appears less often is the recessive gene.) Two different genes can exist for a trait. (Two genes that determine the same trait arecalled alleles.) Genes follow the principle of independent assortment: Plants inherit each trait separatelyfrom all other traits. When plants are crossed that have two different traits, such as height andtexture of the seed, these traits are passed to the offspring independently of one another. Forexample, a tall plant doesn’t always have a smooth seed or always have a wrinkled seed.Mendel’s work received little attention when he announced it in 1865, but scientists rediscoveredit in 1900. He got posthumous credit for his discoveries (for what that was worth).Talking the genetics talkUsing Mendel’s research, scientists later began to create the new language of genetics so that youand I couldn’t possibly understand what they were talking about. I’m going to test my interpretationskills here to walk you through the maze they’ve created.If a person (or a plant, dog, or chimpanzee) has two copies of the same allele, he or she is said tobe homozygous for that gene. If he or she has one of each allele, the person is heterozygous forthat gene. (We now know that, within an entire population, more than two different alleles canexist for each gene. However, any given person, animal, or plant has only two alleles for eachgene because a single individual has only two copies, while others in the population may have twodifferent copies.)The appearance of the trait controlled by a gene is called the phenotype, while the genes that makeup that phenotype are called the genotype. For instance, two tall pea plants may have the sameappearance (phenotype), while their genotype may be different. One plant may have only tall genesand is tall, while the other has a tall gene and a short gene and is still tall — because tallness isthe dominant gene.A quick quiz: Based on your in-depth knowledge of genetics, can two short pea plants havedifferent genotypes? The answer is no, because shortness is the recessive gene. If you throw atallness gene into the mix, the plant is tall. Therefore, all short pea plants must have only the genesfor shortness.Observing the great divideAt the same time that the world was ignoring Mendel’s work, great things were happening under
the microscope. Scientists were seeing that tissues are made up of cells and that new cells comefrom the division of old cells. As two new cells form, the old cell produces two copies ofeverything so that each new cell has exactly what the old cell had. Mitosis is the whole process bywhich one cell becomes two.One particular area of the cell, which looks like a cell within the cell, was especially intriguing toscientists. This area is called the nucleus of the cell. As two new cells are being formed, somesubstances in the nucleus double and separate so that each new cell gets a complete set of thesesubstances, called chromosomes.Over the years, scientists discovered that each plant and animal has a set of chromosomes, but thenumbers of chromosomes may differ between species. For instance, humans have 23 pairs, or 46,chromosomes, while chimpanzees have 24 pairs, or 48, chromosomes. (But chimpanzeechromosomes look more like human chromosomes than ape chromosomes, so don’t be thinking thatyou’re so smart.)Examining the division of egg cells and sperm cells (the so-called germ cells), scientistsdiscovered that each of these cells contains only half the normal number of chromosomes. Inhumans, for example, each egg cell and each sperm cell has one set of 23 chromosomes (whileother human cells have 46 chromosomes). When these cells divide to form more sperm or eggcells through a process called meiosis, the result is again 23 chromosomes per cell. When the eggand the sperm join together in fertilization, the combination, called a zygote, has the normalnumber of 46 (23 pairs) chromosomes.When a zygote forms, one set of its chromosomes comes from the female, and one set ofchromosomes comes from the male; these sets pair up two by two. The members of eachchromosome pair are called homologous chromosomes.As is always the case, the rule that all chromosome pairs have identical sets of genes has anexception. But like the French say, vive le difference. Loosely translated, that means “thankgoodness for this particular set of chromosomes.” I’m referring to the sex chromosomes thatdetermine whether you’re a boy or a girl. All other pairs of chromosomes have matched genes; if agene exists for a given characteristic on one of the chromosomes of the pair, the other chromosomehas a gene for that same characteristic. A female has two matched sex chromosomes (called Xchromosomes), and a male has two different sex chromosomes (called an X chromosome and a Ychromosome).Mapping traits with genes and chromosomes
Any given plant, animal, or human has far more traits than its number of chromosomes.Recognizing this fact, scientists realized that each chromosome must contain many genes.Each chromosome is passed down to its daughter cells — the cells created when a cell divides.Therefore, some genes (and the traits they create) get passed down together from generation togeneration. (They don’t follow the principle of independent assortment.) Genes on the samechromosome are linked.Even though some genes are linked, they sometimes do get inherited independently, just as Mendelpredicted, which happens because crossing over takes place. What is crossing over? During theprocess of meiosis, which produces sperm and egg cells, as the sets of chromosomes line up closetogether, genes on one chromosome can cross over to the other while their alleles cross over in theother direction. In this way, recombinant chromosomes are formed — new combinations that helpto make your offspring different from you.The discovery of crossing over meant that scientists could start to map chromosomes. That is,scientists could determine which genes are on which chromosomes and where, because the closertwo genes are, the less likely they’re separated by a cross-over. The farther genes are from oneanother, the more likely they are to separate.Another way that a new trait replaces an old one is when a mutation takes place. In a mutation, anew gene replaces as old one as a result of faulty copying of the chromosome or an outsideinfluence, such as radiation, chemicals, or the sun. Usually mutation isn’t noticed, either becausethe gene is recessive or because the mutation may kill the individual so that it isn’t reproduced.Once in a while, a mutation is good for the animal or plant in which it occurs, producing a usefultrait.Getting down to the DNAGenes consist of long, long, long chains of nucleic acids. Nucleic acids have three components: asugar called deoxyribose, a phosphate attached at one end of the sugar, and a base, which may beadenine, cytosine, guanine, or thymine, attached to the sugar at another point. The genes containdeoxyribonucleic acid, or DNA.Within the DNA, the number of adenine molecules is always equal to the number of thyminemolecules, while the amount of cytosine equals that of guanine. In 1952, biochemists James D.Watson and Francis H. C. Crick showed that this equality is because each gene contains twochains of nucleic acids. The adenine on one chain is always paired with the thymine on the other,
while cytosine on one chain is always paired with guanine on the other. Other researchers hadshown that DNA has a helical structure, so Watson and Crick called the structure a double helix— a shape that looks like a spiral staircase.One of the best outcomes of the identification of the double helix was that scientists understoodhow the genes copy themselves, or replicate. The helix can break apart into two strands. The twoindividual strands then each act as a template so that a new strand forms on each in the only way itcan, by connecting to the only nucleic acid it can combine with — namely, a nucleic acidcontaining adenine connects to a nucleic acid containing thymine, and a nucleic acid containingcytosine connects with a nucleic acid containing guanine. The result is two new double helixes.The DNA has to somehow control the creation of the animal or plant and the ongoing processesthat allow it to live. The DNA does so by producing ribonucleic acid, or RNA. RNA comprisesnucleic acids just like DNA. But the sugar in RNA is ribose, and the bases are adenine, cytosine,and guanine, with uricil replacing thymine.In the same way that the double helix can break apart to reproduce itself, it can break apart andconstruct a complementary RNA molecule. This process is called transcription. The RNAremains a single strand, not a double helix. The RNA is called messenger RNA because it carriesthe message from the DNA to the next level of control, the enzyme. An enzyme is a protein thatacts as a facilitator for a chemical reaction — for example, the breakdown of a complexcarbohydrate like glycogen (the storage form of glucose — the body’s source of immediateenergy) into small glucose molecules that the body can instantly use.The messenger RNA accomplishes its task by acting as a template in its turn for the production ofthe enzyme or protein in the process of translation. Proteins consist of amino acids. Every threebases in the messenger RNA, called a triplet, causes one particular amino acid to line up oppositethem. Each group of three is a codon, because it codes for a specific amino acid. By making upartificial messenger RNA that contained the same codon again and again, determining which aminoacid each codon selected became possible.With 4 different bases in sets of 3, the maximum number of codons is 64, but only 20 amino acidsexist. Different codons select the same amino acid, and some codons act as the code for the end ofa protein without selecting an amino acid.Just to complicate the issue a little further, the amino acids don’t actually line up opposite thecodons but are carried at one end of another RNA molecule, called transfer RNA. At its other end,transfer RNA has the bases that are complementary to the codon. So the transfer RNA lines upneatly against the messenger RNA, while the amino acids line up next to one another at the other
end. A series of other steps that you don’t need to know to understand hereditary thyroid diseasebind the amino acids into a protein that may be an enzyme or a muscle or whatever.Genes also contain large segments of bases that don’t code anything and, in fact, have to be cut outfrom their complementary RNA before the RNA can produce a protein. These sequences arecalled introns, and scientists don’t know what their function is.Determining whether to be a liver or a heartA fertilized egg reproduces itself by the process of mitosis, creating two identical cells. But howcan each identical cell transform itself into a thyroid cell or a liver cell or even a brain cell?The gene uses a number of techniques to turn gene action on and off. Short sequences of basescalled promoters precede the active gene. When various factors bind to a promoter, it turns on theaction of the gene to begin transcription. Other sequences of elements called enhancers increasethe activity of the gene further, while silencers tend to shut down the activity of the gene. Theprocess of transcription from DNA to messenger RNA comes to a halt when certain sequences ofbases are reached.Because all cells contain the same genetic information, a thyroid cell differs from a brain cell as aresult of the particular genes that are expressed (active) in each cell. Many different factorsdetermine whether a gene is expressed. Promoters and enhancers increase their activity inresponse to various hormones or growth factors that may be present in one cell but not another.The expression of a gene may be controlled at the level of the gene itself, or it may be controlledafter transcription has taken place so that the messenger RNA never makes the protein.In these and in many other ways scientists have yet to discover, cells use only the genes they needto function within their environment.Probing the Origins of Genetic ThyroidDiseasesNow that you have a basic understanding of genetics, you can apply your knowledge to thyroiddiseases that are transmitted through inheritance. A child inherits a thyroid disease in one of threebasic ways:
A single gene from a parent transmits a dominant or recessive trait to the child. Thismethod goes back to Mendel and his peas. The child inherits all of the many genes involved in the inheritance of a disease. An entire chromosome is abnormal. For example, if a female ends up with only one Xchromosome, that lack can produce a condition known as Turner’s syndrome, which oftenincludes a thyroid disorder.Inheriting a disease through a single genePeople inherit many diseases through a single gene, often as a result of a gene mutation, in one ofthree ways: As a recessive gene: Both parents must supply the same gene in order for the disease toappear. As a dominant gene: Only one parent supplies the gene necessary to cause the disease. With the X chromosome in a recessive form: A male gets the disease (because he hasonly one X chromosome), but a female is spared unless both her X chromosomes have thegene.You can find the entire list of diseases transmitted by single-gene inheritance atwww.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM, the homepage of Online MendelianInheritance in Man (OMIM), a huge database compiled by Dr. Victor McKusick at JohnsHopkins University and others. If you search the term “thyroid” from the homepage, 554different thyroid diseases appear (at the time of this writing). A full description accompanieseach one, with citations of all the research that has been done to define the defect and acomplete bibliography at the end of each description.Inherited thyroid diseases can affect every step in thyroid hormone production, transportation, andaction. The ones I list in the following sections are only 14 of the 554 currently listed in the OMIMdatabase. Scientists are discovering new conditions all the time. These 14 are the best understood.Recessive inheritanceMany conditions where the body doesn’t make thyroid hormone properly fall into the category ofrecessive inheritance. Two “bad” genes are necessary to develop one of these conditions. If youhave just one bad gene, you’re a carrier of the disease, but you don’t experience it yourself. Thephenotype (the way this gene makes itself known) is usually a large thyroid that doesn’t producesufficient thyroid hormone. Note that several of the conditions appear to be the same because thefinal result of the condition is absence of thyroid hormone, but each condition involves a defect in
a different step in the production of thyroid hormone. Among the conditions inherited this way arethe following: A defect in the creation of the enzyme that produces thyroid hormone: (see Chapter4): Patients with this condition are hypothyroid (see Chapter 5) and have goiters. Thyroid hormone unresponsiveness: If you inherit a bad gene instead of the gene thatmakes the receptor protein for thyroid hormone, your end organs aren’t responsive to thethyroid hormone your body produces. This condition causes patients to be deaf and havegoiters. With this condition, the T3, T4, and TSH levels are all elevated (see Chapter 4). Pendred syndrome: Patients with this disease are deaf and have goiters, but their thyroidfunction is normal. The disease also causes mental retardation and an increased tendency todevelop thyroid cancer. The defect is in the production of thyroid hormone, but at some pointit improves so that hypothyroidism isn’t present later on. Thyroid transcription–factor defect: Patients have goiters and decreased levels ofthyroglobulin. If you remember that transcription is the term for the production of messengerRNA from DNA, you understand that this defect arises from a failure to produce the enzymenecessary to make thyroid hormone. Defect in thyroid production: This disease is different from thyroid transcription–factordefect. Patients are hypothyroid, have goiters, and experience mental retardation. Lab testsshow a defect in the formation of thyroid hormone. Normally, two molecules of tyrosine withiodine attached couple to form thyroid hormone, but this process fails in this particularinherited condition.Dominant inheritanceMany inherited thyroid conditions pass from parents to children through dominant inheritance: One“bad” gene produces the disease. These diseases tend to be more common than those inherited byrecessive genes. Examples of diseases inherited this way are as follows: Thyroid hormone–receptor defects: A number of receptor defects are possible. Withone of these conditions, your body is resistant to the action of thyroid hormones. At the sametime, you experience mild hyperthyroidism. Patients with this condition have short stature,learning disabilities, deafness, and goiters. Lab tests show high levels of T3, T4, and TSH.These conditions are rare, resulting from a mutation in the gene responsible for the thyroidreceptor. Another type of receptor defect produces a child with severe cretinism of theneurologic form (see Chapter 12). Papillary thyroid carcinoma (see Chapter 8). This type of cancer usually occurs at anearlier age than thyroid cancer that’s not inherited. Thyroid hormone resistance (also found in a recessive form). Patients with this
condition have a goiter and begin to speak at a later than expected age but have normalthyroid function. Lab tests show that T3 and T4 levels are high, but the TSH level is normal. Multiple endocrine neoplasia, type II: This condition causes tumors on multiple organs,including the thyroid (see Chapter 8), the adrenal gland, and the parathyroid glands. Lab testsshow increased levels of epinephrine and calcitonin in the blood. Medullary carcinoma of the thyroid, familial: Patients with this condition havemedullary cancer (see Chapter 8).X-linked inheritanceX-linked inheritance presents fewer examples of thyroid disease because men have only one Xchromosome, and women have two, compared to 44 other chromosomes that can produce adisease by recessive or dominant inheritance. If a disease passed on by the X chromosome isrecessive, both parents must give the gene to a daughter in order for the disease to appear. But ason gets the disease if only one parent passes along the gene. Because Y chromosomes are onlypresent in males, Y-linked inheritance is only found in males, and it’s rare because the Ychromosome is so small. Some examples of diseases inherited this way include Immunodeficiency and polyendocrinopathy: A baby with this condition hasunmanageable diarrhea, diabetes, and thyroid autoimmune disease and usually dies veryyoung. Thyroid-binding globulin abnormality: This condition produces retardation. Lab testsshow that patients with this disease have decreased thyroid-binding globulin (see Chapter 3). Multinodular goiter: The thyroid is larger than normal and multinodular (see Chapter 9).Inheriting a disease through multiple genesThe major thyroid disease inherited as a result of abnormalities of multiple genes is autoimmunethyroiditis. This disease is much more common in women than in men, so you may assume that theinheritance is linked to the X chromosome somehow. But if this is the case, scientists don’t knowthe method by which the X chromosome passes the disease along. One idea is that the female sexhormone influences the occurrence of this disease, but scientists don’t understand just how thismay happen.Autoimmune thyroiditis is easy to diagnose because lab tests show that a person hasautoantibodies (see Chapter 5) that damage the thyroid. Many genes are involved in the productionof autoantibodies. The substance (such as thyroid tissue) that provokes antibodies is called an
antigen. The antigen is broken into small pieces that proteins called major histocompatibilitymolecules bind to cells. This combination of cells and antigens leads to the activation of anothercell called the T cell. The T cell helps yet another cell, the B cell, recognize the antigen andproduce antibodies against it. All these steps involve multiple genes.The major histocompatibility region of the chromosomes is on the short arm of chromosome six. Itis a set of genes that determines which antigens are found on white blood cells. These antigens arethe human leukocyte antigens (HLA). Scientists can identify the antigens chemically. In this way,scientists have shown that in whites, HLA-B8 and HLA-DR3 are the antigens associated withGraves’ disease (see Chapter 6), while in Koreans, the DR5 and DR8 are most common. InJapanese, the antigen most associated with Graves’ disease is DR5, and in Chinese, the DR9. Allof this knowledge is important because doctors can test for these antigens in relatives of affectedindividuals. If the antigens are present, they’re more likely to get the disease.Autoimmune thyroid disease really comprises three different conditions: Graves’ disease: This disease consists of hyperthyroidism, eye disease, and skin disease(see Chapter 6). Chronic thyroiditis: This condition consists of goiter in a person with normal thyroidfunction or hypothyroidism (see Chapter 5). Myxedema: This condition is severe hypothyroidism.When scientists examine the thyroid glands of patients with the preceding conditions, theappearance is amazingly similar despite the completely different clinical outcome. In addition, asthe Dummy family shows throughout this book, different members of the same family can have oneor the other of these conditions. And the same person can have one or the other of these conditionsat different times. Which type of antibody a person’s body is producing determines whichcondition is present. If an antibody that stimulates the thyroid is predominant, then Graves’ diseaseis present. If antibodies that block thyroid-stimulating hormone are predominant, then chronicthyroiditis or myxedema is present.The greater occurrence of other autoimmune conditions in people with autoimmune thyroiditisstrengthens their autoimmune basis for this disease. These other autoimmune conditions include thefollowing: Myasthenia gravis: A disease of muscle weakness that activity worsens and restimproves, resulting from an autoimmune attack at the place where nerves and muscles cometogether.
Pernicious anemia: A reduction in red blood cells caused by a lack of intrinsic factor, asubstance made in the parietal cells of the stomach that’s essential for absorbing vitamin B12into the body. An autoimmune attack destroys the parietal cells. Vitiligo: A loss of pigmentation of the skin caused by autoimmune destruction ofmelanocytes, the cells that produce pigmentation. Type 1 diabetes mellitus: (See my book Diabetes For Dummies, 2nd Edition [Wiley].)A disease caused by excessive levels of glucose in the blood as a result of an autoimmuneattack on the pancreas, which makes insulin, the chemical that controls the blood glucose. Addison’s disease: Failure of the adrenal gland to produce hydrocortisone as a result ofan autoimmune attack on the hydrocortisone- producing adrenal cells. Alopecia areata: Patchy loss of hair in any part of the body, caused by an autoimmuneattack on hair follicles. Ovarian failure: Loss of function of the ovaries, resulting in infertility on account of anautoimmune attack on the ovarian follicles, the structures that nurture the eggs. Testicular failure: Loss of fertility as a result of autoimmune attack on the sperm in thetesticles. Pituitary failure: Loss of function of the pituitary gland with failure to make the hormonesthat stimulate other glands, including the thyroid, the adrenal gland, and the ovaries andtesticles, as a result of autoimmune attack on pituitary cells. Rheumatoid arthritis: Systemic lupus erythematosis and Sjorgren’s syndrome, allexamples of autoimmune attacks on the joints of the body.Whew! That’s really quite a list. But don’t worry. The chances that you’ll get any of the precedingconditions in combination with your autoimmune thyroid disease are quite small, though greaterthan if you don’t have the thyroid condition.Thyroid autoantibodies are also present in several other clinical conditions, but whether they’rethe cause of these conditions or represent a marker for a disturbance in autoimmunity that’s toblame isn’t clear. These clinical conditions are as follows: Increased risk of miscarriage in women attempting to become pregnant by in-vitrofertilization Breast cancer Depression in middle-aged womenAnother disease that’s found more often in people with certain human leukocyte antigens is
postpartum thyroiditis (see Chapter 11). In whites, the antigens are HLA, DR3, DR4, or DR5,while in Chinese, the antigen is DR9. The antigens are not certain for other ethnic groups.Antigens in autoimmune thyroiditisA number of antigens are present in autoimmune thyroiditis against which antibodies areformed, but three antigens are most important. Thyroglobulin is the substance within the thyroid that contains thyroid hormones T4 andT3. Not just one kind of thyroglobulin exists, but different kinds in different people.Thyroglobulin is also present in tissue in the eye. Some of the eye disease of Graves’ diseasemay be due to the reaction of antibodies against thyroglobulin in the eyes. TSH receptor, the second antigen, is the substance on the thyroid cell to which TSH bindsin order to stimulate the thyroid. Antibodies to TSH receptor bind to it and causehyperthyroidism by acting like TSH. Thyroid peroxidase, which used to be called antimicrosomal antigen, is the thirdimportant antigen. As its previous name implies, scientists found it in a part of the thyroid cellcalled the microsome. Its antibody is the most easily measured thyroid antibody and is mostoften positive in autoimmune thyroiditis.Inheriting a chromosome abnormalityDuring the creation of a zygote, as new cells are being formed, a mistake can occur in the divisionof the chromosomes into the two new cells — one cell ends up with an extra chromosome, and theother ends up with one less chromosome. The most well-known conditions associated with thiskind of chromosome mistake are Turner’s syndrome and Down’s syndrome. Both conditions areassociated with hypothyroidism, but Down’s syndrome is also associated with hyperthyroidism onoccasion.Down’s syndrome results when the new cells have an extra chromosome — they have three copiesof the 21st chromosome instead of two. People with this condition have a typical physicalappearance with characteristic facial features that are recognizable at birth. Children with Down’ssyndrome have palms that have a single crease, and their muscles lack tone. Reduced intelligenceand other abnormalities are part of this syndrome.Turner’s syndrome results when an X chromosome is left behind so that a female is born with asingle sex chromosome. The woman has distinctive facial features, including low-set ears, folds of
skin in the inner corner of the eye, and drooping eyelids. The woman also may have diabetesmellitus, cataracts, rheumatoid arthritis, and cardiac abnormalities in addition to chronicthyroiditis.Viewing the Future of Managing HereditaryThyroid DiseaseUp to now, scientists haven’t been successful in their attempts to remove a “bad” gene from ahuman and replace it with a healthy gene — a process known as genetic engineering. Theproblem is that they don’t yet know how to insert the new gene successfully. If scientists candetermine how to do so, they can open the door to preventing diseases that people inherit through asingle gene.Genetic engineeringIf a recessive gene causes a disease, replacing that gene with its dominant form in sufficientamounts should be enough to cure the condition. Usually in a recessive-gene disorder, the diseaseoccurs because that particular gene isn’t functioning at all, so providing even a small level offunction may cure the condition.The disorders that may most easily respond to genetic engineering are disorders of the bloodsystem, because doctors and scientists may easily remove blood. A new gene can be spliced intothe cells and the blood reintroduced to the patient. The first trial of gene therapy, performed in1990, was for a disorder that resulted in severe loss of immunity so that the patient was verysusceptible to any infection, as well as a cancer. Scientists were able to introduce the necessarygene into the blood cells of the patient by connecting the gene to a virus, which infected the cellsand added the gene to their DNA. The cells were grown to increase their number and reinserted.Unfortunately, the trial didn’t work, probably because the efficiency of splicing the gene into thecells was low.Other genetic disorders for which trials of gene therapy have taken place include Familial hypercholesterolemia: Excessive production of cholesterol leads to early deathby heart attack. Cystic fibrosis: Lack of a certain gene leads to excessive production of a thick mucous inthe lungs, resulting in chronic lung infection.
Duchenne muscular dystrophy: Severe muscle deterioration leads to the individualdying by the third decade of life.A trial of gene replacement in all three of these conditions has been unsuccessful.Another novel way of managing diseases caused by defective genes is to find a gene that’s activeduring fetal life (but becomes dormant later on) and that can replace the activity of the defectivegene if it can be made to express itself. A prime candidate for this treatment is sickle cell disease.In this disease, abnormal hemoglobin (hemoglobin is the chemical in red cells that carries oxygento the tissues of the body) leads to the early loss of red blood cells, which become sickled(crescent shaped) in appearance and can block blood flow to tissues, causing great pain. A geneactive during fetal life produces fetal hemoglobin, which doesn’t sickle. If this gene can be turnedon during adult life, it can replace the defective hemoglobin made by the patient. Scientists arelooking for the drug that may be able to turn this gene on.Cancer treatment has seen a lot of activity in the area of gene therapy. Gene therapy can treatcancer of the thyroid in a number of ways, including the following: Inserting a gene that increases the sensitivity of the cancer to a drug, or inserting a poisoninto cells that are injected directly into the tumor. Inserting a gene that increases the activity of the patient’s immune system. Inserting a new gene into blood cells to restore tumor-suppressor activity. This treatmentworks because some tumors arise when the activity of tumor suppressors (chemicals in thebody that suppress the growth of tumors) declines. Using a virus to introduce a gene into a thyroid cancer cell. The virus causes the DNA tochange so that the cell takes up radioactive iodine, which can kill the cell. (This approach isthe newest cancer treatment and is outlined in a paper in Thyroid in June 2004.)All these treatments have seen some success, but no one has yet been cured of cancer with genetherapy.Scientists are also attempting to increase a tumor’s immune response by modifying the tumor sothat it provokes body cells against it. Scientists perform this technique by inserting genes into thetumor that cause it to produce new antigens that the body can fight against. Tumors like malignantmelanoma and colon cancer have been the target of this type of therapy. A similar techniqueinvolves inserting a gene directly into a tumor that activates a cancer-killing agent, which issubsequently injected. These techniques have led to some decrease in tumor size but, so far, nocures of cancer. Interestingly, gene therapy isn’t limited to tumors brought on by faulty genes but
can be directed at any tumor, genetic or not.Exploring the ethics of germline gene therapyYou can see that the range of techniques for using genetic engineering to cure disease is enormous.Scientists are discovering new methods of delivering healthy genes to replace disease-conferringgenes as you read this book. This approach would certainly be the simplest and most successfulway of treating the diseases provoked by inheritance of a single dominant gene. However, thistype of treatment would cure only the particular individual without affecting the transmission of thedisease to his offspring. To eliminate the disease from future generations, genetic engineering hasto take place in the sperm and/or the egg, the germline of the individual.Germline gene therapy raises tremendous ethical questions. If we have the tools for eliminating therecessively inherited Pendred syndrome by replacing a Pendred gene with a normal gene, don’twe also have the tools for changing skin color, height, or any other body characteristic in futuregenerations? An entire field of genetics concerns ELSI, the ethical, legal, and social implicationsof genetic science.So far, germline gene therapy has actually been successful in some animals, but hasn’t been doneon humans for several reasons: The methods used so far are very imprecise, so the final product is uncertain, including thepossible introduction of harmful genes. Many people fear that germline gene therapy may lead to germline enhancement, anattempt to produce a “superior” human being. Whether germline gene therapy is even needed is uncertain, because a harmful recessivetrait requires mating with another human with the same trait to express itself, while dominanttraits are present in only half of a germline. Identifying the sperm or egg with the normal geneand using that gene in fertilization makes more sense than trying to modify the sperm or eggwith the abnormal gene. Scientists should perform genetic testing of the germline if they are toeliminate these diseases.Clearly, genetics is the current frontier in medical science. Genetics promises to prevent or curemany of the diseases that plague humans, including hereditary thyroid disease and nonhereditarytumors. But the road to those cures and preventions is full of cracks and bumps that assure a veryuneven ride.
Chapter 15The Thyroid and Your Mental HealthIn This Chapter Discovering that you’re not alone Coping with an underactive thyroid Understanding the psychology of an overactive thyroid Finding thyroid problems in depressed people Using thyroid drugs to treat depressionThe term myxedema madness may not be familiar to you, but it was popular when it wasintroduced in 1949 and for many years thereafter. Myxedema refers to low thyroid function, orhypothyroidism. The term myxedema madness resulted in the unfortunate association that allpeople with low thyroid function were somehow mad. My goal in this chapter is to clear up thismisconception.The abnormal production of thyroid hormones, which I explain in Chapter 3, can cause changes inthe mood of a patient, and these changes can be severe in rare instances. But for most patients,simply treating their overactive or underactive thyroid allows them to live psychologically andphysically normal lives.In this chapter, I share what doctors currently understand about how changes in the production ofthyroid hormones (both overproduction and underproduction) affect your personality. Youdiscover how often personality or mood disorders are associated with thyroid abnormalities andwhy thyroid hormones play a role in the treatment of depression, even when no thyroid problemexists. Because the emphasis in this chapter is on the psychology of thyroid abnormalities, I don’tdiscuss physical signs and symptoms here; those discussions occur elsewhere in the book,especially in Chapters 5 and 6.The Underactive Thyroid and Your MoodSarah Dummy is a 44-year-old woman who hasn’t been herself for several months. Herhusband, Milton, notices that she is much less talkative than before. She often forgets to pick
up the food that they need at the supermarket or to stop at the dry cleaner’s to pick up clothesshe dropped off.Milton wants to discuss a vacation with Sarah, but she doesn’t seem to care. Sarah is usuallythe one responsible for making plans with their friends, but she hasn’t made any for months.Everything she does seems to take more time than it used to, like preparing dinner or gettingready to go to bed. When she finally gets in bed, she isn’t particularly interested in having sexanymore. The most serious change is that Sarah, usually a happy person, seems sad a lot of thetime.Worried about these changes, Milton encourages Sarah to see Dr. Rubin, who examines herand sends her for some lab tests. A few days later, Dr. Rubin tells Sarah that she hashypothyroidism — her thyroid gland isn’t making enough thyroid hormone. He gives her aprescription for replacement thyroid hormone, and about a month later Sarah is well on herway to becoming her old self. Milton is happy because he has clean underwear again.Sarah is an excellent example of the changes in personality that occur when the body doesn’tproduce enough thyroid hormone. Depending on the level of the deficiency, the changes are moreor less severe and include the following: Decreased talking Memory loss, especially for recent events at first, and for remote events later on General loss of interest Inability to concentrate Withdrawal from society A general slowing of movement and thought Depression, generally mild but sometimes severe (see the “Fighting Depression” section,later in the chapter) Loss of interest in sex In severe cases, a kind of ironic sense of humorPatients and doctors can easily confuse many of the preceding complaints, which are nonspecificand poorly defined, with depression. For this reason, both patients and doctors can easily misstheir significance.No one or group of the preceding mental changes means that you definitely have low thyroidfunction, but they certainly suggest that you need testing to find out.If your doctor determines that lack of thyroid hormone is the cause of your symptoms, then the right
dose of hormone replacement should reverse them. If it doesn’t, then you and your doctor need tolook elsewhere for the cause, which may be underlying depression. See Chapter 5 for a thoroughdiscussion of hypothyroidism.Any person over the age of 60 who has a psychosis and reduced mental ability shouldreceive testing for possible thyroid disease.And keep in mind the following additional hypothyroid–mental illness related issues: Occasionally, a patient who has schizophrenia has hypothyroidism. Giving thyroid pillsmay not completely cure the patient, because some changes may be irreversible. If a patient with manic-depressive psychosis caused by hypothyroidism receives lithium,the lithium may make the problem worse because it causes hypothyroidism as well.The most severe mental symptoms — historical notesYears ago — I’m talking about more than 50 years ago — doctors saw patients with much moresevere and longstanding cases of hypothyroidism and hyperthyroidism than we see today.At one time, doctors saw many more hypothyroid individuals with decreased accuracy ofperception that led to visual and other hallucinations. Still later, bizarre behavior appeared.Patients showed increasing drowsiness, difficulty in arousal, sleeping for long periods, andfinally coma followed by death if they didn’t receive treatment for their hypothyroidism.Doctors found hyperthyroid patients with huge thyroid glands who were visibly shaky andnervous, unable to sit still for more than a few moments, resembling mania. Such severehyperthyroidism very rarely happens now, because doctors usually diagnose the conditionearlier, but rare cases of severe, prolonged hyperthyroidism may result in hallucinations, both invision and hearing. In fact, a severely hyperthyroid patient first caused me to become veryinterested in thyroid disease. She had a large goiter, and I saw her in the medical psychiatricward during my training days at Bellevue Hospital Medical Center at New York UniversitySchool of Medicine.But doctors rarely see patients suffering from such severe symptoms today, and the medicalliterature and descriptions of such cases relies on the observations of people living in a verydifferent society fifty or more years ago.Overactivity of the Thyroid and Your MindSarah Dummy’s sister, Margaret, who is five years younger, began showing some bigpersonality changes a few years ago. Previously a fairly even- tempered person, she now
becomes easily excited and loses her temper after fairly mild provocation. Her small childrennever know when their mother is going to yell at them. She sometimes has a crying spell but, ifasked, can’t give a reason why.At other times, Margaret is extremely happy, but she can’t explain the reason for that either.When she tries to do a task, she often loses interest rapidly and gets distracted. She can’t sitstill for very long and seems to be always moving. Her memory of recent events is poor.Margaret and her husband, Fred, go to see Dr. Rubin about her condition after a few months ofabsolute chaos in their home. During an examination, Dr. Rubin discovers a number ofphysical findings, including a rapid pulse, a large thyroid gland, and a fine tremor ofMargaret’s fingers. He confirms his findings with lab tests (see Chapter 4). Two days later, hetells the concerned pair that Margaret is suffering from hyperthyroidism — her body isproducing too much thyroid hormone. He begins treatment with medication, and in three weeksa definite change begins to occur. After six weeks, Margaret is just about back to normal.Margaret and Fred take the kids to Lollipop Land to make up for all the yelling.Margaret is an excellent example of the psychological changes that occur when the body producesexcessive levels of thyroid hormone. Some of these changes are Increased excitability and agitation Anxiety Impaired concentration Insomnia An emotional roller coaster of moods Outbursts of anger for no reason Crying spells A tendency to get easily distractedPsychiatric illness is present in about 10 percent of patients with hyperthyroidism.Other conditions seem to be indicators of hyperthyroidism but turn out not to be when doctorsperform thyroid function tests. They include An anxiety state or neurosis: A compulsion to do something continuously like washingthe hands, cleaning the windows, or making certain sounds or an extreme and unrealistic fearare examples. Panic attacks: Panic attacks are associated with rapid heart rates that mimichyperthyroidism.
Thyrotoxicosis factitia: This is a condition of false hyperthyroidism brought on by secretingestion of thyroid hormone, usually by nurses. This is a psychiatric disorder. Mania: Characterized by extreme excitability and excessive activity.When hyperthyroidism affects elderly people (who I define as anyone older than I am), thecondition may actually look like hypothyroidism. An elderly patient with hyperthyroidismmay feel sad and depressed, apathetic, and withdrawn from society. I explain how thyroidproblems affect the elderly in Chapter 19.The treatments for hyperthyroidism, which I describe in Chapter 6, are very effective in reversingall the mental and physical symptoms, particularly in younger people who often get the disease. Ifthe mental symptoms are present long enough, however, curing the hyperthyroidism may not curethe manic state.Stress is sometimes blamed for bringing on hyperthyroidism, but little objective evidence supportsthis claim. Hyperthyroidism may precede stress. Most people who live through severe stress don’tdevelop hyperthyroidism. However, some evidence suggests that patients with establishedhyperthyroidism may do better if they’re able to handle stresses that come along while they’rereceiving treatment and afterward. If they’re able to handle the stress, then relapse is less likely.Fighting DepressionDepression may be a symptom of a lack of thyroid hormone. On the other hand, thyroid hormonemay help in the treatment of depression, even when tests indicate that the patient has enoughthyroid hormone. The following sections explain the role that thyroid hormone plays in depression.Determining if the thyroid is the causeDepression is a prominent symptom of thyroid disease, especially hypothyroidism. Therefore,when someone receives a diagnosis of depression, determining whether a thyroid disease is thecause is important.Studies show that most depressed people don’t have hypothyroidism. How- ever, the conditionmay be present in a mild form in as many as 20 percent of depressed people, more often in womenthan in men. If a person receives a diagnosis of hypothyroidism, a doctor should determinewhether the patient is taking a drug for treatment of depression that may actually be causinghypothyroidism (see Chapter 10). Two such drugs are lithium and carbamazepine.
If a drug is responsible for hypothyroidism, a person has two options. The patient can stop takingthe drug, in which case its contribution to the depression disappears, but the patient may still bedepressed for other reasons. Alternately, the patient can receive thyroid hormone as treatment ifthe doctor feels that the drug is helping the depression a great deal and no substitute exists.If you’re receiving treatment for depression and haven’t had thyroid function tests, ask yourdoctor to perform them.TSH, autoantibodies, and depressionThyroid abnormalities are often associated with other chemical changes in the blood besidestoo much or too little thyroid hormone. A patient with hypothyroidism, for example, may havetoo much thyroid-stimulating hormone (TSH) or high levels of thyroid autoantibodies, both ofwhich I explain in Chapter 3. Could these other chemical changes promote depression in somepatients?Doctors haven’t yet found a correlation between levels of TSH and thyroid autoantibodies anddepression. Patients may sometimes have high autoantibodies while their thyroid function isnormal, in which case they don’t experience thyroid-related depression. The level of TSH in theblood doesn’t seem to impact depression either.Current research indicates that the level of the thyroid hormones themselves affects mood, andthe levels of TSH and thyroid autoantibodies don’t.Using thyroid hormone to treat depressionMany doctors believe that replacement thyroid hormone has a role in the treatment of depression,even when no thyroid abnormality is present.Given by itself, thyroid hormone doesn’t seem to reverse depression in a patient who doesn’t havea thyroid disease. However, when a patient takes the thyroid hormone triiodothyronine (seeChapter 3) together with antidepressants, it can improve the effectiveness of the treatment. This isespecially true when a patient is taking a class of drugs called tricyclic antidepressants, whichhave brand names like Elavil, Tofranil, Etrafon, Norpramin, and Sinequan. The thyroid hormone isparticularly effective in turning people who don’t respond to tricyclic antidepressants intoresponders. It also increases the effectiveness of those drugs when they do work.When used to help treat depression in patients who don’t have thyroid disease, the patient can stoptaking the thyroid hormone after a few weeks or months, and the positive effect persists.
Chapter 16What’s New in Thyroid Treatment?In This Chapter Managing hypothyroidism Zeroing in on the right dose of hormone Treating hyperthyroidism Shrinking nodules and goiters Understanding antithyroid drugs Dealing with thyrotoxic periodic paralysis Overcoming thyroid cancer Correcting iodine deficiencyIn November 2005, I visited PubMed, an online search page of the National Library of Medicine(www.pubmed.gov), and did a search for “thyroid disease.” The result was more than 9,500citations to studies done by thousands of scientists that were published in medical journals sincethe first edition of this book. (Thousands more studies were offered for publication but didn’t getinto the journals for one reason or another.) This research represents the cutting edge of medicine.But how do you stay on the cutting edge without slipping and getting sliced up? One of the reasonsyou bought this book is so I can do the work of sifting through the research for you.In this chapter, you find a selection of the most important discoveries in thyroid medicine duringthe last couple years. Some discoveries are single studies of a subject that a similar study canrevise or even overturn. You have to keep an open mind when new (and not necessarily validated)material presents itself in the future.Knowing something about the observer is equally important as knowing what someone isobserving. For instance, one of the studies about whether thyroid nodules shrink when a doctorgives a patient thyroid hormone points out that two different observers differ by as much as 50percent in their observation of the size of the same thyroid nodule. So any change less than 50percent can be observer “error” as much as it can be true change.Furthermore, some observers have a self-interest in what they’re observing. Unfortunately, thedrug or equipment companies pay for most studies of new drugs and techniques that require
special equipment. Is it likely that these companies will continue to fund researchers whoconstantly come up with negative findings? The best studies are those that aren’t connected tospecific companies, but knowing which studies don’t have such connections is sometimes hard. Sodon’t be surprised if today’s magic cure-all turns out to be tomorrow’s source of major sideeffects.Even with no observer bias, results that are excellent when a drug is tested on a fewhundred or thousand people may be very different when hundreds of thousands of peoplebegin to use the drug.As I write this chapter, researchers are studying just about every aspect of thyroid disease, witharticles in every medical journal andnew findings that are getting ready to join the thousands ofstudies before them. Being up to the minute in a book isn’t possible given the constraints of apublishing deadline and the amount of information coming out. If you have a particular problemthat concerns you or a loved one, don’t hesitate to use the enormous amount of free resources atyour disposal. Go to the PubMed Web site (www.pubmed.gov), or check out your local bookstoreand hospital library. And be sure to utilize the references you find in Appendix B of this book.Treating Subclinical HypothyroidismOne of the great debates in thyroid management is what to do about subclinical hypothyroidism,condition in which the patient’s TSH level is slightly elevated (say to 6 or 7), the free T4 level isnormal, and the patient has some nonspecific symptoms that can be the result of hypothyroidism orsomething else. Doctors have been studying these patients, looking for signs of low thyroidfunction or a response to thyroid medication, because they aren’t sure whether treatment isnecessary.One study from Italy, published in the Journal of Clinical Endocrinology and Metabolism inMarch 2001, looked at the function of the heart in 20 people with subclinical hypothyroidism, allof whom showed some abnormality in heart activity. Half of the study participants were giventhyroid treatment, and the other half were given a placebo. The study found that people given thethyroid-treatment drug showed an improvement in heart function, while those given a placeboshowed no change. The study concluded that people with subclinical hypothyroidism havemeasurable abnormalities that thyroid treatment improves.Another study from Germany, published in Thyroid in August 2000, looked at heart disease andheart attacks in patients with subclinical hypothyroidism. The author of the study found that these
patients sustained a definite increase in heart disease and heart attacks over patients without thecondition. Various tests of normal heart function, such as changes in heart rate with exercise,indicated that those functions were impaired in people with subclinical hypothyroidism. The mostat-risk people were women over age 50 who smoked and had TSH levels greater than ten. Givingthe study patients thyroid medication improved these functions and also improved the levels of fatsin the blood. The author of this study felt that these changes justified the use of thyroid treatment insubclinical hypothyroidism. He noted, however, that giving a patient thyroid-replacement hormonetends to speed up the heart rate and may worsen chest pain, which doctors must consider whentreating someone with this condition.A more recent study in the Annals of Family Medicine in July 2004 provides further evidence thatpatients with subclinical hypothyroidism probably don’t need treatment. The authors of the studylooked at people who didn’t have a diagnosis of hypothyroidism and weren’t taking thyroid pills.They found that a subgroup of those people had subclinical hypothyroidism, which they defined asa TSH between 6.7 and 14.9 with a normal thyroxine (T4). The authors looked at the fat levels ofthese patients and found that although they had slightly more total cholesterol, their levels of HDLcholesterol (good cholesterol) and LDL cholesterol (bad cholesterol) as well as triglyceride wereno different from people with normal TSH levels. Even the levels of total cholesterol weren’tdifferent in the two groups when adjusted for age and sex. The authors’ conclusion was thatsubclinical hypothyroidism doesn’t need to be treated, as least as far as treating to benefit fatlevels in the body. They raised the possibility that other abnormalities may benefit from treatment.This remains a very controversial topic. At this time, my bias is to treat subclinicalhypothyroidism since on balance the evidence suggests that these patients suffer heartabnormalities that are improved by thyroid hormone treatment.If you have subclinical hypothyroidism, you and your doctor should look carefully for subtleevidence of low thyroid function and treat the condition with thyroid-replacement hormoneif you find such evidence. Then determining whether thyroid hormone makes a difference inthose subtle findings becomes important.Finding the Right Dose of HormoneA question that keeps coming up among doctors who treat hypothyroidism is “What is the correctdose of thyroid medication?” Some physicians believe that lowering a patient’s level of thyroid-stimulating hormone (TSH) to under five is sufficient to eliminate signs and symptoms of lowthyroid function, but many patients are still symptomatic at that level. In a study published in the
Medical Journal of Australia in February 2001, the authors show that lowering the TSH tobetween ⅓ and 2 may be beneficial.Recent examinations have taken place of the question of whether combined T4 and T3 is bettertreatment for hypothyroidism than T4 alone. A report in the Journal of Clinical Endocrinologyand Metabolism in May 2005 evaluated all the carefully controlled studies comparing treatmentwith T4 and T3 to T4 alone. Nine studies met the authors’ of the report’s criteria, which was thatthe studies were double-blind (neither the patient nor the doctor knew what the patient wasgetting). Only one study found that the patients given both hormones had improved mood, quality oflife, and psychological measurements compared with T4 alone. Later studies didn’t confirm thisstudy. The authors conclude that no evidence supports that combined T4 and T3 have advantagesover T4 alone in treating hypothyroidism.If you’re being treated for hypothyroidism and still have symptoms when your TSH level isbetween three and five, ask your doctor to treat you to lower that level. I believe that doingso will improve your health.Dealing with HyperthyroidismDespite the availability of several treatments for hyperthyroidism (see Chapter 6), specialistsaren’t satisfied with any of them. Each treatment is associated with either frequent failure orundesirable side effects like hypothyroidism. The search for better therapy continues.A study published in January 2001 in the Journal of Clinical Endocrinology and Metabolismemphasizes the importance of measuring calcium levels of patients with thyroid conditions,especially hyperthyroidism. This German study shows that after thyroid surgery,hypoparathyroidism — the loss of parathyroid function — frequently occurs and leads to lowcalcium levels. (A high calcium level, on the other hand, may be caused by hyperparathyroidism— excess parathyroid function. In this study, excess parathyroid function was also relativelycommon in association with thyroid disease.)Both decreased and increased parathyroid function occur at a higher rate in patients withhyperthyroidism than in people who don’t have thyroid disease. If you havehyperthyroidism, be sure to have your calcium level checked regularly.Connecting hyperthyroidism and the heartPeople with hyperthyroidism have an increase in heart disease and death. The main types of heart
disease are heart failure and blood clots from the heart. Thyroid hormone has many effects on theheart, including the following: Increased heart rate Increased force of the heart Increased flow of blood from the heart Increased consumption of oxygen by the heart muscle Enlarged heart Decreased diastolic blood pressure Decreased blood-vessel resistanceBecause of the preceding effects, especially in patients who have other heart problems, diagnosingand treating hyperthyroidism as early as possible is important. These abnormalities lead to anumber of symptoms and signs. The most important are as follows: Feeling that the heart is beating rapidly Intolerance to exercise Shortness of breath on exertion Rapid heart rate Atrial fibrillation (a very irregular rhythm of the heart)In the elderly, atrial fibrillation may be the only sign of hyperthyroidism. An elderly personwith atrial fibrillation should always be tested for hyperthyroidism.Blood clots are a major complication of atrial fibrillation and should be prevented byanticoagulation, administration of a drug that prevents clots.Subclinical hyperthyroidism, where the T4 is normal but the TSH is low, is also associated withheart problems, including a rapid heart rate, reduced tolerance to exercise, and atrial fibrillation.Subclinlical hyperthyroid patients, especially those over 60 with other heart problems, need toreceive treatment to make the TSH normal. But atrial fibrillation, if present, won’t always returnto a normal heart rhythm after treatment.Amiodarone, as I note in Chapter 12, can also induce hyperthyroidism, increasing the blood-iodinelevel 40 times. If the patient was previously deficient in iodine, the result may be hyperthyroidism.As a result of its other properties, amiodarone can conceal hyperthyroidism. Amiodarone also
stays in the body long after it’s stopped, so hyperthyroidism can occur months later.The best treatment for amiodarone-induced hyperthyroidism is to stop the amiodarone. Othertreatments may be more helpful for maintaining a normal heart rhythm and can replace theamiodarone. Scientists are investigating other compounds that work as well as amiodarone butdon’t contain iodine.Exploring hyperthyroid eye diseaseSevere hyperthyroid eye disease, though rare, can lead to blindness. Just exactly why hyperthyroideye disease occurs isn’t clear, but researchers generally believe that it has a basis as anautoimmune disorder (see Chapter 4). One suggestion is that thyroglobulin enters the muscles ofthe eyes, and antibodies react against it. A study from Italy in the journal Thyroid in 2001 showedthat thyroglobulin can, indeed, be found in the muscle tissue of the eyes. The study demonstratedthat the thyroglobulin originated in the thyroid gland, which confirms that the autoimmune reactionin the thyroid is very similar to the autoimmune reaction in the eyes. The findings of the study helpbolster the argument in favor of using anti-immunity therapy for hyperthyroid eye disease, as Idiscuss in Chapter 6.Hyperthyroid eye disease has a very negative impact on quality of life, even when it’s moderate,which is usually the case. Severe eye disease occurs less than 5 percent of the time, but treatmentworks in only two-thirds of patients. The eye disease goes through three phases: First phase: High activity with redness of the eye, pain, tearing, and sensitivity to light. Second phase: Stabilization of the signs and symptoms. Final phase: Improvement of the eye disease, which becomes inactive.The duration of these phases varies, but the eye disease burns out within a couple of years.Steroids are helpful during the first active phase.Steroids given intravenously are more effective than steroids by mouth for thyroid eyedisease. Steroids can be injected right into the muscles around the eye and are effectivethere. Doctors give IV steroids in very high amounts, which can cause liver damage. IVsteroids are effective about 90 percent of the time, while liver damage occurs only 1 percentof the time.If steroids aren’t successful, then doctors perform orbital radiation therapy. This therapy issuccessful about 60 percent of the time. Using both steroids and orbital radiation at the same time
is even better than either alone.Recent studies of other therapies, including drugs called somatostatin analogs and antioxidants,haven’t shown that these therapies are effective. Antioxidants may be useful for mild eye diseasebut not moderate or severe forms.Three factors are definitely important in the progression of hyperthyroid eye disease, and shouldbe managed as strongly as possible: Cigarette smoking: Cigarette smoking not only promotes the development of eye diseasebut blocks the effectiveness of steroid and orbital– radiation therapy treatments. Quittingsmoking is probably the most important preventive measure in this disease. Active thyroid dysfunction: Active thyroid dysfunction, whether hyperthyroidism orhypothyroidism, promotes the progression of eye disease. Both conditions need to becorrected as soon as possible. Radiation therapy: This hyperthyroidism treatment causes progression of the eye diseaseas well. A course of steroids can prevent this progression.Assessing Goiters and NodulesGoiters and nodules remain a very common problem in thyroid medicine. Newer studies arechanging how doctors manage patients with these conditions. Ultrasound studies pick up nodulesin the necks of as many as 67 percent of people who don’t have a nodule by physical examination.Differentiating benign from malignant nodulesThe fine-needle biopsy remains the best way to diagnose a thyroid nodule, but it’s much moreeffective when guided by ultrasound, especially when the nodule is very small (less than 1.5centimeters in size). The fine-needle biopsy guided by ultrasound permits a correct diagnosis ofcancer 60 percent of the time compared to 40 percent when not guided by ultrasound.It’s not possible to make a definite diagnosis about 10 percent of the time with fine-needle biopsy.Of these 10 percent, only 15 percent turn out to be cancers. The problem is how to pick out that 15percent that will need surgery; the other 85 percent can be followed medically. Two chemicalmarkers have recently shown some promise in telling the difference. Doctors can assess both ofthese chemical markers in the clinical laboratory. They may become generally available if theyprove their success in further studies. The two chemical markers are as follows: