RESUMEN
OBJECTIVES/HYPOTHESIS: Hearing loss and enlarged vestibular aqueduct (EVA) can be inherited as an autosomal recessive trait caused by mutant alleles of the SLC26A4 gene. In some other families, EVA does not segregate in a typical autosomal recessive pattern. The goal of this study was to characterize the SLC26A4 genotypes and phenotypes of extended families with atypical segregation of EVA. STUDY DESIGN: Prospective study of cohort of families ascertained between 1998 and 2014 at the National Institutes of Health Clinical Center. METHODS: Study subjects were members of eight families segregating EVA in at least two members who were not related as siblings. Evaluations included pure-tone audiometry, temporal bone imaging, SLC26A4 nucleotide sequence analysis, SLC26A4-linked marker genotype and haplotype analysis, and pedigree analysis. RESULTS: One family had members with EVA caused by different etiologies, and two families had pseudodominant inheritance of recessive mutations of SLC26A4. In five families, the etiology remained unknown and could include inheritance of mutant alleles at another genetic locus, nongenetic influences, or a combination of these factors. CONCLUSIONS: Familial EVA can demonstrate a variety of atypical segregation patterns. Pseudodominant inheritance of SLC26A4 mutations or recessive alleles of other hearing loss genes may be more likely to occur in families in which deaf individuals have intermarried. The etiologic basis of atypical segregation of EVA without detectable SLC26A4 mutations remains unknown. Future studies of these families may reveal novel genes for EVA. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E240-E247, 2016.
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Segregación Cromosómica/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva/genética , Proteínas de Transporte de Membrana/genética , Linaje , Acueducto Vestibular/anomalías , Adolescente , Adulto , Anciano , Alelos , Audiometría de Tonos Puros , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Estudios Prospectivos , Transportadores de Sulfato , Hueso Temporal/diagnóstico por imagen , Adulto JovenRESUMEN
CONTEXT: The effect of obesity and concomitant insulin resistance on pubertal development is incompletely elucidated. OBJECTIVE: To determine how measures of adiposity and insulin resistance are associated with pubertal maturation in boys and girls. SETTING AND DESIGN: Breast and pubic hair Tanner stage and testicular volume by orchidometry were determined by physical examination in 1066 children. Ovarian volume was estimated by trans-abdominal ultrasound. Fat mass, skeletal age, and fasting serum for insulin and glucose, total T, estradiol, estrone, dehydroepiandrosterone-sulfate, and androstenedione were measured at the National Institutes of Health Clinical Research Center. Convenience sample; 52% obese, 59% female. RESULTS: Logistic regression identified a significant interaction between sex and obesity for prediction of pubertal development (P ≤ .01). There was a negative association between boys' testicular volume and body mass index (BMI)/fat mass but a positive association between girls' breast stage and BMI/fat mass. Ovarian volume in girls was positively associated with insulin resistance but not with BMI/fat mass. There was a positive association between obesity and measures of estrogen exposure (breast development and skeletal age) in both sexes. Positive correlations were seen for girls between BMI and pubic hair development and between insulin resistance and T production, whereas adiposity was negatively associated with pubic hair in boys. CONCLUSIONS: Significant sexual dimorphisms in the manifestations of pubertal development are seen in obese girls and boys. Two known effects of obesity, increased peripheral conversion of low-potency androgens to estrogens by adipose tissue-aromatase and increased insulin resistance, may be in large part responsible for these differences.
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Adiposidad/fisiología , Desarrollo del Adolescente , Índice de Masa Corporal , Desarrollo Infantil , Resistencia a la Insulina , Obesidad Infantil/epidemiología , Pubertad/fisiología , Caracteres Sexuales , Tejido Adiposo/crecimiento & desarrollo , Adolescente , Composición Corporal , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Indicadores de Salud , Humanos , MasculinoRESUMEN
CONTEXT: Nephrocalcinosis is a complication of hypoparathyroidism and other metabolic disorders. Imaging modalities include ultrasonography (US) and computed tomography (CT). Few studies have compared these modalities, and standard clinical practice is not defined. OBJECTIVE: The objective of the study was to determine the preferred method for assessing nephrocalcinosis. DESIGN: The design of the study was a retrospective, blinded analysis. SETTING: The study was conducted at a clinical research center. PATIENTS: Twenty-two hypoparathyroid subjects and 7 controls participated in the study. INTERVENTIONS: Contemporaneous renal US and CT images were reviewed in triplicate by 4 blinded radiologists. Nephrocalcinosis was classified using a 0-3 scale with 0 meaning no nephrocalcinosis and 3 meaning severe nephrocalcinosis. MAIN OUTCOME MEASURES: Intraobserver, interobserver, and interdevice agreements were measured. RESULTS: Intraobserver agreement was high, with an overall weighted kappa of 0.83 for CT and 0.89 for US. Interobserver agreement was similar between modalities, with kappas of 0.74 for US and 0.70 for CT. Only moderate agreement was found between US and CT scores, with an intermodality kappa of 0.47 and 60% concordance. Of discordant pairs, 81% had higher US scores and only 19% had higher CT scores. Of nephrocalcinosis seen on US and not CT, 45%, 46%, and 9% were grades 1, 2, and 3, respectively. Overall, US scores were higher than CT with a cumulative odds ratio (95% confidence interval) of 5.97 (2.60, 13.75) (P < .01). In controls, 100% of US ratings were 0, and 95% of CT ratings were 0. CONCLUSIONS: US is superior to CT for assessment of mild to moderate nephrocalcinosis in patients with hypoparathyroidism. This finding, in combination with its low cost, lack of radiation, and portability, defines US as the preferred modality for assessment of nephrocalcinosis.
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Hipoparatiroidismo/complicaciones , Nefrocalcinosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/normas , Ultrasonografía/normas , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Médula Renal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Nefrocalcinosis/etiología , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Método Simple Ciego , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricosRESUMEN
CONTEXT: The testicular phenotype in McCune-Albright syndrome (MAS) has not been well characterized. Boys present with a relatively low incidence of precocious puberty in comparison with girls. Radiographic and histological studies are limited to small series and case reports, which report testicular microlithiasis and Sertoli cell hyperplasia. OBJECTIVE: Our objective was to characterize the biochemical, radiological, and histological spectrum and clinical management of testicular pathology in males with MAS. PATIENTS, DESIGN, AND SETTING: Fifty-four males with MAS participated in this prospective cohort study at a clinical research center. INTERVENTION: Evaluation included testicular exam, pubertal staging, testicular ultrasound, measurement of LH, FSH, and testosterone. Orchiectomies were performed when considered clinically indicated. MAIN OUTCOME MEASURE: Prevalence and characterization of ultrasound lesions with correlation to histology were evaluated. RESULTS: Of 54 males, 44 (81%) presented with ultrasound abnormalities including hyperechoic lesions (49%), hypoechoic lesions (30%), microlithiasis (30%), heterogeneity (47%), and focal calcifications (11%). Eight subjects underwent orchiectomy revealing large foci of Leydig cell hyperplasia, which could not be definitively distinguished from Leydig cell tumor. After no subjects developed clinical malignancy, a conservative approach was instituted, and subsequent subjects were followed with serial imaging. Testosterone and gonadotropins were normal in subjects without precocious puberty or pituitary disease. Eleven (21%) presented with precocious puberty, and a combination of aromatase inhibitors, androgen receptor blockers, and leuprolide resulted in improved predicted adult height. In addition, the first cases of testicular adrenal rest and bilateral germ cell tumors in association with MAS are presented. CONCLUSIONS: Contrary to prevailing thinking, the incidence of gonadal pathology in MAS is equal in males and females. The predominant histopathological finding was Leydig cell hyperplasia, which carries a low risk of malignant transformation and can be managed conservatively.
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Displasia Fibrosa Poliostótica/patología , Displasia Fibrosa Poliostótica/terapia , Enfermedades Testiculares/patología , Enfermedades Testiculares/terapia , Adolescente , Pruebas de Función de la Corteza Suprarrenal , Adulto , Edad de Inicio , Niño , Preescolar , Estudios de Cohortes , Femenino , Displasia Fibrosa Poliostótica/complicaciones , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Lactante , Litiasis/patología , Estudios Longitudinales , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Orquiectomía , Estudios Prospectivos , Pubertad/fisiología , Células de Sertoli/patología , Enfermedades Testiculares/etiología , Testículo/diagnóstico por imagen , Testículo/patología , Testosterona/sangre , Ultrasonografía , Adulto JovenRESUMEN
PURPOSE: To evaluate the safety and efficacy of once-daily intraclot injections of low doses (≤ 10 mg) of tissue plasminogen activator (tPA) for thrombolysis of venous thrombosis. MATERIALS AND METHODS: In prospective studies, 33 patients with subclavian, jugular, and central venous thrombosis (SJ-CVT) (all but two cases associated with central catheters) were treated once a day with ≤ 4 mg/day of tPA, and 30 patients with acute deep vein thrombosis of the lower extremity (DVT-LE) < 14 days old were treated once a day with ≤ 10 mg/leg/day of tPA by intraclot "lacing" of thrombus without continuous infusions of tPA. RESULTS: Patency was restored in 26 (79%) of 33 patients with SJ-CVT using an average total dose of 7.1 mg of tPA/per patient and average of 2.1 treatments or days of therapy. Five patients received thrombolytic therapy for SJ-CVT as outpatients. Initial patency was restored in 29 (97%) of 30 patients with acute DVT-LE using an average total dose of 20 mg of tPA per patient over an average of 2.7 treatments/or days per patient. Follow-up imaging examinations at 6 months showed continued patency in 27 (96%)/of 28 patients. There were no major bleeding complications, and no patient required a blood transfusion. CONCLUSIONS: Intraclot injection of low doses of alteplase is effective for acute venous thrombosis, and pharmacokinetic data suggest potentially greater safety.
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Fibrinolíticos/administración & dosificación , Activador de Tejido Plasminógeno/administración & dosificación , Trombosis de la Vena/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
OBJECTIVE: To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss. DESIGN: Prospective cohort survey. SETTING: National Institutes of Health Clinical Center, a federal biomedical research facility. PATIENTS: The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss. MAIN OUTCOME MEASURES: Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 ((123)I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin. RESULTS: Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P < or = .001) greater percentage of (123)I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles. CONCLUSIONS: Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.
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Pérdida Auditiva Sensorineural/fisiopatología , Glándula Tiroides/fisiopatología , Acueducto Vestibular/patología , Adolescente , Adulto , Niño , Preescolar , Bocio/genética , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Percloratos , Estudios Prospectivos , Transportadores de Sulfato , Pruebas de Función de la Tiroides , Glándula Tiroides/diagnóstico por imagen , Ultrasonografía , Adulto JovenRESUMEN
PURPOSE: To prospectively evaluate the outcome of patients with acute deep vein thrombosis (DVT) of the lower extremity treated with "lacing" of the thrombus with alteplase (recombinant tissue plasminogen activator, or rTPA). MATERIALS AND METHODS: This HIPAA-compliant study was approved by the Institutional Review Board of the National Heart, Lung, and Blood Institute and was funded by the National Institutes of Health. After giving written consent, 20 patients with first-onset acute DVT were treated with direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per leg per day; maximum of four treatments) and full systemic anticoagulation. Alteplase was chosen because its high fibrin affinity obviates continuous infusion of this thrombolytic agent. Ventilation-perfusion (V/Q) scans were performed for evaluation of embolic risks, and clinical and imaging examinations were supplemented with pharmacokinetic studies to enable further assessment of treatment outcomes. RESULTS: The 20 patients included 13 men and seven women aged 18-79 years. Antegrade blood flow was restored throughout the deep venous system in 16 patients (80%) during thrombolytic therapy, with complete resolution of symptoms in 18 patients (90%) after 6 months of anticoagulation. Pharmacokinetic studies showed rapid clearance of circulating alteplase and recovery of plasminogen activator inhibitor-1 levels within 2 hours after termination of alteplase treatment. V/Q scans revealed a 40% incidence of pulmonary embolism before treatment and a 15% incidence of asymptomatic pulmonary embolism during thrombolytic therapy. There were no cases of clinically important pulmonary embolism or serious bleeding during thrombolytic therapy. During a mean follow-up period of 3.4 years, no patient developed a postthrombotic syndrome or recurrent thromboembolism. CONCLUSION: Intraclot injection or lacing of the thrombus with a fibrin-binding thrombolytic agent such as alteplase is an alternative to continuous-infusion thrombolytic regimens and minimizes the duration of systemic exposure to thrombolytic agents.
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Anticoagulantes/administración & dosificación , Activador de Tejido Plasminógeno/administración & dosificación , Trombosis de la Vena/tratamiento farmacológico , Adolescente , Adulto , Anciano , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fibrinolíticos/administración & dosificación , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
The authors studied posterior tibialis tendons in 31 subjects with posterior tibialis tendon pain to compare clinical findings with those of magnetic resonance imaging and ultrasound images. All subjects received clinical, ultrasound, and magnetic resonance imaging examinations using T1-weighted, T2-weighted, and enhanced magnetic resonance imaging, and high resolution ultrasound using power Doppler. Forty-four tendons in 25 women and six men with a mean age 43.3 years (range, 20-73 years) were studied. Magnetic resonance imaging tendon and peritendon enhancement are associated statistically with increasing pain intensity on resistance to testing. Ultrasound tendon and peritendon flow were associated with increasing pain intensity on resistance to testing. There is no statistically significant association between magnetic resonance imaging inhomogeneity and pain intensity on resistance to testing. Clinical and ultrasound examinations positively identify peritendinitis and tendonitis but not inhomogeneity (partial tear) of the posterior tibialis tendon. The magnetic resonance imaging is a more sensitive test for posterior tibialis tendon tear than either clinical or ultrasound evaluation.
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Imagen por Resonancia Magnética , Disfunción del Tendón Tibial Posterior/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dimensión del Dolor , Disfunción del Tendón Tibial Posterior/diagnóstico por imagen , Estudios Prospectivos , UltrasonografíaRESUMEN
PURPOSE: The utility of In-111 DTPA octreotide scintigraphy (SRS) for disease detection in patients with metastatic thyroid carcinoma (TCA) remains controversial. The authors compared the sensitivity of In-111-based SRS, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and extensive conventional radiographic imaging (CRI) in this type of cancer. METHODS: SRS, FDG PET, and CRI were performed concurrently in 21 patients (age, 56.4 +/- 12.9 years) who had aggressive TCA. Concordance rates % of lesion positivity among pairs of different techniques (A and B) were calculated as the ratio of the number of lesions positive with both techniques divided by the sum of the total number of lesions positive with technique A + total number of lesions positive with technique B, which was then multiplied by 200. RESULTS: The combined use of CRI, FDG PET, and SRS resulted in the detection of 105 lesions, presumed to be due to metastatic deposits. Sensitivities for SRS and FDG-PET imaging were 49.5% and 67.6%, respectively. The lesion detection concordance rates were as follows: CRI versus FDG PET, 80.8%; CRI versus SRS, 74.2%; and FDG-PET versus SRS, 58.6%. Importantly, SRS detected five unexpected lesions, which were negative by both CRI and FDG-PET imaging. In two representative patients, a positive correlation (Spearman's rank = 0.71; = 0.0576) existed between the percentage of lesional In-111 DTPA octreotide uptake and the standard uptake value in eight concordant lesions. CONCLUSION: Although SRS has only moderate sensitivity for disease detection in metastatic TCA, sometimes it can reveal lesions that otherwise would be undetectable by either CRI or FDG-PET imaging.
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Carcinoma/diagnóstico por imagen , Carcinoma/secundario , Fluorodesoxiglucosa F18 , Octreótido/análogos & derivados , Ácido Pentético/análogos & derivados , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Estudios de Cohortes , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/secundario , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/secundario , Persona de Mediana Edad , Neoplasias Pleurales/diagnóstico por imagen , Neoplasias Pleurales/secundario , Radiografía , Radiofármacos , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/secundario , Tomografía Computarizada de Emisión/métodosRESUMEN
OBJECTIVE: The purpose of the study is to describe the appearance of the posterior tibialis tendon on MR imaging and high-resolution sonography with color and power Doppler imaging and to determine whether sonography is as accurate for diagnosing tendinosis as MR imaging. SUBJECTS AND METHODS: Fifteen healthy volunteers and 31 patients (44 tendons) who were clinically suspected of having posterior tibial tendinopathy were prospectively evaluated with MR imaging and sonography. RESULTS: On MR imaging, the normal tendon was elliptic on cross section and showed low signal intensity on all sequences. Minimal peritendinous enhancement and fluid were seen. On sonography, the tendon showed homogeneous longitudinal echogenic fibers. No flow was seen in or around the tendon. Tendinopathy was characterized by enhancement of the tendon on MR imaging (19/44 tendons); intratendinous flow on color Doppler sonography (16/44 tendons); increase in the anteroposterior diameter causing a rounding of the tendon (18/44 tendons); and inhomogeneity of the tendon (16/44 tendons on MR imaging and 21/44 tendons on sonography). Peritendinosis was characterized by peritendinous enhancement on MR imaging (29/44 tendons); flow on color Doppler sonography (20/44 tendons); and increased soft tissue (20/44 tendons on MR imaging and 27/44 tendons on sonography). When compared with MR imaging, the sensitivity and specificity of sonography for diagnosing tendinopathy were 80% and 90%, respectively, and for diagnosing peritendinosis were 90% and 80%. Addition of abnormal size to the structural abnormality criteria did not improve diagnostic ability. CONCLUSION: Sonography can be useful as the initial imaging study in evaluating abnormalities caused by posterior tibial tendinopathy.