Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer's disease.

PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aß42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.

Reciprocal Incremental Value of 18F-FDG-PET and Cerebrospinal Fluid Biomarkers in Mild Cognitive Impairment Patients Suspected for Alzheimer's Disease and Inconclusive First Biomarker.

BACKGROUND: In Alzheimer's disease (AD) diagnosis, both cerebrospinal fluid (CSF) biomarkers and FDG-PET sometimes give inconclusive results. OBJECTIVE: To evaluate the incremental diagnostic value of FDG-PET over CSF biomarkers, and vice versa, in patients with mild cognitive impairment (MCI) and suspected AD, in which the first biomarker resulted inconclusive. METHODS: A consecutive series of MCI patients was retrospectively selected from two Memory Clinics where, as per clinical routine, either the first biomarker choice is FDG-PET and CSF biomarkers are only used in patients with uninformative FDG-PET, or vice versa. We defined criteria of uncertainty in interpretation of FDG-PET and CSF biomarkers, according to current evidence. The final diagnosis was established according to clinical-neuropsychological follow-up of at least one year (mean 4.4±2.2). RESULTS: When CSF was used as second biomarker after FDG-PET, 14 out of 36 (39%) received informative results. Among these 14 patients, 11 (79%) were correctly classified with respect to final diagnosis, thus with a relative incremental value of CSF over FDG-PET of 30.6%. When FDG-PET was used as second biomarker, 26 out of 39 (67%) received informative results. Among these 26 patients, 15 (58%) were correctly classified by FDG-PET with respect to final diagnosis, thus with a relative incremental value over CSF of 38.5%. CONCLUSION: Our real-world data confirm the added values of FDG-PET (or CSF) in a diagnostic pathway where CSF (or FDG-PET) was used as first biomarkers in suspected AD. These findings should be replicated in larger studies with prospective enrolment according to a Phase III design.

Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease.

BACKGROUND: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET. OBJECTIVE: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. METHODS: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [18]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). RESULTS: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. CONCLUSION: The study confirms the good accuracy of [18]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.

Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging.

OBJECTIVE: The aim of this study was to investigate the appropriate time for performing an iodine-131 post-therapy whole-body scan (TxWBS) through a qualitative and semiquantitative analysis of early and late scans. MATERIALS AND METHODS: This study evaluated pairs of scans of 134 patients who underwent TxWBS on the third and seventh day. The scans were analyzed to evaluate sites, intensity of uptake, concordance or discordance between the scans, relationship with risk factors, and serum thyroglobulin (Tg) levels. To evaluate early and late radioiodine kinetics in thyroid remnants and metastases, 65/134 pairs of scans (48.5%) were subjected to a semiquantitative analysis. RESULTS: The early and late scans furnished concordant images in 108/134 patients (80.5%). In 10/134 patients (7.5%), early scans provided more information compared with late scans, showing lymph node and distant metastases in seven and three patients, respectively. In 16/134 patients (12%), late scans provided more data compared with early scans, with thyroid remnants and lymph node and distant metastases demonstrated in four, seven, and five patients, respectively. Negative early/positive late TxWBS results in patients were found to be significantly correlated (P=0.007) with elevated serum levels of Tg and a high-risk for recurrence (P=0.003). CONCLUSION: This study suggests that in about 20% of patients early or late TxWBS can miss the visualization of thyroid remnants or lymph node or distant metastases, which can be achieved performing both studies. High-risk patients with elevated serum Tg levels should be considered for a late TxWBS, which can demonstrate a possible metastatic involvement that was not diagnosed or that was downstaged by early TxWBS.

Recombinant thyrotropin use in children and adolescents with differentiated thyroid cancer: a multicenter retrospective study.

CONTEXT: Although recombinant human TSH (rhTSH) is widely used in differentiated thyroid cancer (DTC) to aid diagnostic follow-up procedures and radioiodine thyroid remnant ablation, almost all clinical investigation was in adults. OBJECTIVE: The aim of this study was to characterize rhTSH clinical safety and peak TSH response in DTC patients 18 yr old or younger. DESIGN AND SETTING: We conducted a retrospective study involving 23 tertiary referral centers in 12 European, Asian, and Oceanian countries. PATIENTS: One hundred DTC patients (69% female, 31% male, 84% papillary, 61% N1, 18% M1) ages 4.9-18 yr at first rhTSH administration were studied. INTERVENTIONS: A total of 181 rhTSH courses were administered (range, one to eight per patient; 42% of patients received two or more courses), 92% using the approved adult regimen (one 0.9 mg im injection daily on two consecutive days), 34% including thyroid hormone withdrawal for less than 7 d ("mini-THW"). MAIN OUTCOME MEASURES: Clinical adverse event (AE) incidence, type, and severity, and peak post-rhTSH serum TSH concentrations were assessed. RESULTS: No clinical AEs occurred in 88% of rhTSH courses. Most common clinical AEs were nausea (5% of courses) and vomiting (3%). Multiple or severe AEs were rare (0.6% and 2.8% of courses, respectively); serious AEs were absent. Peak TSH concentration post-rhTSH exceeded 25 mU/liter in approximately 98% of courses. In logistic regression analyses, the rhTSH regimen, "mini-THW," peak TSH concentration, body mass index (BMI), or peak TSH concentration/unit of BMI were not associated with clinical AE occurrence. In analyses of covariance, higher BMI was associated with lower peak TSH concentrations. CONCLUSIONS: rhTSH was clinically well tolerated in pediatric DTC patients although courses preponderantly comprised the adult regimen, and repeated courses were frequent. Both the adult and reduced-dose regimens almost always sufficiently elevate TSH in children and adolescents.

American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.