Insulinoma: Metastatic Recurrence 38 Years Following Initial Diagnosis in Pregnancy.

A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography. In 2022, a third operation was performed, with excision of a 4 × 3 mm tumor adjacent to the pancreatic head, and histology confirming insulinoma. She was again cured of symptoms.

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.

Surgical management of Graves disease in childhood and adolescence: an institutional experience.

BACKGROUND: Graves disease is the most common cause of hyperthyroidism in children. Medical therapy, radioiodine ablation, and thyroidectomy are all treatment options. To evaluate the safety and efficacy of operative therapy, we updated our operative experience with pediatric Graves disease at a single tertiary care center. METHODS: The medical records of children <18 years old who underwent thyroidectomy for Graves disease between 1986-2003 were reviewed. RESULTS: We identified 78 patients (median age, 13.8 years; 87% female). The most common presenting signs and symptoms included heat intolerance (61%), decreased academic performance (50%), tremor (49%), and ophthalmopathy (43%). All patients had clinical and laboratory evidence of autoimmune thyrotoxicosis. Sixty-nine percent chose operative therapy because of failure of medical therapy or adverse drug reactions. Near-total thyroidectomy was the most common surgical procedure performed (65%). Pathology demonstrated previously unrecognized thyroid malignancies in 4 (5%) patients. Operative morbidities were transient and included hypoparathyroidism (6%) and recurrent laryngeal nerve neuropraxia (1%). Three (4%) patients who underwent subtotal thyroidectomy developed recurrent hyperthyroidism; all were treated successfully with radioiodine ablation. Of patients presenting with ophthalmopathy, 85% noted improvement postoperatively, while 1 (3%) patient experienced worsening of symptoms. Only 5% developed new-onset Graves ophthalmopathy after operation. CONCLUSIONS: Near-total thyroidectomy for Graves disease in children is safe and effective when performed by experienced thyroid surgeons. In addition to relief of systemic symptoms, the majority of patients presenting with Graves ophthalmopathy experienced improvement of their ocular disease after operation. In 5% of patients, surgical management allowed for detection and treatment of clinically occult thyroid malignancies.

Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center.

OBJECTIVE: The aim of this study was to review our institutional experience managing pheochromocytomas and paragangliomas in children. METHODS: A retrospective chart review of the Mayo Clinic database from 1975 to 2005 identified 30 patients < 18 years of age with histologically confirmed pheochromocytoma or paraganglioma. RESULTS: There were 12 patients with pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms were hypertension (64%), palpitation (53%), headache (47%), and mass-related effects (30%). Nine patients (30%) had a genetic mutation or documented family history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed that statistically significant risk factors for malignancy were (1) paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma or paraganglioma, and (3) tumor size of > 6 cm. Surgical resection was performed for 28 patients (93%), with perioperative mortality and major morbidity rates of 0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients (83%). All patients with benign disease appeared cured after resection. For patients with malignant disease, the 5- and 10-year disease-specific survival rates were 78% and 31%, respectively, and the mean survival time was 157 +/- 32 months. CONCLUSIONS: The incidence of malignant pheochromocytoma/paraganglioma was high in children (47%), particularly those with apparently sporadic disease, paraganglioma, and tumor diameters of > 6 cm. Patients with a known genetic mutation or familial pheochromocytoma/paraganglioma were more likely to achieve resection with negative microscopic margins and had improved disease-specific mortality rates. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma.

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.

Primary hyperparathyroidism surgical management since the introduction of minimally invasive parathyroidectomy: Mayo Clinic experience.

HYPOTHESIS: Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism (HPT) has equal cure and recurrence rates as standard cervical exploration. Changes in the management of primary HPT have occurred since introducing MIP including localization, anesthesia, intraoperative parathyroid hormone monitoring, and indications for parathyroidectomy. DESIGN: Cohort analysis of 1361 consecutive patients with primary HPT operated on at the Mayo Clinic, Rochester, Minn, from June 1998 through March 2004. Mean follow-up, 25 months. SETTING: Tertiary referral center. PATIENTS: One thousand three hundred sixty-one patients operated on for primary HPT, excluding 160 patients who were reoperated on. INTERVENTION: Standard cervical exploration MIP. MAIN OUTCOME MEASURES: Cure, recurrence, localization, anesthesia, hospitalization, intraoperative parathyroid hormone level monitoring, contraindications to MIP, surgical indications, assessment of osteoporosis and osteopenia, postoperative patient assessment of general patient health, and operative satisfaction. RESULTS: Cure of primary HPT for both conventional exploration and MIP was 97%; only 1 patient who underwent MIP had a potential recurrence. Imaging sensitivity and positive predictive values were as follows: sestamibi scintigraphy, 86% and 93%; ultrasonography, 61% and 87%, respectively. Usage of general vs local anesthesia with intravenous sedation was 46% and 49%, respectively, in patients w ho underwent MIP; 46% were dismissed as outpatients, 49% had single-night stays. The accuracy of intraoperative parathyroid hormone level monitoring was as follows: 98% (8% had true-negative results); the frequency of multiple gland disease was 13%. Accounting for causes precluding MIP, an estimated 60% to 70% of all patients would be eligible for MIP. By preoperative assessment, 79% had osteoporosis-osteopenia; 58% with postoperative bone mineral density measurements were improved. More than 85% were satisfied with the results of their operation. CONCLUSION: With high-quality localization and intraoperative parathyroid hormone level monitoring, MIP can be performed with equal cure rates as standard cervical exploration, with no present evidence of delayed recurrence.

Primary hyperparathyroidism in pediatric patients.

OBJECTIVE: Primary hyperparathyroidism (HPT) is unusual in children. We reviewed our experience with HPT to better characterize these children. METHODS: The retrospective review of patients <19 years old who underwent parathyroid resection for primary HPT from 1970 to 2000 was performed at a single institution.. RESULTS: Fifty-two patients were identified. Median age was 16.8 years (range: 4-18.9) with a female-to-male ratio of 3:2. Eighty-five percent had an elevated parathyroid hormone (PTH) level, and 15% had an inappropriately normal PTH level during hypercalcemia. Serum calcium was elevated in all patients except for 2 with multiple endocrine neoplasma (MEN)-IIA and 1 with familial non-MEN HPT, but both had elevated PTH levels. Alkaline phosphatase levels were significantly higher in children with documented bone involvement. At presentation 41 patients (79%) were symptomatic and end-organ damage (nephrocalcinosis, nephrolithiasis, acute pancreatitis, or bone involvement) occurred in 23 patients (44%). Thirty-four patients (65%) had a single adenoma; hyperplasia was identified in 16 patients (27%), and of these cases, 57% occurred in patients diagnosed with MEN-I. Short-term complications included transient hypocalcemia in 29 patients (56%) and transient vocal cord paralysis in 2 patients (4%). Long-term complications were significant for permanent hypocalcemia in 2 patients (4%) and no recurrent laryngeal nerve injuries. No parathyroid abnormalities were identified during exploration in 4 (8%) children. Long-term follow-up was achieved in 98% of patients for a mean and median of 13 years. Resolution of hypercalcemia was achieved in 94% of cases. CONCLUSION: The diagnosis of primary HPT in pediatric patients is frequently delayed, is commonly symptomatic, and has significant morbidity. For children in whom HPT is suspected, evaluation of serum calcium and PTH levels is diagnostic in 100% of children. Parathyroid resection is effective at restoring normal serum calcium, has few complications, and is the treatment of choice for children with primary hyperparathyroidism.

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.