Biomedical subjects
Publications and source records attributed to B Shapiro.
Adrenocortical scintigraphy provides information concerning cortical function that is not readily available by other means. The ability to map differential adrenal cortical function has great clinical utility and demonstrable cost-effectiveness in the evaluation of adrenocortical disease and in distinguishing benign from malignant lesions in patients with incidentally discovered adrenal masses.
Craniopharyngiomas are benign cystic para-hypophyseal tumors often associated with hypopituitarism and visual-field abnormalities. Their therapy by surgery and external beam radiotherapy is imperfect. The intracavitary instillation of beta-emitting colloid radiopharmaceuticals into the cysts permits the delivery of far higher radiation doses to the cyst lining than is possible by external beam radiotherapy. This technique permits destruction of the lining epithelium with resultant elimination of cyst fluid formation and cyst shrinkage in up to 80% of cases.
Seven patients compound heterozygous for the 3849 + 10kb C --> T mutation in the CFTR gene were found among the 152 patients attending the CHLA CF Clinic. The frequency of this mutation accounts for 2.3 and 3.9% of thetotal and Hispanic CF alleles of CHLA patients. These are significantly higher than the 0.6% of the general CF population. The average age of diagnosis of this group of Hispanics is 3.1 years, which is much younger than that reported for CF patients of other ethnicities with the same mutation. Both pancreatic sufficient and pancreatic insufficient patients were observed. It is concluded that the 3849 + 10kb C --> T mutation is associated with a variable but potentially mild type of CF.
The postpartum period can be a time when profound changes in calcium metabolism and bone mineral density (BMD) occur, particularly in association with lactation. We investigated the hypothesis that calciotrophic hormones [1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH)] are different by lactation practice or hormone status [PTH-related peptide (PTHrP), estradiol, and prolactin] and have a potential role in the bone loss and recovery associated with lactation. 1,25-Dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, femoral BMD, PTHrP, prolactin, estradiol, and bone turnover markers were measured at 2 wk and at 2, 4, 6, 12, and 18 mo postparturition in 115 postpartum women aged 20-40 y (parity: 0-1). Lumbar spine BMD was measured at 2 wk and at 6, 12, and 18 mo during the postpartum period. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations were nonlinear across the 18-mo postpartum period. Between baseline and 18 mo postparturition, PTH and 1,25-dihydroxyvitamin D concentrations did not decline, while there was a substantial decline in 25-hydroxyvitamin D concentrations. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations did not differ by lactation practice or by PTHrP, estradiol, or prolactin status. These classic calciotrophic hormones were not associated with concentrations of bone turnover markers or changes in BMD in lactating women. In summary, patterns of change in calciotrophic hormones (PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D) in the 18-mo postpartum period appeared to be independent of PTHrP, estradiol, prolactin, or lactation status and were not associated with bone turnover markers. These data do not support the hypothesis that these three calciotrophic hormones are a central part of the calcium mobilization associated with the bone loss of lactation.
Varicocele, a varicosity of the gonadal venous plexus, is a well-recognized disorder occurring in up to 10% of men. In women, an analogous varicosity of the salpingo-ovarian plexus is rare. This may be explained, in part, by the lack of obvious findings on clinical examination in women compared with men and the need, until recently, to use invasive venographic methods to confirm the diagnosis. Two cases of "female varicocele" diagnosed by means of echo Doppler and Tc-99m red blood cell scintigraphy and their cure by percutaneous phlebographic occlusion of the ovarian venous varicosity are described.
Intracranial metaiodobenzylguanidine (MIBG) uptake is occasionally and only faintly visualized on diagnostic studies. Recently, intense normal cerebellar uptake was described on posttherapy MIBG images. Experience at the University of Michigan with posttherapy MIBG scintigraphy of pheochromocytoma was reviewed. The patterns and correlates of intracranial uptake after therapeutic 1-131 MIBG in 25 patients (61 patient treatment encounters) were evaluated by review of records and blinded consensus interpretation of diagnostic and posttherapeutic MIBG scans. Thirty-nine (64%) patient treatment encounters demonstrated at least faint (grade 1) MIBG uptake in one or more brain sites; the most common site was the cerebellum. There was a statistically significant relation between intracranial uptake and 1) size of therapeutic dose and 2) patient age, but no relation between intracranial uptake and gender, body mass index, plasma epinephrine level, plasma norepinephrine level, urine metanephrine level, or the therapy-to-imaging interval. Although the influence of age on the pattern and intensity of intracranial uptake is unexplained, the relation to therapy dose may be explained by the possible generation of MIBG metabolites that can cross the blood-brain barrier (high activity administered and the delay until imaging). Further studies are needed to define mechanisms of intracranial uptake and relation to responses and toxicity after MIBG therapy of neuroendocrine tumors.
A 44-year-old woman with Klippel-Trenaunay-Weber syndrome (KTWS) was evaluated for an adrenal mass incidentally discovered on CT. An NP-59 scintigraph showed normal symmetric adrenal tracer uptake, and a Tc-99m labeled RBC scan showed no evidence for an adrenal hemangioma but did show characteristic dilated and tortuous vasculature at multiple other sites. The mass was removed and found to be an adrenal pseudocyst. The pseudocyst was believed to have arisen from a pre-existing, thrombosed and organized adrenal hemangioma. This case demonstrates the previously reported utility of RBC scintigraphy in the depiction of the vascular abnormalities in the diagnosis and treatment of patients with Klippel-Trenaunay-Weber syndrome, as well as the utility of NP-59 scintigraphy in evaluating patients with adrenal masses.
A case of acute cholecystitis in an immunosuppressed patient with hepatocellular dysfunction is reported. The diagnostic dilemmas posed by the lack of specific sonographic findings, the possibility of acute gallbladder disease without early cystic duct obstruction, and the absence of clear guidelines for the interpretation of delayed appearance of the gallbladder on hepatobiliary scintigraphy in this subgroup of patients are discussed.
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Tissue deposits of amyloid may lead to various clinical symptoms and signs, depending on the site of deposition. In addition, a specific subtype of amyloidosis, AL protein type, is associated with multiple myeloma. Two cases representing contrasting examples of altered radiopharmaceutical biodistribution in myeloma and amyloidosis are presented and discussed, with a bone tracer depicting the heart and a heart tracer depicting the bones.
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GH plays a key role during adolescence in longitudinal bone growth and the attainment of peak bone mass. We explored the hypothesis that in early adulthood, bone mineral accretion and/or maintenance in men with normal GH and bone mineral status are related to the magnitude of endogenous GH secretion. Overnight plasma GH concentrations (sampled every 10 min from 2100-0500 h) were measured in 15 healthy, lean, Caucasian men (age, 24+/-1 yr; body mass index, 22.6+/-0.6 kg/m2; mean +/- SE). Total body, femur, and lumbar spine bone mineral mass/density were measured by dual energy x-ray absorptiometry. Total body and femoral bone mineral mass correlated with both total nocturnal GH and maximal GH concentrations even when bone mineral mass was adjusted by height (P = 0.005-0.02; r = 0.58-0.74). Neither spinal nor total body bone mineral density (BMD) correlated with GH. Maximum GH correlated with the BMD of all four femoral sites (P = 0.01-0.04; r = 0.55-0.66), whereas total nocturnal GH correlated with only one (trochanter; P = 0.01; r = 0.64) femoral site. Our data support the hypothesis that GH continues to play a role in the accretion and/or maintenance of bone mass in young men. This relationship is more evident in the bone mineral mass achieved than in the BMD.
There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.
We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.
Metaiodobenzylguanidine (MIBG) was developed 18 yr ago for scintigraphic imaging of the adrenomedullary tumors pheochromocytoma and neuroblastoma. Many studies have shown the usefulness of this agent for the management of patients with neuroblastoma or pheochromocytoma, and the 131I-labeled form was recently approved by the Food and Drug Administration for use in the U.S. This article summarizes our current concepts on the diagnostic use of MIBG in children. The radioisotopes available for labeling of MIBG and related compounds, the dosimetry, metabolism and mechanisms of uptake and retention are discussed. Our protocols for imaging both 131I-MIBG and 123I-MIBG, along with the normal distribution of these compounds, are reviewed. The use of MIBG for the management of neuroblastoma, and comparisons with other radiotracers available for imaging neuroblastomas are also addressed.
UNLABELLED: The goal of this study was to examine the clinical and economic outcomes of alternative diagnostic strategies for differentiating benign from malignant adrenal masses. METHODS: We used cost-effectiveness assessment derived from decision analysis and the economic perspective of the payer of health care services. One-time evaluation with fine-needle aspiration (FNA) and combinations of chemical-shift MRI, noncontrast CT, 131I-6beta-iodomethylnorcholesterol (NP-59) scintigraphy, with or without FNA, in a hypothetical cohort of 1000 patients with incidentally discovered unilateral, nonhypersecretory adrenal masses. We calculated and compared the diagnostic effectiveness, costs and cost-effectiveness of the alternative strategies based on estimates from published literature and institutional charge data. RESULTS: At an assumed baseline malignancy rate of 0.25, diagnostic utility varied from 0.31 (CT0) to 0.965 (NP-59) and diagnostic accuracy from 0.655 [noncontrast CT using a cut-off attenuation value of > or = 0 (CT0)] to 0.983 (NP-59). The average cost per patient per strategy ranged from $746 (NP-59) to $1745 (MRI +/- FNA). The best and worst potential cost-to-diagnostic utility ratios were 773 (NP-59) and 2839 (CT0) and 759 (NP-59) and 1982 (MRI +/- FNA) for cost and diagnostic accuracy, respectively. The NP-59 strategy was the optimal choice regardless of the expected outcome examined: cost, diagnostic utility, diagnostic accuracy or cost-effectiveness. Varying the prevalence of malignancy did not alter the cost-effectiveness advantage of NP-59 over the other diagnostic modalities. CONCLUSION: Based on available estimates of reimbursement costs and diagnostic test performance and using reasonable clinical assumptions, our results indicate that the NP-59 strategy is the most cost-effective diagnostic tool for evaluating adrenal incidentalomas over a wide range of malignancy rates and that additional clinical studies are warranted to confirm this cost-effectiveness advantage.
We report two cases of thyrotoxicosis resulting from hyperfunctioning lung metastases from differentiated thyroid cancer. In both patients, a simultaneous diagnosis of thyrotoxicosis and metastatic thyroid cancer was made, based on thyroid function tests as well as 131I whole-body scans showing low thyroid uptake of radioiodine and multiple foci of intense 131I uptake in the lungs. After total thyroidectomy (performed in Patient 2 only) and 131I therapy (cumulative dose of 12.3 GBq in Patient 1 and 9.6 GBq in Patient 2), there was a rapid clinical improvement with significant reduction of the pulmonary metastatic disease in both patients: Patient 1 became euthyroid, while Patient 2 became hypothyroid. Analysis of the 54 cases reported in the literature, including the 2 cases described here, shows this to be a very rare cause of thyrotoxicosis and one that can pose serious problems for both the diagnostic evaluation and choice of therapeutic strategy when compared with the much more common nonhyperfunctioning metastases from thyroid cancer. Lesser degrees of thyroid hormone secretion by differentiated thyroid cancer may be detected and exploited diagnostically by the chromatographic analysis of serum for endogenously labeled thyroid hormones after 131I administration.
Adrenal scintigraphy with 131I-labeled 6-beta-iodomethyl-19-norcholesterol (NP-59) is a technically demanding and complex procedure. However, it can provide crucial and unique information about the functional status of the adrenal glands and guide the appropriate therapeutic management of patients with biochemically proven disease. Since the introduction of this new investigational drug, scintigraphic imaging has been performed using conventional planar techniques. We present an interesting case of primary aldosteronism in which planar scintigraphy and SPECT were combined in an attempt to increase the sensitivity of the study. SPECT revealed scintigraphic evidence of bilateral adrenocortical hyperplasia. Interestingly, the CT scan of this patient showed only an equivocal abnormality in the left adrenal gland, suggestive of an adenoma.