Biomedical subjects
Publications and source records attributed to M D Gross.
A rational management of pheochromocytoma is outlined, consisting of clinical suspicion, biochemical confirmation, radiologic localization, meticulous preoperative, interoperative, and postoperative monitoring, and pharmacologic intervention. The principles for achieving surgical cure (possible in 90% of cases) are described, as is the pharmacologic, chemotherapeutic, and radiotherapeutic management of malignant or inoperable tumors.
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The control of hormone secretion and substrate uptake by the thyroid and inner adrenal cortex is similar because both glands undergo hypothalamic-pituitary trophic hormone modulation and negative feedback by their respective major secretory products: thyroid hormone and cortisol, respectively. As a result of these parallel mechanisms of endocrine function, thyroidal accumulation of radioiodine or Tc-99m pertechnetate and adrenal cortical accumulation of I-131-6 beta-iodomethylnorcholesterol (NP-59) and other radiocholesterol analogs are strikingly similar. The patterns of imaging of these glands are thus functional maps of the process(es) of substrate accumulation and depict the endocrine pathophysiology of these glands in a variety of dysfunctional states. The well-recognized patterns of thyroid imaging can be shown analogous to those of the adrenal cortex.
In this pilot study of poststroke depression, the authors evaluated regional cerebral blood flow and depression in 14 stroke patients. Volume of ischemia was measured by two methods, which were highly correlated. Depression scores correlated with lesion volume as measured by single photon emission CT.
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.
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The known ability of phospholipid ethers to accumulate in certain tumors prompted the synthesis and evaluation of a radioiodinated phospholipid ether analog as a potential tumor imaging agent. Tissue distribution studies with [125I]-rac-1-0-[12-(m-iodophenyl)dodecyl-2-0-methylglycero-3- phosphocholine in rats bearing the Walker 256 carcinosarcoma showed the tumor to contain the highest concentration of radioactivity at 24 hr (15% of the dose) and a tumor-to-blood ratio of 13. Scintigraphic images taken at 24 hr compared favorably with those obtained with (67Ga)-citrate. In contrast with the latter, however, the phospholipid ether showed little propensity to accumulate in an inflammatory lesion in the rat. Tumor visualization was also accomplished in a rabbit bearing the V x 2 adenocarcinoma. We conclude that phospholipid ethers may represent a new class of carrier molecules for the transport of radionuclides to tumors.
NP-59 concentrates in steroid hormone synthesizing tissues, enabling scintigraphic localization and characterization of endocrine dysfunction in the adrenal cortex and ovary. Studying 108 consecutive cases from 1982 to 1985 and using clinical, biochemical, radiographic, and pathologic data, we performed a rigorous assessment of the accuracy and pitfalls of NP-59 scintigraphy. The evaluation was divided into categories of abnormal hormone secretion: Cushing's syndrome, primary aldosteronism, and hyperandrogenism. Additional categories included euadrenal tumors (without detectable hormone dysfunction) and sites of residual adrenal cortical tissue. The accuracy of NP-59 scintigraphy ranged from 71% in primary aldosteronism and 75% in euadrenal tumors, to 100% for Cushing's syndrome and hyperandrogenism. However, more than in most nuclear medicine studies, NP-59 imaging requires well-defined indications to be met for it to be efficacious, including the fulfillment of clear clinical, biochemical, and radiographic criteria. The high reproducibility of NP-59 scintigraphic interpretation was demonstrated when 40 random cases underwent interinstitutional exchange and through interobserver evaluation at the University of Michigan. Responses of 85/126 medical centers to questionnaires revealed the high level of NP-59 safety.
Blood flow was measured under the ischial tuberosites of seated individuals during electrical stimulation of the gluteus maximus muscles. Eight able-bodied and six spinal cord injured subjects were studied. Muscle blood flow was measured via radioactive tracer (133xenon) clearance. Retention of xenon in adipose tissue prevented accurate measurement of blood flow in cutaneous and subcutaneous tissue. Average muscle blood flow for both subject groups was increased during stimulation as compared to rest. All subjects showed an increase in muscle blood flow during stimulation. The statistical significance from a paired student t-test was greater for able-bodied subjects (p less than .05) than for spinal cord injured subjects (p = .12). The increase in muscle blood flow produced by electrical muscle stimulation in seated individuals supports the hypothesis that electrical muscle stimulation can help prevent pressure sores.
To identify possible mechanisms to explain differences between the maximum time-varying elastance (Emax) and end-systolic pressure-volume (Ees) slope values calculated with radionuclide angiography and to establish whether they have a relationship to heart size, we studied 16 dogs that were instrumented with micromanometer left ventricular catheters and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics and radionuclide angiograms were obtained under control conditions and during six additional steady-state loading conditions. Isochronal Emax averaged 7.14 +/- 2.54 mm Hg/ml, while Ees averaged 5.68 +/- 1.88 mm Hg/ml (p less than 0.01), but they were highly correlated (r = 0.95, p less than 0.001). This observation was related to the assumption of linearity when curvilinearity was present and to the important influence of timing on these relationships. The Emax and Ees slope values were compared to dog weight; left ventricular weight, which ranged from 85 to 142 gm (mean 113 +/- 18 gm); and left ventricular end-diastolic volume, which ranged from 15 to 56 ml (mean 29 +/- 10 ml) using multiple regression analyses. The Emax and Ees slope values demonstrated a comparable inverse linear relationship with only left ventricular end-diastolic volume (r = 0.76 and -0.69, p less than 0.001 and p less than 0.01). We conclude that the differences between Emax and Ees slope values calculated with radionuclide angiography are related to the assumption of linearity when curvilinearity is present and to the importance of the timing of systolic events and that both Emax and Ees are comparably related to left ventricular end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Anterior disclusion has become accepted as an optimal therapeutic model in the restoration of the anterior dentition. The ability to achieve anterior disclusion is influenced by the anterior determinants of esthetics, phonetics, skeletal relation, tooth position, abutment distribution, and alveolar bone support in addition to the posterior condylar determinants. Temporary restorations are made to incorporate these factors and it becomes necessary to transfer the information to working models of the articulator. A technique is described whereby a wax or silicone index fixed partial denture is made at chairside, duplicating the temporary restoration that is directly transferable to the working casts of the articulator. This technique allows the technician to make final restorations according to the index fixed partial denture, thus incorporating the anterior determinants of occlusion in conjunction with the posterior condylar determinants specific to each patient.
Endocrine hypertension secondary to disorders of the adrenal glands is uncommon, but by no means rare. The importance of correct biochemical diagnosis and subsequent localization of the responsible lesion(s) lie in the fact that many of these syndromes occur in younger patients, may exhibit familial patterns of inheritance and are frequently amenable to surgical cure. The radiopharmaceuticals (131)1-6 beta-iodomethyl-19-norcholesterol (NP-59), a marker of adrenocortical cholesterol uptake, and (131)1- and (123)1-metaiodobenzylguanidine (MIBG), a norepinephrine (NE) analog and marker of energy-dependent NE storage vesicle accumulation, can be shown to accurately localize adrenal cortex and sympathoadrenal dysfunction, respectively. In Cushing's syndrome (CS) not only does the pattern of NP-59 uptake depict the adrenal dysfunction and its pathophysiologic basis, but the level of NP-59 accumulation reflects the degree of adrenocortical hyperfunction. Adrenocorticotrophin-independent CS is uniformly and accurately localized, especially in bilateral cortical nodular hyperplasia where even high resolution computed tomography (CT) may fail to depict the often subtle, asymmetric anatomic abnormalities. Dexamethasone suppression NP-59 adrenal scintigraphy has been shown to be highly sensitive and specific, and exceeds the efficacy of CT in the differentiation of adenoma and bilateral hyperplasia in primary aldosteronism. MIBG is useful as a sympathoadrenal imaging agent whose clinical utility has been demonstrated in the localization of pheochromocytoma, especially as a modality to screen the body for multiple and extraadrenal, recurrent, or metastatic lesions. Moreover, the extent of metastatic involvement from neuroblastoma can also be accurately depicted using MIBG. In this review we will examine the role of adrenal scintigraphy in the characterization of hypersecretory disorders of the adrenal cortex, medulla, and related conditions that produce hypertension as part of their symptom(s) complex. This approach, which is complementary to other anatomical modalities of imaging, can be used to advantage in the localization of functioning cortical and medulla adrenal diseases and other neoplasms of adrenergic origin.
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The authors evaluated the potential of magnetic resonance (MR) imaging at 0.35 T to permit differentiation of nine hyperfunctioning adrenal cortical lesions from 21 nonhyperfunctioning adrenal cortical adenomas. Both qualitative data (visual assessment) and quantitative data (signal intensity ratios, T1, and T2) were used for tissue characterization. With a 2,000/56-100 sequence (repetition time msec/echo time msec), the majority of lesions were visually isointense to liver. Of 34 quantitative measures, only lesion-liver and lesion-kidney intensity ratios at 2,000/150 showed statistically significant differences among nonhyperfunctioning adenomas, aldosterone-producing lesions, and corticosteroid-producing lesions; however, the authors question the significance of these differences because of the abundant noise associated with the 2,000/150 sequence. The results suggest that nonhyperfunctioning adrenal cortical adenomas cannot be distinguished from benign hyperfunctioning cortical lesions with use of MR imaging at 0.35 T.
A prominent filling defect was depicted on a radionuclide ventriculogram in a patient with mitral regurgitation. This defect was later shown, by cardiac ultrasound, to be due to mitral valve prolapse into the left ventricle during diastole. This case illustrates that mitral valve prolapse should be added to the list of clinical entities that can result in an intraventricular defect on a radionuclide ventriculogram.
We retrospectively reviewed the imaging studies in 17 proved cases of primary aldosteronism to determine the value of the procedures used to detect adrenal tumors or adrenal hyperplasia. The procedures included CT with 3-, 5-, and/or 10-mm-thick sections (17 patients), 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy (16 patients), and MR imaging (six patients). Proof of the adrenal abnormality was established in cases of tumor (seven adenomas, one carcinoma) by surgery and in cases of adrenal hyperplasia by surgery (three cases); venous sampling (three cases); or combined clinical, biochemical, and imaging data (three cases). Both CT and scintigraphy detected six of the seven adenomas and the adrenal carcinoma (88%). Regarding hyperplasia, CT was correct in five of six and scintigraphy was correct in two of four cases proved by surgery or venous sampling. CT and NP-59 were concordant and suggested the diagnosis of hyperplasia in the remaining three cases without surgical or venous sampling proof. MR detected both cases of adenoma in which it was performed and showed evidence of hyperplasia in one of the four cases of hyperplasia in which it was performed. Although the number of patients in this series is too small to have much statistical power, these results suggest that CT and NP-59 scintigraphy are equivalent in the detection of adrenal abnormalities in patients with primary aldosteronism. The value of MR in the detection of small adrenal contour abnormalities was limited by slice thickness capabilities.
The adrenal gland consists of cortical and medullary components, both of which may be functionally imaged using radiopharmaceuticals designed to take advantage of the specialized physiology of each tissue. Radiolabeled cholesterol derivatives are taken up by normal and abnormal adrenal cortex and provide an in vitro map of adrenocortical function in Cushing's Syndrome, hyperaldosteronism, and hyperadrenogenism. Quantification of uptake shows strong correlation with biochemical parameters of adrenocortical hyperfunction. In the case of incidentally discovered euadrenal masses scintigraphy may help to distinguish between benign, nonfunctional cortical adenomas, and destructive, potentially malignant lesions. Radiolabeled metaiodobenzylguanidine (MIBG) is a tracer of type I uptake and intracellular storage capacity for catecholamines in sympathomedullary tissues and tumors derived from this system. This permits the location of pheochromocytomas of all types (benign and malignant, intra- and extra-adrenal, sporadic and familial) as well as neuroblastomas in all stages. Other neuroendocrine tumors with type I uptake capacity may also be imaged. In suitable cases preliminary data suggests the administration of large doses of MIBG may permit internal radiotherapy of otherwise untreatable neuroendocrine tumors.
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.