Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog.

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.

Scintigraphic evaluation of clinically silent adrenal masses.

UNLABELLED: We studied 229 patients with abnormal adrenal anatomy depicted by CT who were without biochemical evidence of endocrine dysfunction using the presence of 131I-6 beta-iodomethyl-nor-cholesterol (NP-59) adrenal gland uptake as an index of differential adrenal function in the evaluation of the clinically "silent" adrenal mass lesion. METHODS: NP-59 (1 mCi) was injected intravenously with posterior and lateral abdominal images obtained 5-7 days postinjection. RESULTS: One-hundred and fifty-nine of 185 patients with unilateral adrenal enlargement on CT had scintigraphic evidence that the mass represented a functioning (NP-59 avid) but not hypersecretory, (biochemically normal) adrenal cortical adenoma (concordant imaging pattern). Forty-one of 44 patients with intra-adrenal neoplasms were depicted on scintigraphy as decreased or absent NP-59 accumulation on the side of the adrenal mass (discordant imaging pattern). In this study, sensitivity was 71% (41 of 58 patients; 95% confidence interval (CI), 58% to 88%); specificity was 100% (171 of 171 patients; 95% CI, 95% to 100%) and accuracy was 93% (212 of 229 patients; 95% CI, 88% to 96%). CONCLUSIONS: These data confirm our earlier observations that the functional information depicted by scintigraphy complements the morphological evaluation by CT and in the absence of hormonal dysfunction, the presence of concordant CT and 131I-NP-59 scans are characteristic of functioning, but not hypersecretory, benign adrenocortical adenomas. Conversely, discordant CT and 131I-NP-59 scans are suggestive of nonfunctioning, space-occupying, adrenal lesions.

Calcitonin immunoreactivity and hypercalcitoninemia in two patients with sporadic, nonfamilial, gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: Hypercalcitoninemia in gastroenteropancreatic tumors associated with calcitonin immunoreactivity is rare. METHODS: We report here two patients in whom pancreatic neuroendocrine tumors both contained and secreted immunoreactive calcitonin. Both patients experienced elevated basal calcitonin immunoreactivity. RESULTS: The peak responses of immunoreactive calcitonin occurred 5 minutes after pentagastrin administration in these two patients and were 30% and 180% above basal concentrations corresponding to peak increments of 0.39 and 8.78 ng/ml, respectively. The immunoreactive calcitonin response to pentagastrin in these two patients was not significantly different from that seen among five patients with medullary carcinoma of the thyroid gland. CONCLUSION: It does not appear that immunoreactive calcitonin responses to pentagastrin stimulation will discriminate between patients with medullary carcinoma of the thyroid gland and those with nonfamilial, gastroenteropancreatic neuroendocrine tumors that express calcitonin immunoreactivity. In patients with secretory diarrhea and/or flushing, an elevated level of immunoreactive calcitonin, in the absence of a thyroid mass in the neck, may herald the presence of a gastroenteropancreatic neuroendocrine tumor.

The role of adrenalectomy in Cushing's syndrome.

Forty-four patients with Cushing's syndrome were treated by adrenalectomy between 1975 and 1989. Twenty patients had adrenal adenomas: 13 with obvious Cushing's syndrome and 7 whose disease was subclinical, detected after evaluation of an incidentally discovered adrenal mass (es). Twelve patients underwent bilateral adrenalectomies for Cushing's disease after failed transsphenoidal explorations and pituitary irradiation. Six patients had primary adrenal hyperplasia, five as manifestations of Carney's complex. Two others underwent bilateral adrenalectomies for ectopic adrenocorticotropic hormone from carcinoid tumors. Four patients had adrenocortical carcinoma treated with transabdominal adrenalectomy. Three are alive from 8 years to 5 months. There was one postoperative death (2.3%) caused by coagulopathy and multiple organ failure and three (7%) minor postoperative complications. Follow-up showed good to excellent results in 95% of patients. It is concluded that adrenalectomy provides prompt relief from the severe morbidity of Cushing's syndrome regardless of the cause. It is the treatment of choice for adrenal adenomas, carcinomas, primary hyperplasia, and selected patients with Cushing's disease.

The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism.

This report details our continued study of the role of ionized calcium (CAI) in the diagnosis of symptomatic primary hyperparathyroidism (HPT) in patients with persistently normal total serum calcium (CAT) or fluctuating normal total serum calcium levels with elevated CAT. A patient was considered to have fluctuating CAT values if at least 40% of the CAT values were within the normal range. Our previous study demonstrated that CAI provided no additional diagnostic benefit in patients with HPT who had persistently elevated CAT levels. This retrospective study adds 15 additional patients to the four previously reported patients whose workup for HPT included normal or fluctuating normal total serum calcium with elevated CAT values. Eighteen of these 19 patients had complications or symptoms referable to HPT. Nine of these patients had renal calculi. CAT was measured by atomic absorption spectroscopy and CAI was measured by a calcium-selective ion flow-through electrode. One hundred fifty-one concurrent preoperative measurements of CAT and CAI from these 19 patients were used for analysis. Overall, 46 (30.5%) of the CAT values were elevated, whereas 134 (88.7%) of the concurrent CAI values were elevated (P less than 0.001). In three of these 19 patients all preoperative CAT values were within normal limits, however, 20 of the 21 (95%) concurrent CAI values were elevated. In the remaining 16 patients the CAT values fluctuated between normal and elevated. In all of these patients, at least 40% of the preoperative CAT values were normal, and in 15 of these 16 patients at least 50% of the preoperative CAT values were within the normal range. In this fluctuating category there were 130 concurrent values of CAT and CAI. Only 46 of these 130 (35.4%) CAT values were elevated, whereas 114 of the 130 (87.7%) CAI values were elevated (P less than 0.001). All patients underwent parathyroid operation; 15 patients had a parathyroid adenoma and four had hyperplasia. The CAI and CAT values returned to normal in all patients subsequent to operation. These data indicate that the measurement of serum ionized calcium appears to play an important role in the identification of symptomatic HPT in patients who have normal or fluctuating normal total serum calcium with elevated CAT values.

Adrenal scintigraphy of well-differentiated (functioning) adrenocortical carcinomas: potential surgical pitfalls.

Adrenal scintigraphy with 131I-6 beta-iodomethylnorcholesterol (NP-59) has been widely used to evaluate adrenal cortical tumors during the past 20 years. Unilateral visualization on the side of an adrenal tumor has been considered diagnostic of a benign adrenocortical adenoma in the patient with Cushing's syndrome. Bilateral nonvisualization of the adrenal glands in the presence of Cushing's syndrome is considered diagnostic of adrenocortical carcinoma (ACC). ACCs characteristically are unable to incorporate enough NP-59 to be visualized on NP-59 adrenal scintigraphy. Two patients with well-differentiated cortisol-secreting ACCs, in which the primary tumor or subsequent metastases demonstrated intense uptake (visualization) on NP-59 scans are reported here. As a result of these findings on NP-59 adrenal scintigraphy, the lesions were initially misinterpreted to represent benign disease. In each patient the operative approach selected, based on the interpretation of the NP-59 scan, was inappropriate for the management of the respective adrenal neoplasm or its metastasis. A review of the literature reveals 16 other cases of either ACC or their metastases that were visualized with adrenal scintigraphy. Ninety percent of these cases were associated with adrenocortical hormone hypersecretion. It is concluded that in the presence of Cushing's syndrome or another adrenocortical hormone excess state, unilateral visualization of an adrenal tumor on NP-59 scintigraphy cannot be interpreted to represent uniformly benign disease.

Idiopathic aldosteronism masquerading as discrete aldosterone-secreting adrenal cortical neoplasms among patients with primary aldosteronism.

The medical records of 32 patients with primary aldosteronism who underwent adrenalectomy at the University of Michigan Medical Center from January 1975 to February 1988 were reviewed. All 32 patients had the preoperative diagnosis of aldosterone-secreting adrenal cortical neoplasms. Based on pathology reports, however, 21 of 32 (66%) patients were confirmed to have adrenal cortical neoplasms. Ten of 32 (31%) patients had nodular hyperplasia, and 1 of 32 (3%) had diffuse hyperplasia. This report focuses on the results in 11 patients with idiopathic aldosteronism. In six of nine (67%) patients, aldosterone levels rose within 4 hours of patients assuming an upright posture after salt loading. Seven patients had selective adrenal venous aldosterone/cortisol ratios that were interpreted to lateralize to one adrenal gland; however, only four of seven (57%) had ratios of 3:1 or greater than the contralateral adrenal gland. In 6 of 11 (55%) patients, adrenal scans (NP-59) initially demonstrated unilateral uptake. Three of four computerized axial tomographic scans demonstrated a unilateral adrenal mass. Only 3 of 11 (27%) patients with idiopathic aldosteronism were normotensive after surgery. Four of 11 (36%) patients' conditions were improved, in that they became normotensive with antihypertensive medication. These data suggest that if both imaging and functional studies lateralize to one adrenal gland, it is reasonable to expect either a cure or an improvement after adrenalectomy among patients with primary aldosteronism caused by idiopathic aldosteronism. Unilateral adrenalectomy may be the treatment of choice in carefully selected patients with nodular hyperplasia causing primary aldosteronism.

Follicular carcinoma of the thyroid gland: trends and treatment.

Pure follicular carcinoma of the thyroid gland has become a relatively uncommon type of primary thyroid neoplasm in the United States. During a 20-year period (1962 to 1982) 37 cases of pure follicular carcinoma were treated at the University of Michigan Medical Center. Cases of the follicular variant of papillary carcinoma and Hürthle cell carcinoma were excluded. There were 26 women and 11 men in the series. The mean ages were 46.9 +/- 17.5 and 45.3 +/- 11.5 years, respectively. The overall, mean age was 46.4 +/- 15.9 years. Surgical treatment included total thyroidectomy in 83.8% of the cases. Seventy-six percent of the patients were treated after operation with 131I irradiation. The mean total dose was 230.5 mCi. Three patients (8.1%) had regional lymph node involvement. Six patients (16.2%) had distant metastases to bone and/or lung at the time of diagnosis. Seven patients (18.9%) died after a mean survival of 7.7 years. Six patients (16.2%) died of their disease. Twenty-nine patients (78.4%) are alive and disease free after a mean follow-up interval of 11.8 years. Pure follicular carcinoma is decreasing in incidence and usually occurs at an older age than do other forms of differentiated thyroid cancers. It is frequently more aggressive than papillary carcinoma although lymph node metastases are less common. Total thyroidectomy and 131I therapy are the recommended treatments since metastases to bone and/or lung are the usual locations of distant spread. Bone metastases are rarely if ever cured. However, excellent long-term palliation may be achieved.

Traumatic rupture of a cervical parathyroid adenoma.

BACKGROUND: Spontaneous rupture of a hyperplastic parathyroid gland or adenoma resulting in extracapsular hemorrhage is extremely rare. METHODS: We report a case of traumatic rupture of a cervical parathyroid gland adenoma. RESULTS: The patient had progressive stridor, neck swelling, and chest and back pain with evidence of ongoing blood loss resulting in airway compromise. Exploration of the neck and superior mediastinum revealed hypercellular parathyroid tissue consistent with adenoma or hyperplasia. CONCLUSIONS: Traumatic rupture of an enlarged parathyroid gland is a distinct and potentially lethal cause of unexplained cervical or mediastinal hemorrhage after blunt neck trauma. Failure to consider the diagnosis may result in delayed operative intervention with persistent hemorrhage resulting in airway compromise.

Surgical approach to insulinomas. Assessing the need for preoperative localization.

The purpose of this study was to examine our experience with the diagnosis, surgical approach, and outcomes of surgery for organic hyperinsulinemia in the era of transhepatic venous sampling. During the period from 1978 to 1991, 50 patients were evaluated and treated for hyperinsulinemia at the University of Michigan Medical Center, all of whom underwent preoperative localization. Forty-one patients (82%) had solitary, benign tumors; four (8%) had either multiple tumors or islet cell dysplasia; and five (10%) had metastatic disease. Forty-seven patients underwent laparotomy, and the source of the hyperinsulinemia was found in all patients. In three patients (6%) preoperative localization did not accurately locate the tumor due to technical difficulties with the completion of the studies. Overall, computed tomography localized nine (26%) of 35 tumors. Angiography accurately localized 18 (44%) of 41 tumors. Transhepatic venous sampling localized 34 (94%) of 36 tumors, and was essential to successful surgical treatment in 15 patients. Compared with angiography, transhepatic venous sampling was a more accurate method of localization and should be performed in all patients in whom computed tomography and visceral angiography do not clearly identify the site of disease. Preoperative localization plays a critical role in the surgical treatment of patients with organic hyperinsulinemia and eliminates the need for blind pancreatic resection.

Flow cytometric measurements of nuclear DNA and ploidy analysis in Hürthle cell neoplasms of the thyroid.

Nuclear DNA content and nuclear DNA ploidy were measured in 36 Hürthle cell neoplasms (HCNs) to better define their potential roles in predicting the clinical behavior of these lesions. An EPICS V flow cytometer (Coulter Electronics, Hialeah, Fla) was used. Measurements were taken from paraffin-embedded tissue. Isolated nuclei were stained with propidium iodide. The study was conducted in a blinded fashion. Observed NDC and PDY patterns were classified as diploid, aneuploid, or suspicious. Twenty-nine lesions (81%) were diploid and seven (19%) were aneuploid. Twelve (33%) HCNs were malignant, 23 (64%) were benign, and one (3%) was indeterminate. Eight (67%) of 12 malignant HCNs were diploid and four (33%) of 12 were aneuploid. In comparison, 20 (87%) of 23 benign lesions were diploid and three (13%) of 23 were aneuploid. The indeterminate neoplasm was diploid. There were three deaths in this group of patients; all three had aneuploid neoplasms, and all had locally recurrent disease with distant metastases. There was a significant cross correlation between histologic features and DNA content with regard to outcome. These preliminary data suggest that NDC and PDY are not helpful in distinguishing histologically benign from malignant HCNs; however, they may be useful in determining prognosis.

Analysis of gastrinomas by immunohistochemistry and in situ hybridization histochemistry.

Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas.

Radionuclide evaluation of bile leakage and the use of subhepatic drains after cholecystectomy.

Our study addresses the question of efficacy of drainage after cholecystectomy by evaluation of the leakage of radiolabeled bile. Based on our data, drains placed at the time of surgery do not appear to reliably remove bile or to decrease morbidity. Our study reveals that bile leakage after cholecystectomy is frequent, cannot be accurately predicted at operation, is not related to the experience of the operating surgeons, and does not necessarily correlate with morbidity. The shorter postoperative hospital stay in the group of patients with subhepatic bile leakage compared with the group without evidence of leakage after cholecystectomy is not statistically significant. However, this trend does suggest that there is no increase in morbidity associated with bile leakage per se. A large, clinically significant bile leak can easily be treated by modern interventional radiologic techniques if drainage is indicated. A larger, double-blind study is necessary to further evaluate the issues surrounding bile leakage and drainage after cholecystectomy.

Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management.

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.

The measurement of DNA content and ploidy analysis in thyroid neoplasms.

It is clear that the DNA content of endocrine cells is influenced by factors other than neoplastic change and transformation. Although it can be concluded that, in general, the DNA content of neoplasms is increased, it is less clear whether this increase in DNA content is the cause or the effect of neoplastic transformation. The actual consequences of an increased DNA content are still largely unknown. However, based on a substantial body of data on the measure of nuclear DNA content in thyroid neoplasms, several conclusions appear to be reasonable. First, the measurement of nuclear DNA content and ploidy analysis are not sufficiently reliable parameters upon which to distinguish a benign from a malignant thyroid neoplasm. Therefore, this parameter has failed to live up to the expectation that it would be a powerful diagnostic tool. Second, the measurement of nuclear DNA content is useful after a histomorphologic diagnosis has been made since it correlates very well with the prognosis and clinical outcome of the patient. It is clear that aneuploid thyroid carcinomas are responsible for earlier recurrence, an increased likelihood of distant and diffuse metastases, and an increased incidence of death compared with diploid thyroid carcinomas. Except for the rare occasion, diploidy implies a uniformly long-term survival whereas aneuploidy is associated with a variable clinical course. Irrespective of histomorphology, lethal lesions of the thyroid are invariably aneuploid, whereas lesions associated with prolonged survival or a favorable outcome can be either diploid or aneuploid. Aneuploidy in well-differentiated thyroid carcinoma is more likely in older patients, in less well-differentiated neoplasms, and in neoplasms infiltrating beyond the thyroid capsule. Age, type of neoplasm, extrathyroidal extension, and recurrent disease all appear to be more important prognostic variables than is nuclear DNA content. However, nuclear DNA content can increase the prognostic power of these variables and consequently may come to be increasingly useful in the management of some patients with thyroid neoplasms. After a histomorphologic diagnosis has been made, the measurement of nuclear DNA content and a determination of the DNA ploidy may have significant prognostic value.

Hürthle cell neoplasms of the thyroid.

The approach to Hürthle cell neoplasms of the thyroid gland remains controversial because there is no consensus on the criteria used to establish malignancy. Invasion into the thyroid capsule, blood vessels, and contiguous structures in the neck and lymph nodes, or distant metastases establishes malignancy. Benign Hürthle cell lesions should be treated with total lobectomy and isthmusectomy. Total thyroidectomy is the recommended treatment for malignant Hürthle cell lesions.

Complications following adrenal surgery.

The morbidity associated with adrenalectomy can be as high as 40% and the mortality is approximately 2% to 4%. Morbidity following adrenalectomy is associated with intraoperative injury to an adjacent or contiguous structure, postoperative infection, thromboembolism, or adrenal insufficiency. Mortality is most often associated with pulmonary emboli, sepsis, a myocardial event (myocardial infarction or arrhythmia), or as a direct result of the underlying disease for which adrenalectomy is being performed. The posterior approach to adrenalectomy is associated with less blood loss and morbidity, and is best tolerated by the patient. However, the anterior transabdominal approach offers superior access to both adrenals, as well as other pertinent abdominal and retroperitoneal sites, and structures requiring concomitant exploration.

Diagnostic advances in APUDomas and other endocrine tumors: imaging and localization.

The different diagnostic imaging modalities available for determining the location of the various APUDomas are discussed with reference to their advantages and disadvantages. The ability to image these lesions, and to be confident in their role in the underlying pathophysiology, and clinical neuroendocrine syndrome causing symptomatology and illness, has proved to be the key to successful treatment. In many instances it is not the diagnosis that is in question, but it is the extent of disease, the location of the lesion, or whether the anatomical abnormality under study is responsible for the complicating symptoms being considered, that are the crucial questions. The ability to locate APUDomas by a variety of direct and indirect imaging or regionalizing modalities, represent a magnificent advance in the management of these tumors. It should, however, be kept in mind that no one modality or diagnostic method can uniformly be relied upon. It is evident that a multimodal, interactive medical team approach is essential to the successful overall management of patients afflicted with these fascinating tumors.

Hormonal responses associated with early hyperglycemia after graded hemorrhage in dogs.

Trained, awake, splenectomized dogs (n = 17) were studied to examine potential mechanisms for early hyperglycemia after hemorrhage (H). Animals were surgically prepared under halothane-nitrous oxide 3 days before the experiment. Chronic catheters were placed aseptically in the portal vein (PV), femoral vein, and femoral artery. Electromagnetic flow probes were placed around the PV and hepatic artery. After an overnight fast, dogs were hemorrhaged 10, 20, or 30% of their estimated blood volume in 3 min. Flow measurements and blood samples for glucose (G), immunoreactive insulin (IRI), immunoreactive glucagon (IRG), catecholamines (C), and cortisol (F) were taken prior to H and from 5 min to 8 h post-H. Plasma IRI, IRG, and F were measured by radioimmunoassay, plasma C by high-pressure liquid chromatography, and G by a glucose oxidase method. Peripheral G did not change after 10% H but increased significantly after 20 and 30% H from 10 min to 2 h. Similarly, peripheral C did not change after 10% H but increased significantly from 10 min to 2 h after 20 and 30% H. In contrast, the portal venous delivery of IRG did not increase significantly until at least 1 h after any magnitude of H. Peripheral IRI did not change after any magnitude of H. However, portal venous delivery of IRI decreased significantly from 20 min to 6 h after 10% H. Plasma F increased significantly in peripheral blood after all magnitudes of H. These results indicate that an increase in the release of IRG occurs too late to account for the early hyperglycemia that occurs during the 1st h following H.(ABSTRACT TRUNCATED AT 250 WORDS)