Metaiodobenzylguanidine Scintigraphy Research Articles

SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α1-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed.

Cardiac 123I-MIBG Scintigraphy in Neurodegenerative Parkinson Syndromes: Performance and Pitfalls in Clinical Practice.

Purpose: Cardiac [123I]metaiodobenzylguanidine scintigraphy (123I-MIBG), reflecting postganglionic cardiac autonomic denervation, is proposed for early detection of Parkinson's disease (PD; reduced tracer uptake) and separation from Multiple System Atrophy (MSA; preserved tracer uptake). However, several recent studies report on frequent unexpected 123I-MIBG results in PD and MSA. We sought to determine, whether 123I-MIBG is feasible to discriminate PD from MSA in unselected geriatric patients in clinical practice.Materials and Methods: We screened consecutive patients, that underwent 123I-MIBG for diagnostic reasons. Delayed 123I-MIBG uptake (heart/mediastinum ratio; H/M ratio) was verified by clinical diagnosis of PD, MSA, and ET based on a two-stage clinical assessment: comprehensive baseline (including autonomic testing and additional neuroimaging) and confirmatory clinical follow-up.Results: 28 patients with clinical diagnosis of PD (N = 11), MSA (N = 9), and Essential Tremor (ET, N = 8) were identified. In one third (9/28) nuclear medical diagnosis deviated from clinically suspected syndrome. Visual interpretation of 123I-MIBG identified two cases (MSA and ET) with indeed normal 123I-MIBG uptake. Detailed review of clinical phenotypes provided only in two cases (PD and ET) an adequate explanation (correction of initial diagnosis and confounding drug history) for unexpected 123I-MIBG. In conclusion, 123I-MIBG did not match initial clinical phenotype in 27% PD, 44% MSA, and 25% ET patients.Conclusion: 123I-MIBG scintigraphy is a known specific and valuable technique in scientific approaches and well-defined and highly selected samples. However, predictability of 123I-MIBG based nuclear medical diagnosis for individual cases and thus, feasibility in routine clinical practice is limited. Our clinical series emphasize clinical verification of 123I-MIBG results on an individual basis in clinical routine.

Importance of sympathetic nervous system activity during left ventricular functional recovery and its association with in-hospital complications in Takotsubo syndrome.

The relationship between activation of the sympathetic nervous system (SNS) and improvement of left ventricular (LV) function and how this correlates with clinical outcomes are not fully explored in Takotsubo syndrome (TS). The purpose of this study is to evaluate the relationship between activation of the SNS and LV function improvement and how this correlates with clinical outcomes in TS. Patients with TS were retrospectively identified. Patients were divided into two groups according to the timing of LV function improvement: < 1month (S group) and ≥ 1month (L group). Activation of the SNS was assessed by plasma catecholamine measurement and Iodine-123 meta-iodobenzylguanidine (I123-MIBG) scintigraphy. In-hospital complications included heart failure, cardiogenic shock, the use of invasive or noninvasive ventilation, life-threatening arrhythmia, cerebrovascular event and all-cause death. A total of 90 patients with TS were enrolled. Of these, 39 patients were in the S group and 51 in the L group. There were no significant differences between the two groups in clinical demographics. The L group was characterized by enhanced SNS activation, including higher levels of catecholamines and lower late heart-mediastinum ratio followed by higher washout rate in I123-MIBG scintigraphy, compared with the S group. In-hospital complications were increased in the L group (56% vs. 33.3%, p = 0.03), including higher rates of heart failure (45% vs. 23%, p = 0.03) and in-hospital death (8.0% vs. 0%, p = 0.03). In patients with TS, high activity of the SNS was observed in patients with delayed LV function recovery, which was associated with in-hospital adverse outcomes.

Lewy body constipation.

We systematically reviewed literature regarding “Lewy body constipation”, i.e., constipation due to Lewy body diseases (LBD), with minimal neurologic symptoms. Epidemiology and pathology studies showed that LBD can start with constipation alone, mostly due to neuronal loss and appearance of Lewy bodies in the myenteric plexus. Because LBD significantly increases with age, “Lewy body constipation” may also increase with age. Neuroimaging methods such as metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter (DAT) scan provide a way to detect “Lewy body constipation.” Key for “Lewy body constipation” includes minimal non-motor features such as REM sleep behavior disorder (night talking). Add-on therapy may be required to ameliorate constipation in patients. Diagnosis is not always easy; therefore, collaboration of gastroenterologists and neurologists is highly recommended to maximize patients' quality of life. In conclusion, “Lewy body constipation” might become a distinct category among geriatric constipation, regarding patients' follow-up and their management.

Indication of 99mTc-MDP bone scan after 123I-MIBG scintigraphy in patients with neuroblastoma

123I-MIBG (metaiodobenzylguanidine) scintigraphy and 99mTc-MDP bone scintigraphy (bone scan) are widely used in diagnosis and staging of NB. Consecutively using both methods lead to overall radiation exposure. As most of the patients need additional anesthesia to perform these diagnostic procedures, which accordingly increase the side effect, workload and expenditure. To minimize the exposure, side effect, workload and expenditure, we set the tasks to optimize the diagnostic algorithm. Determine the indications of bone scan after 123I-MIBG scintigraphy. Materials and Methods: 129 patients with NB were included in retrospective study who underwent both diagnostic procedures at interval of less than 30 days at the stage of initial diagnostic procedure using standard protocols. Out of 83 MIBG positive patients bone scan was able to detect metastatic lesions only in 48 patients. However, bone scan had revealed metastatic lesions in 3 out of 14 MIBG-negative patients. Bone scan is indicated only in MIBG-negative neuroblastoma patients; and in cases where the MIBG uptake cannot be determined for example after operative treatment or after starting of chemotherapy.

Spinocerebellar ataxia type 31 associated with REM sleep behavior disorder: a case report

BackgroundSpinocerebellar ataxia type 31 (SCA 31) is a slowly progressive neurodegenerative disorder characterized by pure cerebellar ataxia. Unlike other CAG repeat diseases, sleep-related problems have not been reported in patients with SCA 31 so far.Case presentationA 67-year-old woman was admitted to our hospital with dysarthria and gait disturbance after onset age of 62 years. Neurological examination revealed pure cerebellar ataxia. Genetic analysis detected expansion of a TGGAA repeat in the coding region of the BEAN/TK2 gene on chromosome 16p22.1, confirming the diagnosis of SCA 31. One year later, her husband noticed the patient talking loudly during sleep once or twice a week. Overnight polysomnography showed rapid eye movement sleep without atonia. Cardiac scintigraphy with iodine-123-labeled meta-iodobenzylguanidine revealed a low heart/mediastinum ratio, indicating reduced uptake, and a high washout rate.ConclusionTo our knowledge, this is the first report of a patient with SCA 31 associated with rapid eye movement sleep behavior disorder (RBD). In the future, evaluation of autonomic function, assessment of the frequency of RBD, and performance of cardiac iodine-123-labeled meta-iodobenzylguanidine scintigraphy in a larger number of SCA 31 patients could be useful to resolve important issues regarding the mechanism of RBD.

Molecular Imaging of Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia. The core clinical features of DLB include fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. Molecular imaging is a powerful tool to assess the brain function in vivo. In this chapter, we reviewed the positron emission tomography, single-photon emission computed tomography, and [123I]-metaiodobenzylguanidine scintigraphy studies evaluating the pathological processes underlying DLB, including altered brain metabolism and neurotransmitter pathways, abnormal protein aggregation, and neuroinflammation. These techniques can aid in the differential diagnosis of DLB (versus Alzheimer's disease and related dementia) and in the monitoring disease progression and treatment efficacy of disease-modifying drugs. Furthermore, we explored the limitations of current imaging biomarkers and future directions, particularly focusing on the vital need for tracers that have high affinity for alpha-synuclein.

Usefulness of the combination of iodine-123-metaiodobenzylguanidine scintigraphy and iodine-123-ioflupane scintigraphy in new-onset Parkinson's disease.

The aim of this study was to study the significance of combining iodine-123-cardiac metaiodobenzylguanidine scintigraphy (I-MIBG scintigraphy) and iodine-123-ioflupane (I-ioflupane) dopamine transporter scintigraphy (I-ioflupane scintigraphy) in patients suspected of having Parkinson's disease (PD). We carried out a retrospective study from April 2014 to December 2015 in 48 patients suspected of having new-onset PD who underwent both I-MIBG and I-ioflupane scintigraphies within 3 months. Cases included 37 patients diagnosed as having PD. Controls included 11 patients who had never been diagnosed as having PD or other diseases showing parkinsonism. The cutoff for diagnosing PD was a heart to mediastinum ratio (H/M ratio) of less than or equal to 2.2 for I-MIBG scintigraphy in the delayed phase and a specific binding ratio (SBR) of less than or equal to 3.8 for I-ioflupane scintigraphy. The combined use of both scintigraphies was studied using the formula SBR×H/M ratio as a marker for the logistic regression model. Sixteen (33.3%) patients had SBR of greater than 3.8: eight with PD; eight were controls. Five of eight patients had an H/M ratio of less than or equal to 2.2 (62.5%) and had PD. In the receiver-operating characteristic analysis, the SBR×H/M ratio cutoff was 12.5, with an area under the curve of 0.844 (95% confidence interval: 0.619-1). In an age-adjusted regression analysis in patients with SBR of greater than 3.8, the SBR×H/M ratio was associated significantly with an odds ratio of 0.69 (95% confidence interval: 0.48-0.98, P=0.041). If SBR is greater than 3.8, the SBR×H/M ratio can help diagnose PD. The combined use of the two scintigraphies can improve the diagnosis of PD.

Outcomes of surgery for functional cardiac paragangliomas: A single-center experience of 17 patients

ObjectiveCardiac paragangliomas are rare neuroendocrine tumors. Early surgical treatment improves clinical symptoms and prolongs survival. We review our experience in 17 patients who underwent surgical resection for functional cardiac paraganglioma. MethodsSeventeen patients underwent surgery for functional cardiac paraganglioma from 2004 to 2017 were identified. Clinical data and long-term outcomes were extracted and analyzed. ResultsAll 17 patients with cardiac paraganglioma (11 males) with a median age of 35 years (range, 11 to 51 years) were hormonally functional and underwent operations. A 24-hour urine catecholamine assay documented elevation of norepinephrine, epinephrine, and dopamine. Tumors were determined with octreotide scintiscan in all 17 patients and metaiodoben-zylguanidine scintigraphy in 10 of 15 patients. Tumor sites were right atrioventricular groove in 4 patients, between the main arteries in 10 patients, and interatrial groove in 4 patients. All patients underwent complete resection. Concomitant surgeries were: structural reconstruction in 16 patients (94%) and coronary artery bypass graft in 8 patients (47%). One patient had a history of incomplete resection of an intra-atrial tumor. One patient died postoperatively. Operative mortality is 5.8%. During follow-up (mean, 6.5 years; range, 1.5 to 14.2 years), 16 patients are alive in functional class I or II. Two patients developed tumor recurrence and 14 remained symptom-free with normal urinary catecholamines. ConclusionsWith a multidisciplinary treatment, early diagnosis, complete resection for the tumor along with complex reconstruction is achievable for most patients, and it offers promising long-term survival.

What a neurologist should know about PET and SPECT functional imaging for parkinsonism: A practical perspective

The diagnosis of a parkinsonian syndrome based on clinical criteria remains sometimes difficult, especially at disease onset. Brain or heart molecular imaging techniques (SPECT or PET) can provide a major help to improve and speed up diagnosis, influencing treatment strategies. Presynaptic dopaminergic imaging using either [18F]-Dopa PET or 123I -2β-Carbomethoxy-3β-(4-Iodophenyl)- N-(3-Fluoropropyl) Nortropane ([123I]-Ioflupane)SPECT demonstrates or rules out the presence of a dopaminergic degenerative process. This allows to distinguish Parkinson's disease, Parkinson “plus” syndromes and dementia with Lewy bodies (reduced radiotracers binding) from essential tremor, psychogenic, post-neuroleptic or vascular parkinsonisms, dopa-responsive dystonia and Alzheimer's disease (normal radiotracers binding). For differential diagnosis between Parkinson's disease and Parkinson “plus” syndromes, brain molecular imaging with [18F]-Fluorodeoxyglucose ([18F]-FDG) PET or 99mTc-HMPAO SPECT can provide useful information, whereas [18F]-Dopa PET or [123I]-Ioflupane does not separate these entities. Finally, sympathetic cardiac [123I]-Metaiodobenzylguanidine ([123I]-MIBG) scintigraphy or SPECT can help distinguishing Parkinson's disease and dementia with Lew bodies (decreased binding) from multiple system atrophy and progressive supranuclear palsy (normal binding). New radiotracers notably those targeting the pathological process itself such as Tau aggregates are under development and may provide interesting informations to delineate the different Parkinson “plus” syndromes.

Impact of an exercise training program on cardiac neuronal function in heart failure patients on optimal medical therapy: A randomized Iodine-123 metaiodobenzylguanidine scintigraphy study

BackgroundThe syndrome of heart failure (HF) is characterized by left ventricular dysfunction and a compensatory chronic over activation of the sympathetic nervous system. We wanted to investigate if the beneficial effects of exercise training (ET) in HF patients on optimal medical therapy (OMT) are associated with alterations in cardiac sympathetic activity. MethodsCardiac sympathetic activity was evaluated at baseline and after 12 weeks using metaiodobenzylguanidine scintigraphy in 23 patients with stable HF participating in the SmartEx trial. Patients with HF in New York Heart Association class II or III and left ventricular ejection fraction <35 % were randomized to three different ET groups. ResultsWe found no statistically significant changes in cardiac sympathetic activity after 12 weeks of ET. Heart to mediastinum (H/M) ratio at 15 minutes (0.00174 ± 0.0841, P = 0.922), H/M ratio at 4 hours (−0.00565 ± 0.1163, P = 0.818) and washout ratio (WR) (−1.2666 ± 16.5412, P = 0.717). A further group-wise analysis of the three ET groups did not show any difference between the groups. ConclusionA 12-week ET program did not alter the abnormal cardiac sympathetic activity in stable HF patients on modern OMT.

Sensitivity and specificity of cardiac metaiodobenzylguanidine scintigraphy in the early diagnosis of Parkinson's disease.

Metaiodobenylguanidine (MIBG) scintigraphy has been shown to enhance the probability of correct diagnosis in patients with parkinsonian syndromes (PS). Thus far, studies of the clinical usefulness of MIBG have been confined to cross-sectional assessments, which are inevitably associated with diagnostic uncertainty during the early stages of these syndromes. In this study, the initial clinical diagnosis was reevaluated longitudinally to assess the sensitivity and specificity of clinical and MIBG parameters in the early diagnosis of PS. 167 patients with PS (age 67.03 ± 8.92years (mean ± standard deviation), duration of symptoms 2.48 ± 5.27years, median Hoehn and Yahr score 2) underwent an initial clinical assessment and MIBG scintigraphy. Eighty seven of those patients (56 with Parkinson's disease (PD), 1 with multiple system atrophy (MSA), 23 with atypical PS, 7 with tremor syndrome) were clinically reevaluated a mean of 3years later in order to verify their initial diagnosis. The use of a lower limit of normal value of 1.74 for the heart-to-mediastinum ratio (HMR) achieved the best discrimination between PD and other PS. The sensitivity of MIBG scintigraphy to PD was 94%; it also had a specificity of 65%, a positive predictive value of 88%, and a negative predictive value of 79%. MIBG scintigraphy was better than initial clinical diagnosis alone (sensitivity 83%, specificity 39%) or levodopa responsiveness (sensitivity 92%, specificity 10%). However, a combination of clinical diagnosis and MIBG scintigraphy was found to be especially clinically useful (specificity 95%, sensitivity 83%, positive predictive value 95%, negative predictive value 83%). MIBG scintigraphy was demonstrated to be a reliable tool for the diagnosis of early PD. The best diagnostic accuracy was achieved by combining a clinical examination with MIBG scintigraphy.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review

BackgroundCardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient.Case presentationA 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months.ConclusionOur case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Early diagnosis of Lewy body disease in patients with late-onset psychiatric disorders using clinical history of rapid eye movement sleep behavior disorder and [123 I]-metaiodobenzylguanidine cardiac scintigraphy.

Rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease or dementia with Lewy bodies. The purpose of this study was to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late-onset psychiatric disorders. Study subjects included 19 patients with late-onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward. Clinical profiles and radiological findings by cardiac [123 I]-metaiodobenzylguanidine ([123 I]-MIBG) scintigraphy and imaging for the dopamine transporter (DAT) were compared between patients with and without RBD symptoms. The correlations between the percentage of RWA in the total rapid eye movement sleep (%RWA) and radiological findings were also investigated. Nine patients reported RBD symptoms only on specific questioning, but clinical profiles, including the prevalence of antipsychotropic usage, did not differ when compared to the remaining 10 patients without RBD (incidental RWA group). The median %RWA was significantly higher in the definite RBD group than in the incidental RWA group. Although the cardiac [123 I]-MIBG uptake was significantly lower in the definite RBD group than in the incidental RWA group, there was overlap in the specific binding ratio on DAT scan. The severity of %RWA was highly correlated with the value of cardiac [123 I]-MIBG uptake, but not with specific binding ratio on DAT scan. Clinical history of RBD and cardiac [123 I]-MIBG scintigraphy are helpful for an early differential diagnosis of LBD from late-onset psychiatric disorders, even before parkinsonism or dementia appears.

Pediatric opsoclonus-myoclonus-ataxia syndrome: Experience from a tertiary care university hospital.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder; there is limited experience regarding its clinical course and therapeutic response. To describe the clinical profile, investigations, and therapeutic outcome in pediatric OMAS. Fourteen children (age: 27.1 ± 7 months; male: female = 1:2.3) suffering from OMAS seen over a period of 10 years (2006-2015) were included in the study. Their clinicodemographic profile, investigations, therapeutic outcome at follow-up, and relapses were reviewed. Ten children reported antecedent events (respiratory infection: 7; gastrointestinal infection: 1; vaccination: 2). The most common referral diagnosis was acute cerebellitis (n = 8). Hypotonia (n = 9), abnormal behavior (n = 10), and neuroregression (n = 6) were also the frequent manifestations. Brain magnetic resonance imaging, cerebrospinal fluid, and urinary vanillylmandelic acid were normal in all the patients. Seven patients had an underlying tumor (abdomen: 4; thorax: 2; neck: 1) detected by ultrasound (n = 2/14), computed tomography (CT) (n = 6/12), and fluorodeoxyglucose - positron emission tomography (n = 2/2). CT scan identified the tumor in 2 patients where metaiodobenzylguanidine scintigraphy was negative. All patients received steroids for 22.3 ± 20 months (3 months to 5 years). Eight required prolonged immunomodulation (>12 months). Complete remission after follow-up of 31.3 ± 19 months (7 months to 5 years) was noted in 5 patients, whereas the rest had persisting behavioral and cognitive abnormalities. Relapses were noted in 6 patients related to intercurrent infections (n = 5) and discontinuation of steroids (n = 1). The patients presented with isolated symptoms of the full-blown syndrome during their relapses. OMAS in children runs an indolent course requiring careful monitoring and long-term immunomodulation. An abnormal behavior is common and the outcome is variable.

Pheochromocytomas and Hypertension

Pheochromocytomas and paragangliomas (PPGLs) are uncommon catecholamine-producing neuroendocrine neoplasms that usually present with secondary hypertension. This review is to update the current knowledge about these neoplasms, the pathophysiology, genetic aspects and diagnostic and therapeutic algorithms based on scientific literature mostly within the past 3years. Eighty to eighty-five percent of PPGLs arise from the adrenal medulla (pheochromocytomas; PCCs) and the remainder from the autonomic neural ganglia (paragangliomas; PGLs). Catecholamine excess causes chronic or paroxysmal hypertension associated with sweating, headaches and palpitations, the presenting features of PPGLs, and increases the cardiovascular morbidity and mortality. Genetic testing should be considered in all cases as mutations are reported in 35-40% of cases; 10-15% of PCCs and 20-50% of PGLs can be malignant. Measurements of plasma-free metanephrines or 24-h urine-fractionated metanephrines help biochemical diagnosis with high sensitivity and specificity. Initial anatomical localization after biochemical confirmation is usually with computed tomography (CT) or magnetic resonance imaging (MRI). 123Iodine metaiodobenzylguanidine (123I-MIBG) scintigraphy, positron emission tomography (PET) or single-photon emission computed tomography (SPECT) is often performed for functional imaging and prognostication prior to curative or palliative surgery. Clinical and biochemical follow-up is recommended at least annually after complete tumour excision. Children, pregnant women and older people have higher morbidity and mortality risk. De-bulking surgery, chemotherapy, radiotherapy, radionuclide agents and ablation procedures are useful in the palliation of incurable disease. PPGLs are unique neuroendocrine tumours that form an important cause for endocrine hypertension. The diagnostic and therapeutic algorithms are updated in this comprehensive article.

Complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine scintigraphy after a single session of 131I-metaiodobenzylguanidine therapy: a case report

BackgroundPheochromocytomas are rare neuroendocrine tumors, with a malignancy frequency of approximately 10%. The treatment of malignant pheochromocytoma is palliative, and the traditional management strategy has limited efficacy. Furthermore, no clear criteria exist for the treatment of metastatic pheochromocytoma, especially for unresectable lesions. We report a case of complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine (MIBG) scintigraphy after a single session of 131I-MIBG therapy.Case presentationA 61-year-old woman had a right adrenal grand tumor and lymph node metastasis on the hilum of the right kidney, both of which incorporated MIBG. After surgery, immunostaining of a tumor specimen showed expression of the tumor makers chromogranin and synaptophysin. One year postoperatively, abdominal computed tomography revealed a local recurrence and retroperitoneal lymph node swelling. The local recurrence was positive for MIBG uptake, whereas the swollen retroperitoneal lymph nodes were negative. She underwent surgery again, but the local recurrence was unresectable because of rigid adhesion to the surrounding tissue. Immunostaining of an intraoperatively extracted swollen retroperitoneal lymph node showed expression of tumor markers. The patient then underwent a single session of 131I-MIBG therapy (7.4 GBq, 200 mCi), after which the residual lesions no longer incorporated MIBG, and a complete response in 123I- metaiodobenzylguanidine (MIBG) scintigraphy was achieved. The 131I-MIBG treatment was repeated 6 months later. None of the lesions were positive for MIBG uptake.Conclusions131I-MIBG therapy efficaciously treats unresectable lesions that are positive for MIBG uptake.

Investigation into cardiac sympathetic innervation during the commencement of haemodialysis in patients with chronic kidney disease

BackgroundPatients with chronic kidney disease (CKD) who undergo chronic haemodialysis (HD) show altered sympathetic tone, which is related to a higher cardiovascular mortality. The purpose of this study was to investigate the effect of transition from pre-HD to HD on cardiac sympathetic innervation.MethodsEighteen patients aged 58 ± 18 years (mean ± standard deviation [SD]), 13 males and five females, with stage 5 CKD and nine healthy control subjects aged 52 ± 17 (mean ± SD), three males and six females, were included in this prospective study between May 2010 and December 2013. All patients underwent 123I-labelled meta-iodobenzylguanidine (123I-MIBG) scintigraphy for cardiac sympathetic innervation and electrocardiographically gated adenosine stress and rest 99mTc-labelled tetrofosmin single-photon emission computed tomography for myocardial perfusion imaging prior to (pre-HD) and 6 months after the start of HD. Results of 123I-MIBG scans in patients were compared to controls. Impaired cardiac sympathetic innervation was defined as late heart-to-mediastinum ratio (HMR) < 2.0.ResultsMean late HMR was lower in patients during HD (2.3) than in controls (2.9) (p = 0.035); however, in patients it did not differ between pre-HD and after the start of HD. During HD, two patients showed new sympathetic innervation abnormalities, and in three patients innervation abnormalities seemed to coincide with myocardial perfusion abnormalities.ConclusionsCKD patients show cardiac sympathetic innervation abnormalities, which do not seem to progress during the maintenance HD. The relationship between sympathetic innervation abnormalities and myocardial perfusion abnormalities in HD patients needs further exploration.

Imaging of Nonmalignant Adrenal Lesions in Children.

The adrenal glands in children can be affected by a variety of benign lesions. The diagnosis of adrenal lesions can be challenging, but assessment of morphologic changes in correlation with the clinical presentation can lead to an accurate diagnosis. These lesions can be classified by their cause: congenital (eg, discoid adrenal gland, horseshoe adrenal gland, and epithelial cysts), vascular and/or traumatic (eg, adrenal hemorrhage), infectious (eg, granulomatous diseases), enzyme deficiency disorders (eg, congenital adrenal hyperplasia [CAH] and Wolman disease), benign neoplasms (eg, pheochromocytomas, ganglioneuromas, adrenal adenomas, and myelolipomas), and adrenal mass mimics (eg, extralobar sequestration and extramedullary hematopoiesis). Multimodality cross-sectional imaging helps to define the origin, extent, and relationship of these lesions to adjacent structures, as well as to guide treatment management. The anatomic and functional imaging modalities used to evaluate pediatric adrenal lesions include ultrasonography, computed tomography (CT), magnetic resonance imaging, and iodine 123 metaiodobenzylguanidine scintigraphy. Identifying the imaging features of nonmalignant adrenal lesions is helpful to distinguish these lesions from malignant adrenal neoplasms. Identifying characteristic imaging findings (eg, enlarged adrenal glands, with cerebriform surface, and stippled echogenicity in CAH; a T2-hyperintense mass with avid contrast enhancement in pheochromocytoma; low CT attenuation [<10 HU] and signal intensity drop on opposed-phase chemical shift images in adenoma; and enhancing suprarenal mass supplied by a systemic feeding artery in extralobar sequestration) can aid in making the correct diagnosis. In addition, clinical features (eg, ambiguous genitalia in CAH and hypertension in pheochromocytoma) can also guide the radiologist toward the correct diagnosis. ©RSNA, 2017.

Thyrotoxic and pheochromocytoma multisystem crisis: a case report

BackgroundThyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management.Case presentationA 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm).A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave’s hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor. After retroperitoneal laparoscopic adrenalectomy on hospital day 33, his condition stabilized. He was discharged on hospital day 58.ConclusionsSince he required more intensive cardiovascular management for thyrotoxic crisis, beta blockade was increased under intensive care unit monitoring even though initial alpha blockade is recommended in pheochromocytoma. When these crises occur simultaneously, cardiovascular management can be very challenging.