Hypothyroidism Causes and Treatments

The Hypothyroidism Revolution

During Phase 1 of the Hypothyroidism Revolution Program, the magic begins to happen as you begin to notice many positive changes occurring. You will begin your progressive transition towards the ideal thyroid healing diet that will give your thyroid the big boost that it needs to help your cells produce more than enough energy for you. By the end of Phase 1, your energy levels will be rapidly on the rise and you will feel amazingly satisfied with zero food cravings. You will feel in control again as your mood drastically improves and any sign of depression and anxiety begin to disappear. Your family and friends are going to notice some major positive changes in you. You will also begin to experience many of the outer changes that come with improved thyroid function. Youre skin will begin to clear up and glow while your hair and nails will begin to look healthy again. As you ease into the thyroid healing diet, you will progressively remove the foods that suppress your thyroid, disrupt your hormone pathways, cause digestive upset and irritation, and cause toxic byproducts that congest your liver. At the same time, you will be progressively adding the foods that will be supplying your cells with the right balance and combination of nutrients that they need to thrive and produce endless amounts of energy. Continue reading...

The Hypothyroidism Revolution Overview


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Brief Comment On The Treatment Of Hypothyroidism With T3

The generally accepted treatment for hypothyroidism is T4. However, there has been a lot of discussion in recent years about adding T3 to T4 in patients who do not feel well on T4 alone despite a normal TSH level. T3 is the active hormone at the nuclear receptor. It has been well established that a portion of T4 is converted to T3 in the liver and other tissues. Most of the trials of combined therapy with T3 and T4 have not shown an improvement in patients treated with combined therapy over T4 therapy alone. However, some physicians feel that a trial of combined therapy may be reasonable in occasional hypothyroid patients who are not feeling well on T4 alone. Generally, the approach is to decrease the T4 dosage and add a small dose of T3 (5-12.5 mg), with the goal of keeping TSH in the low-normal range. If it is used, the T3 dose should be kept low, and T3 should probably be avoided in patients with heart disease.

Generation of Hypothyroid Rats and Mice

The induction of severe hypothyroidism is essential to observe changes in gene expression by thyroid hormone. Moderate hypothyroidism leads to physiological changes aimed at maintaining T3 concentrations in neural tissue within normal levels. The most important mechanism concerns deiodinase type 2 (D2). D2 is a selenoenzyme that catalyzes the removal of the iodine atom in the 5' position of T4 to generate the active hormone, T3. D2 activity is inhibited by T4 through a mechanism involving increased degradation of the enzyme in proteasomes. In situations of low T4, the increased expression and activity of D2, with the concomitant increased efficiency of T4 to T3 conversion, tends to maintain T3 concentrations constant (30). Therefore, only under very severe hypothyroid conditions are T3 concentrations low in the brain, in contrast with other tissues, such as the liver or kidney. Hypothyroidism can be induced in the rat by surgical or chemical means. Surgical thyroidectomy procedures...

Generation of Hypothyroid Hyperthyroid and Euthyroid Mice

Hypothyroid mice are generated by feeding them with a low iodine (loI) diet supplemented with 0.15 propylthiouracil (PTU) purchased from Harlan Teklad Co. (Madison, WI) for 4 wk. 2. Serum thyroid-stimulating hormone (TSH) measurements (kindly measured by Dr. Samuel Refetoff, University of Chicago, Chicago, IL) show that mice littermate control and transgenic mice treated with PTU were profoundly hypothyroid. 3. Hyperthyroid mice are generated by injecting hypothyroid mice intraperitoneally with 100 g L-T3 (Sigma) per 100 g mouse body weight in phosphate-buffered saline (PBS) for 6 h.

Chronic Lymphocytic Thyroiditis Hashimotos Thyroiditis

Aspirates are variably cellular depending upon the degree of fibrosis of the thyroid gland, and in the small subset of cases of the fibrosing variant of Hashimoto's thyroiditis, the specimen is hypocellular. Aspirates of chronic lymphocytic thyroiditis are characterized by a combination of two features (1) a mixed population of lymphocytes, plasma cells, and lymphohistio-cytic aggregates, and (2) occasional cohesive clusters of follic-ular cells with oncocytic features (Hurthle cells) (Figures 4.3-4.6). The inflammatory component that consists of an abundance of mature B and T lymphocytes as well as centro-cytes and centroblasts generally predominates the sample. Lymphohistiocytic aggregates with associated folliclular dendritic cells and tingible body macrophages are often easily identified (Figure 4.4) such that the aspirate closely resembles a reactive lymph node. Plasma cells can be seen among the mixed population of lymphocytes and, in some cases, can be the predominant cell....

Reidels Thyroiditis

Aspirates of Reidel's thyroiditis are hypocellular and often unsatisfactory for evaluation due to scant cellularity. Microscopically, fragments of collagenous fibrous tissue, scattered cytologically bland spindle cells with plump elongate nuclei, and some background chronic inflammatory cells are seen (Figures 4.9, 4.10). Follicular cells, lymphohistiocytic aggregates, and abundant lymphocytes are absent, helping to exclude chronic lymphocytic thyroiditis. Cytologic Features of Reidel's Thyroiditis Figure 4.9. Reidel's thyroiditis. Aspirates are hypocellular and contain occasional clusters of bland spindle cells and collagenous fibrous tissue. (Smear, Papanicolaou.) Figure 4.9. Reidel's thyroiditis. Aspirates are hypocellular and contain occasional clusters of bland spindle cells and collagenous fibrous tissue. (Smear, Papanicolaou.) Figure 4.10. Reidel's thyroiditis. Spindle cells form loose aggregates and have delicate cytoplasm and bland elongate nuclei with fine chromatin. (Smear,...

Subacute Thyroiditis

Aspirates of subacute thyroiditis are usually hypocellular and consist of multinucleated giant cells that surround and engulf colloid. In addition, loose aggregates of epithelioid histiocytes (granulomas) are characteristic (Figures 4.7,4.8). Care should be taken not to misinterpret the epithelioid histiocytes with their curved nuclei and abundant granular cytoplasm as an epithelial neoplasm. A variable amount of background mixed inflammatory cells including lymphocytes, plasma cells, eosinophils, and neutrophils are sometimes seen. Follicular cells are generally sparse and, when present, can show onco-cytic features as well as degenerative changes with reactive atypia. Cytologic Features of Subacute Thyroiditis Figure 4.7. Subacute thyroiditis. Collections of epithelioid histio-cytes (granulomas) with their curved nuclei and abundant granular to foamy cytoplasm should not be mistaken for an epithelial neoplasm. (ThinPrep, Papanicolaou.) Figure 4.8. Subacute thyroiditis....

Thyroid Disease

Thyroid hormones, which are produced by the thyroid gland in the lower front of the neck, regulate the body's energy level. When levels of thyroid hormones are unusually high, a condition known as hyperthyroidism, the body burns energy faster and many vital functions speed up. In other instances, levels of thyroid hormones can be abnormally low, a condition known as hypothyroidism. Feeling cold and sleepy during the daytime is a hallmark of this disorder. People with low thyroid levels tend to gain weight and their muscles don't work as well as they should both situations can bring about obstructive sleep apnea. Hypothyroidism can be treated with replacement doses of synthetic thyroid hormones.

Approach To Evaluati On Of The Thyroid Patient

This section discusses the approach that I have used for many years in evaluating patients with possible thyroid disease. Because most of my patients are referred for suspected thyroid disease, it is easier for me to focus in on the problem. It is more difficult for the primary care physician (PCP) who must distinguish possible patients with thyroid problems from the large number of patients seen in the office every day. However, I think this general approach may be utilized by the PCP when thyroid disease is considered in the differential diagnosis. Risk Factors for Hypothyroidism Age > 60 years Hyperthyroidism Other autoimmune disease Addison's disease Pernicious anemia Diabetes mellitus (type 1) Subacute thyroiditis (overt or silent) Head neck cancer (treated) Family member with thyroid disease Medication use Lithium carbonate Amiodarone Iodine (any form) Routine tests (if previously done) TSH, thyroid-stimulating hormone TPO, thyroid peroxidase. (From Sawin CT. Thyroid disease...

Indication Of Hyperthythroidism

This 52-year-old man was referred because of an abnormal TSH of less than 0.03. He had a long history of ischemic heart disease with serious arrhythmias. Over the previous several months, he had noted heat intolerance, shakiness, and a 30-lb weight loss despite increased food intake. He denied recent palpitations. His first coronary artery bypass graft surgery was at age 33 years and the second at age 45 years. More recently, he had noted recurrent chest pain requiring angioplasty. He had several episodes of ventricular fibrillation and was started on amiodarone 2 years previously. An implantable defibrillator was in place, but it had not fired for about 9 months. The amiodarone was effective in controlling the arrhythmia, and his cardiologist felt it could not be safely discontinued. Family history was negative for thyroid disease. Other medications included Lasix, potassium, Isordil, Lanoxin, and Pravachol. Hyperthyroidism secondary to amiodarone is very difficult to treat and can...

Rc655b69 2005

Thyroid Disease A Case-Based and Practical Guide for Primary Care, by Dr. Emanuel Brams, is a supremely readable cased-based approach to understanding the myriad of disorders that encompass thyroid disease. Using cases derived from his busy practice, Dr. Brams gives us the history and physical examination details of each case, along with test results. Then, through a series of questions similar to that which any good clinician asks while caring for a patient, Dr. Brams explains an optimal approach to diagnosis, treatment, and follow-up of thyroid disease, with an emphasis on the practical and common issues that primary care physicians see in their offices. This is an important book for primary care physicians because thyroid disease is common in the population we take care of and accounts for 3-5 of primary care visits. It is often cited as an area that primary care physicians find confusing. Dr. Brams clarifies thyroid disease and, through his generous sharing of cases, allows us to...


As with any patient, the first step is to obtain a good history (Fig. 1). Because most of the symptoms of thyroid dysfunction are nonspecific, the PCP must first think about possible thyroid disease from the presenting complaints. For example, the patient might present with weight loss. The physician might think about hyperthyroidism as a diagnostic possibility along with such entities as infection, neoplasm, and anorexia. If many of the findings noted here are present on history and in the physical examination, the next step is to get some help from the laboratory. We are fortunate to have one blood test that will rule in or out the diagnosis of hyperthy-roidism or hypothyroidism in more than 90 of patients. That test is the sensitive TSH, which has been available for more than 15 years and is the TSH test now used by all clinical laboratories (the TSH test is discussed in more detail in Chapter 2). A normal TSH would make thyroid dysfunction very unlikely. In hyperthyroidism, the...

Thyroid Physiology

This brief discussion of thyroid-pituitary physiology will help the reader interpret thyroid test results. The thyroid gland produces the thyroid hormones, triiodothyronine (T3) and thyroxine (T4) under the control of the pituitary gland's secretion of thyroid-stimulating hormone (TSH). TSH secretion is also controlled by thyroid-releasing hormone (TRH) from the hypothalamus. A classic endocrine feedback loop (Fig. 1) functions to keep thyroid hormone levels normal in a patient without thyroid or pituitary disease. Thus, a small increase in thyroid hormones in the blood is detected by the pituitary gland (and hypothalamus), and secretion of TSH is decreased. When thyroid hormone levels fall, pituitary TSH secretion rises. The thyroid synthesizes and secretes both T4 and T3. However, much of the T4 that is secreted is deiodinated to T3 in the liver and other peripheral tissues. T3 is the active hormone at the level of the peripheral cell nuclei and at the pituitary and hypothalamic...

Thyroid Imaging

The previous discussion applies to thyroid testing in the outpatient setting where most thyroid testing is ordered. However, thyroid function tests are less reliable in seriously ill patients in the hospital, especially those in the intensive or coronary care units. The term nonthyroidal illness refers to patients who have abnormal thyroid tests but do not have thyroid disease or who may have transient thyroid disease secondary to the acute illness. This section attempts to briefly summarize this rather complex subject. Thyroid tests are often ordered in acutely ill patients because of such findings as atrial fibrillation which suggests the possibility of hyperthyroidism, or lethargy and confusion which may in turn suggest hypothyroidism. Although the TSH alone is adequate to screen for thyroid disease in most outpatients, it is not sufficient in the intensive care unit. The TSH in this setting may be low for a number of reasons unrelated to thyroid disease, including drugs such as...

Selected Sources

Baloch Z, Carayon P, Conte-Devoix B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003 13 3-126. Attia J, Margetts P, Guyatt G. Diagnosis of thyroid disease in hospitalized patients a systematic review. Arch Intern Med 1999 159 658-665


The patient claimed that the heat intolerance was intermittent. She also admitted to diarrhea, nervousness, and a hyper feeling recently. She had gained 10 lb over the previous 9 months since she quit smoking. TSH was 0.1 (0.4-4.5). She denied any family history of thyroid disease, but her mother recalled that a cousin of the patient had Graves' disease and was treated with thyroid surgery. The patient's only medication was a P-blocker prescribed recently by her family doctor. The patient is clinically hyperthyroid, as confirmed by the low TSH. Although Graves' disease is the most likely diagnosis, the differential diagnosis includes autoimmune (silent) thyroiditis and subacute thyroiditis with hyperthyroidism. Treatment options discussed with the patient included radioactive iodine (RAI), antithyroid drugs, and surgery. RAI was recommended, and the patient agreed to treatment. The side effect of permanent hypothyroidism and the possibility of thyroid eye problems were discussed....


The third case, an older woman, presented to an eye doctor because of diplopia. The optometrist did not think about thyroid disease and prescribed prism glasses. Fortunately for the patient, the second eye doctor thought about Graves' disease, took a more complete history, and ordered some thyroid testing. Diagnosis and treatment were delayed several months.

Case 1

This 34-year-old woman was referred by her family physician regarding a thyroid nodule and possible hyperthyroidism. She told me she had noted a lump in the left side of her neck 2 or 3 weeks previously. She denied pain in the area, but she had noted a slight pressure sensation. On questioning, she admitted to the recent onset of heat intolerance and intermittent palpitations. She felt hyper at times, but denied tremor. She was about 1 year postpartum with her second child and had suffered a miscarriage 6 weeks prior to this visit. She had not had a period since her dilation and curettage and thought she might be pregnant again. She had a strong family history of thyroid disease, including hyper-thyroidism in her mother and a cousin. Her grandmother and an aunt had surgery for goiter. She was on no medications. Options for treatment were discussed at length with the patient, including radioactive iodine (RAI), thyroidectomy, and antithyroid drugs (ATDs). She was told that ATDs were...

Case 3

This 49-year-old woman was referred with a 2-month history of pain in the jaw and ear and tightness in her lower neck with swallowing. She had noted fatigue, heat intolerance, sweating, palpitations, and shakiness for 2 mo, along with slight hair loss. She had no past or family history of thyroid disease. TSH was less than 0.1 (0.4-5), FT4 was 2.6 (0.8-1.8). Silent (autoimmune) thyroiditis with hyperthyroidism. The patient was now hypothyroid by testing but asymptomatic. I elected to follow her without treatment. Hypothyroidism in this setting is often transient. The patient was advised that her thyroid function was now normal. No treatment was needed at this point. She was advised that hypothyroidism or hyper-thyroidism could recur, and she was told what to look for. She was asked to return for follow-up in 1 year or as needed. This woman presented with neck and jaw pain and symptoms of hyperthyroidism. Her workup showed a low TSH and elevated free T4 compatible with hyperthyroidism....

Case 4

This woman was hyperthyroid on history and physical examination. The low TSH confirmed the diagnosis. The differential diagnosis was between Graves' disease and hyperthyroidism secondary to thyroiditis. Autoimmune (silent) thyroiditis with hyperthyroidism. The patient was seen 3 months later. She was asymptomatic on no medication. Symptoms of hyperthyroidism and hypothyroidism were discussed and it was agreed that she would call if she developed any of these complaints. Otherwise she would be re-evaluated in 1 year. This woman has autoimmune thyroiditis with hyperthyroidism rather than Graves' disease. The low RAIU is the differential test. The high TPO antibody level, normal sedimentation rate, and absence of pain point toward autoimmune (silent) thyroiditis with hyperthyroidism rather than subacute thyroiditis. If the TSH confirms hyperthyroidism, order an RAIU to differentiate Graves' disease (high uptake) from thyroiditis with hyperthyroidism (low uptake). It is important to...

Case 5

A 27-year-old woman was referred to me because of abnormal thyroid function tests. She had delivered her third child about 8 months previously and there was no history of thyroid problems with her previous pregnancies. After her last delivery, she noted mood swings, fatigue, and heat intolerance along with a 15-lb weight gain. She was having regular menses. There was no family history of thyroid disease. The diagnosis is PPT with borderline or subclinical hyperthyroidism that had resolved and might be progressing toward hypothyroidism in view of the recent borderline low-normal FT4 with normal TSH. This 27-year-old woman had clinical and laboratory evidence of mild PPT disease. Her thyroid tests at 6 months postpartum were compatible with sub-clinical hyperthyroidism and the very low RAIU confirmed PPT as the etiology rather than Graves' disease. Her TSH then normalized and the FT4 dropped to the lower edge of normal with low-normal total T3. She will require careful follow-up to see...


The issue of permanent hypothyroidism and long-term medication requirement can be compared with the problems of long-term ATDs. The patient may ask, Why take the radiation and substitute one medication for another The doctor can point out that these medicines are very different. Thyroid hormone is similar to what the patient's own thyroid would produce and does not usually cause side effects. Also, the dosage is pretty stable and most patients only require a yearly check-up. Taking thyroid hormone is much like taking an aspirin in the morning, perhaps safer. ATDs do have side effects and need much closer follow-up with frequent visits and tests. Most importantly, ATDs do not cure the problem in 80 of patients, even after 1 or 2 years of treatment. Thus, the patient may take medicine for 1 to 2 years with some potential risks and then face the need for RAI therapy. It can be explained to the patient that, although RAI is not a perfect treatment, it is the best option for most patients...

Dietary components and health

The availability of food in Europe has never been as good as in recent decades. Affluent though European countries are, sub-groups of populations experience the deficiency of minerals and micronutrients that play a vital role in health and development (Serra-Majem, 2001). A significant proportion of European infants and children are today experiencing a low dietary intake of iodine and iron (Trichopoulou and Lagiou, 1997a WHO, 1998). The iodine deficiency leads to several disorders collectively referred to as Iodine Deficiency Disorders (IDD), with goitre (hyperplasia of thyroid cells), cretinism (mental deficiency) and severe brain damage being the most common. It is estimated that IDD may affect approximately 16 of the European population. Furthermore, inadequate levels of folate have been implicated with a rise in the blood homocysteine levels, leading possibly to increased risk of cardiovascular disease (CVD). European policies address such deficiencies either by recommending the...

Differential Diagnosis1

Hyperinflation as seen on chest x-ray. In addition, pancreatic insufficiency and failure to thrive are also common characteristics of the disease. In most cases, the diagnosis of CF involves elevated Na+ and Cl sweat concentrations as measured by quantitative pilocarpine iontophoresis. Elevated sweat tests can be seen in patients with other disorders such as fucosidosis, glycogen storage disease type 1 mucopolysaccharidosis, hypothyroidism, celiac disease, malnutrition, and asthma. These diseases are clinically distinguishable from CF, and an elevated sweat test (> 60 mmol L) is usually sufficient for CF diagnosis. However, atypical CF cases have been described in which the sweat chloride values were below 60 mmol L.2 The sensitivity of sweat chloride determined by quantitative pilocarpine iontophoresis using a cutoff of 60 mmol L is 98 with a specificity of 83 . One drawback of sweat analysis is that a minimum weight of sweat collected (75 mg) is required to ensure accurate results...

The Etiology of Major Depression

Among the endocrine disorders that can provoke major depression are Cushing syndrome, hypothyroidism, and hyperparathyroidism. Although the mechanism for the association is not known to be endocrinologic, major depression is seen more frequently with pancreatic carcinoma than with other gastrointestinal neoplasms, and the mood disturbance often precedes local signs of the tumor.

Evaluation and Management of New Onset Ascites

Heart failure, constrictive pericarditis, malignancies, chronic peritoneal infection (especially tuberculosis), pancreatic duct leak, and hypothyroidism. Therefore, every patient with ascites should have an examination of the ascitic fluid obtained by paracentesis that assesses cell and differential count, cytology, glucose, LDH, amylase, total protein, and albumin.2 Determining the difference between serum and ascitic fluid albumin concentrations (the serum-ascites albumin gradient) has been found particularly useful for differential diagnosis a wide gradient (> 1.1 g dL) suggests that the ascites is due to chronic liver disease or cardiac failure, whereas a narrow gradient (< 1.2 g dL) suggests peritoneal carcinoma, peritoneal inflammation, or a hollow organ leak.

Wolfgang H Dillmann and Bernd R Gloss 1 Introduction

Thyroid hormone (T3) is an important signaling molecule for cardiac function. Chronic exposure of the heart to either elevated levels of thyroid hormone (hyperthyroidism) or lower thyroid hormone levels (hypothyroidism) have profound effects on cardiac output. Hyperthyroidism increases the risk of cardiac failure dramatically, and hypothyroidism is associated with a diminished contractile performance of the heart, which is frequently compensated by cardiac hypertrophy. The molecular mechanisms that underlie these complex changes in cardiac performance, which are dependent on thyroid hormone are not yet fully understood. We and others have identified key target genes for thyroid hormone that are expressed in the heart and can account for some of the cardiac phenotypes observed in hyper- and hypothyroidism. Because there are reports that thyroid hormone may have so-called extranuclear effects, and there may also be the possibility of indirect effects of thyroid hormone on the heart, we...

Cigarettes and the brain

Doctors usually diagnose the condition by excluding other illnesses with similar symptoms. As yet, there is no indicator or diagnostic test that can clearly identify the disorder. Overlapping symptoms can occur with several diseases, such as fibromyalgia, Gulf War illnesses, and multiple chemical sensitivities. Lupus, hypothyroidism, and Lyme disease also have similar symptoms and will need to be ruled out when making a diagnosis.

Definition of the Disease

Goiter with hyperthyroidism, exophthalmos, and pretibial myxedema are the pathognomonic triad of Graves disease. Graves disease is a classic organ-specific autoimmune disease where there is a humoral autoimmune response to the TSH receptor. In Graves disease goiter i.e., hyperplasia of the thyroid with palpable (and often visible) gland enlargement and hyperthyroidism (i.e., hyperfunction of the thyroid) result from IgG autoantibodies that bind to and stimulate the TSH receptor. Such agonist autoantibodies i.e., thyroid-stimulating immunoglobulins (TSIs) can be identified in 80-100 of subjects with Graves disease. In contrast, TSIs are detected in 0-10 of control populations and up to 20 of subjects with Hashimoto thyroiditis.

Differential Diagnosis

The causes of primary hyperthyroidism include Graves disease, the destructive phase of Hashimoto thyroiditis, postpartum thyroiditis, toxic thyroid nodules (either single or multiple), viral thyroiditis (subacute thyroiditis also known as de Quervain thyroiditis), pregnancy-induced hyperthyroidism (i.e., from an hCG-sensitive TSH receptor mutation), hCG-secreting tumors (e.g., choriocarcinoma), struma ovarii (i.e., ectopic thyroid tissue in an ovarian teratoma), and exogenous administration of excess thyroid hormone (e.g., factitious hyperthyroidism). Functional thyroid nodules (i.e., hot nodules) are almost never malignant. Iodine-induced primary hyperthyroidism appears to result when an otherwise hyperthyroid patient is euthyroid, at least in part, because of iodine deficiency. Iodine replenishment then allows the clinical expression of hyperthyroidism as more thyroid hormone can now be synthesized. Iodine-induced hyperthyroidism can be referred to as the Jod Basedow syndrome. The...

Inflammatory Lesions and Lymphoma

Thyroiditis comprises a diverse group of inflammatory thyroid lesions and is one of the most common endocrine disorders in clinical practice. The most frequently encountered form is chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), first described in 1912, and a major cause of goiter and hypothy-roidism in the United States. Clinically, patients are young to middle-aged women who present with a moderately enlarged nodular thyroid that is nontender. Approximately 90 of patients have high circulating titers to thyroid peroxidase and, to a lesser extent, thyroglobulin. Hashimoto's thyroiditis is an autoimmune disorder that is thought to be caused by a derangement of suppressor T lymphocytes. Possible contributing factors to this disease include genetic associations with HLA-DR3,HLA-DR5, and HLA-B8 viral and infectious factors have also been proposed.Approximately 10 of cases are the fibrosing variant of Hashimoto's thyroiditis that presents as severe hypothyroidism in elderly...

Thyroid Hormone and Brain Development

In the most studied model of thyroid hormone deficiency, the severely hypothyroid rat, there are no gross alterations of brain morphology. However, there are defects of myelination, alterations of cell migration in the cerebral cortex and the cerebellum, and abnormal differentiation of many neurons, including cholinergic cells and cerebellar Purkinje cells, with severe functional consequences (2).

Dietary sources supplementation and fortification

The addition of minerals and other nutrients to foods to increase their nutritional value is widely practised. In the 1920s iodised salt was introduced in some countries to help combat endemic goitre. Iodised salt, as well as other iodised foods such as bread and monosodium glutamate, are today widely used in parts of the world where iodine deficiency diseases (IDD) are still endemic, such as India, and China, Papua New Guinea, Central Africa and the Andean region of South America.

Other minerals iodine and selenium

The non-metallic element iodine is an essential nutrient that, apparently, has a single function in the body as a component of the thyroid hormones thyroxine (T4) and triiodotyronine (T3). These hormones are necessary for a range of body processes, the most important of which are the control of metabolic rate, cellular metabolism, growth and neural development. Production of T4 and T3 is controlled by tissue demands which are mediated by the secretions of the pituitary gland and by the supply of iodine in the diet. Deficiency of iodine can result in a number of diseases, ranging from severe cretinism with mental retardation to barely visible enlargement of the thyroid gland. Goitre is the name given to enlargement of the gland that occurs as the body attempts to compensate for a reduction of its supply of iodine by increasing the size of the gland. The amount of enlargement is related to the degree of iodine deficiency. The condition is widespread throughout the world, with up to a...

Differential Diagnosis and Pitfalls

A challenging diagnostic problem in thyroid cytology is the distinction of Hashimoto's thyroiditis from MALT lymphoma because of the heterogeneous population of lymphocytes in each. Cytologic differences between these two can be very subtle, but features favoring Hashimoto's thyroiditis include a combination of lymphocytes in all stages of maturation with a predominant population of small mature lymphocytes and admixed plasma cells, and lymphohistiocytic aggregates with tingible body macrophages and activated follicle-center cells. Because of the cytologic overlap between Hashimoto's thyroiditis and MALT lymphoma, the ultimate distinction between these two entities depends upon evaluation of light chain restriction through immunophenotyping by flow cytom-etry or immunocytochemistry. Cytologic Features Favoring Hashimoto's Thyroiditis Over MALT Lymphoma The presence of giant cells in thyroid aspirates raises a differential diagnosis that includes subacute thyroiditis as well as...

Clinical Management and Prognosis

For cases in which clinical hypothyroidism is present, chronic lymphocytic thyroiditis is managed by thyroid hormone replacement. Approximately 20 of patients with chronic lymphocytic thyroiditis are hypothyroid at presentation, and approximately 5 of the patients who are euthyroid progress to hypothyroidism each year. Surgical intervention is reserved for those cases in which the thyroid is so enlarged that the patient develops compressive symptoms. When dominant nodules or rapid diffuse thyroid enlargement occur in the setting of chronic lymphocytic thyroiditis, FNA is used to rule out the possibility of a neoplastic condition, particularly lymphoma and PTC. Subacute thyroiditis is a self-remitting painful disorder that in some cases can be associated with hypothyroidism lasting up to several months. Most cases are treated with nonsteroidal antiinflammatory drugs to manage the associated pain, but in some cases the pain is so severe that oral corti-costeroid therapy is needed. A...

Suggested Reading

The various presentations of thyroiditis diagnostic considerations. Ann Intern Med 1986 104 219. Lerma E, Arguelles R, Rigla M, et al. Comparative findings of lymphocytic thyroiditis and thyroid lymphoma. Acta Cytol 2003 47 575-580. Poropatich C, Marcus D, Oertel YC. Hashimoto's thyroiditis fine-needle aspirations of 50 asymptomatic cases. Diagn Cytopathol 1994 11 141-145. Weetman AP, Mcgregor AM. Autoimmune thyroid disease further developments in our understanding. Endocr Rev 1994 15 788.

Colloid Predominant Lesions

The term goiter refers to any enlargement of the thyroid gland. However, most goiters are caused by a nonneoplastic, dynamic process in which there is hyperplasia and regression of the follicular epithelium and accumulation of colloid within the enlarged follicles. Grossly, this can lead to the development of multiple nodules of varying sizes within the gland, termed multinodular goiter. Often the largest or dominant nodule is the target of the fine needle aspiration (FNA). Iodine deficiency is a major cause of multinodular goiter in some countries however, in geographic areas where dietary iodine is sufficient, the etiology of multinodular goiter is unknown. It may involve abnormalities in thyroid hormone production and variable sensitivity of follicular cells to thyroid-stimulating hormone (TSH). For unclear reasons, multinodular goiters are more common in women and increase with age.

Why Consider A Career In Internal Medicine

Internists are knowledgeable in many aspects of medical care. They treat acute and chronic conditions, not to mention common and rare disease entities. Even if you choose another specialty, no physician can avoid the basics of internal medicine. For instance, orthopedic surgeons have to treat hypokalemia, obstetricians-gynecologists need to be well versed in the management of hypertension, and psychiatrists must be able to recognize the signs and symptoms of hypothyroidism. Internal medicine is, in a way, the foundation for all fields of medicine. If you are excited by the prospect of providing care for adults as a diagnostician, healer, motivator, and patient advocate, you would certainly find a career in internal medicine rewarding.

General Diagnostic Approach

Hurthle cells are found in a variety of neoplastic as well as nonneoplastic follicular lesions of the thyroid. Consequently, Hurthle cell lesions tend to fall into either the epithelium-predominant, colloid-predominant, or inflammatory categories of the diagnostic algorithm (Figure 7.1). Because lesions in these categories are managed very differently, FNA is utilized as a screening test for Hurthle cell carcinoma. Adenomatous nodules and Hashimoto's thyroiditis are two of the most common benign processes that can have Hurthle cells admixed with other benign components. In contrast, aspirates of true Hurthle cell neoplasms are pure populations of Hurthle cells. The key to the FNA diagnosis of thyroid nodules containing Hurthle cells is to separate those for which surgery is indicated (Hurthle cell adenomas and carcinomas) from those that can be diagnosed as benign (adenomatous nodules with oncocytic changes and Hashimoto's thyroiditis) and thus managed without surgical intervention....

Inborn errors of metabolism 271

Inborn errors of metabolism A group of more than 200 inherited disorders in which the body cannot metabolize food components normally. These disorders are usually caused by gene defects that cause a particular enzyme to be defective or missing. Enzymes are proteins that help the body use food, produce energy, and do work. The particular enzyme involved determines what the body cannot do and what the resulting problem may be. The likelihood of having an inborn error of metabolism is about one in 5,000 live births. some of the more common inborn errors of metabolism are cystic fibrosis, hypothyroidism, sickle-cell disease,

Molecular Cloning of TR Sequences from RTH Syndrome Patients

RTH syndrome patients are identified initially in the clinic as individuals manifesting aberrantly high levels of circulating T3 and T4 thyronine hormone, normal or elevated levels of thyroid-stimulating hormone (TSH), and overt or compensated hypothyroidism (1-4). Typically, once patients are diagnosed with RTH syndrome, genomic DNA is isolated from blood samples and subjected to PCR (PCR) so as to recover adequate material for molecular cloning and for sequence analysis (e.g. 34 ). These approaches generally focus on exons 4 to 10 of the TRP gene, which encode all but the first 8 amino acids of the open reading frame of the receptor. The sequences of the patient TRP genes are then compared to the wild-type TRP sequence to identify any specific base pair substitutions, deletions, or additions (see Note 1). Once a specific TRP mutation has been identified, it can be introduced into a variety of expression vectors for further experimental characterizations. Usually, the RTH syndrome...

Newborn screening tests

Congenital hypothyroidism This is the disorder most commonly identified by routine screening. Affected babies do not have enough thyroid hormone, which can lead to retarded growth and brain development. The thyroid, a gland at the front of the neck, releases chemical substances that control metabolism and growth. If the disorder is detected early, a baby can be treated with oral doses of thyroid hormone to permit normal development.

Extraintestinal Manifestations

CD has been shown to be closely associated with a number of other disorders. Dermatitis herpetiformis, a skin disease characterized by symmetric pruritic papulovesicular lesions and the presence of granular deposits of IgA in the skin, affects 10-20 of patients with CD and responds to withdrawal of gluten from the diet. CD is also strongly associated with type I diabetes and autoimmune thyroid disease, especially hypothyroidism. The prevalence of CD in type I diabetes patients is 3-8 .2 Patients with untreated CD have an increased risk of certain types of cancer, specifically non-Hodgkin lymphoma, enteropathy-associated T-cell lymphoma, small intestinal adenocarcinoma, and esophageal or oropharyngeal squamous carcinoma. Neurological disorders, including peripheral neuropathy, cerebellar ataxia, epilepsy, and migraine, have also been shown to be associated with CD. Women with untreated CD may present with infertility, and infertility secondary to impotence or abnormally low sperm count...

Thyroid hormone and the hippocampus

But this hypertrophy is not necessarily to the benefit of the treated animal. On one hand, in the rat experiments cited earlier, both male and female hyperthyroid animals are slower to acquire a hippocampal-dependent spatial learning task and are somewhat impaired in showing long-term potentiation in the hippocampus (Pavlides et al., 1991). On the other hand, a strain of mice that normally shows poor spatial learning and may have a congenital deficiency of thyroid hormone secretion during early development displays a beneficial effect of the same kind of neonatal thyroid hormone treatment (Schwegler et al., 1991). Thus there is an optimal level of thyroid hormone that is associated with optimal cognitive performance, and deviations in the direction of both hyper- and hypothyroidism result in deficiencies in neural development and cognitive function. Changes in response to thyroid hormones have been studied in hippocampus as a function of developmental age. In the CA3 region, the main...

Branchial Cleft Cysts and Ultimobranchial Body Cysts

Ultimobranchial Cyst

Branchial cleft-like cysts (lymphoepithelial cysts) and ulti-mobranchial body cysts (cystic solid cell nests) are rare in the thyroid gland, and when they do occur it is often in association with Hashimoto's thyroiditis. Aspirates of branchial cleft cysts of the neck and branchial cleft-like cysts of the thyroid are similar and contain turbid proteinaceous fluid and degenerate squamous cells, as well as glandular cells that may be mucin containing or ciliated.Variable amounts of background lymphocytes can be seen, but colloid and follicular cells are absent. Without clinical information, it may be impossible to distinguish a branchial cleft cyst from a thyroglossal duct cyst on the basis of cytologic features alone. An abundance of background lymphocytes and germinal center fragments favors a branchial cleft cyst, but lymphocytes are not always present.

The Thyroid Hormone Axis

TRH neurons are located in the paraventricular nucleus where the presence of the orexin-2, but not orexin-1 receptor mRNA has been reported (30). The presence of OX2R or OXjR receptors specifically on TRH neurons and orexin (hypocretin) projections to TRH neurons have not been reported. Nevertheless, an interaction between orexins and the thyroid axis is intriguing and requires further study since thyroid hormones are important in the regulation of energy expenditure and catecholaminergic responses and, the orexins also influence these systems. No changes in prepro-orexin mRNA or orexin receptor levels with medical thyroidectomy or hyperthyroidism, however, have been observed (31). The effects of thyroid hormone manipulations on peptide content and release have not been reported. Since the orexins have been shown to have profound effects on sleep, wakefulness, and locomotor activity, changes in orexin levels may parallel or oppose the effects of low thyroid hormone status on these...

Hypocretin Status In Hypersomnia In Various Neurological Conditions

Arii et al. (55) reported on a 16-yr-old girl with hypersomnia after removal of a hypothalamic suprasellar grade II pilocystic astrocytoma. MRI showed that the bilateral, medial, and lateral hypothalamic areas and right posterior hypothalamus were damaged. This patient had diabetes insipidus, hypothyroidism, weight gain, no cataplexy, sleep latency of 1.7 min by MSLT, no SOREMPs, and a hypocretin-1 level of 104 pg mL she was HLA DR2 negative. Marcus et al. (52,112) reported on an 11-yr-old boy in a vegetable state following astrocytoma resection and CNS hemorrhage. MRI revealed a large suprasellar mass that extended into the sella inferiorly and was displaced posteriorly. The boy developed hypothyroidism and syndrome of inappropriate antidiuretic hormone (SIADH). In the nocturnal EEG study, sleep was fragmented, with 16 short REM cycles. The daytime EEG showed frequent REM periods. HLA DR2 and DQB1*0602 were negative. Hypocretin-1 was at an undetectably low level. His EDS improved...

NCoRi Animal Model to Study Biological Function of NCoR in Liver

Hollenberg et al. (37) have reported that a variant form of NCoR, NCoRi, lacks the repression domains in the amino terminus, but retains the nuclear receptor interaction domains. NCoRi is derived from a 3.1 kb cDNA that was originally isolated from a human placental library. NCoRi protein contains the TR interaction domains and surrounding amino acids (AA 1539-2453), but lacks the repressor domains (AA 1-1120) present in full-length murine NCoR. It also has been shown that NCoRi has dominant negative activity on endogenous NCoR as it blocked basal repression by TR in in vitro transfection assays (37). To study the biological function of NCoR in vivo, we constructed an expression vector containing the NCoRi cDNA and the mouse albumin promoter to target expression of NCoRi to the liver (38) (Fig. 2). NCoRi mRNA was expressed 17 to 146 times higher than endogenous NCoR mRNA in transgenic mouse lines in the euthyroid state (38). Northern blot analysis of various tissues showed that NCoRi...

Differential Diagnosis of Hyponatremia

Hypothyroidism In hypoosmotic hyponatremia with normal volume status, the most common etiologies are the syndrome of inappropriate ADH (SIADH), primary polydypsia, hypothyroidism, or adrenal insufficiency. SIADH is usually a result of ectopic or otherwise inappropriate ADH production arising from a variety of conditions and results in excessive H2O retention. SIADH often is diagnosed by a urine osmolality that is greater than plasma osmolality in the setting of hyponatremia, but only when renal, adrenal, and thyroid functions are normal.

Voice Disorders of Aging

Age-related changes in the endocrine system also affect the voice. Secretion disorders of the thyroid (both hyperthyroidism and hypothyroidism) occur commonly in the elderly and often produce voice symptoms, either as a consequence of altered hormone levels or as a result of increased pressure on the recurrent laryngeal nerve. In addition, voice changes are possible with thy-roidectomy, even if the procedure is uncomplicated (e.g.,

The Fatigued Attorney

A 28-year-old attorney reported for her yearly physical examination complaining of tiredness, difficulty concentrating on her work, and a noticeable decline in her memory over the past several months. She attributed many of these symptoms to the severe stress generated by her legal caseload. Further questioning by her physician revealed that the frequency of her bowel movements had decreased from once daily, 6 months ago, to once every 2 or 3 days. She was having difficulty keeping her weight down, and despite warm weather, she felt chilled without a light sweater. Her only medication was an oral contraceptive. Family history was significant for hypothyroidism in her mother and older sister. The initial clinical impression was that of moderate hypothyroidism of several months' duration. The texture of her thyroid gland and the occurrence of hypothyroidism in her family suggested an autoimmune etiological factor. The following serum values were reported The laboratory results, low free...

Laboratory Investigation of SIADH

Hyponatremia Investigation

Since hyponatremic plasma can be either hyperosmotic, isotonic, or hypoosmotic, the measurement of plasma osmolality is an important initial step in the assessment of hyponatremia. As described above, in hypoosmotic hyponatremia with normal volume status, the most common etiologies are SIADH, primary polydypsia, hypothyroidism, or adrenal insufficiency. In this patient the mild edema suggests slight excess of TBW. If SIADH is suspected in a patient with mild hyponatremia, a water-loading test can be performed to confirm the diagnosis. The test is based on the rationale that in normal patients there is an inverse correlation between plasma osmolality and ADH release. Briefly, 2 hours after the patient has a light breakfast in the morning, plasma and urine osmolalities are measured. The patient is then given water to drink (20 mL kg) over a 15-30-minute period, followed by collection of hourly urine and plasma specimens for the next 4 hours for assessment. Total urine output is also...

Management of CVD Risk Factors Behavioral Risk Factors

Prior to the initiation of any therapies, secondary causes of dyslipidemia are ruled out including alcohol, diabetes, hypothyroidism, liver kidney disease, and concurrent drug therapy. Using the recommendations from the SCORE chart, TC and LDL-C goals are used to guide the decision process and, in general, should be kept < 190

Impact on health absorption and recommended intakes

Uptake of certain minerals from food can be affected by other components of the diet. Thus phytic acid and phytates in cereals can inhibit absorption of iron and zinc. The same effect can be caused by oxalate in certain vegetables. Iodine absorption can be limited by sulphur-containing compounds known as goitrogens, which occur in certain plants, such as some brassicae and cassava. Consumption of these vegetables can acerbate iodine deficiency and increase the likelihood of goitre.

Middle Aged Woman with Colles Fracture

On physical examination, the patient is a 5-ft-tall, 94-lb middle-aged woman who describes herself as physically fit and in good health. She reports running 3-4 miles 3 times per week and participating in additional physical exercise that includes weight and resistance training. Her past medical history includes two full-term, uneventful pregnancies, menopause at age 41, but no history of thyroid disease, diabetes, or Cushing syndrome. A daily multivitamin supplement is her only current medication. She has never received hormone replacement therapy. She has no documented family history of osteoporosis, although she recalls her grandmother losing height as she aged and developing a dowager's hump, and notes that her 80-year-old mother appears to be losing height as well. The following laboratory results were obtained

Thyroid Hormone

The control of the central nervous system by thyroid hormone has been known for many years from analyzing hypothyroid rats. The absence of thyroid hormone during maturation of the central nervous system leads to irreversible mental retardation (12-14, and references therein). There is retarded development of the neurophil and Purkinje cells accompanied by diminished dendritic branching, elongation, and altered distribution of dendritic spines, delayed cell proliferation, and migration. Furthermore, deficiencies in myelination have been observed. poles to adult frogs is under strict control of thyroid hormone. In early developmental stages, TRs are present, but thyroid hormone is not produced, indicating an important biological role for unliganded TRs. Experimentally induced lack of thyroid hormone prevents the metamorphosis resulting in giant tadpoles, while addition of hormone to young tadpoles leads to earlier metamorphosis and very small frogs. However, exactly how thyroid hormones...

Using the Laboratory

If major depression is diagnostically certain on clinical grounds, the physician should always obtain thyroid function studies. Hypothyroidism (and, more rarely, hyperthyroidism) may present with severe depression and few or no physical findings. Screening tests for other endocrine or metabolic abnormalities are usually not indicated unless the physical examination or medical history suggests them. Here, however, the physician must also consider the potential medical complications of severe depression, including dehydration, malnutrition, and the consequences of immobility (e.g., atelectasis, venous thrombosis).


For most patients with a thyroid nodule, their clinical history does not contribute significantly to the FNA diagnosis. Features of the clinical history that do raise the suspicion of a thyroid malignancy in patients with a thyroid nodule include male gender, age less than 20 years or greater than 70 years, dysphagia or hoarseness, a history of neck irradiation during childhood or adolescence, a family history of thyroid disease especially papillary thyroid carcinoma (PTC), medullary carcinoma (MC), or multiple endocrine neoplasia (MEN) , or a rapid increase in the size of a long-standing goiter. Other useful clinical information includes a history of Hashimoto's thyroiditis, a history of Graves' disease or 131I therapy, or a history of a nonthyroid malignancy. Family history of thyroid disease, especially PTC or MC Family or personal history of an MEN syndrome Dysphagia or hoarseness

Helpful Notes

All the findings and problems associated with nephrosis can best be understood when viewed as a consequence of protein loss. Thus, it is important to consider the pathophysiological mechanism of nephrotic syndrome in evaluating the patient. For example, the symptomatic treatments suggested above reflect the need to deplete fluid from the tissue space rather than from the vascular space. Trace minerals that are protein bound (e.g., zinc) may be depleted because of albuminuria. Loss of other proteins may cause alterations in laboratory values, such as the decreased serum calcium concentration that reflects loss of albumin as a binding protein and the decreased serum total thyroxine that reflects loss of thyroxine-binding globulin. These changes are seldom of physiological consequence since ionized calcium concentrations and free thyroxine should be normal. However, vitamin D binding protein is lost in the urine, so 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels may be low12 and...

Thyroid Dysfunction

The thyroid gland secretes hormones that control your metabolism, the rate at which your body burns energy. When the thyroid doesn't function properly, it can make your metabolism run too quickly or too slowly. Either problem can interfere with learning and memory. Research with animals demonstrates that changes in levels of thyroid hormones cause physiological changes in the hippocampus. An overactive thyroid (hyperthyroidism) can impair your memory and your ability to sustain attention. Hyperthyroidism is also associated with anxiety, insomnia, and tremor. An underactive thyroid (hypothyroidism) can cause generalized cognitive slowing, sluggishness, and psychiatric symptoms. If you suffer from thyroid problems, getting the proper medical treatment should help prevent or diminish memory difficulties.

Value SI Units

Exophthalmos results from edema of the retroorbital muscles and adipose tissue hyperplasia. While the etiopathogenesis of exophthalmos is controversial, TSIs are believed to be involved. Some investigators have demonstrated TSH receptors on retro-orbital tissues. Pretibial myxedema is a marker of autoimmune thyroid disease (AITD) in general because pretibial myxedema can be observed in both Graves disease and Hashimoto thyroiditis. TSIs have also been implicated in the genesis of pretibial myxedema. Susceptibility to autoimmune thyroid disease, both Graves disease and Hashimoto thyroiditis, appears to be inherited in an autosomal dominant pattern with increased penetrance in women. The genetic locus providing this susceptibility has eluded definitive identification. Onset of AITD can occur during childhood or adulthood. Both Graves disease and Hashimoto thyroiditis are strongly familial and can occur in the same family. Among female siblings, mothers and offspring within a single...


Usually satisfactory because T3 testing is not a first-line screening test for thyroid dysfunction. Furthermore, because of its higher concentration, in analytical terms total T3 is more easily measured than FT3. T3 (or FT3) should usually only be measured to rule in or rule out T3 toxicosis. Even in the setting of hypothyroidism, a low T3 in addition to a low FT4 provides no additional diagnostic or therapeutic information. Isolated depressions in T3 with normal TSH and FT4 concentrations are not uncommon in sick inpatients displaying sick euthyroid syndrome (e.g., nonthyroidal illness). To avoid confusion with sick euthyroid, inpatient thyroid function testing should only be performed when myxedema coma or heart failure, or thyroid storm are clinical considerations that would require immediate medical therapy if recognized. Furthermore while FT4 and T3 are both elevated in thyroid storm, the diagnosis of storm is not based on laboratory values but is based on the clinical status of...


Worldwide, iodine deficiency is still the most common cause of hypothyroidism an estimated 400 million people are at risk. In regions with sufficient iodine, particularly North America and Europe, autoimmune thyroid disease (primarily Hashimoto's thyroiditis) is the usual cause of hypothyroidism. The incidence of congenital hypothyroidism (cretinism), in iodine-sufficient countries, is approximately one in 4000 births and may be associated with the most severe neuropsychological abnormalities.1 This high incidence has resulted in the institution of neonatal screening programs in many developed countries. Clinical features include feeding problems, hypotonia, umbilical hernia, constipation, enlarged tongue, dry skin, characteristic facies, and open posterior fontanelle. On radiological examination, poor skeletal maturation can be seen as retardation in the appearance of ossification centers. Failure to institute early treatment with thyroid hormone leads to significant brain damage....


The most common cause of dementia is Alzheimer disease, which accounts for approximately 60 percent of cases. Alzheimer disease is a diagnosis of both inclusion and exclusion. Inclusion criteria are the gradual development of cognitive decline over months or years, impairments in memory, and at least one other cognitive dysfunction (i.e., aphasia, apraxia, or agnosia). The exclusion criterion is that other causes (e.g., cerebrovascular disease, Parkinson disease, major depression, hypothyroidism, pernicious anemia, subdural hematoma) have been ruled out. Potentially curable dementias are rare but should be considered. Chronic subdural hematoma, hydrocephalus (characterized by dementia, gait disorder, and incontinence), major depression, gradually developing renal failure, endocrinopathies (e.g., hypothyroidism, hyperparathyroidism), and chronic central nervous system (CNS) infection (e.g., human immunodeficiency virus HIV , syphilis) can cause partially or fully reversible dementias.

The Reluctant Chef

These laboratory results confirmed the clinical impression of euthyroidism and gave no serological evidence for autoimmune thyroid disease. Evaluation of the thyroid biopsy smears revealed clusters of pleomorphic cells with eccentrically located nuclei and presence of intranuclear cytoplasmic inclusions. Immunoperoxidase staining identified calcitonin granules in the cytoplasm. The cytological diagnosis was medullary carcinoma of the thyroid. Biopsies of the cervical lymph nodes revealed the presence of cells identical to


A thorough history and physical examination (including neurologic examination) should be carried out. This is important because most curable causes of dementia are revealed by their characteristic symptoms (e.g., cold intolerance in hypothyroidism) and signs (e.g., hyporeflexia).

Genes of Myelination

Myelination in the CNS is carried out by oligodendrocytes, a special type of glial cells whose terminal differentiation is greatly influenced by thyroid hormone (7). Accordingly all the genes encoding proteins of myelin (8), such as myelin basic protein (MBP), myelin-associated glycoprotein (MAG), proteo-lipid protein (PLP), and cyclic nucleotide phosphohydrolase (CNP) are under thyroid hormone control in vivo with a similar timing. Dependency of these genes from thyroid hormone is transient, so that in the hypothyroid neonatal rat there is a delayed accumulation of mRNA and protein, but eventually they reach normal levels even in the absence of thyroid hormone treatment and become thyroid hormone independent.

The Tired Teenager

Review of his family history revealed that his 42-year-old mother developed Hashimoto thyroiditis at age 16. The maternal aunt had Graves disease that was diagnosed at age 22. In light of the family history of autoimmune thyroid disease, the finding of primary autoimmune adrenal failure as the etiology of the patient's Addison disease is not unexpected. Because multiple autoimmune endocrine diseases can occur in the same individual, the reference laboratory was asked to test the patient's serum sample for islet autoantibodies e.g., islet cell cytoplasmic autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and insulin-associated 2-autoantibodies (IA-2A) , thyroperoxidase autoantibodies (TPOA), and steroidal cell autoantibodies (SCA). Whereas ICA, GADA, IA-2A, and SCA were negative, TPOA was strongly positive. Thyroid function studies revealed the following results

Hurthle Cell Lesions

Fine needle aspiration (FNA) is highly sensitive at detecting Hurthle cell carcinomas, but unfortunately the specificity of an FNA diagnosis of a Hurthle cell neoplasm for carcinoma is low, hence its role as a screening test rather than as a diagnostic test.Approximately 14 to 30 of patients diagnosed by FNA as having a Hurthle cell neoplasm actually have a Hurthle cell carcinoma, whereas the majority of the remaining patients prove to have Hurthle cell adenomas approximately 10 are adenomatous nodules with oncocytic changes or Hashimoto's thyroiditis.

Interleukin 261

Interleukin-2 (IL-2) is a protein produced by activated T cells in the body. It plays a central role in the regulation of immune responses against infection or cancerous cells. In people living with HIV, IL-2 levels are abnormally low. It is thought that this deficiency contributes to the overall deterioration of the immune system in HIV disease. IL-2 was discovered in 1976 at the National Cancer Institute and was originally called T cell growth factor. IL-2 stimulates the growth and activities of a range of cells, including cytotoxic t lymphocytes (CTLs), lymphokine-activated killer cells (LAK cells), and tumor-infiltrating lymphocytes (TIL cells). As HIV disease progresses, levels of IL-2 are reduced. As alpha interferon has been, IL-2 has been synthesized and is approved for treatment of kidney cancer in several countries. In addition, it is under development as a treatment for other diseases, including HIV. It is known that IL-2 induces the multiplication of CD4 (T-helper) cells...

Diagnostic Criteria

Placed, giving a plasmacytoid appearance, and binucleation is common (Figures 7.3,7.4). Colloid (a characteristic feature associated with adenomatous nodules) is very scant or absent, and background chronic inflammation (a feature associated with Hurthle cells in Hashimoto's thyroiditis) is also not present.

Associated Features

PTC often contains multinucleated giant cells that are his-tiocytic in origin. Although the presence of multinucleated cells raises the possibility of PTC, they are nonspecific and can also be seen in palpation thyroiditis or true granuloma-tous inflammatory conditions such as tuberculosis or subacute thyroiditis (see Chapter 4). At least one study indicates that the multinucleated giant cells associated with PTC tend to have more dense cytoplasm and more abundant nuclei than the foreign-body-type giant cells seen in other processes. Densely staining, ropey colloid (also called bubble gum colloid) is also a feature of PTC, but this, too, is nonspecific (Figure 9.9).

Warthins Like Variant

Occasional papillary cores containing lymphocytes and plasma cells are seen, especially in cell block material. This tumor behaves like conventional PTC, but it is important to distinguish it from Hashimoto's thyroiditis or a follicular lesion with oncocytic changes (Figure 9.15).


Because follicular cells in other thyroid lesions can also have enlarged nuclei. Because of its enlarged nuclei and variable grooves, Hurthle cell lesions, particularly those associated with Hashimoto's thyroiditis, are included in the differential diagnosis of PTC. However, in contrast to the nuclei of PTC, the nuclei of Hurthle cells are typically round, rather than oval, and usually contain a prominent central nucleolus. The abundant granular cytoplasm in Hurthle cells is also a potential pitfall as it can resemble the cells seen in oncocytic variant of PTC. Graves' disease can also cause marked nuclear enlargement with nuclear grooves, but the nuclei are more round and are surrounded by abundant cytoplasm containing secretory vacuoles and extracellular fire flares. 131I therapy can also induce striking nuclear enlargement and atypia, but the atypical nuclei tend to be random, rare, often multinucle-ated, and surrounded by abundant, vacuolated cytoplasm (Figures 9.21-9.23, Table...

Hypoechoic Changes

Hypo And Hypertyroidism Comparison

Fig. 616a, b Subacute de Quervain thyroiditis. a B-mode image patchy hypoe-choic thyroid gland (TG compare with muscle, M). b CDS individual color spots. The hypoechoic areas are largely devoid of vessels Fig. 616a, b Subacute de Quervain thyroiditis. a B-mode image patchy hypoe-choic thyroid gland (TG compare with muscle, M). b CDS individual color spots. The hypoechoic areas are largely devoid of vessels n Acute and subacute de Quervain thyroiditis (Fig. 616) This disease presents clinically with acute malaise, local tenderness, inflammatory laboratory parameters, and frequent transient hyperthyroidism. CDS increased vascularity. Sclerotic areas are hyperechoic and hypovascular n Chronic lymphocytic Hashimoto thyroiditis (Fig. 617) Patients present clinically with asymptomatic hypothyroidism of early onset and a shrunken, fibrotic gland. Other findings are an elevated ESR and high titers of thyroid peroxidase (TPO) antibodies and thyroglobulin (Tg) antibodies (see also Fig. 245, p....

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