Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer.

BACKGROUND: Cervical recurrences, predominantly in lymph nodes, occur in 14% to 30% of patients with papillary thyroid cancer (PTC). Postoperative surveillance for recurrent PTC increasingly includes thyrotropin-stimulated thyroglobulin and high-resolution ultrasonography (US). This combination commonly can detect recurrent disease as small as 5 mm. HYPOTHESIS: Preoperative US will increase detection and assessment of the extent of lymph node metastasis (LNM) in patients with PTC. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. PATIENTS: From January 1, 1999, to December 31, 2004, a total of 770 patients were seen, 551 (381 female and 170 male; median age, 47 years; age range, 9-89 years) who underwent initial surgical management and 219 (154 female and 65 male; median age, 44 years; age range, 5-90 years) who underwent cervical reoperation for PTC. The US images were obtained preoperatively for 486 initial and 216 reoperative patients. Therapeutic radioactive iodine was administered to 151 (68.9%) of the reoperative patients before the subsequent operation (median dose, 5.6 x 10(9) Bq; range, 7.4 x 10(8)-3.7 x 10(10) Bq). RESULTS: Ultrasonography identified nonpalpable lateral jugular LNMs in 70 (14.4%) of the patients undergoing initial exploration. Similarly, in reoperative patients, nonpalpable lateral LNMs were detected via US in 106 (64.2%), and 61 (28.2%) had LNMs detected in the central neck. Even when nodes were palpable preoperatively (37 [6.7%] of the initial and 56 [25.6%] of the reoperative patients), US assessment of the extent of LNM involvement altered the operation in 15 (40.5%) of the initial and 24 (42.9%) of the reoperative patients. The sensitivity, specificity, and positive predictive value for US were 83.5%, 97.7%, and 88.8% in initial patients, and 90.4%, 78.9%, and 93.9% in reoperative patients. CONCLUSIONS: Overall, preoperative US detected nonpalpable LNMs in 231 (32.9%) of the 702 patients with PTC who underwent US, thereby altering the operative procedure performed. In addition, even in patients with palpable LNs, US helped to guide the extent of lymphadenectomy.

Inferior laryngeal paraganglioma mimicking a primary thyroid tumor.

OBJECTIVE: To report an unusual case of inferior laryngeal paraganglioma that manifested as a thyroid neoplasm. METHODS: A case report is presented, including ultra-sonographic, surgical, histologic, and immunohistochemical findings, and diagnostic and therapeutic strategies are discussed. RESULTS: In a 33-year-old man with a mass in the left side of his neck, color Doppler ultrasonography revealed an extremely hypervascular lesion that appeared to arise in the left lobe of the thyroid gland. Fine-needle aspiration was noncontributory because of bloody samples, but core biopsy specimens suggested a nonthyroidal neoplasm. At surgical intervention, a 3.5-cm mass was found immediately posterior to the left thyroid lobe, not involving the thyroid capsule. Because the mass could not be dissected free from the thyroid, performance of a left thyroid lobectomy and isthmectomy was necessary. The pathology specimen was a paraganglioma. CONCLUSION: Paragangliomas may be sonographically similar to thyroid neoplasms and may be included in the differential diagnosis of a hypervascular thyroid mass.

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease.

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.

Laparoscopic adrenalectomy for pheochromocytoma.

OBJECTIVE: To determine the safety and results of laparoscopic resection of benign pheochromocytomas. PATIENTS AND METHODS: We retrospectively reviewed the medical charts of all patients who underwent laparoscopic adrenalectomy for benign pheochromocytomas at all 3 Mayo Clinic sites between January 1, 1992, and December 31, 2001. Demographics, comorbidities, clinical presentation, imaging studies, biochemical findings, operative intervention, and outcome were examined. Long-term follow-up was obtained via chart review and/or by direct telephone contact with the patient or a relative. RESULTS: Twenty-four women and 23 men with a mean age of 53.1 years (range, 16-81 years) underwent attempted laparoscopic resection of pheochromocytomas. In 5 patients, the procedure was converted to open laparotomy because of bleeding (2), inadequate exposure (2), and adhesions (1). The mean tumor size was 4.3 cm. The mean operative time (181.8 vs 1405 minutes; P = .03), mean hospital stay (6.00 vs 2.64 days; P < .001), and mean blood loss (340 mL vs 80 mL; P < .001) were greater in patients who underwent open laparotomy vs those who underwent laparoscopic resection. All specimens were classified as benign. The mean follow-up was 41 months (range, 10-89 months). No patients experienced a recurrence or developed metastatic disease. CONCLUSIONS: In light of surgical and anesthesia expertise, laparoscopic resection of benign pheochromocytomas is safe and effective with resultant short hospital stays. A low threshold to convert to an open procedure reduces operative times and decreases potentially serious complications. Although there have been no recurrences to date, long-term follow-up is required for all patients, especially those with hereditary forms of pheochromocytomas.

Current treatment of nodular goiter with hyperthyroidism (Plummer's disease): surgery versus radioiodine.

BACKGROUND: First described 9 decades ago by H. S. Plummer, thyroidectomy and radioiodine remain the 2 therapeutic modalities for toxic nodular goiter. The aim of this study was to determine its optimal treatment. METHODS: The presentation, operative treatment, pathology, and clinical course of 362 consecutive patients treated at our institution for Plummer's disease from 1990 to 1999 were retrospectively reviewed. RESULTS: Three hundred forty-six patients (63 men and 283 women) were treated surgically (181, 53%), with radioiodine (RAI, 157, 45%), or a combination of both (8, 2%). Mean age was 62 years (surgical, 55 years; RAI, 69 years). Nearly half were symptomatic, 51 (15%) with airway or swallowing compromise and 110 (32%) with cardiac complications. The estimated goiter size was larger (60 g or greater) in surgical (72 patients, 38%) than medically treated (45 patients, 29%) patients. RAI treatment dose averaged 28 mCi; 10 patients (6%) required a second treatment, and 8 patients failed treatment and required subsequent thyroidectomy. Types of thyroidectomy included total (29 patients, 16%), near-total (47 patients, 26%), bilateral subtotal (46 patients, 25%), and unilateral (58 patients, 32%). One month after treatment, hyperthyroidism had resolved in 96% of the surgical patients but only 6% of the RAI patients (mean time to resolution, 5.4 months). Only 55 (38%) of the RAI patients' goiters reduced in size. Recurrent laryngeal nerve paralysis and hypoparathyroidism each occurred in 3 (2%) patients. CONCLUSIONS: Surgical treatment results in rapid, reliable resolution of hyperthyroidism and removal of the nodular goiter with low morbidity and no mortality. RAI is also safe and effective, usually requiring a single dose, but the results are delayed and it usually fails to resolve a goiter.

Role for adrenal venous sampling in primary aldosteronism.

BACKGROUND: The aim of this study was to determine the effect of adrenal venous sampling (AVS) on the management of patients with primary aldosteronism. METHODS: From September 1990 through October 2003, 203 patients with primary aldosteronism (mean age, 53 years; range, 17-80; 163 men) were selected prospectively for AVS on the basis of degree of aldosterone excess, age, desire for surgical treatment, and computed tomographic (CT) findings. RESULTS: Both adrenal veins were catheterized in 194 patients (95.6%). Notable among the 110 patients (56.7%) with unilateral aldosterone hypersecretion were 24 (41.4%) of 58 patients with normal adrenal CT findings, 24 (51.1%) of 47 with unilateral micronodule (< or =10 mm) apparent on CT (7 had unilateral aldosterone hypersecretion from the contralateral adrenal), 21 (65.6%) of 32 with unilateral macronodule (>10 mm) apparent on CT (1 had unilateral aldosterone hypersecretion from the contralateral adrenal), 16 (48.5%) of 33 with bilateral micronodules, and 2 (33%) of 6 with bilateral macronodules. CONCLUSIONS: On the basis of CT findings alone, 42 patients (21.7%) would have been incorrectly excluded as candidates for adrenalectomy, and 48 (24.7%) might have had unnecessary or inappropriate adrenalectomy. AVS is an essential diagnostic step in most patients to distinguish between unilateral and bilateral adrenal aldosterone hypersecretion.

Aldosterone-secreting adrenocortical carcinomas are associated with unique operative risks and outcomes.

BACKGROUND: Adrenocortical carcinoma (ACC) that produces aldosterone is an extremely rare, uncharacterized endocrine malignancy. Our aim was to characterize this neoplasm in terms of its clinical behavior and patient outcomes. METHODS: A retrospective review was made of all patients who had operative management of aldosterone-secreting ACC from 1957 to 2000 at the Mayo Clinic. Comparisons were made to patients with non-aldosterone-secreting ACC treated during the same period. RESULTS: Of 141 patients with ACC, we identified 15 patients with aldosterone-secreting ACC. Isolated aldosterone hypersecretion was present in 10 patients, and mixed hormonal secretion was detected in 5. Mean tumor size and weight were 10.8 cm and 453 g, respectively. Surgical management included curative resection in 10 patients (67%). Perioperative mortality was 20%. Disease recurred in 7 patients (70%) with a median interval of 17 months. Five-year survival was 52%. Patients with aldosterone-secreting ACC had an increased risk of perioperative mortality (20% vs 5%), yet they had an overall survival of 63 months compared to 19 months for patients with non-aldosterone-secreting ACC. CONCLUSIONS: Aldosterone hypersecretion occurs in 11% of all ACCs and is associated with unique operative risk and outcome. Although patients harboring aldosterone-secreting ACC appear to have an increased risk of perioperative death, survivors may have an improved overall survival rate compared with patients with non-aldosterone-secreting ACC.

Pheochromocytomas and paragangliomas in von Hippel-Lindau disease: a role for laparoscopic and cortical-sparing surgery.

HYPOTHESIS: Von Hippel-Lindau disease (VHL) is an autosomal-dominant disorder characterized by benign and malignant tumors involving the central nervous system, kidneys, pancreas, adrenal glands, and paraganglia. Appropriate management of pheochromocytomas and paragangliomas in VHL is evolving as we better understand the genetics and natural course of the disease and master advanced surgical techniques for adrenalectomy. DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: A total of 109 patients identified at the Mayo Clinic, Rochester, Minn, with VHL (60 males and 49 females) between January 1, 1975, and June 30, 2000. Seventeen patients (16%) had an identifiable adrenal mass and 3 patients had paragangliomas. Follow-up was complete in all but 2 patients. MAIN OUTCOME MEASURES: Clinical presentation, preoperative evaluation, surgical management, and outcome. RESULTS: Three patients with paragangliomas and 13 of 17 patients with adrenal masses underwent surgical resection. Median age at time of diagnosis was 30 years (range, 16-47 years); 8 (40%) were asymptomatic. Fractionated urinary catecholamine and metanephrine concentrations were normal in one third of patients. Computed tomographic scanning identified 20 (83%) of 24 tumors. Adrenalectomies were performed as unilateral or bilateral, open or laparoscopic, and, finally, total or cortical-sparing. Seven (50%) of the patients underwent other concurrent abdominal procedures. There were no deaths, with an overall operative morbidity of 2 patients (14%). Only the 2 patients in whom bilateral total adrenalectomies were performed became corticosteroid dependent. No recurrences have been noted to date. CONCLUSIONS: A multidisciplinary approach is imperative for proper examination and monitoring of patients with VHL. Evaluation should begin early in life and always before elective surgery and childbirth. All adrenal masses in patients with VHL should be thoroughly evaluated and most should be resected. Early intervention and advanced surgical techniques better allow for cortical-sparing and laparoscopic procedures. With low recurrence rates, corticosteroid independence can be maintained for prolonged periods.

The predictive value of laboratory findings in patients with primary hyperparathyroidism.

BACKGROUND: Despite extensive preoperative imaging and intraoperative "gadgetry" to facilitate localization of abnormal parathyroid glands, the onus of identification and resection remains with the surgeon in the operating room. We pondered the relative usefulness of routine laboratory studies to the surgeon as predictive guides to the intraoperative findings in patients with primary hyperparathyroidism (HPT). STUDY DESIGN: Pre- and postoperative laboratory data were analyzed in 166 consecutive patients (1998 to 1999) undergoing successful cervical exploration for sporadic primary HPT and were correlated with the pathologic findings. Patients with secondary HPT, multiple endocrine neoplasia, familial HPT, and parathyroid carcinoma were not included in this study. RESULTS: One hundred eighteen women and 48 men (mean age = 63 years) with parathyroid adenoma (n = 155) and sporadic hyperplasia (n = 11) were evaluated. Mean parathormone (PTH) levels varied little with the pathology: adenoma = 9.6 pmol/L and hyperplasia = 10.2 pmol/L (p > 0.05). In patients with parathyroid adenoma, analysis of preoperative measures showed a positive correlation (r = 0.48, p < 0.0001) with PTH and gland weight. The correlation appeared to be the strongest in the tails of the distribution; in 22 of 23 (96%) cases with PTH levels lower than 6 pmol/L, the offending lesion or lesions were less than 400 mg; in all six cases with PTH levels higher than 18.0 pmol/L, the abnormal gland or glands weighed more than 800 mg. PTH levels between 6 and 18 pmol/L revealed mean adenoma weight of 757 mg (median = 420 mg; range = 50 to 5,500 mg). CONCLUSIONS: Extreme values of PTH in patients with single-gland parathyroid disease alert the surgeon to the likelihood of small or large parathyroid adenomas. Laboratory studies do not differentiate adenoma from hyperplasia, nor do they pinpoint the size of abnormal glands with moderate-range PTH values.

Prolonged survival of a patient with multiple endocrine neoplasia type 2b and stage IV medullary thyroid carcinoma.

OBJECTIVE: To present a case of multiple endocrine neoplasia type 2B (MEN2B) with a prolonged course. METHODS: We describe the clinical, laboratory, and radiologic findings in a patient with MEN2B and review the various interventions during a period of approximately 3 decades. RESULTS: In 1962, a 19-year-old man with a marfanoid body habitus presented with multiple thyroid nodules and neurofibromas of the tongue. Total thyroidectomy demonstrated multicentric medullary thyroid carcinoma with cervical lymph node metastatic involvement. At the time of the first description of the MEN2B syndrome, the patient was enrolled in a surveillance program. An increase in urinary metanephrines resulted in bilateral adrenalectomy for multinodular pheochromocytoma in 1972. Increased serum calcitonin levels and the appearance of cervical lymphadenopathy led to modified radical neck dissection 12 years after the initial diagnosis of medullary thyroid carcinoma. In 1975, angiography revealed extensive hepatic lesions metastatic from the medullary thyroid carcinoma; this finding was confirmed by open liver biopsy in 1988. The patient lived 16 years after the initial diagnosis of liver metastatic disease and died 29 years after the initial examination. CONCLUSION: The 3-decade course of this patient not only represents a classic case of MEN2B but also allows us to present the history of this disease from its discovery to the current era of genetic testing and exemplifies the possibility of long-term survival in a patient with liver metastatic involvement from medullary thyroid carcinoma.

de Quervain's thyroiditis: surgical experience.

OBJECTIVE: To review a 35-year experience with management of de Quervain's thyroiditis (dQT), an uncommon inflammatory process of the thyroid gland that is usually treated medically and seldom necessitates surgical intervention. METHODS: A retrospective review was performed of medical records of patients with dQT treated surgically at a single institution between 1966 and 2000. The study group consisted of 11 women and 6 men (mean age, 50 years; range, 23 to 66). All pathology specimens were reviewed. RESULTS: Of the 17 study patients, 14 had surgical treatment before 1980. Typical symptoms of dQT, including pain and tenderness of the thyroid gland, occurred in eight patients, and two had dysphagia from an enlarged thyroid gland. Seven patients were asymptomatic. The indications for operation were a clinically indeterminate thyroid nodule (N = 14), dysphagia (N = 2), and hyperthyroidism with nodular goiter (N = 1). Fine-needle aspiration biopsy (FNAB) was performed in only two patients; biopsy findings were suspicious for a malignant lesion in one patient, and nondiagnostic in the other patient. Thyroid function tests (N = 14) revealed that 12 patients were euthyroid and 2 had hyperthyroidism. Surgical treatment consisted of unilateral lobectomy in 4 patients, near-total thyroidectomy in 12, and total thyroidectomy in 1. Temporary vocal cord palsy and temporary hypocalcemia occurred in one patient each. Fourteen patients (mean follow-up, 204 months) required long-term thyroid replacement therapy. No patient required further thyroid surgical intervention or had further thyroid disease. CONCLUSION: Although surgical intervention is not the primary treatment for dQT, when resection is performed it can be done safely and with low associated morbidity. In the modern era, with routine use of FNAB, fewer patients with this rare entity will require surgical exploration. Patients with atypical features and ones with euthyroidism are more likely candidates than others for surgical intervention.

Intraoperative monitoring of parathyroid hormone with a rapid automated assay that is commercially available.

The Mayo Clinic was one of the first institutions to develop an in-house rapid parathyroid hormone (PTH) assay that used homegrown antibodies to monitor plasma PTH levels during parathyroidectomy. This PTH assay is economical, but it requires highly trained technologists and an experienced laboratory director and it is difficult to perform in the operating suite. We sought a fully automated multipurpose autoanalyzer with bar code reader to identify different patients' names and capacity to manage specimens from several patients who are having simultaneous operations. In addition, after complete tumor removal, the plasma PTH level should decrease to < 25% of the baseline level; otherwise, it may indicate that the antibodies used in the assay have cross-reacted with long half-life fragments other than intact PTH, which has a half-life of only approximately 2 min. An automated multipurpose analyzer, the Immulite 1000 with a Turbo PTH kit (DPC), fits these criteria and has replaced our in-house rapid assay. Of 47 patients who had parathyroidectomy for primary hyperparathyroidism and were tested with the new equipment, 45 (96%) had their plasma PTH levels decrease to < 25% of the baseline levels. In 41 of 47 patients (87%), the PTH value decreased to < 5 pmol/L (provisional reference range) within 20 min after tumor excision. The usefulness of the PTH assay extends from the traditional diagnosis of parathyroid disease to intraoperative monitoring, helping to ensure a higher cure rate.