Surgery for Cushing's syndrome: an historical review and recent ten-year experience.

BACKGROUND: Cushing's syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10-year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management. MATERIALS AND METHODS: From 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five-year survival rates were calculated where applicable by the Kaplan-Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC). RESULTS: Two-hundred thirty-one patients (78%) had ACTH-dependent CS and 67 patients (22%) had ACTH-independent CS. One-hundred ninety-six patients (66%) had pituitary-dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty-four patients (18%) had cortisol-secreting adenomas, 10 patients (3%) had cortisol-producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five-year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively. CONCLUSIONS: Surgery for CS is highly successful for pituitary-dependent CS and most ACTH-independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross-sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today's management of the complex patient with CS.

Anaplastic thyroid carcinoma: an overview.

Thyroid cancer is an uncommon malignancy that accounts for roughly 1% of all new cancers. Although anaplastic lesions constitute fewer than 5% of thyroid cancers, they represent over half of thyroid cancer-related deaths. The relative rarity of anaplastic thyroid cancer, its aggressive nature, and its rapidly fatal course have contributed to the difficulty in developing effective treatment for this disease. Radiation, chemotherapy, and surgery are rarely curative, but combinations of these modalities appear to offer greater benefit than any single treatment. New treatment modalities are desperately required, and promising molecular-based therapies are being investigated.

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.

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.

Surgical management of amiodarone-associated thyrotoxicosis: Mayo Clinic experience.

Amiodarone-associated thyrotoxicosis (AAT) is often poorly tolerated owing to underlying cardiac disease, and it is frequently refractory to conventional medical treatment. The goal of this study was to describe the patient characteristics, management, and outcomes of all the patients treated surgically for AAT at a single institution. We conducted a retrospective chart review of all patients managed surgically for AAT (April 1985 through November 2002) at the Mayo Clinic in Rochester, Minnesota. Altogether, 29 men and 5 women, ages 39 to 85 years (median 60 years), treated with amiodarone for 3 to 108 months underwent near-total or total thyroidectomy. Frequent symptoms were worsening heart failure, fatigue, weight loss, and tremor. Altogether, 12 patients failed medical management of their AAT, and 21 received no preoperative medical therapy. One patient had been successfully managed medically but required definitive treatment. Common indications for operation were the need to remain on amiodarone, cardiac decompensation, medically refractory disease, and severe symptoms, both hyperthyroid and cardiac, necessitating prompt resolution. The median+/-SD American Society of Anesthesiologists (ASA) classification (1 = healthy through 5 = moribund) was 3.00+/-0.58. A total of 27 specimens had histology consistent with AAT. Complications included death (n = 3), rehospitalization (n = 3), symptomatic hypocalcemia (n = 2), pneumonia (n = 2), cervical hematoma (n = 1), prolonged ventilatorywean (n = 1), and stroke (n = 1); one patient developed hypotension, adult respiratory distress syndrome, and sepsis. Of the 31 surviving patients, 25 (80%) remained on amiodarone postoperatively. The median follow-up was 29 months, at which time all surviving patients were free of hyperthyroid symptoms. Thyroidectomy is an effective treatment for AAT but has a high incidence of perioperative morbidity and mortality. The cardiovascular co-morbidities and high operative risk in this group of patients may account for the increased complication rate.

Focused cervical exploration for primary hyperparathyroidism without intraoperative parathyroid hormone monitoring or use of the gamma probe.

Selected patients with primary hyperparathyroidism (pHPT) who have a positive preoperative sestamibi scan can be managed safely and successfully with a focused cervical exploration without either adjuvant intraoperative parathyroid hormone (PTH) monitoring or use of a gamma probe. This article reports a retrospective analysis of a consecutive series of patients surgically treated at a tertiary referral center. From August 1998 to August 2002, 100 patients (68 women, 32 men; mean age 63 years [range: 29-89 years]) underwent a focused cervical approach without intraoperative PTH monitoring or use of the gamma probe after perioperative sestamibi injection. The study group comprised 9% of all patients (n = 1063) undergoing cervical exploration for pHPT during the study period. Ninety patients underwent an initial exploration, and 10 others underwent repeat cervical exploration following prior parathyroid (n = 7) or thyroid (n = 3) operation. Sestamibi scanning correlated with one enlarged parathyroid gland in all patients. Other enlarged glands were, however, not demonstrated in three patients (true positive = 97%; false negative = 3%). The single enlarged glands excised in all patients had a mean weight of 795 mg (range: 90-3640) and were histologically compatible with an adenoma. Postoperatively, 97% of patients were eucalcemic. Three patients remained hypercalcemic (3%). Of the three patients with persistent hypercalcemia, one underwent successful re-exploration with excision of a 500 mg second adenoma, whereas the other two patients (with confirmed familial HPT) remained hypercalcemic. Mean hospitalization was 0.5 days (range: 0-3 days). There was no operative mortality. No patients had permanent hypocalcemia. Postoperative morbidity occurred in three patients: two self-limiting cervical hematomas and one permanent vocal cord paralysis. Selected patients with pHPT due to single-gland disease and an unequivocally positive preoperative sestamibi scan can safely and successfully be managed with a focused unilateral cervical exploration without either intraoperative PTH monitoring or use of the gamma probe. Further experience with this surgical approach seems warranted to determine the overall cure rate, operative morbidity, and the sensitivity and specificity of preoperative localization studies.

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.

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.

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.

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.