Familial extra-adrenal pheochromocytoma. A new syndrome.

Pheochromocytomas in the same anatomic site, the right renal hilum, occurred in a family over three successive generations. For two patients in the latter two generations, scintigraphy with iodine 131-tagged metaiodobenzylguanidine (MIBG) showed tumors only in the region of the right renal hilum, thus indicating that they were primary lesions. At surgery, except for lymph node metastases noted microscopically in one patient, tumors were found only near the right renal hilum. The adrenal glands seemed normal on inspection, palpation, and computed tomography. In another family, a mother and son had primary pheochromocytomas arising from the urinary bladder. We suggest that primary extra-adrenal pheochromocytoma is a syndrome in which specific genetic abnormalities determine sites of tumor development.

Identification and differentiation of congenital gallbladder abnormality by quantitative technetium-99m IDA cholescintigraphy.

Failure to visualize the gallbladder in its usual location along the right inferior hepatic border suggests many possibilities including acute cholecystitis. The case described here reveals the importance of proper protocol for hepatobiliary imaging with 99mTC-IDA agents, the necessity of quantification of function as an integral part of imaging to enable proper differential diagnosis. A case of bilobed gallbladder presenting as a Valentine heart in an unusual location in the liver is described. The measurement of the CCK-8 induced gallbladder ejection fraction for each lobe facilitated proper diagnosis.

Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo labeling.

This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.

Evaluation of metaiodobenzylguanidine heart and lung extraction fraction by first-pass analysis in pigs.

Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that can be used to study cardiac sympathetic innervation. Most of the kinetic data on MIBG, however, have been obtained in vitro from adrenal chromaffin cells. To elucidate MIBG cardiac kinetics in vivo, we measured the first-pass extraction fraction (EF) of MIBG in pig heart and lungs and determined the relationship between the cardiac EF and myocardial blood flow (MBF) before and after dipyridamole, cocaine and imipramine. The first-pass lung EF was 24% +/- 0.80% (mean +/- s.e.). The baseline cardiac EF of MIBG was 79% +/- 1.6%. With dipyridamole, MBF increase significantly and the EF fell (82% +/- 2.5% to 71% +/- 3.5% baseline compared to 0.03 mg/kg/min dipyridamole, p less than 0.001), indicating that the cardiac EF of MIBG is dependent on MBF. Cocaine infusion had no effect on MBF or EF. Imipramine caused a significant increase in the EF (72% +/- 3.5% versus 77% +/- 2.5%, baseline versus imipramine p = 0.032) without a change in MBF. In adrenal chromaffin cells, cocaine and imipramine decrease MIBG uptake, suggesting that adrenal chromaffin cells may be an inappropriate model for studying MIBG kinetics in cardiac sympathetic neurons.

Evaluation of metaiodobenzylguanidine uptake by the norepinephrine, dopamine and serotonin transporters.

Metaiodobenzylguanidine (MIBG) is taken up by sympathetic neurons, but the precise mechanism of uptake has not been elucidated. Uptake of monoamines by presynaptic neurons is mediated by plasma membrane proteins, the monoamine transporters. The human norepinephrine transporter (hNET), the bovine dopamine transporter (bDAT) and the rat serotonin transporter (r5HTT) have been cloned, sequenced and expressed in various cell lines. This study involves the measurement of MIBG uptake by cell lines that have been transfected with complementary DNAs encoding these monoamine transporters. At 20 nM MIBG, hNET transfected cells demonstrate a ninefold greater uptake of MIBG than nontransfected cells. MIBG uptake in hNET transfected cells is inhibited by 3 x 10(-6) M norepinephrine (87% inhibition) and by hNET transport inhibitors: 10(-7) M desipramine (94% inhibition) and 10(-7) M mazindol (97% inhibition). hNET transfected cells exhibit a Km for MIBG transport of 264 nM. Percent nonspecific uptake rises with increasing concentrations of MIBG while specific uptake is saturable. There is no significant uptake by bDAT or r5HTT. The NET appears to be responsible for the specific uptake of MIBG.

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants.

Iodine-123 metaiodobenzylguanidine ([123I]MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with [123I]MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiac transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.

Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man.

Metaiodobenzylguanidine (MIBG) localizes in adrenergic neurons; MIBG labeled with 123I then serves as an analog of norepinephrine, and concentrations of [123I]MIBG reflect sites of adrenergic neurons in organs. Movements of [123I]MIBG into and out of organs were measured by quantitative scintigraphy in man. We perturbed adrenergic neuron function in several ways, and [123I]MIBG concentrations in the heart were subsequently altered in patterns consistent with the concept that [123I]MIBG resides mostly in adrenergic neurons. Uptake of [123I]MIBG into the heart was inhibited by the tricyclic drug, imipramine, and this agent also accelerated the rate of loss of [123I]MIBG. Phenylpropanolamine, a sympathomimetic drug that acts by displacing norepinephrine from neurons, increased the rates of loss of [123I]MIBG from the heart. Exercise was followed by a movement of [123I]MIBG into blood and urine. Generalized autonomic neuropathies were associated with marked diminutions of [123I]MIBG uptake into the heart. We conclude that quantitative scintigraphy in patients will enable determinations of regional disturbances in integrity (by measuring uptake of [123I]MIBG) and function (by measuring rates of loss of [123I]MIBG) of the adrenergic nervous system in the heart.

Portrayal of pheochromocytoma and normal human adrenal medulla by m-[123I]iodobenzylguanidine: concise communication.

The radiopharmaceutical m-[131I]iodobenzylguanidine (I-131 MIBG), which is readily taken up by adrenergic vesicles, produces scintigraphic images of pheochromocytomas in man but rarely visualizes normal adrenal glands. Iodine-123 has many potential advantages over I-131 as a radiolabel for MIBG, including shorter half-life, freedom from beta emissions, and increased gamma-camera efficiency. In this study, diagnostic doses of MIBG labeled with I-131 and I-123, with nearly equivalent radiation dosimetry, were compared as imaging agents in eight patients with known or suspected pheochromocytoma. Images of superior quality were obtained with I-123 MIBG, and lesions not visualized using I-131 MIBG were portrayed. In addition, the normal adrenal medullae were visualized on the I-123 MIBG scintigrams in six out of eight patients.

Radiopharmaceutical treatment of malignant pheochromocytoma.

Apart from relieving effects of secreted catecholamines, treatments of malignant pheochromocytoma have achieved little success. When the radiopharmaceutical, meta-[131I] iodobenzylguanidine (I-131 MIBG ), was found to concentrate in some malignant pheochromocytomas, we calculated that this agent could impart therapeutic doses of radiation to these tumors. We therefore treated five patients with two to four doses of I-131 MIBG prepared in high specific activity, 8-11 Ci/mmol. Individual doses were given at 3- to 10-mo intervals and in 97- to 197-mCi amounts. Two patients exhibited subjective and objective benefits. Their tumors declined in size (to 28% and 30% of original volumes) and in hormone secretion (to 50% or less of baseline rates). The other three patients manifested few symptoms before treatment and showed few or no objective improvement afterward. The tumors of the patients who responded to I-131 MIBG (a) appeared to be more rapidly growing, (b) received more cumulative rads, and (c) were more predominantly in soft tissues (in contrast to bone) than those in the patients who obtained little benefit. No toxic effects were encountered during the treatments, and only minor and temporary untoward responses were seen later.

A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency.

BACKGROUND: Patients treated long-term with supraphysiologic doses of glucocorticoids experience secondary adrenal insufficiency and are routinely given large doses of steroids in the perioperative period to prevent hypotension. Because the dose of steroids required to prevent hypotension is not known, we conducted a randomized, double-blind study to determine whether patients treated long-term with glucocorticoids actually require increased steroids in the perioperative period. METHODS: Patients who had been taking at least 7.5 mg prednisone daily for several months and had secondary adrenal insufficiency as defined by adrenocorticotropic hormone testing formed the study population. Patients were randomized to two groups. One group received perioperative injections of saline solution alone; the other received perioperative saline solution and cortisol. All patients received their usual daily prednisone dose throughout the study. RESULTS: Six patients were in the steroid-treated group and 12 were in the saline-treated group. Most subjects underwent major operations such as joint replacements, abdominal operations, and miscellaneous other procedures. Two patients had hypotension, one in each group. Hypotension resolved with volume replacement in both patients. The average pulse rates and blood pressures were similar in both groups during the perioperative period. CONCLUSIONS: Patients with secondary adrenal insufficiency do not experience hypotension or tachycardia caused by inadequate glucocorticoid levels when given only their daily dose of steroids for surgical procedures.

Effects of hypothyroidism and thyrotoxicosis on metaiodobenzylguanidine kinetics in the rat heart.

Metaiodobenzylguanidine (MIBG), a norepinephrine (NE) analogue, has been used to study cardiac sympathetic innervation. Although MIBG uptake and washout generally parallel the kinetics of cardiac NE (an accepted marker of sympathetic nerve function), quantitative differences exist between NE and MIBG. To determine the value of MIBG as a marker of cardiac sympathetic nerve function, cardiac MIBG uptake and washout were measured in rats with hypothyroidism and thyrotoxicosis which cause increased and decreased sympathetic nerve function, respectively. Rats were made hypothyroid by the ingestion of water containing 0.03% methimazole and thyrotoxic by the intraperitoneal injection of L-thyroxine. After 3 weeks of treatment, rats were injected with 25 mu Ci of 125I-MIBG. Rats were sacrificed at 1.5, 4, 8 and 24 h after injection and heart MIBG activity was determined. Initial uptake and cardiac washout (T1/2) were calculated in both treated groups and compared to controls. MIBG washout was similar in all three groups although it tended to be faster in the hypothyroid group. Uptake was highest in the hypothyroid group (130% of controls) and lowest in the hyperthyroid group (79% of controls). These results suggest that MIBG may be a marker of cardiac sympathetic nerve function although its kinetics may differ from NE.

The effect of gadolinium contrast media on radioiodine uptake by the thyroid gland.

OBJECTIVE: Patients with thyroid cancer may require detailed anatomic imaging before 131I therapy. Imaging by contrast-enhanced CT is contraindicated because it may result in saturation of tissues with iodine, decreasing the avidity of thyroid or thyroid cancer cells to subsequent radioiodine for extended intervals. Gadolinium-enhanced MRI offers an alternative to CT for detailed anatomic imaging. However, it is not known whether gadolinium contrast affects uptake of iodine by the thyroid gland since lanthanides affect ion transport in a variety of ways. The objective of this project was to determine whether the gadolinium MRI contrast injection alters thyroid uptake of radioiodine. METHODS: Radioiodine uptake by the thyroid gland was measured at 6 h and 24 h after the oral administration of 100 microCi 123I-Na-I. Three to seven days later, a standard dose (20 mL) of Magnevist (gadolinium DTPA) was administered intravenously. Another capsule of 100 microCi 123I Na-I immediately was given orally, and 6-h and 24-h radioiodine uptake by the thyroid gland was again measured and compared to baseline values. RESULTS: There was no statistically significant difference in uptake of radioiodine uptake by the thyroid gland between baseline values and those acquired immediately after the administration of Magnevist. CONCLUSION: Contrast-enhanced MRI may be safely performed before contemplated determinations of thyroid uptake of radioiodine, 131I therapy for hyperthyroidism, and postsurgical 131I imaging and therapy for well-differentiated thyroid cancer.

Intestinal malrotation diagnosed by cholescintigraphy.

Malrotation of the gut is a congenital abnormality in which the primitive intestinal loop fails to undergo rotation to its normal adult position. Rotation of the gut may become arrested at any stage, producing abnormal locations of the intestines within the abdomen. Malrotation may cause intestinal obstruction or volvulus or may remain asymptomatic. The case presented here illustrates asymptomatic malrotation of the gut, first detected by cholescintigraphy.

Detection of bile leakage from traumatic right hepatic duct laceration with technetium-99m DISIDA cholescintigraphy.

A woman was admitted to the hospital after blunt abdominal trauma. Initial ultrasound was equivocal but suggested a localized hepatic laceration. The patient was discharged but returned three weeks later with ascites and mild pain in the right upper abdominal quadrant. Hepatobiliary imaging identified a large bile leak originating from the porta hepatis but showed no evidence of parenchymal injury. No hepatic injury was found at surgery, but a laceration of the right hepatic duct was identified. Hepatobiliary imaging is the procedure of choice in diagnosing bile leaks from the extrahepatic biliary system.

Medical resources on the Internet.

Advances in telecommunications technology in the last decade have fostered the development of computer networks that allow access to vast amounts of information and services. Of the many computer networks that have been developed, the most prominent is the Internet. Originally intended to be a way to share computing resources among academic and research institutions in the United States, the Internet has gradually evolved into a worldwide network of computers that provides various services reflecting the eclectic nature of its component networks. The recent upsurge in interest in the Internet is due to several mutually reinforcing factors: increased ease and availability of access to the Internet, lower access charges, faster communications, and more organizations offering commercial and noncommercial services over the Internet. Of particular interest to the medical community is the large and increasing number of technical, scientific, and biomedical resources that can be accessed through the Internet. Most large medical centers have publicly accessible information, and some large organizations, such as the National Institutes of Health, have extensive databases and services that can be used by medical researchers, clinicians, and educators. In addition, many medical organizations and some medical journals are advertising their services over the Internet and can be contacted through electronic mail. As the cost of telecommunications decreases and the speed of telecommunications increases, new forms of computer communication, such as long-distance, real-time audio, and video services will become available. Computer networks in general and the Internet in particular are likely to play more important roles in many aspects of medicine in the future.

Patient motion artifacts on scintigraphic gastric emptying studies.

Patient motion during scintigraphic gastric emptying studies can result in the false diagnosis of gastroesophageal reflux or of accelerated gastric emptying. A simple means of detecting patient motion, by generating a time-activity curve from a region of interest drawn about a Tc-99m marker, is described.