What is hypothyroidism?Hypothyroidism (underactivity of the thyroid gland)occurs when the thyroid gland produces less than thenormal amount of thyroid hormone. The result is theslowing down of many bodily functions. Although hypothyroidismmay be temporary, it usually is a permanentcondition. Of the nearly 25 million people suffering froma thyroid condition, most have hypothyroidism.What are the features ofhypothyroidism?In its earliest stage, hypothyroidism may cause few symptoms,since the body has the ability to partially compensatefor a failing thyroid gland by increasing the stimulationto it, much like pressing down on the acceleratorwhen climbing a hill to keep the car going the same speed.As thyroid hormone production decreases and the bodysmetabolism slows, a variety of features may result. Pervasive fatigue Drowsiness Forgetfulness Difficulty with learning Dry, brittle hair and nails Dry, itchy skin Puffy face Constipation Sore muscles Weight gain and fluid retention Heavy and/or irregular menstrual flow Increased frequency of miscarriages Increased sensitivity to many medicationsWhat are the major causes ofhypothyroidism?AU TO IMMU N E THY RO I D I T I S(Hashimotos thyroiditisseparate brochure available)The bodys immune system may produce a reaction in thethyroid gland that results in hypothyroidism and, mostoften, a goiter (enlargement of the thyroid). Other autoimmunediseases may be associated with this disorder,and additional family members may also be affected.R A D I OA C T I V E I O D I N ET R E ATME N THypothyroidism frequently develops as a desired therapeuticgoal after the use of radioactive iodine treatmentfor hyperthyroidism.THY RO I D O P E R AT I O NHypothyroidism may be related to surgery on the thyroidgland, especially if most of the thyroid has been removed.ME D I C AT I O N SLithium, high doses of iodine, and amiodarone (Cordarone,Pacerone) can cause hypothyroidism.S U B A C U T E THY RO I D I T I SThis condition may follow a viral infection and is characterizedby painful thyroid gland enlargement and inflammation,which results in the release of large amounts ofthyroid hormone into the blood. Fortunately, this conditionusually resolves spontaneously. The thyroid usuallyheals itself over several months, but often not before atemporary period of hypothyroidism occurs.P O S T PA RT UM THY RO I D I T I SFive percent to ten percent of women develop mild tomoderate hyperthyroidism within several months of givingbirth. Hyperthyroidism in this condition usually lasts forapproximately one to two months. It is often followed byseveral months of hypothyroidism, but most women willeventually recover normal thyroid function. In some cases,however, the thyroid gland does not heal, so the hypothyroidismbecomes permanent and requires lifelong thyroidhormone replacement. This condition may occur againwith subsequent pregnancies.S I L E N T THY RO I D I T I STransient (temporary) hyperthyroidism can be caused bysilent thyroiditis, a condition which appears to be the sameas postpartum thyroiditis but not related to pregnancy. It isnot accompanied by a painful thyroid gland.CONGENITAL HYPOTHYROIDISMAn infant may be born with an inadequate amount ofthyroid tissue or an enzyme defect that does not allownormal thyroid hormone production. If this conditionis not treated promptly, physical stunting and/or mentaldamage (cretinism) may develop.P I T U I TA RYHY P OTHY RO I D I SMTSH is produced by the pituitary gland, which is locatedbehind the nose at the base of the brain. Any destructivedisease of the pituitary gland may cause damageto the cells that secrete Thyroid-Stimulating HormonehypothyroidismYOUR THYROIDA KEY TO GOOD HEALTHPowe r of P r e v e n t ion (TSH), which stimulates the thyroid to produce normalamounts of thyroid hormone. This is a very rare cause ofhypothyroidism.How is hypothyroidismdiagnosed?Characteristic symptoms and physical signs, which canbe detected by a physician, can signal hypothyroidism.However, the condition may develop so slowly that manypatients do not realize that their body has changed, so itis critically important to perform diagnostic laboratorytests to confirm the diagnosis and to determine the causeof hypothyroidism.T SH ( THY RO I D - S T IMU L AT I N GHO RMO N E O R THY ROT RO P I N )T E S TAn increased TSH level in the blood is the most accurateindicator of primary (nonpituitary) hypothyroidism.Production of this pituitary hormone is increasedwhen the thyroid gland even slightly underproducesthyroid hormone.OTHE R T E S T S Estimates of free thyroxine - the active thyroidhormone in the blood. It is important to note thatthere is a range of free thyroxine levels in the bloodof normal people, similar to the range for height,and that a value of free thyroxine that is withinnormal limits for the general population may notbe appropriate for a particular individual. Thyroid autoantibodies - indicates the likelihood ofauto-immune thyroiditis being the cause of hypothyroidism.A primary care physician may make the diagnosis ofhypothyroidism, but assistance is often needed from anendocrinologist, a physician who is a specialist in thyroiddiseases.How is hypothyroidismtreated?Hypothyroidism is generally treated with a single dailydose of levothyroxine, given as a tablet. An experiencedphysician can prescribe the correct form and dosage toreturn the thyroid balance to normal. Older patientswho may have underlying heart disease are usually startedat a low dose and gradually increased while youngerhealthy patients can be started on full replacement dosesat once. Thyroid hormone acts very slowly in some partsof the body, so it may take several months after treatmentfor some features to improve.Since most cases of hypothyroidism are permanent andoften progressive, it is usually necessary to treat this conditionthroughout ones lifetime. Periodic monitoring ofTSH levels and clinical status are necessary to ensure thatthe proper dose is being given, since medication dosesmay have to be adjusted from time to time. Optimaladjustment of thyroid hormone dosage is critical, sincethe body is very sensitive to even small changes in thyroidhormone levels. Levothyroxine tablets come in 12different strengths, and it is essential to take them in aconsistent manner every day. A dose of thyroid hormonethat is too low may fail to prevent enlargement of the thyroidgland, allow symptoms of hypothyroidism to persist,and be associated with increased serum cholesterol levels,which may increase the risk for atherosclerosis and heartdisease. A dose that is too high can cause symptoms ofhyperthyroidism, create excessive strain on the heart, andlead to an increased risk of developing osteoporosis.It is extremely important that women planning to becomepregnant are kept well adjusted, since hypothyroidismcan affect the development of the baby. During pregnancy,thyroid hormone replacement requirements oftenchange, so more frequent monitoring is necessary. Variousmedications and supplements (particularly iron) mayaffect the absorption of thyroid hormone; therefore, thelevels may need more frequent monitoring during illnessor change in medication.Thyroid hormone is critical for normal brain developmentin babies. Infants requiring thyroid hormonetherapy should NOT be treated with purchased liquidsuspensions, since the active hormone may deteriorateonce dissolved and the baby could receive less thyroidhormone than necessary. Instead, infants with hypothyroidismshould receive their thyroid hormone by crushinga single tablet daily of the correct dose and suspending itin one teaspoon of liquid and administering it properly.Appropriate management of hypothyroidism requirescontinued care by a physician experienced in the treatmentof this condition.

Supplement to The Journal of Family Practice June 2006 S1Thyroid dysfunction is the one of the most commonlyencountered endocrine abnormalities in primary care,with mild hypothyroidism occurring in about 4% to10% of the US population and in up to 18% of those overage 60; for women in this age group, the prevalence ofhypothyroidism may be as high as 20%.1,2 Primary hypothyroidismis a graded disorder, with a wide spectrum of severitybetween mild and overt disease.3 Because hypothyroidismis associated with several other comorbid disorders andmany vague symptoms, the diagnostic workup may includescreening tools for a variety of other diseases, such as depressionand anxiety, to rule these out as a primary diagnosis.Although hypothyroidism has significant clinical consequences,it is also readily treatable. As in diagnosis, nuancesin treatment can present important clinical challenges.This supplement focuses on the clinical consequencesand diagnosis of hypothyroidism, including identification ofspecial populations. It also discusses management ofhypothyroidism and use of thyroid hormone replacementtherapy, particularly levothyroxine (synthetic T4) (Levo-T,Levolet, Levothroid, Levoxyl, Novothyrox, Synthroid,Practice recommendationsClinical UpdateCopyright 2006 Dowden Health Media andthe Primary Care Education Consortiumwww.jfponline.comJune 2006 Hypothyroidism is a commonly encountered endocrinedisorder with serious clinical consequences, but it is readilytreatable. (SOR: A) Screening of thyroid function is clearly indicated in personswith signs/symptoms of hypothyroidism. Other possiblegroups include those with subclinical hypothyroidism,diabetes mellitus, previous thyroid surgery or neck irradiation,the elderly, and others. (SOR: C) Underdosing thyroid replacement puts patients at risk forclinical sequelae of continued hypothyroidism, such ashypercholesterolemia or depression. (SOR: A) Ovedosing thyroid replacement puts patients at risk forclinical sequelae of hyperthyroidism, such as osteoporosis oratrial fibrillation. (SOR: A) Although the FDA has recognized bioequivalent levothyroxineproducts, the current standards potentially allow forsignificant differences in the bioavailability of products ratedas bioequivalent. (SOR: B)Managing the Challengesof HypothyroidismJeffrey R. Garber, MD, FACE James V. Hennessey, MD, FACP Joseph A. Lieberman III, MD, MPHCharlene M. Morris, PA-C, MPAS Robert L. Talbert, PharmDDisclosures: Dr Garber reports that he is a consultant to KingPharmaceuticals and Abbott Laboratories. Dr Hennesseyreports that he has received grant or research support fromNovartis and Abbott Laboratories, serves as a consultant toAbbott Laboratories, and participates on the speakers bureaufor Aventis. Dr Lieberman reports that he serves as a consultantto Abbott Laboratories, Ortho McNeil, Pfizer Inc, Sanofi,and Takeda, and that he serves on the speakers bureau forTakeda. Ms Morris reports that she is a consultant to AbbottLaboratories and is on the speakers bureau for Eli Lilly andBoehringer Ingelheim. Dr Talbert reports that he serves as aconsultant to Abbott Laboratories.Jeffrey R. Garber, MD, FACEChief of EndocrinologyHarvard Vanguard Medical AssociatesBoston, MAJames V. Hennessey, MD, FACPAssociate Professor of MedicineBrown University School of MedicineAssociate Physician, Rhode Island HospitalHallet Center for Diabetes and EndocrinologyThe CORO Center, Providence, RIJoseph A. Lieberman III, MD, MPHProfessor of Family MedicineJefferson Medical CollegePhiladelphia, PACharlene M. Morris, PA-C, MPASStaff Physician AssistantHalyburton HospitalCherry Point, NCRobert L. Talbert, PharmDProfessor of Pharmacy Medicine andPharmacologyUniversity of Texas Health Science CenterSan Antonio, TXThis supplement to THE JOURNAL OF FAMILY PRACTICE is supportedby a grant from Abbott Laboratories. It was developed by thePrimary Care Education Consortium and the Texas Academyof Family Physicians and has been edited and peer-reviewed byTHE JOURNAL OF FAMILY PRACTICE.FAMILYPRACTICETHE JOURNAL OFSupplement toS2 June 2006 Supplement to The Journal of Family PracticeUnithroid, and generics) and briefly addresses hyperthyroidismresulting from overtreatment of hypothyroidism.Central hypothyroidism, caused by pituitary-based deficienciesof thyrotropin-stimulating hormone or thyrotropinreleasinghormone, will not be discussed.BACKGROUNDThe pituitary hormone thyrotropin (thyroid-stimulatinghormone [TSH]) is responsible for maintaining normalthyroid morphology and for providing the primary stimulusfor synthesis and secretion of the thyroid hormonesthyroxine (T4) and triiodothyronine (T3).4 An inverserelationship exists between TSH levels and circulating T4and T3, where high TSH levels typically indicatehypothyroidism and too little thyroid secretion. Thyroidhormone has many critical roles for both homeostasis andgrowth and development; therefore, an imbalance of thyroidhormone may severely impact patient functioning.The most common cause of permanent hypothyroidismin North America is a chronic autoimmunecondition, Hashimotos thyroiditis.5 High titers ofantithyroid peroxidase autoantibodies may be present inup to 95% of those with Hashimotos thyroiditis and arehelpful in diagnosis.6 Other permanent causes ofhypothyroidism include thyroidectomy, radioactiveiodine therapy, head or neck irradiation, and congenitaldefects. Hypothyroidism may temporarily arise from aninflammation of the thyroid gland, from some medications,or from too much or too little iodine.6SCREENINGScreening in asymptomatic patients is controversial evenamong expert groups (TABLE 1). The American Academy ofFamily Physicians recommends routine screening for personsbeginning at age 60 years, while some groups recommendbeginning screening at an earlier age. Thyroid functiontests are clearly indicated for patients who have signsand symptoms indicative of hypothyroidism and are alsoappropriate for those with subclinical hypothyroidism,since they are at increased risk for progression to overthypothyroidism; patients with diabetes, previous thyroidsurgery or neck radiation, premature gray hair, or perniciousanemia; and the elderly, especially women and thosewith dementia. Women in the second trimester of pregnancyshould be screened for antimicrosomal antibodies sinceat least 5% of women develop postpartum thyroiditis, 25%of whom develop chronic hypothyroidism requiring lifelongtherapy.7 Additionally, any patient with an unexplainedlaboratory abnormality (eg, hypercholesterolemia, hyponatremia,anemia, hypercalcemia, elevated creatine phosphokinase)likely warrants a serum TSH test. The incrementalcost of adding a TSH determination to quintennial cholesterolscreening starting at age 35 years has been estimatedto be $9200 per quality-adjusted life year for women and$22,600 for men; these figures are comparable to those forscreening for breast cancer and hypertension.7Routine thyroid function screening is not recommendedfor patients who are hospitalized with acute illness but haveno evidence of thyroid dysfunction, since these patients havea high frequency of transient thyroid function abnormalities.7DIAGNOSISSigns and symptoms. The presentation and clinicalmanifestation of hypothyroidism vary widely. Classic clinicalsigns of hypothyroidism are often subtle and insidious inonset and include fatigue, cold skin, and a general slowingof activity5 (TABLE 2). In addition, comorbid disorders orserum abnormalities are often present and may make accuratediagnosis more difficult. One of the most common ishypercholesterolemia, but others include carpal tunnel-likesymptoms of tingling in the hands, menstrual changes,infertility, or arthritis-like aches in and around the joints.6Patients with subclinical hypothyroidism may be asymptomaticor have nonspecific signs and symptoms such asManaging the Challenges of HypothyroidismProfessional association Summary of TSH screening recommendationAmerican Thyroid Association Age 35 years and every 5 years thereafter (2000)American Association of Clinical Endocrinologists Older, especially women (2002), pregnancy (1999)American College of Physicians Women >50 years with 1 or more symptomspossibly caused by thyroid disease (1998)US Preventive Services Task Force Insufficient evidence for or against adultroutine screeningAmerican Academy of Family Physicians Routine screening for patients >60 years (2002)Recommendations for thyroid testing among professional organizationsTABLE 1Supplement to The Journal of Family Practice June 2006 S3FAMILYPRACTICETHE JOURNAL OFdepression, cognitive dysfunction, and weight gain. Use ofavailable screening tools for depression and anxiety mayhelp narrow the diagnosis or identify other underlying causesof the symptoms. Other symptoms may also includeabnormalities in cardiac, gastrointestinal, or reproductivefunction.5,8 The effects of subclinical disease on the cardiovascularsystem and mental health and its impact during pregnancyare less established than for overt hypothyroidism.Thyroid physical exam. The normal isthmus is severalmillimeters thick, with a felt-like consistency. Extendingfrom the isthmus upward and either left or right of midline,a pyramidal lobe may be palpable in the presence of generalizedthyroid enlargement as seen in Hashimotos thyroiditisor Graves disease and may be mistaken for an isthmusnodule or a pretracheal, delphian lymph node.The physician should examine the patients thyroidlobes for size, texture, consistency, and the presence ofnodules or tenderness. The right lobe may be somewhatlarger than the left, and each is expected to be about 4 to5 cm long and 2 to 3 cm wide, approximately the size ofthe distal phalanx of the patients thumb. The volume ofthe thyroid gland varies directly with body size, gender,and, to a lesser degree, age.The consistency of normal thyroid tissue is described asrubbery. A spectrum of increasing firmness of thyroid tissuehas been described, ranging from the softness associatedwith Graves disease to the firmness of colloid goiter andearly Hashimotos thyroiditis.The physician should note the size, location, and consistencyof nodular lesions palpated in the course of the thyroidexam. When an apparent solitary nodule is palpated,multiple occult nodules are likely to be present in about halfof patients. Only about 6% of nodules 2 cm are reliablydetected by experienced examiners. Pain in the thyroidmay indicate the presence of thyroiditis.TSH values. An appropriate laboratory evaluation is criticalto establish the diagnosis and etiology of hypothyroidism,and to do so most cost-effectively.5 The sensitiveTSH assay has become the single best screening test forhypothyroidism (and hyperthyroidism),5 but establishmentof a single TSH reference range to diagnose and monitorthyroid disease continues to be controversial. In theNHANES III study, serum TSH levels fell in the range of0.45 to 4.12 mU/L,1 while The National Academy ofClinical Biochemistry proposed a normal TSH range of 0.4to 4.0 mU/L;9 other organizations propose 0.3 to 3.0 mU/L.Complicating matters, each laboratory may use a differentTSH reference range. For the purposes of this supplement,a normal TSH is considered to be 0.45 to 4.12 mU/L;although physicians should be aware that there is some flexibilityin interpretation.Other assays. Free-T4 level testing is important to determinethyroid gland function and, in conjunction with TSHtesting, the cause of the hypothyroidism. A high TSH leveland low free-T4 level indicate primary hypothyroidism,while a low TSH level and low free-T4 level indicate secondaryhypothyroidism. A high TSH level and normal free-T4level indicate subclinical hypothyroidism.6 Free-T3 level testingis not useful in diagnosing hypothyroidism.Measurement of antithyroid antibodies is useful fordetermining if the etiology of primary hypothyroidism is anFatigueSlow speechDepressionWeight gainDry skin, yellow skinCold intoleranceHair loss or coarse hairHoarse voiceConstipationFluid retentionDecreased concentration, forgetfulness,and other evidence of intellectual impairmentFacial puffinessMacroglossiaReflex delay in the relaxation phaseAtaxiaIrregular or heavy menses and infertilityMyalgiasHyperlipidemiaBradycardia and hypothermiaMyxedema or nonpitting edemaAnemiaSigns and symptoms of hypothyroidismTABLE 2S4 June 2006 Supplement to The Journal of Family Practiceautoimmune disorder. Antithyroid peroxidase antibodiesare especially helpful in predicting progress from subclinicalto overt hypothyroidism10 and in screening for preclinicalhypothyroidism in children whose parents both haveautoimmune thyroid disease.11Referral. Although most primary care physicians can diagnoseand treat hypothyroidism, referral to an endocrinologistmay be warranted for children and adolescents, patientsunresponsive to therapy, pregnant or postpartum women,severly ill and cardiac patients, those taking amiodarone orphenytoin, patients with sodium levels