The Natural Thyroid Diet

The Natural Thyroid Diet

The Natural Thyroid Diet can help you get the nutrition your thyroid needs. And when your thyroid is working better you will have more energy and it becomes much easier to lose weight. Find out why soy foods can actually harm your thyroid. Discover why going gluten free may not be a perfect dietary solution. Identify & treat the underlying factors that are driving your thyroid problem. Find out how to get a real medical diagnosis with specific pathology tests. How to assess your thyroid activity at home with a simple testing procedure. Find out which specific nutrients help enhance natural thyroid activity. Discover why iodine is such a critical mineral for the thyroid. Reduce thyroid stress & skyrocket your metabolism with a few simple activities. Learn about reverse T3 dominance & how to treat this common thyroid problem. How to detox your home to reduce the toxic load on your thyroid. Find out how to interpret the medical test results from your doctor. Get a natural thyroid diet with actual daily meal plans and food lists. Continue reading...

The Natural Thyroid Diet Summary

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Oncogenes Connected to Thyroid Stimulating Hormone

Thyroid-Stimulating Hormone Receptor Mutations The idea that physiologic pathways may be constitutively activated by genetic alterations of single components of these pathways was compelling but hard to prove. For thyroid tumors, the TSH receptor (TSH-R) had to be cloned before studies of the structure and expression of this receptor could be performed. Cloning of the human TSH-R by Parmentier and colleagues in 19899 was an important breakthrough in this field. The knowledge that all G protein-related receptors develop from a common progenitor and demonstrate specific protein structures (i.e., an intracellular carboxyterminal end, an extracellular ligand-specific end, and a seven-transmembrane loop region) made it possible to use experiences from P-adrenergic receptor studies for TSH-R investigations. Liggett10 and Hausdorff and their colleagues used site-specific deletions of the p-adrenergic receptor. They were able to modulate specifically hormone-stimulated cyclic adenosine...

Thyroid Disease Goitre

Thyroid swelling may result from iodine deficiency (simple goitre), autoimmune (Hashimoto's) thyroiditis, adenoma, carcinoma or thyrotoxicosis. Nodules of the thyroid gland may be 'hot' (secreting thyroxine) or 'cold'. The goitre may occasionally cause respiratory obstruction. Retrosternal goitre may in addition cause superior vena caval obstruction. The presence of a goitre should alert the anaesthetist to the possibility of tracheal compression or displacement. A preoperative X-ray of neck and thoracic inlet may be useful, and a selection of small-diameter, armoured tracheal tubes should be available. Preoperative assessment of thyroid function is essential.

Thyroid Eye Disease Thyroid Orbitopathy

Hyperthyroidism may induce an orbitopathy in some patients. In such cases, there is diffuse hyperplasia of the thyroid and infiltrative ophthalmopathy. Thyroid eye disease is seen in association with thyroid dysfunction, although thyroid function test results may be normal. With thyroid orbitopathy, the extraocular muscle becomes infiltrated this may occur even when the disease appears to be under good systemic control. The precise extraocular mechanism is unknown and the genetic predisposition uncertain. Graves' ophthalmopathy occurs in approximately 95 of patients with Graves' thyroid disease, but is only rarely seen with Hashimoto's thyroid disease. The diagnosis of euthyroid Graves' ophthalmopathy is primarily a clinical diagnosis, confirmed with orbital CT imaging. Clinical characteristics include hypotropia, esotropia, or a combination of vertical and horizontal strabismus. Many patients are euthyroid at diagnosis, but there may be a history of previous thyroid dysfunction....

Anaplastic Thyroid Carcinoma

This aggressive thyroid cancer is generally quite large and is associated with extra-thyroidal extension and is usually not respectable. For the occasional case where the lesion is small and intra-thyroidal, resection may be considered. Early development of distant metastasis and an aggressive course make this a most deadly disease.

A102 Thyroidstimulating hormone and the thyroid gland

The thyroid-stimulating hormone acts on the thyroid gland in the neck and stimulates the release of the thyroid hormones thyroxine and tri-iodothyronine. The thyroid hormone stimulates metabolism by acting on the cells to speed up the rate at which food is used up and converted to heat and energy. The thyroid gland is unique in that it stores its hormones as a colloid in small vesicles in the gland. The other glands store their secretions in the cells themselves. The formation of the thyroid hormone requires iodine ingested in the diet. In regions where populations may encounter a deficiency of iodine in their diets, the addition of iodine to salt (iodized salt) has helped in the prevention of thyroid disease, particularly the enlargement of the thyroid gland known as goitre. Deficiency of the thyroid hormone (also called hypothyroidism) in a child causes cretinism, where the development of the nervous system is affected and the child is mentally retarded. In an adult, deficiency of...

Treatment of Hypothyroidism

Thyroid Hormone Products A number of thyroid hormone products are marketed in the United States (Table 44-3). These products include synthetic LT4 and T3, combinations of synthetic LT4 and T3, and animal-derived products. Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic LT4 is the treatment of choice for almost all patients with hypothyroidism.11 12 Using LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. Peripheral tissues convert T4 to T3 as needed, based on metabolic demands. If T3 is used to treat hy-pothyroidism, the peripheral tissues lose their ability to control local metabolic rates. LT4 also has distinct pharmacokinetic advantages over T3. With a 7 to 10 day half-life, LT4 provides a very smooth dose-response curve with little peak and trough effect. In a small number of patients who have impairment of conversion of T4 to T3, addition of T3 may be warranted. T3, with a 24-hour...

Sequelae of Hypothyroidism

Hypothyroidism is a chronic disease that may result in significant long-term sequelae. Hypercholesterolemia is associated with hypothyroidism, increasing the long-term risk of cardiovascular disease and cardiovascular mortality.14 Between 4 and 14 of patients with hypercholesterolemia are found to be hypothyroid. The Colorado Thyroid Health Study showed a direct correlation between the degree of TSH elevation and the rise in serum cholesterol. Hypothyroidism also may result in increased systemic vascular resistance, decreased cardiac output, and increased diastolic blood pressure. Hypothyroidism can cause significant neuropsychiatric problems, including a dementia-like state in the elderly that is reversible with LT4 therapy. Maternal hypothyroidism can have dire consequences for the developing fetus. The fetus is almost completely dependent on maternal thyroid hormones during the first trimester, a time crucial for development of the CNS. Inadequately treated maternal hypothyroidism...

Painful de Quervains Thyroiditis

Painful thyroiditis is a transient inflammatory thyroid disorder that was first described by de Quervain in 190421 and is the most common cause of a painful thyroid gland. Other eponyms for this condition include granulomatous thyroiditis, subacute granulomatous thyroiditis, or pseudogranulomatous thyroiditis. Painful thyroiditis is thought to be viral in origin or result from a post-viral inflammatory response. This theory is supported by the following observations 3. Cytopathic viruses have been cultured from thyroid tissue. There is also evidence for a genetic predisposition, manifested by its strong association with the HLA-B35 haplotype.23 A model of pathogenesis suggests that antigens (either directly from viruses or from damaged thyroid tissue) are presented by macrophages in the context of HLA-B35 and stimulate cytotoxic T lymphocytes. These lymphocytes proceed to damage thyroid follicular cells. This autoimmune process, however, is self-limiting. Antibodies directed against...

Rationale for Parathyroidectomy

Changes in the frequency of symptoms after surgery in parathyroid and thyroid patients. (From Chan AK, Duh QY, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy A case-control study. Ann Surg 1995 222 402.) FIGURE 40-1. Changes in the frequency of symptoms after surgery in parathyroid and thyroid patients. (From Chan AK, Duh QY, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy A case-control study. Ann Surg 1995 222 402.) FIGURE 40-2. Changes in the frequency of associated conditions after surgery in parathyroid and thyroid patients. (From Chan AK, Duh QY, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy A case-control study. Ann Surg 1995 222 402.) Parathyroid (N 121) Thyroid (N 93) Parathyroid (N 121) Thyroid (N 93) FIGURE 40-3. Neuromuscular recovery after parathyroidectomy in primary...

Acute Suppurative Thyroiditis

Gastrografin Swallow

Acute thyroiditis was first described by Bauchet in 1857 and accounted for approximately 0.1 of thyroid surgeries before the advent of antibiotic therapy.1 The thyroid gland has an innate resistance to infection due to its extensive blood and lymphatic supply, high iodide content, and fibrous capsule.2 Despite these protective mechanisms, acute thyroiditis may be caused by infectious agents that seed the thyroid gland (1) by the hematogenous or lymphatic route, (2) by direct spread from persistent pyriform sinus fistulas or thyroglossal duct cysts, or (3) as a result of penetrating trauma to the thyroid gland.3 Takai and associates first demonstrated that acute suppurative thyroiditis can result from persistent pyriform sinus fistulas.4 Since then, several investigators have demonstrated that pyriform sinus fistulas are responsible for a large proportion of cases of recurrent acute thyroiditis. These fistulas are commonly believed to be fourth branchial pouch remnants and originate at...

Papillary Thyroid Carcinoma Rationale for Total Thyroidectomy

Considerable controversy continues about whether all or part of the thyroid gland should be removed for patients with differentiated thyroid cancer of follicular cell origin (papillary, mixed papillary follicular, follicular, and Hurthle cell), because there are no controlled, prospective studies comparing the results of different methods of treatment (lobectomy, near-total thyroidectomy, or total thyroidectomy). Patients with these thyroid cancers also generally have a good prognosis, with an overall mortality of about 20 , so that studies comparing survival must include large numbers of patients who are monitored for a long period. The rate of thyroidectomy complications, including vocal cord paralysis resulting from recurrent laryngeal nerve injury and hypoparathyroidism, should be low but ranges from less than 1 to more than 10 .14 Complications are reported to increase in patients having more extensive thyroid operations, especially when thyroidectomy is associated with central...

Definition Advantages and Disadvantages of Hemithyroidectomy

Hemithyroidectomy can be used in a patient with low-risk papillary thyroid carcinoma that is macroscopically localized in one thyroid lobe. In this procedure, the whole involved lobe, the isthmus, and occasionally the medial portion of the contralateral lobe are resected. When the medial third of the contralateral lobe is included in the resection, the thyroid operation is referred to as subtotal thyroidectomy in the United States41 and in Japan.8,24 We include patients who had subtotal thyroidectomy in our group of hemithyroidectomy patients. We have performed subtotal thyroidectomy and lobectomy (removal of one lobe without resection of the isthmus) in 71 and 13 , respectively, among our group of 408 patients with low-risk papillary thyroid carcinoma (Table 11-3). The advantages of this surgical approach are that, when compared with total thyroidectomy, surgical complications including permanent hypoparathyroidism and bilateral recurrent laryngeal nerve palsy are lower, even when an...

Metastases to the Thyroid

The true incidence of metastases to the thyroid gland has not been clearly established. Autopsy studies have reported an incidence ranging from 2 to 25 .156159 In the study by Mortensen and colleagues, 4 of patients with metastatic neoplasms had secondary tumors of the thyroid gland.159 Silverberg and Vidone157 found the incidence to be much higher. In their study, they meticulously examined the thyroid and found the incidence of metastatic disease to the thyroid to be 24 in patients dying from metastatic cancer. This study suggested that the incidence of microscopic disease in the thyroid is greater the more diligently it is looked for. Shimaoka and coworkers156 studied the occurrence of thyroid metastases for a given primary neoplasm. In their autopsy study of patients who died of metastatic cancer, they found that metastases to the thyroid occurred in 39 of melanoma patients, 21 of breast cancer patients, 12 of renal cancer patients, 10 of lung cancer patients, and 10 of patients...

Thyroid and Parathyroid Tumors

10cm Mri Chiba Needle Cost

THYROID TUMORS Diseases of the thyroid gland represent a common medical and surgical problem. A variety of inflammatory lesions and neoplasms are noted by endocri-nologists and surgeons interested in thyroid pathology. Various pathologic conditions include Hashimoto's thyroiditis, nodular goiter, solitary thyroid nodule, adenomas and thyroid cancer. Although thyroid disease is extremely common, thyroid cancer is relatively uncommon and forms less than 2 percent of all human cancers. Approximately 19,500 new patients with thyroid cancer will be seen in the United States during the year 2001, while approximately 1,300 patients will die of thyroid cancer.1 The prevalence of nodular goiter has decreased considerably in the United States due to the routine use of iodized salt. However, it is still quite prevalent in other parts of the world, particularly in certain European countries around the Alps, and in Asia near the Himalayas. The routine use of ultrasonography has shown a very high...

Thyroid Disease in Pregnancy

Pregnancy can exacerbate an already-existing thyroid disorder, thus requiring extra vigilance by the family physician. Careful monitoring and proactive clinical intervention are key. The majority of women with hypothyroidism, who are euthyroid on stable doses of thyroid replacement, will require increased doses of thyroxine replacement during their pregnancy. Being aware of this need and prepared to make dosage adjustments in a timely manner is important. Consulting an endocrinologist to help with the care of these patients is advised (Shankar et al., 2001). Silent (postpartum) thyroiditis during pregnancy is essentially a benign, short-term disease and requires only symptomatic treatment. Occasional checks of sTSH and FT4 levels are justified to monitor recovery. Table 35-3 Drugs that Affect Thyroid Function at the Peripheral Level Table 35-3 Drugs that Affect Thyroid Function at the Peripheral Level Inhibit Inhibit Thyroid For the rare pregnant patient who requires suppression of T4...

Recommendations for the Use of Levothyroxine in Thyroid Cancer

The consensus recommendation currently is that TSH suppressive therapy should be given postoperatively to all patients with differentiated thyroid cancer. The exact definition of appropriate TSH suppression to suppress tumor growth adequately remains unclear. Studies with very large numbers and follow-up would be required to detect significant differences. The true efficacy of ablative 131I has never been established in a controlled clinical setting.228,229 In the postoperative setting in the cases believed to be high risk (the older male patient with a tumor larger than 4 cm with either capsular or angioinvasion if follicular or extensive lymphadenopathy if papillary), T4 replacement therapy is avoided for 4 to 6 weeks. This allows maximal TSH stimulation to occur and permits a valuable assessment of postoperative thyroglobulin levels (because thyroglobulin levels increase as serum TSH levels increase in patients with remnant normal thyroid tissue or metastatic thyroid cancer after...

Surgical Anatomy of the Thyroid and Parathyroid Glands

Ligament Berry

The normal adult thyroid gland weighs about 17 g. It is wrapped around the anterolateral portion of the upper tracheal rings and larynx. Each lobe occupies a bed between the trachea and the esophagus medially the carotid sheath posteriorly and the sternocleidomastoid, the sternohyoid, and the sternothyroid muscles laterally and anteriorly. If the sternothyroid and sternohyoid muscles are to be divided transversely, they must be transected high, at the cricoid level, to preserve their motor nerve, the ansa hypoglossi. Section of the strap muscles has no clinical functional consequence. The normal thyroid is soft, dark wine-red in color, and covered with a thin capsule. It is loosely attached to neighboring structures. The variations in fixation of the gland may arouse suspicion of pathologic change, particularly when the history suggests acute thyroiditis or cancer. Normally, the gland adheres only to the cricoid cartilage and the upper tracheal rings. This is the posterior suspensory,...

Rationale and Indications for Hemithyroidectomy

Before 1945, thyroid cancers were more aggressive tumors in most other parts of the world except Japan. This is probably because in Japan there was high iodine intake as a result of the consumption of seaweed and seafood. In the United States, the addition of iodine to table salt, bread, and water was begun in the 1920s and 1930s, and in European countries it was added after the end of World War II. Currently, most of the Western countries have become iodine sufficient, and some even iodine rich, such as the United States. Whereas the biologic characteristics of thyroid cancers have remained virtually unchanged in Japan, there have been considerable changes in clinical and survival patterns in patients with thyroid cancers in the United States.2646 In iodine-rich areas, approximately 90 of all differentiated thyroid cancers of follicular cell origin are papillary thyroid carcinomas, and of these, approximately 90 are low-risk cancers.20 The introduction of fine-needle aspiration...

Differentiated Thyroid Cancer of Follicular Cell Origin

The minimal test for determining the diagnosis of a thyroid nodule is fine-needle aspiration cytology with or without ultrasonography. Use of these two tests enables one to discriminate benign from malignant thyroid tumors in about 85 of patients. The remaining 15 of thyroid malignancies are follicular cancer, Hiirthle cell cancer, and some follicular variants of papillary thyroid cancer. Various imaging techniques are used for detecting regional and or distant metastasis and identifying local invasion of adjacent structures. Since the advent of high-resolution ultrasonography, it is sometimes possible to establish the diagnosis of papillary cancer with only ultrasonography, and fine-needle aspiration cytology is used to confirm the diagnosis.14 Papillary cancer is most frequently thyroid cancer ( 80 ). The presence of calcification, irregular shape, absence of a halo and hypo-echogenicity, and local invasion suggest it is a malignant nodule. Calcification is identified as multiple,...

Restoration of Differentiated Thyroid Function

DTCs of follicular cell origin (papillary and follicular cancers) are usually well differentiated and behave in a nonaggressive manner. However, some lose differentiated functions (dedifferentiation) and behave more aggressively. These cancers become refractory to thyroid-specific therapies that are based on differentiated thyroid function such as radioiodine therapy and thyrotropin (TSH)-suppressive therapy. Restoring differentiated functions in these tumors may not only slow tumor growth but also resensitize tumors to thyroid-specific therapy such as treatment with radioactive iodine. Redifferentiating therapies are tissue specific and generally less toxic than nonspecific chemotherapy. There are several redifferentiating agents for thyroid cancers (1) retinoids, (2) aromatic fatty acids, (3) peroxisome proliferator-activated receptor y (PPARy) agonists, and (4) histone deacetylase inhibitors. Retinoids have been shown to modulate cell growth and differentiation by binding to their...

Thyroid Stimulating Hormone Suppression and Thyroid Cancer

Controversy exists in thyroid cancer management about the extent of surgery, the use of 131I ablation therapy, the place of thyroglobulin assay in follow-up, and the role and level of TSH suppressant treatment. Further, there is debate about the degree of TSH dependence of differentiated thyroid carcinomas and the importance of other thyroid growth factors. Thyroid Growth Factors and Thyroid Carcinoma Thyroid tumors vary markedly in prognosis, and the natural history of differentiated tumors is long. The control of thyroid cell growth is complex and is influenced by many hormones and growth factors operating through distinctly different cell signal transduction systems. Classically, TSH is considered the major thyroid growth hormone, and, although there is no dispute about its role in stimulating thyroid gland function, its effects on thyroid growth and particularly abnormal growth are in question. TSH stimulates differentiated thyroid functions, most notably iodine uptake and...

Lateral Approach for Parathyroid Exploration

The lateral approach for parathyroidectomy was first described by Feind.73 This approach involves dissection between the anterior border of the sternocleidomastoid muscle and the posterior border of the strap muscles.74 The omohyoid muscle is usually divided. Retraction of the sternocleidomastoid muscle and the carotid sheath laterally and the strap muscles medially exposes the lateral aspect of the thyroid gland, the tracheoesophageal groove, the recurrent laryngeal nerve, and the parathyroid glands.

Hashimotos Thyroiditis

Hashimoto's thyroiditis, known as an autoimmune or chronic lymphocytic thyroiditis, is the leading cause of hypothyroidism. The pathogenesis of hypothyroidism is complex. Three mechanisms have been proposed (1) thyroid cell damage by the thyroid antibody-mediated complement attachment (2) T-cell-mediated cytotoxicity and (3) enhanced apoptosis (programmed cell death). The initial event is the formation of antibody in response to self-antigen such as thyroid peroxidase (TPO) and thyroglobulin this event does not normally happen. If self-antigen is falsely recognized by the immune system, antibody formation takes place to the specific self-antigen, creating organ-specific autoimmunity. This leads to immune complex deposition in the basement membrane of follicular cells and complement activation, as suggested in 1977.9 Weetman and associates confirmed the presence of terminal complement complexes around thyroid follicles.10 Thyrocytes attacked by complement through antibodies were shown...

Persistent Recurrent Hyperparathyroidism in MEN 1 Patients

The combination of oblique planar images and singlephoton emission CT yields the most sensitive information (Figs. 76-3A and 76-4A).102 Sensitivities in the range of 70 to 85 have been reported.98102 SPS falls short in patients with multigland disease (but less so when only one or two glands remain) and in patients with nodular thyroid disease. It is particularly helpful in patients with mediastinal and ectopic glands.64 Cervical ultrasonography is the second most frequently used imaging study. It is very observer dependent, with reported sensitivity rates varying between 25 and 9Q 60,65-68 The Mayo Clinic and the University of California-San Francisco have reported sensitivities of 48 to 55 with large numbers of patients.70'71 Ultrasound is hampered by thyroid nodules, enlarged lymph nodes, and tumors directly adjacent to the trachea and bony structures. Using ultrasound guidance, a fine-gauge needle can be inserted into the gland in question. Cells can then be sent for cytology and...

Nonthyroidal Illness as a Diagnostic Dilemma

Nonthyroidal illness is an alteration of serum thyroid hormone levels due to the presence of medical illness or fasting or after surgery. The nature of this disorder and a practical approach to this disorder have been well described.65,66 Initially, these patients present with low serum triiodothyronine (T3) levels due to decreased deiodinase 1 activity that converts T4 to T3. As the disease progresses, total T4 concentrations are reduced. When FT4 was measured by equilibrium dialysis, FT4 levels were usually normal,67 whereas FT4 measured by the analog method is low.68 The analog method is used in automated thyroid testing in most clinical laboratories and is significantly altered by high or low serum protein levels.68 Serum TSH levels vary depending on the stage of nonthyroidal illness. During the recovery stage of illness, serum TSH levels tend to be elevated. This causes difficulty in determining whether patients are hypothyroid. History of medical illness, careful physical...

Hypothyroidism after Subtotal or Total Thyroidectomy

Subtotal thyroidectomy is still an excellent form of treatment for patients with Graves' disease, particularly when antithyroid drugs and 1311 therapy are not suitable.51 Surgical approach has three advantages over radioactive iodine therapy. First, the incidence of overt hypothyroidism is considerably less than after radioactive iodine therapy. Second, the incidence of hypothyroidism does not increase as much in later years. Third, patients with Graves' ophthalmopathy are less likely to develop progression than after radioactive iodine therapy. Kuma and associates characterized the type of postoperative hypothyroidism after surgery in patients with Graves' disease who underwent subtotal thyroidectomy.52 Nearly 40 to 50 of patients experienced subclinical hypothyroidism during the first 4 years after surgery, and the incidence correlates inversely with the size of the thyroid remnant. Palit and colleagues reviewed 35 published papers regarding subtotal thyroidectomy for Graves'...

Technique of Parathyroidectomy

Level using a two-site immunoassay.2729 Localization studies of enlarged parathyroid glands are necessary only in patients having exploration of the neck for persistent or recurrent hyperparathyroidism and in patients undergoing parathyroidectomy with local anesthesia.30,31 We believe that pre- and postoperative laryngoscopy to assess vocal cord function is mandatory in (para)thyroid surgery.32 preferentially in a natural skin crease, 3 to 4 cm cranially to the suprasternal notch. An incision that is located too close to the suprasternal notch is likely to become a hypertrophic scar. The incision should not extend beyond the sternocleidomastoid muscles. After incising the platysma, the cranial skin-platysma flap is dissected upward to the notch of the thyroid cartilage and downward to the suprasternal notch. A self-retaining retractor is used to withdraw the upper and lower skin-platysma flaps. A midline incision is made in the cervical fascia from the cricoid cartilage down to the...

Lymphoma of the Thyroid

Primary lymphomas of the thyroid are rare, accounting for only 1 to 2 of thyroid malignancies and less than 2 of extranodal lymphomas.26 126128 Most thyroid lymphomas are non-Hodgkin's lymphomas of B-cell origin, although Hodgkin's disease of the thyroid has been described.126129 In a large proportion of cases, thyroid lymphomas are associated with Hashimoto's thyroiditis and histologically may be difficult to distinguish from this chronic lymphocytic disease.25 130 Follow-up studies have estimated the relative risk of thyroid lymphoma in patients with chronic lymphocytic thyroiditis to be 70 to 80 times higher than in controls.131 The actual relationship between Hashimoto's thyroiditis and thyroid lymphomas remains obscure. Whether the presence of lymphocytes in the thyroid provides the tissue in which the lymphoma can develop or whether the chronic stimulation of the lymphocytes predisposes the cells to develop malignant clones has not been defined. Clinically, primary lymphoma...

NonMEN Familial Hyperparathyroidism

The clinical information concerning the 16 patients with NMFH from 14 families treated at UCSF is summarized in Table 55-1. The most striking clinical feature of NMFH is the high incidence of profound hypercalcemia, which rarely occurs in patients with sporadic HPT or HPT associated with MEN 1 or 2. In the UCSF series, the patients with NMFH had hypercalcemia ranging from 10.5 to 20.3 mg dL (mean, 13.9 mg dL) 44 of these patients had profound hypercalcemia (serum calcium > 15 mg dL), and 31 presented in hypercalcemic crisis, requiring emergency hospitalization. As seen in Table 55-2, 45 of 51 patients in die literature presented with a serum calcium of 15 mg dL or greater and 67 with a serum calcium of 13.5 mg dL or greater. Thus, unlike the non-MEN familial medullary thyroid cancer that is less aggressive than sporadic medullary thyroid cancer or MEN 2B, NMFH appears to be more aggressive than other forms of the disease. Thyroid Thyroid nodule Coexistent thyroid disease occurred in...

Oncogenesis in Thyroid Cancers of Follicular Cell Origin

THYROID-STIMULATING HORMONE RECEPTOR The thyroid-stimulating hormone (TSH) receptor is a transmembrane glycoprotein that is G protein coupled. TSH, acting through its receptor, is the main regulator of thyro-cyte function and growth. Its function is mediated via the adenylate cyclase and phospholipase C intracellular pathways.5 Constitutively activating mutations in the TSH receptor occur in the transmembrane segment and intracy-toplasmic loop in hot thyroid nodules ( 30 ) but are usually absent in cold thyroid nodules or thyroid cancers (Table 31-1).510 Unfortunately, the frequency of TSH receptor-activating mutations observed in hot thyroid nodules has been variable, ranging from 3 to 82 .5-12 This discrepancy is likely due to several factors such as small sample size, screening of only part of the TSH receptor gene, less sensitive screening techniques (single-strand conformation polymorphism), inaccurate characterization of thyroid nodule function, and the quality of DNA in tissue...

NIS and Thyroid Cancer

As previously mentioned, the treatment of patients with WDTC includes three modalities thyroidectomy, radioiodine (131I) ablation, and TSH suppression. Unfortunately, about 25 of WDTCs are initially resistant and about 50 of recurrent thyroid cancers are resistant to 131I treatment. These patients have a worse prognosis, and many studies have attempted to enhance radioiodine uptake in thyroid cancer cells in such patients. 1,2'34'37'3S Since the discovery of the NIS gene, much attention has been focused on the symporter because it is a marker for differentiation and also the mechanism by which radioactive iodide therapy works. Thyroid diseases directly affect the function of the NIS symporter. Three mechanisms, as previously stated, have been proposed for poor iodide uptake in thyroid carcinoma (1) NIS gene mutations,39 (2) suppression of the NIS gene expression,6,3944 and (3) post-transcriptional modifications of the NIS protein.24'26 Congenital ITD is an infrequent autosomal...

Chemotherapy for Thyroid Cancer

As with salivary gland tumors, thyroid cancer constitutes a spectrum of histologic subtypes and clinical sumption of an iodine-rich diet, inadequate levels of thyroid stimulating hormone (TSH), or persistence of a significant amount of native thyroid cancer may all affect the efficacy of RAI treatment for the tumor. For RAI-refractory disease, initial observation is appropriate for selected patients, as the tumor may grow slowly. If chemotherapy is indicated, doxorubicin is the most studied and widely used drug, with response rates in the 30 to 40 percent range.148,149 Cisplatin, carboplatin, methotrexate, and etoposide also have activity.150 Combination chemotherapy may improve response rate but has unproven benefit in terms of palliation and survival. Chemotherapy and radiation have been combined for the treatment of compelling local disease with good local effect in most patients.151152 The possible use of agents intended to Anaplastic thyroid cancer is an aggressive subtype with a...

Treatments Independent of Differentiated Thyroid Function

Hyperthyroidism Nis

Antitumor activity of gemcitabine is also observed in thyroid cancer cells in vitro. Gemcitabine induced apoptosis, cell cycle arrest in the S phase, and upregulation of Fas in poorly differentiated or anaplastic thyroid cancer cell lines.74'75 A multimeric form of gemcitabine appears to be more potent for inhibition of tumor cell growth than the monomelic form in thyroid cancer cells in vitro.74 In a medullary thyroid cancer cell line, TT, gemcitabine also induced an antiproliferative effect and decreased neuroendocrine activity.76 Gemcitabine and cisplatin in combined treatment are also synergistic in thyroid cancer cell lines. Voigt and colleagues reported that combined treatment is schedule dependent and effective only when gemcitabine is followed by cisplatin, not vice versa, in anaplastic thyroid cancer cell lines.77 Although small numbers of patients with thyroid cancer were included in phase I clinical trials using gemcitabine, further clinical studies are required to confirm...

Acquired Juvenile Hypothyroidism

Hypothyroidism occurs in either sex from infancy through adulthood but most commonly presents during pubertal development in girls (LaFranchi 1992). In pediatric populations, acquired hypothy-roidism typically results from autoimmune destruction of the thyroid gland. Classic symptoms of acquired hypothyroidism include poor growth, weight gain, poor concentration, depression, and fatigue. Similar to congenital hypothyroidism, acquired hy-pothyroidism is treated with levothyroxine (Fisher and Grueters 2008). tests (Wu et al. 2006). Subclinical hypothyroidism consists of mild elevation of thyroid-stimulating hormone with normal thyroid hormone levels (Biondi and Cooper 2008) (see Figure 19-1). The observation of Wu et al. (2006) agrees with an earlier report of decline in school performance following treatment for acquired juvenile hypothyroidism (Rovet et al. 1993). The authors of these studies speculated that the decreased arousal associated with hypothyroidism may underlie better...

Differentiated Thyroid Carcinoma

Pure follicular carcinoma appears to be decreasing in frequency and now makes up about 10 of differentiated thyroid cancers. This proportion may be different in geographic areas with insufficient dietary iodine or with different pathologic definitions.4041 Follicular cancers are diagnosed by the invasion of the follicular cells into or through the veins or tumor pseudocapsule or into metastatic sites. Minor tumor pseudocapsular involvement or only minor vessel involvement within the tumor itself may define follicular carcinoma, but such technically defined follicular adenocarcinomas have little, if any, risk of recurrence, metastases, or death from disease, regardless of age or risk group. Such a follicular cancer with minor capsular involvement may be found in retrospect in a patient presenting with distant metastases, but this is rare. Extensive data from the Mayo Clinic14 and Lahey Clinic9 34 confirm the essential absence of risk of recurrence or death in such patients. In the...

Long Term Followup of Thyroid Disorders

For patients receiving long-term thyroid therapy for hypothyroidism, monitoring is through sTSH unless there is hypotha-lamic-pituitary disease. It takes 2 to 4 weeks after initiating treatment (or changing dose) before clinically significant change occurs in sTSH level. In most patients, checking sTSH once monthly is sufficient until steady state is reached. After the patient is stabilized, sTSH can be checked annually unless the patient develops new symptoms or dosing changes. Patients with benign nodules should be followed annually with careful palpation of the thyroid gland. Unless there is a change in size, no additional testing is required. Ultrasound of the thyroid is not recommended for follow-up of nodules less than 1.0 cm. Repeat ultrasound is required in patients with an enlarging nodule, evidence of a new thyroid mass, or who complain of pain or pressure. Unless the patient is experiencing symptoms of hyperthyroid or hypothyroid, repeat testing of sTSH or FT4 is not...

Acquired Juvenile Hyperthyroidism

Acquired hyperthyroidism in childhood results primarily from Graves' disease, an autoimmune disorder that occurs most often in adolescent girls. Hyperthyroidism results from thyroid-stimulating antibodies that affect overproduction and secretion of thyroid hormones. Symptoms of Graves' disease include agitation, hyperactivity, poor memory, and poor concentration (Fisher and Grueters 2008). Treatment options for Graves' disease include anti-thyroid medications, radioiodine, and surgery (Glaser and Styne 2008).

Resistance to Thyroid Hormone

RTH is a rare disorder that results from target cell in-sensitivity to thyroid hormones. Newborn screening for congenital hypothyroidism can detect RTH if both T4 and thyroid-stimulating hormone are measured. The incidence of RTH is the same for males and females. Clinical presentation varies in individuals affected by RTH, and some people are asymptomatic. Behavioral characteristics (and their overall frequency) associated with RTH include emotional disturbances (73 ), attention-deficit hyperactivity disorder (70 ), hyperactivity (19 -42 ), learning disabilities (21 -32 ), and hearing deficits (25 ) (Hauser et al. 1993 Weiss and Refe-toff 2000). Limited data indicate that supraphysio-logical treatment with fast-acting thyroid hormone reduces the expression of both hyperactivity and im-pulsivity in children with RTH (Weiss et al. 1997).

Clinical Application of Indicators of Thyroid Tumor Aggressiveness

The ready application of a variety of risk group definitions (AMES, AGES, MACIS) indicates that all patients should be so characterized before initial surgery and again at completion of surgery. Age and tumor size can be determined preoperatively, whereas local invasion, distant metastases, resectability, and tumor histology or grade are usually determined postoperatively. By characterizing the risk group, the surgeon can make an initial preoperative estimate of the need for and extent of thyroid and regional lymph node resection and, postoperatively, the need for RAI treatment. When the risk of recurrence is only 3 and the risk of death only 1 in the low-risk MACIS, AMES, or AGES risk definition categories, it is impossible to prove the advantage of total thyroidectomy with RAI in contrast to a more limited or unilateral operation. Although no randomized trial has been conducted because of the infrequency of thyroid carcinoma even in young patients, studies addressing the issue of...

Thyroid Stimulating Hormone Suppression and the Post Thyroidectomy Patient

Levothyroxine may prevent clinical hypothyroidism after bilateral or subtotal thyroidectomy and occasionally after unilateral lobectomy.139 In three randomized, controlled trials comparing levothyroxine with placebo, there was no demonstrable difference in nodular recurrence after a range of thyroid operations in the TSH-suppressed patients.140142 Miccoli and colleagues142 demonstrated an advantage for suppressive as opposed to substitutive T4 dosing on echographic follow-up at 3 years, but this was in an area of endemic goiter in northern Italy, where the rate of nodular recurrence postoperatively is normally relatively high. The particularly high early recurrence of echographically demonstrable postoperative recurrence after thyroidectomy in the latter article (78 on substitutive T4 therapy) may not be indicative of the general Western experience. Large, uncontrolled, retrospective series, however, with prolonged follow-up over periods ranging from 5 to 8 years, have failed to...

Thyroid Stimulating Hormone Suppressive Treatment of the Multinodular Goiter

There is considerable debate about the efficacy of levothyroxine suppressive treatment of the nonendemic, nontoxic multinodular goiter, and the results are even less satisfying in many cases than those for solitary nodular disease because of the greater amount of pathologic thyroid tissue that is likely to be hormonally insensitive, the variability of TSH dependence given the likelihood of multiple other thyroid growth factors, and the difficulty in objectively evaluating the response of dominant nodules. This should be coupled with the fact that up to 10 of dominant masses within multinodular goiters may actually spontaneously regress during follow-up.119 A randomized study of 115 patients showed a total reduction in thyroid volume of more than 13 (by ultrasonographic measurement) in 58 of patients receiving TSH suppressive doses of levothyroxine for an average of 9 months. The thyroid volume was also shown to increase on cessation of levothyroxine therapy.9 No clear response...

Thyroid Hormone Treatment

There are three thyroid hormone preparations l-thyroxine (T4), T3, and combined T4 and T3 (desiccated thyroid Thyrolar ). Synthetic levothyroxine (l-T4) is used most often and has distinct advantages long half-life of 7 days and efficient conversion to T3. Thus, this medication is given once a day, and missing a dose for 1 to 2 days is not harmful. l-T4 also generates T3 in the liver, the kidney, the brain and other tissues, providing tissue T3. The dose of l-T4 of 1.7 Jig kg (0.075 to 0.15 mg day) should normalize the serum TSH level in most patients with hypothyroidism.70 The daily requirement of T4 is 100 to 150 fig for adults, 50 to 100 Xg for children, and 50 Xg for infants. These are commonly used doses the dose may need to be adjusted for some patients depending on body weight and severity of hypothyroidism. Patients with myocardial ischemia or cardiac arrhythmia, such as atrial fibrillation, should be treated using a small starting dose of thyroxine (0.0125 to 0.025 mg once a...

Screening for Thyroid Disease

Screening for asymptomatic thyroid disease is controversial, although screening in specific populations may be beneficial. Women over age 50 have the highest incidence of spontaneous hypothyroidism compared with all males and mixed younger populations, approaching 5 per year. Thus, screening has a good chance of finding disease early. However, the evidence supporting benefit from early intervention is weak and probably does not justify cost. Patients who present with paroxysmal atrial fibrillation should be routinely screened for hyperthyroidism, although the incidence of positive findings is low (AACE, 2002). One area where screening is advantageous is patients with newly diagnosed dementia. This is especially true if the clinical course is atypical or accelerated. Both hypothyroidism (myxedema) and hyperthyroidism (apathetic thyrotoxicosis) can present with dementia-like symptoms, and in these patients, timely intervention can completely reverse the signs and symptoms of dementia or...

Other Forms of Hypothyroidism

Depending on the degree of injury to the thyroid gland, thyroiditis (postpartum, sporadic, and subacute) can result in a transient hypothyroid state, with eventual recovery. Subacute thyroiditis is more likely to undergo this process, with insufficient T4 production for 3 to 6 months. Treatment is usually unnecessary, but low-dose thyroxine replacement can be used on a temporary basis for patients who become symptomatic.

Circulating Thyroid Hormones

Biosynthesis of thyroid hormone is unique among endocrine glands because final assembly occurs extracellularly in the fol-licular lumen. The source of thyroid hormones (T4 and triiodothyronine, or T3) is thyroglobulin (Tg), an iodoprotein produced by thyroid follicular cells. Thyroglobulin is the major portion of intraluminal colloid and is the most important protein of the thyroid gland (Kopp, 2005). Thyroglobu-lin provides a matrix for the synthesis of thyroid hormones and a vehicle for subsequent storage. Stored thyroglobulin is oxidized by thyroid peroxidase (TPO), adding an iodine molecule to tyrosine to form monoiodotyrosine (MIT) and diio-dotyrosine (DIT). MIT and DIT are then assembled into the final products, tetraiodothyronine (T4) and triiodothyronine (T3), which are stored in the follicular colloid for future use. When stimulated by serum thyrotropin (sTSH), thyroglobulin within the colloidal space is internalized by thyroid cells and enzymatically degraded to release T4...

Congenital Hypothyroidism

The hypothalamic-pituitary-thyroid axis is active by midgestation and mature by birth. Prior to midges-tation, fetal development relies on maternal thyroid hormones (Greenspan and Gardner 2004). Congenital hypothyroidism occurs in approximately 1 of 4,000 live births and is usually due to thyroid dysgenesis or deficits in thyroid hormone production. Congenital hypothyroidism is one of the most common causes of mental retardation however, because maternal thyroid hormones transfer across the placenta, early diagnosis and treatment with L-thyrox-ine can result in normal cognitive development of affected children (New England Congenital Hypothyroidism Collaborative 1990). Maternal hypothy-roidism alone, or in conjunction with fetal hypothy-roidism, leads to cognitive impairment in children despite postnatal therapy. This observation illustrates the importance of thyroid hormone exposure during early fetal development for subsequent cognitive function (Haddow et al. 1999 Morreale de...

Causes of Hypothyroidism

Of patients with autoimmune thyroiditis have circulating anti-TPOAbs. The autoim mune inflammatory response results in a lymphocytic infiltration of the thyroid gland and its eventual destruction. Iatrogenic hypothyroidism can follow thyroid irradiation or surgery and excessive doses of antithyroid drugs. Several drugs can cause hypothyroidism, including iodine-containing drugs such as amiodarone and iodinated radiocontrast media, lithium, in-terferon-a, sunitinib, -aminosalicylic acid, ethionamide, sulfonylureas, valproic acid, and aminoglutethimide.13 Iodine deficiency is a common worldwide cause of hypothyroidism, including congenital hypothyroidism in newborns. Patients with hypo-thalamic or pituitary disease often have other signs of piuitary disease, such as hypo-gonadism, and the TSH level will be low.

Epidemiology of thyroid disease

A number of studies have assessed the epidemiology of thyroid hormone abnormalities. The 1999 to 2002 National Health and Nutrition Examination Survey (NHANES)1 reported the prevalence of thyroid hormone disorders in 4,392 people 12 years of age and over in a sample representing the geographic and ethnic distribution of the U.S. population. Hypothyroidism was found in 3.7 (3.4 mild) and hyperthyroidism in 0.5 of the sample. The prevalence of hypothyroidism was higher in also had a higher prevalence of hypothyroidism. The Colorado Thyroid Health Sur-2 vey assessed thyroid function in 25,862 subjects attending a health fair. The overall prevalence of an abnormal TSH level was 11.7 of the study population, with 9.4 hypothyroid (9 subclinical) and 2.2 hyperthyroid (2.1 subclinical). Of the 916 subjects taking thyroid medication, 60 were euthyroid, with an equal distribution between subclinical hypothyroidism and hyperthyroidism. The NHANES study also found that many patients receiving...

Spectrum of thyroid disease

There are two general modes of presentation for thyroid disorders changes in the size or shape of the gland and changes in secretion of hormone from the gland. In some cases, structural changes can result in changes in hormone secretion. Thyroid nodules and goiters in euthyroid patients are common problems. Patients with a goiter who are biochemically euthyroid often require no specific pharmacotherapy, unless the goiter is due to iodine deficiency. In developing countries, iodized salt is the primary therapy in treating goiter. Thyroid nodules, seen in 4 to 7 of adults, may be malignant or may autonomously secrete thyroid hormones. A discussion of thyroid nodules is beyond the scope of this chapter however, thyroid cancer will be discussed briefly in the context of levothyroxine (LT4) suppressive therapy. Refer to other resources for a more extensive review of thyroid cancer management. Changes in hormone secretion can result in hormone deficiency or excess. While patients with overt...

Laboratory Testing for Detection of Hypothyroidism

The diagnosis of hypothyroidism is now focused on a single or most cost-effective test. A single TSH test was advocated for screening of thyroid dysfunction in 1993.62 Serum TSH measurements use highly sensitive second- and third-generation assays, based on lower limits of detection of 0.1 and 0.01 (xU mL, respectively. The TSH test accurately measures thyroid function and helps provide accurate thyroid hormone treatment. The limitation of the single TSH test is missing central hypothyroidism, since serum TSH concentrations in most patients with central hypothyroidism are normal.63 In addition, some patients have elevated serum TSH concentrations (immunologically active and biologically inactive TSH) despite the presence of central hypothyroidism.63 Using serum free thyroxine (FT4) alone as a diagnostic test of hypothyroidism detects hypothyroidism and monitors rapidly changing function better, but it cannot detect subclinical hypothyroidism. Also, low FT4 alone is not sufficient to...

Iodide Induced Hypothyroidism

Hypothyroidism caused by excessive iodine intake has also been observed in patients having the following conditions or underlying diseases history of postpartum thyroiditis, after a previous episode of subacute thyroiditis, and recombinant INF-a treatment.55 The hypothyroidism is transient, and thyroid function returns to normal 2 to 3 weeks after iodide withdrawal however, long-term follow-up is needed for these patients because some subsequently develop permanent primary hypothyroidism.55

Hypothyroidism Caused by External Radiation to the Neck

External radiation to the neck is known to cause thyroid disorders, including hypothyroidism.47 Radiation doses of 4500 cGy or more cause hypothyroidism by 20 years in approximately 50 of patients of all ages,48 and more cases occur thereafter. The effect of radiation therapy on the development of hypothyroidism is dose and duration dependent. The higher the dose and the longer the observation period, the higher the incidence of hypothyroidism. The timing of development of hypothyroidism after the initial radiation therapy can be 4 months to years, depending on the dose and duration received.49 Ionized radiation releases reactive oxygen species from the water molecule.50 This appears to be the mechanism of radiation-induced hypothyroidism. In addition to hypothyroidism, radiation therapy to the neck also predisposes to hyperthyroidism, thyroid cancer, Hashimoto's thyroiditis, and benign thyroid nodules.48 49 Lifelong observation is needed in patients who received external radiation...

Hypothyroidism Caused by Iodine Therapy

Radioactive iodine (13'I) is one of the common methods of treating patients with Graves' disease. This treatment leads to the development of hypothyroidism in most patients. The dose of 131I administered affects the onset of hypothyroidism. Of patients who receive 370 MBq (10 mCi) or more (> 5.55 MBq g of thyroid tissue), about 50 of patients become hypothyroid 1 year after treatment and about 70 of patients are hypothyroid 10 years after treatment.4445 Euthyroidism can initially be attained by treatment with a low dose of radioactive iodine (1.48 to 2.59 MBq g of thyroid tissue delivered) however, most patients subsequently develop hypothyroidism by 10 years or later.46

Thyroid Stimulating Hormone Suppression and Miscellaneous Benign Goiters

In both benign and malignant nodules of the thyroid as well as an increase in parathyroid adenomas.159162 Controversy exists in regard to the optimal management of patients both with and without palpable thyroid nodules who have been exposed to low-dose irradiation to the thyroid area. Evidence suggests that thyroid suppressive therapy is as likely to be successful in this group of patients as in those with sporadic multinodular goiter, but the main difficulty seems to be in the delineation of underlying malignancy.95 163'164 Shimaoka and coworkers163 were the first to conduct a double-blind study of suppressive treatment using T3, desiccated thyroid, or both, in irradiated patients with measurable thyroid nodules. In 1500 patients exposed with a 34 incidence of nodules and an average interval between radiation exposure and nodule detection of 27 years, TSH suppression of nodules was possible in 18 of patients over 6 months of therapy. This approach was uncontrolled, however, and made...

Parathyroid Hormones And Calcium Homeostasis

Humans have four parathyroid glands, two on each side of the neck. The glands have a variable position in the neck and may even be found in the mediastinum. In common with all endocrine glands, they are richly vascularized with fenestrated capillaries. They derive their blood supply from the inferior thyroid arteries. There are two cell types in the parathyroid glands chief cells have prominent endoplasmic reticulum, Golgi apparatus and numerous secretory vesicles oxyphil cells are rich in mitochondria and oxyphilic granules. Chief cells are thought to be responsible for the synthesis and secretion of parathyroid hormone (PTH), while oxyphil cells are thought to be degenerated chief cells. The parafollicular cells (or clear C cells) of the thyroid gland produce calcitonin. It is a linear polypeptide of 34 amino acids with molecular weight 3500 Da. Calcitonin acts via a G-protein-linked receptor in the bones and kidneys. It inhibits bone resorption and causes an increase in calcium...

Thyroid hormone physiology and biosynthesis

The thyroid gland is the largest endocrine gland in the body, residing in the neck, anterior to the trachea, between the cricoid cartilage and the suprasternal notch. The thyroid gland produces two biologically active hormones, thyroxine (T4) and triiodo- thyronine (T4). Thyroid hormones are essential for proper fetal growth and development, particularly of the CNS. After delivery, the primary role of thyroid hormone is in the regulation of energy metabolism. These hormones can affect the function of virtually every organ in the body. The parafollicular C cells of the thyroid gland produce calcitonin. The function of calcitonin and its therapeutic use are discussed in other chapters in this book. T4 and T3 are produced by the organification (binding of iodine to tyrosine residues of thyroglobulin) of iodine in the thyroid gland. Iodine is actively transported into the thyroid follicular cells. This inorganic iodine is oxidized by thyroid peroxidase and covalently bound to tyrosine...

Subclinical Hyperthyroidism

Graves' disease is an autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, exophthalmos and other eye findings, and skin findings. The prevalence of Graves' disease in the United States is approximately 0.4 in women and 0.1 in men. The peak age of incidence is 20 to 49 years, with a second peak after 80 years of age. Hyperthyroidism results from the production of TSHR-SAbs in at least 80 of patients with clinical Graves' disease. These antibodies have TSH agonist activity, thereby stimulating hormone synthesis and release. These antibodies cross-react with orbital and fibroblastic tissue, resulting in ophthalmopathy and dermopathy. While the underlying cause of Graves' disease is not known, heredity seems to play a role. Subclinical Graves' disease may become acutely overt in the presence of iodine excess, infection, stress, parturition, smoking, and lithium and cy-tokine therapy. Dermopathy occurs in 5 to 10 of patients with Graves' disease and usually is...

Primary hyperthyroidism

Graves' disease Toxic multinodular goiter Toxic adenoma Thyroid cancer Struma ovarii Subacute thyroiditis Silent (painless) thyroiditis Excess thyroid hormone intake (thyrotoxicosis factitia) Drug-induced (amiodarone, iodine, lithium, interferons) hCG, human chorionic gonadotropin TSH, thyroid-stimulating hormone. From Refs. 36-38.

Nonthyroidal illness euthyroid sick syndrome

A number of changes in the hypothalamic-pituitary-thyroid axis occur during acute illness.46,47 These changes are termed nonthyroidal illness or euthyroid sick syndrome. The type and degree of abnormalities depend on the severity of illness. Mild to moderate medical illness, surgery, or starvation causes a decrease in serum T3 levels owing to decreased peripheral conversion of T4 to T3. The reduced T3 levels do not correlate with ultimate mortality and are thought to be an adaptive response to stress. Patients with more severe illness, especially those in the intensive-care unit, frequently have reduced total T4 levels, although FT4 levels usually are normal. In the critically ill, there is a correlation between the degree of serum T4 reduction and mortality. In most acutely ill patients who are euthyroid, the TSH level is normal. However, administration of dopamine, octreotide, or high doses of glucocorticoids can reduce TSH levels. During recovery from acute illness, the TSH level...

Causes of Thyrotoxicosis Hyperthyroidism

Thyrotoxicosis is any syndrome caused by excess thyroid hormone. Hyperthyroidism is related to excess thyroid hormone secreted by the thyroid gland. Thyrotoxicosis can be related to the presence or absence of excess hormone production (hyperthyroid-ism). The common causes of thyrotoxicosis are shown in Table 44-6 ' disease is the most common cause of hyperthyroidism. Thyrotoxicosis in the elderly is more likely due to toxic thyroid nodules or multinodular goiter than to Graves' disease. Excessive intake of thyroid hormone may be due to overtreatment with prescribed therapy. Surreptitious use of thyroid hormones also may occur, especially in health professionals or as a self-remedy for obesity. Thyroid hormones can be obtained easily without a prescription from health food stores or Internet sources. Refer to Clinical Presentation and Diagnosis of Hyperthyroidism for information regarding screening and diagnosis.

Unusual Thyroid Cancers

Unusual thyroid cancers, including the intermediately differentiated carcinomas, account for only 10 to 15 of all primary thyroid neoplasms (Table 19-1). This unique group of neoplasms behaves differently than the more common type the well-differentiated thyroid cancers (WDTCs). They therefore present a challenge to both the surgeon and the endocrinologist-oncologist. Most of these cancers behave in an aggressive fashion and, at times, present as a medical emergency. Multimodality therapy is the mainstay of treatment for these tumors. As a result, it is important for the endocrine surgeon to have a clear understanding of the nature of these tumors and recognize when surgery is indicated. Primary extramedullar plasmacytomas are rare forms of plasma cell tumors. Solitary extramedullar plasmacytomas may develop in any organ, but they occur predominantly in the upper respiratory tract.14 The thyroid gland is one of the rarer sites approximately 50 cases of solitary lesions have been...

Troubleshooting for a Missing Parathyroid Gland

Three normal parathyroid glands have been identified but the (right) upper parathyroid gland cannot be localized (Fig. 47-5). In this circumstance, the space dorsal to the thyroid gland and the esophagotracheal groove should be explored. The space between the esophagus and the vertebrae should be opened. Digital palpation for the parathyroid tumor can be helpful. Situation 2. Three normal parathyroids have been identified, but the (right) lower gland is absent at the lower pole of the thyroid and in the thyrothymic ligament (Fig. 47-6). The thymus on the side of the missing lower parathyroid should be exposed. The thymus is lighter in color and smoother than the surrounding fat. The retrosternal part of the thymus can be mobilized by applying light tension on the thyrothymic ligament while freeing the thymus by delicate blunt dissection with a peanut sponge.66 As the extraction of the thymus When the parathyroid tumor has not been found after performing the steps...

Treatment of High Risk Papillary Thyroid Carcinoma

Patients with high-risk papillary thyroid carcinomas may have local extrathyroid invasion and distant metastases. The cancer-related mortality rate is about 40 at 20 years after surgery.16 The main causes of death are either locally progressive cervical disease or distant metastases. Most experts from the United States and from European countries advocate total thyroidectomy followed by 131I whole-body scan and ablation with TSH suppression therapy more for high-risk than for low-risk patients.12,16,41,52,58 If the cancer invades into the adjacent structures and it is not possible to resect the tumor with negative margins, radioiodine treatment should be given. When there is no or inadequate uptake or progression of disease, external irradiation is used.20,52 Older patients with high-risk papillary thyroid carcinoma appear to be much less sensitive to both TSH suppression therapy and radioactive iodine therapy than younger patients with low-risk cancers. We, therefore, believe that...

Thyroid Stimulating Hormone Suppression and the Solitary Thyroid Nodule

Studies in this area are confusing in that they include a heterogeneous collection of goiters (such as nodules with functional autonomy or cystic degeneration), are frequently uncontrolled and poorly randomized, fail to establish compliance or consistent TSH suppression, and do not objectively evaluate nodule size and treatment response. Inclusion in a suppressive treatment arm relies on the absolute ability to distinguish a benign from a malignant nodule largely on the basis of accurate fine-needle aspiration cytology.8286 TSH suppressive therapy is of unproven benefit in the solitary nodule. The reported incidence of reduction in thyroid nodule size varies from 9 to 68 ,87,88 although disappearance of the nodule is rare. Several controlled, randomized, double-blind trials have failed to show significant reduction in nodular size on the basis of volumetric calculation by high-resolution ultrasonography, although most studies have shown a marked reduction in contralateral thyroid...

Thyroid Surgery for Nodular Disease

Thyroid and other endocrine surgery requires a multidiscipli-nary team approach with, in particular, an anesthesiologist and surgeon both skilled in this particular field. At open operation, the ipsilateral side is initially examined together with the nodule, its characteristics are assessed, and any lymphadenopathy is noted. The contralateral lobe is palpated through the strap muscles to determine whether any nodularity is present that may not have been clinically evident. Solitary Thyroid Nodule Thyroiditis FIGURE 9-8. Scheme of management for solitary thyroid nodule. FNAC fine-needle aspiration cytology. (Adapted from Farndon JR. Endocrine Surgery A Companion to Specialist Surgical Practice, 2nd ed. Philadelphia, WB Saunders, 2001.) If the nodule is truly unilateral, a total thyroid lobectomy (removing isthmus and pyramidal lobe en bloc) is indicated, preserving both parathyroid glands, the external branch of superior laryngeal nerve, and the recurrent laryngeal nerve. This...

Thyroid Hormone Regulation

Thyroid hormone production and release are under the control of the hypothalamic-pituitary-thyroid axis (Fig. 1-5), acting in a negative-feedback cycle. TSH is the major regulator of thyroid gland activity. Increased levels of TSH lead to hypertrophy and increased vascularity of the gland, whereas decreased levels of TSH lead to gland atrophy. A glycoprotein secreted by the anterior pituitary, TSH is composed of an a subunit and a p subunit. The a subunit is common to a family of glycoprotein hormones, including FIGURE 1-5. Negative-feedback regulation of thyroid hormone production. TRH thyrotropin-releasing hormone TSH thyroid-stimulating hormone T3 triiodothyronine T4 thyroxine. Thyroid FIGURE 1-5. Negative-feedback regulation of thyroid hormone production. TRH thyrotropin-releasing hormone TSH thyroid-stimulating hormone T3 triiodothyronine T4 thyroxine. TSH binds to a specific receptor on the surface of the thyroid cell. The TSH receptor is a G protein-coupled receptor. After...

Thyroid Growth Regulating Factors

TSH has traditionally been considered the major stimulator of the thyroid function.4 TSH is a heterodimeric glycoprotein consisting of noncovalently associated a and P chains and has a total molecular weight of about 28 kd. Thyroid follicle cells are stimulated by TSH binding to specific cell surface receptor proteins, the TSH receptor (TSH-R). Activation of the TSH-R results in an increase in the intracellular level of cAMP as the major intracellular second messenger for most of the TSH effects.4 However, TSH through the TSH-R has also been demonstrated to increase the PI turnover as a second messenger system for the action of TSH. The amount of TSH needed for stimulation of the PI pathway is 5- to 10-fold greater than that needed for TSH activation of AC.5 The general concept of TSH as a trophic pituitary hormone regulating both function and growth of the thyroid has been questioned. The positive effect on the functional activity is undisputed however, the stimulatory effect of TSH...

Thyroid Growth Inhibiting Factors

The TGF-P family consists of three members (TGF (51 to (53), and three different TGF-(5 receptors (TGF-(3-R I to III) have been identified. Normal and diseased thyroid tissues express and produce TGF-P protein (TGF-P l).63 The expression of TGF-P 1 mRNA was increased in the hyperplastic thyroids of goitrogen-treated rats64 as well as after iodide administration to thyrocytes in vitro.65 Addition of TGF-P 1 to thyroid follicle cells has been shown to result in growth inhibition.66 Grubeck-Loebenstein and colleagues63 suggested that TGF-p has a role in goiter formation because lower production of TGF-P was observed in thyroid follicle cells from patients with nontoxic goiter than in normal follicle cells.

Thyroid Embryology and Developmental Abnormalities

The thyroid gland has a double origin from the primitive pharynx and the neural crest. The main body of the thyroid gland is derived from epithelial cells of the endoderm of the primitive pharynx. These cells will form the greater portion of the follicular elements of the thyroid tissue. They arise as a diverticulum from the midline of the pharyngeal floor. It soon develops as a bilobed, encapsulated structure that descends in the midline of the neck. With further development, this diverticulum remains attached to the buccal cavity by a narrow tract the thyroglossal duct. Its distal end may become the pyramidal lobe. The neural crest is the source of the parafollicular cells, or C cells, which secrete calcitonin.12 These C cells migrate from the neural crest of the ultimobranchial bodies of the fourth branchial pouch (PIV) and the fifth branchial pouch. The incorporation of the fifth pouch with the P IV leads to the formation of the caudal-pharyngeal complex, which includes not only...

Thyroid Embryogenesis

Thyroid primordial cells develop from pharyngeal ectoderm, forming a visible medial anlage by human gestational days 16 to 17.' The thyroid diverticulum then migrates caudally to reach its final position in the thyroid primordial body anterior to the cricoid cartilage (Fig. 1-1). Subsequently, these cells begin to express markers of mature thyrocyte differentiation, including proteins that are intrinsic to thyroid secretory function (thyroglobulin, thyroperoxidase, and the sodium-iodide symporter NIS ), and the thyroid-stimulating hormone (TSH) receptor that controls both thyroid growth and secretory function. The foramen caecum, at the junction between the anterior two thirds and posterior third of the tongue base, remains as an embryologic reminder of thyroid origin. Thyrocytes form thyroid follicles, while intervening cells derived from the ultimobranchial body within the fourth pharyngeal pouch develop into calcitonin-secreting C cells (see Fig. 1-1). The parathyroid glands...

The Accurately Performed Thyroidectomy A Challenge with a Bad Response

Thyroid surgery has been and always will be the most common endocrine surgical operation. Some subspecialists in endocrine surgery are performing only thyroid and parathyroid operations. Even in specialized centers in which the rarer endocrine tumors (adrenal and gastrointestinal) constitute an appreciable part of the workload, thyroid gland operations are still the most common procedures. An accurately performed operation on the thyroid gland requires both experience and technical ability. In my experience, including more than 20 years of highly specialized endocrine surgery in a large university hospital, a good thyroid operation presents a greater challenge and requires more technical precision and skill than an adrenalectomy or removal of any gastrointestinal endocrine tumor. Many other experienced endocrine surgeons are of the same opinion. The thyroid operation is considered by many to be at the zenith of endocrine surgery the surgeon who can perform a good thyroidectomy can,...

Surgical Strategy in Patients with Primary Hyperparathyroidism

No routine localization study is necessary before the initial neck exploration for patients with primary hyperparathyroidism.29,30 A small, low cervical incision along the skin crease is made. The strap muscles are dissected and separated but are not divided. The surgical plane of dissection is different for parathyroidectomy and thyroidectomy. For thyroidectomy, I dissect as close to the thyroid gland as possible, taking individual branches of the thyroid vessels on the thyroid gland and leaving the parathyroid glands lateroposteriorly in the surrounding tissue to preserve vascularity when the thyroid gland is removed. For parathyroidectomy, I dissect more laterally along the carotid sheath, leaving the parathyroids on the posterior surface of the thyroid gland, thus making them easier to find. Both sides of the neck are explored, and all four glands are tentatively identified before any gland is resected. I rarely perform mediastinotomy during initial operation unless the patient is...

Surgery for Thyroid Disease

In the foregoing chapters, the indications for thyroid surgery for different pathologic entities have been discussed. Naturally, benefits of surgical therapy must outweigh the risks involved, About 1 in 10 solitary thyroid nodules is malignant.3 Therefore, a selective approach must be used to determine who will benefit from thyroidectomy and who can be safely observed. The same applies to the extent of thyroid surgery (e.g., total vs. subtotal thyroidectomy) or of surgery for lymph node metastases (node picking or radical neck dissection).

Results of Unilateral Parathyroidectomy Original Approach

When patients are considered for unilateral parathyroidectomy, it is important to exclude familial HPT because these patients usually have multiple abnormal parathyroid glands. Patients who had previous operations in their neck for either parathyroid disease or thyroid disease are not candidates for unilateral parathyroidectomy because the functional parathyroid reserve cannot be evaluated.

Relation between the Parathyroid Glands and the Recurrent Laryngeal Nerve

Emphasis has been placed on the relationship of the parathyroid glands and the recurrent laryngeal nerve. A predictable relation of both the superior and inferior parathyroid glands to the recurrent laryngeal nerve is noted within a rectangular area that can be imagined visually when the lobe of the thyroid is rotated medially. The superior boundary of this rectangle is the most cephalad portion of the thyroid lobe the inferior boundary is a point on the trachea 4 cm below the inferior pole of the thyroid gland posteriorly, the esophagus and anteriorly, the surface of the thyroid lobe and trachea. The usual course of the recurrent laryngeal nerve should divide this rectangle into two triangles, one lying ventral and the other dorsal to the nerve. After analyzing 100 autopsy specimens, Pyrtek and Painter13 found that 93

Recommendations for the Use of Thyroxine in the Solitary Thyroid Nodule

These nodules ideally should be associated with a normal thyroid profile and negative thyroglobulin and thyroid peroxidase autoantibody status. Patients with a large nodule, particularly if it possesses echogenic heterogeneity or has been present for longer than 2 years, or in whom there is a history of head and neck irradiation, should not be treated in this manner. One may aim for a TSH suppression level of 0.05 to 0.10 mU L in premenopausal patients without cardiac risk factors and for a level of 0.1 to 0.3 mU L in postmenopausal women, particularly those with a known history of osteoporosis, and in men older than 65 years with a recognized cardiac history. Treatment is continued for 6 months to 1 year with clinical and ultrasonographically calculated nodular volume based on anteroposterior length and width, assuming the nodule to be a spherical ellipsoid. This is complemented by assessment of the contralateral thyroid lobar volume to gauge response to suppression.102...

Predictors of Thyroid Tumor Aggressiveness

The antecedents of attempts to predict thyroid cancer behavior date back to the 1930s, when the concept of lateral aberrant thyroid12 was established, because thyroid tissue appearing in lymph nodes in the neck was known to be associated with an innocent clinical behavior pattern in a vast majority of cases. As a result, these cases were considered to be not cancer but an arrested embryonic migration phenomenon, until Crile convincingly demonstrated small primary papillary cancers in such cases.3 That was also an era when 15 to 20 of all thyroid cancers were of an anaplastic variety that was almost uniformly and rapidly fatal4 median survival associated with anaplastic cancers was only 3 or 4 months, and all but a few patients were dead within 6 months. This wide range of clinical behavior from cancers arising from the same thyroid follicular cell was noteworthy, even then, in displaying the extremes of tumor biologic behavior. Currently, of course, we have several well worked-out and...

Peripheral Transport and Metabolism of Thyroid Hormones

More than 99 of circulating thyroid hormones are bound to serum proteins, including thyroxine-binding globulin (TBG), transthyretin, and albumin.27 TBG is a glycoprotein that contains only one binding site per molecule. TBG is responsible for the transport of more than three fourths of thyroid hormone in the blood, and its levels are significantly increased by elevated levels of estrogens, as occurs in pregnancy. Dissociation of the free hormone from its binding proteins is rapid and efficient. Thyroid hormones are lipophilic and are capable of passive diffusion into cells, although specific transporters may also regulate intracellular thyroid hormone content.28 T3 synthesized directly by the thyroid forms a relatively small proportion of the effective T3 concentration in tissues, which is mainly derived from peripheral deiodination of T4. This reaction is catalyzed by two deiodinases with characteristic tissue distributions. Type I deiodinase (5'DI) is predominant in liver, kidney,...

Peripheral Action of Thyroid Hormones

The major effects of thyroid hormone action occur through the intranuclear action of T3, with T4 being largely a prohormone.29 It remains controversial as to whether T4 might also regulate non-nuclear biologic responses in some contexts, for instance, the activation of certain mitochondrial or cellmembrane enzymes.29 In the 1960s, Tata and associates observed that T3 treatment resulted in the rapid synthesis of nuclear RNA, which preceded increases in protein synthesis and mitochondrial oxygen consumption.30 Subsequently, subcellular fractionation demonstrated specific nuclear binding sites for T3 and identified the anterior pituitary, liver, brain, and heart as having high binding capacity for T3.31 Thus, the current concept of thyroid hormone action is that its nuclear receptor binds to specific regulatory regions in target genes and regulates gene transcription in response to T3.32-34 Thyroid hormone receptors (TRs) are members of the steroid hormone receptor superfamily. There are...

Pathology of Tumors of the Thyroid Gland

Tumors of the thyroid gland can be problems for endocrinologists, surgeons, and pathologists. Carcinomas of the thyroid gland range from the innocuous occult papillary carcinoma to the extremely lethal anaplastic form. Approximately 12,000 new cases of thyroid cancers are discovered each year in the United States however, fewer than 1 of deaths caused by cancers are due to thyroid cancers.1 Because only 9 of patients affected by the disease die from it, malignant tumors of the thyroid gland are not a significant public health problem. The treatment of carcinoma of the thyroid gland continues to engender controversy. The extent of thyroidectomy in the treatment of papillary and follicular carcinomas is controversial. The role of radioactive iodine in the postoperative treatment of patients is still debated, and histologic criteria for the pathologic diagnoses of certain thyroid tumors are uncertain. This chapter concentrates on the epithelial tumors of the thyroid gland. The discussion...

Parathyroid Embryology and Developmental Abnormalities

At the 13- to 14-mm stage, the P HI and P IV migrate together with the thymus and ultimobranchial bodies, respectively. The P III-thymus complex separates from the pharyngeal wall and moves toward the caudal and medial regions. Because of the extension of the cervical spine and the descent of the heart and great vessels, the thymus and the P III are drawn toward the superior mediastinum. At the 20-mm stage, the cephalic regression of the thymus brings about its separation from the P III, which are thus abandoned at the level of the anterior or posterolateral region of the inferior poles of the thyroid lobes or at the level of thyrothymic ligaments, vestigial structures indicative of their former connections. This embryologic migration results in an extensive area of dispersal of the normal P III. In 61 of cases, they are situated at the level of the inferior poles of the thyroid lobes on the posterior, lateral, or anterior aspects. In 26 of cases, they are situated in the thyrothymic...

Papillary Thyroid Carcinoma

DNA copy number changes are uncommon in papillary thyroid carcinomas as compared with other poorly differentiated and well-differentiated thyroid carcinomas. Papillary thyroid carcinomas in CGH studies have variable rates of genetic aberrations and specific sites of aberrations. Nonetheless, several common aberrations have been identified, including gains on chromosomes lq, 5q, 6q 9q 13q, 19q, 21q, 4 and 7, and losses on chromosomes lp, 9q, 16q, 17, 19, and 22.911 Hemmer and associates10 found genetic aberrations in only 3 (12 ) of 26 papillary thyroid carcinomas and reported a positive correlation between the presence of aberrations and older age (> 70 years) and cervical lymph node metastasis. Singh and colleagues11 identified genetic aberrations in 10 (48 ) of 21 papillary thyroid carcinoma cases. They reported that the loss of chromosome 22 was found only in younger patients (< 45 years) and was associated TABLE 36-1. Comparison of Chromosomal Aberrations In Six...

Medullary Thyroid Carcinoma

Apart from the RET protooncogene (RET) point mutation of chromosome 10, no other genes have been found to be involved in the original growth of medullary thyroid carcinomas. Germline RET mutations have been identified in about 98 of patients with familial medullary thyroid carcinoma, and somatic RET mutations have been frequently detected in sporadic medullary thyroid carcinomas.51 In sporadic medullary thyroid carcinomas, the RET gene is mutated in codon 918, where a methionine is substituted to a threonine (M918T). Chromosomal aberrations have been detected by CGH in approximately 50 to 60 of the patients with medullary thyroid carcinoma.10 51 The number of chromosomal aberrations in medullary thyroid carcinoma appears to be lower than in other thyroid carcinomas that arise from thyroid follicular cells.10 Frisk and coworkers51 reported that chromosomal regions 19q, 19p, 13q, and llq may be involved in medullary thyroid carcinogenesis but that medullary thyroid carcinoma is a...

Lymphatic Drainage of the Thyroid

The thyroid has an extensive lymphatic drainage, which may flow in a variety of directions.2-3 Thyroid follicles are enveloped with lymphatic vessels. The intraglandular lymphatic connections are extensive and enable lymphatic drainage from one lobe to the other through a complex of intrathyroidal and pericapsular nodes.4 The major lymph vessels running efferently follow the branches of the thyroid arteries and veins in three main directions superiorly, laterally, and inferiorly. The upper region of the thyroid is drained along the superior thyroid vessels to the upper jugular lymph nodes. From the isthmus, the lymph vessels run to the prelaryngeal, or Delphian, nodes, which are connected to the upper jugular nodes. Lateral lymph vessels follow the medial thyroid vein to the mid- and lower jugular nodes. The lower lymphatic drainage is to the pretracheal and para-tracheal nodes and the lower jugular chain. Connections to the anterior mediastinal nodes and retropharyngeal nodes are...

Hypoparathyroidism Postsurgical

Surgical destruction of the parathyroid glands is the most common cause of hypoparathyroidism. Hypoparathyroidism can occur after any surgical procedure that involves the anterior neck but is most commonly seen as a complication of parathyroid surgery or thyroid surgery, or after extensive resection for head and neck cancer. Trauma to the parathyroid vascular pedicles or inadvertent removal of the glands leads to either transient or permanent hypoparathyroidism. Estimates of the incidence of post-thyroidectomy hypoparathyroidism vary widely, ranging from 6.9 to 46 for transient and 0.4 to 33 ' for permanent hypoparathyroidism. A survey by the American College of Surgeons reported an incidence of hypoparathyroidism following total thyroidectomy of 8 .2 A multicenter prospective trial of 5846 patients undergoing total thyroidectomy revealed an incidence of transient hypoparathyroidism of 7.3 and permanent hypoparathyroidism of 1.5 .' Characteristics of the surgical procedure associated...

Hiirthle Cell Thyroid Tumor

Hurthle cell thyroid tumors comprise 1 to 5 of all thyroid neoplasms and have been classified as variants of follicular thyroid tumors. They differ from follicular thyroid carcinomas by their inability to trap radioiodine and by the accumulation of mitochondria and eosinophilic cytoplasm on histology. They are also more likely to be multifocal, have nodal metastasis, and appear to be clinically aggressive. Hiirthle cell carcinomas are similar to follicular thyroid carcinomas in that they usually cannot be diagnosed by fine-needle aspiration biopsy or frozen section. It is also difficult to distinguish Hiirthle cell adenomas from carcinomas preoperatively or intraoperatively. Some investigators previously recommended that all Hiirthle cell tumors should be considered as malignant and be treated aggressively because of their malignant potential.27-28 Others suggested that Hiirthle cell tumors are separated into adenomas (which have no capsular and vascular invasion) and carcinomas,...

Follicular Thyroid Tumor

Thyroid tumors of follicular cell origin serve as a good model for studying possible genetic events regarding tumor origin, transformation, and progression. Multiple genetic events appear to be responsible for the progression from adenoma to carcinoma in some tumors (see Fig. 36-1).1,2,22,23 Follicular adenomas have close cytologic and morphologic similarity to follicular carcinomas the defining difference is the presence of capsular invasion and or vascular invasion in carcinomas. Because of this similarity, it has been proposed that follicular carcinomas originate from preexisting adenomas. Follicular adenomas could represent premalignant tumors that could transform into carcinomas, through copy number changes in critical genes controlling invasion, angiogenesis, and metastasis. Clinical evidence that follicular carcinomas are obviously larger than follicular adenomas supports this theory.

Follicular Neoplasms of the Thyroid

In the normal thyroid gland, the basic functional unit is the follicle. Follicles are single-layer spheres of follicular cells surrounding a lake of viscous colloid that primarily stores thyroglobulin. Other cell types that are present in the thyroid gland are interposed between these follicular spheres. These cells include perifollicular cells, also called C cells, which secrete calcitonin, as well as some supportive fibrous tissue, vascular structures, and nerves. The most common tumors of the thyroid gland arise from the follicular cells, including both papillary tumors and follicular tumors. Papillary tumors are discussed elsewhere in this text however, follicular cancers are probably best described in the ways in which they differ from papillary tumors. Papillary tumors consist of single layers of thyroid cells arranged around vascular stocks, forming papulations. A substantial minority of papillary tumors (-40 ) also include laminated calcified spheres called psammoma bodies....

Familial Hyperparathyroidism

Although most cases of primary hyperparathyroidism (HPT) occur sporadically, familial clusters have been reported. Most of these familial cases occur in association with multiple endocrine neoplasia (MEN). Goldman and Smyth in 1936 were the first to report a patient with familial HPT who had no other manifestations of MEN.1 Many more familial cases have subsequently been reported.233 Similarly to the classification of medullary thyroid cancer, HPT can be classified into four types (1) sporadic HPT, (2) familial HPT with MEN 1 and 2, (3) non-MEN familial HPT (NMFH) or familial isolated HPT(FIH), and (4) non-MEN familial HPT associated with jaw tumor syndrome. Because NMFH is uncommon, these patients are frequently included in the series of patients with familial HPT with MEN, or they are confused with patients with benign familial hypocalciuric hypercalcemia (BFHH).7,34 From our experience at the University of California, San Francisco (UCSF) (Table 55-1) and from a review of the...

Etiology of Primary Hyperparathyroidism

Patients with multiple endocrine neoplasia (MEN) types 1 and 2A are more likely to have hyperparathyroidism, as are family members of patients with familial hyperparathyroidism. In the mouse, deletion of the MEN 1 tumor suppressor gene in the parathyroid gland results in parathyroid neoplasia and hypercalcemic hyperparathyroidism.9 Patients with Cowden's disease10 (breast cancer, thyroid neoplasm, and gastrointestinal polyps) and McCune-Albright syndrome11 (caused by activating mutations of the stimulating guanosine triphosphate-binding protein) are also at higher risk for developing primary hyperparathyroidism.

Embryology of Parathyroid Glands

The parathyroid glands develop from the third and fourth pharyngeal pouches.2 The upper parathyroid glands originate from the dorsal tips of pharyngeal pouch IV.3 The ventral portion of pharyngeal pouch IV consists of the ultimobranchial body, which is incorporated into the lateral part of the developing thyroid and eventually supplies the parafollicular or C cells. The common embryologic origin of the lateral part of the thyroid and the upper parathyroids accounts for the occasional intrathyroidal location of upper parathyroids, although this is a rare observation.4 The lower parathyroid glands arise from the dorsal part of pharyngeal pouch III. The thymus, which originates from the ventral part of pharyngeal pouch III, and the lower parathyroid gland descend as a complex in a plane ventrally to pharyngeal pouch IV. Therefore, the lower parathyroids are usually found in a more anterior position than the upper parathyroids. At the caudal descent, the lower parathyroid usually...

Embryology and Anatomy of Parathyroid Gland

Parathyroid glands arise from the fourth pharyngeal pouch.5 Because third pharyngeal pouch derivatives (i.e., the inferior parathyroid glands and thymus) migrate farther, these parathyroid glands are more likely to be in ectopic or aberrant positions than are the superior parathyroid glands. Despite this observation, about 80 of the inferior parathyroid glands are situated anterior to the recurrent laryngeal nerve on the lower (dorsal position) aspect of the thyroid gland, within 1 cm of where the inferior thyroid artery crosses the recurrent laryngeal nerve (Fig. 53-1). About 15 of lower parathyroid glands are found in the thymus or perithymic fat.6 Occasionally, parathyroid glands fail to descend. This results in an undescended parathymus.7

Childhood Thyroid Carcinoma

The nuclear accident at Chernobyl in 1986 refocused interest on radiation as a factor in the development of thyroid carcinoma.113122 Prior to 1950, irradiation was frequently used to treat acne, enlarged tonsils and adenoids, chronic sinusitis, and other benign conditions.115 External radiation was commonly used to irradiate enlarged thymuses in infants and young children. The latent period, the interval from exposure to the appearance of thyroid cancer, was assumed to be 10 years and increased for at least 3 decades. Childhood thyroid cancer appeared within 4 years after the Chernobyl accident. Thyroid carcinomas in children and adolescents are rare and differ from adult carcinomas of the thyroid gland in the The histologic categories for the thyroid tumors found in irradiated patients include113121 The results of investigations of thyroid cancers occurring after the Chernobyl accident led to the consideration of these questions concerning postradiation cancers in children Does the...

Arterial Blood Supply to the Parathyroids

The length of the artery is variable, usually between 8 and 12 mm. When long, the arteries are commonly tortuous when the pedicle is short, it holds the parathyroid hard against its vessel of origin. Generally, pedicles of the superior parathyroid are shorter than those of the inferior ones. Both the superior and inferior parathyroid glands most frequently borrow their blood supply from the inferior thyroid artery. In particular, superior parathyroid glands receive their arterial blood supply from this artery in approximately 80 of the cases. In 15 , the blood supply is provided by the superior thyroid artery, and in 5 , by anastomoses running between the two systems. When the superior thyroid artery supplies the superior parathyroid, the supply almost always comes from the posterior branch or from an artery arising from the posterior branch and destined for the esophagus or the larynx. In approximately 10 of the cases, inferior parathyroid glands are vascularized by the superior...

Anatomy of Parathyroid Glands

Eighty percent of the upper parathyroid glands are found at the cricothyroid junction, about 1 cm cranial to the intersection of the recurrent laryngeal nerve and the inferior thyroid artery (Fig. 47-1).6 The upper parathyroids, which are tucked posteriorly to the upper pole of the thyroid, are usually covered by a fascial sheath connecting the thyroid to the pharynx. More anteriorly situated upper parathyroids are located on the surface of the thyroid, frequently underneath the capsule of the thyroid. The unique feature of these subcapsular parathyroids is the freedom of movement of the parathyroids within the capsule. This feature distinguishes parathyroids from thyroid nodules, which cannot move freely. The occurrence of intrathyroidal parathyroids is rare and controversial. A subcapsular parathyroid is easily confused with a true intrathyroidal parathyroid, which is surrounded by thyroid tissue. Akerstrom and colleagues noted true upper intrathyroidal parathyroid glands in three...

Differentiated Thyroid Cancers

The two primary types of differentiated thyroid cancers are papillary and follicular. Several variants exist and include a follicular variant of papillary carcinoma, a tall cell variant of papillary carcinoma and a Hurthle cell carcinoma which is a variant of follicular carcinoma. The latter two subtypes are more ominous lesions. Primary surgery is the initial treatment approach. The surgical therapeutic decisions are based on prognostic variables. At Memorial Sloan-Kettering Cancer Center, those patients who are felt to be at high risk are assessed based on GAMES, for example (1) Grade high, (2) Age > 45 years, (3) Metastasis positive, (4) Extracapsular extension positive, (5) Size > 4 cm.89 The patients at low risk do well irrespective of the extent of surgery. The surgical goal is to remove all gross disease that is clinically detectable. The different operations represent the variations in the volume of the thyroid gland that is resected and include partial thyroidectomy and...

NonMEN Familial Hyperparathyroidism and Parathyroid Cancer

In some patients with NMFH and parathyroid cancer, one or more of the other parathyroid glands were also abnormal.21,35,43 This occurrence raises the possibility of the transformation of benign parathyroid neoplasms to parathyroid cancer similar to the transformation of C-cell hyperplasia to medullary thyroid carcinoma. In most studies, however, there is no evidence of transformation proceeding from hyperplastic glands to parathyroid cancer because 60 of these patients have only parathyroid cancer.36,37,3942 At operation, when one encounters a parathyroid tumor that is hard, grayish white, lobulated, or invasive, parathyroid cancer must be suspected. An en bloc excision of the parathyroid neoplasm and ipsilateral thyroid lobe or other adherent tissues is recommended (especially for patients with profound hypercalcemia). For such patients with recurrent or metastatic disease, an aggressive surgical approach, even when palliative, is recommended to palliate symptoms of HPT41 and to...

Imaging of Metastases of Thyroid Cancer with Fluorine 18 Fluorodeoxyglucose

FDG-PET is primarily used to localize recurrent differentiated and poorly differentiated thyroid cancers, especially in patients who are serum thyroglobulin positive and 13II WBS negative. Serum thyroglobulin determination and diagnostic l3'I WBS provide the diagnosis of recurrent disease. Recurrent differentiated thyroid cancer may or may not take up radioiodine. 'A patient whose recurrent tumor is detected by radioiodine scanning has a significantly better prognosis than does a patient whose tumor does not take up l3'I.2 FDG-PET can be positive in the same site as a WBS-positive site or WBS-negative site, or both can be present in the same patient. Grunwald and associates3 reported that FDG-PET was particularly useful in WBS-negative patients, showing a high sensitivity of 85 . Patients with poorly differentiated thyroid cancers were more likely to be WBS negative and FDG-PET positive. Those patients also have a worse prognosis FDG-PET helps stage the disease and guide treatment...

Surgical Treatment of Recurrent or Persistent Medullary Thyroid Cancer

A, Computed tomography (CT) of liver from patient with multiple endocrine neoplasia type 2A, recurrent medullary thyroid carcinoma (MTC), and elevated calcitonin levels. There is no evidence of liver metastases on the scan. B, Laparoscopic view of liver from the same patient showing multiple small raised whitish lesions on and just beneath the surface of the liver, confirmed to be metastatic MTC by biopsy. These small, multiple metastases are often not seen with routine CT scanning or other imaging modalities, including nuclear scanning. (From Tung WS, Veseley TM, Moley JF. Laparoscopic detection of hepatic metastases in patients with residual or recurrent medullary thyroid cancer. Surgery 1995 18 1024.) FIGURE 15-5. A, Computed tomography (CT) of liver from patient with multiple endocrine neoplasia type 2A, recurrent medullary thyroid carcinoma (MTC), and elevated calcitonin levels. There is no evidence of liver metastases on the scan. B, Laparoscopic view of liver from...

Synthesis of Thyroid Hormone

After uptake into the follicular cells through the basal membrane (Fig. 1-2), inorganic iodide is rapidly oxidized. Thyroid hormones are then synthesized by the combination of iodine with tyrosyl residues within the protein thyroglob-ulin. This reaction is catalyzed by thyroperoxidase in two principal steps. In the first reaction, iodide reacts with FIGURE 1-2. Uptake of iodide into the follicular cell by active transport, with subsequent iodide oxidation, tyrosine iodination, and iodotyrosine coupling occurring at the apical membrane, catalyzed by thyroid peroxidase. DIT diiodotyrosine MIT monoiodotyrosine T3 triiodothyronine T4 thyroxine. FIGURE 1-2. Uptake of iodide into the follicular cell by active transport, with subsequent iodide oxidation, tyrosine iodination, and iodotyrosine coupling occurring at the apical membrane, catalyzed by thyroid peroxidase. DIT diiodotyrosine MIT monoiodotyrosine T3 triiodothyronine T4 thyroxine. tyrosyl residues in thyroglobulin to form...

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