Citations

AbstractAmiodarone‐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 ventilatory wean (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.

AbstractSelected 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.

ABSTRACT Toll receptors in Drosophila contribute to host defense and establish the body plan. Mammalian homologues of Toll, the Toll‐like receptors (TLRs), are thought to function only in host defense. Here, we report that mice harboring mutations in TLR4 or in CD14, a co‐receptor for TLR4, have an “ideal” body plan consisting of increased bone mineral content, density, and size as well as decreased body fat. These mutant mice live long lives, have normal activity and fertility, and show no evidence of infection. Unlike many strains of caged wild‐type mice, they do not become obese. Although all mice continue to gain body fat, bone content, and overall weight, the difference in bone content and body fat between mutant and wild‐type mice increases with age. Thus, defects in TLR4/CD14 complex generate an “Adonis” phenotype, characterized by this ideal body type, and this function could potentially be exploited for the treatment of osteoporosis and obesity.

AbstractGushing syndrome (CS) caused by ectopic adrenocorticotropic hormone (ACTH) production (EA) poses major challenges diagnostically by mimicking the pituitary‐dependent form of CS and therapeutically by producing severe, life‐threatening hypercortisolemia. This retrospective follow‐up study describes the clinical characteristics and course of EA in a large referral center. Computer‐based cross‐index codes for EA, CS, and bilateral adrenalectomy were used to identify patients treated at the Mayo Clinic between 1956 and 1998. EA was confirmed in 106 patients. Gender distribution showed a slight female predominance (61:45). Bronchial carcinoid was the most frequent cause of EA (25%), followed by islet cell cancer (16%), small‐cell lung carcinoma (11%), medullary thyroid cancer (8%), disseminated neuroendocrine tumor of unknown primary source (7%), thymic carcinoid (5%), pheochromocytoma (3%), disseminated gastrointestinal carcinoid (1%), and other tumors (8%). No tumor was found in 16% of patients. Altogether, 28 patients were managed medically, and the others underwent curative tumor resection (13 patients) or bilateral adrenalectomy (65 patients). Surgically treated patients had longer survival, but this was most likely affected by treatment bias. The diagnoses of CS and ACTH‐secreting neoplasm were usually concurrent, although, there were remarkable cases in which the two conditions were diagnosed several years apart. Curative resection of the tumor producing EA was possible in a small proportion of patients (12%). When curative resection is not possible, patients who are reasonable surgical candidates are likely to benefit from adrenalectomy. Additional experience with bilateral laparoscopic adrenalectomy should increase the number of patients who benefit from adrenal‐directed surgery.

Abstract Background Papillary thyroid cancer (PTC) has a generally favourable prognosis, but elderly patients with distant metastases or extracapsular invasion fair poorly. In small studies with short follow-up, young patients presenting with such extracapsular invasion and pulmonary metastases have faired well. This retrospective study was undertaken to clarify the long-term prognosis of such patients with advanced PTC. Methods Twenty-one children and young adults (median age 14 (range 6–20) years) presenting with PTC and pulmonary metastases were treated at a single institution between 1947 and 1998. Mean maximal tumour diameter was 4·65 cm. Initial surgical treatment consisted of total thyroidectomy (n = 16), subtotal thyroidectomy (n = 4) and isthmectomy (n = 1), coupled with a variety of lymph node dissections (n = 20). After operation, 19 patients were treated with ablative and incremental doses of iodine-131 until disease free. All patients were placed on suppressive thyroid hormone after operation. Mean length of follow-up was 21 years (range 3 months to 47 years). Follow-up was less than 3 years in four patients. All patients have undergone post-treatment radionucleotide and radiological evaluation. Results Nine of the 21 patients developed recurrent disease. The risk of recurrence at 5 years was 39 (95 per cent confidence interval 14–57) per cent. Eight had cervical lymph node recurrence and no patient developed recurrent pulmonary disease. All patients with identifiable recurrent disease underwent selective lymph node resection, which involved multiple resections in four. At follow-up, 18 patients remain completely free of disease, one patient has recurrent cervical node disease and two patients have died. The disease-free survival at 5 years was 95 (95 per cent confidence interval 86–100) per cent. Cause-specific death occurred in a single patient who died from extensive local disease at age 29 years after 12 years of multiple cervical lymph node recurrences. Conclusion A stepwise treatment approach including total thyroidectomy, high-dose iodine-131 treatment and early surgical reintervention for suspected local recurrent disease allows long-term survival and frequent ‘cure’ for young patients with PTC and concomitant pulmonary metastases.

Abstract Background The authors have reported a newly recognized hypoglyacemic disorder, non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), which is characterized by postprandial hyperinsulinaemic hypoglycaemia, negative 72-h fast, negative transabdominal and intraoperative ultrasonography, spiral computed tomography and coeliac axis angiography, positive selective arterial calcium stimulation test (SACST), absence of insulinoma but presence of islet hypertrophy and nesidioblastosis, and relief of symptoms from gradient-guided partial pancreatectomy. Experience with the next five patients with this disorder (6–10; 1998–1999) compared with the original five (1–5; 1996–1998) is reported. Results Wide age range, male predominance, postprandial occurrence of symptoms, negative radiological localization, nesidioblastosis/islet hypertrophy, but no insulinoma characterized all ten cases. Response to SACST indicated widespread islet hyperfunction in patients 1 and 5; limitation to distribution of the SPA and GDA in patients 3, 4, 6 and 8, to distribution of the SPA in patients 2, 7 and 9, and to distribution of the SMA in patient 10. Except for patient 5, pancreatic resection to the left of the SMV was performed when only the SPA was positive on the SACST. Patients 5 and 8 have had recurrence of symptoms; they resolved within 3 months for patient 5. Conclusion NIPHS can usually be treated successfully with gradient-guided partial pancreatectomy.

The trend toward limited exploration for primary hyperparathyroidism (1° HPT) has stemmed from advances in sestamibi scanning, gamma probe technology, and intraoperative parathyroid hormone monitoring (iPTH). Prior to widespread application, directed parathyroidectomy must be shown to meet the high standards of conventional cervical exploration. In this prospective, nonrandomized trial, results of parathyroidectomy utilizing the gamma probe, iPTH, or neither technique were evaluated. Altogether, 150 patients underwent parathyroidectomy utilizing the gamma probe (n = 50), iPTH (n = 50), or neither technique (n = 50). Each group was evaluated for operating time, length of hospitalization, cure rate, morbidity, mortality, and cost. A telephone survey was conducted with 25 patients in each group (n = 75) to address patient satisfaction. The gamma probe localized the abnormal gland in 66% of patients and confirmed cure intraoperatively in 84%. In the iPTH group, a more than 50% decrease from baseline occurred in 98%. The mean operating times were 76, 84, and 90 minutes, respectively (p = 0.16); and the mean length of hospitalization was 1 day. The biochemical cure rates were 98%, 100%, and 96%, respectively (p = 0.17). Total costs were $4476, $3918, and $3905, respectively. A total of 96% of patients in all three groups were "very satisfied" with their surgical procedure. Directed parathyroidectomy utilizing the gamma probe or iPTH assay does not significantly alter the operating time, length of hospitalization, cure rate, morbidity, mortality, or patient satisfaction when compared to conventional exploration in our practice. The probe is more expensive and was not a consistently reliable tool for localizing parathyroid pathology. PTH monitoring reliably predicts cure intraoperatively.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause‐specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient‐years. The 25‐year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40‐year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10‐year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10‐year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near‐total thyroidectomy and conservative nodal excision.