Complications to thyroid surgery: results as reported in a database from a multicenter audit comprising 3,660 patients.

BACKGROUND AND AIM: During recent years, more radical surgery for thyroid disease, i.e., total instead of subtotal resection, has been evident. Results following this strategy on national levels are scarce. MATERIALS AND METHODS: From 2004 to 2006, 26 Scandinavian Departments registered 3,660 thyroid operations in a database. Risk factors for complications were analyzed with multiple logistic regression. RESULTS: After thyroidectomy, re-bleeding occurred in 2.1% and was associated with older age (OR 1.04; p < 0.0001) and male gender (OR 1.90; p = 0.014). Postoperative infection occurred in 1.6% and associated with lymph node operation (OR 8.18; p < 0.0001). Postoperative unilateral paresis of the recurrent laryngeal nerve was diagnosed 3.9% and bilateral paresis in 0.2%. Unilateral paresis was associated with older age, intrathoracic goiter, thyreotoxicosis, and if routine laryngoscopy was practiced (OR 1.92; p = 0.0002). After 6 months, the incidence of nerve paresis was 0.97%. After bilateral thyroid surgery (n = 1,648), hypocalcaemia treated with vitamin D analogue occurred in 9.9% of the patients at the first follow-up and in 4.4% after 6 months. CONCLUSION: Complications to thyroid surgery are not uncommon. The high frequency of hypocalcaemia treated with vitamin D after 6 months is a cause of concern.

Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice.

We explored whether inhibition of the enzyme dipeptidyl peptidase IV (DPP IV) increases endogenous levels of glucagon-like peptide-1 (GLP-1) and improves glucose tolerance and insulin secretion in mice. Glucose (150 mg) was administered through a gastric gavage with or without the inhibitor of dipeptidyl peptidase IV, valine-pyrrolidide (100 micromol/kg), in high-fat fed glucose intolerant or control C57BL/6J mice. The increase in plasma GLP-1 after gastric glucose was potentiated by dipeptidyl peptidase IV inhibition (P<0.05). Valine-pyrrolidide also potentiated the plasma insulin response to gastric glucose and improved the glucose tolerance in both groups of mice (P<0.001). In contrast, valine-pyrrolidide did not affect glucose-stimulated insulin secretion from isolated islets. This suggests that valine-pyrrolidide improves insulin secretion and glucose tolerance through indirect action, probably through augmentation of levels of GLP-1 and other incretin hormones. Therefore, inhibition of dipeptidyl peptidase IV activity is feasible to exploit as a treatment for glucose intolerance and type 2 diabetes.

Differential changes in islet amyloid polypeptide (amylin) and insulin mRNA expression after high-fat diet-induced insulin resistance in C57BL/6J mice.

Islet amyloid, derived from islet amyloid polypeptide (IAPP or amylin), frequently occurs in type 2 diabetes. Availability of this peptide for amyloid formation may be enhanced by increased islet expression of IAPP. In the insulin resistant state, euglycemia is maintained by hypersecretion of insulin. Whether

Islet perturbations in rats fed a high-fat diet.

The islet response to a high-fat diet, which induces insulin resistance, was investigated in Sprague-Dawley rats. It was found that the insulin response to glucose (15 or 25 mg/min, i.v.) was not different between rats given a high-fat diet and control rats after 2 weeks but was significantly reduced in rats fed high-fat diets after 4 (by 46+/-9%; p<0.001) and 8 weeks (by 68+/-12%; p<0.001). However, after 2 weeks of a high-fat diet, stimulated insulin secretion from isolated islets incubated for 60 min in 5.6, 8.3, and 11.1 mM glucose was impaired. When islets isolated from rats given a high-fat diet for 2 weeks were perifused, it was evident that the first-phase insulin secretion was impaired (seen during the first 6 min after increase of glucose from 3.3 to 8.3 mM). Insulin gene expression, examined by quantitative in situ hybridization, was impaired after 2 weeks of high-fat diet (52% decrease in mRNA-labeling; p<0.001). Islet hypertrophy was not evident in rats given high-fat diet, as determined by areas of either islet profiles in dark-field images or isolated islets. Islet innervation, as revealed by immunostaining for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was increased after 2, 4, and 8 weeks of high-fat diet. Thus induction of insulin resistance by high-fat diet in Sprague-Dawley rats results after 2 weeks in impaired glucose-stimulated insulin secretion in vitro, impaired insulin gene expression, and hyperinnervation of the islets without any sign of islet hypertrophy, whereas the in vivo insulin response to glucose, although normal after 2 weeks, is impaired after 4 weeks.

Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment.

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical characteristics, treatment and survival in patients with pancreatic tumors causing hormonal syndromes.

Eighty-five patients with endocrine pancreatic tumors associated with clinical syndromes of hormone excess were retrospectively analyzed regarding symptomatology, means of diagnosis, and results of surgical and medical treatment during follow-up of 3-18 years (median 8 years). The combination of angiography and computed tomography was most successful in pre-operative localization of both primary tumors and metastases. Surgery provided long term cure in 39 of 44 patients with benign islet cell lesions, the majority having insulinomas. Forty-one patients had malignant tumors, which at the time of diagnosis or operation were associated with liver and/or regional lymph gland metastases in 56% and 24%, respectively. Sixteen patients with metastatic disease and/or very large tumors were considered inoperable, 5 patients underwent palliative resection of their malignant tumors, while grossly radical tumor removal was accomplished in 20 patients. Long-term cure was achieved in 5 patients by excision of primary tumors and localized liver or lymph gland metastases. Half of the patients, particularly those with insulinoma, gastrinoma, or vipoma, showed response to streptozotocin, in combination with other cytostatics, for a median of 24 months or a response to interferon for a median of 10 months. The overall 5-year and 10-year survival among the patients with malignant islet cells tumors was 54% and 28%, respectively. Absence of liver metastases at time of operation/diagnosis, smaller size of the primary tumor, grossly radical tumor resection as well as response to medical therapy predicted the more favorable survival.

Effects of neuropeptide Y on insulin and glucagon secretion in the pig.

Neuropeptide Y (NPY)-nerves occur in the pancreas. We therefore infused synthetic porcine NPY directly into the pancreatic artery in anaesthetized pigs to study its direct in vivo influence on pancreatic blood flow and on insulin and glucagon secretion. NPY was given both under basal, normoglycemic conditions, and during an ongoing intravenous infusion of glucose, which raised plasma glucose levels to 20 mM. NPY was infused at 0.5 (n = 2), 5 (n = 3), 35 (n = 7), or 175 (n = 5) pmol/min. We found that NPY at 5, 35, and 175 pmol/min inhibited glucagon secretion. Furthermore, at 35 and 175 pmol/min, NPY also reduced pancreatic blood flow. In contrast, only at 175 pmol/min, NPY inhibited basal and glucose-stimulated insulin secretion. We conclude that in the pig NPY might participate in the regulation of glucagon secretion (as an inhibitor) and of pancreatic blood flow (as a vasoconstrictor). In contrast, NPY does not seem to be involved in the regulation of insulin secretion.

Pancreatic release of pancreastatin in the pig.

It is known that pancreastatin-like immunoreactivity (PLI) occurs in the secretory granules of the islet B- and D-cells in the pig pancreas, and that porcine pancreastatin inhibits insulin secretion in rats and mice. In this study, we characterized the porcine plasma PLI and examined whether PLI is released from the pig pancreas in vivo. We found that PLI in unextracted pig plasma largely consists of two high-molecular fractions, with Mr values of 80-85,000 and 300-350,000, respectively. In addition, a small peak of PLI eluted after gel filtration at the position of synthetic porcine pancreastatin. After extraction on octadecylsilyl silica, virtually all PLI disappeared except in the fraction co-eluting with porcine pancreastatin. In thiopenthal-anesthetized pigs, plasma samples were obtained from the carotid artery and the superior pancreaticoduodenal vein. By multiplying the venous-arterial concentration difference by the pancreatic venous plasma flow, a net pancreatic output of PLI of 420 +/- 120 pmol/min was found. This pancreatic PLI output was significantly reduced by electrical stimulation of the local autonomic nerves along the superior artery during atropine administration (p less than 0.001). Furthermore, the pancreatic venous PLI levels were elevated during intravenous infusion of glucose (p less than 0.01). We conclude that pig plasma PLI levels can be measured by radioimmunoassay after extraction on octadecylsilyl silica and that there is a net pancreatic output of PLI, which is reduced by sympathetic stimulation and enhanced during hyperglycemia.

Localization and peptide content of endocrine pancreatic tumors.

Endocrine pancreatic tumors contain and frequently secret neurohormonal peptides. This phenomenon can be used as a diagnostic and classifying tool. This study analyzes 31 patients operated on because of an endocrine pancreatic tumor, including the diagnostic procedures and the localization methods. In 15 insulinoma cases only 6 patients had a positive arteriography, while all 11 selective pancreatic vein samplings were positive. The immunoreactivity showed that, besides insulin, most tumors also contained other peptides. Of four gastrinoma cases the arteriography was positive in three, but the selective vein sampling localized the tumor in all. The tumor's content of peptides showed mixed patterns. In the four glucagonomas, the arteriography was positive in all and the venous sampling performed in three of the cases also was positive. In five pancreatic polypeptide-containing tumors (PP-omas) the arteriography was positive in four and sampling performed in two was positive in both. In the PP-omas the peptide pattern showed that these tumors frequently contain several peptides. We used selective pancreatic vein sampling in 21 cases with positive result in all. In the cases in which arteriography was negative, the sampling results helped the surgeon to find the tumor. The peptide pattern in the tumors varied greatly and most tumors were multihormonal.

Galanin of the homologous species inhibits insulin secretion in the rat and in the pig.

It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species-specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg-1) abolished the glucose- (0.56 mmol kg-1) induced increase in plasma insulin levels. In vitro, rat galanin (10(-9) to 10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min-1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.

Pancreatic nerve stimulation releases neuropeptide Y- but not galanin- or calcitonin gene-related peptide-like immunoreactivity from the pig pancreas.

We investigated the possible release of galanin-, calcitonin gene-related peptide (CGRP)-, and neuropeptide Y (NPY)-like immunoreactivity from the pancreatic nerves in thiopental-anaesthetized pigs. Ten minutes stimulation of the mixed autonomic pancreatic nerves during infusion of atropine (8 or 40 Hz, 5 ms, 10 mA, n = 5) inhibited insulin secretion, during both normoglycemia (9.1 +/- 0.2 mmol/l) and hyperglycemia (28.1 +/- 0.4 mmol/l). Concomitantly, pancreatic venous concentrations of NPY-like immunoreactivity increased. For example during normoglycemia, a nerve stimulation by 8 Hz increased the pancreatic venous levels of NPY-like immunoreactivity from 294 +/- 26 pmol/l to 391 +/- 23 pmol/l (P less than 0.001). In contrast, the pancreatic venous concentrations of galanin- or CGRP-like immunoreactivity did not change during the nerve stimulation. We conclude that electrical pancreatic nerve stimulation in the pig releases NPY-like immunoreactivity without affecting the pancreatic venous concentrations of galanin- or CGRP-like immunoreactivity.

To drain or not to drain in thyroid surgery. A controlled clinical study.

Drainage after thyroid surgery is widely used to prevent postoperative complications by evacuation of blood and fluids. However, to our knowledge no study has shown the benefit of drainage. Therefore, we performed a prospective, randomized study on the rate of complications after drainage or no drainage in thyroid surgery. One hundred fifty patients were allocated to drainage or no drainage. No difference was seen between the two groups according to the experience of the surgeon, type of operation, diagnosis, weight of thyroid specimens, operation time, and hospital stay. All complications were recorded and resulted in two patients receiving reoperation because of bleeding, two permanent laryngeal nerve palsies, one case of permanent hypocalcemia, ten minor hematomas, one wound infection, and one lymphatic leakage. No difference was seen between the groups. This study does not support prophylactic routine drainage after uncomplicated thyroid surgery.

Cholecystokinin (CCK)-4 and CCK-8 stimulate islet hormone secretion in vivo in the pig.

It is known that cholecystokinin (CCK) stimulates islet hormone secretion under a variety of experimental conditions. Since CCK occurs in several different molecular forms, with 58, 39, 33, 12, 8, or 4 amino acid residues, the question has evolved as to which is the shortest active form of CCK. We therefore investigated the influences of the C-terminal octapeptide of CCK, CCK-8 (sulfated form) and of the C-terminal tetrapeptide, CCK-4, on the secretion of insulin, glucagon, and somatostatin from the pig pancreas in vivo by infusing each of the two peptides into the superior pancreatic artery. We found that islet hormone secretion increased promptly upon infusion of both CCK-8 and CCK-4. Thus, the secretion of insulin was stimulated from 51 +/- 12 to 295 +/- 70 microU/min during the first 2 min after injection of CCK-8 and from 40 +/- 12 to 240 +/- 78 microU/min after injection of CCK-4. Similarly, the secretion of glucagon was stimulated from 240 +/- 45 to 357 +/- 38 pg/min after CCK-8 and from 282 +/- 44 to 335 +/- 43 pg/min after CCK-4, and somatostatin secretion was stimulated from 112 +/- 7 to 226 +/- 12 pg/min by CCK-8 and from 105 +/- 11 to 246 +/- 16 pg/min by CCK-4. With regard to the efficiency to stimulate the secretion of these three islet hormones, CCK-8 and CCK-4 were equipotent. We conclude that in pigs, CCK-8 and CCK-4 both stimulate the secretion of insulin, glucagon, and somatostatin from the pancreas in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

A mixed endocrine adrenal tumour causing steatorrhoea.

A 60 year old man developed steatorrhoea, weight loss, mild diabetes mellitus, labile hypertension and limb cramps. Raised plasma concentrations of catecholamines, particularly noradrenaline and a computed tomography-scan showing an adrenal tumour strongly suggested a pheochromocytoma. Adrenoreceptor blockade reversed the symptoms, decreased faecal fat, and increased duodenal trypsin to normal concentrations. After adrenalectomy the patient was asymptomatic and there was no steatorrhoea. The blood glucose concentrations became normal. Immunocytochemistry revealed the tumour cells to store large amounts of enkephalin and somatostatin reactive material and moderate amounts of immunoreactive beta-endorphin and dynorphin.

Location of parathyroid glands by thallium-technetium subtraction scintigraphy.

In 36 patients with biochemical and clinical evidence of primary or secondary hyperparathyroidism (HPT), preoperative scintigraphic studies were performed with a thallium-technetium subtraction technique. The patients were given 30 MBq technetium pertechnetate and, after a delay of 10-15 minutes, 55 MBq thallium chloride. Data were collected with a gamma camera equipped with a pinhole collimator and dedicated computer. Images were recorded simultaneously in two channels, in order to provide identical positioning for the thallium and technetium images. A standardized gradual computer subtraction was then carried out. Parathyroid adenoma was present in 28 patients, primary parathyroid hyperplasia in two, and secondary hyperplasia due to chronic renal failure in six. The scintigrams located 24 (86%) of the adenomas, but only four (13%) of the total 32 hyperplastic glands. The scintigraphic technique offers considerable advantages in the preoperative location of parathyroid adenomas, which may be of particular interest in persistent or recurrent HPT.

Effects of calcitonin gene-related peptide (CGRP) on islet hormone secretion in the pig.

Calcitonin gene-related peptide occurs in intrapancreatic nerves and endocrine cells. The peptide is therefore a candidate for being of physiological importance for pancreatic function. We examined the direct effects of calcitonin gene-related peptide on islet hormone secretion in the pig by infusing the peptide into the superior pancreatic artery. We found that 15 min intrapancreatic infusion of calcitonin gene-related peptide (22 pmol/min) decreased baseline pancreatic insulin output from 48 +/- 10 microU/min to 8 +/- 7 microU/min (p less than 0.01). Moreover, calcitonin gene-related peptide inhibited glucose-induced insulin secretion by 45% compared to controls (p less than 0.01), yet left terbutaline (beta 2-adrenoceptor)-stimulated insulin secretion unaffected. Furthermore, while being without effect on baseline glucagon output, calcitonin gene-related peptide potentiated terbutaline-induced glucagon secretion more than seven-fold (p less than 0.001). In contrast, the peptide did not affect baseline or stimulated pancreatic somatostatin output. We conclude that in pigs calcitonin gene-related peptide inhibits insulin secretion and potentiates glucagon secretion by direct effects on the pancreas that are not mediated by primary alterations in pancreatic somatostatin secretion. We suggest that the neuropeptide calcitonin gene-related peptide might be of importance for the intrapancreatic regulation of insulin and glucagon secretion in pigs.

Chest radiography in the carcinoid syndrome.

The chest films of 44 patients with liver metastases from intestinal carcinoid tumors were reviewed in order to evaluate the frequency of significant carcinoid heart disease. Only two patients had obvious signs of cardiac involvement, which is contradictory to most other studies.

Thyroid tissue characterization by proton magnetic resonance relaxation time determination.

Measurements were performed at 37 degrees C on 49 fresh samples excised from cancerous (n = 16) or non-malignant (n = 33) thyroid tissues of 23 patients. They were carried out for protons at a frequency of 10.7 MHz with pulse sequences (90 degrees-t-90 degrees) and (90 degrees-t-180 degrees-t) for T1 and T2 respectively. The estimates were correlated to histopathology with quantitative measurements of the proportions of colloid, thyroid epithelium, fibrosis, and haemorrhage tissue. Discriminant analysis of malignant and non-malignant tissues using T1 and T2 values, was not successful. T1 and T2 values were correlated to each other. Both were correlated to the proportions of water, thyroid epithelium and haemorrhage and inversely correlated to the amount of colloid. Multiple regression analysis revealed that T2 values were more tissue-specific than T1 values. The analyses indicate possibilities to identify different thyroid tissues by magnetic resonance imaging, especially by T2 weighted MR images.