the remainder in the afternoon or




evening. Patients taking 120 mg or more daily areencouraged to consider splitting the dose, in or-der to avoid receiving a large amount of T3 at onetime. Most patients taking larger doses, however,do not feel any different with once-a-day dosingthan with split dosing.

In patients in whom severe hypothyroid-ism and hypoadrenalism coexist, the administra-tion of thyroid hormone prior to correcting theadrenal insufficiency can trigger an “adrenal cri-sis.” In a proposed milder version of this scenario,the inability of a clinically hypothyroid patient totolerate even 15 mg desiccated thyroid daily sug-gests the possibility of subtle (sub-laboratory)hypoadrenalism. In such cases, thyroid hormoneis discontinued and the patient is invited to try anextract of licorice root (for example, 6-10 dropsof a 1:1 tincture twice daily). Licorice root(Glycyrrhiza glabra) delays the breakdown ofadrenal hormones by the liver and was consideredthe treatment of choice for adrenal failure prior tothe discovery of adrenal steroid hormones. In thisauthor’s experience, treatment with licorice rootmay either lead to a resolution of “hypothyroid”symptoms or (more commonly) allow for the re-sumption of low-dose thyroid hormone withoutthe previous side effects. It should be noted thatcorrecting hypothyroidism (when the treatment istolerated) may ameliorate hypoadrenalism80 and,conversely, correcting hypoadrenalism may ame-liorate hypothyroidism.81 Although the amount oflicorice used is not likely to raise blood pressureor cause potassium depletion, patients taking lico-rice are advised to have their blood pressure moni-tored and to consume abundant amounts of potas-sium in their diet.

Discontinuing TherapyMost patients with sub-laboratory

hypothyroidism who have responded to treatmentare urged to try weaning themselves from thyroidhormone after approximately 18 months oftreatment. In one-half to two-thirds of patients,symptoms do not return when the treatment isstopped. In the other cases, symptoms recur assoon as the first day the dose is reduced to as longas several months after the treatment is stopped.

If symptoms do recur, then the treatment isresumed for at least another 18 months. Becauseit can take four weeks or more for the thyroid glandto compensate for the loss of exogenoushormone,82 the weaning process is usually doneover a four-week period: half the usual dose fortwo weeks, then one-fourth the usual dose for twoweeks, then discontinue. In contrast to adrenalsuppression that results from long-termglucocorticoid therapy, neither severe nor long-term suppression of thyroid-gland function occurs,even after treatment with thyroid hormone formany years.

Side Effects, Precautions, andInteractions

In addition to the common side effectsdescribed previously, treatment with thyroid hor-mone can trigger atrial fibrillation, particularly inthe elderly and in people with heart disease. Forthis reason, an attempt should be made to use thelowest effective dose. Although treatment withthyroid hormone can increase the pulse rate, pre-existing tachycardia is not necessarily a contrain-dication to the use of thyroid hormone. In severalpatients with tachycardia (100-110 beats perminute) treatment with thyroid hormone was as-sociated with a reduction in the pulse rate by 20-30 beats per minute. The need for thyroid hormonetends to decrease as people age; therefore, thedosage requirement should be re-evaluated peri-odically, particularly in the elderly. Thyroid hor-mone should not be discontinued during pregnancysince doing so may increase the risk of spontane-ous abortion.83 If anything, the requirement forthyroid hormone increases during pregnancy.84

While the use of excessive doses ofthyroid hormone may promote the developmentof osteoporosis, treatment of hypothyroid patientswith physiological doses of thyroid hormone doesnot appear to lead to accelerated osteoporosis orto an increased risk of fractures.85 The effect oftreating sub-laboratory hypothyroidism on bonedensity has not been investigated, however.Therefore, to be cautious, patients undergoinglong-term treatment with thyroid hormone arestrongly encouraged to supplement with




micronutrients that play a role in preserving bonedensity (e.g., calcium, magnesium, trace minerals,B vitamins, vitamin D, and vitamin K).85

Patients receiving DHEA will, on occa-sion, require a reduction in the dosage of thyroidhormone, possibly because of a potentiating ef-fect of DHEA on the action of thyroid hormone,as has been reported in rats.86 Patients receivingboth hormones should, therefore, be monitoredclosely.

ConclusionHypothyroidism appears to be consider-

ably more prevalent than is generally appreciatedin the medical community. Reliance solely on theconventional diagnostic approach will overlookmany people who could benefit from thyroid-re-placement therapy. A careful history and physicalexamination, combined with the results of a basalbody temperature test, can be used successfullyto identify potential candidates for treatment. Insome cases, desiccated thyroid produces betterclinical results than levothyroxine. While thyroidhormone is generally well tolerated, it has the po-tential to cause significant side effects and should,therefore, be used with caution and respect. Prop-erly administered, thyroid hormone can benefitmillions of people for whom a diagnosis of hy-pothyroidism is currently not being considered.

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“Sub-laboratory” Hypothyroidism and the Empirical use of ... Hypothyroidism .pdf · treatment with desiccated thyroid has produced better clinical results than levothyroxine