Henry N. Wellman

Primary Aldosteronism: Diagnosis, Localization, and Treatment

New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.

Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Predictors of Bone Mass in Perimenopausal Women: A Prospective Study of Clinical Data Using Photon Absorptiometry

STUDY OBJECTIVE To determine whether clinically available data on risk factors are adequate to identify perimenopausal women with either low or high bone mass. DESIGN Cross-sectional observational study of a cohort of perimenopausal women (mean age, 50.8 years). SETTING Community volunteers in a university hospital. SUBJECTS One hundred twenty-four white volunteers established as perimenopausal by history and serum concentrations of estrogens and follicle-stimulating hormone. MEASUREMENTS AND MAIN RESULTS Models were constructed to predict bone mass in the radius, lumbar spine, and hip using risk factors (age, height, weight, calcium and caffeine intake, alcohol and tobacco use, and urinary markers of bone turnover). Although highly significant predictive models were developed for all skeletal sites, none of the models correctly identified more than 70% of women with low bone mass at any site. However, for the radius, a model was constructed that never overestimated bone mass by more than 0.10 g/cm. A small subgroup (7%) with short stature, low body weight, low calcium intake, and who were heavy smokers always had low radial bone mass. Using these models, about 30% of our population could be assessed without bone mass measurements. Predictions for the spine and femur were less efficient, suggesting that direct measurements are required if therapy decisions are to be based on bone mass at these sites. CONCLUSIONS Risk factors for osteoporosis are of limited use in identifying women with low bone mass around the time of menopause. Measurements of bone mass are probably necessary if the risk for osteoporosis is to be the basis for deciding on estrogen replacement therapy.

Influence of Disodium Etidronate on Clinical and Laboratory Manifestations of Paget's Disease of Bone (Osteitis Deformans)

Abstract A six-month double-blind controlled study was performed to determine effectiveness and dose response of disodium etidronate on Pagets disease (osteitis deformans). Forty-seven subjects were studied with pain related to radiologically documented Pagets bone sites as well as marked elevation of serum alkaline phosphatase and hydroxyproline excretion. There was significant (p<0.05) reduction of alkaline phosphatase, hydroxyproline and radiofluoride or radiostrontium uptake over Pagets bone lesions after orally administered disodium etidronate at doses of 5, 10 and 20 mg per kilogram per day for six months. There was a dose-response relation of administered disodium etidronate to improvement of pain, with moderate or marked improvement of pain in six of seven subjects on 20 mg per kilogram per day. In all dosage groups the most marked relief of pain was at sites of Pagets involvement of long bones. Apparent side effects were limited to occasional abdominal cramps. (N Engl J Med 289:1379–1384, 1973)

Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.

Feasibility of low doses of I-131 for thyroid ablation in postsurgical patients with thyroid carcinoma

The feasibility of using low doses of l-131 (30 mCi) for ablation of thyroid remnants following surgery for papillary and follicular thyroid carcinoma was examined in 21 patients. Six weeks following near-total thyroidectomy and three days following intramuscular thyroidstimulating hormone (10 IU), patients were given 30 mCi of l-131 and scans were performed 24 to 72 hours later. Remaining thyroid tissue was identifiable in the thyroid bed in 19 patients, and two patients also had evidence of cervical metastases. Patients with metastases received an additional 100 mCi of l-131. Follow-up l-131 scans were performed at nine to 15-month intervals in ten patients who initially received 30 mCi of l-131, and only one patient showed complete ablation of the residual thyroid tissue, whereas the remaining nine patients had persistent uptake of l-131 in the same regions in which the uptake was seen in the initial postoperative scans. One of the nine patients had evidence of a cervical metastasis as well. It is therefore apparent that total or near-total thyroidectomy rarely removes all thyroid tissue and that an “out-patient” dose of l-131 is not adequate for ablation of postoperative thyroid remnants.

CONTRAST AND NUCLEAR ARTHROGRAPHY IN LOOSENING OF THE UNCEMENTED HIP PROSTHESIS

The recent popularity of ingrowth or uncemented hip arthroplasties has presented problems in the radiographic diagnosis of loosening because there is no longer a cement interface in which lucencies may be seen. We evaluated a combination of positive contrast and nuclear arthrography to see whether these studies could accurately detect loosening of uncemented femoral components of hip prostheses. We performed routine contrast and nuclear arthrography in 21 patients with ingrowth total hip arthroplasties or bipolar endoprostheses. The results were surgically confirmed in 12 patients. The contrast arthrogram was true positive in 5 and false negative in 5. There were no false positives and 2 true negatives. The nuclear arthrogram was true positive in 7 patients, false negative in 3, and true negative in 2. Taken together, there was only 1 patient in whom both contrast and nuclear arthrography were false negative, and there were no false positives. Thus, when either contrast or nuclear arthrography is positive, the sensitivity of the combined procedures is 90%; when both studies are negative, the specificity is 100%. The combination of contrast and nuclear arthrography is an accurate method of determining loosening of the femoral component of an uncemented hip arthroplasty or bipolar endoprosthesis in the patient with postoperative hip pain.

Comparison of technetium-99m sulfur colloid and in vitro labeled technetium-99m RBCs in the detection of gastrointestinal bleeding

Twenty-seven paired Tc-99m sulfur colloid (SC) and Tc- 99m RBC studies were evaluated for the detection of Gl bleeding. The only two positive Tc-99m SC studies had positive early Tc-99m RBC studies as well. There were 15 other positive Tc-99m RBC studies (three during the first hour) and these were associated with normal Tc- 99m SC scans. Approximately 70% of the positive Tc- 99m RBC studies occurred after 1 hour. Tc-99m RBCs should be the initial test in patients with Gl bleeding.

Pulmonary thromboembolism: Current status report on the role of nuclear medicine

The normal perfusion study continues indisputably to rule out the presence of pulmonary embolism (PE) with reasonable certainty. However, the abnormal perfusion study requires additional specificity. Many retrospective and one prospective correlation of contrast pulmonary angiography (CPA) have largely substantiated the efficacy of ventilation imaging and increasing specificity, especially with a high-probability (HP) interpretation to approximately a 90% predictive value. In most studies, the predictive value of a low-probability (LP) interpretation also approaches 90%. Intermediate-probability (IP) ventilation-perfusion (V-P) studies are the most frequent reason for performing pulmonary angiography, although LP studies with a stated prior clinical HP should also have CPA. Ventilation imaging technique is not as uniformly established as for perfusion studies, leading to some continued variability in interpretative criteria; yet criteria proposed by Biello and his colleagues have begun to be widely adopted. Aerosol inhalation imaging is developing, but has not been widely used, while problems continue with central airways deposition. The importance of contemporary correlative chest x-rays (CXR) especially when normal, have been emphasized, as well as new findings of the import of serial post-V-P CXRs, especially in HP studies without CPA or negative CPA. CPA continues to be the most specific diagnostic test for PE when properly performed, and is complimented and enhanced by use of prior V-P findings; although it is clear that too few CPAs are being performed. Consequently, there has been too much clinical dependence on V-P imaging. The value of prospective clinical probability estimates in patient management has been better substantiated. Reemphasis on thromboembolism as a systemic disease with use of some objective evaluation of the presence of peripheral thrombosis is becoming a part of clinical rationale, with the integrated long-leg radionuclide venograms (RNV) being one of the reasonable approaches. Multicenter studies have demonstrated, contrary to prior contentions, that V-P imaging leads to a significant net reduction and use of anticoagulants, as well as having overall significant efficacy in effecting patient management in suspected PE. Some of the controversies surrounding V-P imaging are expected to be resolved with the completion of the ongoing multiinstitute Prospective Investigation of Pulmonary Embolic Diagnosis (PIOPED) study.(ABSTRACT TRUNCATED AT 400 WORDS)

Meningomyelocele and Syringohydromyelia

Twenty meningomyelocele patients with nonfunctional ventricular shunts or no shunts were studied radiologically. This group was compared to a second group of 4 patients with functional shunts. The various techniques are compared and discussed. Pantopaque ventriculography is a potentially dangerous procedure. Radioisotope ventriculography appears to be a safe and useful method of diagnosing syringohydromyelia. Ventricular decomposition by means of a shunt appears to be an effective treatment.