Latest Treatment of Hypothyroidism

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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Hashimotos thyroiditis

Hashimoto's thyroiditis is a disease of middle-aged women that results from a B- and T-cell response to different components of the thyroid gland such as thyroglobulin and epithelial cell microsomes. There is an intense lymphocyte infiltration of the gland and the thyroid follicles are progressively destroyed. In an attempt to regenerate the gland becomes enlarged with a rubbery hard consistency, but patients are ultimately rendered hypothyroid. Treatment during the acute phase is with steroids and thyroxine. If pressure symptoms develop, a subtotal thyroidectomy should be performed (Fig. 11.14).

Ecology of Iodine Deficiency

The better known areas that are leached are the mountainous areas of the world. The most severely deficient soils are those of the European Alps, the Himalayas, the Andes, and the vast mountains of China. However, iodine deficiency is likely to occur to some extent in all elevated regions subject to glaciation and higher rainfall, with runoff into rivers. It has become clear that iodine deficiency also occurs in flooded river valleys, such as the Ganges in India, the Mekong in Vietnam, and the great river valleys of China. Figure 1 The iodine cycle in nature. The atmosphere absorbs iodine from the sea, which then returns through rain and snow to mountainous regions. It is then carried by rivers to the lower hills and plains, eventually returning to the sea. High rainfall, snow, and flooding increase the loss of soil iodine, which has often been already denuded by past glaciation. This causes the low iodine content of food for man and animals. (Reproduced from Hetzel BS (1989) The...

TABLE 2071 Etiologies of Hypothyroidism

Primary hypothyroidism usually has an insidious onset. Clinical signs and symptoms of hypothyroid patients are listed in TabJ.e2.0Z 2 Individuals with suspected uncomplicated hypothyroidism may be evaluated as outpatients. Typical laboratory findings in primary hypothyroidism include low thyroxine (T 4) and high thyrotropin (thyroid-stimulating hormone or TSH). Triiodothyronine (T3) is an unreliable indicator of hypothyroidism and is not routinely measured. There is little urgent need for performing thyroid function tests, and typically they are not available during an emergency department visit. However, obtaining blood for testing in the emergency department may be helpful to a patient's health provider in follow-up care. In many cases, elderly patients with hypothyroidism may exhibit a paucity of symptoms. Because of the high prevalence of hypothyroidism in women over age 60, it is recommended that they be routinely screened with a serum TSH measurement.56

TABLE 2072 Symptoms and Signs of Hypothyroidism

Primary uncomplicated hypothyroidism is treated with T4 administration. Initiation of oral therapy begins at a dose of 50 to 100 Mg day and is gradually increased. The average daily adult dose is 75 to 150 Mg. Elderly patients with underlying heart disease are treated with lower initial dosages. Therapy is monitored to ensure that appropriate serum thyrotropin levels are achieved after 6 to 8 weeks following initiation of therapy. If hypothyroidism is due to less common secondary etiologies, initiation of thyroid hormone replacement may exacerbate preexisting adrenal insufficiency. Therefore, the etiology of hypothyroidism (primary versus secondary failure) should be determined prior to initiating T 4 replacement. Initiation of therapy in the emergency department is rarely warranted for simple hypothyroidism. Clinical clues that may differentiate primary and secondary hypothyroidism are listed in T b e.207 3. TABLE 207-3 Differentiation of Primary and Secondary Hypothyroidism7

Correction of Iodine Deficiency Iodized Salt

Successful programs have been reported from a number of countries, including those in Central and South America (e.g., Guatemala and Colombia) and Finland and Taiwan. However, there has been great difficulty in sustaining these programs in Central and South America mainly due to political instability. Following the breakup of the Soviet Union, iodine deficiency recurred in the Central Asian republics.

Thyroid Hormones and Anti Thyroid Drugs Hypothyroidism

Deficiency of thyroid hormones is treated with replacement therapy usually with L-thyroxine (T4). If a rapid onset of action is required (e.g. hypothyroid coma) then tri-iodothyronine (Liothyronine) is used. This is effective within a few hours and lasts up to 48 H. Specific anti-thyroid drugs have a variety of effects the thioureylenes (such as carbimazole) block organification of iodine, potassium iodide inhibits secretion of thyroid hormones and radio-iodine causes destruction of thyroid follicle cells.

Amiodarone induced thyroid disease

Amiodarone is a lipid soluble benzofuranic antiarrhythmic drug that has complex effects on the thyroid and may interfere significantly with thyroid hormone metabolism.17 18 Owing to its high iodine content amiodarone may cause thyroid dysfunction in patients with preexisting thyroid disease it can also cause a destructive thyroiditis in patients with an inherently normal thyroid gland. The combined incidence of hyper- and hypothyroidism in patients taking amiodarone is 14-18 and, because of its extraordinarily long half life, either problem may occur several months after stopping the drug.

Amiodarone induced hypothyroidism

Amiodarone may cause hypothyroidism in patients with pre-existing Hashimoto's thyroiditis. However, the presence of a raised serum TSH concentration before or during treatment is not a contraindication to the use of amiodarone as the thyroid failure is readily treated with thyroxine. Amiodarone will induce hyper- or hypothyroidism in up to 20 of subjects, and thyroid dysfunction may persist for several months or develop for the first time after the drug has been stopped. Thyroid status should be evaluated thoroughly before introducing the drug because patients with pre-existing (often occult) thyroid disease are at particularly high risk.

Iodine Deficiency Disorders

The effects of iodine deficiency on the growth and development of a population that can be prevented by correction of iodine deficiency, denoted by the term IDD, are evident at all stages, including Figure 2 A mother and child from a New Guinea village who are severely iodine deficient. The mother has a large goiter and the child is also affected. The larger the goiter, the more likely it is that she will have a cretin child. This can be prevented by eliminating the iodine deficiency before the onset of pregnancy. (Reproduced from Hetzel BS and Pandav CS (eds.) (1996) SOS for a Billion The Conquest of Iodine Deficiency Disorders, 2nd edn. Oxford Oxford University Press.) Table 1 Spectrum of Iodine Deficiency Disorders Figure 2 A mother and child from a New Guinea village who are severely iodine deficient. The mother has a large goiter and the child is also affected. The larger the goiter, the more likely it is that she will have a cretin child. This can be prevented by eliminating the...

Iodine Deficiency and Excess Iodine Deficiency

Iodine deficiency is the most common cause of preventable mental retardation in the world. This fact, along with the recognition that iodine deficiency is not limited to remote rural populations, has stimulated agencies and governments to mobilize resources to eliminate this problem. This global effort, focusing primarily on iodization of salt for human and animal consumption, is slowly succeeding in eliminating a hidden set of disorders that have plagued mankind for centuries. Unlike many nutritional deficiencies that are more directly related to socioeconomic status, insufficient intake of iodine is a geographical disease, related to lack of iodine in the environment. Iodine originally present in soil was subjected to leaching by snow and rain, and while a portion of the iodine in the oceans evaporates and is returned to the soil in rainwater, this amount is small. Thus, many areas have insufficient iodine in the environment, and this is reflected in plants grown in that...

Physiologic Effects Of Thyroid Hormones

One of the most striking effects of thyroid hormones is on bodily growth (see Chapter 44). Although fetal growth appears to be independent of the thyroid, growth of the neonate and attainment of normal adult stature require optimal amounts of thyroid hormone. Because stature or height is determined by the length of the skeleton, we might anticipate an effect of thyroid hormone on growth of bone. However, there is no evidence that T3 acts directly on cartilage or bone cells to signal increased bone formation. Rather, at the level of bone formation, thyroid hormones appear to act permissively or synergistically with growth hormone, insulin-like growth factor (see Chapter 44), and other growth factors that promote bone formation. Thyroid hormones also promote bone growth indirectly by actions on the pituitary gland and hypothalamus. Thyroid hormone is required for normal growth hormone synthesis and secretion. The importance of the thyroid hormones for normal development of the nervous...


Normal thyroid physiology is discussed in Chapter206, Hyperthyroidism and Thyroid Storm. Hypothyroidism occurs when there is insufficient hormone production or secretion. A general hypometabolic state is the principle feature of this disease. Hypothyroidism occurs more frequently among women than men. The prevalence of hypothyroidism among women ranges from 0.6 to 5.9 percent.1 The most common etiologies of hypothyroidism are primary thyroid failure due to autoimmune diseases (of which Hashimoto thyroiditis is most common), idiopathic causes, postablative therapy, and iodine deficiency. 2 Hypothyroidism may be transient as in some cases of thyroiditis. The pathophysiology of this entity is unclear but may be viral in origin. Postpartum thyroiditis occurs within 3 to 6 months postpartum and reportedly occurs in 2 to 16 percent of women.1 Secondary (due to pituitary tumors, infiltrative disease, or hemorrhage) or tertiary (hypothalamic disease) etiologies of hypothyroidism are less...

Thyroid Hormones

As already mentioned in Chapter 39, growth is stunted in children suffering from unremediated deficiency of thyroid hormones. Treatment of hypothyroid children with thyroid hormone results in rapid catch-up growth rates, which are accompanied by accelerated maturation of bone. Conversely, hyperthyroidism in childhood increases the rate of growth, but, because of early closure of the epiphyses, the maximum height attained is not increased. Thyroidectomy of juvenile experimental animals produces nearly as drastic an The effects of thyroid hormones on growth are intimately entwined with GH. T3 and T4 have little if any growth-promoting effect in the absence of GH. Plasma concentrations of both GH and IGF-I are reduced in hypothyroid children and adults and restored by treatment with thyroid hormone (Fig. 13).


Thyrotoxicosis secondary to thyroiditis is uncommon. It is typically transient and self-limited. It may occur as a result of chronic lymphocytic or Hashimoto's thyroiditis, silent or painless thyroiditis, subacute or de Quervain's thyroiditis and h radioiodine-induced thyroiditis. Silent, subacute and radioiodine-induced thyroiditis M are all characterized by the inability to trap iodine, follicular cell destruction and release of preformed thyroid hormone resulting in thyrotoxicosis with a low radioiodine uptake. In contrast, radioiodine uptake is increased in patients with thyrotoxicosis secondary to chronic lymphocytic or Hashimoto's thyroiditis. The pathogenesis of thyrotoxicosis in chronic lymphocytic thyroiditis is felt to be similar to that of Graves' disease. Thyrotoxicosis in patients with chronic lymphocytic or Hashimoto's thyroiditis, referred to as Hashitoxicosis, is uncommon. It typically occurs in the early stages of the disease and is transient in nature. It is thought...

Zinc and Other Minerals

Unusual to find a documented case of clinical zinc deficiency apart from occasional cases of acroder-matitis enteropathica, there has been recent concern over the possibility of relative zinc deficiency, especially among chronically ill patients with excessive intestinal secretions. Zinc deficiency could lead to impaired taste (hypogeusia) and appetite and immunodeficiency as well as affecting growth. A large group of adolescents in Shiraz, Iran was described to be of very short stature because of dietary zinc deficiency. Similarly, a group of people in Keshan, China was found to develop cardiomyopathy because of a selenium deficiency in the soil. Iodine deficiency is surprisingly common worldwide, perhaps involving up to half of the world population or 3 billion people, especially in areas of Southeast Asia where it is not supplemented in salt. It may cause hypothyroidism, goiter (neck masses), cretinism, or impaired intelligence if severe.

Immunogenetics and disease association

HLA-DR3 and or DR4, except when the disease occurs as part of type 1 autoimmune polyglandular syndrome. A high prevalence of other autoimmune diseases (ovarian failure, Graves disease, Hashimoto's disease, hypothyroidism and insulin-dependent diabetes mellitus) is associated with Addisons disease (see Table 1).

Thyroid Hormone Effects

Thyroid hormone affects protein, fat, and carbohydrate metabolism through several mechanisms. Protein synthesis is most likely increased by moderate doses of T3 in humans, as indicated by studies of radiolabeled proteins in hypothyroid patients. In animals, this effect is biphasic, and excess thyroid hormone inhibits protein synthesis. In children, normal amounts of thyroid hormone are necessary for normal growth, with both insufficient and excessive amounts of thyroid hormone leading to growth retardation. Normal amounts of thyroid hormone are necessary for the production and release of growth hormone. Vitamin metabolism is also affected by thyroid hormone, with requirements for water-soluble vitamins (vitamin C, vitamin B12, thiamine, riboflavin) increasing in states of thyroid hormone excess. Thyroid hormone is necessary for the synthesis of retinol from vitamin A. Vitamin A, in turn, is synthesized from carotene, another thyroid hormone dependent reaction. This effect is...

Supraventricular Dysrhythmias

Clinical Significance Sinus bradycardia represents a suppression of the sinus node discharge rate. Sinus bradycardia can be (1) physiologic (in well-conditioned athletes, during sleep, or with vagal stimulation), (2) pharmacologic (digoxin, narcotics, reserpine, b-adrenergic antagonists, calcium channel blockers, quinidine), or (3) pathologic (acute inferior myocardial infarction, increased intracranial pressure, carotid sinus hypersensitivity, hypothyroidism).

Solitary Thyroid Nodule

The primary goal in the evaluation of the solitary thyroid nodule is to distinguish those nodules that require surgical excision from those that can be safely observed. Many thyroid diseases can present clinically as a solitary thyroid nodule, such as colloid cysts, adenomas, Graves' disease, thyroiditis, infections, and malignancies (Table 2.1). Given the large numbers of patients with palpable thyroid nodules, i.e., 5-7 of the North American population, it is important for this evaluation to be cost efficient, while avoiding inadvertently missing a thyroid cancer. As many as 10 million people in the United States may be diagnosed with a palpable thyroid nodule however, only about 16,000 new thyroid cancers are diagnosed per year. While typically minimally aggressive, thyroid cancer can be lethal. Therefore, the most important distinction in working up a solitary thyroid nodule is whether or not the lesion represents a malignancy.

Table 22 Important clinical factors in the diagnosis of thyroid cancer

Dysphagia, dysphonia, dyspnea, hoarseness or hemoptysis may all reflect esophageal or tracheal involvement by a thyroid cancer. These symptoms can also occur with benign causes of thyroid enlargement, such as hemorrhagic degeneration or subacute thyroiditis. Other symptoms that may serve as a clue regard hyperthyroidism (weight loss, nervousness, heat intolerance) or hypothyroidism (weight gain, depression, fatigue, cold intolerance). Nodules associated with hyper-thyroidism are usually benign functioning adenomas whereas a nodule in a patient with hypothyroidism is often caused by autoimmune thyroiditis.

Laboratory Examination

Most blood tests are usually of little value in the evaluation of a patient with an asymptomatic solitary thyroid nodule. An exception may be thyroid function tests. Blood studies for serum thyroxine (T4), triiodothyronine (T3) resin uptake and thyroid stimulating hormone (TSH) may be obtained in the proper clinical setting to establish hyperthyroidism or hypothyroidism. Abnormalities in thyroid gland function are most often associated with a benign nodule, although most benign nodules have normal thyroid function tests. Malignant thyroid nodules generally have normal thyroid function tests.

Considering environmental factors

Endometriosis is related to environmental contamination. Dioxin, one of the first pollutants scientists studied, is an example (see the sidebar Understanding dioxin exposure earlier in this chapter) of an environmental effect on endometriosis. Likewise, scientists can link pollutants to multiple sclerosis, lupus, thyroid disease, chronic fatigue syndrome, fibromyalgia, and even cancer.

Gastric parietal cells

Autoantibodies are readily detected by IIF with sections of rodent stomach (mucosa) as tissue substrate. The pattern of staining resembles that seen with mitochondrial antibodies therefore, a control test on kidney should also be performed. Parietal cell antibodies are found in 90 or more of patients with pernicious anemia. Recently, the autoantigen has been identified as the a and 3 subunits of gastric H+,K+-ATPase. An ELISA using this enzyme and a western blotting technique using gastric extracts have been developed. These antibodies are also present in a number of other conditions, such as chronic thyroiditis (33 ), Sjogren's sicca syndrome (15 ), atrophic gastritis (60 ), gastric ulcer (22 ), etc. The antibodies are also found in the normal population, with an incidence that varies according to age and sex i.e. from 2 in subjects under 20 years old to 16 in subjects over 60 years old. They are more frequent in women than in men.

Other endocrine organs

Autoimmunity also develops against other endocrine organs such as the adrenal gland, pancreas islet cells, parathyroid, pituitary and ovary. The autoantibodies are much less prevalent than with thyroid disease but, if present, help in diagnosis. The reactivities, assays and primary associated disorders are summarized in Table 1.

Chicken strains and genetic variability

With very few exceptions, the inbred strains are based on the White Leghorn type of domestic chicken. Attempts to inbreed other types of chicken or species of bird (ducks, Japanese quail) have been made, but have not generally been successful. There are lines of chickens with hypogammaglobulinemia resulting from abnormal bursal development, a line in which a disease similar to systemic scleroderma can be induced, and 'obese' chicken strains which develop a spontaneous autoimmune thyroiditis similar to Hashimoto's disease. Transgenic chickens can be produced by DNA transfer into fertilized eggs viral vectors which can give high levels of somatic transgenesis are available. A chicken genome mapping project is under way.

Nondiagnostic Biopsies

Use of ultrasound-guided fine needle aspiration biopsy in the management of thyroid disease. American Surgeon 1998 64(8) 738-742. After reviewing 76patients undergoing U S guided FNAB, the authors recommend the use of ultrasound when evaluating nodules that are difficult to palpate or had nondiagnostic FNABs. 6. Gharib H, Mazzaferri EL. Thyroxine suppressive therapy in patients with nodular thyroid disease. Ann Intern Med 1998 128(5) 386-94. Taking data from randomized and non-randomized trials of thyroxine from 1986-1996, the authors found that suppressive therapy failed to shrink most nodules.

Radioactive Iodine Therapy

Radioactive iodine has been used for the treatment of toxic goiter, however its use in the management of the patients with a non-toxic goiter is a recent event. In 1964 Keiderling first reported the benefits of radioactive iodine therapy in non-toxic goiter in 400 patients. Since then there have been sporadic reports of similar use. Its use in substernal goiter had not been evaluated until 1994 when Huysmans et al reported a prospective study of patients with large compressive goiters.11 Nine of their 19 patients had intrathoracic extension for more than 2 cm. Using MRI they were able to demonstrate a 40 reduction in the volume of the goiter. They also showed a 10 decrease in both the tracheal narrowing and deviation in three-quarters of their patients. Unfortunately, one-third of their patients did not experience any improvement in their symptoms of dyspnea. Radiotherapy is not without its potential complications. Radiation induced thyroiditis and a transient increase in volume may...

Clinical Evaluation and Management

Measurement of the patient's rectal temperature is a vital component of the patient's care. Hypothermia can be due to environmental exposure, near drowning, sedative drug overdose, hypothyroidism, and Wer-nicke's disease. Hypothermic patients with temperatures below 34 C (93.2 F) should be warmed slowly to a body temperature higher than 36 C (96.8 F). Since hypothermia below 80 F results in coma, resuscitative measures are indicated in all hypothermic patients even if vital signs are absent. The presence of fever in a comatose patient requires investigation for an underlying infection.

Table 41 Differential diagnosis for thyrotoxicosis

Iodine-induced (amiodarone, intravenous contrast material, iodine-containing expectorants, kelp, topical antiseptics) Hashimoto's or chronic lymphocytic thyroiditis Trophoblastic tumors (hydatiform mole or choriocarcinoma) Thyrotropin-producing pituitary tumor Thyroid hormone resistance syndromes B) Not associated with hyperthyroidism Subacute, painless, or radiation thyroiditis

Duties And Obligations

What should the states' obligations be, particularly in light of competing needs for limited resources Mandatory screening adopted with public health rationale does not necessarily mean that everyone benefits from testing. Health care consumers, particularly those in areas using multiplayer systems of care, have widely differing levels of access to tests and interventions. Changes to one's health insurance can create substantial potential for harm if insurers refuse to pay for expenditures associated with a ''preexisting'' (genetic) condition, or impose premium increases that make treatments (even co-pays) unafford-able. Furthermore, the type of genetic test reporting can have devastating consequences. For example, California's newborn screening reporting requirements does not require reporting actual values, but rather only abnormal results. A recent case resulted in permanent injury because the actual values, which showed consistency for congenital hypothyroidism, were not reported....

Postoperative Management

Iodine-131 scanning plays an essential role in the postoperative management of differentiated thyroid cancer. Most authorities agree that iodine-131 scanning is indicated in the vast majority of patients with follicular carcinoma, excluding only young patients with the minimally invasive variety or with primary lesions less than 1 cm in size. There are two basic strategies for obtaining such a scan. The first strategy involves radioiodine scanning six weeks following thyroidectomy. The patient is started on T3 replacement therapy (liothyronine) in the immediate postoperative period, a form of therapy which has a much shorter half-life than that of T4 (thyrox-ine). Liothyronine is continued for four weeks at which time it is discontinued to induce a state of hypothyroidism in preparation for radioiodine scanning. Once the TSH level has increased to a value greater than 40 U ml typically two weeks following the cessation of T3 the iodine-131 scan is performed. The administration of T3...

Epidemiology and Classification

Thyroid carcinoma is classified by many subtypes (Table 6.1) and accounts for 1.5 of all cancers in the United States. The age-adjusted annual incidence for thyroid carcinoma in the U.S. is less than 40 cases per one million people and 12,000-15,000 new cases are diagnosed each year.1,2 While 4-5 of the population have thyroid nodules, only four of these nodules actually contain differentiated thyroid carcinoma. Several factors however, can increase this incidence. Patients, for example, who are exposed to low dose irradiation to the head or neck, commonly develop nodular thyroid disease and harbor thyroid carcinoma in 30-40 of these thyroid nodules. Ten percent of all differentiated thyroid carcinomas occur in children and adolescents as they are uniquely sensitive to radiation exposure as a major risk factor for thyroid carcinogenesis. These young patients generally have more aggressive tumors, higher rates of recurrence and are more likely to develop cervical lymph node metastasis...

TABLE 1235 Acute and Chronic Constipation

In older children, one should not automatically think that the cause is functional. Constipation is seen in children who are anorexic or who have cerebral palsy, neuromuscular disease, dehydration, hypercalcemia, hypokalemia, hypothyroidism, or depression or who have ingested drugs such as diuretics, antihistamines, anticholinergics, or narcotics. A thorough history and physical examination, including rectal, are necessary. An empty rectal vault does not rule out constipation. If there are signs of bowel obstruction, tumor, or serious illness, one should consult an appropriate specialist.

The Need to Improve Micronutrient Intakes in Developing Countries

Table 2 illustrates that, in general, diets in developing countries are not only poor in energy (less than 77 adequacy) but also in zinc, iron, calcium, vitamin B12, folate, vitamin A, and vitamin B2. Adequacies of these micronutrients are from 35 to 70 of the estimated average requirement (EAR). Vitamin B1, niacin, and vitamin C have better adequacies, although these are still unsatisfactory, being in the order of 70-100 of the EAR. Iodine deficiency, as in most human societies in the world, is

Clinical Presentation and Diagnosis

Most patients with differentiated thyroid carcinoma initially present with nodular thyroid disease or a cervical mass. The nodule is more likely to contain carcinoma in children, adolescents, males, patients exposed to low doses of radiation to There are no effective serum tumor markers useful in screening patients for differentiated thyroid carcinoma. Initial laboratory evaluation includes the measurement of serum ultrasensitive thyroid-stimulating hormone (TSH), free thyroid hormone levels, antithyroid autoantibodies, and serum calcium to exclude coexistent parathyroid disease which can be found in patients with nodular thyroid disease and thyroid carcinoma. Most patients with thyroid nodules and thyroid carcinomas are biochemically euthyroid, but subclinical or biochemical hyperthyroidism associated with uninodular or multinodular thyroid disease can be detected by laboratory screening. Such patients have a 3-6 incidence of associated thyroid carcinoma. The presence of thyroid...

Smell And Sexual Arousal

Besides purely anatomical similarities, the linkage between olfactory function and sexual function is recognized in a clinical setting. More than 17 of individuals with chemosensory dysfunction develop impaired sexual desire or other sexual dysfunction (28). Genetic disorders can affect both systems for example, those with Kalliman's syndrome have both olfactory deficit and impaired sexual drive and functioning (29). Other diseases impair olfactory ability and sexual functioning concomitantly, including cerebral vascular disorders (18,30), Parkinson's disease (31,32), senile dementia of the Alzheimer's type (33), hypothyroidism (34,35), and vitamin deficiency states including B12 deficiency (36).

Surgical and Medical Treatment

Total thyroidectomy is optimal treatment for most patients with preoperative identification of differentiated thyroid carcinoma.8 Microscopic, occult or minimal papillary thyroid carcinomas noticed incidentally on final histopathologic examination of the surgical specimen may be adequately treated by the complete ipsilateral lobectomy and contralateral subtotal thyroid resection which is the minimal surgical resection recommended for all forms of nodular thyroid disease. Completion thyroidectomy after 8-12 weeks is advisable for certain patients with follicular thyroid carcinomas that could not be identified with preoperative FNAB cytology or intraoperative histopathologic methods. Multicentricity or unexpected cervical lymph node metastases may also mandate completion thyroidectomy in young patients

Diagnostic and Therapeutic Radioactive Iodine131

Postoperative total body radioactive iodine scanning is recommended for all high-risk patients with DTC as this modality decreases the local recurrence and death rates (Table 6.5). Most low risk patients are also candidates but, selective use is acceptable in low-risk node negative patients with small, occult, minimal, or incidentally discovered differentiated thyroid carcinoma. Figure 6.1 illustrates the protocol for performing a total body radioiodine scan 6-12 weeks after thyroidec-tomy that begins by withholding thyroid hormone medication (LT4) from the patient for approximately 4 weeks. The use of a LT3 hormone preparation such as Cytomel for the first two of these four weeks can alleviate the problems of symptomatic hypothyroidism. The serum TSH level is checked at the end of four weeks and should be greater than 30-50 IU prior to radioisotope administration.2 This is also the best time to establish an accurate baseline for serum thyroglobulin levels for use as a future...

Functional Anorectal Disorders Constipation

Patients with a dilated rectum and faecal impaction (idio-pathic megarectum) are usually teenagers or young adults of either sex. They have often soiled since childhood. In some the problem has a behavioural basis, whereas in others there may be subtle neuromuscular abnormalities of the gut. Constipation with faecal impaction is also seen in elderly patients, especially those in care. Poor general health, impaired mobility, inadequate toilet facilities, endocrine abnormalities (such as hypothyroidism) and drugs may all contribute. Patients with idiopathic megarectum should have their bowel emptied completely before titrating an osmotic laxative. Such a laxative may be required in the long term, although behavioural treatment seems also to help some of these patients. Hirschsprung's disease should always be considered in the differential diagnosis for patients with severe intractable constipation as, although usually diagnosed and treated in infancy, the diagnosis may have been missed....

Regulation of Metabolism

As discussed below, alterations in homocysteine metabolism also occur after menopause, in diabetes, and in hypothyroidism. These observations suggest that hormones, including estrogen, insulin, thyrox-ine, and thyroid-stimulating hormone, may directly or indirectly affect homocysteine metabolism. As for oxidative stress, the mechanisms by which these hormones affect homocysteine metabolism are poorly understood.

Step 5 Followup laboratory evaluation

Prolactin secretion can be transiently increased by stress or eating. Therefore, serum prolactin should be measured at least twice before cranial imaging is obtained, particularly in those women with small elevations (< 50 ng mL). These women should be screened for thyroid disease with a TSH and free T4 because hypothyroidism can cause hyperprolactinemia.

Cytodiagnostic Categories

Several benign causes of thyroid nodules can be accurately and reliably diagnosed by cytology. Colloid nodules show flat sheets of follicular epithelium in a honeycomb arrangement against a background of colloid. A report of blood, degenerative debris and histiocytes that are often hemosiderin laden is consistent with degenerating lesions or cysts. Other benign nodules that may be diagnosed on FNAB include some adenomas and different forms of thyroiditis, including Hashimoto's.

Metabolic Functions

Separating the role of iodine from the complex and pervasive function of the thyroid gland is difficult since iodine is a critical component of the hormones that mediate these functions, and whatever other roles iodine may have are poorly understood. Thyroid hormones affect a wide range of physiological functions, from liver and kidney to heart and brain. Earlier work supported a role for thyroid hormones in affecting the energy generating capacity of cells through biochemical changes in mitochondria. More recent work has shown, however, that these hormones act on specific genetic receptors in cell nuclei, and perhaps through other extranuclear mechanisms. The nuclear receptors belong to a large family of receptors that bind other extranuclear molecules including vitamins A and D and steroids. Through this interaction, along with a number of other proteins, thyroid hormones modify genetic expression. A great deal of research currently focuses on these thyroid hormone receptors, and...

Assessment of Iodine Status

Urinary iodine reflects iodine sufficiency, and output decreases with diminished intake. Since this indicator reflects the amount of iodine per unit volume of urine, its accuracy is impaired by variable fluid intake and factors affecting the concentration of the urine. Therefore, as a measure of iodine status in an individual, it is less accurate than as a measure of iodine status of a population. Median urinary iodine values are used extensively to assess population prevalence of iodine deficiency. Thyroid size, either estimated by palpation or using ultrasound volume determination, reflects iodine status since deficiency results in thyroid enlargement, or goitre. Due to the relative ease of palpation, that measure has been a traditional standard to assess populations for iodine deficiency and has been particularly useful in schoolchildren. In adults, where long-standing thyroid enlargement from iodine deficiency may be minimally responsive to corrected iodine intake, palpation may...

Factors Enhancing Toxicity

A variety of factors increase susceptibility to digitalis toxicity. True end organ sensitivity is seen with myocardial disease or ischemia, and metabolic or electrolyte abnormalities. Hypokalemia, hypomagnesemia, and hypercalcemia all predispose to increased toxicity.3 The elderly are more susceptible to toxicity. Decreased renal function, hepatic disease, hypothyroidism, chronic obstructive pulmonary disease, and drug interactions can all augment toxic effects. 5 Drug interactions potentially resulting in digitalis toxicity include quinidine, procainamide, b blockers, calcium channel blockers, amiodarone, spironolactone, indomethacin, clarithromycin, and erythromycin.

Magnitude of the Problem

The number of cases of IDD throughout the world was estimated by WHO in 1990 to be 1.6 billion, including more than 200 million cases with goiter and more than 20 million cases with some degree of brain damage due to the effects of iodine deficiency in pregnancy. Recent estimates of the population at risk have been increased to 2.2 billion, with the recognition that even mild iodine deficiency in the mother has effects on the fetus. There are now estimated to be 130 IDD-affected countries, including the most populous Bangladesh, Brazil, China, India, Indonesia, and Nigeria. Therefore, there is a global scourge of great magnitude, which provides one of the major challenges in international health today.

The Role of the United Nations

International Council for Control of Iodine Deficiency Disorders (ICCIDD) working in close collaboration with UNICEF and WHO. Since 1989, a series of joint WHO UNICEF ICCIDD regional meetings have been held to assist countries with their national programs for the elimination of IDD. The impact of these meetings has been that governments now better realize the importance of iodine deficiency to the future potential of their people. A dramatic example is provided by the government of the People's Republic of China. As is well-known, China has a one child per family policy, which means that an avoidable hazard such as iodine deficiency should be eliminated. In China, iodine deficiency is a threat to 40 of the population due to the highly mountainous terrain and flooded river valleys in excess of 400 million people at risk. In recognition of this massive threat to the Chinese people, in 1993 the government held a national advocacy meeting in the Great Hall of the People sponsored by the...

The Global Partnership

A more recent development is the establishment of the Global Network for the Sustainable Elimination of Iodine Deficiency, in collaboration with the salt industry. The achievement of the global elimination of iodine deficiency will be a great triumph in international health in the field of noninfectious disease, ranking with the eradication of the infectious diseases smallpox and polio. However, the goal of elimination is a continuing challenge. Sustained political will at both the people and the government level is necessary to bring the benefits to the many millions who suffer the effects of iodine deficiency.

Sensorimotor Examination

Parkinson's disease, and normal pressure hydrocephalus. Dysarthria would alert the clinician to possible extrapyramidal disorders, bilateral strokes, de-myelinating disease, and motor neuron disease. Sensory abnormalities (e.g., peripheral neuropathy) may be associated with B12, other vitamin deficiency states, thyroid disease, or a paraneoplastic syndrome. Cerebellar signs might raise concerns about cerebrovascular disease, spinocerebellar degeneration, a paraneoplastic syndrome, and Creutzfeldt-Jakob disease. In Alzheimer's disease, especially early in its course, the sensorimotor examination tends to be relatively benign. Some researches have pointed out that the presence of extrapyramidal signs in patients with a profile otherwise consistent with Alzheimer's disease suggests a worse prognosis (33). Extrapyramidal signs may indicate the presence of Lewy body variant of AD (34). In general, if a patient with dementia presents with focal or multifocal neurological signs, the...

Familial Type IV and Type V Hypertriglyceridemias

Type V hyperlipidemia is a much more rare disorder. Usually the first signs of this abnormality are abdominal pain or pancreatitis. VLDL levels are high and chylomicrons are present in the fasting state. This abnormality has not been linked to any specific molecular defect. Besides the primary genetic defect, other secondary causes of type V hyperlipidemia are poorly controlled diabetes melli-tus, nephrotic syndrome, hypothyroidism, glycogen storage disease, and pregnancy. Recent data indicate increased susceptibility to atherosclerosis.

Siegfried M Pueschel MD PhD Jd Mph

Postoperatively, we had more time to examine her thoroughly. We noted that not only did she have most of the characteristics of a person with Down syndrome, but she also had signs of hypothyroidism, verified by appropriate laboratory examinations, and precocious sexual development (Pueschel et al., 1966). The subsequent investigations of the interrelationship of Down syndrome, hypothyroidism, and sexual precocity led to my first publication on the subject of Down syndrome. And during this time period, my son Christian was born.

Regulation Of Thyroid Function

Thyroid-stimulating hormone binds to a single class of heptihelical G protein-coupled receptors (see Chapter 2) in the basolateral surface membranes of thyroid follicular cells. The TSH receptor is the product of a single gene, but it is comprised of two subunits held together by a disulfide bond. It appears that after the molecule has been properly folded and its disulfide bonds formed, a loop of about 50 amino acids is excised proteolytically from the extracellular portion of the receptor. The a-subunit includes about 300 residues at the amino terminus and contains most of the TSH binding surfaces. The -subunit contains the seven-membrane-spanning a-helices and the short carboxyl-terminal tail in the cytoplasm. Reduction of the disulfide bond may lead to release of the a-subunit into the extracellular fluid, and may have important implications for the development of antibodies to the TSH receptor and thyroid disease (see below). Binding of TSH to the receptor results in activation...

Use of Diuretics in the Treatment of Hypertension in Renal Impairment

Hypertension is a consequence of renal impairment and if untreated accelerates the decline in renal function to end-stage renal failure. Moreover, hyperlipidemia and glucose intolerance are more common in chronic renal failure, and cardiovascular morbidity and mortality are significantly increased, particularly in patients on dialysis in whom BP control is often difficult. The major cause of hypertension in renal failure is sodium retention and ECV expansion, so-called volume-dependent hypertension. Additional factors may include increased sympathetic nerve acuity, hyperparathyroidism, hypothyroidism, increased and decreased production and or action of endogenous vasoconstrictors (e.g., angiotensin II, endothelin, nitric oxide inhibitors), and vasodilators (e.g., prosta-

Antidysrhythmic Drug Therapy

Antidysrhythmic drugs with class III and or beta-blocking activity may be of some value in protecting patients at high risk of SCD. In the randomized, double-blind, placebo-controlled European Myocardial Infarct Amiodarone Trial (EMIAT), the type III antidysrhythmic drug amiodarone reduced all-cause mortality (primary endpoint) and cardiac mortality dysrhythmic death (secondary endpoints) in survivors of myocardial infarction who had a left ventricular ejection fraction of less than 40 percent.24 The Cardiac Arrest in Seattle Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antidysrhythmic drug therapy in VT and VF survivors who were thought to be at high risk for VT or VF recurrence. Therapy with empirical amiodarone was compared to therapy with other antidysrhythmic agents as guided by electrophysiologic testing and or Holter recording. Survival was better in patients treated with amiodarone than in patients treated with other antidysrhythmic agents. Patients...

Clinical Manifestations

Clinical manifestations of hyperthyroidism reflect increased catabolism and excessive sympathetic activity caused by excess circulating thyroid hormones. Symptomatic manifestations of hyperthyroidism include weight loss despite normal or increased appetite, heat intolerance, anxiety, irritability, fatigue, muscle weakness, palpitations, and oligomenorrhea. Signs of hyperthyroidism include goiter, tremor, hyperreflexia, fine or thinning hair, thyroid bruit, muscle wasting, and cardiac arrhythmias such as sinus tachycardia or atrial fibrillation. The presentation of hyperthyroidism varies with age. Young patients typically present with hypermetabolism, while older patients may present primarily with tachyarrhythmias or cardiac failure. Rarely, elderly patients experience only muscle wasting, apathy, confusion, or a state of depression known as apathetic hyperthyroidism. Clinical features of hypothyroidism include cold intolerance weight gain constipation edema of the hands, feet, and...

TABLE 1998 Commonly Treated Forms of Internal Contamination

RADIOIODINE Inhalation or ingestion of radioiodine is particularly hazardous to the thyroid with a potential risk of causing hypothyroidism or thyroid cancer. I-131 is the predominant internal contaminate resulting from incidents that involve the release of nuclear fission products such as a nuclear reactor accident or nuclear weapons test. Studies on the health effects of the Chernobyl accident have shown that populations in heavily contaminated areas have an increase in thyroid cancer presumed to have resulted from radioiodine exposure. The number of thyroid cancers reported in these areas continues to increase, with the highest prevalence in individuals who were under the age of 10 years at the time of the accident.4

Abnormalities of Secretion Deficient Secretion

Hypothyroidism can be either primary, where the fault lies within the thyroid gland or secondary, where there is a deficiency of TSH secretion from the pituitary. Under secretion of thyroid hormones leads to the clinical picture of myxoedema. Causes of primary hypothyroidism include iodide deficiency or inflammation of the gland ('thyroiditis'). The low T3 and T4 levels lead to elevated TSH and enlargement of the gland (goitre formation). In secondary hypothyroidism, because TSH levels are low, there is thyroid atrophy rather than goitre.

TABLE 2075 Clinical Presentation of Myxedema Coma

Diagnosis of myxedema coma requires high clinical suspicion. A patient suspected of presenting with myxedema coma commonly has a prior history of primary hypothyroidism or previous thyroid surgery. Medication noncompliance or coexisting stressors such as cold exposure, severe infection, or the addition of new medications may precipitate the onset of myxedema coma. The decline in function is usually gradual and insidious in onset. The physical examination may confirm a history of long-standing hypothyroidism. In addition, there may be clinical findings of hypothermia, hypoventilation, hypotension, bradycardia, and alteration or deterioration of the patient's mental status.

TABLE 2129 Laboratory Evaluation of Patients with von Willebrands Disease

A variety of tests are used to establish the diagnosis of vWD. Coagulation screening tests will show a normal PT, normal TCT, and usually normal aPTT, although it may be prolonged in moderate or severe vWD due to the decreased factor VIII activity. The other tests used in the evaluation of vWD are outlined in T.a.b e ,.2 1 2 -. . The diagnosis of vWD can be difficult to establish because of variability in test results. Oftentimes, patients have to be tested repeatedly when there is a high index of suspicion in order to establish the diagnosis. The tests can be affected by estrogens, progesterones, oral contraceptive agents, thyroid disease, infections, and exercise.

Lambert Eaton myasthenic syndrome

This disorder is much less common than myasthenia gravis. It is characterized by proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation and autonomic changes, including dry mouth and constipation. Onset can be in adolescence, but is usually after 40 years of age. Other autoimmune diseases may associate, notably thyroid disease and vitiligo, and other autoantibodies occur at increased frequency.

Table 153 Etiology of extraocular movement disorders

Mechanical Aneurysm, intracranial neoplasm, arteriovenous malformation, cavernous sinus disease, intracranial hemorrhage, orbital fracture with muscle entrapment, retrobulbar hematoma, abscess Systemic Diabetes, hypertension, thyroid disease, Wernicke's syndrome, giant cell

Obesity Associated with Recognized Medical Condition

Hypothyroidism Growth, hormone deficiency Cushing's syndrome Polycystic ovarian syndrome Hydrocephalus Meningoencephalitis Steroid treatment Sodium valproate Down's syndrome children are also prone to develop obesity in late childhood and adolescence. This is generally unrelated to recognized pathophy-siological explanations for the obesity, although the syndrome is associated with an increased incidence of autoimmune thyroiditis and hypothyroidism (which exacerbates obesity). Obesity may be an associated feature of other pathology in childhood. Endocrine problems, such as hypothyroidism and Cushing's syndrome, lead to obesity, but linear growth retardation does also, which often draws attention to the problem before obesity is severe. Hypothalamic damage (e.g., hydro-cephalus and meningoencephalitis) and problems leading to immobility (e.g., spina bifida and Duchenne's muscular dystrophy) may also predispose to obesity. Nonpathological childhood obesity is usually associated with...

Other polyendocrine autoimmunity syndromes

Hashimoto's thyroiditis and autoimmune thrombocytopenia. Serological markers include a raised erythrocyte sedimentation rate (HSR), hypergammaglobulinemia and hypocomplementemia. The POEMS syndrome is a rare form of plasma cell dyscrasia with polyneuropathy, organomegaly (liver and or spleen), endocrinopathy (hypogonadism, hypothyroidism or diabetes mellitus), monoclonal gammopathy and skin changes, these features giving rise to the acronym. It is likely that the POEMS syndrome represents a variant of osteosclerotic myeloma. The endocrine dysfunction may be caused by specific autoantibodies but this remains unproven.

Endocrine Abnormalities

THYROID HORMONE The most common findings of hypothyroidism include lethargy, fatigue, dry coarse skin, facial and extremity swelling, hoarseness, constipation, and weakness. Oral manifestations are related to the accumulation of glycosaminoglycans in the oral tissues, causing macroglossia and thickened lips. If hypothyroidism occurs in childhood, teeth may fail to erupt, although tooth formation is unimpaired. 19

Parathyroid Localization Studies

There are some disadvantages to using MRI as well. The most significant one is that the normal cervical lymph nodes have an appearance on MRI that is the same as that of abnormal parathyroid glands. Consequently, MRI can only differentiate between these two structures on the basis of shape and location. Fortunately, this is usually fairly straightforward. Likewise, other structures in the neck, such as cervical ganglia, can also appear similar to an abnormal parathyroid gland. Because of their embryologic origins, occasionally ectopic glands may be found within the thyroid itself. This can be problematic, since up to 40 of thyroid glands can contain high T2 signal foci, even when no thyroid disease is present. Finally, the MRI scan may not identify all of the

Radiosensitivity of lymphoid tissues

Localized irradiation of human thymus, as shown by studies of individuals irradiated prophylactically in infancy for an enlarged thymus to prevent 'status thymolymphaticus', resulted not only in an increased frequency of tumors, but also increased frequency of asthma and other autoimmune disorders (including sarcoidosis, enteritis, thyroiditis and others). However, no impairment of delayed hypersensitivity reactions was noted, suggesting that T cells with regulatory functions are more radiosensitive than those with effector roles.

Complications of Thyroid Surgery

Thyroid surgery has progressed dramatically since the mid-1850s when half or more of the patients undergoing this operation would die from the procedure. Currently, thyroidectomy is a very safe operation which has an associate mortality rate that approaches zero. In other words, the mortality of a thyroidectomy is really the mortality of a general anesthetic. The morbidity associated with thyroid surgery is also very low. Nevertheless, the complications of thyroidectomy remain a matter of concern especially since thyroid disease often occurs in younger patients who have long life expectancy. Most complications associated with thyroidectomy can be minimized or even avoided by an experienced thyroid surgeon who has in depth knowledge of the anatomy of the central neck compartment and who employs meticulous surgical technique to protect the vital structures within it. The general problems that occur with thyroidectomy are related to the underlying thyroid disease, the patient's...

Intestinal Pseudoobstruction

Intestinal pseudo-obstruction encompasses several intestinal motor disorders characterized by episodes that suggest intestinal obstruction because defecation stops and abdominal distension, pain, and vomiting occur, but in which no mechanical obstruction is found. It may be due to primary abnormalities of the visceral muscle or nerves or be secondary to chronic renal failure, hypothyroidism, diabetes mellitus, amyloidosis, scleroderma, or muscular dystrophy. There is no effective treatment that is specific for intestinal pseudo-obstruction. If the patient has bacterial overgrowth, this should be treated with antibiotics. If nutrition is impaired, administration of liquid, low-residue feeds enterally is required rarely, parenteral (intravenous) feeding is necessary.

Table 42 Symptoms and signs of thyrotoxicosis

Once the diagnosis of thyrotoxicosis is confirmed, a measurement of radioactive iodine uptake may be helpful (Fig. 4.1). The presence of hyperthyroidism is established by an elevated 24-hour radioiodine uptake. A low radioactive iodine uptake is seen in patients with subacute or silent thyroiditis, iodine-induced hyperthyroid-ism, and excess thyroid hormone ingestion. A thyroid scintiscan, preferably obtained with iodine-123, is important in differentiating a hypofunctioning nodule in a patient with Graves' disease from a solitary toxic nodule. Adjunctive measurement of thyroid Silent thyroiditis (nontender thyroid enlargement, 'f' antithyroid antibodies) de Quervain's thyroiditis (neck pain and tenderness, 1s ESR) Postradiation thyroiditis (radioiodine treatment) Struma ovari intra-abdominal nodule on 1-123 scintiscan) Trophoblastic tumor Ch 3-HCG) Chronic lymphocytic thyroiditis (T antithyroid antibodies) stimulating immunoglobulins and antithyroid antibodies is useful in...

Postpartum thyroid dysfunction

An interesting variant of the group of AITDs are the syndromes of transient postpartum thyroid dysfunction (PPTD). Described initially in Japan by Amino and his colleagues, these syndromes occur in at least 5 of women postpartum. Women who are shown to have autoantibodies to TPO when they present to prenatal clinics and who are (if Caucasian) HLA-Al, -B8, -DR3 positive, are at particular risk of developing PPTD, irrespective of their past medical history. The syndromes are usually subclinical but biochemical monitoring of the postpartum period reveals changes in thyroid function which include hyperthyroidism, hypothyroidism or hyperthyroidism followed by hypothyroidism. The syndromes are important to recognize since they may well contribute to the etiology of the well-documented changes in mood and behavior that occur in the postpartum period and, more importantly, although initially transient they may be the first signals of subsequent permanent thyroid failure. The pathogenesis of...

Iodine Supplementation

Until universal salt iodization is guaranteed in the third of the world in which iodized salt is not yet available, especially in remote populations in which goiter is endemic, supplements should be used during pregnancy and early childhood. In the past, it was common to provide annual intramuscular injections of iodized oil to women of reproductive age in order to ensure iodine status during the first months of pregnancy when the risk of cretinism is greatest. In more recent years, oral iodized oil capsules have proven to be as efficacious and more effective in controlling iodine deficiency in both women of reproductive age and schoolchildren. Oral iodine supplements initially based on expensive poppy seed oil have since been replaced by cheaper rapeseed and peanut oil preparations, which are equally effective.

Molecular Analyses Of Peripheral Blood And Postoperative Surveillance Of Thyroid Carcinomas

The application of RT-PCR to detect circulating thyroid-specific mRNA in recurrent thyroid cancer was first reported in a study in which all patients with thyroid carcinoma and metastases were tested positive for circulating thyroglobulin (TG) mRNA, whereas patients without metastases were tested negative. 9 In a subsequent study, 10 circulating mRNA transcripts of TG, thyroid peroxidase (TPO), and RET PTC1 were used as tumor markers in patients with thyroid disease. Although there was a correlation between existence of these transcripts in peripheral blood and diagnosis of thyroid carcinoma, TG and TPO mRNA transcripts could be detected in the peripheral blood of all control subjects as well as in several human cell lines when PCR assay sensitivity was increased. Finally, an optimistic study was published, 11 which reported an RT-PCR assay to detect blood-borne TG mRNA that was more sensitive than the conventional TG serum assay. However, in the study of the authors, 12 only a weak...

Mental Disorders Due to a General Medical Condition

DSM-IV has implemented a major change in the classification of psychiatric symptoms caused by medical conditions. The previous terminology of organic brain syndrome and the subtypes organic mood disorder, organic delusional disorder, for example, have been eliminated because of the implication that the functional mental disorders were unrelated to biologic changes in brain function. Using DSM-IV, where there is evidence that a psychiatric disturbance is a direct physiologic consequence of a general medical condition or substance, the mental disorder is specified as due to the medical problem for example, major depression due to hypothyroidism. Common medical causes of psychotic and mood disorders are covered in Chap 281,

Physical Examination

A physical examination should be conducted on every patient. Vital signs are a simple physical screening test of patients with altered behavior. Abnormal vital signs, when observed, must not automatically be dismissed as secondary to anxiety or stress. Bradycardia can be seen in patients with hypothyroidism, Stokes-Adams syndrome, or elevated intracranial pressure. Tachycardia may be apparent in patients suffering from hyperthyroidism, infection, heart failure, pulmonary embolus, or alcohol withdrawal. Fever is often associated with extreme hyperthyroidism or thyroid storm, vasculitis, alcohol withdrawal, sedative-hypnotic withdrawal, meningitis, or various inflammatory processes. Hypothermia is observed in sepsis, dermal disease, hypoendocrine status, CNS dysfunction, and intoxication. Hypotension may be an indicator of shock, Addison's disease, hypothyroidism, or medication side effects. Hypertension may be associated with hypertensive encephalopathy or stimulant abuse. Tachypnea is...

Treatment of hyperthyroidism

Radioiodine (iodine131) is the treatment of choice in patients over 40 years of age, but in younger patients most centres adopt the empirical approach of prescribing a 12-18 month course of carbimazole and recommending surgery if relapse occurs. There should be a noticeable clinical improvement within 10-14 days, and most patients will be biochemically euthyroid within 4-6 weeks of starting carbimazole 40 mg daily. Patients with Graves' disease are likely to become hypothyroid within a year of treatment with radioiodine, but this is an unusual occurrence in patients with nodular goitre. There may be an exacerbation of hyperthyroidism a few days after treatment with radioiodine, owing to a transient increase in serum thyroid hormone concentrations in patients with atrial fibrillation and cardiac failure it is therefore good practice to render the patient euthyroid with an antithyroid drug before giving radioiodine.

Effects on thyroid hormone metabolism

Amiodarone administered chronically to eu-thyroid patients with no evidence of underlying thyroid disease results in raised serum T4 concentrations (free T4 up to 80 pmol l) with low normal T3. These changes are caused by the potent inhibition of 5'-deiodinase which converts T4 to T3. Serum TSH concentrations may increase initially then return to normal, but in some patients are suppressed at less than 0.05 mU l. This may make it difficult to decide whether a patient is euthyroid or hyperthyroid, particularly as the antiadrenergic effects of amiodarone can mask the clinical features of hyperthyroidism.

Type I amiodarone induced hyperthyroidism

18 mg of inorganic iodine which is 100 times the recommended daily allowance. Chronic exposure of patients with underlying thyroid autonomy, such as Graves' disease in remission or nodular goitre, to these excessive quantities of iodine may induce hyperthyroidism (type I amiodarone induced hyperthyroidism). This is not necessarily an indication to stop amiodarone because many patients can be managed satisfactorily by introducing concomitant anti-thyroid medication. However, this form of hyperthyroidism can be difficult to treat, especially in areas with relative iodine deficiency as is the case in much of mainland Europe. Standard doses of carbimazole, methimazole or propylthiouracil are often ineffective and it may be necessary to add potassium perchlorate in an attempt to reduce further the iodine uptake, and therefore hormone synthesis, by the thyroid. Treatment with iodine131 is not usually advisable because of the relatively poor ability of the already iodine rich gland to...

Type II amiodarone induced hyperthyroidism

Amiodarone per se may cause a drug induced destructive thyroiditis in patients with no pre-existing thyroid disease (type II amiodarone induced hyperthyroidism). In most cases this will resolve within 3-4 months whether or not amiodarone is discontinued. The disturbance of thyroid function is similar to that found in other forms of destructive thyroiditis, such as de Quervain's (subacute) or postpartum thyroiditis, with a few weeks of hyperthy-roidism caused by the release of preformed thyroid hormones, followed by a brief spell of hypothyroidism, and then recovery.

Assessment of thyroid function before and during treatment

In an attempt to minimise the risk of type I hyperthyroidism we recommend that before initiating treatment with amiodarone patients should be examined for the presence of goitre or Graves' ophthalmopathy and measurements made of serum T3, T4, TSH, antiperoxidase (microsomal) and, if possible, TSH receptor antibodies. Clinical evidence of thyroid disease and or a suppressed serum TSH concentration, particularly if associated with antithyroid antibodies, should prompt a reconsideration of the use of amiodarone, and discussion with an endocrinologist. 10. Bastenie PA, Vanhaelst L, Neve P. Coronary artery disease in hypothyroidism. Observations in preclinical myxoedema. Lancet 1967 ii 1221-2. 11. Tanis BC, Westendorp RJ, Smelt AM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism a re-analysis of intervention studies. Clin Endocrinol 1996 44 643-9. 14. Spencer C, Eigen A, Shen D, et al. Specificity of sensitive assays of thyrotropin (TSH)...

Natural Plant Toxins In Foods

Allyl isothiocyanates are a group of major naturally occurring compounds that confer the pungent flavor to foods such as mustard and horseradish, where it is present at about 50 to 100 ppm. These compounds are in Brassica vegetables such as broccoli and cabbage, and in cassava and other tropical staple foods, but at much lower concentrations. Normal dietary exposure to isothiocyanate-containing foods releases milligram amounts of isothiocyanates. Nominal processing steps (chopping, rinsing, milling) renders the food safe when wash water is discarded. In high doses, isothiocyanates are carcinogenic in rats but nonmutagenic in bacteria. Isothiocyanates do not occur in foods per se but occur as glucosinolate conjugates that are hydrolyzed when the plant releases enzymes as it is disturbed, such as during chopping, processing, or ingestion (Fig. 1). The major concern with isothiocyanates is their goitrogenic properties in that they inhibit binding of iodine in the thyroid gland. Because...

Recognition of Zinc Deficiency in Developing Countries

Children is relatively recent in contrast to the earlier recognition of the importance and widespread occurrence of deficiencies of iodine, vitamin A, and iron. Coordinated efforts to address vitamin A deficiency in less developed countries were formally initiated by the establishment of the International Vitamin A Consultative Group (IVACG) in 1975. In the mid-1980s, similar groups were founded for the control of iodine deficiency disorders (International Council for the Control of Iodine Deficiency Disorders ICC IDD) and iron deficiency (International Nutritional Anemias Consultative Group INACG). It was not until the year 2000 that a similar group emerged, the International Zinc Nutrition Consultative Group (IZiNCG), to promote the control of zinc deficiency in more vulnerable populations. The detection of zinc deficiency in populations and the recognition of its association with health outcomes have been somewhat more challenging for zinc than for other nutrients, contributing to...

Erythema multiforme and toxic epidermal necrolysis

Hypothyroidism (see also Chapter 20) Feline hypothyroidism is a rare condition. A congenital aetiology appears to be more common than acquired hypothyroidism. Congenital hypothyroidism has been associated with thickened skin, soft fluffy coat and alopecia. In a tiger cub with congenital disease there was bilateral alopecia behind the ears, and alopecia of the dorsal aspect of the neck and the palmar aspect of the forelimbs. In acquired hypothyroidism signs may include generalised erythematous dermatitis, a dry, dull coat with seborrhoea sicca, poor hair growth and easily epilated hairs on the trunk and abdomen. One case had a non-healing wound, poor hair coat and generalised fine scale (Daigle et al., 2000). Experimentally induced hypothyroidism has been associated with seborrhoea sicca and bilateral alopecia of the pinnae (Van den Broek & Thoday, 1994).

Clinical Features

Once a physician determines that a patient truly is constipated, the physician must attempt to determine the cause. Ihe differential diagnosis is broad ( Iab e Z9.-3). Determining the onset of the constipation helps narrow the differential diagnosis. Acute constipation represents intestinal obstruction until proven otherwise. Iumors, strictures, and volvuli can all present as acute constipation. Physicians often mistake subacute for chronic constipation. Ihe important distinction here is to determine exactly when bowel habits changed. Generally, acute and subacute conditions have the same differential diagnosis. Chronic constipation, that is, a lifelong or persistent habit, is usually less ominous and, if uncomplicated, can often be managed on an outpatient basis. Ihe presence or absence of associated symptoms may help guide decision making. Vomiting rarely accompanies benign constipation. Inability to pass flatus also raises concern about obstruction. A history of gradually...

Diagnosis of Megaloblastic Anemia

Frequently, an FBC would also form part of an outpatient work-up or might be ordered by a GP through an associated hospital or laboratory. Where the hemoglobin level is below the reference value with respect to sex and age indicating anemia, the mean corpuscular volume (MCV) is assessed. This parameter essentially gives a mean of the size of red blood cells in the circulation. Mega-loblastic anemia usually results in larger than normal red cells in the circulation and thus a raised MCV however, sometimes quite advanced stages of megaloblastic anemia can be accompanied by a normal and, infrequently, even below normal MCV. This can arise because of the concomitant presence of iron deficiency. A raised MCV accompanying the anemia seen in the FBC (macrocytic anemia) moves the diagnosis to being one of megaloblastic anemia, although other causes of macrocytosis such as hypothyroidism or excess alcohol consumption may need to be considered also. Conventionally, the next step is...

The immunological role of calcitriol

Administration of calcitriol can prevent the development of experimental autoimmune encephalomyelitis and thyroiditis in mice and prolong the survival of transplanted skin allografts in mice. In normal mice, administration of la-hydroxyvitamin D, la(OH)D, , a synthetic vitamin D analog that is converted to calcitriol in the organism, leads to an increased primary antibody response, but the same treatment suppresses the hyperimmune response induced by concomitant administration of colchicine. Reports have demonstrated a reduction in antibody formation in ricketic rats challenged with diphtheria toxin or Sendai virus, a more fulminant spread of pneumococcal and Klebsiella infection when ricketic rats were inoculated with these organisms, and a decrease in antibody-forming cells in the spleen from ricketic rats. Several studies have shown that treatment with calcitriol or la(OH)D, can restore deficient macrophage and lymphocyte functions in vitamin D-deficient rats and patients with...

Regulation Of Thyroid Hormone Secretion

As already indicated, secretion of thyroid hormones depends on stimulation of thyroid follicular cells by TSH, which bears the primary responsibility for integrating thyroid function with bodily needs (Chapter 38). In the absence of TSH, thyroid cells are quiescent and atrophy, and, as we have seen, administration of TSH increases both synthesis and secretion of T4 and T3. Secretion of TSH by the pituitary gland is governed by positive input from the hypothalamic hormone thyrotropin-releasing hormone (TRH) and negative input from thyroid hormones. Little TSH is produced by the pituitary gland when it is removed from contact with the hypothalamus and transplanted to some extrahypotha-lamic site, and disruption of the TRH gene reduces the TSH content of mouse pituitaries to less than half that of wild-type litter mate controls. Positive input for thyroid hormone secretion thus originates in the central nervous system by way of TRH and the anterior pituitary gland. TRH increases the...

Step 2 Assess the history

Hyperthyroidism Hypothyroidism Diabetes mellitus Exogenous androgen use D. Step 4 Basic laboratory testing. In addition to measurement of serum hCG to rule out pregnancy, minimal laboratory testing should include measurements of serum prolactin, thyrotropin, and FSH to rule out hyperprolactinemia, thyroid disease, and ovarian failure (high serum FSH). If there is hirsutism, acne or irregular menses, serum

Over replacement with thyroxine

Sequential chest x rays from a patient with longstanding hypothyroidism that was complicated by congestive cardiac failure. (A) Before treatment. Cardiomegaly was caused by a combination of dilatation of all the cardiac chambers and pericardial effusion. (B) After treatment with thyroxine for nine months. (C) Seven years later, two years after the patient has stopped taking thyroxine, against medical advice, and had re-presented to the same physician with the symptoms and signs of heart failure. Reproduced from Davidson's principles and practice of medicine, 18th ed, p 570, with permission of the publisher Churchill Livingstone. Figure 35.3. Sequential chest x rays from a patient with longstanding hypothyroidism that was complicated by congestive cardiac failure. (A) Before treatment. Cardiomegaly was caused by a combination of dilatation of all the cardiac chambers and pericardial effusion. (B) After treatment with thyroxine for nine months. (C) Seven years later, two...

Thyroid Autoimmunity Animal Models

That autoimmunity is a major cause of thyroid disease has been evident for over 35 years, but many critical questions about the immunopathogenesis remain unanswered. This entry focuses on the proto-typic autoimmune thyroid disease, chronic thyroiditis or Hashimoto disease, and aims to answer these questions by reference to experimental models. The questions pertain primarily to the molecular and genetic basis of autosensitization, to the principal thyroid antigens and the immunological characteristics of pathogenetic autoimmunity. Two types of models are available for study in the research laboratory spontaneous and experimentally induced thyroiditis. Injection of thyroglobulin, usually with an adjuvant, induces thyroiditis in a variety of animals including rabbits, rats, mice, guinea pigs, dogs, rhesus monkeys and chickens. This method has the advantages of dealing with a well-characterized antigen and beginning at a defined point in time and, therefore, lends itself to precise...

Spontaneous animal models for organspecific autoimmune diseases

Obese strain of chickens as an animal model for Hashimoto's thyroiditis During the first few weeks after hatching, obese strain (OS) chickens develop a hereditary spontaneous autoimmune thyroiditis (SAT) that resembles human Hashimotos disease in all clinical, histopathological, endocrinological and immunological aspects. The thyroid glands of OS chickens become heavily infiltrated by mononuclear cells, finally resulting in complete destruction of their architecture entailing clinical symptoms of hypothyroidism (Figure 1), such as small body size - albeit with relatively high body weight due to the deposition of subcutaneous and abdominal fat - lipemic serum, long silky feathers, cold sensitivity, low laying capacity, diminished fertility and poor hatchability. In common with Hashimoto's thyroiditis, the infiltrated thyroid glands show high numbers of well-developed germinal centers as a characteristic hallmark that is unique to this model and absent in EAT. The serum of OS chickens...

Pathology Pathogenesis and Carcinogenesis

Other factors such as iodine deficiency, autoimmune thyroid disease, hyperthyroidism, sex hormone status and alcohol intake have all been implicated in the development of thyroid carcinoma, but remain unproven. Possible genetic patterns of differentiated thyroid carcinoma include patients with Gardner's syndrome (familial colonic polyposis) and Cowden's disease (familial goiter and skin hamartomas), but less than 3 of all papillary and or follicular thyroid carcinomas are truly familial.3 Cigarette smoking has not caused an increase in the incidence of thyroid carcinoma.

Wheel model for IDD Elimination Program

Figure 6 Wheel model for the iodine deficiency disorders (IDD) elimination program. The model shows the social process involved in a national IDD control program. The successful achievement of this process requires the establishment of a national IDD control commission, with full political and legislative authority to carry out the program. (Reproduced from Hetzel BS (1989) The Story of Iodine Deficiency An international Challenge in Nutrition. Oxford Oxford University Press.) Figure 6 Wheel model for the iodine deficiency disorders (IDD) elimination program. The model shows the social process involved in a national IDD control program. The successful achievement of this process requires the establishment of a national IDD control commission, with full political and legislative authority to carry out the program. (Reproduced from Hetzel BS (1989) The Story of Iodine Deficiency An international Challenge in Nutrition. Oxford Oxford University Press.) In addition, a community education...

Other Causes of Hyperhomocysteinemia

Other pathophysiological causes of hyperhomocys-teinemia include renal dysfunction and hypothyroid-ism. The kidney is a major site of homocysteine metabolism and renal disease leads to a significant reduction in the body's overall capacity to metabolize this amino acid. The resulting moderate to severe hyperhomocysteinemia can be attenuated, in part, by high-dose B vitamin supplements, which putatively maximize the residual renal metabolism, as well as the metabolic capacities of the extrarenal organs. Mild elevations in homocysteine occur in patients with hypothyroidism, which resolve to normal with thyroid replacement therapy. This observation implies that thyroxine and or thyroid-stimulating hormone influence homocysteine metabolism directly, perhaps through up- or downregulation of key homocysteine-metabolizing enzymes. Alternatively, homocysteine may become elevated in hypothyroid patients secondary to mild impairment of renal function that may accompany the disorder.

Which type of hyperthyroidism

Although there are features which help to distinguish between the two types of hyperthy-roidism (table 35.1), the differentiation may be diYcult and in some patients both mechanisms may be operating. In such circumstances it is sensible to institute a trial of carbimazole and to withdraw the drug after 3-4 months. If the patient remains euthyroid or becomes hypothyroid the diagnosis is likely to be type II hyperthyroidism evidence of persistent hyperthyroidism suggests a diagnosis of type I hyperthyroidism and the need to maintain car-bimazole treatment for as long as the amiodarone is necessary and beyond. Pre-existing thyroid disease Goitre Subsequent hypothyroidism Hypothyroid

Animal models of Addisons disease

Idiopathic Addisons disease occurs spontaneously in dogs and more rarely in cats. In the few cases that have undergone autopsy, atrophy, regeneration of adrenocortical cells and chronic inflammation of the adrenal cortex have been observed. The cause of adrenal insufficiency in dogs is probably of autoimmune, not tubercular, origin. A preferential occurrence in Chow-Chow dogs suggests a genetic predisposition. Adrenal autoimmunity with lesions of the chronic inflammatory type has been experimentally induced by immunization of monkeys, rabbits, guinea pigs, rats and mice with suspensions of adrenal cortex in complete Freund's adjuvant. Circulating autoantibodies to the adrenal cortex have been demonstrated in these models, whereas there is paucity of reports on cellular autoimmunity. As for other experimental models, adrenalitis was induced in histocompatible recipients by adoptive transfer of lymph node cells from animals with adrenal autoimmunity. Modern immunogenetic studies are...

TABLE 2062 Signs and Symptoms of Symptoms of Hyperthyroidism

Palliative treatment for mild hyperthyroidism can be accomplished by using various b-blocker medications, the most common of which is propranolol. The goals of therapy include decreased heart rate, decreased tremor, increased muscle strength, and overall improvement in the patient's sense of well-being. 5 Treatment of Graves' disease may include long-term antithyroid medication, propylthiouracil or methimazole (MMI), radioiodine (iodine 131), or surgical ablation (subtotal thyroidectomy). Toxic multinodular goiter and solitary adenomas may also be treated with radioiodine. Hyperthyroidism due to thyroiditis is usually self-limited, and specific therapy is rarely needed. Common causes of thyroidtis are subacute (painful) thyroiditis (due to viral causes), silent thyroiditis (lymphocytic infiltrate), and postpartum thyroiditis (transient immune destruction). Thyrotoxicosis factitia may be suspected with the absence of thyromegaly, low serum thyroglobulin levels, and decreased or absent...

Micronutrients Alleviating Nutritional Disorders By Nutraceuticals

Iodine deficiency is the greatest single cause of preventable brain damage and mental retardation in the world today. More than 2 billion people around world live in iodine deficiency environments. Deficiency in iodine occurring in late infancy and childhood have been demonstrated to produce mental retardation, delayed motor development, and stunted growth, occurrence of neuromuscular disorders, and speech and hearing defects. Even mild iodine deficiency has been reported to decrease intelligence quotients by 10-15 points (22,31).

International Context International Promotion

The more specific targets of the World Summit for Children (1990) to be reached by the year 2000, included (i) reduction in severe as well as moderate malnutrition among children younger than 5 years old by half of 1990 levels, (ii) reduction in the rate of low birth weights (2.5 kg or less) to less than 10 , (iii) reduction of iron deficiency anemia in women by one-third of the 1990 level, (iv) virtual elimination of iodine deficiency disorders, and (v) virtual elimination of vitamin A deficiency and its consequences, including blindness. These have clearly not been reached, and the setting of such unobtainable targets has been criticized on the grounds that they divert the attention of nutrition planners away from local priorities to global issues.

Ischaemic heart disease

Overt hypothyroidism is associated with hyper-lipidaemia and coronary artery disease. Approximately 3 of patients with longstanding hypothyroidism report angina, and a similar proportion report it during treatment with thy-roxine. In most patients the angina does not change, diminishes or disappears when thyrox-ine is introduced however, it may worsen and up to 40 of those patients who present with hypothyroidism and angina cannot tolerate full replacement treatment. Moreover, myocardial infarction and sudden death are well recognised complications of starting treatment, even in patients receiving as little as 25 ig of thyrox-ine daily. For these reasons it is customary to begin treatment with thyroxine in patients with symptomatic ischaemic heart disease in a dose of 25 ig daily, increasing by 25 ig increments every three weeks until a dose of 100 ig daily is reached. After a further six weeks, serum free T4 and TSH should be measured and the dose of thyroxine adjusted to ensure that...

Animal models of autoimmune gastritis

There is no animal model in which the primary disease is autoimmune gastritis although atypical forms of autoimmune gastritis are present in a proportion of animals whose primary autoimmune disease is one of the diseases associated with autoimmune gastritis. For example BB W rats whose primary disease is insulin-dependent diabetes mellitus may have gastric parietal cell antibodies and histologic evidence of mild to moderate gastritis. However they have no reduction in acid secretion or fall in level of vitamin B12. Another example, the obese strain chicken model of Hashimoto's thyroiditis may also have gastric parietal cell antibodies but the chicken provides a poor model of the human gastritis.

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