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1.  Congenital adrenal hyperplasia patient perception of ‘disorders of sex development’ nomenclature 
As the benefits of patient-centered care have become more widely recognized, it is important to understand patients’ sentiments regarding aspects affecting their care. In an effort to display more sensitivity to patient concerns, the term “disorders of sex development” (DSD) was proposed in 2006 as new nomenclature to replace older terms that were considered to have negative connotations.
The objective of the study was to examine the views of congenital adrenal hyperplasia (CAH) patients and their caregivers regarding the new nomenclature. The study was observational to evaluate the views of the CAH community, and the primary endpoint was perception of the term DSD. The study was conducted as a survey about views regarding DSD nomenclature. The survey was sent via email to eligible subjects. Along with a short introduction explaining the term DSD, the survey was sent to eligible CAH patients and their caregivers. 589 CAH patients or family members participated in the survey.
A total of 589 responses were received (255 classical females, 104 non-classical females, 174 males, 56 not specified) (547 U.S., 42 international) (128 CAH patients, 408 parents or other family members). 70.6% had never heard the term DSD. 71.0% disliked or strongly disliked the term DSD. 83.6% stated they did not identify with the term DSD. 76.0% felt that the term DSD has a negative effect on the CAH community. There was no significant difference in opinion of DSD between classical females and other CAH patients, between US and international, between surgical and non-surgical patients, or between patients and parents. There was no correlation with patient age.
Our results indicate that the majority of parents and patients with CAH are dissatisfied with the term DSD. Our results highlight the challenges within the field of DSD to reach a consensus regarding a sensitive topic and to bridge the gap between current medical practice and patient satisfaction. It is the authors’ belief that reconsideration of the current nomenclature and ongoing dialogue between the medical community and patients will eventually lead to removal of stigmatization, better management protocols, and improved outcomes.
PMCID: PMC4360949  PMID: 25780368
Congenital adrenal hyperplasia; Disorders of sex development; Nomenclature
2.  Renal dysfunction in patients with thalassaemia 
British journal of haematology  2011;153(1):111-117.
Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine. We calculated creatinine clearance and urine calcium-to-creatinine ratio and measured urinary β2-microglobulin, albumin, and protein. We used multivariate modelling to identify clinical, therapeutic, and laboratory predictors of renal dysfunction. One-third of thalassaemia patients who were not regularly transfused had abnormally high creatinine clearance. Regular transfusions were associated with a decrease in clearance (P = 0·004). Almost one-third of patients with thalassaemia had hypercalciuria, and regular transfusions were associated with an increase in the frequency and degree of hypercalciuria (P < 0·0001). Albuminuria was found in over half of patients, but was not consistently associated with transfusion therapy. In summary, renal hyperfiltration, hypercalciuria, and albuminuria are common in thalassaemia. Higher transfusion intensity is associated with lower creatinine clearance but more frequent hypercalciuria. The transfusion effect needs to be better understood. Awareness of underlying renal dysfunction in thalassaemia can inform decisions now about the use and monitoring of iron chelation.
PMCID: PMC4250090  PMID: 21332704
thalassaemia; kidney; creatinine clearance; hyperfiltration; hypercalciuria; albuminuria; proteinuria; transfusion
3.  Changes in bone micro-architecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual 
Calcified tissue international  2010;86(6):484-494.
Osteoporosis and fractures occur frequently in patients with beta thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta chain genes. The heterozygote th3/+ mouse has moderate anemia, and serves as a model of beta thalassemia intermedia (TI), which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta thalassemia major (TM), which is characterized by life-threatening anemia requiring regular transfusions to sustain life.
Compared to controls: i) Micro-CT of trabecular bone showed decreased bone volume fraction, number of trabeculae and trabecular thickness in both th3/+ and th3/th3 (p<0.05). ii) Cortical bone analysis showed thinner cortices and increased marrow area in th3/+ animals (p<0.05). iii) Micro-CT abnormalities in th3/+ mice were present by 2 months and did not worsen with age. iv) Histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3. Similarly, cathepsin K and osteocalcin expression from bone of both th3/+and th3/th3 animals was reduced (p<0.05). vi) Biomechanics showed reduced maximum load, maximum moment and structural stiffness in both th3/+and th3/th3 (p<0.01).
In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans, and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover, and develop early on during the period of bone accrual.
PMCID: PMC2917203  PMID: 20449578
4.  Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem 
Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z-scores < −2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.
PMCID: PMC3276604  PMID: 18505376
DXA; BMD; fractures; vertebral morphometry; thalassemia
5.  Extended-release glipizide overdose presenting with delayed hypoglycemia and treated with subcutaneous octreotide 
The onset of symptomatic hypoglycemia in children with ingestions of second-generation sulfonylureas has never been documented to be later than 21 hours post-ingestion. We report a case with the longest known interval, 45 hours, between ingestion of a sulfonylurea and the onset of hypoglycemia requiring medical intervention. The hypoglycemia was severe and required multiple dextrose boluses in addition to continuous dextrose infusion for 36 hours. This patient was also treated with multiple doses of subcutaneous octreotide because of persistent hypoglycemia despite the above management. This case represents the first report of subcutaneous octreotide used as a treatment for pediatric hypoglycemia secondary to sulfonylurea exposure.
PMCID: PMC3810394  PMID: 19449674
Sulfonylurea; hypoglycemia; octreotide
6.  Psychiatric Adverse Effects of Rimonobant in Adults with Prader-Willi syndrome 
Prader Willi syndrome (PWS) without strict environmental modifications can lead to obesity associated with significant morbidity and mortality. In addition to increased appetite, these individuals have decreased energy expenditure with lower insulin like growth factor 1 (IGF-1), which contributes to adiposity. No effective treatment is available for this condition. Endocannabinoid receptor CB1 antagonist, rimonobant, has been effective for treatment of obesity in adult subjects. Rimonabant promotes weight loss by multiple proposed mechanisms, including decreased appetite and lipogenesis, and increased energy expenditure. Therefore, we conducted this pilot study to evaluate the effect of rimonabant on body weight and composition of adults with PWS.
This was a double blind placebo controlled study. Body weight, total fat mass, fasting ghrelin, leptin, IGF1 and insulin like growth factor binding protein (IGFBP3) were collected at baseline, and after 90 and 180 days of treatment with placebo or 20 mg of rimonabant.
Due to psychiatric adverse effects, 50% of subjects in the rimonabant group withdrew, and the study was terminated early (N=10) for safety concerns. There was a trend for weight loss, lower fat mass and higher IGF1 level at the end of study in this group. Leptin followed the fat mass and decreased with rimonabant treatment.
Rimonabant administration may be efficacious for weight loss in adults with PWS; unfortunately it is associated with an unacceptably high risk of psychiatric side effects. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition.
PMCID: PMC3038245  PMID: 20965292
Prader Willi syndrome; Obesity; CB1 cannabinoid receptor; Rimonabant
7.  Relationship between Chronic Transfusion Therapy and Body Composition in Subjects with Thalassemia 
The Journal of pediatrics  2010;157(4):641-647.e2.
To measure body composition in patients with thalassemia and explore its relationship to abnormal growth and bone mass.
Study design
Cross-sectional, multi-center study. Fat, lean, and bone mineral density (BMD) were assessed by DXA. Medical history, food frequency and physical activity questionnaires were conducted in 257 transfused thalassemia patients (23.7 ± 11 yr, Mean±SD, 51% male) compared with 113 non-transfused patients (21.3 ± 13 yr, 44% male).
Subjects with thalassemia were leaner compared with healthy Americans from NHANES III data. Transfused subjects had higher percentage body fat compared with non- transfused after controlling for age, sex and ethnicity; 11.8% of non-transfused pediatric subjects were considered underweight, significantly lower than NHANES data (p=0.03). Hemoglobin level was positively related to lean mass (p=0.008). Body fat and lean mass were positive predictors for both height and BMD Z-scores after adjustment for transfusion status, age, sex, ethnicity, calcium intake and physical activity (all p<0.001).
Though the majority of adult patients with thalassemia had healthy body composition with rare obesity, young, non-transfused patients appear at risk for being underweight. Optimizing physical activity and appropriate use of transfusion therapy may improve growth and bone health in these at risk patients.
PMCID: PMC2936667  PMID: 20547400
DXA; lean mass; fat mass; body mass index (BMI); calcium
8.  Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative 
Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH.
PMCID: PMC3025377  PMID: 21274448

Results 1-8 (8)