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...

Clinical and Pathologic Characteristics

Although it may arise sporadically, MEN 2B more frequently occurs as a familial disorder inherited in an autosomal dominant fashion. MEN 2B is less common than MEN 2A. FIGURE 83-2. A diagram of the ret protooncogene demonstrating both highly conserved elements and sites of mutation known to be responsible for sporadic and familial medullary thyroid carcinoma (MTC) as well as the multiple endocrine neoplasia (MEN) 2 syndromes. Vertical bars within the diagram indicate sites of cysteine codons....

Pathology

Pancreatic endocrine tumors are commonly termed neuroendocrine tumors. However, some researchers indicate that it is unclear whether these tumors originate from the pancreatic islets.3 Pancreatic endocrine tumors may contain ductu-lar structures may produce hormones that are not produced by the normal pancreas, including gastrin and vasoactive intestinal polypeptide (VIP) and may produce more than one hormone.35 These findings suggest that pancreatic endocrine tumors originate from...

Surgical Treatment of Recurrent or Persistent Medullary Thyroid Cancer

Because of the lack of success reported for other modalities in the treatment of persistent or recurrent MTC, surgical 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 the same patient showing multiple small raised whitish lesions on and just beneath the surface of the liver,...

Image Diagnosis of Medullary Cancer

All patients with a preoperative diagnosis of medullary cancer of the thyroid should be tested for a ret protoonco-gene germline point mutation and also be screened for pheochromocytoma and hyperparathyroidism (see other chapters regarding medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism). Medullary cancer secretes calcitonin and carcinoembryonic antigen (CEA) and occasionally neuron-specific enolase, serotonin, chromogranin, gastrin-releasing peptide, substance P,...

Imaging of Metastases of Thyroid Cancer with Fluorine 18 Fluorodeoxyglucose

FDG is a D-glucose analog, which is converted in cells to FDG-6-phosphate by hexokinase. FDG-6-phosphate is metabolically trapped and accumulates in tissue where glucose-6-phosphatase is lacking. Metabolic trapping is the key factor responsible for the biodistribution of 18F-2-deoxyglucose.109 Because other enzymes that act on glucose-6-phosphate have only a negligible affinity for FDG-6-phosphate and membrane permeability is low, the rate of accumulation of FDG-6-phosphate is proportional to...

Molecular Carcinogenesis

The pathogenesis of radiation-induced thyroid cancer has not yet been elucidated. Gene rearrangements may play an important role in the process. Nikiforova and associates found that radiation-induced tumors had a 4 prevalence of BRAF point mutations and a 58 prevalence of RET PTC rearrangements, and sporadic papillary thyroid cancers demonstrated a 37 prevalence of BRAF point mutations and only a 20 prevalence of RET PTC rearrangements.34 Similarly, RET PTC3 rearrangement was found in...

NonMEN Familial Hyperparathyroidism and Parathyroid Cancer

Both parathyroid cancer and NMFH are rare parathyroid disorders. The association of these rare conditions suggests a common cause. Until 2002, 29 patients with NMFH and parathyroid cancer in 22 families were reported.16,21,23,27*33,35,43 Sixteen of these families have NMFH-JT or FIH-JT, and about one fourth of reported NMFH families have one or two affected members suffering from parathyroid cancer. Endocrinologists and surgeons should be aware of this association for proper management of these...

Adrenal Medulla

The adrenal medulla constitutes about 15 of the adrenal and is surrounded by the cortex. The major constituent of the medulla, the catecholamine-containing cells, are of two types the norepinephrine and the epinephrine cells. These cells are often called chromaffin cells because they stain with chromium salts, and this was an early method used to detect these cells.5 Chromaffin cells in adults are primarily confined to the adrenal medulla, although they also occur in extra-adrenal locations....

Adrenocortical Carcinoma

Adrenocortical carcinoma is a rare malignant disease with a dismal prognosis and an estimated incidence of 0.5 cases per 1 million individuals per year.45 Patients with nonfunctioning tumors have manifestations attributable to a large abdominal mass. Forty percent to 70 of adrenocortical carcinomas are secretory,4546 and these patients usually present with clinical features of hormone excess. The clinical features depend on the predominant excess steroid production glucocorticoid-secreting...

Anatomy of Parathyroid Glands

The presence of four parathyroid glands is most common in humans. In dissection studies of 428 human subjects by Gilmour, four parathyroid glands were found in 87 of all patients and three parathyroids in 6.3 .5 Akerstrom and colleagues reported comparable rates in an autopsy study of 503 cases.6 Four parathyroids were found in 84 and three parathyroids in 3 of all patients in this study. The occurrence of supernumerary parathyroid glands is a rare entity that nevertheless has important...

Assessment of Cure and Followup

Several reports suggest that at least one half of all Z-E syndrome patients explored, with the expectation to extirpate tumor and cure, continue to have hypergastrinemia postoperatively.84'96 Typically, a small duodenal gastrinoma or lymph node containing tumor has been excised, but an elevated serum gastrin level indicates that more tumor remains. A follow-up plan is needed for such patients. Should such a patient be re-explored or monitored Should re-exploration be done only when localizing...

Bone Disease

Although historically most patients with normocalcemic hyperparathyroidism were identified because of renal calculi, an increasing number of patients have recently been identified by screening patients for osteoporosis with dual-energy x-ray absorptiometry (DEXA) scans. Traditionally, hyperparathyroidism was associated with overt bone disease in a significant number of patients. This traditional bone disease was frequently symptomatic and associated with radiologic findings such as bone cysts,...

Carcinoid Syndrome

Treatment of the carcinoid syndrome is more complicated because it is often associated with hepatic metastases. Carcinoid syndrome occurs with 5 of all neuroendocrine tumors but occurs more often in patients with small bowel carcinoids.59 Many different approaches, such as liver resection, tumor debulking, radiofrequency ablation, chemoem-bolization, and liver transplantation, as well as treatment with somatostatin analogs and interferon-a make it difficult to choose the optimal therapy....

Causes of Goiter

Several mechanisms, including the interplay of intrinsic and extrinsic factors in the thyroid, cause goiter. The goitrogenic process involves genetic, environmental, dietary, endocrine, and other factors. The most common worldwide cause of endemic nontoxic goiter, as mentioned earlier, is iodine deficiency. In patients with sporadic goiter, the cause is usually unknown. Sporadic goiter is a result of environmental or genetic factors that do not affect the general population. The various types...

Clinical Characteristics

The diagnosis of primary hyperaldosteronism is usually made between the ages of 30 and 60 years. The disease is more common in women than in men. The ages of the patients in our series ranged from 17 to 74, with a mean of 47.0 years. The female-to-male ratio was 1.5 1 (131 85) in our series, which corresponds to that in most other studies.1723 The hypertension of primary aldosteronism is moderate to severe and is indistinguishable from that seen in other disorders. The highest blood pressure...

Clinical Evaluation

Careful clinical assessment with particular attention to clinical risk factors (Table 9-1) gives important indicators for the diagnosis and requirements for surgery. Most thyroid nodules are asymptomatic, presenting as a chance finding by the patient or during a medical examination. Pain is uncommon, but a malignant lesion may occasionally cause discomfort in the neck. With respect to single and multiple nodules, current evidence suggests that when a dominant nodule appears in a multinodular...

Clinical Features

The clinical manifestations of Cushing's syndrome usually begin gradually (Table 70-1). Patients frequently report increasingly severe asthenia, enhanced appetite, and weight gain. In premenopausal women, oligomenorrhea is common and may occur before any other apparent clinical change. Typically, these patients have centripetal obesity with moon face, fullness of the supraclavicular fat pads, and a buffalo hump. The limbs look thin in relation to the rest of the body, and muscular hypotrophy...

Clinical Manifestations

Most patients diagnosed with primary hyperparathyroidism today do not have the classic or historical clinical manifestations of this disorder such as osteitis fibrosa cystica, nephrolithiasis, nephrocalcinosis, peptic ulcer disease, gout, or pseudogout. The pentad of symptoms painful bones, kidney stones, abdominal groans, psychic moans, and fatigue overtones is more common, although most patients have few dramatic symptoms. The symptoms and other associated complications of primary...

Clinical Presentation

In sporadic MTC, tumors are usually single and unilateral. There is no family history and no other endocrinopathies are present. Sporadic MTC arises as a mass in the neck, and metastases to lymph nodes in the neck are usually present at the time of diagnosis. Familial forms of MTC are the multiple endocrine neoplasia (MEN) type 2A and 2B syndromes and the related disorder of familial non-MEN MTC (FMTC) (Table 15-1, Fig. 15-3).3'5 In these autosomal dominant...

Complications of Neck Dissection

More extensive neck dissections, especially in the central neck compartment, are associated with a higher risk of hypoparathyroidism and other complications.34-69 With complete resection of all fatty and lymph node tissue from the central neck, the recurrent laryngeal nerves and the vascular supply to the parathyroid glands are at risk, especially when combined with total thyroidectomy.14-47-62'69-94-96 Awareness of these potential problems emphasizes the importance of meticulous dissection and...

Conclusion

In conclusion, new findings concerning thyroid oncogenes and tumor suppressor genes, as well as studies of growth factors, are starting to explain why patients acquire specific thyroid tumors with different behaviors. 1. Brabant G, Hoang-Vu C, Cetin Y, et al. A differentiation marker in thyroid malignancies. Cancer Res 1993 53 4987. 2. Dremier S, Goldstein J, Mosselmann R, et al. Apoptosis in dog thyroid cells. Biochem Biophys Res Commun 1994 200 52. 3. Coclet J, Fourean F, Ketelbant P, et al....

Conclusions

Fewer patients now undergo classic open bilateral neck exploration for PHPT because of the desire for smaller scars, shorter postoperative stay, and less postoperative distress. Better preoperative localization studies now allow for patient selection for targeted parathyroidectomies with low rates of persistent disease.23 Endoscopic parathyroidectomy offers thorough exploration of the neck, unilaterally23 or even bilaterally.1024 The use of qPTHa reduces the possibility of missing a second...

Desensitization of Signal Transduction

Continuous agonist stimulation of receptors usually leads to a decrease in receptor-mediated AC activity and cAMP levels. This process is termed desensitization. Desensitization, or a decreased response to the same or repetitive stimuli, is an important physiologic process and a well-described mechanism of receptor-signaling modulation that occurs in a variety of cell systems. There are two types of desensitization homologous and heterologous. Homologous desensitization is agonist specific,...

Diagnosis

The limitations of a clinical diagnosis for insulinoma became apparent as early as 1935, when Whipple noted that 40 of explorations performed for insulinoma up to that time failed. Noting the numerous causes of hypoglycemia, Whipple set forth the strict diagnostic triad that bears his name (1) the signs and symptoms of hypoglycemia occur during periods of fasting or exertion (2) at the time of symptoms, blood sugar levels must be less than 45 mg dL and (3) symptoms are ameliorated by the...

Diagnostic Studies

All patients with recurrent renal calculi and or severe osteopenia or osteoporosis should be screened for PHPT because of the benefits provided by surgical correction. Patients with the combination of an elevated serum ionized calcium and an elevated iPTH have hyperparathyroidism, even in the absence of elevated serum total calcium. An elevated serum iPTH in the absence of elevated ionized or total calcium does not confirm the diagnosis of normocalcemic hyperparathyroidism. The iPTH can be...

Etiology of Hyperplasia

The development of hyperplastic parathyroid glands in patients with renal failure is primarily due to hypocalcemia, although other factors, including low calcitriol or 1,25-hydroxy-vitamin D3, high phosphate levels, and local growth factors, are involved. The decrease in serum calcium levels results from a decrease in the enzyme la-hydroxylase in the kidney that converts 25-dihydroxy vitamin D3 to 1,25-dihydroxyvitamin D. Hyperphosphatemia in patients with renal failure decreases the activity...

Flank Approach

Like the posterior approach, the flank approach is extraperitoneal. It is most useful for obese patients in whom exposure offered by other approaches would be compromised. In these patients, the flank approach uses gravity to assist with retraction by allowing the patient's adipose tissue to fall away from the incision. The flank approach is also useful in the presence of a large adrenal mass in a patient with scarring and adhesions in the abdomen from previous surgeries. Finally, the flank...

Genes Protooncogenes and Thyroid Cancers

Thyroid carcinomas and familial adenomatous polyposis (FAP) Thyroid carcinoma and Cowden's disease RET protooncogene encodes a transmembrane receptor that is a member of the receptors of the tyrosine kinase family and is found on chromosome 10 (lOql 1.2).31123 The gene is expressed normally in thyroid gland, adrenal gland, nerve tissue, and developing kidney and pathologically in neuroendocrine tumors (MTC, pheochromocytomas) and hyperplasia and neoplasia of parathyroid glands. The RET gene...

Goiter Growth

Goiters result from focal follicular cell hyperplasia at one or multiple sites within the thyroid gland. Iodine deficiency works synergistically with other causes of goiter but does not appear to change the basic mechanisms of goitrogenesis. There is a positive correlation between the total DNA content of the goiter and goiter weight. The increased amount of interstitial tissue and colloid formation usually contributes little to the total goiter growth. An intrinsically abnormal growth pattern...

Histopathologic Varieties of PHPT

A variety of pathologic conditions cause PHPT (Fig. 49-1). The most common cause of PHPT (85 to 90 ) is a solitary benign parathyroid adenoma. Malignant tumors of the parathyroid gland are extremely unusual, occurring in less than 1 of cases parathyroid cancers are sometimes difficult to distinguish from atypical adenomas. Parathyroid tumor metastases are certainly a sign of malignancy. Chief cell FIGURE 49-1. Various forms of hyperparathyroidism encountered in the surgical practice. MEN...

Historical Aspects

The striking clinical malady of exophthalmic goiter, with its distinctive protruding eyes, tachycardia, nervousness, and enlarged thyroid, has been known for more than 150 years. Thyrotoxicosis was first described in 1786 by Parry, a physician in England, but was not reported until after his death in 1825. It was also noted by von Basedow and a handful of others.1 To this day, on the continent of Europe, it is known as Basedow's disease. In the English-speaking world it is named for Robert...

Historical Introduction

In 1869, Paul Langerhans showed that islands of characteristic cells are distributed throughout the pancreas and that these islands are richly innervated.1 After the demonstration that diabetes evolves after pancreatectomy,2 it was suggested in 1901 that the disease is caused by lack of a factor produced by these islets of Langerhans.3 Although several researchers were close to the discovery of insulin, the critical pieces of work in this area were performed by Banting, Best, MacLeod, and...

Importance of LThyroxine Suppressive Therapy

Both the function and the growth of some metastatic thyroid tumors are under TSH control. It is a common observation that bone or lung metastases increase in size and take up radioiodine during periods of T4 withdrawal, whereas a reduction in size and lack of uptake are observed during periods of T4 therapy. Serum Tg, a marker of cell function, increases dramatically during hypothyroidism (see Fig. 17-1), whereas Tg levels return to low values during treatment with T4. In the classic article by...

Incidence

Pheochromocytoma has an incidence of 2 to 8 cases per million persons annually,6 7 which constitutes a curable form of hypertension in 0.1 to 1 of hypertensive patients,8 and as many as 800 persons may die annually in this country from associated complications.9 Of patients with pheochromocytomas discovered only at the time of autopsy, 75 died suddenly from either myocardial infarction or a cerebrovascular catastrophe. Moreover, one third of the sudden deaths occurred during or immediately...

Indications

The indications for laparoscopic adrenalectomy are basically the same as those for open adrenalectomy, with few exceptions. These indications include the following 1. Functional adrenal cortical masses (1) Cushing's syndrome caused by benign cortisol-producing adenoma (2) Cushing's disease after failed pituitary surgery or after failure to control or find an ectopic adrenocorticotropic hormone (ACTH)-producing tumor (3) aldosterone-producing adenoma (Conn's syndrome) and (4) rare virilizing...

Indications for Operative Treatment

As discussed earlier, the clinical profile of primary hyperparathyroidism has undergone a distinct change over the past few decades, particularly with the introduction of automated blood chemistry panels. The 1990 National Institutes of Health Consensus Development Conference on the Management of Asymptomatic Primary Hyperparathyroidism was convened to set forth evidence-based diagnosis and management guidelines for this group of patients. The panel recognized surgery as the only definitive...

Indications for Transplantation with Cryopreserved Tissue

The indications for autotransplantation with cryopreserved tissue are straightforward persistent, permanent hypocalcemia in patients for whom cryopreserved tissue is available. There is no fully agreed-on definition of permanent hypocalcemia however, dependence on oral calcium and vitamin D TABLE 60-2. Clinical Success with Cryopreserved Parathyroid Autotransplants TABLE 60-2. Clinical Success with Cryopreserved Parathyroid Autotransplants Some patients may be included repeatedly in reports by...

Interpretation of the Fasting Test

A plasma insulin concentration of 6 (iU mL (36 pmol L) by radioimmunoassay (or 3 (iU mL by immunometric assay) when the plasma glucose concentration is below 45 mg dL (2.5 mmol L) indicates an excess of insulin and is consistent with insulinoma. Unfortunately, plasma glucose concentrations fall below 50 mg dL (2.8 mmol L) in some normal subjects and remain above 50 mg dL in an occasional patient with an insulinoma.16 Plasma C Peptide Concentrations. It is...

Invasive Preoperative Methods

Invasive localization studies are indicated when the combined results of the noninvasive tests are negative, equivocal, or conflicting. FIGURE 46-8. Sestamibi scan with thymic parathyroid adenoma. FIGURE 46-8. Sestamibi scan with thymic parathyroid adenoma. I TABLE 46-2. Characteristics of the Most Common Noninvasive Localization Studies Tl-TC thaHium-technetium US ultrasonography CT computed tomography MRI Fine-needle aspiration (FNA) of the parathyroid tumor performed under sonographic...

Islet Function

A key role for the pancreatic islets is to deliver an optimal amount of peptide hormones into the bloodstream to optimize carbohydrate metabolism. Of most importance in this respect is insulin, which facilitates the transport of glucose into insulin-dependent cells for storage as glycogen and fat with a concomitant reduction in blood glucose and free fatty acid levels as a consequence. One of the most important target organs for insulin action is the liver, in which at least 50 of the insulin...

Laparoscopic Ultrasound

We used laparoscopic ultrasonography in 15 selected cases. In 1 patient it showed the location of a 0.7-cm aldosteronoma in an adrenal gland after open surgery failed to find the organ. In 2 patients, no adenoma was found, necessitating only biopsy and closure rather than adrenalectomy. In 2 patients with large masses (10 and 12 cm), no extra-adrenal or lymph node involvement was found. The masses were completely removed laparoscopically and proved to be histologically benign. In 1 patient,...

Localizing Procedures

The adrenal imaging techniques used as localizing procedures are adrenal scintigraphy, computed tomography (CT), FIGURE 70-2. Different clinical appearances of patients with Cushing's syndrome in relation to early diagnosis. A to C, The faces of some patients observed in 1982, 1987, and 1995, respectively. FIGURE 70-2. Different clinical appearances of patients with Cushing's syndrome in relation to early diagnosis. A to C, The faces of some patients observed in 1982, 1987, and 1995,...

Mortality after Surgery for Primary Hyperparathyroidism

Three Scandinavian studies examined long-term mortality after surgery for PHPT. Basic data from the three Scandinavian series are given in Table 43-1. The first two series included patients who had been treated during the same 24-year period.910 The third series included more patients than the other two together and covered a 30-year period. This series also had the longest follow-up.1113 In the Helsinki study, for the first time, the long-term mortality after surgery for PHPT was compared with...

Natural History of Treated Primary Hyperparathyroidism

In 1925, Mandl of Austria performed the first operation for primary hyperparathyroidism (PHPT).1 His patient had sustained a spontaneous thigh bone fracture and was immobilized. Three months after a parathyroid adenoma had been excised, the patient could walk with crutches. The effect of the operation was conspicuous. During the next 4 decades, most patients with PHPT continued to have obvious symptoms relieved by surgery. In the mid-1960s, the number of operations for PHPT started to increase...

Nodule Formation

With increasing age, most thyroid glands and goiters become nodular. Initially, many goiters are diffuse however, with intermittent stimulation, some diffuse goiters outgrow their blood supply and become nodular (Fig. 4-2).20,21 Some thyroid cells are more sensitive to growth factors and become larger nodules. If these nodules trap and organify iodine, the nodule may be hot or autonomous rather than cold. Hot nodules are associated with TSHR and gsp mutations. In general, formation of thyroid...

Operative Technique Laparoscopic Approach

Since the publication of the last edition of this text, a dramatic and exciting change in the overall approach to adrenalectomy has occurred. Whereas previously only a limited number of laparoscopic adrenalectomies had been reported in total,32 some involving significant bleeding33 and a few including removal of pheochromocytomas,32 34 laparoscopic adrenalectomy has become the accepted standard method, even to remove pheochromocytomas. Multiple advantages of the laparoscopic approach have been...

Other Sporadic Islet Cell Tumors

Most other functional islet cell tumors such as glucagonomas, vasoactive intestinal polypeptide tumors (VIPomas), and somatostatinomas are too large at diagnosis to be amenable to enucleation and require resection when feasible.2123 More than half of these tumors are malignant with either local invasion or hepatic metastases at the time of diagnosis. Whenever feasible, debulking of tumors is desirable short of Whipple's procedure even when hepatic metastases are present. When local invasion of...

Pancreas

The introduction of insulin therapy for the management of diabetes mellitus is one of the greatest milestones in the history of medicine. Beta-cell replacement therapy is the only treatment that reestablishes and maintains long-term physiologic normoglycemia,81 because intensive subcutaneous insulin regimens cannot completely mimic the physiologic fluctuations of in vivo insulin secretion.82 The two options for replacement of beta-cell function in patients are whole-organ pancreas...

Pancreastatin

Another peptide that is produced by the islet B cells is pancreastatin, which is a carboxyterminal amidated TABLE 78-1. Endocrine Peptides and Neuropeptides in the Istet Cells and Gastrointestinal Peptide Hormones Affecting Islet Cell Hormone Secretion Effect on Insulin Effect on Glucagon TABLE 78-1. Endocrine Peptides and Neuropeptides in the Istet Cells and Gastrointestinal Peptide Hormones Affecting Islet Cell Hormone Secretion Effect on Insulin Effect on Glucagon 49-amino acid peptide...

Parathyroid

The treatment of surgically acquired and idiopathic hypoparathyroidism requires life-long treatment with vitamin D and oral calcium supplementation. This is not, however, a perfect physiologic replacement because, although it sufficiently regulates blood calcium and phosphate levels, it does not reverse the lowered urinary calcium reabsorption and excessive urinary calcium excretion, which may result in renal stones.25 Owing to the complexity of parathyroid hormone's metabolic interactions,...

Parathyroid Calcium Sensor Proteins

A calcium sensor protein on the parathyroid cell surface was identified by monoclonal antibodies generated by immunization with human adenoma cells.49 Such a monoclonal antibody abolished the calcium-regulated Ca2+ and PTH release of normal and pathologic parathyroid cells.50 51 The antibody blocked the calcium-induced Ca2+, transient intracellular calcium mobilization as well as the steady-state elevation resulting from calcium influx. Because the antibodies also competed with calcium binding...

Parathyroid Embryology and Developmental Abnormalities

The inferior parathyroid glands arise from the dorsal part of the P III. The thymus arises from the ventral portion of the same pouch. This common origin justifies labeling P III and thymus as parathymus. The dorsal part of the PIV gives rise to the superior parathyroids. The fate of the ventral portion of the P IV is little understood in humans. Gilmour4 regarded it as the origin of the thymus IV (rudimentary thymus IV), which rapidly undergoes involution. The fatty lobules sometimes found at...

Parathyroid Hormone Assays

Assaying for PTH in vivo has been notoriously difficult because of its picomolar concentrations in the circulation as well as its molecular heterogeneity. This heterogeneity is due to parathyroid gland secretion of various carboxyterminal PTH fragments (especially when PTH release is suppressed), hepatic proteolysis, and accumulation of midregional and carboxyterminal fragments caused by slow renal clearance in kidney disease. In principle, PTH may be assayed for bioac-tivity as well as by...

Pathologic Features

Aldosterone-producing adenomas are usually solitary tumors involving only one adrenal gland (Fig. 68-1). Most adenomas are smaller than 2 cm in diameter. The mean diameter in 210 patients with surgically proven aldosterone-producing adenomas in our series was 1.8 cm, which is consistent with previous reports.12 The cut surface usually has a characteristic golden yellow appearance. Microscopically, the typical tumor is mostly composed of large lipid-laden clear cells. In contrast, idiopathic...

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...

Pathophysiology of Endemic Goiter

Endemic goiter is the end result of the physiologic and morphologic changes in the thyroid gland as an adaptation to an insufficient supply of dietary iodine. When iodine intake is low, thyroid hormone synthesis is impaired. This impairment leads to an increased thyroidal clearance of iodide from the plasma and decreased urinary excretion of iodide, an adaptation toward iodine conservation. T3, being three to four times more potent than T4 but containing only three fourths as much iodine as T4,...

Pituitary Tumors

In MEN 1 kindreds, pituitary tumors are found less frequently than primary HPT or PETs.40 Signs and symptoms related to a pituitary adenoma are the initial clinical presentation of MEN 1 in up to 25 of first in the kindred cases but in less than 10 of familial cases that are TABLE 76-2. Indications for Genetic Screening At-risk family members in known MEN t kindreds Young patients (< 50 years) with multigland or recurrent HPT (normal renal function) Patients with prolactinomas 14 MEN 1)...

Postoperative Adjuvant Therapy

Because of the excellent prognosis of most patients with low-risk papillary thyroid carcinoma, it has been difficult to demonstrate any benefit from adjuvant therapy in the form of radioiodine or TSH suppression therapy. Vickery,39 Cady,1'38 and their associates concluded that the usual course of low-risk papillary carcinoma treated by conservative surgery is generally so benign that further beneficial effects of radioiodine, thyroid suppressive treatment, or total thyroidectomy have never been...

Postoperative Care

Oral fluids are started on the day of surgery. Nasogastric tubes are unnecessary for most patients. If a Jackson-Pratt drain has been inserted at surgery, it is removed the next morning. Oral analgesics are provided to help patients tolerate the postoperative pain. However, during the first 12 hours, some patients require parenteral analgesia. The postoperative course is similar to that for laparoscopic cholecystectomy, except that some endocrine disorders necessitate hormonal support and...

PPoma and Nonfunctioning Neuroendocrine Tumor

PPomas secrete pancreatic polypeptide, but this hormone does not appear to cause symptoms in men and this tumor is considered nonfunctional. PPomas and nonfunctioning pancreatic neuroendocrine tumors are tumors that have no functional syndrome. Dopamine agonists have been shown to decrease circulating levels of PP and chromogranin A in patients with large unresectable islet cell tumors.75 PPomas produce symptoms by tumor mass effects. This tumor is diagnosed because the patient has cachexia,...

Preoperative Tumor Localizing Techniques

Tumor-localizing techniques for gastrinoma have continued to evolve since Zollinger and Ellison's first report.1 Their first two Z-E syndrome patients had only barium swallows, demonstrating mucosal changes in the stomach and small bowel related to excess acid. In Ellison's 1956 report, the first reported series of ulcerogenic tumor patients, no tumors were identified preoperatively by any imaging technique, and the concept of preoperative localizing was not even mentioned. Abdominal plain...

Preventive Surgery for Multiple Endocrine Neoplasia Type 2 Gene Carriers

Individuals with MEN 2A, 2B and FMTC are virtually certain to acquire MTC at some point in their lives (usually before age 30 years). Therefore, at-risk family members who are found to have inherited the RET gene mutation are candidates for thyroidectomy regardless of their calcitonin levels. It has been shown in several series that RET mutation carriers often harbor foci of MTC in the thyroid gland even when stimulated calcitonin levels are normal.14'18-33'34'4547 In a series from Washington...

Renal Calculi

Most patients with normocalcemic hyperparathyroidism are identified because of renal calculi and many of these patients have hypercalciuria. Most patients with renal calculi and hypercalciuria, however, have idiopathic hypercalciuria, a condition also associated with normocalcemia. Patients with idiopathic hypercalciuria have 24-hour urinary calcium values of 250 mg per 24 hours or higher in females, 300 mg per 24 hours or higher in males, or 4 mg kg in males or females on a daily intake of...

Screening and Diagnosis

Screening for MEN 2B should be reserved for a few well-defined populations (1) family members of known MEN 2B patients, (2) patients newly diagnosed with medullary thyroid carcinoma or pheochromocytoma, and (3) individuals exhibiting the characteristic phenotype of marfanoid habitus and mucosal neuromas. Screening is mandatory in these patients to maximize the opportunity to perform curative thyroidectomy or adrenalectomy, or both, before metastasis of the endocrine tumors. Screening of family...

Special Situations

As has been emphasized previously, there are no certain cytologic characteristics that distinguish benign from malignant pheochromocytomas. The presence of local invasion into surrounding soft tissue or the presence of these tumors in sites other than along the sympathetic chain is the only reliable indicator of malignancy. Patients with apparently benign, sporadic, well-encapsulated tumors have developed distant metastases that have proved fatal (Fig. 71-10).51 The most common sites of...

Staging Surgical Indications and Preoperative Treatment

Adrenocortical carcinomas are classified according to stages described by MacFarlane and modified by Sullivan (Table 69-3). This classification has one major drawback (i.e., malignancy in stage I is based on histologic criteria only). Whether all of these tumors are malignant is unknown, and the assumption that all are malignant may lead to an overly optimistic affirmation of the results of surgery. All tumors at stage I, II, or III, whether diagnosed preop-eratively or intraoperatively, should...

Summary

Aerodigestive tract invasion by thyroid cancer affects approximately 6 of patients with thyroid cancer, representing one of the most demanding disease-related complications in endocrine surgical oncology. Two thirds of patients with advanced thyroid cancer suffer from invasion of the upper airway, whereas pharyngoesophageal involvement accounts for only approximately 20 to 25 . Because of the more aggressive biology of the tumors and older age of the patients, aerodigestive tract involvement...

Surgical Strategy in Patients with Primary Hyperparathyroidism

The primary goal of parathyroidectomy for patients with primary hyperparathyroidism is to cure the primary hyperparathyroidism and to achieve normocalcemia. The best surgical strategy should achieve this goal with minimal complications, such as persistent hyperparathyroidism, recurrent hyperparathyroidism, postoperative hypoparathyroidism, and recurrent laryngeal nerve injury, and with efficient use of operating time and resources. The most important variable that influences the success of...

Surgical Technique

The term endoscopic parathyroidectomy must be clearly defined a parathyroidectomy can be considered to be endoscopic when endoscopic equipment is used during the procedure. Techniques such as video-assisted parathyroidectomies that require the endoscope during one step but not necessarily during the whole operation should also be considered endoscopic procedures. The three endoscopic neck procedures in most widespread use are described in the following. Other techniques that have been proposed...

Techniques

Parathyroidectomy

Although several approaches have been proposed as endoscopic parathyroidectomy, the most commonly used are the (1) endoscopic parathyroidectomy (Gagner, 1997),2 (2) video-assisted parathyroidectomy with external retraction (Miccoli, 1997),3,4 and (3) videoscopic parathyroidectomy by a lateral approach (Henry, 1998).5 Endoscopic parathyroidectomy was the first technique described for endoscopic parathyroidectomy. It uses steady gas flow, not exceeding 8 mm Hg pressure.6 A 5-mm endoscope (0...

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...

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. > 4 cm diameter 1...

Thyroxine and Lipid Metabolism

There is an overall increase in hyperlipidemia in overt hypothyroidism, and there have been claims of higher mortality from ischemic heart disease in undertreated patients.63,64 In subclinical hypothyroidism the biologic efficacy of thyroid hormone replacement has been confirmed with observed changes in serum lipoprotein concentration, improvement in cognitive performance and indices of cardiac function, and reduction of subjective symptoms. The majority of patients show no fundamental changes...

Treatment

The first step in the management of hypercalcemic crisis is to lower the serum calcium level and then identify its etiology. Therapy must be directed toward increasing the urinary excretion of calcium and decreasing bone resorption.3,9 Increasing renal calcium excretion in hypercalcemic crisis by means of hydration and loop diuretics (furosemide) is quicker and easier than decreasing bone resorption (Table 62-2).1 Immediate therapy must achieve as rapid and complete volume reexpansion as...

Treatment Modalities

Patients with parathyroid carcinoma frequently present with symptomatic hypercalcemia. They need prompt treatment and correction of renal and cardiac dysfunction because of the metabolic consequences of the high serum calcium levels. Rehydration with saline and additional electrolytes, including magnesium, restores glomerular function and increases urinary excretion. Loop diuretics also increase urine calcium secretion, provided that the patient is well hydrated. Calcitonin is an osteoclast...

Treatment of Asymptomatic Hyperparathyroidism

The changing presentation of 1 HPT is a result of the increased recognition of a milder form of the disease. The intention of the NIH consensus guidelines for parathyroidectomy was to FIGURE 44-1. The Parathyroidectomy Assessment of Symptoms (PAS) scores for primary hyperparathyroidism (HPT).The HPT patients were significantly more symptomatic than the thyroid comparison group preoperatively (P < .05). After surgery, the HPT patients demonstrated a significant decrease in their PAS scores (P...

Treatment of Hypercalcemia

There are two points of attack on hypercalcemia.54,55 One is to inhibit osteoclastic bone resorption, thus reducing the flux of calcium into the extracellular fluid. The other is to increase the urinary excretion of calcium, potentiating the only homeostatic mechanism to clear an excess calcium load. The urinary clearance of calcium is often impaired in patients with malignancy-associated hypercalcemia. The glomerular filtration rate is reduced both by direct effects of hypercalcemia and by the...

Troubleshooting for a Missing Parathyroid Gland

The enlarged parathyroid gland can remain undiscovered after routine exploration of the neck in some patients. Several of such classic situations are described next. It is of great importance to identify the normal parathyroid glands during the exploration of the neck because a parathyroid missed at its normal localization can indicate the site of the migrated enlarged parathyroid. Situation 1. Three normal parathyroid glands have been identified but the (right) upper parathyroid gland cannot...

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 Gut and Insulin Secretion

It has long been known that oral ingestion of glucose results in high levels of plasma insulin, although the increase in plasma glucose is only marginal.100'101 This is due to the action of gut hormones, called incretins, that are released into the circulation during meal intake and stimulate insulin secretion. The most important incretins are glucose-dependent insulinotropic polypeptide (GIP also called gastric inhibitory polypeptide) and GLP-1.102 103 GLP-1 is a 30-amino acid peptide produced...

Endocrine Pancreas and Type 2 Diabetes

From the previous discussions, it is clear that the endocrine pancreas is a complexly regulated organ that integrates incoming impulses of nutrient, hormonal, and neural nature. The endocrine pancreas converts these impulses to an optimal secretion of the islet hormones mainly for the regulation of carbohydrate homeostasis. An example of the consequences that follow derangement of the endocrine pancreas is type 2 diabetes. A primary event during the development of this disease is a reduced...

Glucose and Insulin Levels

Currently, the diagnosis of insulinoma is confirmed by demonstrating a circulating insulin level that is inappropriately high for the serum glucose level, measured at the time of hypoglycemia (Fig. 79-3). When a patient presents with symptoms of hypoglycemia (i.e., coma, convulsions, or other neurologic symptoms), blood samples should be taken for the determination of both insulin and glucose levels. Samples should be drawn as early as possible to avoid complications of hypoglycemia and before...

Measurement of Proinsulin and C Peptide

Proinsulin is the precursor molecule for insulin and is found in the rough endoplasmic reticulum of the beta cells in the pancreatic islets. As shown in Figure 79-2, the proteolytic conversion of proinsulin results in the formation of equimo-lar amounts of insulin and its connecting peptide, C peptide. In the presence of an insulinoma, there is an elevation of both proinsulin and C peptide.1015 Furthermore, proinsulin levels, which are usually less than 20 of the total immunoreactive insulin in...

Insulin Glucose Ratio

The insulin-glucose (I G) ratio provides a relationship between these two values that aids in the determination of the presence of an insulinoma. In a normal individual, the ratio is always less 0.4, but in patients with an insulinoma the ratio approaches 1.0 and may in some cases exceed 1.0. The I G ratio is important because as many as one third of patients with an insulinoma have insulin levels within normal limits when they have symptomatic hypoglycemia. FIGURE 79-3. Plasma insulin (in...

Insulinomas

Ninety percent of insulinomas are benign and are smaller than 2 cm in diameter. Ninety-nine percent are located in the pancreas. A variety of preoperative imaging modalities for the detection of insulinomas are currently available, such as US, CT, MRI, somatostatin receptor scintigraphy (SRS), and various invasive methods, including endosonography (ES), selective angiography (SA), selective portal venous sampling (PVS), and selective hepatic venous sampling after arterial stimulation (modified...

Physiologic Effects of Corticosteroids

Aldosterone regulates electrolyte excretion and the intravascular volume through its effects on the distal tubules and cortical collecting tubes of the kidney. It binds to a miner-alocorticoid receptor in the cytosol and moves into the nucleus to increase transcription.8 The early effect is to increase the Na absorption through the Na channels. Via changes in electrical potential across the renal tubule, K and H secretion are increased. This leads to an expanded intravascular volume and...

Clinically Inapparent Adrenal Mass Incidentaloma or Adrenaloma

Historically, the adrenal tumor that was discovered incidentally, usually during an imaging procedure such as computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography for symptoms unrelated to adrenal disease, (e.g., back pain) was called an incidentaloma.1 As more physicians (and patients on their own) ordered these easily available imaging studies for common diseases potentially related to adrenal pathology (and not the known syndromes), such as mild and nonparoxysmal...

The Goal of Evaluation

Although by definition the clinically inapparent adrenal masses appear nonfunctioning, on the basis of clinical and essential laboratory findings more and more investigators have shown that a high percentage of them may be subclinical functioning and or associated with other metabolic abnormalities. In a multicenter, retrospective evaluation of 1096 patients with adrenal incidentaloma, the work-up revealed that 9.2 had subclinical Cushing's syndrome, 4.2 had pheochromocytoma, and 1.6 had...

Diagnostic Procedures

When Cushing's syndrome is suspected and iatrogenic causes have been excluded, the diagnosis should be confirmed by both an overnight dexamethasone suppression test (1 mg of dexamethasone is given at 11 pm, and a plasma Cortisol measurement is obtained in the morning) and the 24-hour urinary free Cortisol measurement. When the dexamethasone suppression test is normal (plasma Cortisol < 50 mmol L) and the urinary free Cortisol is normal (< 135 nmol 24 hours), the patient does not have...

Environmental Radiation Exposure

As with the medical radiation exposure just described, environmental radiation exposure of the thyroid can be from external sources as well as internal ingestion of radioisotopes of iodine. The populations exposed are geographically related to discrete regional events involving either nuclear weapons or nuclear power plant accidents. The largest, best studied population exposed to acute external radiation from an environmental source includes survivors of the atomic bombs detonated at Hiroshima...

Radiation Exposure

The association between radiation exposure and increased risk of thyroid cancer was first recognized by investigators studying the increasing clinical problem of childhood thyroid cancer in the mid-20th century.5 6 The number of cases of thyroid cancer diagnosed and treated in children or adolescents was quite low only 18 cases of childhood thyroid cancer were reported in the medical literature before 1930 (Fig. 26-1).7 Duffy and Fitzgerald recognized an increased incidence of this disease and...

Environmentally Induced Goiter

Endemic goiter is discussed in Chapter 3. An inadequate adaptive mechanism of the thyroid to protect from severe iodine deficiency results in the development of goiter. These adaptive mechanisms include increased iodide clearance, increased production of triiodothyronine (T3) relative to thyroxine (T4), and increased mass of thyroid follicular cells.1 Pregnancy increases the need for iodine and T4, which results from significant transfer of thyroid hormone from the mother to the fetus and also...

Thyroid Stimulating Hormone Suppression and Miscellaneous Benign Goiters

Levothyroxine has been advocated for a variety of benign goitrous conditions, most notably in the follow-up of patients who have experienced irradiation to the head and neck in some cases of functionally autonomous nodules and in postpartum and neonatal goiter. Irradiation during childhood or adolescence for a range of benign conditions (tinea capitis, tonsillar and thymic enlargement, acne vulgaris, or head and neck vascular malformations) has been associated with a substantial increase in...

Incidence and Etiology

Carcinoma of the thyroid gland affects approximately 11,000 people in the United States each year, with a female-to-male ratio of nearly 3 1. It accounts for 90 of all endocrine malignancies and kills approximately 1300 people annually.5 In the United States, childhood thyroid carcinoma constitutes approximately 3 of all childhood cancers. Its incidence rate is three to five cases per million per year.6-7 Childhood DTC is so uncommon that even the largest referral centers in the United States...

Tumor Suppressor Genes

The p53 tumor suppressor gene is one of the most common genetic alterations observed in human cancers. The p53 gene, located on chromosome 17pl3, encodes a 53-kd nuclear phosphoprotein and functions as a key cell cycle regulator. p53 mutations lead to altered protein conformations that are nonfunctional and accumulate in the cell nucleus. A p53 mutation needs to occur in only one allele to lead to deregulated cellular growth. Most p53 gene mutations (98 ) occur in exons 5 through 8.643 p53...

Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma is an extremely aggressive cancer, with a median survival after diagnosis of just a few months.39 The outcome is so poor that the American Joint Committee on Cancer (AJCC) classifies all patients with this tumor as having stage 4 thyroid cancer. Fortunately, anaplastic thyroid carcinoma accounts for less than 2 of all thyroid carcinomas in the United States and has been decreasing in incidence.40-41 TABLE 36-4. Common Chromosomal Aberrations in 13 Hiirthle Cell...

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...

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...

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