Causes of Failed Initial Exploration for Hyperparathyroidism

HPT following a prior cervical or mediastinal exploration for hypercalcemia can be divided arbitrarily into persistent (defined as hypercalcemia recurring within 6 months after initial operation) or recurrent (hypercalcemia recurring after 6 months of normocalcemia following initial operation).2 3 The former denotes missed pathology and the latter refers to newly developed pathology. The distinction of these two categories has been loosely applied since it is possible that a physiologically...

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...

Genetic Testing for Hereditary MTC

Germiine defects in the RET protooncogene are responsible for MEN 2A, MEN 2B, and FMTC.4143 RET encodes a transmembrane growth neurotrophic receptor with tyrosine kinase activity. In MEN 2A and FMTC, gain-of-function mutations within codons specifying cysteine residues in the extracellular ligand-binding domain of the RET gene product are most commonly found (see Table 15-2). In MEN 2B, a mutation is found in the intracellular tyrosine kinase domain. Changes in protein structure and function...

Diagnosis of Primary Hyperparathyroidism

The biochemical diagnosis of primary hyperparathyroidism is made by documenting an elevated serum PTH in a patient with hypercalcemia (serum calcium > 10.5 mg dL) without hypocalciuria. Patients with benign familial hypocalciuric hypercalcemia (BFHH) are also hypercalcemic and have an inappropriately high PTH. Virtually all patients with other causes of hypercalcemia have a suppressed serum PTH level. Patients with BFHH have elevated levels of PTH in the presence of hypercalcemia because of...

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...

Adenoma

Adenomas are the most common benign tumors of the thyroid gland. They are of follicular cell origin, encapsulated with varying histology. They have been subdivided according to their histology, but no additional information is gained by this practice. Thyroid adenomas are probably common because of the inability of pathologists to separate consistently cellular adenomatous nodules in nodular goiters from adenomas. The majority of adenomas are most likely adenomatous nodules. The atypical...

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....

Adrenal Neoplasia and Hyperplasia

Thirty-five percent to 40 of MEN 1 patients harbor adrenocortical lesions, and these are clearly overrepresented in the MEN 1 syndrome.1517 Most lesions are hyperplastic, bilateral, and nonfunctioning. Aldosterone- and cortisol-secreting adenomas, however, have been reported.1517 Hypercortisolism in MEN 1 can be the result of an ACTH-secreting pituitary process, a cortisol-secreting adenoma carcinoma or, rarely, due to an adrenocorticotropic hormone (ACTH)- or corticotropin-releasing...

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...

Advantages and Disadvantages

It is difficult to assess the advantages offered by minimally invasive parathyroid surgery because of the many different techniques considered minimally invasive. Similarly, conventional parathyroidectomy includes both bilateral and unilateral explorations. Furthermore, early sporadic reports of minimally invasive parathyroidectomy included only few cases that had inadequate follow-up and were not prospective studies. Possible advantages include cosmetic outcome and postoperative distress....

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...

Anterior Approach

At times, either for intra-abdominal procedures that cannot be accomplished laparoscopically or for other reasons, an anterior open approach may be chosen. A surgical headlight may be helpful in the dissection of these tumors, which can be situated very high and deep in the retroperitoneum. We prefer the exposure of a right adrenal pheochromocytoma through a long right subcostal incision with the patient positioned supine, sometimes with elevation of the right side of about 15 degrees. After...

Are Preoperative Localization Tests Beneficial

There is no question that preoperative localization tests are essential for all reoperative cases of insulinoma. However, for the initial operation of an insulinoma, some differences of opinion exist. Some investigators shun most preoperative testing and rely almost exclusively on IOUS with careful palpation.40,43 Others, however, favor administering a battery of preoperative localization tests before the initial operation. In a national study of German institutions, it was shown that when no...

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...

Autocrine Regulation of Parathyroid Cell Secretion and Proliferation

Sparse information is available on the expression and actions of growth factors in the parathyroid parenchyma. Insulin-like growth factor I and its receptor seem to be expressed by parathyroid tissue, and EGF may play a role in cellular proliferation.100 Fibroblastic growth factors (FGFs) are mitogenic peptides synthesized by parathyroid epithelial and endothelial cells. Production of acidic FGF increases under hypocalcemic conditions, when high-affinity receptors for this peptide seem to...

Autoregulatory Mechanisms

The thyroid can also control its own stores of thyroid hormone by intrinsic autoregulatory mechanisms. These mechanisms are principally seen in response to alterations in iodide availability. For example, an excess of dietary iodide leads to autoregulated inhibition of iodide uptake into the follicular cells, whereas iodide deficiency results in increased iodide transport and uptake. Large doses of iodide have more complex effects, including an initial increase followed by a decrease in...

B

As a result, the serum TSH level increases, stimulating thyroid growth.17 The increase must be relatively short lived and intermittent because most patients have normal serum TSH levels. Other growth factors are obviously involved since the sizes of various nodules vary considerably in the same patient. Furthermore, goiters may grow despite administration of T4 in doses that reduce the serum TSH level to a subnormal level or in patients with toxic nodular goiter....

Benefits of Parathyroidectomy in Patients with Primary Hyperparathyroidism

Patients with untreated primary hyperparathyroidism have an increased risk of death from cardiovascular disease and cancers. This increased risk of death is similar in magnitude to that associated with smoking, and the risk appeared to correlate with parathyroid tumor size and the peak calcium level.17,18 Parathyroidectomy benefits most patients with primary hyperparathyroidism. Muscle strength and fine motor function19 as well as psychiatric symptoms20 improve within 1 month after...

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,...

Brief Review of Results of Reoperative Parathyroid Surgery

A summary of results reported by referral centers with extensive experience in parathyroid reoperations is shown in Table 58-4. Some of these results included all patients with persistent or recurrent HPT, but others, such as at the National Institutes of Health, only included patients with sporadic disease and one abnormal gland. From 1989 to 1997 at the Mayo Clinic, 124 patients with benign persistent or recurrent primary HPT underwent 106 cervical explorations (86 ), 9 mediastinal...

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....

Catecholamine Effects

The influence of catecholamines on insulin secretion was initially thought to be inhibitory because norepinephrine and epinephrine were demonstrated to reduce the insulin secretory response to glucose.70'80'81 However, the influences of the catecholamines are dependent on the degree of expression of various adrenergic receptors. Thus, activation of postsynaptic a-adrenergic receptors, mainly of the 0C2 subtype on the islet B cells, inhibits insulin secretion,82 whereas activation of the...

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...

Chemotherapy for Unresectable Endocrine Neoplasms

Edmiston, MD Nilima A. Patwardhan, MD Neoplasms arising from endocrine organs are rare and have unique clinical features. In contrast with most solid tumors, symptoms from endocrine neoplasms may arise as a result of the production of biologically active substances by the tumor or invasion of surrounding structures and their ability to metastasize. Tumors that are biologically active may become clinically apparent as a result of endocrine hyper-function, whereas...

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...

Clinical Characteristics

Hurthle cells are large polygonal, eosinophilic cells with pleomorphic, hyperchromatic nuclei and fine granular, acidophilic cytoplasm, representing an abundance of mitochondria (Fig. 14-1). The individual cells are 10 to 15 pm in diameter and can vary in shape and size from small dumbbells to bizarre giant cells. Hurthle cell neoplasms are encapsulated collections of Hurthle cells (Fig. 14-2). Therefore, the presence of nonencapsulated Hurthle cells does not signify a neoplastic process,...

Clinical Course after Successful Parathyroidectomy

The overall clinical result is considered good in 70 to 85 of the patients. Bone pain improves in few days in 60 to 80 of patients, joint pain in 85 , and malaise in 75 .4 Abdominal pain and irritated eyes are less likely to improve.4 Muscle weakness is relieved in one third of the patients and radiologic signs improve in 95 .48 Itching decreases overnight in almost all patients and disappears in 60 to 80 .4,48 Successful PTX improves nonvisceral calcification in 50 to 60 but does not change...

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...

Clinical Presentation and Diagnosis

Goiter is classified according to the size of the thyroid gland on inspection and palpation, and the following grading system was proposed by WHO in I96032 Stage 0 no goiter Stage la goiter detectable only by palpation and not visible even when the neck is fully extended Stabe lb goiter palpable but visible only when the neck is fully extended Stage II goiter visible with the neck in the normal position palpation is not needed for diagnosis FIGURE 3-2. Classification of goiter size. 1, Stage la...

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 and Future Aspects

High-quality preoperative localization procedures such as sestamibi scintigraphy and ultrasonography as well as the introduction of intraoperative monitoring for intact PTH serum levels have facilitated the treatment of patients with solitary parathyroid adenoma. Minimal invasive parathyroidectomy is the ideal surgical treatment for patients with PHPT due to a single parathyroid adenoma. In a survey of the members of the International Association of Endocrine Surgeons, more than half of them...

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...

Corticotropin Producing Tumor

Cushing's syndrome associated with a pancreatic neuroendocrine tumor that secretes corticotropin usually occurs in patients with neuroendocrine tumors that secrete another peptide and cause another syndrome.55 Malignant neuroendocrine tumors commonly secrete more than one peptide. Excessive production of corticotropin by a pituitary tumor may occur in patients with MEN 1 but is usually mild and clinically insignificant.55 Cushing's syndrome has also been reported in 5 of patients with...

Criteria of Malignancy of Cortical Tumors

The criteria determining whether an adrenal neoplasm is benign or malignant are not precise. Currently, the only accepted criteria are metastasis, either synchronous or TABLE 69-1. Adrenal Surgery in Lille, France, during the Period January 1985 to December 1999 TABLE 69-1. Adrenal Surgery in Lille, France, during the Period January 1985 to December 1999 *54 malignant adrenal tumors 46 adrenocortical carcinoma, 8 others. *54 malignant adrenal tumors 46 adrenocortical carcinoma, 8 others....

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...

Diazepam Binding Inhibitor

Another peptide that is produced by the human D cells is diazepam-binding inhibitor (DBI), which is an 86-amino acid peptide that binds to the benzodiazepine recognition site within the y-aminobutyric acid (GABA)-receptor complex.60 Immunocytochemical studies have localized DBI to D cells in human islets, although in rat islets the peptide seems to be confined to the A cells.61 Because DBI inhibits glucose-stimulated insulin secretion,6162 the two peptides produced by the D cells, somatostatin...

Embryology

The pancreas is a derivative of the caudal part of the primitive foregut. It develops embryologically from dorsal and ventral pancreatic primordia, which appear at days 26 and 32 of fetal development, respectively.1 The dorsal pancreatic bud originates as an endodermal outpouching from the dorsal aspect of the duodenum, and the smaller ventral pancreatic bud arises from the base of the hepatic diverticulum, closely related to the common bile duct (Fig. 75-1).2 As the descending duodenum...

Established Criterion for Evaluation of Intraoperative Hormone Levels

The QPTH criterion to predict operative success (normal or low calcium levels for at least 6 months after parathyroidectomy) used in our institution is a drop in the PTH level of 50 or more from the highest level, either preincision or pre-excision, 10 minutes after complete resection of all hyperfunctioning tissue. This criterion was studied and selected before 1993 when the assay was used with previously standard bilateral neck explorations and has proven to be effective through prospective...

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...

Etiology of Primary Hyperparathyroidism

About 80 of patients with primary hyperparathyroidism have a single adenoma, 15 have hyperplasia of all four glands, and 5 have double adenomas.2 The cause of parathyroid adenoma or hyperplasia is not known. Head and neck irradiation increases the risk of primary hyperparathyroidism by 11 per centigray.3-4 Ten percent of parathyroid adenomas have a PRAD-1 oncogene (cyclin D gene activated by PTH promoter). Mutations in the calcium sensor protein appear not to be an important cause of primary...

Experience with Endoscopic Parathyroidectomy by the Lateral Approach

We developed the technique for endoscopic parathyroidectomy by the use of a lateral approach on the line of the anterior border of the SCM in 1998.13 Since then, over the course of 5 years (1998 to 2002), we operated on 528 patients with PHPT.34 An endoscopic approach was proposed for patients with sporadic PHPT, without associated goiter and without previous neck surgery, in whom a single adenoma was localized by means of sonography and sestamibi scanning. The procedure was performed by a...

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...

Follicular Adenoma

Pathologic Features of Follicular Adenoma Follicular adenomas are benign tumors of the thyroid gland that grow in glandular or follicular patterns. They can occur in any portion of the thyroid and in any age group they are more common in young adults. Adenomas are usually solitary and less than 3 cm in size, although significant numbers of exceptions to these rules exist.6 The lesions tend to grow slowly within a capsule of surrounding compressed thyroid glandular tissue. Over time, they...

General Discussion

In view of the high prevalence figures for PHPT found in population studies, it is apparent that only a proportion of all subjects with PHPT are surgically treated.23,24 This is also true in the city of G teborg, where the medical community has a liberal attitude toward PHPT surgery. Subjects who are under medical care for other diseases are more likely to have PHPT diagnosed and treated. This means that a possible bias has been introduced in all three Scandinavian studies. In the G teborg...

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...

Genetic Factors

The thyroid gland contains a series of enzymes that are essential for the biosynthesis and secretion of thyroid hormones. A defect in any of these hormones can result in diminished hormone synthesis and a condition of goiter formation known as dyshormonogene sis. Because the defects are inherited disorders, dyshormonogenesis is also known as familial goiter. These enzyme defects may be partial or complete. Patients with a more severe enzymatic defect may develop goiter and cretinism early in...

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...

GRFoma

GRFomas, first described in 1982,66,67 are neuroendocrine tumors that secrete excessive amounts of GRF. Patients with these tumors have acromegaly. GRF is a peptide that is similar to VIP.66'67 GRFomas can occur (in order of decreasing frequency) in the lung (bronchus), pancreas, jejunum, adrenal, and retroperitoneum.68 Patients with GRFoma commonly have a large pancreatic neuroendocrine tumor (> 6 cm) that is metastatic in one third of cases at diagnosis. Approximately 50 of patients with...

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 FIGURE 36-6. Summary of chromosomal aberrations analyzed by comparative genomic hybridization in 15 Hiirthle cell adenomas and 13 Hiirthle cell carcinomas. the accumulation of mitochondria and eosinophilic cytoplasm on histology. They are also more likely to be...

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...

Hyperplasia

It is common knowledge that nodules develop in normal thyroid glands with aging.67 In growing thyroids, the development of the goiter is almost invariably accompanied by the development of multiple nodules of varying size.68 The nodules are generally softer than normal tissue. The surface of a sectioned hyperplastic gland appears granular, and the histopathologic picture shows a dysplastic arrangement with wide variation of follicle size and areas with increased cell density (Fig. 28-3)....

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...

Illustrative Cases

A 44-year-old woman had persistent symptomatic hypercalcemia after two unsuccessful cervical explorations for primary HPT with removal of an enlarged left superior parathyroid gland and identification of all except ihe right inferior parathyroid gland. The diagnosis of persistent primary HPT was reconfirmed biochemically. Review of the previous pathology revealed a normal left superior gland. US of the neck revealed a 2- x 5.4- x 1.7-cm nodule posterior to the lower pole of the right lobe of...

Imaging Consequences

Because of the central location within the abdominal cavity and the vicinity of numerous viscera, plain films are rarely informative. Occasionally, a large adrenal mass may be suggested by the downward displacement of the kidney, but this appearance is rarely seen, and differentiation from renal, splenic, pancreatic, gastric, and retroperitoneal tumors requires further investigation. Calcification may be seen in the adrenal glands and can be idiopathic or result from neonatal causes...

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...

Intracellular Messengers Regulating Parathyroid Hormone Release

Regulation of hormone release involves translation of extracellular signals through interacting second messenger systems such as cytoplasmic Ca2+j, cAMP, and diacylglycerol production through phosphoinositol hydrolysis. It has been demonstrated that external calcium acts through all of these messenger systems of the parathyroid cell.31 Calcium interferes with parathyroid adenylate cyclase and cAMP-dependent protein kinases.32 This mode of action has been seen in many agents besides calcium and...

Intraoperative Localization Methods

High-resolution intraoperative US may be useful once the peak of the learning curve has been reached and operating time can be reduced significantly. Kem and colleagues51 found it to be more effective than any other preoperative technique for intrathyroid or perithyroid glands. The benefit of the routine use of intraoperative US in reoperative parathyroid surgery has not been established . Tc 99m sestamibi is the most common localization test in recurrent parathyroid disease. It is possible to...

Intraoperative Management

Before the patient undergoes induction of anesthesia, appropriate pharmacologic agents must be available. Adequate peripheral access plus a radial arterial catheter, in addition to a urinaiy catheter, is routinely utilized and, rarely a Swan-Ganz catheter may be placed if indicated on the basis of cardiac disease or other problem. Sodium nitroprusside (Nipride) was previously the intraoperative agent of choice for rapid control of acute hypertension. It is a powerful direct-acting vasodilator...

Intraoperative Protocol Blood Sample Collection Time and Processing

In the operating room, a 14- or 16-gauge cannula is placed into an antecubital or other available peripheral vein. If not available, an arterial line can be used. This vascular access is maintained without heparin using a saline drip with extension tubing and a three-way stopcock at the head of the table. This allows blood sampling at the required intervals. Such access can also be used by the anesthesiologist as long as administered drugs are not collected with the blood samples used for PTH...

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 Blood Flow

The pancreatic islets have a rich blood supply compared with the surrounding exocrine tissue. Approximately 10 of the pancreatic blood flow is directed to the islets, which make up only approximately 1 to 2 of the pancreatic mass. The microvasculature of the pancreatic islets exhibits a characteristic feature, which has been carefully studied in the rat.14 It has been shown that the arterioles nourishing an islet enter into the central B-cell mass, where fenestrated and highly permeable...

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...

Islet Nerves

The pancreatic islets are richly innervated by the autonomic nerves (see Fig. 78-1).1516 These nerves are postganglionic sympathetic nerves with their nerve cell bodies in the celiac ganglion, and postganglionic parasympathetic nerves with their nerve cell bodies in intrapancreatic ganglia. Preganglionically, the nerve impulses pass through the splanchnic and vagus nerves, respectively. The nerves primarily innervate the vessels, but some fibers also enter into the islets and terminate in close...

Islet Neurotransmitters Sympathetic Effects

It was initially thought that the neurotransmitter mediating the sympathetic effects is norepinephrine because this is the classic adrenergic neurotransmitter and is known to inhibit glucose stimulated insulin secretion.70 However, combined adrenergic blockade does not abolish the influences of sympathetic nerve stimulation on insulin and glucagon secretion and norepinephrine only partially reproduces the stimulation of glucagon secretion that accompanies sympathetic nerve activation.71'72...

Laboratory Investigations

In patients with hypercalcemia, it is usually relatively easy to make the diagnosis of primary hyperparathyroidism by documenting an increased blood intact or two-site parathyroid hormone (PTH) level and normal or increased urinary calcium concentration. The two-site or intact PTH (iPTH) assays do not cross-react with PTHrP, the most common peptide secreted by nonparathyroid cancers.26 PTHrP cross-reacts with some mid- or C-terminal PTH assays and causes a falsely elevated PTH value. Some...

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,...

Limitations and Difficulties of Comparative Genomic Hybridization

CGH only detects genomic aberrations that involve loss or gains of DNA sequences. Balanced translocations or inversions are therefore not detectable, nor are small intragenic rearrangements and point mutations. CGH also only detects DNA sequence copy number changes relative to the average copy number in the entire tumor sample. The relative green-to-red ratios can be transformed to indicate actual copy numbers if the absolute copy number in several loci are independently determined or if the...

Localization

Whereas 3 decades ago bolus nephrotomography or angiography might have provided the mainstay of localization, three excellent localization modalities are currently available. Soon after the development of CT scanning, the adrenal was noted to be exceptionally well depicted,19 and CT is now considered the most reliable, efficient, precise, and widely available localization technique (Fig. 71-2). Because 90 of tumors are located in the adrenal glands, a high-quality CT scan is likely to identify...

Localization of Persistent or Recurrent Medullary Thyroid Carcinoma

Computed Tomography and Ultrasonography A number of methods have been used to localize residual or recurrent disease in patients with persistent or recurrent calcitonin elevation after surgery for MTC. Careful physical examination may reveal adenopathy in the jugular and para-tracheal regions. Patients with advanced metastatic disease may acquire subcutaneous tumors of the trunk and extremities. Imaging studies that have been reported to be successful in localization include ultrasonography...

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,...

Medical Management versus Operation

Optimum treatment recommendations for patients with Z-E syndrome have undergone continuing change during the 40 years since Zollinger and Ellison reported on their first two patients, both of whom required a TG to control the complications of recurring peptic ulcer disease. These changes in Z-E syndrome management have come with a better understanding of the natural history and pathophysiology of Z-E syndrome, the RIA for gastrin, new imaging technologies that preoperatively and...

Medullary Carcinoma

The C cell is the cell of origin for medullary carcinoma and is at the basal portion of follicular epithelium adjacent to the basement membrane. C cells are best demonstrated by immunohistochemical stains for calcitonin and markers for neuroendocrine cells, such as neuron-specific enolase, chro-mogranin, and synaptophysin. The clinical syndromes encountered with C cells include Familial medullary carcinoma Nonfamilial or sporadic medullary carcinoma Seventy-five percent of medullary carcinomas...

Men

The most common functional islet cell tumor in MEN 1 patients is the gastrinoma,22'27 34 MEN 1 patients account for approximately 30 of all patients with the ZES, and, even without a family history or other symptoms, all sporadic ZES patients should be evaluated for the possibility of MEN 1 and at least a serum calcium and prolactin level obtained. The surgical treatment of ZES in the MEN 1 patient has remained controversial because of a previously high failure rate in curing the...

Molecular Characterization of the NIS Gene

The molecular characterization of NIS was accomplished in 1996 when Dai and colleagues cloned the transporter3 from Xenopus laevis oocytes, using the complementary DNA (cDNA) libraries derived from FRTL-5 cells (functional rat thyroid-derived cell line). The cDNA encoding the human NIS (hNIS) gene was identified on the expectation that hNIS would be highly homologous to rat NIS.7 The hNIS gene is located on chromosome 19pl2-13.2. It comprises 1929 base pairs encoding a 643-amino acid...

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...

Multiple Endocrine Neoplasia

When talking of multiple endocrine neoplasia type 1 (MEN 1), a proper definition is difficult to establish because the syndrome can result from up to 20 different combinations of endocrine and nonendocrine tumors.1'2 No definition could cover all registered cases or families. Thus, a patient with MEN 1, or Wermer's syndrome, is one who presents with alterations of hypersecretion or hyperplasia, or both, from two of the three main MEN 1-related endocrine tumors that is, parathyroid adenomas,...

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...

Neurotensinoma

Pancreatic neuroendocrine tumors that secrete neurotensin have been reported.72'73 Neurotensin is a peptide that is present in the brain and the gastrointestinal tract.72 Neurotensin can cause hypotension, tachycardia, cyanosis, pancreatic secretion, intestinal motility, and small intestinal secretion.72 Patients with neurotensinomas have diarrhea with hypokalemia, weight loss, diabetes, cyanosis, hypotension, and flushing. Patients may be cured by tumor resection, and others have responded to...

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...

Nontoxic Multinodular Goiter Theories of Pathogenesis and Thyrocyte Regulation

The pathogenesis and hence the treatment of multinodular goiter are debatable. If a goiter were simply induced by uninhibited TSH stimulation, one might expect it to be a diffuse goiter. Early studies by Taylor suggested a natural progression from diffuse toward multinodular.104 Indeed, TSH levels are in general not elevated in sporadic goiters. Studer and Ramelli105 suggested that newly generated follicles involve thyrocyte clones that may retain the ability to concentrate iodine (hot nodules)...

Operative Approach

Operative exposure may be achieved through a bilateral subcostal or long midline incision. Upon entering the peritoneal cavity, a thorough exploration is performed to exclude metastatic disease. Tru-Cut needle or wedge biopsy of any suspicious liver lesions is performed and suspicious lymph nodes are sent to the pathologist for frozen section analysis. A generous Kocher maneuver is then performed from the level of the right gonadal vein to the aorta medially. At this time, the head and neck of...