The Natural Thyroid Diet

The Natural Thyroid Diet

The Natural Thyroid Diet is a guide written to show people suffering from thyroid how to treat it the most natural and effective way. The guide was put together to be something that can be done at home without a need to visit an expert as regards its use. This program is a proven home method useful in eliminating Thyroid rapidly and permanently. It is a combination of useful diets system to help you permanently get rid of your thyroid within 4 weeks. The foods have been tested and have been proven to solve this problem for you. The book is a quick fix that has been designed to help you get a cure for your Thyroid in 4 Weeks. The methods employed in this book are natural ones that have been proven by many specialists. The book is in a digital format (PDF) and has been created at a very affordable price. There are a lot of stress, frustrations and disappointments that come with trying programs after programs. This is one thing that happens in the name of fighting Thyroid; however, this program has been designed to help you stop worrying about programs after programs. The creator is assured of its work that you are allowed to ask for a refund if nothing happens after 4 weeks of its usage. Read more here...

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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 61 Histologic classification of thyroid carcinoma

Differentiated Thyroid Carcinoma Follicular thyroid cell origin Papillary thyroid carcinoma Follicular, tall cell, mucoid, or insular variant Follicular thyroid carcinoma Hurthle cell carcinoma Anaplastic thyroid carcinoma Medullary Thyroid Carcinoma Parafollicular or C cell origin Sporadic medullary thyroid carcinoma Non-MEN familial medullary thyroid carcinoma Multiple endocrine neoplasia type 2A (MEN 2A) Multifocal medullary thyroid carcinoma Parathyroid hyperplasia Pheochromocytoma Multiple endocrine neoplasia type 2B (MEN 2B) Multifocal medullary thyroid carcinoma Pheochromocytoma Table 6.2. Distinguishing features. Papillary and follicular thyroid carcinoma Table 6.2. Distinguishing features. Papillary and follicular thyroid carcinoma marizes some of the distinguishing features of papillary and follicular carcinomas of the thyroid gland. The median age at diagnosis for DTC is 40-50 years and papillary thyroid carcinoma is three to four times more common in women than in men....

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).

Recurrent Thyroid Carcinoma

The presence of a new cervical mass or cervical lymphadenopathy after thy-roidectomy is usually the first sign of recurrence of differentiated thyroid carcinoma. A conventional radiologic imaging study such as cervical ultrasonography often begins the investigation. Fine needle aspiration biopsy with or without ultrasonographic guidance is useful to establish a cytologic diagnosis of recurrent thyroid carcinoma. Computerized tomography of the neck with contrast is usually avoided unless extensive local, tracheal, or mediastinal invasion is suspected. The large dose of iodinated oral and intravenous contrast necessary to complete this study may make diagnostic and therapeutic radioactive iodine ablation problematic. Surgical resection of any palpable cervical disease is advisable if safe performance can be accomplished.1 This may include a modified radical neck dissection and or completion thyroidec-tomy depending on the site and extent of recurrent disease. Palliative endoscopic...

Thyroidectomy in Carriers of RET Gene Mutations

Several series have reported the performance of preventative thyroidectomy on members of at-risk MEN 2A and FMTC kindreds who are found to be carriers of RET gene mutations by genetic testing. The first two such reports were from S. A. Wells et al in the Department of Surgery at Washington University in St. Louis and K. Lips et al from the Netherlands.1,3 In the series from Washington University, one hundred thirty-two individuals from seven different kindreds affected by MEN 2A were evaluated.1 Of the 132 individuals, 48 had an established diagnosis of MEN 2A and 58 were at 50 risk for inheriting the disease but had no clinical evidence of endocrine neoplasia. Twenty-six unaffected spouses of MEN 2A kindred members served as controls. All individuals were evaluated by both direct and indirect genetic testing for the presence of RET gene mutations. In patients at 50 risk for disease (having an affected parent or sibling), stimulated calcitonin levels were also determined. In 21...

Management ofPersistent or Recurrent Medullary Thyroid Carcinoma

When medullary thyroid carcinoma presents as a neck mass, as in patients with sporadic disease, and those hereditary cases which did not have the benefit of screening, over 50 will have persistent or recurrent elevation of calcitonin levels following primary surgery, indicating the presence of persistent tumor. In one study of patients who presented with palpable tumors, 15 18 (83 ) of patients with hereditary disease and 11 20 (55 ) patients with sporadic tumors had persistent disease as indicated by elevated calcitonin levels postoperatively. Patients with persistently high levels of calcitonin following thyroidectomy may do well and remain asymptomatic for many years.7 Other patients develop local or distant recurrences which may cause symptoms and death. A Norwegian study of 84 cases of MTC found that over 50 of patients who presented with cervical node metastases eventually died of disease. Medullary thyroid carcinoma cells do not take up radioactive iodine, and this form of...

Regulation Of Thyroid Function

Effects of Thyroid-Stimulating Hormone Although the thyroid gland can carry out all of the steps of hormone biosynthesis, storage, and secretion in the absence of any external signals, autonomous function is far too sluggish to meet bodily needs for thyroid hormone. The principal regulator of thyroid function is the thyroid-stimulating hormone (TSH), which is secreted by thyrotropes in the pituitary gland (see Chapter 38). It may be recalled that TSH consists of two glycosylated peptide subunits including the same -subunit that is also found in FSH, and LH (Chap. 38). The -subunit is the part of the hormone that confers thyroid-specific stimulating activity, but free -subunits are inactive, and stimulate the thyroid only when linked to a-subunits in a complex three dimensional configuration. 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...

Thyroid Hormones In Blood

More than 99 of thyroid hormone circulating in blood is firmly bound to three plasma proteins. They are thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin. Of these, TBG is quantitatively the most important and accounts for more than 70 of the total protein-bound hormone (both T4 and T). About 10-15 of circulating T4 and 10 of circulating T3 is bound to TTR and nearly equal amounts are bound to albumin. TBG carries the bulk of the hormone even though its concentration in plasma is only 6 of that of TTR and less than 0.1 of that of albumin because its affinity for both T4 and T3 is so much higher than that of the other proteins. All three thyroid hormone binding proteins bind T4 at least 10 times more avidly than T3. All are large enough to escape filtration by the renal glomerular membranes and little crosses the capillary endothelium. The less than 1 of hormone present in free solution is in equilibrium with bound hormone and is the only hormone that can escape from...

Mechanism Of Thyroid Hormone Action

As must already be obvious, virtually all cells appear to require optimal amounts of thyroid hormone for normal operation, even though different aspects of cellular function may be affected in different cells. Thyroid hormones are quite hydrophobic and may either diffuse across the cell membrane or enter target cells by a carrier-mediated transport process. T3 formed within the target cell by deiodination of T4 appears to mix freely with T3 taken up from the plasma and to enter the nucleus, where it binds to specific receptors (see Chapter 2). Thyroid hormone receptors are members of the large family of nuclear hormone receptors and bind to specific nucleotide sequences (thyroid response elements or TREs) in the genes they regulate. Unlike most other nuclear receptors, thyroid hormone receptors bind to their response elements in the absence of hormone. They bind as monomers or as homodimers composed either of two thyroid hormone receptors, or they may form heterodimers with other...

Protein Binding of Thyroid Hormone

Most thyroid hormone in the circulation is bound to protein, primarily thyroid-binding globulin (TBG). Only a small fraction of thyroid hormone is in the unbound (biologically active) form. Increases in concentration of TBG, as occurs during pregnancy, may increase the total concentration of T3 and T4 without affecting the level of free hormone. Figure EP.6 Synthesis of thyroid hormones Figure EP.6 Synthesis of thyroid hormones Figure EP.7 Control of thyroid secretion Figure EP.7 Control of thyroid secretion

TABLE 2066 Treatment of Thyroid Storm

Comorbid factors that may have precipitated thyroid storm must also be treated. Electrocardiograms, chest radiographs, urinalysis, blood cultures, and administration of empiric antibiotics should always be considered in patients presenting in thyroid storm. Standard therapy for heart failure due to ischemic or hypertensive heart disease may be utilized. All patients should be admitted to an appropriately monitored setting for further evaluation and care. Definitive therapy is usually via radioiodine administration once the patient is stable and euthyroid.

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.

Complications Following Thyroidectomy

Transient hypocalcemia commonly occurs 24-48 h after thyroidectomy, but infrequently requires treatment. Adult patients who are markedly symptomatic or who have serum calcium below 7 mg dL are given one to two ampules (10-20 mL) of 10 percent calcium gluconate intravenously, followed by oral calcium carbonate. On occasion, a calcium drip may be required. To prepare this, six ampules of 10 percent calcium gluconate, each containing 90 mg elemental calcium are added to 500 cc D5W to achieve a concentration of approximately 1 mg elemental calcium per cc. The drip is run at a cc per hour rate equivalent to the patient's weight in kilograms to achieve replacement of 1 mg kg h. Permanent hypoparathyroidism is uncommon after total thyroidectomy. Normal parathyroid tissue removed or devascularized at the time of total thyroidectomy may be autotransplanted into sternocleidomastoid muscle to prevent postoperative hypocalcemia.9 RLN injury is a devastating complication of thyroidectomy that...

Parathyroid Carcinoma

Parathyroid carcinoma is rare and accounts for less than 1 percent of patients with HPT. Approximately 50 percent of these patients have a palpable neck mass, and serum calcium levels may exceed 15 mg dL. Surgical treatment is radical local excision of the tumor, surrounding soft tissue, lymph nodes, and ipsilateral thyroid lobe when the disease is recognized preoperatively or intraoperatively. Patients with parathyroid carcinoma and some patients with benign HPT may develop hyperparathyroid crisis. Symptoms of this acute, sometimes fatal, illness include profound muscular weakness, nausea and vomiting, drowsiness and confusion. Hypercalcemia (16-20 mg dL) and azotemia are usually present. Ultimate treatment of parathyroid crisis is parathyroidectomy however, hypercalcemia and volume and electrolyte abnormalities should be addressed first. Treatment is warranted for symptoms or a serum calcium level greater than 12 mg dL. First-line therapy is infusion of 0.9 percent NaCl to restore...

Parathyroid Glands And Parathyroid Hormone

Human beings typically have four parathyroid glands, but as few as two and as many as eight have been observed. Each gland is a flattened ellipsoid measuring about 6 mm in its longest diameter. The aggregate mass of the adult parathyroid glands is about 120 mg in men and about 140 mg in women. These glands adhere to the posterior surface of the thyroid gland or occasionally are embedded within thyroid tissue. They are well vascularized and derive their blood supply mainly from the inferior thyroid arteries. Parathyroid glands are comprised of two cell types (Fig. 6). The chief cells predominate and are arranged in clusters or cords. They are the source of PTH and have all of the cytological characteristics of cells that produce protein hormones rough endoplasmic reticulum, prominent Golgi apparatus, and some membrane-bound storage granules. The oxyphil cells, which appear singly or in small groups, are larger than chief cells and contain a remarkable number of mitochondria. Oxyphil...

Parathyroid Localization Studies

Computed tomography has been used to evaluate the parathyroid glands, and is most useful in the setting of persistent or recurrent hyperparathyroidism after initial neck exploration. This is because CT can help delineate scarred tissue planes. It is also useful for visualizing glands in the mediastinum, and in locations in the neck which are difficult to visualize using ultrasound, such as retroesophageal or juxtavascular locations. When CT is used, the protocol includes thin cuts (either 3-4 mm cuts or overlapping 6-8 mm cuts). The scanning volume should include the neck from the hyoid bone to the apices of the lungs initially. In the setting of previous operations, the mediastinum should be included as well, to reduce the chance of missing an ectopic gland. An initial noncontrast scan should be done, followed by a contrast-enhanced scan. The contrast scans can be especially helpful in the setting of glands located near the thyroid. The thyroid, because of its high affinity for...

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. As with most operations, the complications associated with thyroidectomy can be listed as general and local. General...

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. Excess of thyroid secretions may be treated in several ways. Surgical reduction of the thyroid gland, inhibition of the peripheral actions (P adrenoceptor antagonists) or specific targeting of thyroid hormone synthesis and secretion. 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.

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...

Cricothyroidotomy Indications and Contraindications

Cricothyroidotomy remains the quickest, safest, and easiest way to obtain an airway on an emergency basis when attempts at orotracheal and nasotracheal intubation have failed. It is contraindicated if any other less radical means of securing an airway is feasible. The advantages of cricothyroidotomy to secure an airway emergently are ease, safety, rapidity, and avoidance of injuring the thyroid isthmus or blood vessels that are encountered when performing a tracheostomy where the tracheal incision is made more inferiorly. Although these lifesaving benefits are specific to cricothyroidotomy in contrast to tra-cheostomy for establishing a surgical airway emergently, the risk of vocal cord injury and subglottic tracheal stenosis is significantly higher.

Parathyroid Reoperations

Ultrasonography has been effectively employed to identify abnormal parathyroid glands within or immediately adjacent to the thyroid gland (Fig. 16.1). Libutti3 et al have reported their experience with a series of patients in whom preoperative or intraoperative ultrasound (IOUS) was helpful in localizing intrathyroidal parathyroid glands. Although noninvasive, readily available and inexpensive, ultrasound is not useful in detecting glands located in the retrosternal, mediastinal, or retrotracheal positions. Further, accurate interpretation requires an ultrasonographer and radiologist skilled in assessing these structures. If a lesion is identified on ultrasound, these images can be used to guide percutaneous aspiration biopsy. This technique requires a skilled individual, and the sample is analyzed for PTH and cytology, including staining with an anti-PTH antibody. Upper thyroid capsule 1 Fig.16.1. Ultrasound of the neck. Parathyroid adenoma is the echopenic lesion relative to the...

Rationale For Molecular Diagnostic Testing In Patients With Suspected Thyroid Cancer

The initial workup of a thyroid nodule consists of ultrasonography and if indicated a fine-needle aspiration biopsy (FNAB). Despite the fact that cytological examination of FNAB by an experienced pathologist provides the most accurate and cost-effective means of diagnosing thyroid neoplasms, in some situations, cyto-logical examination may not provide a conclusive diagnosis. For example, biopsy samples are cytologically found to be ''intermediate'' or ''suspicious,'' but most of these lesions are benign. In addition, preoperative diagnosis of lesions with follicular histology is difficult, and a consistent number of not otherwise specified ''follicular nodules'' are surgically resected more for diagnosis than therapeutic purposes. Because operation could be recommended only to those patients with a high risk of malignancy, the use of a molecular-based approach with detection of tissue- or tumor-specific mRNA transcripts may provide a more objective method to assure reliable diagnosis....

Effects of thyroid hormones on the cardiovascular system

The thyroid secretes two active hormones thyroxine (T4) which is a prohormone and tri-iodothyronine (T3) which acts as the final mediator. In hyperthyroidism there is excessive production of T3, owing to hypersecretion by the thyroid gland, and an increase in the peripheral monodeiodination of T4, which leads to profound changes in the cardiovascular system through both nuclear and non-nuclear actions at the cellular level.1 There is a complex interaction between thyroid hormones and the adrenergic system, and many of the clinical features of hyperthy-roidism such as tachycardia, increased pulse pressure, and tremor resemble the heightened P adrenergic state of phaeochromocytoma. However, serum and urinary catecholamine concentrations are normal or even low in hyperthyroidism, and there is no good evidence of greater sensitivity to catecholamines despite an increased density of P1 adrenoceptors in cardiac muscle. It may well be that thyroid hormones and catecholamines act...

Medullary Thyroid Carcinoma

In medullary thyroid carcinoma (MTC), laboratory tests for preoperative diagnosis and postoperative follow-up are performed using basal as well as pentagastrin-stimulated serum calcitonin (CT), which is supplemented by estimation of serum levels of carcinoembryonic antigen (CEA). In contrast to papillary and follicular thyroid carcinoma, to date only a few studies have been published concerning the preoperative diagnosis of MTC using PCR-based methods. The reason for that discrepancy may be that patients with MTC are usually readily diagnosed by conventional cytology and serum calcitonin measurements. One study reported the preoperative diagnosis of MTC by RT-PCR using RNA extracted from leftover cells of FNAB. 7 As transcripts specific for MTC, calcitonin, carcinoembryonic antigen, and RET proto-oncogene mRNA, respectively, were used. In another study using identical primer sequences, calcitonin mRNA was found in all samples of FNAB derived from patients with MTC, but not in samples...

Molecular Analyses Of Peripheral Blood And Postoperative Surveillance Of Thyroid Carcinomas

Papillary and Follicular Thyroid Carcinoma 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...

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.

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.

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. Measurement of serum concentrations of T3, T4, and TSH should be made three and six months after starting amiodarone treatment and every six months thereafter, including during the first year after the drug is stopped. Table 35.2 shows the different patterns of abnormal thyroid function test results which may occur. Serum T3 concentration is the best indicator of hyperthyroidism, but in some circumstances a trial of carbimazole for 6-8...

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...

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...

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. T3 is the most valuable and sensitive measure of thyroid function in patients who have received amiodarone because, even among euthyroid patients, the inhibition of the peripheral conversion of T4 to T3 may produce a high T4 and low TSH.

Which type of hyperthyroidism

Pre-existing thyroid disease Goitre Radioiodine uptake by thyroid TSH receptor antibodies in serum Antiperoxidase (microsomal antibodies in serum) Serum IL-6 Table 35.2 Patterns of thyroid function tests which may occur during treatment with amiodarone Table 35.2 Patterns of thyroid function tests which may occur during treatment with amiodarone Euthyroid (effect of amiodarone on thyroid hormone metabolism)

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...

Metabolism Of Thyroid Hormones

Because T4 is bound much more tightly by plasma proteins then T3, a greater fraction of T3 is free to diffuse out of the vascular compartment and into cells where it can produce its biological effects or be degraded. Consequently, it is not surprising that the half-time for disappearance of an administered dose of 125I-labeled T3 is only one-sixth of that for T4, or that the lag time needed to observe effects of T3 is considerably shorter than that needed for T4. However, because of the binding proteins, both T4 and T3 have unusually long half-lives in plasma, measured in days rather than seconds or minutes (Fig. 7). It is noteworthy that the half-lives of T3 and T4 are increased with thyroid deficiency and shortened with hyperthyroidism. Although the main secretory product of the thyroid gland and the major form of thyroid hormone present in the circulating plasma reservoir is T4, abundant evidence indicates that it is T3 and not T4 that binds to the thyroid hormone receptor (see...

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...

Table 22 Important clinical factors in the diagnosis of thyroid cancer

Associated symptoms (pain, dysphagia, dysphonia, dyspnea) Growth on thyroid hormone suppression past medical history include symptoms of pheochromocytoma or hyperparathyroidism, long-standing constipation and or diarrhea, hypertension and or episodes of nervousness. These should alert the clinician to the possibility of thyroid carcinoma in association with a familial MEN syndrome. In questioning the patient about the nodule, the time course for its development can be an important piece of information. A nodule that has been stable in size for years is almost always benign. Very rapid development, such as over hours or days, would suggest a thyroid cyst or hemorrhage. Thyroid malignancies usually develop over weeks or months. There are also specific symptoms that would be worrisome of malignancy. Invasion of the thyroid capsule, entrapment of the recurrent laryngeal nerve or spread into adjacent tissues can lead to local pain in the neck or radiating to the jaw and ear. Dysphagia,...

Thyroid Hormone Effects

Virtually no organ or tissue escapes the effects of thyroid hormone. Sufficient amounts are necessary for brain development, normal growth and metabolism. Thyroid hormone affects the rate of synthesis and degradation of many hormones and enzymes. Thyroid hormone raises the basal metabolic rate and stimulates heat production. This may occur by increasing mitochondrial metabolism, by enhancing Na+ K+ ATPase activity, or by increasing futile cycles of carbohydrate or lipid metabolism. Oxygen consumption increases which necessitates an increased ADP ATP exchange 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...

Thyroid arteries

The superior thyroid artery arises at the origin of the external carotid artery, runs downwards to the superior pole of the thyroid lobe, divides into 2-3 branches and enters the lobe on its posterior aspect. The inferior thyroid artery arises from the thyro-cervical trunk which originates from the first part of the subclavian artery. It ascends initially, then turns medially at the level of the cricoid cartilage. From here it passes posterior to the internal jugular vein, the common carotid artery and the vagus nerve in the carotid sheath, and also behind the sympathetic trunk. It enters the posterior aspect of the thyroid at about the middle of the lobe. The thyroid ima artery is rare and enters the thyroid isthmus inferiorly. It may arise from the brachiocephalic trunk, the left common carotid artery or even the aortic arch.

Thyroid Hormones

The thyroid hormones are a-amino acid derivatives of tyrosine (Fig. 3). The thyronine nucleus consists of two benzene rings in ether linkage, with an alanine side chain FIGURE 2 Histology of the human thyroid. Simple cuboidal cells (arrows) make up the follicles. C, thyroid colloid (thyroglobulin), which fills the follicles. (From Borysenko M, Beringer T. Functional histology, Boston Little, Brown, 1979, p. 312.) FIGURE 2 Histology of the human thyroid. Simple cuboidal cells (arrows) make up the follicles. C, thyroid colloid (thyroglobulin), which fills the follicles. (From Borysenko M, Beringer T. Functional histology, Boston Little, Brown, 1979, p. 312.)

Thyroid Storm

Patients with thyroid storm present with fever, volume depletion, cardiac decompensation. Thyroid storm has been associated with a mortality rate of up to 25 percent. Patients are treated with intravenous fluids, oxygen, antipyretic agents, as well as PTU 400 mg PO q8 h and sodium iodide 1 gm IV in 500 mL of intravenous fluid each day. Long-term use (> 10 days) of sodium iodide results in a high incidence of fetal goiter and hypothyroidism. Propranolol 40 mg PO q6 h is administered unless evidence of cardiac failure is present. Acetaminophen is used for treatment of hyperthermia a cooling blanket may also be used. Steps should be taken to improve uterine blood flow, such as administration of oxygen as well as maintenance of adequate maternal hydration and left lateral uterine displacement. Radioactive iodine therapy is not used, as the fetus will concentrate iodine 131 after the tenth to twelfth week of gestation, and congenital hypothyroidism results.

Hypoparathyroidism

Total serum calcium includes ionized and protein-bound fractions. A common cause of measured hypocalcemia is hypoalbuminemia. However, symptoms of hypocalcemia occur only if the ionized fraction of calcium is reduced. The differential diagnosis for hypocalcemia is large (Table 10.5). Hypocalcemia due to hypoparathyroidism is uncommon. The most common cause is inadvertent devascularization or removal of the parathyroid glands during thyroid or parathyroid surgery. Hypocalcemia can result from reduced PTH secretion secondary to hypoparathyroidism or decreased end-organ responsiveness to PTH. This second disorder is termed pseudohypoparathyroidism. In pseudohypoparathyroidism, PTH is available but its affect at target tissues is decreased. The inability to respond normally is the result of dysfunction at the target cell level. This is due to a deficiency of the G-protein to couple the PTH receptor to the adenylate cyclase enzyme.

Thyroid Imaging

Thyroid imaging is most often accomplished with ultrasound or radionu-clide scanning. Other imaging modalities, including computed tomographic (CT) scanning and magnetic resonance imaging (MRI) are useful in special circumstances. Technetium thyroid scanning 20 min after the intravenous injection of technetium-99m (99mTc) is useful in determining the size of the thyroid and in differentiating solitary functioning nodules from multinodular goiter. Hypofunctioning areas (cyst, neoplasm, or suppressed tissue adjacent to autonomous nodules) are cold, whereas areas of increased synthesis are hot. Thyroid scans alone are not able to differentiate benign from malignant thyroid nodules. Cold nodules have a 15-20 percent risk of malignancy, and therefore ought to be surgically removed. Hot nodules are almost never malignant. 99mTc thyroid scans are most useful as adjunctive tests to assess risk of malignancy in patients with indeterminate thyroid nodule cytology or in hyperthyroid patients...

Normal Thyroid State

Regulation of synthesis and release of thyroid hormone is under the control of the anterior pituitary gland via thyroid-stiumulating hormone (TSH), or thyrotropin. Regulation of TSH in turn is by hypothalamic thyrotropin-releasing hormone (TRH) and also by means of a feedback loop to the pituitary gland by circulating thyroxine (T4) and triiodothyrinine (T3) levels. Thyroid hormone production depends on adequate iodine intake and synthesis of thyroglobulin. Following release from the thyroid, thyroid hormones are reversibly bound to various circulating plasma proteins, of which thyronine-binding globulin (TBG) is the major constituent. The free, unbound portions of the hormone are biologically active. Normally, T 4 is the predominant circulating hormone. T4 is peripherally deiodinated to T3 and is responsible for producing 80 percent of the circulating T 3 hormone. Free T3 is biologically more active than T 4 but has a shorter half-life (1 day versus 1 week). Thyroid hormone exerts...

Hypothyroidism

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 Neoplasms

Differentiated (papillary and follicular) thyroid cancers are among the most curable of human cancers.7 These cancers are rare in children and increase in frequency with age. The female to male ratio is approximately 2.5 1.0. The cause of these cancers is unknown, but childhood exposure to radiation is the best known etiologic factor. Approximately 30 percent of exposed children develop thyroid nodules, and of these an estimated 30 percent are malignant. The appropriate initial procedure for a solitary thyroid nodule suspected of being malignant is lobectomy and isthmusectomy. Controversy exists about the extent of surgery that ought to be performed for patients with biopsy-proven differentiated thyroid cancer, principally because these patients have a good prognosis irrespective of the surgical treatment. Prognosis depends mostly on the patient's age as well as extent and histologic subtype of disease. Papillary thyroid carcinoma (PTC) represents 85 percent of thyroid carcinomas and...

TSHthyroid axis

Acute illness or trauma induces alterations in thyroid hormone equilibrium within hours. Although serum TSH usually remains normal, circulating T3 rapidly drops, partly due to reduced conversion of T4 to T3 and or increased turnover of thyroid hormones. The extent of the T3 drop within 24 hours reflects the severity of illness (Schlienger et al 1991, Rothwell & Lawler 1995). Serum reverse T3 (rT3) levels increase partly due to reduced rT3 degradation. In animal models hepatic nuclear T3 receptors appear to decrease in number and occupancy. The absence of a TSH elevation in the presence of low circulating T3 levels suggests that there is also an altered feedback setting at the hypothalamic pituitary level. Experimental data indicate that reduced TRH gene expression as well as enhanced nuclear T3 receptor occupancy within the thyrotrophs may be involved (Kakucska et al 1994, St Germain & Galton 1985). The mechanism responsible for the low T3 syndrome remains speculative. Increased...

Parathyroid Cancer

On physical examination patients with parathyroid carcinoma are much more likely to have a palpable neck mass than those patients with benign parathyroid pathology. A parathyroid adenoma or hyperplastic gland is almost never palpable and Albright's Rule states that a palpable neck mass in a patient with benign hyper-parathyroidism is usually a thyroid nodule. Any patient with hyperparathyroidism and palpable cervical lymphadenopathy should be suspected of having a parathyroid malignancy. Although, one must remember that malignancies other than parathyroid cancer, including lymphoma and lung cancer, can cause hypercalcemia and cervical adenopathy. Finally, if the patient has hoarseness, one should think of a parathyroid cancer invading or compressing the recurrent laryngeal nerve. This is almost never seen with benign parathyroid disease. The procedure of choice for a patient with a parathyroid cancer should be radical or en bloc resection of the parathyroid gland and, at the minimum,...

Thyroiditis

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...

Table 11 Conditions affecting TBG concentration

Total T3 unreliable as an indicator of thyroid function, since the total T4 or total T3 level may be altered secondary to changes in the level of the bound (inactive) hormone, while the level of free T4 or free T3 may be unchanged. Most free T4 is converted to T3 in the peripheral tissues (liver and kidney) by type I 5'deiodinase. Type I 5'deiodinase is inactivated by propylthiouracil. Two other deiodinase enzymes have been isolated. Type II deiodinase is located in the pituitary, brain, and brown fat. It also converts T4 to T3. In the pituitary, this serves to inhibit TSH release. Type III 5'deiodinase converts T4 and T3 to reverse T3, an inactive derivative. T3 is the biologically active form of thyroid hormone. Whether T4 has any biological effect or is simply a prohormone is not clear. Both T4 and T3 are transported across cellular membranes by a carrier mediated, adenosine triphosphate (ATP)-dependent process. The two iodothyronines do not compete with each other for cellular...

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.

Ultrasound Guided Biopsy

Over the past decade, ultrasound has become an extremely useful tool for the surgeon. Ultrasound of the thyroid has been used preoperatively to evaluate thyroid nodules, however, alone, the sensitivity, specificity and positive predictive value for ultrasound is quite low. Despite this, its use in guiding biopsies can be extremely helpful. By using ultrasound in conjunction with FNAB, more information can be obtained about the entire gland. More importantly, ultrasound-guided FNAB can increase the percentage of diagnostic biopsies.5 Smaller lesions that are more difficult Fig. 2.1. Diagnostic approach to a solitary thyroid nodule. Fig. 2.1. Diagnostic approach to a solitary thyroid nodule. to biopsy by palpation, are more accessible to ultrasound guided biopsies. The clinician can be assured that the tip of the needle is within the lesion during aspiration. Likewise, nondiagnostic biopsies often result from the tip of the needle sitting in a cystic or degenerative portion of the...

Indeterminate Lesions

When the FNAB demonstrates a cytologic appearance of follicular or Hurthle cell neoplasm, surgery is indicated in order to make the diagnosis. An exception to this rule may be when the nodule is hyperfunctioning, as these are predictably benign. As previously mentioned, when the situation arises of an FNAB consistent with follicular neoplasm and thyroid function tests are consistent with hyperthyroidism, a thyroid scintiscan may be an appropriate test. If the nodule is hot, it may be observed, treated with 131I or surgically excised. If the plan is to treat a hyperfunc-tioning nodule with surgery, the thyroid scan is not necessary and the patient may proceed directly to surgical excision.

Table 31 Incidence of the substernal goiter

Country Year Thyroidectomies Substernal goiter embryonal thyrocytes that have descended into the chest along with the arch of the aorta. Secondary goiters are cervical goiters that have migrated to the intrathoracic location. Negative mediastinal pressure and the fixation of muscle and soft tissue superiorly favors the downward extension of the goiter into the space of least resistance. Key differences between the primary and secondary goiter are listed in Table 3.2. Secondary goiters in the anterior mediastinum usually originate from the lower pole of the thyroid gland. The goiter descends along the anterolateral aspect of the trachea and anterior to the recurrent laryngeal nerve and the carotid vessel. Occasionally a goiter originating from the posterolateral aspect of the thyroid may descend into the posterior mediastinum pushing the esophagus to the opposite side. It causes forward displacement of the trachea associated with tilting of the larynx. In this case, the recurrent...

Pathology and Pathogenesis

Most substernal goiters are benign in nature.2,5,7,8 The incidence of malignancy varies from 6-16 (Table 3.3). In endemic areas, lack of iodine is the predominant stimulus for its growth. In some areas of the world specific goitrogens are found in the diet. Palm tree fruit in Brazil, seaweed in Japan, cassavas in Nigeria, and millet in Sudan are such examples of goitrogens. A defect in thyroxine synthesis stimulates secretion of thyroid stimulating hormone (TSH), which in turn accelerates the growth of the follicular cells. This mechanism forms the basis for iodine and suppressive thyroxine therapy in the management of endemic goiter.

Current Research and Its Applications

Evidence suggests that multinodular goiter is a non-neoplastic, hyperplastic proliferation of thyroid cells. Thyroid cells proliferate and form large follicles. The rate of proliferation is not uniform and as one follicle develops, matures and ceases to grow, new follicles develop from new cells. This form of growth explains why a partial resection of a goiter may be followed by a recurrence. Failure of thyroxine therapy to prevent recurrence of the goiter following partial resection has stimulated research for identification of growth factors other than TSH several growth factors have been identified as possible stimuli for thyroid cell proliferation. Epidermal growth factor (EGF) and an insulin-like growth factor (IGF-1) have been implicated in the pathogenesis of the goiter. While the precise molecular events controlling the thyrocytes' growth have not yet been completely established, transformation of a normal thyroid cell to a proliferative cell is probably secondary to an...

Table 35 Indication for sternotomy for substernal goiter

Responsible for malignant thyroid tumors play a role in the pathogenesis of subster-nal goiter is yet to be determined. It is possible that in the future manipulation of growth related proto-oncogene and or growth factors may provide alternative forms of therapy for substernal goiter.

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 Excess thyroid hormone ingestion (iatrogenic, thyrotoxicosis factitia, hamburger thyrotoxicosis) Struma ovari Functioning metastatic thyroid cancer

Toxic Multinodular Goiter

Toxic multinodular goiter, also known as Plummer's disease, is characterized by thyrotoxicosis which occurs as a result of multiple autonomous functioning thyroid nodules in a pre-existing multinodular goiter. Toxic multinodular goiter accounts for 5-15 of cases of thyrotoxicosis. It typically occurs in elderly patients with a long-standing history of multinodular goiter. It more commonly affects women. Toxic multinodular goiter is thought to occur as a result of progressive generation of autonomously functioning thyroid follicles overtime that have a greater capacity to synthesize T4 and T3. This eventually results in transition from a nontoxic to a toxic multinodular goiter. Thyrotoxicosis is generally mild in comparison to patients with Graves' disease. Cardiovascular manifestations occur more commonly because the patients are older. The onset of thyrotoxicosis is insidious and often preceded by a long period of subclinical hyperthyroidism. Patients with toxic multinodular goiter...

Solitary Toxic Nodule

A solitary toxic nodule is a discrete, autonomous, hyperfunctioning nodule that occurs in an otherwise normal thyroid gland and causes hyperthyroidism. It accounts for approximately 3-10 of all cases of spontaneous thyrotoxicosis. The term hyperfunctioning nodule is used to describe the scintigraphic appearance of a nodule that takes up greater radioiodine than the normal adjacent thyroid tissue (Fig. 4.6). Only 25 of all hyperfunctioning nodules are toxic nodules. A solitary toxic nodule is autonomous, meaning that it functions independently of the hypothalamic-pitu-itary-thyroid feedback mechanism and secretes thyroid hormone despite suppressed TSH levels. The manifestations of thyrotoxicosis are generally milder than in patients with Graves' disease. A solitary toxic nodule may occur at any age, although it is more common in women and in patients less than 50 years of age. Physical examination reveals a single, discrete nodule in the thyroid gland. The initial diagnostic test...

Iodine Induced Thyrotoxicosis

Iodine-induced thyrotoxicosis usually occurs in elderly patients with a pre-existing multinodular goiter who are given a large iodine load (Table 4.3). It is the only cause of hyperthyroidism with a low radioiodine uptake. It accounts for less than 1 of all causes of thyrotoxicosis. The pathogenesis is not completely understood. In normal individuals, large doses of iodine lead to an inhibition of iodine transport and a rapid decrease in thyroid hormone synthesis and release, a phenomenon known as the Wolff Chaikoff effect. Iodine-induced thyrotoxicosis may occur as a result of supplying excess iodine to areas of autonomous function in the thyroid gland, the so called Jod Basedow effect. It also may occur as a result of an increase in the iodine set point of the thyroid gland which leads to increased thyroid hormone synthesis at iodine levels which normally reduce synthesis and release of thyroid hormone.

Table 43 Sources of large iodine load precipitating iodineinduced thyrotoxicosis

The diagnosis of iodine-induced thyrotoxicosis is suspected by a history of a recent exogenous iodine load in a patient with a goiter. The diagnosis is supported by a serum iodide concentration greater than 1.5 ig dl and a 24 hour urinary iodide excretion greater than 1000 mg. Treatment most often consists of simple discontinuation of the source of iodide, although this may be problematic in patients with refractory arrhythmias on amiodarone.10 Thioamide drugs may also be used either alone in combination with potassium perchlorate which competitively inhibits iodine uptake by the thyroid gland. A beta adrenergic antagonist may also be used in conjunction with a thioamide drug. Radioiodine therapy is not an option because the high iodine load suppresses radioiodine uptake by the thyroid gland. A beta adrenergic antagonist may also be used in conjunction with a thioamide drug. Radioiodine therapy is not an option because the high iodine load suppresses radio-iodine uptake by the thyroid...

Steven A De Jong Introduction

Differentiated thyroid carcinoma (DTC) refers to both papillary and follicular carcinomas which arise from the thyroid follicular cell. Thyroid cancers associated with low-dose external radiation exposure to the head or neck are also included, as most of these malignancies are papillary carcinoma. DTC is uncommon but highly curable when compared to other epithelial carcinomas and is usually discovered during the evaluation of a thyroid nodule, cervical mass, and or cervical lymphad-enopathy. Controversy surrounds the extent of surgical treatment required, the indication for use of radioactive iodine and the use of thyroxine for TSH suppression. Important advances have recently been made in understanding the potential causes and tumor biology of DTC, improving methods for diagnosis, staging and management and predicting the clinical behavior and prognosis of individual tumors. Cost effective strategies for early diagnosis have been developed, and treatment and follow up are often...

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...

Staging and Prognostic Factors

There have been several staging and classification systems proposed for characterizing differentiated thyroid carcinoma. The simplest appears to be the AMES classification which divides patients into low risk and high risk for aggressive tumor behavior and recurrence (Table 6.3). Factors such as age, extrathyroidal tumor extension, tumor size, and presence of metastasis are all factors important in this classification system.7 A modification of this staging system, known as AGES, includes histologic tumor grade in the classification and combines metastases and extrathyroidal extension in the category described as extent of disease at presentation. This classification system is also widely used and can be associated with a scoring system to predict prognosis based on the aforementioned clinical features. Low risk patients have small thyroid carcinomas confined to the gland itself with no lymphatic or distant metastases. Factors placing patients in the high risk group include males...

Surgical and Medical Treatment

A total or near total thyroidectomy remains the gold standard for treating differentiated thyroid carcinoma and achieving the goal of removing all thyroid tissue and involved cervical lymph nodes from the neck. Complications are minimal when meticulous preservation of the recurrent laryngeal nerves and parathyroid tissue is accomplished.8 Complications such as hypoparathyroidism, unilateral or bilateral recurrent nerve injury, and cervical hematoma should occur in less than 1-2 of all patients undergoing this procedure when meticulous dissection along the thyroid capsule is performed. Liberal use of parathyroid autotransplantation into the ster-nocleidomastoid muscle or the muscles of the forearm, when anatomic preservation is impossible, will further minimize the incidence of hypoparathyroidism after thyroidectomy. Total thyroidectomy is associated with the lowest recurrence rates for DTC in the central and lateral neck. Recurrence is a poor prognostic sign as 40-50 of these patients...

Lymphatic and Distant Metastasis

Lymphatic metastasis from papillary thyroid cancer can be present in as many as 30-40 of patients. In contrast, follicular thyroid carcinoma spreads preferentially via a hematogenous route and the rate of cervical lymph node metastases for these patients ranges from 10-20 . Preoperative cervical ultrasonography or computerized tomography may identify cervical lymphadenopathy associated with the thyroid tumor and raise the suspicion of cervical lymph node metastasis. Optimal treatment involves an important distinction between central lymph node metastasis located between the jugular veins, and lateral, jugular or posterior cervical lymph node involvement.1 Central lymph nodes consist primarily of superior pretracheal (Delphian nodes), inferior pretracheal lymph nodes, and the perithyroidal lymph nodes adjacent to the thyroid capsule, inferior thyroid artery and recurrent laryngeal nerve. Lateral lymph nodes consist generally of all jugular, supraclavicular, and posterior triangle...

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...

Postoperative Surveillance

The goal of following patients with DTC is to detect recurrence or distant metastasis at an early and treatable stage. Thyroid hormone supplementation should be given to all patients with thyroid carcinoma to achieve complete suppression of their serum TSH. Physical examination of the neck, serum TSH, thyroglobulin and free thyroid hormone levels are usually evaluated every 3-4 months for the first 2 years after thyroidectomy and every 6-12 months thereafter.1 Adjustments in the dose of thyroid hormone may be necessary on a periodic basis. Any abnormal physical findings can be evaluated with cervical ultrasonography and patients at high risk for recurrent thyroid carcinoma usually undergo periodic cervical ultrasonography as an additional tool for surveillance and early detection of recurrent disease. The use of chest radiography on a routine basis for these patients has become somewhat controversial. The yield of positive studies is understandably low in patients with no detectable...

Jeffrey F Moley Introduction

Medullary thyroid carcinoma (MTC) is a tumor of the thyroid C-cells, which are neuroendocrine cells, also known as the parafollicular cells. C-cells are found in small groups of two or more, adjacent to the thyroid follicles. C-cells secrete a number of substances, the most important of which is calcitonin, which is an excellent marker for the presence of MTC. Measurement of calcitonin levels following the administration of the secretagogues calcium and pentagastrin has been extremely useful in the screening of individuals predisposed to the hereditary forms of the disease, and in the follow-up of patients who have been treated. MTC cells may also secrete carcinoembryonic antigen (CEA), and a number of other substances, including neuron-specific enolase, somatostatin, adrenocortical stimulating hormone, serotonin, chromogranin, and substance P. Medullary thyroid carcinoma may be unilateral or bilateral and is often associated with a proliferative lesion, C-cell hyperplasia,...

Primary Surgical Treatment

Surgical treatment of medullary thyroid carcinoma is influenced by several factors. First of all, MTC cells do not take up iodine and radioactive iodine treatment is ineffective. Second, MTC is multicentric in 90 of patients with the hereditary forms of the disease, and in 20 of patients with the sporadic form. Third, with the exception of children whose MTC is discovered as part of a genetic or biochemical screening program, over 50 of patients who present with MTC have nodal metastases. Last, the ability to measure postoperative stimulated calcitonin levels has allowed assessment of the adequacy of surgical extirpation. Total thyroidectomy is therefore widely accepted as appropriate treatment of the primary tumor, accompanied by a central node dissection. This operation entails complete extirpation of the tumor, with removal of all thyroid tissue and all nodal tissue from the level of the hyoid bone superiorly to the innominate vessels inferiorly is removed. After the parathyroid...

Current Research Genetic Testing for MEN 2A MEN 2B and FMTC

The development of genetic testing for MEN 2A, MEN 2B, and FMTC has simplified and improved screening of at-risk patients in affected families. Reliance on calcium-pentagastrin stimulated calcitonin testing for clinical screening has several drawbacks. First of all, a positive test usually indicates that cancer has already developed, and there are a few patients who will develop distant metastatic disease, even after thyroidectomy with removal of small primary tumors. These patients would benefit from earlier thyroidectomy. Second, because the disease is inherited in an autosomal dominant fashion, 50 of those tested will never develop disease and would be spared the expense and inconvenience of routine scheduled testing if a definitive genetic test were applied. Third, the provocative calcitonin test is unpleasant and uncomfortable and patients do not like it. Some patients have refused to return for subsequent testing because of fear of the test. Genetic testing obviates the need for...

Cytodiagnostic Categories

Benign, malignant, indeterminate and nondiagnostic. The results of the FNAB will then guide the management of the thyroid nodule (Fig. 2.1). 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. Fine-needle aspiration biopsy is a very sensitive and specific test for thyroid malignancies. The cytopathologist can usually make a diagnosis of cancer if the nodule is papillary carcinoma, medullary carcinoma, anaplastic carcinoma or a meta-static carcinoma. Thyroid lymphoma can also be diagnosed by FNAB if multiple cells of the lymphoid series with various degrees of...

Clinical Presentation

Anaplastic thyroid cancer is generally seen in elderly patients. There is a higher incidence in women, probably related to overall higher incidence of thyroid cancer and nodular goiter in females. It accounts for 2 of all thyroid cancers in Japan.5 The incidence varies between 5-14 in Europe and the United States. It is commonly a disease of sixth-decades onwards, but a small number of patients below the age of 40 are also seen with anaplastic thyroid cancer.4 The most common clinical presentation is a rapidly growing thyroid mass in the central compartment of the neck. The history is generally of short duration, extending between 3-4 months. The other associated symptoms are hoarseness, dysphagia, pain in the cervical region, and sometimes dyspnea. A patient may occasionally give a history of pre-existent nodular goiter for a long period of time that shows a sudden change in size and rapid growth. A patient may also present with wide-spread metastatic disease to the neck nodes and...

Ashok R Shaha Introduction

Approximately 16,000 new patients with thyroid cancer are expected to be seen in the United States in 2000. There appears to be a steady increase in the incidence of thyroid cancer in the United States, but the mortality from thyroid cancer (1,200) has essentially remained unchanged in the past twenty years. The overall incidence of anaplastic thyroid cancer in various series ranges between 4-6 .1-3 It appears that there is a decrease in the incidence of anaplastic thyroid cancer in the United States, however there appears to be a higher incidence in areas of iodine-deficiency and regions of endemic goiters. Anaplastic thyroid cancer forms one of the most deadly tumors among all human neoplasms. It is interesting that in the same human organ there exists one of the best cancers (papillary) and one of the worst cancers (anaplas-tic thyroid). The average survival in anaplastic thyroid cancer is approximately 6-12 months. The majority of patients die of advanced local disease, distant...

Subhash Patel Introduction

The term 'goiter' is often used to describe enlargement of the thyroid gland. It is derived from the Latin word 'tumidum gutter' meaning the swollen throat. Extension of the goiter beyond the confines of the neck into the thoracic cavity with more than 50 of the mass inferior to the thoracic inlet is called substernal goiter or the intrathoracic goiter. Since the earliest description by Haller in 1749, many distinguished surgeons like Billroth, Kocher, Halsted, Mikulicz, Mayo, Criles, and Lahey have contributed important advances in the treatment of the goiter.1 Of all the thyroid goiters, the substernal location poses the most unique challenges to the surgeon. Most of these goiters are slow growing and often do not cause symptoms for a considerable period of time. When the mass reaches a critical size, it impinges upon the surrounding structures causing compression symptoms. Although the majority of these lesions are benign, significant numbers may be malignant and a few may exhibit...

Embryology and Anatomy

During the 4th and 5 th weeks of life, brachial arches begin to develop as neural crest cells migrate into the future head and neck region of the embryo. Each arch consists of a core of mesenchyme covered externally by surface ectoderm and internally by endoderm. Externally the arches are separated by branchial groves and internally by extensions of the pharynx called branchial pouches. The superior parathyroid glands arise from the fourth branchial pouch. The ventral portion of the fourth pouch fuses with the thyroid gland (Fig. 10.1). It gives rise to the parafollicular cells or C-cells of the thyroid gland which migrate from the neural crest cells of the ultimobranchial bodies of the fourth and fifth branchial pouches. Embryologically, it makes sense that both the parafollicular cells and the parathyroid glands produce substances that are involved in calcium regulation. The superior parathyroid glands tend to be located near the point of intersection of the middle thyroid artery...

Table 101 Effect of hormonal regulators at target organs

Calcitonin is a 32-amino-acid peptide hormone that plays a lesser role in calcium metabolism. Calcitonin is produced by the parafollicular cells of the thyroid gland and its release is stimulated by hypercalcemia. Calcitonin's main function is to lower serum calcium levels. It inhibits bone resorption by binding to osteoclast receptors and blocks the release of calcium and phosphate from bone. In the kidney, calcitonin inhibits the reabsorption of calcium and phosphate at the ascending loop of Henle and therefore promotes calcium excretion in the urine. The role and importance of calcitonin in calcium homeostasis must be relatively minor since patients after total thyroidectomy with absent levels and patients with medullary thyroid carcinoma and very high levels do not have problems maintaining normal serum calcium levels.

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 Thyroid radio iodine uptake 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) Pituitary resistance to thyroid hormone (MRI...

Multiple Endocrine Neoplasia Syndrome

Multiple endocrine neoplasia (MEN) syndromes are autosomal dominantly inherited syndromes. Patients with MEN syndromes have a propensity to develop tumors of various endocrine glands, such as the parathyroid, pituitary, pancreas, adrenal and thyroid glands. There are three well-defined types of MEN syndromes (Table 31.1). The individual endocrine tumors developed in patients with MEN are similar to those that occur sporadically. There is, however, a tendency for hyperplasia and multiple tumors. Thus the treatment of these patients may be more complicated. In addition, treatment decisions are also influenced by the possible presence of other tumors (such as pheochromocytomas in patients with medullary thyroid cancer or hyperparathy-roidism in patients with gastrinoma) and the consideration for genetic screening and prophylactic operations.

Serum calcium calcitonin urinary metanephrines CEA

Medullary Thyroid Carcinoma (MTC) Surgical treatment for MTC and pheochromocytoma is the same as for patients with MEN 2A. Because MEN 2B is more virulent, prophylactic total thyroidec-tomy is indicated as soon as the diagnosis is made even in young children. 2. Hofstra RM, Landsvater RM, Ceccherini I et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 1994 367 375-6. Germ-line mutations ofthe RET proto-oncogene have recently been reported in association with MEN 2A and familial MTC. All mutations occurred within codons specifying cysteine residues in the transition point between the RET protein extracellular and transmembrane domains. This paper showed that MEN2B is also associated with mutation ofthe RET proto-oncogene. Ledger GA, Khosla S, Lindor NM et al. Genetic testing in the diagnosis and management of Multiple Endocrine Neoplasia type II. Ann Intern Med 1995 122 118-24. Early studies...

Pathology Pathogenesis and Carcinogenesis

The pathology of papillary and follicular thyroid carcinoma differs in many aspects, but both malignancies originate from the thyroid follicular cell. Papillary carcinoma is an unencapsulated tumor with papillary and follicular architecture, consisting of single layers of thyroid cells arranged around vascular stalks that form papillae. The cells are characterized by overlapping nuclei with a ground-glass appearance, longitudinal grooves, and invaginations of cytoplasm into the nuclei. Laminated calcified spheres, known as psammoma bodies, are also seen in 40-50 of tumors. Encapsulated, follicular, tall-cell, columnar-cell, clear-cell, and diffuse scle-rosing carcinomas are all recognized histologic variants of papillary thyroid carcinoma. The follicular variant of papillary carcinoma behaves much like papillary carcinoma, but the presence of tall cells within the tumor suggests an aggressive clinical course. Multicentricity is found in 30-50 of these tumors and is commonly seen...

Differential Diagnosis

Carcinoma of the thyroid, pheochromocytoma, and primary hyperparathyroidism. Serum calcitonin levels serve as a useful tumor marker for medullary carcinoma of the thyroid. A history of headaches, excessive sweating, tachycardia, palpitations, or hypertension should alert the clinician about the possibility of an associated pheochromocytoma. Measurement of 24-hour urinary levels of catecholamines, metanephrines, and vanillylmandelic acid is the best screening test for pheochromocytoma.

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 the head or neck, and patients older than 60 years of age. Associated symptoms suggesting differentiated thyroid carcinoma include hoarseness from a vocal cord paresis, recent onset or rapid growth of a solitary nodule, dysphagia, hemoptysis, or cervical pain related to the nodule or cervical spine. Uncommon presentations include cervical lymphadenopathy with or without obvious thyroid pathology, symptomatic bone pain from metastatic disease to the spine, pelvis or ribs, asymptomatic pulmonary metastases found radiographically, and focal neurologic abnormalities from distant spread to the brain. Physical examination may reveal a hard, irregular, solitary, fixed thyroid mass causing local compressive symptoms with or without associated cervical...

Nondiagnostic Biopsies

If surgery is to be performed without a definite diagnosis, then a lobectomy should be performed. The decision to do a more extensive resection should be based on the patient's history or characteristics of the nodule. Frozen section analysis of the nodule may be of assistance if the FNAB is atypical and depending on the skill of the pathologist. Otherwise, given the low incidence of malignancy in this situation, the routine use of frozen section is excessively costly and false-positive results could lead to unnecessary thyroidectomies.8 1. Zohar Y, Strauss M, Laurian N et al. Adolescent versus adult thyroid carcinoma. Laryngoscope 1986 96 555-9. The authors outline several significant differences between adolescent and adult thyroid carcinoma, including epidemiological, clinical, pathological and surgical findings. 2. Campbell JP, Pillsbury HC. Management of the thyroid nodule. Head & Neck 1989 11 414-25. A review of the data regarding the prevalence and clinical significance of...

Postoperative Management

All patients with follicular carcinoma require lifelong treatment with exogenous thyroid hormone to suppress TSH synthesis, the production of which can stimulate the growth of differentiated thyroid cancer. Thyroid-stimulating hormone suppression lowers the recurrence rate of follicular carcinoma by diminishing the stimulation of TSH receptors which are present on the surface of differentiated thyroid tumors.9 Ideally, TSH levels should be suppressed to undetectable levels with the lowest possible dose of thyroid hormone, especially since replacement therapy can cause side effects such as osteoporosis and thyrotoxicosis.4 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...

Embryology

The thyroid is the first endocrine gland to develop in the embryo, and starts to form at 24 days. It begins as an endodermal thickening in the midline of the primitive pharynx and grows to extend inferiorly, forming the thyroid diverticulum. As the embryo lengthens and the tongue bud grows, the thyroid descends inferiorly, passing anterior to the hyoid bone and larynx. The thyroglossal duct continues to connect the thyroid to its origin in the tongue until it reaches its destination in the neck. At this point the duct degenerates this is usually complete by the seventh week, but remnants may persist as thyroglossal duct cysts. These may be located anywhere in the midline along the thyroid's path of descent from the base of the tongue to the mediastinum. Heterotopic thyroid tissue may also be located anywhere along this path. In fact, a pyramidal lobe of the thyroid may occur in 30 of the population and represents a remnant of the inferior end of the thyroglossal duct (see Fig....

Anatomy

The normal adult thyroid gland weighs between 15-20 grams. Lying anterior to the trachea, it is composed of two lateral lobes joined by a bridge of tissue called the isthmus. The superior aspects of the lateral lobes overlie the inferior portion of the thyroid cartilage. The isthmus is located anterior and inferior to the cricoid cartilage and covers the second, third, and fourth tracheal rings. If a pyramidal lobe is present, it remains as a midline finger of tissue extending upward from the isthmus. A thin capsule invests the gland. Posteriorly this capsule blends with the pretracheal fascia. Fig. 1.1. Thyroid embryology. A, B, and C are sagittal views of the head and neck of an embryo at 4, 5, and 6 weeks of development. Note the thyroglossal duct connecting the gland to its origin at the foramen cecum. Reprinted with permission from Moore KL. The developing human clinically oriented embryology. Philadelphia W.B. Saunders Company, 1988 185. Fig. 1.1. Thyroid embryology. A, B, and C...

Arterial Supply

The arterial supply of the thyroid is principally from the superior and inferior thyroid arteries. The superior thyroid arteries are paired vessels that supply the upper poles and anterior surface of the lateral lobes. They are the first branches of the external carotid arteries and pass inferiorly and medially to enter the upper poles. The inferior thyroid arteries arise from the thyrocervical trunks which come off of In less than ten percent of the population, an unpaired thyroidea ima (lowest thyroid) artery arises from the brachiocephalic artery or aortic arch to run along the midline of the trachea to the isthmus (Fig. 1.2).

Histology

The thyroid consists of follicular cells that secrete thyroid hormone, and parafollicular cells that secrete calcitonin. The follicular cells are arranged in a single layered sphere, the center is filled with colloid consisting of a thyroglobulin matrix. The amount of colloid in the follicular lumen depends on the level of thyroid activity. It becomes depleted in states of high or excess thyroid activity and accumulates during periods of thyroid inactivity. The eosinophilic layer of follicular cells surrounding the lumen becomes flattened as gland function diminishes. Parafollicular cells are much fewer in number and are located between follicles. There are some occasional parafollicular cells scattered in the follicular wall. These cells are not evenly distributed throughout the gland, being concentrated along the middle and upper thirds of the lateral lobes posteriorly.

Physiology

Thyroid function is regulated by a negative feedback loop involving the hypothalamus, pituitary, and thyroid gland. Thyrotropin releasing hormone (TRH, or thyroliberin) is released from the hypothalamus into the portal circulation of the pituitary, where it stimulates the pituitary to release thyroid stimulating hormone (TSH, or thyrotropin). TSH in turn stimulates the synthesis and release of thyroxine Fig. 1.2. Arterial supply of the thyroid. A thyroid ima artery is present in less than 10 of the population. Fig. 1.2. Arterial supply of the thyroid. A thyroid ima artery is present in less than 10 of the population. Fig.1.3. Lymphatic drainage of the thyroid Fig.1.3. Lymphatic drainage of the thyroid (T4) from the thyroid gland. Thyroxine inhibits the release of TRH from the hypothalamus and TSH from the pituitary, thus forming a negative feedback loop. Virtually all steps of thyroid hormone synthesis and release are stimulated by TSH, including the gland's iodine trapping mechanism....

Calcitonin

The parafollicular cells (C cells) of the thyroid secrete calcitonin, a polypeptide hormone that inhibits bone resorption and leads to hypocalcemia in lower animals. In humans, physiologic concentrations of calcitonin have never been proven to have an important influence on calcium homeostasis. Exogenous calcitonin is used in the treatment of Paget's disease and hypercalcemia secondary to vitamin D toxicity or hyperparathyroidism. It exerts its effect on the serum calcium level by inhibiting bone resorption. Salmon calcitonin is the most commonly used preparation and is more potent than human calcitonin. Parafollicular cells are neural crest cells derived from the ultimobranchial bodies of the developing thyroid. As cells of neuroendocrine origin, they may give rise to a neuroendocrine malignancy called medullary thyroid carcinoma. These rare tumors comprise 5 or less of thyroid cancers and are familial in 20 of patients. Medullary thyroid cancer is a component of the Multiple...

Scintiscan

Until recently, radionuclide scanning had routinely been the first test used in the evaluation of the thyroid nodule. Radioisotopes of iodine or technetium are used with the theory that malignant thyroid tissue neither traps nor incorporates iodine. They should appear nonfunctioning, or cold, on uptake scan. Normally functioning nodules are warm and hyperfunctioning nodules appear as hot on the scan. The incidence of malignancy is higher in cold nodules as compared with warm or hot nodules. Thyroid scans have generally been replaced as a first-line test by FNAB. Recognizing that thyroid scanning has fallen out of favor as a first-line test, many still recommend its use as a secondary examination. Thyroid scan has been suggested in those situations in which the FNAB is read as suspicious or follicular neoplasm. In patients with indeterminate cytology, hyperfunctioning or hot nodules are almost always benign no such differentiation can be made for cold or warm nodules. Unfortunately...

Benign Lesions

If the cytologic diagnosis indicates a benign nodule, there are three options for the clinician. These include surgery, observation and hormone suppression. If the nodule is causing symptoms, or is aesthetically displeasing to the patient, surgery may be considered. Thyroid surgery for benign disease is safe with complications being quite rare. Surgery should also be considered in those patients who are at increased risk for thyroid cancer despite a benign FNA. If the patient does not require surgery, the nodule may either be observed or suppressed with Levothyroxine. The goal of thyroid hormone administration is to eliminate TSH stimulation by total exogenous replacement of the body's need for thyroid hormone. This should either reduce the size of the nodule or prevent its further growth. While this was a more commonly used approach for diagnosis and treatment in the past, it is being used less often. This is probably due in part to the increased diagnostic potential of FNAB, as well...

Malignant Lesions

Well-differentiated cancers, such as papillary, follicular and mixed papillary-fol-licular carcinomas are the most common malignancies of the thyroid. In those situations where the diagnosis has been made on FNAB, the patients require no further work-up prior to surgery. Either an ipsilateral lobectomy with isthmusectomy or a near-total or total thyroidectomy may treat unilobar disease. The extent of thyroid resection is controversial. Supporters of total thyroidectomy argue that lobectomy leads to increased local recurrence, although survival rates are approximately equal. Supporters of conservative surgery feel that the equal survival rates do not justify the increased morbidity of a total thyroidectomy. In the hands of an experienced surgeon however, there is very little increased morbidity between the two approaches. Factors that may push one towards performing a total thyroidectomy include a history of head and neck radiation, increased size of the nodule, palpable...

Incidence

About 5 of the world population has a goiter. But with the increasing use of iodination programs there has been a substantial decrease in the incidence of endemic goiters. Nevertheless, a large population in the U.S.and in endemic areas of the world continue to have thyroid goiters in the absence of iodine deficiency. Based on routine screnning chest x-rays the incidence of substernal goiter is reported to be about 0.2 in the U.S.2 This is compared with the year 1921 when Pemberton reported an incidence of 13.6 among 4006 patients undergoing thyroidectomy at the Mayo Clinic.3 In the recent world literature, the incidence of substernal goiter among patients undergoing thyroid surgery is reported to range from 5-19 (Table 3.1).4-9 Thyroid goiter accounts for about 5 to 11 of all mediastinal masses.3

Diagnosis

Both computed tomography (CT) scan and magnetic resonance imaging (MRI) can provide more precise information about the relationship between the various intrathoracic organs and the goiter (Fig. 3.3). This information guides the surgeon in planning the operative approach for ectopic goiters and goiters in the posterior mediastinum. Use of iodinated urographic contrast material during CT scanning may help to differentiate thyroid tissue from other mediastinal masses. However, because iodine uptake in the thyroid is variable, one should expect variable enhancement of the thyroid tissue after a bolus injection of contrast. Ultrasonography has only limited use in the chest secondary to image interference from the rib cage and sternum and air shadowing. A radionuclide thyroid scan may be useful in differentiating goiter from other mediastinal masses. Nevertheless, a solitary, large cyst may appear as a cold nodule on thyroid scan and thus provide a false negative result. Fine needle...

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