Pancreatic endocrine tumors--the search goes on.
Explore the source record for details and available documents.
Adenoma, Islet Cell↗
Biomedical subjects
J L Doppman
Publications and source records attributed to J L Doppman.
Intratesticular masses associated with abnormally functioning adrenal glands.
Explore the source record for details and available documents.
Adolescent↗
Curative resection in Zollinger-Ellison syndrome. Results of a 10-year prospective study.
Since 1980, 73 patients with Zollinger-Ellison syndrome (ZES) without radiographic evidence of liver metastases were studied on a prospective protocol including medical management of gastric acid hypersecretion, extensive radiographic tumor localization, and exploratory surgery to find and resect gastrinoma for potential cure. Each patient had gastric acid hypersecretion effectively controlled with either H2-blockers or omeprazole. Patients were divided prospectively into two groups, with all patients undergoing the same preoperative localization studies and extensive laparotomy. In contrast to group 1 (1980-1986) (36 patients), group 2 (1987-Oct. 1990) (37 patients) also underwent additional procedures (transillumination and duodenotomy) at surgery to find duodenal gastrinomas. Preoperative imaging studies localized tumor in 38 (52%) patients, and portal venous sampling for gastrin determinations was positive in 49 (67%) patients. Gastrinomas were found and resected in 57 (78%) patients. Significantly more gastrinomas (92% of patients) were found in group 2 than in group 1 patients (64%) (p less than 0.01). This increase was due to increased numbers of duodenal gastrinomas in group 2 than in group 1 patients (43% versus 11%; p less than 0.01). The increased ability to find duodenal gastrinomas did not significantly improve the immediate disease-free rate, which was 58% for all patients. Duodenal primary gastrinomas were found to have a significantly greater incidence of metastases (55%) and a significantly shorter disease-free interval (12 months) than pancreatic gastrinomas (22% and 84 months, respectively) suggesting that duodenal gastrinomas may be more malignant and not more frequently curable than pancreatic gastrinomas. Operations were performed with no deaths and 11% morbidity rate. Long-term follow-up showed that 50% of patients initially rendered disease free would develop recurrent disease by 5 years. Survival was excellent for all patients, and none died of malignant spread of the tumor or uncontrolled peptic ulcer disease, with a mean follow-up of 5 years. This finding is in contrast to patients who presented with metastatic disease on imaging studies and had a 20% 5-year survival rate. This study suggests that all patients with localized sporadic ZES can have the gastric acid hypersecretion managed medically, that overall survival of these patients is excellent, most (78%) can have all gastrinoma found and resected, and some (30%) will be cured (long-term disease-free survival).
Adult↗
Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.
Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.
Adenoma↗
Zollinger-Ellison syndrome: technique, results, and complications of portal venous sampling.
All 95 portal venous sampling (PVS) procedures performed in patients with Zollinger-Ellison syndrome in the past 10 years at the authors' institution were reviewed. It was possible to catheterize at least one branch of the pancreaticoduodenal venous arcade in all but two procedures (98%). The highest concentration of gastrin was found in a selective sample from the pancreaticoduodenal venous arcade or the transverse pancreatic vein in 56 of 91 procedures (62%). Selective sampling of pancreatic head veins yielded a gastrin gradient sufficient for localization in 60 patients (63%). Among 55 solitary sporadic gastrinomas identified at surgery, PVS allowed correct localization of the tumor in 32 (58%); if selective samples had not been obtained, only eight (15%) would have been localized (P less than .0005). Sensitivity was the same for tumors in the gastrinoma triangle (64%) and the body or tail of the pancreas (60%). There were no false-positive results. The overall complication rate was 20%, but most complications were abdominal pain lasting 3 days or less. Six patients (6%) had serious complications.
Abdominal Pain↗
Corticotropin-secreting carcinoid tumors of the thymus: diagnostic unreliability of thymic venous sampling.
Three patients with Cushing syndrome due to ectopic production of corticotropin underwent total thymectomy on the basis of elevated concentrations of corticotropin in selective samples from thymic veins but in the absence of a radiographically detectible thymic mass. In one patient, radiologic examination demonstrated hyperplasia of neuroendocrine cells staining positively for corticotropin throughout the thymus but no discrete mass. This patient had complete remission after total thymectomy. The other two patients had no evidence of an intrathymic source of corticotropin, and both had persistent Cushing syndrome. Elevated levels of corticotropin in thymic vein samples may reflect corticotropin production by pulmonary bronchial carcinoid tumors, mediastinal metastases, thymic carcinoids, or diffuse hyperplasia of intrathymic neuroendocrine elements. In the absence of a demonstrable intrathymic mass, corticotropin gradients in thymic veins do not reliably indicate a thymic source of corticotropin and should not necessarily be used as a basis for exploratory thoracotomy or blind thymectomy.
Adrenocorticotropic Hormone↗
Distinction between hyperaldosteronism due to bilateral hyperplasia and unilateral aldosteronoma: reliability of CT.
Hyperaldosteronism due to a unilateral adenoma must be distinguished from hyperaldosteronism due to bilateral hyperplasia to enable the proper choice between surgical treatment (for adenoma) or medical treatment (for hyperplasia). To compare the efficacy of computed tomography (CT) and adrenal venous sampling, both examinations were performed in 24 patients with primary aldosteronism. All patients with a diagnosis of adenoma based on findings at venous sampling underwent adrenalectomy. The CT-based diagnosis was unilateral aldosteronoma in 17 patients and hyperplasia in seven patients. On the basis of venous sampling, unilateral adenoma was diagnosed in 22 patients; this diagnosis was confirmed by means of unilateral adrenalectomy in 21 patients. The most common error was diagnosis of hyperplasia based on the presence of bilateral nodules on CT scans: In six of seven patients with such a diagnosis, venous sampling and subsequent surgery revealed a unilateral adenoma. In hyperaldosteronism with multiple bilateral nodules, CT cannot reliably permit distinction between hyperplasia and adenoma.
Adenoma↗
Neurologic complications of petrosal sinus sampling.
Petrosal sinus sampling has been described as an innocuous, essentially risk-free procedure. The authors report on two patients from two different institutions who sustained brain stem injury as a result of petrosal sinus sampling and two other patients in whom brain stem injury was avoided. Major neurologic complications have occurred in only 0.2% of procedures (one of 508) performed at the National Institutes of Health and in 0.5% of a subset of these procedures (one of 184) that were performed with a specially designed petrosal sinus catheter. The cause of these complications is unclear but is presumed to be localized venous hypertension. Tip-deflector catheter-guide-wire systems, if available, are recommended for petrosal sinus sampling. Inadequate data exist to permit recommendation of any other catheter. Brain stem injury is preventable if the catheter is withdrawn at the earliest sign of even a minor, seemingly insignificant problem. Subtle symptoms and signs that may not appear to be neurologic may herald a clinical catastrophe if not heeded.
Adult↗
Stress-induced adrenal hyperplasia simulating metastatic disease: CT and MR findings.
Explore the source record for details and available documents.
Adrenal Gland Neoplasms↗
Prospective study of the use of intraarterial secretin injection and portal venous sampling to localize duodenal gastrinomas.
BACKGROUND: Duodenal gastrinomas producing Zollinger-Ellison syndrome (ZES) are rarely imaged on preoperative studies. Measurement of serum gastrin levels by transhepatic portal venous sampling (PVS) or by sampling from hepatic veins after intraarterial secretin injection have been advocated as useful tests to identify these tumors before operation. METHODS: As part of a prospective study, selective intraarterial secretin injection has been performed in 36 consecutive patients with ZES, PVS has been performed in 30 of these patients, and the results have been compared. RESULTS: Gastrinomas were found at laparotomy in 33 of 36 patients (92%). Duodenal tumors were found in 18 patients (50%). The remaining patients had liver, pancreatic, or nodal disease (n = 15). Thirty-two of 36 patients (89%) had positive results with intraarterial secretin injection study, whereas 18 of 30 (60%) had a positive PVS gradient (p = 0.02, Fisher's exact test). The most common positive gradient with intraarterial secretin injection was found with injections of the gastroduodenal artery, and the most common positive gradient with PVS was found in the inferior pancreaticoduodenal (IPDV) or superior pancreaticoduodenal vein (SPDV). Fourteen of 18 (78%) patients with duodenal gastrinomas had a positive GDA injection, whereas five of 18 (28%) without duodenal tumors had a positive GDA injection (p = 0.006). Five of 16 patients with duodenal gastrinomas had a positive gradient in the IPDV or SPDV, whereas four of 14 without duodenal tumors had a positive gradient in the IPDV or SPDV (not significant). CONCLUSIONS: Intraarterial secretin injection is more sensitive than PVS at localizing duodenal gastrinomas and should replace PVS in patients with ZES and occult tumors.
Adult↗
Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome.
BACKGROUND: Measurement of adrenocorticotropin levels in plasma from the inferior petrosal sinuses of patients with Cushing's syndrome can distinguish adrenocorticotropin-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion from an occult tumor. However, it is unknown whether such measurement consistently identifies patients with Cushing's disease and whether testing with corticotropin-releasing hormone (CRH) enhances the value of the procedure. METHODS: We prospectively studied 281 patients with Cushing's syndrome to evaluate the diagnostic efficacy of the procedure. Bilateral sampling was successfully accomplished in 278 patients, with no major morbidity; 262 of these patients underwent sampling before and after administration of ovine CRH. The adrenocorticotropin levels in the samples were used to calculate the ratio of the concentration in plasma from the inferior petrosal sinuses to the concentration in peripheral-blood plasma (the IPS:P ratio). RESULTS: The diagnosis of 246 patients was confirmed surgically as Cushing's disease in 215, as ectopic adrenocorticotropin syndrome in 20, and as primary adrenal disease in 11. An IPS:P ratio greater than or equal to 2.0 in basal samples identified 205 of the 215 patients with Cushing's disease (sensitivity, 95 percent), with no false positive results (specificity, 100 percent). A peak IPS:P ratio greater than or equal to 3.0 after CRH administration identified all 203 of the patients with Cushing's disease who received CRH (sensitivity, 100 percent), with no false positive results (specificity, 100 percent). The sensitivity was much lower when the adrenocorticotropin concentrations in the samples from one sinus were considered alone. In patients with Cushing's disease a difference of greater than or equal to 1.4-fold between the concentrations in the two sinuses (the adrenocorticotropin gradient) predicted the location of the microadenoma in 68 percent of 104 patients during basal sampling and in 71 percent of 105 patients after CRH administration. CONCLUSIONS: Simultaneous bilateral sampling of plasma from the inferior petrosal sinuses, with the adjunctive use of CRH, distinguishes patients with Cushing's disease from those with ectopic adrenocorticotropin secretion with high diagnostic accuracy.
ACTH Syndrome, Ectopic↗
A novel testis-stimulating factor in familial male precocious puberty.
BACKGROUND: Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. METHODS: We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. RESULTS: The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies. CONCLUSIONS: These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder.
Animals↗
Localization of parathyroid tumors in patients with asymptomatic hyperparathyroidism and no previous surgery.
A number of recently published series were reviewed evaluating noninvasive localizing studies (ultrasound, thallium-technetium subtraction scintigraphy, computed tomography, and magnetic resonance imaging) in patients with primary hyperparathyroidism and no previous surgery. The average true positive (%) and false positive (%) rates were (1) ultrasound, 66 and 12; (2) Th/Tc scanning 55 and 13; (3) computed tomography, 63 and inadequately documented; (4) magnetic resonance imaging, 75 and 18. The success rate of initial operation in this group of patients is over 90%. There is no evidence that preoperative localizing studies shorten operating time or prevent surgical failures. For these reasons, noninvasive localization studies are not indicated in patients with primary hyperparathyroidism before initial surgery.
Humans↗
Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism.
Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity.
Adenoma↗
Petrosal sinus sampling: technique and rationale.
Bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive, specific, and accurate test for diagnosing Cushing disease and distinguishing between that entity and the ectopic ACTH syndrome. It is also valuable for lateralizing small hormone-producing adenomas within the pituitary gland. The inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins. The anatomy of the anastomoses between the inferior petrosal sinus, the internal jugular vein, and the venous plexuses at the base of the skull varies, but it is almost always possible to catheterize the inferior petrosal sinus. In addition, variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient. Advance preparation is required for petrosal sinus sampling. Teamwork is a critical element, and each member of the staff should know what he or she will be doing during the procedure. The samples must be properly labeled, processed, and stored. Specific needles, guide wires, and catheters are recommended for this procedure. The procedure is performed with specific attention to the three areas of potential technical difficulty: catheterization of the common femoral veins, crossing the valve at the base of the left internal jugular vein, and selective catheterization of the inferior petrosal sinuses. There are specific methods for dealing with each of these areas. The sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus. Images must always be obtained to document correct catheter position. Special attention must be paid to two points to prevent potential complications: The patient must be given an adequate dose of heparin, and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully. When the procedure is performed as outlined, both inferior petrosal sinuses can be catheterized in more than 98% of patients. The complication rate is low, and the theoretical risk of major morbidity or death is less than 1% (neither has yet occurred, to our knowledge). The most common complication is groin hematoma.
ACTH Syndrome, Ectopic↗
Insulinomas: localization with selective intraarterial injection of calcium.
To facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter, the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling (ASVS) technique. In four patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg) was injected directly into branches of the celiac plexus (gastroduodenal, splenic, and hepatic arteries) and the superior mesenteric artery. In all patients, serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor; injection into an artery not supplying the tumor did not result in a similar rise. Accurate localization of the insulinomas was verified at surgery in three patients. In the fourth patient, who did not undergo surgery, arteriographic results were positive for insulinoma at the predicted site. On the basis of these results, the authors believe noninvasive ASVS may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas.
Angiography↗
Zollinger-Ellison syndrome: prospective assessment of abdominal US in the localization of gastrinomas.
The ability of abdominal ultrasound (US) to help localize gastrinomas was prospectively studied in 79 patients with Zollinger-Ellison syndrome. The results were assessed by means of laparotomy, autopsy, or percutaneous liver biopsy. For hepatic gastrinoma, US had a sensitivity of 63% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 89%. US was slightly less sensitive for detecting gastrinoma in the liver than were computed tomography (CT) (66%) and selective angiography (78%). For detection of extrahepatic gastrinoma, US had a sensitivity of 30%, a specificity of 94%, a positive predictive value of 100%, and a negative predictive value of 25%. US enabled detection of tumor in eight cases not detected with CT and in four not detected with angiography. Specificity for extrahepatic gastrinoma was similar for all three modalities (89%-95%). CT and US were equally effective for the detection of extrahepatic gastrinoma, and angiography was significantly more effective than both US and CT (P less than .01). The authors conclude that US, although of low sensitivity, remains useful as the initial imaging modality in patients with Zollinger-Ellison syndrome.
Abdomen↗
von Hippel-Lindau disease: inadequacy of angiography for identification of renal cancers.
Selective renal angiograms were retrospectively evaluated for the identification of renal cell cancers in patients with von Hippel-Lindau disease (VHL). Seven patients underwent angiography and surgery because of solid or complex renal masses identified at cross-sectional imaging. Nine kidneys underwent detailed examination by the surgeon and by a pathologist. There were 31 renal cancers. Angiography had enabled identification of only five cancers (16%), and six others (19%) had been suspected. Cancers detected angiographically were larger than those not detected (P less than .05). Solid tumors tended to appear less hypervascular than expected and occasionally had the angiographic appearance of atypical cysts. There were no false-positive angiograms. Angiography revealed only one cancer not previously suspected and changed the surgeon's approach for only one kidney (11%). The sensitivity and specificity of angiography were 35% and 100%, respectively. In these patients, selective renal angiography is not helpful for the detection or exclusion of cancer in a kidney. It does not have a limited role for vascular mapping prior to partial nephrectomy or tumor enucleation.
Adult↗