Atypical patterns of segregation of familial enlargement of the vestibular aqueduct.

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.

Effect of fasting on the size of lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Background: Lymphangioleiomyomas occur in 38% of patients with sporadic lymphangioleiomyomatosis (LAM) and may cause pain and increased abdominal girth, mimicking the presence of a malignancy. Lymphatic involvement in LAM is closely associated with elevated serum levels of vascular endothelium growth factor-D (VEGF-D). Because lymphangioleiomyomas undergo diurnal variation in volume, we hypothesized that daytime ingestion of food, by increasing chyle formation and lymphatic flow, is the cause of an increase in lymphangioleiomyoma volume.

Sexual dimorphisms in the associations of BMI and body fat with indices of pubertal development in girls and boys.

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.

Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.

Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer.

Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center.

mutation testing for hearing loss associated with enlargement of the vestibular aqueduct.

Pendred syndrome (PS) is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct (EVA), and mutations of the gene. However, not all EVA patients have PS or mutations. Two mutant alleles of are detected in ¼ of North American or European EVA populations, one mutant allele is detected in another ¼ of patient populations, and no mutations are detected in the other ½.

Ultrasound is superior to computed tomography for assessment of medullary nephrocalcinosis in hypoparathyroidism.

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.

Characterization and management of testicular pathology in McCune-Albright syndrome.

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.

SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct.

Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene.

Low-dose, once-daily, intraclot injections of alteplase for treatment of acute deep venous thrombosis.

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.

Hereditary hearing loss with thyroid abnormalities.

Mutations in SLC26A4 can cause deafness and goiter in Pendred syndrome (PDS) or isolated non-syndromic enlargement of the vestibular aqueduct (NSEVA). PDS is one of the most common hereditary causes of deafness. It is characterized by autosomal-recessive inheritance of sensorineural hearing loss, enlarged vestibular aqueducts (EVA), and an iodide organification defect with or without goiter.

Evaluation of the thyroid in patients with hearing loss and enlarged vestibular aqueducts.

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.

Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?

Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl(-)/I(-)/HCO(3)(-) exchanger. Pendrin's critical transport substrates are thought to be I(-) in the thyroid gland and HCO(3)(-) in the inner ear. We previously reported that bi-allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA.

The role of type 1 and type 2 5'-deiodinase in the pathophysiology of the 3,5,3'-triiodothyronine toxicosis of McCune-Albright syndrome.

Context: McCune-Albright syndrome (MAS) is caused by mutations in GNAS (most often R201C or R201H) leading to constitutive cAMP signaling and multiple endocrine dysfunctions, including morphological and functional thyroid involvement.

Objective: The objective of the study was to characterize the clinical and molecular features of the MAS-associated thyroid disease in a large cohort of patients.

Design: This was a retrospective analysis.

Deep vein thrombosis of lower extremity: direct intraclot injection of alteplase once daily with systemic anticoagulation--results of pilot study.

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.

Uterine development in Turner syndrome.

Objective: To evaluate uterine development of women with Turner syndrome (TS) receiving conventional medical care.

Study Design: In a cross-sectional study we used ultrasonography for uterine evaluation in 86 women with TS 18 to 45 years of age participating in an intramural NIH study, and who had abnormal karyotypes in >70% of white blood cells. Outcomes were uterine dimensions and shape.

Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study.

Context: Girls with McCune-Albright syndrome (MAS) and related disorders have gonadotropin-independent precocious puberty due to estrogen secretion from ovarian cysts. Their puberty does not respond to GnRH agonist therapy, and short-acting aromatase inhibitors have had limited effectiveness.

Objective: Our objective was to assess the effectiveness of the potent, third-generation aromatase inhibitor letrozole in decreasing pubertal progression in girls with MAS and to assess the response of indices of bone turnover associated with the patients' polyostotic fibrous dysplasia.

Brachial artery aneurysms in Menkes disease.

Generalized vascular tortuosity caused by deficiency of the copper enzyme lysyl oxidase is frequently noted in Menkes disease, but reported examples of peripheral aneurysms are rare. We describe bilateral brachial artery aneurysms in a 10-month-old infant with classical Menkes disease.

A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas.

Background: Preoperative imaging studies localize insulinomas in less than 50% of patients. Arteriography with calcium stimulation and venous sampling (ASVS) regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with the other localization procedures in patients with a sporadic insulinoma.

Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth.

Objective: Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels.

Patients: Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied.

Transient spleen enlargement in peripheral blood progenitor cell donors given G-CSF.

The administration of granulocyte colony-stimulating factor (G-CSF) to peripheral blood progenitor cell (PBPC) donors causes spleen length to increase, but the duration of enlargement is not known. Eighteen healthy subjects were given 10 microg/kg of G-CSF for 5 days and a PBSC concentrate was collected by apheresis. Ultrasound scans were used to assess craniocaudal spleen length before and after G-CSF administration.

G-CSF-induced spleen size changes in peripheral blood progenitor cell donors.

Background: PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and assessed factors affecting size changes.

Study Design And Methods: Twenty healthy adults were given G-CSF (10 microg/kg/day) for 5 days and a PBPC concentrate was collected by apheresis.

Ultrasound, magnetic resonance imaging, and posterior tibialis dysfunction.

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.

In-111 DTPA-octreotide scintigraphy for disease detection in metastatic thyroid cancer: comparison with F-18 FDG positron emission tomography and extensive conventional radiographic imaging.

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.

Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism.

Patients with recurrent or persistent primary hyperparathyroidism have increased operative risk because of scarring in the operative field and the frequent presence of an ectopic gland. Preoperative imaging studies will identify the hyperfunctioning parathyroid gland in the majority of circumstances. The best types or combination of imaging tests has not been definitely established.