Improvement of sleep disturbance and neurocognitive function after parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: To investigate the frequency of the nontraditional symptoms of sleep disturbance and impaired cognitive functioning in patients with primary hyper-parathyroidism (PHPT) and to assess changes in such patients after parathyroidectomy. METHODS: In this study, we used formal neurocognitive assessment of patients undergoing parathyroidectomy for PHPT. The Brief Sleep Disturbance Inventory assessed sleep disturbance, and Stroop tests evaluated for cognitive impairment. Study patients underwent preoperative and postoperative neurocognitive testing. RESULTS: Fifty-five patients underwent neurocognitive evaluation; the 43 women and 12 men had a mean age of 63 years. Sleep disturbance was assessed in all 55 patients, whereas evaluation for cognitive impairment was performed in 47. Sleep disturbance was identified preoperatively in 24 (44%) of the 55 patients. This disorder affected 17 (31%) of 55 patients postoperatively (P<0.01). Impaired executive functioning was found at baseline in 6 (13%) of 47 patients and decreased to 1 (2%) of 47 post-operatively (P<0.01), whereas impaired cognitive processing speed was detected in 12 (26%) of 47 patients at baseline and decreased to 3 (6%) of 47 after parathyroidectomy (P<0.01). Eight patients did not meet the National Institutes of Health consensus statement criteria for parathyroidectomy; 4 of these patients had preoperative impairment of sleep or cognitive functioning, 3 of whom showed improvement postoperatively. CONCLUSION: Sleep disturbance and neurocognitive impairment occur in patients with PHPT, and these disorders improve after parathyroidectomy. Further objective evaluation of nontraditional symptoms in patients diagnosed as having PHPT is warranted.

Followup of patients with papillary thyroid cancer: in search of the optimal algorithm.

BACKGROUND: Cervical recurrence occurs in up to 30% of patients after surgical treatment for papillary thyroid cancer. This study sought to determine an appropriate algorithm for followup evaluation. STUDY DESIGN: Patients undergoing total thyroidectomy for papillary thyroid cancer were identified. Clinicopathologic data were recorded, as were the results of all followup evaluations including radioiodine scan, cervical ultrasonography, and serum thyroglobulin levels. The disease recurrence-free survival probability was estimated, and risk factors for recurrence were determined. RESULTS: Thyroidectomy with or without neck dissection was performed in 162 patients. We excluded 36 patients (followup less than 6 months in 26, extracervical disease at diagnosis in 4, unknown tumor size in 6) from the analysis. Of the remaining 126 patients, 109 (86.5%) had no evidence of disease, with serum thyroglobulin < 1 ng/mL at last followup; 4 (3.2%) had no evidence of disease (negative imaging), with serum thyroglobulin > 1 ng/mL, and 13 (10.3%) had recurrent disease. Cervical recurrence occurred in nine patients, all detected by routine ultrasonography. Pulmonary metastases occurred in four patients; three were diagnosed by chest CT and one by radioiodine scan. Thyroid stimulating hormone-suppressed thyroglobulin levels were available in 11 of the 13 patients and were elevated in 9. Patients with high T stage (extrathyroidal extension), or high N stage had an increased risk of recurrence. CONCLUSIONS: A followup strategy emphasizing routine cervical ultrasonography and unstimulated thyroglobulin is effective in identifying patients with recurrent papillary thyroid cancer, and may minimize the indiscriminate use of therapeutic radioiodine for radiographically occult disease. Surgery remains the optimal treatment of cervical recurrence, which is the dominant pattern of treatment failure.

Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography.

BACKGROUND: Four-dimensional computed tomography (4D-CT) provides both functional and highly detailed anatomic information about parathyroid tumors. The purpose of this study was to compare 4D-CT with sestamibi imaging and ultrasonography as methods for the accurate preoperative localization of hyperfunctioning parathyroid glands before parathyroidectomy. METHODS: A study of 75 patients with primary hyperparathyroidism was performed at a tertiary-care institution. Sestamibi imaging, ultrasonography, and 4D-CT were performed on each patient preoperatively. Results of the imaging studies were compared with operative findings, pathologic data, and biochemical measurements to assess the sensitivity and specificity of each of the imaging modalities. RESULTS: 4D-CT demonstrated improved sensitivity (88%) over sestamibi imaging (65%) and ultrasonography (57%), when the imaging studies were used to localize (lateralize) hyperfunctioning parathyroid glands to 1 side of the neck. Moreover, when used to localize parathyroid tumors to the correct quadrant of the neck (ie, right inferior, right superior, left inferior, or left superior), the sensitivity of 4D-CT (70%) was significantly higher than sestamibi imaging (33%) and ultrasonography (29%). CONCLUSION: 4D-CT provides significantly greater sensitivity than sestamibi imaging and ultrasonography for precise (quadrant) localization of hyperfunctioning parathyroid glands. This allows improved preoperative planning, particularly for the case of reoperation. In addition to the data that are provided, we present a novel classification scheme for use in parathyroid localization.

Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

INTRODUCTION: Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence. To help resolve this controversy, we retrospectively analyzed the clinical characteristics, surgical treatment, and clinical outcome of patients with MEN1-related PETs. METHODS: All patients had histologic or radiographic confirmation of a PET in the setting of MEN1. Disease progression was defined radiographically as the development of new pancreatic tumors or distant metastases. Progression-free survival (PFS) and overall survival (OS) were used as the endpoints of this analysis. RESULTS: We identified 98 patients with MEN1, 55 (56%) of whom had PETs, including 27 women and 28 men with a median age of 37 years (range 8-69 years) at the time of diagnosis. Functioning PETs were present in 35 (64%) of 55 patients, and nonfunctioning tumors were present in 20 (36%). Pancreatic surgery was performed in 38 (69%) of the 55 patients; and the first operation included enucleation (n = 4), total pancreatectomy (n = 3), Whipple procedure (n = 4), and distal pancreatectomy (n = 27). The median size of the resected tumors was 2.8 cm (range 0.6-11.0 cm). Recurrent disease developed in the residual pancreas in 7 (20%) of 35 at-risk patients a median of 7.8 years after the first operation, and distant metastases occurred in 5 (14 %) of 36 surgically treated patients without distant metastasis (2 patients had distant metastases when surgery on the primary tumor was performed) at a median of 2.7 years following surgery. At last follow-up, 16 (29%) of 55 patients with PETs had died, 12 (22%) were alive with disease, 26 (47%) were alive without evidence of disease, and 1 (2%) was lost to follow-up. The median OS was 19.5 years (range 13-26 years) and was significantly longer for patients who had functioning PETs versus those with nonfunctioning tumors (P = 0.0007), for patients who underwent surgical resection of their PETs versus those who did not (P = 0.0043), and for patients with localized versus metastatic PETs at the time of diagnosis (P < 0.0001). Multivariate analysis revealed that younger age, hormonal function, and PET resection were independently associated with longer OS. CONCLUSIONS: Our data suggest that early diagnosis and surgical excision of MEN1-related PETs improves survival. However, translating these data into a surveillance strategy for the early detection of PETs is complex owing to the potential morbidity of pancreatic resection and the risk of long-term insulin dependence.

Abdominal visceral lesions in von Hippel-Lindau disease: incidence and clinical behavior of pancreatic and adrenal lesions at a single center.

INTRODUCTION: Von Hippel-Lindau disease (VHL) is a dominantly inherited multi-system syndrome. Although pheochromocytoma is the hallmark endocrine neoplasm, pancreatic lesions occur frequently, and their management can be complex. This report describes 26 patients from a single institution with pancreatic or adrenal lesions (or both) in the background of VHL. METHODS: We reviewed records for all patients treated for adrenal (type 2 VHL) or pancreatic manifestations of VHL at our institution from 1990 to 2004. RESULTS: Forty patients with VHL were identified from 24 pedigrees; 26 (65%) had adrenal or pancreatic involvement (or both). Seven patients had isolated pheochromocytomas, 16 had isolated pancreatic lesions, and 3 had both. Of the 10 patients with pheochromocytomas, 4 had bilateral adrenal involvement. All but three pheochromocytomas were diagnosed in patients aged 40 years or younger. Of the 19 patients with pancreatic lesions, 8 had cystic lesions, 8 had neuroendocrine tumors, and 3 had both. Of 11 patients with neuroendocrine tumors, 4 had metastases (3 hepatic, 1 nodal). No patient with cystic pancreatic lesions developed carcinoma. CONCLUSIONS: VHL should be familiar to the endocrine surgeon because of the high incidence (65% in our series) of visceral endocrine lesions (pancreas 40%, adrenal gland 18%, both 7%). As seen in other hereditary endocrinopathy syndromes, pheochromocytomas are frequently bilateral; therefore,close follow-up of the contralateral gland in young patients with a unilateral lesion is critical. Cystic lesions of the pancreas may be closely monitored, whereas neuroendocrine tumors should be removed because of the risk of metastasis. Pancreatic pathology is not uncommon in VHL patients with pheochromocytoma and should be sought during the preoperative assessment.

Laparoscopic resection of adrenal cortical carcinoma: a cautionary note.

BACKGROUND: While laparoscopic removal of small, benign, functioning adrenal tumors is accepted, laparoscopic resection of adrenal tumors that may be adrenal cortical carcinoma (ACC) remains controversial. METHODS: The records of all patients with ACC evaluated at a single institution from 1991 through 2004 were reviewed retrospectively. RESULTS: Among 170 patients with ACC, 153 patients underwent open anterior adrenalectomy, 6 underwent laparoscopic adrenalectomy, 1 was treated via an open flank approach, and 10 had no operation. At a median follow-up of 28 months, 115 (86%) of 133 patients who had undergone open anterior resection of primary ACC had had a recurrence. Local recurrence and peritoneal carcinomatosis were components of initial failure in 46 (35%) and 11 patients (8%), respectively. In contrast, all 6 patients who underwent laparoscopic resection of ACC had recurrences, and peritoneal carcinomatosis was a component of initial failure in 5 (83%) of them (open vs laparoscopic resection, Fisher exact test P = .0001). CONCLUSIONS: Laparoscopic resection of ACC is associated with a high risk of peritoneal carcinomatosis. Open adrenalectomy remains the standard of care for patients presenting with an adrenal cortical tumor for which ACC is in the differential diagnosis.

RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors.

Hereditary medullary thyroid carcinoma (MTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. Associations between specific RET mutations (genotype) and the aggressiveness of MTC and presence or absence of other endocrine neoplasms (phenotype) are well documented. Mutations in six exons (10, 11, 13, 14, 15, and 16) located in either cysteine-rich or tyrosine kinase domains cause one of three distinctive clinical subtypes: familial MTC, multiple endocrine neoplasia (MEN) type 2A (including variants with Hirschsprung's disease and cutaneous lichen amyloidosis), and MEN 2B. Hallmarks of MEN 2A include MTC, pheochromocytoma, and hyperparathyroidism. MEN 2B is associated with an earlier onset of MTC and pheochromocytoma, the absence of hyperparathyroidism, and the presence of striking physical stigmata (e.g., coarse facies, ganglioneuromatosis, and marfanoid habitus). Familial MTC is not associated with other endocrine neoplasms; however, the accurate distinction between familial MTC and MEN 2A may be difficult in kindreds with small size, incomplete histories, or a predominance of young individuals who may not have yet fully manifested the syndrome. Genetic testing detects greater than 95% of mutation carriers and is considered the standard of care for all first-degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and the extent of surgery are based upon a model that utilizes genotype- phenotype correlations to stratify mutations into three risk levels.

Surgical management of thyroid carcinoma.

Thyroid carcinoma has a unique biologic behavior characterized by early spread to regional lymph nodes and occasional extrathyroidal soft tissue extension but a low incidence of distant metastasis and infrequent disease-related death. Therefore, controversy exists over the proper extent of thyroidectomy and regional lymph node dissection in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific mortality makes it unlikely that the extent of surgery will ever be the subject of a prospective randomized trial. Although more extensive cervical surgery may have only a limited effect on the duration of survival in patients with DTC, it may significantly improve quality of life by minimizing cervical recurrence. The high rates of cervical recurrence in patients with DTC and MTC have alerted physicians to the importance of fine-needle aspiration biopsy and ultrasonography for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In patients with MTC, death caused by disease is uncommon in the absence of radiographically evident distant metastasis at the time of thyroidectomy. Cervical recurrence is even more common with MTC, and the need for compartment-oriented lymphadenectomy is accepted as standard surgical treatment to minimize disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide clinical management, but basal CT levels should not be used to direct the timing of prophylactic thyroidectomy in affected high-risk patients with familial MTC.

Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1.

HYPOTHESIS: Three-gland parathyroidectomy with trans-cervical thymectomy and cryopreservation is the preferred initial surgical approach for hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with multiple endocrine neoplasia type 1 who underwent 1 or more surgical procedures for HPT from January 1, 1973 to April 30, 2004. RESULTS: At initial parathyroid surgery, 16 (43%) of 37 patients had fewer than 3 parathyroid glands resected (group 1); 16 (43%) had at least 3 but fewer than 4 glands (group 2), and 5 (14%), 4 or more glands (group 3). Follow-up of at least 6 months after initial surgery was complete for 31 (84%) of 37 patients. CONCLUSIONS: Recurrent HPT in patients with multiple endocrine neoplasia type 1 is frequent if fewer than 3 glands are removed at initial parathyroidectomy. Optimal surgical intervention must balance the risk of recurrent hypercalcemia with the morbidity of permanent hypoparathyroidism. Three-gland parathyroidectomy, transcervical thymectomy, and parathyroid cryopreservation constitute our preferred initial surgical procedure.

Surgical treatment of non-functioning pancreatic islet cell tumors.

Pancreatic endocrine tumors (PETs) are rare neoplasms originating from the amine precursor uptake and decarboxylation (APUD) stem cells. Although the majority of PETs are sporadic, they frequently occur in familial syndromes. PETs may cause a variety of functional syndromes or symptoms of local progression if they are non-functional. General neuroendocrine tumor markers are highly sensitive in the diagnostic assessment of a PET. Imaging studies for tumor localization and staging include computer tomography (CT) scan, magnetic resonance imaging (MRI), In(111)-octreotide scan, MIBG, and endoscopic ultrasonography (EUS). Treatment of PETs often requires a multi-modality approach; however, surgical resection remains the only curative therapy for localized (non-metastatic) disease. Treatment of metastatic disease includes biologic agents, cytotoxic chemotherapy, and liver-directed therapies.

Pheochromocytoma and medullary thyroid carcinoma: a new genotype-phenotype correlation of the RET protooncogene 891 germline mutation.

Prior experience in kindreds with a codon 891 RET protooncogene mutation indicates that carriers of this mutation develop only hereditary medullary thyroid carcinoma without evidence of other manifestations of multiple endocrine neoplasia type 2. In this paper, we report the first documented case in which medullary thyroid carcinoma and pheochromocytoma were clinically expressed in members of a family affected by the codon 891 RET mutation. Genetic analysis of the RET protooncogene in this family revealed an exon 15 missense mutation at codon 891 that resulted in a serine to alanine amino acid substitution. These findings indicate that patients with this mutation should be screened for pheochromocytoma.

A novel point mutation of the RET protooncogene involving the second intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma, a tumor that arises from the parafollicular cells of the thyroid gland, occurs in isolation (as in familial medullary thyroid carcinoma), in association with hyperparathyroidism and pheochromocytoma (as in multiple endocrine neoplasia type 2A), or in association with pheochromocytoma, marfanoid habitus, and mucosal neuromas (as in multiple endocrine neoplasia type 2B). These genetic syndromes are associated with germline-activating mutations of the RET protooncogene, a cell surface tyrosine kinase receptor, which is believed to modulate specific intracellular signaling pathways involved in the regulation of C cell proliferation and apoptosis. RET-activating mutations involve two important functional areas of the receptor: the cysteine-rich extracellular domain and the intracellular tyrosine kinase domain. Multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma are more commonly associated with mutations in the cysteine-rich extracellular domain, whereas multiple endocrine neoplasia type 2B is exclusively associated with mutations involving the second intracellular tyrosine kinase domain. Here, we describe a novel missense mutation of the RET protooncogene that substitutes arginine for proline at codon 912 of the intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.

Surgical management of hereditary pheochromocytoma.

BACKGROUND: Surgical treatment of hereditary pheochromocytoma remains controversial because of the need for lifelong corticosteroid therapy and the risk of Addisonian crisis associated with bilateral total adrenalectomy. We examined our large series of patients with hereditary pheochromocytoma to evaluate postsurgical outcomes, particularly in those who underwent cortical-sparing adrenalectomy. STUDY DESIGN: We retrospectively reviewed the outcomes of all patients with histopathologic diagnoses of hereditary pheochromocytoma treated at our institution from 1962 to 2003. Familial disease was initially determined by pedigree analysis, genetic testing, or both for multiple endocrine neoplasia (MEN) types 1, 2A, or 2B; von Hippel-Lindau disease (VHL); neurofibromatosis type 1 (NF-1); or familial paraganglioma syndrome (FP). RESULTS: Adrenal pheochromocytomas were present in 56 of 59 patients (95%): MEN2A (39), MEN2B (7), VHL (6), MEN1 (2), NF-1 (2). Paragangliomas (extraadrenal pheochromocytomas) were present in the remaining 3 of 59 patients (5%): FP (2) and NF-1 (1). Thirty-eight of 56 patients with pheochromocytomas had cumulative operations resulting in total or subtotal bilateral adrenalectomy. Acute adrenal insufficiency (Addisonian crisis) occurred in 4 of these 38 patients (11%). Cortical-sparing adrenalectomy was performed in 26 patients who underwent bilateral adrenal resection; 17 (65%) were corticosteroid independent at a median followup of 71 months. Recurrent pheochromocytoma developed in an adrenal remnant in 3 of 30 patients (10%) who underwent unilateral or bilateral cortical-sparing procedures. Metastatic disease did not develop in any patient with pheochromocytoma, but has occurred in two of three patients with paragangliomas. CONCLUSIONS: Our data suggest that a cortical-sparing adrenalectomy can successfully avoid the need for corticosteroid replacement in the majority of patients who undergo a bilateral adrenalectomy. Long-term followup should include monitoring of the remnant gland for recurrent pheochromocytoma with yearly biochemical screening studies.

Preventable reoperations for persistent and recurrent papillary thyroid carcinoma.

BACKGROUND: Cervical recurrence occurs in up to 25% of patients with papillary thyroid carcinoma (PTC) due either to the aggressive biology of PTC or to inadequate treatment. This retrospective study was designed to determine the frequency of inadequate surgical or medical therapy as a cause of persistent or recurrent PTC. METHODS: We identified all patients who underwent reoperation for persistent (within 6 months of initial or pre-referral operation) or recurrent (greater than 6 months after initial or pre-referral operation) PTC from 1992 to 2003. Medical records including initial preoperative imaging, operative, and histopathology reports were reviewed. The initial surgical procedure was considered incomplete if all gross neoplasm was not removed or if "node plucking" was performed, and a subsequent recurrence occurred in the same cervical compartment. RESULTS: Seventy-two consecutive patients underwent reoperation for persistent (17) or recurrent (55) PTC. Of the 17 patients with persistent PTC, reoperation was judged to have been possibly preventable in 14 (82%) due to inadequate preoperative imaging or incomplete initial surgery. Of the 55 patients with recurrent PTC, reoperation was judged to have been possibly preventable due to incomplete initial surgery in 14 (25%). Based on the National Comprehensive Cancer Network guidelines, 33 (46%) of 72 patients with persistent or recurrent PTC received inadequate initial local treatment. CONCLUSIONS: Reoperation in 28 (39%) of 72 patients with persistent or recurrent PTC was potentially preventable. Accurate preoperative staging and adherence to the suggested National Comprehensive Cancer Network treatment guidelines may minimize the need for cervical reoperation.

Potential role for intraoperative gamma probe identification of normal parathyroid glands.

BACKGROUND: Patients undergoing central neck surgery are at risk for hypoparathyroidism. We hypothesized that gamma probe identification of sestamibi-labeled parathyroid glands might help maximize parathyroid preservation. METHODS: Records of 351 patients who underwent central neck surgery were reviewed. A subgroup of patients underwent sestamibi injection followed by gamma probe-directed parathyroid gland identification. RESULTS: Operation was performed for malignancy in 73% of patients and represented a reoperation in 34%. Persistent hypoparathyroidism was more common in patients who underwent reoperation versus a primary operation (6.8% versus 1.7%; P = 0.02). Thirteen patients underwent gamma probe-directed identification of sestamibi-labeled parathyroid glands; in 6 of these patients, sestamibi-labeled parathyroid glands were salvaged from the resected specimens and autografted. None of these 13 patients developed persistent hypoparathyroidism. CONCLUSIONS: Patients undergoing reoperative central neck surgery are at increased risk for postoperative hypoparathyroidism. Gamma probe-directed salvage of sestamibi-labeled parathyroid glands may help maximize parathyroid preservation, especially in complex or reoperative central neck surgery.

Fine-needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients.

BACKGROUND: False-positive, false-negative, and indeterminate fine-needle aspiration (FNA) biopsy results complicate the management of patients with thyroid nodules. METHODS: Thyroid FNA results from 240 consecutive patients (seen 1991 to 2002) were categorized into four groups: positive for malignancy, negative for malignancy, indeterminate for malignancy, and nondiagnostic. Indeterminate results included follicular neoplasm, Hürthle cell neoplasm, and suspicious for papillary carcinoma. The FNA results were compared with histopathologic analysis after thyroidectomy. RESULTS: The FNA results were 76 (32%) positive for malignancy, 53 (22%) negative for malignancy, 100 (42%) indeterminate for malignancy, and 11 (5%) nondiagnostic. There were 3 (4%) false-positive and 2 (4%) false-negative FNA results. Among the 100 indeterminate FNA results, carcinoma was found in 11 (15%) of 73 follicular neoplasms, 2 (20%) of 10 Hürthle cell neoplasms, and 14 (82%) of 17 suspicious for papillary carcinoma. For the 73 patients with follicular neoplasms, nodule diameter >2 cm was associated with an increased risk of malignancy (P <0.03). CONCLUSIONS: False-negative FNA results are uncommon, supporting the practice of observation in most of these patients. Among those with indeterminate biopsy results, high-risk subgroups include patients with FNA results suspicious for papillary carcinoma and follicular neoplasms >2 cm.

Medullary thyroid carcinoma: results of a standardized surgical approach in a contemporary series of 80 consecutive patients.

BACKGROUND: The surgical management and follow-up strategy in patients with medullary thyroid carcinoma (MTC) remain controversial because of the lack of data on the natural history of these tumors and their patterns of progression. METHODS: We reviewed the records of all patients who underwent a cervical operation for MTC between 1991 and 2002. Compartment-oriented surgery (COS) was performed to minimize the risk of cervical recurrence. RESULTS: We identified 92 consecutive patients who underwent a cervical operation for MTC: 80 had invasive MTC, and 12 had C-cell hyperplasia after prophylactic thyroidectomy for familial MTC. Ten (13%) of the 80 patients with invasive MTC presented with distant metastases and underwent COS to achieve local-regional control; cervical recurrence developed in none, but three have died of MTC. The remaining 70 patients underwent COS for primary (n=23) or recurrent (n=47) MTC. Disease recurred in 18 (26%) of these 70 patients at a median follow-up of 35 months, with 10 (14%) of the recurrences being cervical. Recurrent disease was associated with a basal calcitonin level of >250 pg/mL in all but four patients, two of whom showed tumor dedifferentiation. In contrast, only 5 (11%) patients without evidence of recurrence had basal calcitonin levels of >250 pg/mL at last follow-up. CONCLUSIONS: Complete COS minimizes cervical recurrence. Radiographic evidence of recurrent disease is unlikely when the calcitonin level is < or =250 pg/mL. These data could be used to develop a logical, cost-effective treatment and follow-up strategy for patients with MTC.

Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.

BACKGROUND: Cervical recurrence occurs in up to 30% of patients with differentiated thyroid carcinoma. We retrospectively compared preoperative transcutaneous ultrasonography and physical examination (PE) results in the detection of local-regional metastases (lymph node and soft tissue) in patients with thyroid cancer. METHODS: Data were collected retrospectively from the medical records of patients with thyroid carcinoma who underwent preoperative ultrasonography. Patients were divided into 3 groups: group 1, those undergoing primary thyroid/neck surgery; group 2, those undergoing reoperation for persistent disease; and group 3, those undergoing reoperation for recurrent thyroid carcinoma. For each group, we recorded the frequencies with which ultrasonography detected disease in a neck compartment (central or lateral) that was normal on PE. RESULTS: Two hundred twelve patients underwent operation for primary, persistent, or recurrent papillary (n=130), medullary (n=61), or follicular/Hürthle cell (n=21) carcinoma. Ultrasonography detected additional sites of metastatic disease not appreciated on PE in 21 (20%) of 107 group 1 patients, 9 (32%) of 28 group 2 patients, and 52 (68%) of 77 group 3 patients. The surgical procedure performed was altered by the information obtained from preoperative ultrasonography in 82 (39%) of the 212 patients. Of the 107 group 1 patients, cervical recurrence has been detected in only 6 (6%) at a median follow-up of 36 months, in spite of 67 (63%) having tumors larger than 2 cm or lymph node metastases. CONCLUSIONS: Preoperative high-quality ultrasonography detected lymph node or soft-tissue metastases in neck compartments believed to be uninvolved by PE in 39% of patients. Ultrasound findings altered the operative procedure in these patients, facilitating complete resection of disease and potentially minimizing local-regional recurrence.