Efficacy of alpha-Blockers on Hemodynamic Control during Pheochromocytoma Resection:A Randomized Controlled Trial

CONTEXT: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL). OBJECTIVE: To determine which type of α-adrenergic receptor blocker provides the best efficacy. DESIGN: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898). SETTING: Multicenter study including 9 centers in The Netherlands. PATIENTS: 134 patients with non-metastatic PPGL. INTERVENTION: phenoxybenzamine or doxazosin starting 2-3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized. MAIN OUTCOME MEASURES: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (i.e., SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score. RESULTS: Median cumulative time outside blood pressure targets was 11.1% [IQR: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% [5.3-20.2] in the doxazosin group (P=0.75, r=0.03). The hemodynamic instability score was 38.0 [28.8-58.0] and 50.0 [35.3-63.8] in the phenoxybenzamine and doxazosin group, respectively (P=0.02, r=0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P=0.68). There was no mortality after 30 days. CONCLUSIONS: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome

Crystal IS on the move

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis 18 years and follow-up 5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (emean 14.5 versus 15.8cm/s, P=0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac agin

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

Contains fulltext : 81280.pdf (publisher's version ) (Open Access)BACKGROUND: Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. METHODS: We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. RESULTS: A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. CONCLUSION: The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL

Endomyocardial Fibrosis: Still a Mystery after 60 Years

The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution

Subklinische schildklierfunctiestoornissen

Subclinical hypothyroidism is associated with aspecific complaints such as tiredness, cognitive and depressive complaints, subtle disturbances in lipid values, an increased risk of cardiovascular disease, ovulatory dysfunction and a negative effect on foetal psychomotor development and pregnancy outcome. Subclinical hyperthyroidism is associated with atrial fibrillation, osteoporosis and dementia. Not enough prospective randomised studies with hard outcomes are available to provide evidence-based general recommendations. Therefore, the decision as to whether or not a patient should be treated needs to be made on an individual basis. For subclinical hypothyroidism it is advisable to consider treatment in the case of positive thyroid peroxidase antibody tests, a TSH concentration higher than 10 mU/l, the presence of one or more risk factors for cardiovascular disease, infertility on the basis of ovulatory dysfunction, and pregnancy. In the case of complaints of tiredness and certainly in the case of depression or cognitive dysfunction, a 3-month trial treatment can be considered. This leads to a decrease of the complaints in about 25% of cases. As negative effects are associated with the treatment, we advise an expectant approach in all other cases with a yearly monitoring of the TSH concentration. For subclinical hyperthyroidism it is advisable to consider treatment in the case of a nodular goitre, and especially in the case of atrial fibrillations. If subclinical hyperthyroidism persists in the absence of nodular thyroid disease, an expectant approach appears to be justifie

Subklinische hyperthyreoïdie: niet per se een schildklieraandoening

Three women, aged 16, 70 and 72 years, were seen in our outpatients' clinics with a decreased TSH value. In two of them, thyroid dysfunction was not the cause of the low TSH activity. In patient A, the cause was diminished food intake and in patient B, who was also known with nodular thyroid disease, the cause was the use of glucocorticoids. Only patient C had subclinical hyperthyroidism due to goitre with concomitant atrial fibrillation. She was recommended for treatment with 131I. Patients A and B recovered spontaneously. Subclinical hyperthyroidism is being increasingly encountered due to the availability of sensitive assays for measuring TSH activity and the increased frequency with which general practitioners test thyroid function. However, in about 55% of cases suppressed TSH values normalise spontaneously. This means that it is important to establish if thyroid disease is truly present. The treatment of subclinical hyperthyroidism should be initiated on the basis of individual dat

Löffler's endomyocarditis in the idiopathic hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome (HES) is a leukoproliferative disorder characterized by sustained eosinophilia (> 1.5 x 10(9)/l) and (multi-)organ dysfunction caused by infiltration of eosinophils. Especially the heart is frequently affected. In this report, we describe 2 patients with HES and Löffler's endomyocarditis. Prednisone is the drug of choice for treatment. Both our patients responded very well to prednisone and came into remission. If prednisone fails, there are other therapeutic options like myelosuppressive drugs (hydroxyurea and vincristine) or interferon-alpha. We review the literature with regard to clinical presentation, diagnosis and treatmen

Tijdige herkenning en behandeling van zwangeren met hypothyreoïdie: het belang voor het kind

Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid whilst on levothyroxine treatment. Two women had previously received 131iodine therapy due to Graves' disease. During pregnancy the levothyroxine dose required to maintain a normal TSH level increased. The serum TSH-binding inhibiting immunoglobulins (TBII) activity was still very high (188 U/l) in one of the women, but decreased to 26 U/l in the last trimester. Foetal or neonatal thyrotoxicosis was not observed. The levothyroxine dose was decreased after delivery and none of the women experienced any adverse effects as a result of this. It is recommended that all women taking levothyroxine should have their serum TSH activity measured during the first trimester. The daily dose of levothyroxine required will usually increase by 50 micrograms during pregnancy. The determination of serum TBII activity is indicated in the case of Graves' disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal thyrotoxicosi

Severe neurological complications in association with Epstein-Barr virus infection

Involvement of the nervous system in infectious mononucleosis is common. About 50% have headache on presentation. Neck stiffness without meningitis is a frequent finding. Severe neurological complications are rare though, occurring in fewer than 0.5%. We describe two patients with unusual and severe neurological complications in association with serological evidence of EBV-infection: a 32-year old female developed a bilateral optic neuritis combined with a transverse myelitis and a 72-year old man developed mononeuritis multiplex, autonomic neuropathy and a salt-wasting nephropath