The Natural Thyroid Diet

Thyroid Factor

Thyroid Factor is a program that was created by Dawn Sylvester to help women deal with thyroid issues. Dawn Sylvester is a 57 years old lady that has worked with 1,000's of real women. She has over the time tried to investigate the underlying reason why majority of women lose energy and also struggle with belly fat and fatigue as they age. It is a comprehensive program thatcomprises of Thyro pause, 11 kinds of thyroid saving foods that will work to help you boost fat burning Free T3. The program also teaches you all the hidden causes of thyroid which are making you fat and later a highly reliable Thyroid reboot plan which is an excellent plan you need to tackle your weight. Additionally, there are tips to reduce bulging fat fast and eventually obtain a healthy body. You also get several bonuses all aimed at helping you solve all the problems that comes with being overweight. The three bonuses you get are 21 Day Thyroid weight loss system, 101 Thyroid boosting foods and Thyroid Jumpstart Guide. Read more...

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Thyroid Ultrasonography

Now a mainstay in the diagnosis of thyroid nodules, ultrasonography provides a high pretest probability of cancer when certain characteristics exist in a nodule, namely a solid or partly cystic nodule with irregular and blurred margins, mixed hypoechoic isoechoic areas and microcalcifications, and intranodular vascular pattern 99 . Malignant cervical lymph nodes have a characteristic pattern, appearing round, without a hilar area and containing intranodu-lar vascular flow. A Solbiati index (SI ratio of largest to smallest diameter) of about one and a complex echoic pattern or irregular hypere-choic small intranodular structures and irregular diffuse intranodular blood flow are the best indicators of malignancy in a lymph node 100 , which often provides information that alters the surgical approach 72 . These features are reviewed in detail in Chapter 26 by Dr Richardson.

Thyroid Hormone Therapy

The idea that TSH stimulates both the iodine transport and growth of thyroid carcinoma (only DTC) is the basis for the wide use of T4 in treating this disease. Like normal thyroid tissue, most PTCs and FTCs have functional TSH receptors, but whether postoperative T4 alone improves survival is less certain. Although there have been no prospective randomized trials of this question, there is evidence that TSH stimulates tumor growth 168 . PTC in patients with Graves' disease may be more aggressive, presumably as a result of stimulatory effects of circulating TSH receptor antibodies 82 . Rapid Patients with thyroid cancer are usually treated with T4 to lower TSH secretion below normal, thereby deliberately causing subclinical if not overt thyrotoxicosis. One potential consequence of this is bone mineral loss, even in children 79 , but especially in postmenopausal women with thyroid carcinoma 171-173 . This may be prevented by estrogen or bisphosphonate therapy. More importantly, using...

Medullary Thyroid Cancer MTC

A section of the guidelines is devoted to medullary thyroid cancer (MTC), a rare disease that requires a dedicated, multidisciplinary regional service, dovetailing with that for MEN1 and MEN2. Developments in the molecular genetics of MTC have facilitated a rational framework for management, but the use and interpretation of molecular diagnostics requires The mainstay of treatment for MTC is total thyroidectomy and central node dissection the adequacy of the initial operation largely determines the long-term outcome of the disease. Prophylactic surgery is recommended for disease-free carriers of germline RET mutations the precise mutation found will guide the timing of the surgery 25 . Life-long follow-up is essential and includes monitoring of the tumor marker calcitonin. More detailed consensus guidelines for the diagnosis and management of the MEN2 syndromes are available 25 .

Thyroid Cancer Multidisciplinary Team and the Organizational Paradigm

British Thyroid Association These are established in those district general hospitals that are large enough to have clinical teams with the expertise and facilities to deal with the more common cancers, such as breast, lung, and colorectal (bowel) cancers Differentiated thyroid cancer Fine-needle aspiration cytology Immunometric assay Intensity modulated radiotherapy - special technique of external beam radiotherapy where high doses can be given to tumors close to vital structures like spinal cord twithout exceeding the tolerance dosage of the vital organ by controlling the energy deposited in real time in different parts of the radiation field by complex computer based treatment planning Improving Outcomes Guidance The Ionising Radiation (Medical Exposures) Regulations 2000 Ionising Radiations Regulations Manual of Cancer Services

Importance of the MDT in Thyroid Cancer Management

The importance of MDT working for thyroid cancer is well recognized and is recommended by most thyroid clinicians across the world. In the UK the British Thyroid Association Guidelines have recommended that MDT working should be a mandatory requirement for any center involved in the management of thyroid cancer 21-30 .

Management of Thyroid Incidentalomas

Small nonpalpable thyroid nodules are common in the general population and with increasing use of imaging techniques such lesions are frequently detected in asymptomatic subjects. The prevalence of thyroid cancer in such lesions is thought to be low (about 1-2 ) 54 . However, recent data suggest that in some series the inci dence of cancer may be as high as 12 and often associated with cervical lymph node metastases or multifocal tumors 55,56 . These findings are contradictory to the experience in other centers and until wider evidence to the contrary is available, observation of small (10 mm diameter appears to be similar to palpable nodules 58 and such nodules ought to be investigated.

Followup of Benign Thyroid Nodules

Some authors recommend that a benign FNAB should be confirmed by a second FNAB 6-12 months later, because of a false-negative rate of up to 6 of the initial FNAB 59 . The decision to subject patients to a second FNA has to be balanced against the probability of nondiagnostic aspirate,false-positive results (e.g. Thy3 in up to 7 of cases) necessitating surgery, reduction in cost-effectiveness, and heightened patient anxiety 35 . A small proportion of patients will develop new nodules or enlargement of their existing nodule, and some will develop thyroid dysfunction therefore some form of follow-up seems appropriate, although the optimal means of achieving this is unknown.

Organizational Aspects of a Thyroid Nodule Service

Ideally a one stop clinic with access to biochemical testing of thyroid function (if not already available), cytology, and diagnostic ultrasound can provide rapid diagnosis and planning for those cases that require treatment. Patients can be assessed clinically, FNAB performed, cytology reported and if necessary repeated until an adequate sample can be obtained. Those patients who require surgery either for diagnosis or for treatment can have a consultation with the surgeon and the operation planned. Only a few centers are able to provide such a facility because of limited resources. The crucial aspect of a thyroid nodule service, however, is that it is staffed by clinicians and cytologists who are appropriately trained and experienced in dealing with thyroid nodules.

Making the Diagnosis of Thyroid Cancer in General Practice

It presents as an isolated thyroid nodule, and has an annual incidence of between 0.5 and 10 per 100000 population 3 . In Australia in 1998, the average GP in a major city had a practice of 1028 patients (up to 1960 in remote areas) 4 . Therefore, a full-time GP will see one thyroid cancer every 10 years at most. If the lower figure is taken there will be some GPs who will never see a case in a 40-year working life. By contrast, the prevalence of clinically detectable (i.e. detectable by clinical examination) benign thyroid nodules is much higher in the general population than is thyroid cancer, the main differential diagnosis. A population-based study in Finland found thyroid nodules by ultrasound in 27.3 of subjects tested. Of these, only 5 were clinically detectable. This equates to a prevalence of 1.4 in the general population 5 . The average Australian GP practice will thus have 14 patients with a clinically detectable nodule. A Spanish study of the...

Where to Refer Patients with Possible Thyroid Cancer

Euthyroid patients with a thyroid nodule may have thyroid cancer and should be referred to a member of a multidisciplinary thyroid cancer team if it is available. Patients with hyper- or hypothyroidism and a nodule or nodular goiter should be referred routinely to an endocrinologist. Patients should be referred to a surgeon or endocrinologist who has a specialist interest in thyroid cancer and preferably is a member of a multidisciplinary team (MDT) if one is available. A clinical oncologist or nuclear medicine physician, preferably a member of an MDT, may also be appropriate. Patients with unexplained hoarse voice may have a thyroid cancer, and should be considered for referral as above. However, smokers with a hoarse voice (and no goiter) are more likely to

Evaluation of Clinical Risk Factors for Thyroid Cancer

The history and physical examination of the patient may give important clues with regard to the nature of a thyroid nodule. Features suggesting malignancy are external neck irradiation during childhood, family history of thyroid cancer, male sex, age 60 years, hoarseness, dysphagia, rapid increase of nodule size over weeks or months, nodules that are firm in consistency and irregular or attached to surrounding tissues, and palpable neck lymph nodes. If there is a very high clinical suspicion of thyroid cancer, one may already conclude that thyroid surgery is necessary irrespective of the fine-needle aspiration cytology (FNAC) results 9 . Table 10.1 Role of the endocrinologist in the presurgical (diagnostic) phase of thyroid cancer 1. Evaluation of clinical risk factors (including family history) for thyroid cancer A family history of benign thyroid disease will decrease and a family history of thyroid cancer will increase the suspicion of malignancy. Medullary thyroid cancer in the...

Long Term Followup with Search for Residual Thyroid Cancer at Regular Intervals

In view of the long natural history of the disease, thyroid cancer patients require life-long follow-up. For medullary thyroid cancer, serum calci-tonin and CEA can be used as tumor markers a progressive rise in their serum concentrations will demand imaging studies, but otherwise appropriate time intervals for follow-up visits are 6-12 months. For papillary and follicular thyroid carcinoma, the long-term follow-up is important in view of (a) late recurrences which can be successfully treated, (b) monitoring of the consequences of suppressed TSH, and (c) evaluation of late side effects of 131I such as leukemia or second tumours, although fortunately these are very rare. Most important is the measurement of serum thyroglobulin (Tg) as a tumor marker, but for a valid interpretation of the Tg test results the endocrinologist should make sure TgAbs are absent in the sample under investigation close collaboration with the clinical chemistry laboratory is helpful in this respect, and the...

Management Plan for Recurrent or Metastatic Thyroid Cancer

Once recurrent or metastatic cancer has been diagnosed, consultations within the multidis-ciplinary team should lead to the most appropriate management plan. For recurrence in the thyroid bed or cervical lymph nodes, surgical re-exploration usually followed by 131I therapy is mostly preferred. Bone metastases can be treated with 131I, external radiotherapy, embo-lization, or orthopedic intervention. Metastases in the lungs and elsewhere not amenable to surgery can be treated with 131I. In otherwise uncontrolled end-stage disease chemotherapy with doxorubicin and cisplatinum has been tried, with limited success. death in 106 fatal cases of thyroid carcinoma were respiratory insufficiency (43 ), circulatory failure (15 ), hemorrhage (15 ), and airway obstruction (13 ) 43 .

Enlarged Thyroid Goiters

Depending upon how massive the enlargement is, various techniques may need to be employed to obtain access and deliver the gland. The patient must be placed in as much cervical extension as is safe to passively pull the thyroid out of the chest and into the neck as far as possible. The skin incision is generally larger, and extends at least from the medial aspects of the sternocleidomastoid muscle on each side of the neck. The subplatysmal flaps are sometimes raised to the level of the hyoid bone. Removing the strap muscles can be difficult as they are stretched, thin, and overlie engorged veins. Careful dissection is a must to prevent bleeding. If the superior aspect of the gland is enlarged, then the strap muscles are separated as superiorly as possible (they are innervated via the ansa hypoglossi which enters inferiorly). The superior laryngeal nerve is at great risk in massively enlarged goiters, as the nerve has been found even lateral to the superior pedicle in normal size...

Complications of Thyroid Surgery

Complication rates associated with thyroid surgery and the consequences of thyroid surgery can be evaluated through follow-up data, local and national audit initiatives (e.g. the British Association of Endocrine Surgeons Audit), and analyses of case series. When obtaining consent for a procedure and in the approach to the final decision to move to an operation, patients should be given information about commonly occurring complications, which enables them to make their decision as to whether or not to proceed based upon a realistic understanding of the complications and the likely outcome of the operation.

Hypothalamicpituitarythyroid Axis Components and Function

The thyroid gland, composed of two central lobes connected by an isthmus, synthesizes the hormones thyroxine (T4) and triiodothyronine (T3). These The hypothalamic-pituitary-thyroid (HPT) axis is composed of three main parts, as its name suggests. The tripeptide (pGlu-His-Pro-NH2) thyr-otropin-releasing hormone (TRH) is synthesized predominantly in the PVN of the hypothalamus and stored in nerve terminals in the median eminence, where it is released into the vessels of the hypothalamo-hypophyseal portal system (Figure 4.3). TRH is then transported to the sinusoids in the anterior pituitary, where it binds to thyrotropes and releases the peptide thyroid-stimulating hormone (TSH) into the systemic circulation. TRH is heteroge-neously distributed in the brain, which strongly suggests a role for this peptide as a neurotransmitter as well as a releasing hormone. Thus TRH itself can produce direct effects on the CNS independent of its actions on pituitary thyrotrophs. The HPT axis exhibits...

Treatment of Hypothyroid States

As noted above, thyroid hormone extracts from sheep or cattle were the first treatments used that demonstrated efficacy in ameliorating the signs and symptoms of hypothyroidism. Several synthetic derivatives were introduced in the 1960s which quickly replaced desiccated thyroid tissue for the treatment of patients with thyroid disease. Among these are levothyr-oxine (Levoxyl, Levothroid, Synthroid), synthetic forms of thyroxine (T4) and liothyronine (Cytomel), and the synthetic levorotatory isomer of triio-dothyronine (T3). Moreover, in part due to the seminal work carried out by Prange and collaborators in the United States in the 1960s, the use of thyroid hormones in augmenting antidepressant response in depression was established.

Evaluation at the Time of Radioiodine Ablation of Thyroid Remnants

Camera with thick crystals and high-energy collimators. Whole-body images are taken with spot images of the neck and any other suspicious area 9 . An accurate anatomical view of any neck uptake will differentiate whether the uptake is present in normal thyroid remnants or lymph node metastases. Indeed, high uptake in thyroid remnants will obliterate visualization of lower uptake in neck lymph nodes. This emphasizes the paramount importance of performing a total thyroidectomy with the aim of achieving an uptake in thyroid remnants lower than 1-2 of the administered activity. The risk of artifacts should be minimized by having the patient drink lemon juice and large amounts of liquid, chew gum, and shower and change clothes before scanning. Iodine contamination should be avoided by the patient's following a low iodine diet for a few weeks before radioiodine treatment, and is ruled out by testing of urinary iodine concentration. A diagnostic TBS or even a measurement of neck uptake is...

Patients with Large Thyroid Remnants

In patients with large thyroid remnants who are treated with radioiodine, immediate postablation TBS may be poorly sensitive for detecting uptake outside the thyroid bed also, the abla tion rate is lower than in patients with small thyroid remnants. Detectable serum Tg may be related to persistent thyroid remnants. For these reasons, a dxTBS at 6 to 12 months may be indicated. Whenever rhTSH is used to provide TSH elevation for dxTBS, an activity of at least 148MBq (4mCi) of 131I should be administered one day after the last injection of rhTSH. This underlines that performing a total thyroidec-tomy in all DTC patients will improve the quality and ease of the follow-up.

Evidence for a Genetic Predisposition to Nonmedullary Thyroid Cancer

A number of epidemiological studies have investigated the risk of malignancy associated with a family history of thyroid cancer (Table 22.1). Ron et al. 3 performed a small case-control study of 159 cases and 285 controls, and demonstrated an odds ratio (OR) of 5 for a Table 22.1 Familial risks of thyroid and other cancers in epidemiological studies Table 22.1 Familial risks of thyroid and other cancers in epidemiological studies Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid (PTC or FTC) Thyroid (PTC or FTC) in sons Thyroid (PTC or FTC) Thyroid (PTC or FTC) in daughters Thyroid (anaplastic) Thyroid (anaplastic) in sons Thyroid (anaplastic) Thyroid (anaplastic) in daughters Thyroid (PTC) Thyroid (PTC) Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid CI,confidence interval FTC,follicular thyroid cancer PTC, papillary thyroid cancer. a Defined by the authors as breast, ovarian, endometrial, or prostate...

Medullary Thyroid Carcinoma

MTC originates in calcitonin-producing cells (C cells) of the thyroid. C cells are of neuroecto-dermal origin and do not accumulate iodine. There exist both familial and sporadic variants of MTC. Patients with MTC or its precursor condition, C-cell hyperplasia (CCH), have

Anaplastic Thyroid Carcinoma

RAS oncogene activation is a rather frequent event in ATCs, but it also occurs in WDTCs 27 as an early event in thyroid tumorigenesis 26 . The p53 gene (locus on 17p13.1) is a tumor suppressor gene and is the most commonly affected gene in human cancers 45 . The p53 gene product,the TP53 protein,plays an essential role in cell cycle regulation, specifically in the transition from G0 to G1. Inactivating point mutations of p53 are frequently present in anaplastic TC but not in differentiated TC, suggesting that p53 mutations play an important role in the pro

Papillary Thyroid Carcinoma

PTC usually is unencapsulated, well differentiated, and sharply circumscribed from the surrounding thyroid parenchyma. PTCs bear almost pathognomonic cytomorphological changes, including nuclear grooves, folds, and invaginations, in addition to central nuclear clearing 47 . The cancer may be multicentric. PTC foci have a moderately dense fibrous stroma and tend to invade the space between follicles. Psammoma bodies are a cardinal feature of PTC 47 . The tumors may spread to normal surrounding thyroid parenchyma and regional lymph nodes. However, they are capable of distant dissemination as well. PTCs characteristically grow slowly 48 .

Response to Thyroid Hormone Suppression Therapy

The rationale for thyroid hormone suppression therapy (THST) is based on evidence that TSH is the main stimulator of thyroid growth and function, at least in normal thyrocytes 60 . It is not clear whether long-term levothyroxine (L-T4) therapy to partially suppress TSH is effective in treating thyroid nodules, which are of course composed of neoplastic (not normal) thyroid tissue 61 . The use of high dose L-T4 to fully suppress TSH in patients with benign thyroid disease is neither beneficial nor completely safe 62 . Therefore, THST for unknown nodular thyroid disease is not recommended for pedi-atric patients.

Epidemiology of Thyroid Cancer Induced by Ionizing Radiation

The association between ionizing radiation and thyroid cancer was first suggested in 1950 in children who received X-ray therapy in infancy for an enlarged thymus 1 . More conclusive evidence for a causal relationship between external radiation exposure in childhood and thyroid cancer was obtained from pooling the data from several large studies following radiation treatment to the thymus, tonsils, or scalp, and showing a dose-dependent increase in relative risk for development of thyroid cancer 2 .Since the early 1960s, when the use of radiotherapy for benign conditions was abandoned, the incidence of radiation-associated thyroid malignancy in children has gradually decreased 3 . Currently, radiation therapy for other malignancies continues to be a source of radiation-associated thyroid cancer 4,5 . However, this association has been more difficult to establish, in part because radiation is used more often for adults where the thyroid is less sensitive to its effects 6 . An increased...

Clinical Characteristics of Radiation Induced Thyroid Cancers from Chernobyl

The average latency between radiation exposure and cancer diagnosis was 6.9 years in a series of 472 patients from Belarus reported by Pacini et al. 11 . Prior to Chernobyl, the latency period for radiation-induced thyroid cancer was considered to be at least 5 years,typically 5-10 years. However, the Chernobyl experience has clearly demonstrated that it can be as short as 4 years. The clinical characteristics of thyroid cancers arising in children exposed to radiation after Chernobyl differed in significant respects from those arising in children without known radiation exposure treated in Italian and French centers 11 . The vast majority of post-Chernobyl pediatric thyroid cancers were papillary carcinomas (94 ) 11 , which is consistent with what was found in other populations exposed to ionizing radiation. Although papil lary carcinomas were also the dominant tumor type in the sporadic Western European pediatric cases, the prevalence was significantly lower (82 ). When compared...

Radiation Induced Thyroid Autoimmunity

Children and adolescents living in the most heavily contaminated regions of Belarus were found to have a markedly higher prevalence of thyroid autoantibodies than age-matched controls residing in Braslav, a village in Belarus that was largely spared from radioactive fallout 31 . The increase in prevalence of plasma antithy-roglobulin and antiperoxidase antibodies was already apparent in individuals who were in utero or newborn at the time of the accident. In children who were 9 years, the prevalence of autoantibodies was striking, reaching 35 . At the time of the study, there was no evidence of thyroid dysfunction, as serum free T4, free T3, and TSH levels were unaffected. Similar findings were reported in a smaller study of children from two iodine-deficient areas of western Russia, one of which received significant radioactive contamination 32 . Despite the fact that in these early studies there was no evidence of thyroid dysfunction in the exposed populations, there is well-founded...

Approaches to Reduce Exposure of the Thyroid Gland to Radiation

After release of large amounts of radioactive iodine isotopes into the atmosphere, prompt measures need to be taken to minimize thyroid exposure, particularly in children 33 . First and foremost the population needs to be alerted about the risk immediately. Although this is an obvious measure, it is sobering that for various reasons this was not appropriately implemented in some of the most notorious environmental disasters to date, such the Marshall Islands and Chernobyl. People should be instructed to remain indoors and keep doors and windows closed to minimize exposure by inhalation. Because 90 of radioiodine exposure is through contaminated food, and the half-life of the most prevalent iodine radioisotopes is less than 9 days, consumption of fresh milk from local dairies and fresh vegetables should be avoided for several weeks after the accident. Because stable iodine reduces radioiodine uptake, administration of potassium iodide is recommended to saturate the iodine transport...

Staging Thyroid Malignancy

The size of the lesion is usually easily and accurately measured using US. Smaller than or equal to 2cm is T1,2-4cm is T2 and greater than 4cm is T3 for tumors confined to the thyroid. Confusion arises when there are multiple nodules in contact with each other. The differentiation between the nodules may be indistinct, making measurement of individual nodules difficult. Local extension beyond the thyroid can be identified but again this can be unclear with large multinodular goiters.

Amiodarone and Thyroid Disease

Risk of thyroid dysfunction is lower with lower doses TSH prior to therapy, at 4-mo intervals on amio, and for 1 y after if amio d c'd (3) direct immune-mediated thyroid destruction Type 1 underlying multinodular goiter or autonomous thyroid tissue diagnostic studies T thyroid blood flow on Doppler U S treatment methimazole Type 2 destructive thyroiditis

Medullary Thyroid Cancer

In a patient undergoing investigation for thyroid nodules, the identification of bilateral nonfunctioning nodules on the 99mTc pertechne-tate thyroid scan raises the possibility of MTC associated with familial MTC (FMTC), multiple endocrine neoplasia type 2A (MEN2A), or MEN2B 54 . The main role for 99mTc(V)-DMSA imaging is in the follow-up of patients after surgery 56 . In primary MTC, 99mTc(V)-DMSA can confirm a clinical suspicion of MTC while the calcitonin results are awaited. Papillary and follicular tumors of the thyroid do not take up 99mTc(V)-DMSA and positive uptake in a cold nodule on a 99mTc pertechnetate scan is strongly suggestive of MTC. 99mTc(V)-DMSA whole-body imaging is also useful when planning surgery to stage the disease. It is probably the most effective imaging agent for demonstrating soft-tissue and bone metastases.

Metastases to the Thyroid

The majority of metastases to the thyroid remain undetectable in clinical practice 37 . However, incidence in postmortem studies varies between 1.2 and 24 in patients with widespread malignancy 2,38,39 . Based on these figures, thyroid metastases are 10 times more frequent than primary thyroid tumors 40 . This is not surprising given that the thyroid has a rich blood supply, second only to the adrenals. Involvement may arise by direct spread from adjacent structures, hematogenous spread, or retrograde lymphatic spread. Postmortem studies report breast (26 ), lung (25 ), and malignant melanoma (11 ) to be the most frequent cancers to metastasize to the thyroid, with disease usually remaining clinically occult. In contrast, the largest clinical series 41 found that the kidney was the most common primary site (33 ) followed by lung (16 ), breast (16 ), and esophagus (9 ). Metastasis may be the first presentation of a distant cancer treated several years previously typically there is a...

Emerging Therapies for Thyroid Cancer

In comparison to many epithelial cancers, thyroid cancer therapy has long been rationally based on the specific characteristics of thyroid cancer cells in particular, the retained expression and function of thyroid-specific proteins, such as the thyrotropin receptor (TSHR) and the Na, I symporter (NIS), that have created targets for therapies. Indeed, the use of TSH suppressive doses of levothyroxine (L-T4) and radioiodine, in combination with surgery, has resulted in long-term survival rates for patients with localized thyroid cancers that approach 98 at 20 years 1-4 . However, some thyroid cancers lose expression and or function of these two critical proteins, a feature that leads to poor responses to traditional therapies and a high incidence of cancer-related death. Alternative therapies, including cytotoxic chemotherapeu-tic agents, have yielded disappointing results with high morbidities. There has therefore been an effort to devise targeted therapies for aggressive thyroid...

Other Emerging Therapies for Thyroid Cancer

Another approach for new therapies for thyroid cancer and other malignancies is to target the mechanisms by which cancer cells develop resistance to chemotherapeutic agents. For example, multiple drug resistance genes (MDR) result in resistance to a number of chemotherapy agents, such as those with documented activity for some patients with anaplastic thyroid cancer, including taxanes and doxorubicin 53-57 . Immunotherapy remains a major area of interest for thyroid cancer, and for a number of other malignancies 58,59 . The use of tumor vaccines with or without agents to enhance immune responses, or to induce thyroiditis in patients on chemotherapy using interferons, are avenues of potential treatment for thyroid cancer in the future. Chemoprevention is another alternative for thyroid cancer that remains relatively unexplored other than the use of iodide after accidental exposure to iodine isotopes. Chemo-preventive strategies could include administration of apoptotic-promoting agents...

Clinical Trials for Thyroid Carcinoma Past Present and Future

In 1999, I was asked to speak at the 72nd annual meeting of the American Thyroid Association on the selected topic of Multicenter Clinical Trials in Thyroid Cancer. The assigned task was to summarize the state of the field and identify both the challenges to and opportunities for advancement of improved clinical care and outcomes for our patients. Surveying the medical literature of the last quarter of the 20th century in preparation for that lecture led to certain obvious yet unsatisfying conclusions about the state of affairs in 1999 No data existed from randomized controlled trials testing any of the primary treatments commonly used for thyroid carcinoma (surgery, radioiodine, and thyroid hormone suppression for differentiated carcinoma surgery for medullary carcinoma and chemotherapy and external beam radiation with or without surgery for anaplastic carcinoma). Pharmaceutical companies, with rare exception, had not developed or supported clinical trials to address new therapies...

Completion Thyroidectomy

Residual tumor is common in the contralateral thyroid lobe but cannot be predicted on the basis of the tumor size in the ipsilateral lobe or the presence of regional lymph node metastases 45 but is more likely if there are multiple tumors in the ipsilateral thyroid lobe and if the serum thyroglobulin level is very high 46 . Completion thyroidectomy should be considered for tumors that have the potential for recurrence because large thyroid remnants are difficult to ablate with 131I 47 and almost always leave the serum thyroglobulin detectable 48 . Completion thyroidectomy has a low complication rate and is appropriate to perform routinely for tumors 1cm or larger because about half the patients have residual cancer in the contralateral thyroid lobe 49-53 . This is more common when the tumor is familial, or when it is associated with head and neck irradiation or other familial syndromes (see Chapter 1). When there has been a local or distant tumor recurrence after lobectomy, residual...

Ablation of Residual Normal Thyroid Tissue

In the management of differentiated thyroid cancer (DTC) ablation of thyroid remnants with 131I aims to destroy all residual normal thyroid tissue. Total (or near-total) thyroidectomy will permit this to be achieved with a modest administered activity. Remnant ablation after lobectomy is more difficult and a repeat administration may be required. Ablation of a large remnant may cause radiation thyroiditis with neck pain and swelling. Furthermore thyroid-stimulating hormone (TSH) levels may fail to rise above 30mU L following hormone withdrawal, resulting in suboptimal 131I uptake. The advantages of remnant ablation are that it permits subsequent identification by iodine whole-body scan (WBS) of any residual or metastatic carcinoma and facilitates interpretation of serial serum thyroglobulin (Tg) monitoring 1 (Figure 15.l). A large remnant may show a star burst artifact on WBS, obscuring tumor uptake in abnormal cervical nodes. Measurement of stimulated Tg is also facilitated following...

Primary Thyroidectomy

An incision is made in a skin crease about 2 cm cephalad to the clavicles. Once a surgeon gains more experience with this procedure, the transverse incision decreases in length from about 8 cm to about 4-5 cm. This generally results in an imperceptible scar, and negates the benefits of endoscopic assisted thyroidectomy, a much more complex and lengthy procedure. Superior and inferior flaps are raised in a subplatysmal plane. These really only need to be done in between the sternocleidomastoid muscles as more lateral dissection does not improve visualization. This is the basis for reducing the size of the incision to 4 cm in primary cases. The strap muscles are separated in the midline and elevated off of the thyroid gland. Only in rare circumstances (extremely enlarged goiter, direct cancer invasion) are the strap muscles divided. These muscles assist in swallowing and so are preserved intact when possible. The thyroid gland is now exposed. We prefer to divide the superior pole...

Surgical rehabilitation of the patient with dysthyroid eye disease

Compressive Optic Neuropathy

Upper eyelid retraction in thyroid eye disease occurs due to a combination of primary factors (adrenergic stimulation, inflammation and fibrosis) and secondary retraction due to inferior rectus fibrosis - with secondary overaction of the superior rectus levator complex. If secondary upper eyelid retraction is present, the restriction of ocular motility should be addressed first, with inferior rectus recession. Primary upper eyelid retraction is treated by one of the several techniques for graded levator tenotomy (Chapter 7), but with all methods it is particularly important to completely divide the lateral horn of the levator aponeurosis and to maintain a levator action on the medial part of the upper eyelid.

Papillary and Follicular Thyroid Cancer

Papillary Thyroid Cancer Pet Scan

The role of imaging in the investigation of patients with suspected thyroid cancer is controversial, reflecting the high incidence of nodules in the normal population and low prevalence of thyroid malignancy. In a patient with a palpable nodule in the thyroid, the simple technique of imaging the thyroid using 99mTc pertechnetate will identify whether the palpable nodule is functioning or nonfunctioning. Thyroid cancer typically appears as a hypofunctioning cold nodule on 99mTc pertechnetate thyroid imaging but this is a nonspecific finding (Figure 27.1A). Specificity varies with the iodine status of the population studied. In Austria, prior to iodine supplementation, the incidence of thyroid cancer in cold thyroid nodules was 3.5 19 compared with 21 in the iodine-replete USA 20 . In 1978, Tonami et al. 21 described the use of 201Tl in investigating patients with cold thyroid nodules. However, Harada et al. 22 demonstrated that 201Tl could not distinguish between benign and malignant...

Thyroid Papillary Carcinoma In Hla Identical Sibs

In vitro models of thyroid cancer. Cancer Surv 1993 16 115-134. 3. Ron E, Kleinerman RA, Boice JD, Jr, LiVolsi VA, Flannery JT, Fraumeni JF, Jr. A population-based case-control study of thyroid cancer. J Natl Cancer Inst 1987 79(1) 1-12. 4. Stoffer SS, Van Dyke DL, Bach JV, Szpunar W, Weiss L. Familial papillary carcinoma of the thyroid. Am J Med Genet 1986 25(4) 775-782. 5. Pal T, Vogl FD, Chappuis PO, et al. Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer a hospital-based study. J Clin Endocrinol Metab 2001 86(11) 5307-5312. 7. Hemminki K, Dong C. Familial relationships in thyroid cancer by histo-pathological type. Int J Cancer 2000 85(2) 201-205. 9. Ron E, Kleinerman RA, LiVolsi VA, Fraumeni JF, Jr. Familial nonmedullary thyroid cancer. Oncology 1991 48(4) 309-311. 23. Crail HW. Multiple primary malignancy arising in the rectum, brain and thyroid. Report of cases. UN Navy Med Bull 1949...

Cancer Predisposition Syndrome Associated Nonmedullary Thyroid Cancer

An association between FAP and thyroid cancer was first described by Crail in 1949 23 , and since then over 50 other cases have been reported (Table 22.2). The great majority (over 90 ) of cases reported have been PTCs, usually detected within 10 years of a diagnosis of FAP. Although thyroid cancer has a female Table 22.2 Reported associations of familial adenomatous polyposis coli (FAP) and thyroid cancer Table 22.2 Reported associations of familial adenomatous polyposis coli (FAP) and thyroid cancer Age Thyroid cancer Thyroid cancer histology Three systematic studies have investigated the risks of thyroid cancer in FAP. In a retrospective review of 316 FAP patients on the St Mark's Hospital registry, Plail et al. 24 reported four women with PTC, and estimated a relative risk of PTC in females under 35 years of age to be 160 (95 confidence interval (CI) 44-410). A subsequent retrospective analysis of 245 patients on the Danish polyposis register 25 demonstrated two thyroid cancer...

Relapse Rates and the Extent of Initial Thyroid Surgery

Mazzeferri Thyroid Cancer

Recurrence rates are high with large thyroid gland remnants. Some find that patients treated by lobectomy alone have a 5 to 10 recurrence rate in the opposite thyroid lobe 16,29 and an overall long-term recurrence rate over 30 (versus 1 after total thyroidectomy and 131I therapy 3 ) and the highest frequency (11 ) of subsequent pulmonary metastases 30 . Higher recurrence rates are also observed with cervical lymph node metastases and multicentric tumors, which also provide justification for more complete initial thyroid resection 3 . In one study from the Mayo Clinic 31 of patients with papillary carcinoma, tumor recurrence rates during the first 2 years after surgery were about fourfold greater after unilateral lobectomy than after total or near-total thy-roidectomy (26 versus 6 , P 0.01). In a subsequent report from the same institution, patients with papillary carcinoma whose AGES score was 4 or more had a 25-year cancer mortality rate almost twice as high after lobectomy than...

Non Syndromic Familial Nonmedullary Thyroid Cancer

In addition to an association with readily identifiable cancer predisposition syndromes such as FAP, a number of families with non-syndromic clustering of thyroid cancers (primarily PTCs) have been described (Table 22.3). Although on first inspection it might be thought that familial clustering is secondary to ascertainment bias, this is statistically highly unlikely. For example, a nuclear family with two offspring with NMTC (e.g. the family reported by Lote et al. 49 ) would be expected to occur by chance alone less than once every 100 years. Furthermore, analysis of the familial cases has shown a marked excess of bilateral and multiple primary or multicentric cancer, compatible with an inherited predisposition. In addition, nodal involvement and distant spread are frequent at the time of presentation, suggesting an aggressive phenotype. There is also evidence of sex limitation, with a preponderance of female cases, and a number of the published pedigrees are consistent with...

Well Differentiated Thyroid Carcinoma

Whether total (or near-total) thyroidectomy (T NTT) or subtotal thyroidectomy should be the procedure of choice 67 . Although there is very seldom an indication for radical neck dissection in pediatric patients, extensive functional neck dissection for removal of infiltrated lymph nodes is certainly warranted in selected cases 68 . Regardless of the surgical procedure, surgery should be performed by an experienced thyroid surgeon, preferably one familiar with the anatomic vagaries of the pediatric neck. A few surgeons recommend subtotal thyroidec-tomy because they believe that the literature has not provided enough support for the conclusion that T NTT leads to better survival than more conservative procedures 69 . This group of surgeons also makes the argument that T NTT may increase the incidence of serious complications, such as permanent hypoparathyroidism and recurrent laryngeal nerve damage. Most surgeons currently perform T NTT in pediatric patients with WDTC on the basis of a...

Radioactive Iodine 131I Therapy Thyroid Remnant Ablation

This is defined as 131I therapy administered to destroy presumably normal residual thyroid tissue. Routine 131I remnant ablation, although questioned by some 116 , is widely used and has appeal for several reasons. First, it may destroy occult microscopic cancer 18,62 . Second, it enables earlier detection of persistent tumor by post 131I treatment whole-body scans (RxWBS) 81 . Third, it greatly facilitates the use of serum Tg measurements during follow-up. Few metastases can be visualized by 131I scanning when appreciable amounts of normal thyroid tissue remain after surgery. Lastly, serum Tg concentration, which is the most sensitive marker of persistent disease, is unreliable when a large thyroid remnant is present 117 . Thus 131I is given postoperatively even to patients without known residual disease who have a good prognosis 38,118,119 . Still, this approach continues to engender debate and calls for randomized clinical trials 120 , but they are so difficult to design that they...

The Structure and Function of the Thyroid Cancer MDT in the UK the NICE Guidance

And commissioning of cancer services for thyroid cancer as well. The following is a summary. For the details the reader is advised to consult the manual 20 or the website -www.nice.org.uk. The responsibility of the thyroid MDT would be to provide a service usually for a population base of over 1 million and generally should be established in a cancer center or involve several cancer units. Thyroid cancer MDT can either be part of a currently existing head and neck cancer team or operate as a separate endocrine oncology team who discuss predominantly malignant but also benign thyroid conditions. outcome is likely to be better in centers with a larger volume of work in thyroid cancer surgery and management than in centers that see only a few patients a year, as already indicated earlier in this chapter. In the long term, it is likely that surgery will be centralized so that it is done by specialized surgeons. Also more reliable and meaningful audits or studies can be carried out and...

Thyroid Cancer Conclusion

Nuclear medicine imaging continues to have an established role in the management of patients with papillary and follicular thyroid cancers, with 131I scanning remaining the routine imaging technique for localizing remnant and recurrent disease. The development of recombinant human TSH offers increased flexibility for imaging and treatment, whilst reducing the side effects of thyroxine withdrawal. The newer radionuclide imaging techniques remain underutilized, despite good evidence for their sensitivity in detecting tumor recurrence. The development of new agents continues with the potential for new therapeutic agents. The importance of the development of evidence-based strategies for the optimal integration of radionuclide imaging in the diagnosis and follow-up of patients with thyroid cancers needs to be recognized.

Thyroid Cancer from the Perspective of a Patient

In October 1997, following a bit of a cold, I noticed a tiny lump, about the size of a pea, in the middle of my throat. That night I rang Professor Newman-Taylor, who had been such a help in the past, and told him about my discovery. He asked me some questions did it move up and down when I swallowed He then said he thought it was my thyroid and asked me to keep him informed when I had seen my GP. on my thyroid, he explained, had been benign, but I was horrified to hear him add that the attached tissue was abnormal - and you don't need a degree in medicine to know what that means. They had found traces of cancer. If Frank Bruno had punched me I would not have been more winded. I had been feeling light-hearted that morning because I had been working hard at my fitness - and with a great deal of success - but now I sat at the desk in my office in a state of shock as Mr Rhys Evans quietly confirmed that a second operation would be necessary. I gently replaced the phone. I was so angry, I...

Prevalence of Thyroid Cancer in the Population

There are about 300000 patients in the USA 3 and 200000 in Europe 184 living with thyroid cancer. Virtually all require lifelong follow-up, which until recently, was done mainly with serum Tg determinations obtained during T4 suppression of TSH and 131I DxWBS performed after thyroid hormone withdrawal. More recently, follow-up has become more complex, and is substantially more accurate. Older antithyroglobulin antibody assays did not detect low levels of anti-Tg antibody 184 , which factitiously lower serum Tg results from immunometric assays. Also, 3 to 5mCi 131I DxWBS, computed tomography (CT), and magnetic resonance imaging (MRI) were the mainstays of imaging, but are now known to be far less capable of locating tumor than are newer more sensitive ultrasound and Doppler techniques, and 131I RxWBS and 18FDG-PET imaging studies. Identifying persistent DTC late in its course was the consequence of using insensitive tests that often identified tumor relapse decades after initial...

Psychological Aspects of Thyroid Cancer

Thyroid cancer is a relatively rare disease, with an incidence of 3.1 per 100000 per year 11 . Differentiated thyroid cancer, accounting for the majority of cases, is curable in 90 of patients given appropriate treatment 12 . On this basis many patients are told that thyroid cancer is a good cancer to have. However, medullary carcinoma, accounting for 4 of cases, has a 10-year survival rate of 75 . Undifferentiated, or anaplastic, carcinomas account for only 2 of cases, but carry a very poor prognosis, with a 3-year survival rate of only 3 11 . There is limited published information related to the long-term physical health of survivors of thyroid cancer, and very little published material describing psychological and social outcomes 13 . However, there are a number of descriptive studies offering accounts of patients' perspectives and nursing care needs. As part of a wider survey of adult survivors of cancer, Shultz and colleagues 13 described medical and psychosocial outcomes of 518...

Role of the Clinical Psychologist in Thyroid Cancer

It is apparent that patients undergoing treatment and surveillance for thyroid cancer may be experiencing much greater levels of psycholog ical distress than healthcare staff have generally anticipated, based on a relatively good prognosis. A significant minority of people with any type of cancer experience clinical levels of distress at some point in their cancer journey and it may well be that those with thyroid cancer experience higher levels of distress than some other subgroups. Therefore a key role of the clinical psychologist is to educate other staff about psychological responses to diagnosis, treatment, and surveillance. This may start with advice to managers in order to influence the provision of resources and facilities for example, understanding of patients' need for careful preparation for treatment may support the case for having specialist nurses allocated to thyroid cancer. Considering the impact of the immediate environment on psychological wellbeing may strengthen...

Treatment of dysthyroid eye disease

Most patients with thyroid eye disease will have relatively few symptoms and signs, and many will require only topical lubricants during the active phase of the disease and no long-term therapy. Patients without proptosis when the disease is inactive, but with persistent lid retraction or incomplete lid closure, may need eyelid surgery to protect the cornea (Chapter 7). Likewise, squint surgery Management of more severe and significant thyroid eye disease should be first directed towards suppression of orbital inflammation and later the restoration of orbital function.

Thyroid Cancer and the Endocrinologist

The long-term outcome of treatment for papillary and follicular thyroid cancer is generally good the overall 10-year survival for adult patients with differentiated thyroid carcinoma is 80-90 . However, local or regional recurrences develop in up to 30 of patients, distant metastases in up to 20 , and 8-10 of patients die of their disease 1,2 . Thyroid cancer patients thus require a very long-term follow-up. Adequacy of surgical treatment and 131I ablation apparently have an important influence on the long-term outcome 1,3,4 . Nevertheless, audits on existing clinical practices identified several shortcomings from what might be considered optimum management of thyroid cancer 5-7 . In one particular study, adequacy of surgery was considered deficient in 20 , adequacy of T4 suppression in 22 , monitoring by serum thyroglobulin in 15 , and use of 131I therapy in 12 7 . Deficiencies were observed more often where patients were seen by a number of generalists (probably related to poor...

The Efficacy of Total or Near Total Thyroidectomy in the Treatment of DTC

Many surgeons perform an operation called near-total thyroidectomy, but its definition is open-ended,leaving much doubt as to the actual extent of surgery and the amount of thyroid tissue left behind. For this reason, the National Cancer Center Network guidelines 28 on the treatment of thyroid cancer avoid this term. In practice, many patients have substantial thyroid remnants when evaluated by thyroid ultra-sonography and thyroglobulin (Tg) determina tions even after reportedly undergoing total thyroidectomy. Thyroid ultrasound may be useful when the extent of surgery is in question, since leaving a thyroid remnant smaller than 2g facilitates postoperative 131I ablation.

Revision Thyroidectomy

This operation is one of the most difficult of the thyroid operations. To one degree or another, the pristine surgical planes have been violated, which greatly increases the odds of damage to vital structures RLN, parathyroid glands, trachea, and esophagus. The first step is to get a clear understanding of the previous operation. If the contralateral lobe was resected for a nodule of indeterminate pathology and returned as cancer, returning to the operating room within the week is imperative so as to access the remaining lobe before the scarring sets in. If a different surgeon operated on the first side, then the details of the operation are needed, especially to ascertain if the RLN and parathyroids were already dissected on the remaining side. Even through scar, the important structures may once again be dissected free, but a wider exposure is needed and the surgeon must prepare for a longer, more tedious dissection. Also, active monitoring of the RLN with a specialized probe on the...

The Proposed Structure and MDT Standards for Thyroid Cancer

A proposed thyroid MDT standards list is given in Table 3.1. This has been modified from the Breast Cancer Standards 2004 and therefore is not the definitive document. Thyroid cancer MDT measures based on the NICE IOG will be published by the Department of Health in due course. However, Table 3.1 will give some idea about the comprehensive nature of the standards that an MDT will have to follow and can act as a discussion paper for development of multidisciplinary practice for any center wanting to develop a reliable service framework.

Molecular Pathogenesis of Radiation Induced Thyroid Cancer

Genetic analysis of papillary cancers in children exposed to radiation following Chernobyl implicated the RET oncogene in the pathogene-sis of these tumors 16-18 . RET is a tyrosine kinase receptor primarily expressed in cells of neural crest derivation. RET is normally not expressed or present at very low levels in thyroid follicular cells. RET activation in papillary carcinomas occurs through chromosomal recombination resulting in illegitimate expression of a fusion protein consisting of the intracellular tyrosine kinase (TK) domain of RET coupled to the N-terminal fragment of a heterologous gene, giving rise to the RET PTC oncoproteins. Several forms have been identified, which differ according to the 5' partner gene involved in the rearrangement. The two most common are RET PTC1 and RET PTC3. RET PTC1 is formed by an intrachromosomal inversion of the long arm of chromosome 10 leading to fusion of RET with the H4 D10S170 gene 19 . RET PTC3 is also a result of an intrachromosomal...

Thyroid Remnant Ablation

Another condition for which rhTSH is becoming an alternative to prolonged thyroid hormone withdrawal is postsurgical 131I ablation therapy. Between 2001 and the present, four studies employing rhTSH to promote 131I remnant ablation under TSH suppressive therapy have been published. Two studies were performed at Memorial Sloan-Kettering Cancer Center 27,28 . In the first article 27 , 10 patients were given rhTSH (0.9 mg IM each day for 2 days) followed by 131I (mean dose 110.3mCi). Follow-up diagnostic scans, obtained 5 to 13 months later, showed no visible uptake in the thyroid bed in any patient. The second study 28 was a retrospective comparison of 87 patients with differentiated thyroid cancer who had undergone thyroid remnant ablation after a regimen of rhTSH (n 45) or L-thyroxine withdrawal (n 42). The mean amounts of radioiodine given for ablation were 110.4mCi and 128.9mCi, respectively. At follow-up diagnostic scanning done about 11 months after ablation, it was found that 84...

The Thyroid and Iodine

Iodine is an essential component of the iodine-containing thyroid hormones thyroxine (T4) and triiodothyronine (T3). Severe iodine deficiency (intake less than 50 mg day) causes mental retardation, cretinism, and endemic goiter. Even in developed countries such as Germany endemic goiter with thyroid enlarge ment and or nodules is still prevalent in approximately 30 of the adult population 2 . The daily supply of iodine should amount to 90 mg in children aged 0-7 years, 120 mg in children aged 7-12 years, 150 mg in adolescents and adults, and 200 g in pregnant and nursing women ( 3 ,http www.ICCIDD.org). In cases of iodine deficiency, the thyroid enlarges and more actively transports iodine from the bloodstream, thus allowing uptake of sufficient iodine for the maintenance of normal thyroid function. In contrast, when the iodine supply is excessive (more than 500 mg day) the sodium iodide sym-porter (NIS) of thyrocytes is downregulated, thus inhibiting iodide transport from the...

Thyroid Cancer and the General Practitioner

The different ways general practice operates across the world causes some difficulties in attempting to describe a primary care approach to thyroid cancer. The approach of practitioners in areas where the specialist team may be immature or nonexistent will differ to that where the specialist team is highly developed and close at hand. We have identified the highest diagnostic and management level that a general practitioner (GP) might be expected to exercise in a remote context. GPs in better served areas may not need to exercise these skills, but should be aware of the tasks required for comprehensive care of these patients.

Thyroid Cancer Management Patterns of Care Studies

Until recently we had a kind of Panglossian view about the outcome of thyroid cancer 2 . It was thought that thyroid cancer was rare and highly curable and that the management process was very satisfactory with the best possible outcome. However, there is evidence that the incidence of papillary thyroid cancer is rising worldwide 3 and the survival figures for thyroid cancer in the UK are worse than the European average 4 .While factors such as registration and case mix might partly explain this difference it is also likely that differences in management strategies have a significant effect on overall survival. The thyroid cancer service in the UK in the past has been rather patchy, inconsistent, and fragmented and did not follow any specific guidelines. Recent publications have suggested that there is considerable room for improvement. Reports from other countries also suggested the need for more organization of multidisciplinary management and treatment according to consensus...

Thyroid Disease Conclusion

Efforts should be made to reduce at least some of the radiation sources to the gonads. These include generous hydration (2-3 liters per day) with frequent micturition and avoidance of constipation using regular laxatives prior and during iodine administration. As with any form of radiotherapy, careful appraisal of the risks and benefits of radioiodine treatment is mandatory, especially when advising repeated doses to young patients 23 . Since there is evidence of cumulative gonadal damage with repeated iodine administration, it is recommended that the total cumulative iodine activity should be kept as low as possible 24 . In vivo dosimetry, which measures the actual absorbed dose received by remnant thyroid tissue, functioning metastatic disease, and normal organs with a view to optimizing the administered iodine dose, may help in achieving this goal 25 .

Retrosternal thyroid

The patient should be euthyroid before elective surgery. Careful questioning, examination and thyroid function tests should be performed. If the mediastinal mass is compressing the trachea, then the patient may be symptomatic. If the tracheal diameter is reduced by more than 50 , then the patient will develop stridor, which may be positional or occur only on exercise. CT or MRI should be used to gain more information about the degree of tracheal compression. If significant, removal of the thyroid should take priority over elective varicose vein surgery. If there is no, or minimal, compression, then surgery may proceed. Regional block is an anaesthetic option.

Thyroid Scintigraphy

Thyroid scintiscans may in specific circumstances help to distinguish a benign hyperplas-tic nodule from a potential follicular neoplasm. Hyperplastic nodules are characteristically hot on scintiscans, whereas thyroid cancers are typically cold. Hot nodules have a very low incidence of malignancy 39 . However, technetium-99 thyroid scanning may be misleading and 123I scanning is preferable for classifying thyroid nodules as hot or cold. 123I is expensive, and the classification of a nodule into the hot or cold category may subjective 47 . For these reasons most centers do not perform thyroid scintiscans as part of the initial assessment of thyroid nodules.

Hyperthyroid States

Although a number of conditions, including pituitary adenomas, can lead to hyperthyroid states, the most common non-iatrogenic cause of thyroid hormone excess is Graves' disease. In Graves' disease, the body generates an autoantibody to the TSH receptor which directly stimulates thyroid follicular cells to secrete excessive amounts of T3 and T4. In this state, the normal negative feedback exerted by T3 and T4 on TRH and TSH release is disrupted. The clinical manifestations of thyroid hormone excess are exaggerations of the normal physiologic effects of T3 and T4 they include diaphoresis, heat intolerance, fatigue, dyspnoea, palpitations, weakness (especially in proximal muscles), weight loss despite an increased appetite, hyperdefecation, increased psychomotor activity, and visual complaints. Psychiatric manifestations are also common and include anxiety (13 of unselected cases), depression (28 of patients) and cognitive changes (approximately 7 of patients). Psychotic manifestations...

Thyroid Disorders

Nostic Studies in Thyroid Disorders Thyroid-stimulating hormone (TSH) Thyroid antibodies Antithyroid peroxidase (TPO) Hashimoto's Thyroid-stimulating Ig (TSI) Graves' disease i'd in thyroid injury, inflammation, and cancer ( useful marker of recurrence of papillary and follicular cancer) no uptake subacute painful or silent thyroiditis, exogenous thyroid hormone, struma ovarii, recent iodine load, or antithyroid drugs Figure 7-1 Approach to thyroid d tor iert Figure 7-1 Approach to thyroid d tor iert hypothyroidism Thyroid hormone Thyrotoxicosis Thyroiditis

Rare Thyroid Cancers

While the relatively low mortality rate of thyroid cancer in general is due to the preponderance of well-differentiated carcinoma, a subset of rare thyroid tumors exist that exhibit aggressive behavior and poor prognosis. These require careful consideration and different treatment paradigms to optimize clinical outcome. Extremely rare types of thyroid cancer include thymus-like tumors, mucoepidermoid carcinoma, spindle cell tumor, mixed medullary fol-licular cancers, and teratoma. In view of the limited literature on their management these extremely rare types are not covered in this chapter.

Thyroid cancer

T B D Malignancy arising in the thyroid gland, types include papillary, follicular, medullary and anaplastic tumours. a R Childhood exposure to radiation (papillary tumours). Medullary thyroid carcinomas may be familial and are associated with MEN syndrome type Ila or lib (20 cases). Lymphoma is associated with Hashimoto's thyroiditis. ZH A slow-growing thyroid neck lump nodule. The patient may complain of discomfort while swallowing and a hoarse voice. Palpable nodules or diffuse enlargement of the thyroid. If cervical nodes are I Blood TFT (if hyperthyroid, thyroid nodule is less likely to be malignant), bone profile, serum thyroglobulin (tumour marker for papillary and follicular tumours) and calcitonin (tumour marker for medullary carcinoma). FNAC or ultrasound-guided core needle biopsy Allows for histological diagnosis. Excision lymph node biopsy If there is an enlarged cervical lymph node. Isotope scan May be necessary if nature of thyroid lump is not known. Staging CT or MRI...

Thyroid Lymphoma

Primary thyroid non-Hodgkin's lymphoma (NHL) is uncommon, representing 4 of all thyroid cancers 1 . Only 2 of extranodal lymphomas arise within the thyroid. Secondary involvement is more frequent as a manifestation of generalized disease, which occurs in 10 of all lymphomas and leukemias 2 . The mean age at presentation is 60-70 years with a female male predominance of 3 1. Presentation before age 40 is rare. Preexisting Hashimoto's thyroiditis is a significant risk factor 3 and may be the result of chronic antigen stimulation. Radiation exposure is not associated with an increased risk. Primary thyroid lymphoma is usually of B-cell type and CD20 positive 4 T-cell lym phoma is very rare. Approximately 80 of tumors are of the diffuse large-cell type (histiocytic) and the majority of these are high grade. The remainder comprise follicular (nodular), mixed, plasmacytoid, and lymphocytic subtypes. NHL of the thyroid is classified into MALT (mucosa-associated lymphoid tissue) positive and...

Histology and Other Tumor Features

Each is unique and has its own features that may portend either a difficult and nagging problem of persistent disease, or a relatively easy and swift course that ends happily for the patient. Knowing the characteristics of the tumor and its probable clinical behavior is the first place to begin anticipating a patient's needs and long term prognosis. In Chapter 9, Dr McNicol reviews the salient pathology features that play a role in the long-term outcome of patients with thyroid cancer. Tumors that arise from thyroid follicular cells secrete thyroglobulin (Tg) and tend to grow slowly and have a good prognosis 19 .However, tumor recurrences are common with PTC, ranging as high as 30 if the initial therapy is incomplete 18 . Classic PTC, the most common form of thyroid cancer, is often a mixed papillary-follicular tumor but a few have a purely papillary pattern, features that have no bearing on prognosis but may cause confusion about its pathological...

Tumor Features That Influence Prognosis

PTC smaller than 1 cm, termed microcarcinoma, is often found unexpectedly during surgery for benign thyroid conditions. While most pose no threat to survival and require no further surgery 58 , about 20 are multifocal and as many as 60 have cervical lymph node metastases, some of which are palpable 59 . Lung metastases occur rarely, especially with multifocal tumors with cervical metastases, which are the only microcarcinomas with significant morbidity and mortality 59,60 . With these exceptions, the recurrence and cancer mortality rates are near zero 58,59 . In our series, 30-year recurrence rates with DTC smaller than 1.5 cm were less than one-third those associated with larger tumors 19 . There is a linear relationship between tumor size and cancer recurrence and mortality for both papillary and follicular carcinomas 19 . Still, management decisions for patients with these tumors are exceedingly complex, and are extensively reviewed by Drs Drucker and Robbins in Chapter 29. About...

Patient Features Affecting Prognosis

Nearly every study shows that the patient's age at the time of diagnosis is an important prognostic variable and that thyroid carcinoma is more lethal after about age 40 years. The risk of death from cancer increases with each subsequent decade of life, dramatically rising after age 60 years (Figure 1.3). The pattern of tumor recurrence is quite different. Recurrence rates are highest (40 ) at the extremes of life, before age 20 and after age 60 years (Figure 1.3) 19,73,79 . Yet despite the clear effect of age upon survival, there is disagreement about how it should be factored into the treatment plan, especially in children and young adults. Children commonly present with more advanced disease than adults and have more tumor recurrences after therapy, but their prognosis for survival is good 79 . Some believe that young age has such a favorable influence upon survival that it overshadows the prognosis predicted by the tumor characteristics 80 . The majority, however, believe that the...

Clinical Staging Systems and Prognostic Indexes

Tance of tumor stage tends to be diminished. This concept, however, does not appear to be widely accepted among practicing physicians because young patients with low prognostic scores often have tumor recurrence. At an international consensus conference in 1987, only 5 of 160 participants treated younger patients more conservatively 91 . Similarly, in a 1988 international survey of thyroid specialists 92 and a 1996 survey of clinical members of the American Thyroid Association 93 , age was not used by the majority of respondents in their therapeutic decisions. Current recommendations for the treatment of children now suggest the same therapy as is given to adults with similarly staged tumors 79 . (See Chapter 23.)

Current Diagnostic Approach

The diagnostic approach to thyroid nodules differs somewhat according to the type of physician who first sees the patient in consultation and the availability of specialist teams. This is apparent in Section II, which reviews the diagnosis of thyroid cancer in four separate chapters by Drs Perros, Mitchell and Leith, McNicol, and Wiersinga (Chapters 7-10). Each has the same general approach but with a somewhat different slant, according to the circumstances of their practice and specialty. Still, the overall approach is the same in most urban areas.

History and Physical Examination

Although most patients with thyroid nodules have no serious symptoms, a few have such a distinctive presentation that the diagnosis of thyroid cancer is obvious (Table 1.2). Patients who present with rapidly growing tumors, vocal cord paralysis, tumor that is fixed to surrounding tissues, or large multiple cervical lymph nodes are so likely to have thyroid cancer that even with a negative biopsy, the patient should undergo surgery. This is also true for familial medullary thyroid carcinoma (FMTC) syndrome, MEN2A or MEN2B syndromes or familial nonmedullary thyroid cancer 94,95 , or one of the syndromes associated with nonmedullary thyroid cancer (familial adenomatous polyposis (FAP) or Gardner syndrome 96 , Cowden syndrome 97 ) (Table 1.2, Figure 1.8) 98 . (See Chapters 21 and 22.) Table 1.2 Clinical findings suggesting the diagnosis of thyroid cancer in a patient with a thyroid nodule Family history of thyroid cancer (medullary thyroida cancer or nonmedullary thyroid cancerb) Rapid...

Serum Thyroglobulin Tg

Paradigms for the follow-up of patients who appear to be free of tumor after total thyroidec-tomy and thyroid remnant ablation have shifted to performing neck ultrasonography and measuring Tg during TSH suppression and after rhTSH stimulation, or T4 withdrawal (which produces symptomatic hypothyroidism that many patients choose to avoid) 184,186 . These paradigms are used by many US physicians (Figures 1.10,1.11,and 1.12).Accurate serum Tg measurement is the cornerstone of this follow-up paradigm (Professor Spencer and Dr Fatemi review this in Chapter 18). Serum Tg and ultrasonography identifies almost all patients with residual tumor, thus preventing unnecessary additional testing in those without residual tumor. For those who are cured, as confirmed by a serum Tg that fails to rise in response to rhTSH and a negative thyroid ultrasound examination, the T4 dose can be reduced to maintain the TSH level in the low normal range, thus avoiding the potential harmful effects of...

Development of the Guidelines

The guidelines were compiled under the auspices of the British Thyroid Association by a panel of national experts representing all relevant disciplines, colleges, and societies in the UK. Patient representatives were fully involved in the process of guideline development, as well as the preparation of patient information literature. The development followed the process recommended in the literature available at the time for the development and use of guidelines, such as the series in the British Medical Journal (1999 volume 318, edited by M. Eccles and J. Grimshaw). A systematic review of the literature was undertaken. The definition of Types of Evidence and the Grading of Recommendations follows that of the Agency for Health Care Policy and Research (AHCPR, 1994). Randomized trials are generally not available for thyroid cancer, and evidence is therefore based on large retrospective studies such that the level of evidence according to AHCPR is generally II or III as a result there is...

Case of Need for Guidelines

Although differentiated thyroid cancers are not common they are of similar frequency to cervical cancer and multiple myeloma and are the commonest malignant endocrine tumors. Furthermore they are among the few curable cancers. When managed according to best practice, the vast majority of patients can expect cure, and thus good management is mandatory. The annual reported incidence in the UK for 1971-1995 was 2.3 per 100000 women and 0.9 per 100000 men, with approximately 900 new cases and 220 deaths recorded every year in England and Wales 6 . More recent data give the incidence in England for year 2000 as 3.3 women and 1.3 men per 100000, suggesting a possible increase (see NICE Guidelines at www.nice.org.uk). In the USA an estimated 17000 new cases are diagnosed and 1300 deaths from thyroid cancer occur annually 7 . From large American series the 10-year survival rates for papillary and follicular thyroid cancer were 93-94 and 84-85 respectively 8,9 local or regional recurrences...

Diagnosis and Referral

Patients with suspected or newly diagnosed thyroid cancer should be referred to a member of the MDT. Guidelines for the investigation and management of thyroid swellings can be found in Chapter 7. Clinical features which should give rise to suspicion, and which indicate the need for urgent referral (within 2 weeks), are any of the following in association with a thyroid lump newly presenting lump or increasing in size, a family history of thyroid cancer, a history of previous neck irradiation, young patients (65 years) Diagnostic assessment will include clinical examination, thyroid function tests, thyroid autoantibodies, and fine-needle aspiration cytology (FNAC) with or without ultrasound scan guidance.

Fine Needle Aspiration Cytology FNAC and Pathology

FNAC is an essential diagnostic procedure that is used in the planning of surgery. The cytology should be reported by a cytopathologist who has a special interest in thyroid disease and is a member of the MDT. An adequate sample is required and reports should be based on descriptive text, but should include a numerical coding as a guide towards specific further investigation or therapeutic action.

Volume Outcome Relationships Centralization Regionalization of Service

While much discussion is taking place about the implications of this approach it is also becoming clear from many publications that outcomes of major and specialized cancer surgery and treatment of rare cancers like thyroid cancer have a positive volume-outcome relationship in that outcomes might be better in high volume hospitals than in hospitals that see only a few patients a year 12-16 . On the basis of these and other publications it may be that in the future thyroid cancer surgery and management will be centralized or concentrated in higher volume settings, which in other countries is a concept known as regionalization 17,18 .

The Future and Development of International Best Practice Models

In the absence of randomized controlled trials the treatment of thyroid cancer across the world is largely based on national guidelines and consensus statements. Although different centers in different countries have their own framework for commissioning and service delivery for thyroid cancer, there are some common Thyroid-specific standard Thyroid-specific standard thyroid cancer every week (for discussion depending on caseload and local variables) Thyroid-specific standard Core MDT nurse spends at least 50 of time on thyroid cancer (for discussion) Thyroid-specific standard Thyroid cancer clinicians would be trained to appropriate guidelines, for example BAHNO of Endocrine Surgeons, British Thyroid Association, ARSAC, IRR, IR(ME)R etc. Thyroid-specific standard Thyroid-specific standard Thyroid-specific standard Thyroid-specific standard Thyroid-specific standard Thyroid-specific standard MDT Network agreed guidelines for thyroid cancer follow-up (although rare for thyroid cancer)...

The Development of the Specialist Nurse Role

Most patients with thyroid cancer, particularly differentiated thyroid cancer (DTC), have a good prognosis 1,2 . The standard combined treatments are considered to be well tolerated, with low health-related quality of life (HRQOL) morbidity. Some patients have been told that DTC is the best cancer to have 3 . In patients with such a good prognosis and low symptom morbidity, what is the role of a specialist nurse (SN) To date the role of the SN in thyroid cancer care has developed into three main branches A recently expressed criticism of modern thyroid cancer care is the perceived failure to focus on the human being who bears the burden of the cancer 3-5 . As one patient put it doctors and others seem to treat thyroid cancer lightly (in an emotional sense) because it is usually quite curable. That's not at all how it felt to me 6 . There is a growing body of research to suggest that patients and carers do suffer a significant amount of psychological distress with HRQOL morbidity...

The Role of the SN in Patient Carer Psychological Support and Information

It is suggested by the British Thyroid Association that in order to best meet a patient's psychological information needs, a patient should be encouraged to attend consultations with a family member, friend, or carer, who should also have full access to support from the multidisci-plinary team (MDT). It is also recommended that an SN should be made available for support 13 . It is hoped that the SN can engage in open and honest discussion to create a forum where each patient carer's psychological information needs can be best identified. It is anticipated Table 5.1 Reported psychological reactions by patients following thyroid cancer diagnosis and treatment planning 3-4,6,9 The SN can also promote patient choice and availability of useful resources patient support groups, patient information websites, and useful contacts 14 . The SN needs a good clinical insight into all types of thyroid cancer such as papillary, follicular, medullary, and the different treatment pathways in order to...

Other Types of Nodule

Functioning thyroid adenomas ( toxic nodules ) often have somatic constitutively activating mutations of the TSH receptor 27 . Molecular rearrangements or mutations in the pathogenesis of differentiated thyroid cancer (RET PTC, BRAF) have been implicated 26,28 . Medullary thyroid cancer is frequently associated with activating somatic or germline mutations of the RET gene. Mutations in tumor suppressor genes (p53) have been reported in anaplastic thyroid cancer 29 . External beam irradiation to the thyroid in childhood increases the incidence of both benign and malignant thyroid nodules 30 .

Biochemistry and Immunology

Patients with a toxic adenoma, toxic multinodular goiter, Hashimoto's thyroiditis, or relapsed Graves' disease after subtotal thyroidectomy need not be investigated further with regard to the nature of the nodule, unless there are worrying features on palpation or there is a clear history of recent increase in size. Patients with abnormal thyroid function should be referred routinely to an endocrinologist. Thyroid function tests are therefore an important useful early screening test for selecting patients who require further assessment in order to exclude cancer, and should be performed by the primary care physician in all patients presenting with a thyroid nodule. Serum calcitonin may be elevated in patients with nodules due to medullary thyroid cancer, a rare cause of thyroid nodule with a prevalence of about 0.5-0.7 33 . Routine measurement of serum calcitonin in all patients with thyroid nodules has been advocated by some and retrospective evidence suggests a better outcome in...

Fine Needle Aspiration Biopsy

Surgical removal of nodules was used extensively several years ago as a means of excluding thyroid cancer. This, however, was an unnecessary procedure in 95 of cases where the histology turned out to be benign 35 . The introduction of fine-needle aspiration biopsy (FNAB) has been shown to reduce the rate of thyroidectomies, increase the incidence of thyroid cancer in resected thyroid lobes, and to be cost-effective 36 . The sensitivity, specificity, and accuracy of FNAB vary between 70 and 100 in different series 37,38 . The experience of the person performing the biopsy and of the cytologist, as well as the threshold for accepting a specimen as adequate, determine the diagnostic utility of this test 37,39 . False-positive FNABs are generally rare 38 , although the false-negative rate can be as high as 6 , but in most series it is approximately 1 19,39,40 . FNABs are usually classified into one of six categories no follicular thyroid cells present (Thy0) follicular thyroid cells...

Management of Patients with Nondiagnostic Cytology

Patients with adequate cytology which is intermediate (Thy3 and Thy4), require surgery in order to obtain an accurate diagnosis. The risk of malignancy is approximately 20-25 in Thy3 nodules 52,53 and 40-50 in Thy4 lesions 41 . Lobectomy is the operation of choice for nodules with indeterminate cytology (Thy3 or Thy4). If the histology is benign, the contralateral thyroid lobe will be adequate in most cases for maintaining euthyroidism without a need for thyroxine therapy. If, however, the lesion is malignant, the surgeon can proceed to a completion thyroidectomy without having to reexplore the same lobe, thus minimizing the risks of hypoparathyroidism and recurrent laryngeal nerve injury.

Diagnostic Frameworks for General Practice

'The masqueraders can be grouped into primary and secondary groups. The primary (most common) masqueraders are depression, diabetes mellitus, drugs, anemia, thyroid disease, spinal dysfunction, and urinary tract infection. A secondary (less common) list includes chronic renal failure, HIV AIDS, rare bacterial infections (e.g. subacute bacterial endocarditis, tuberculosis), systemic viral infections (e.g. infectious mononucleosis, hepatitis A, B, C, D, E), neurological dilemmas (e.g. Parkinson's disease, multiple sclerosis), connective tissue disorders (e.g. systemic lupus erythe-matosus, polymyalgia rheumatica). It is in this context that problems in identifying and managing cancer of the thyroid in general practice become obvious.

Role of the GP in Initial Diagnosis

GPs will often be the first port of call for a patient who has found a thyroid nodule, and may be the one who identifies the nodule incidentally either on physical examination or on ultrasound. Should a diagnosis of thyroid cancer be possible, it is essential that the possibility is canvassed with the patient before referral to the specialist. Responses to the diagnosis in other cancers when patients are not forewarned can range from disbelief to anger, and specialist colleagues are put in an invidious position when there is no preparation 16 .

Informing the Patient

The patient should be informed of the diagnosis by a member of the specialist team. Written information concerning thyroid cancer and its treatment should be available to the patient in the specialist clinic. Patients may have difficulty understanding all this information at a single consultation and an opportunity for further explanation discussion should be offered by the specialist team. However given the easier access and often longstanding relationship with their GP, patients may approach primary care for further information, interpretation of the specialist consultation, and help. It is therefore essential that the GP and his nursing colleagues have access to and understand the information being given to the patient by secondary care. In the UK, patients may receive information from secondary care in the form of leaflets explaining (1) tests and treatment, (2) thy-roidectomy, and (3) radioactive iodine ablation therapy. These have been formulated into three patient information...

Support of Patients During Treatment and Followup

GPs should be familiar with the treatment procedure during and after the initial phase of diagnosis. Ablation of all thyroid tissue with 131I is usually performed at the time that TSH production is maximal - usually around 4 weeks post surgery. Thereafter, the patient will require replacement therapy with thyroxine (T4). This will only be ceased in the weeks prior to periodic reassessment with radioactive iodine scans. GPs will need to monitor thyroxine levels. Serum thyroglobulin levels can also be monitored as this hormone is a sensitive marker of well-differentiated thyroid tumors 3 . Serum calcium and parathyroid hormone surveillance should be considered until it is established that the parathyroid gland preserved at the time of surgery is functioning adequately. If a total thyroidectomy is required, autologous transfer of a parathyroid gland into a muscle mass will be performed. The most common forms of thyroid cancer -follicular and papillary - have excellent survival rates,...

Other Variants of Papillary Carcinoma

An oncocytic variant is recognized 41 and the Warthin-like tumor is an oncocytic tumor with an extensive chronic inflammatory infiltrate 42 that resembles the tumor of the salivary gland. Clear cells may be admixed with oncocytic cells in some lesions, or may predominate. Immunopositivity for thyroid transcription factor 1 (TTF-1) 19 and thy-roglobulin will confirm them as of thyroid origin. These patterns have no behavioral significance. The diffuse sclerosing variant occurs in young people and shows multiple foci of tumor within lymphatics with marked squamous metaplasia, stromal fibrosis, prominent psam-moma bodies, and a lymphocytic infiltrate 43,44 . Lymph node metastases are common and lung metastases are present in about a quarter of patients at presentation. The rare tall cell variant 45 occurs in older patients, usually men, and is often a large tumor with extrathy-roidal extension and an aggressive course. The cells are oncocytic and are two to three times as tall as they...

Hyalinizing Trabecular Tumor

The lesion has also been defined as paragan-glioma-like adenoma of thyroid (PLAT). However, none express calcitonin and all show immunopositivity for thyroglobulin, implying an origin from follicular cells. Focal positivity for general neuroendocrine markers has been described in a minority, raising the possibility of dual differentiation. The relationship to papillary carcinoma has been most widely debated. The nuclear features resemble those of papillary carcinoma and psammoma bodies are sometimes present. Papillary carcinomas can be found in the thyroid gland in about one third of cases of hyalinizing trabecular tumor and both appearances may coexist within the same nodule. Immunohistochemical data are inconsistent. Some have reported positivity for CK19 while others have found them negative. Recent studies have shown RET PTC arrangements in some of these lesions, suggesting that they are a variant of papillary carcinoma 57,59 . However, not all cases show these changes and they...

Outline of the Management Plan

Based on the clinical evaluation and the FNAC report a management plan should be designed, preferably by the multidisciplinary team and in consultation with the patient. In most cases thyroid surgery is the first procedure in the treatment plan, for diagnostic reasons in case of follicular lesions and otherwise for removal of tumor. The presence of the nuclear medicine physician in the team at this stage is helpful for logistic reasons to plan future 131I ablative therapy. The extent of the thyroidectomy, and whether or not lymph node dissection should be done, should be discussed. The decision to operate may not be straightforward with papillary micro carcinomas (2 mm in 25 and decreased by 2mm in 10 19 . In such cases a common policy supported by all members of the team can avoid confusion.

Evaluation of Prognosis According to TNM or Other Classification Systems

Prognostic factors associated with poor survival are older age, male sex, family history, histology (particular variants of papillary and follicular cancers, capsular invasion), large tumor size, and lymph node and distant metastases. Multi-variate analysis reveals three independent prognostic factors age, histological type, and tumor extent. The preoperative evaluation, the findings during surgery and the pathology of the surgical specimen will usually allow correct classification of the cancer in a prognostic scoring system in the immediate direct postoperative period. Several prognostic scores have been developed for use in thyroid cancer. The multidisciplinary term should decide which scoring system is to be used in their institution. Which score is selected will depend more on local preference than on superiority of one score over the others predictability of patient outcome is very similar for different staging systems (including TNM, EORTC, ASES, AMES, and MACIS scores) in...

Administration of TSHSuppressive Doses of LThyroxine

After thyroidectomy and 131I ablation there is a need for life-long T4 replacement therapy. In patients with nonmedullary thyroid cancer the prescribed daily T4 dose is usually higher than the replacement dose in order to reach suppression and not just normalization of serum TSH values. For a number of studies have shown that TSH suppression is associated with a longer disease-free interval 4 .A French study reports a longer relapse-free survival in patients with constantly suppressed TSH (all values 1 mU L) the degree of TSH suppression predicted relapse-free survival independently of other factors 32 . In a US cooperative study the degree of TSH suppression was an independent predictor of disease progression in high risk patients with papillary carcinoma, but not in low risk patients or when radioiodine treatment was included in the model 3 . A Finnish study reports that a nonsuppressed TSH is an independent predictor for recurrence in multivari-ate analysis 33 . A study from Taiwan...

Attention to Quality of Life

The physician in charge of the continuity in care of the thyroid cancer patient (likely the endocri-nologist) is instrumental in promoting compliance with the long-term follow-up and the required repeat investigations. Compliance can be enhanced by giving attention to many details which - although not determining the main outcome of the disease - may severely affect the patient's life. The cost of care should not be forgotten, as patients may have no or insufficient insurance 44 . The incidence of chronic xerostomia as a result of 131I-induced sialadenitis may decrease considerably with amifostine pretreat-ment 45 . During thyroid hormone withdrawal, hypothyroid symptoms are common such as fatigue, weight gain, peripheral edema, muscle cramps, skin dryness, anxiety, constipation, cold, depression, and impairment of memory and concentration these complaints are more pronounced in the elderly than in younger patients 45 . It is thus not surprising that quality-of-life questionnaires...

Training in Endocrine Surgery Obtaining the Skills and Knowledge

Two levels of endocrine surgery training now exist surgical residency and endocrine surgery fellowship training. The baseline level of training for thyroid surgery is received in surgical residency and is a mandatory component of general surgery and otolaryngology programs. This chapter will focus on the general surgery perspective. Additional surgical endocrinology fellowship training remains an informal process at present, but discussion regarding the standardization of formal fellowship training is under way within many associations, including the American Association of Endocrine Surgeons (AAES).

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