Insights from an advisory board: Facilitating transition of care into adulthood in brain cancer survivors with acquired pediatric growth hormone deficiency.

OBJECTIVE: Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition. DESIGN: An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients. RESULTS/CONCLUSIONS: Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.

LONG-TERM NONOPERATIVE RATE OF THYROID NODULES WITH BENIGN RESULTS ON THE AFIRMA GENE EXPRESSION CLASSIFIER.

OBJECTIVE: The primary objective was to assess the operative rate in patients with a benign result from the Afirma gene expression classifier (GEC) during long-term follow-up at nonacademic medical facilities. The secondary endpoint of this study was the treating physician's opinion regarding the safety of GEC use compared to the hypothetical situation of providing thyroid nodule management without the GEC. METHODS: This was a retrospective study of nonacademic medical practices utilizing the GEC. Those clinicians utilizing the GEC testing who had three or more 'benign' results during the data collection period (September 2010 through June 2014) were invited to participate. Operative status and patient demographics were documented for patients with GEC testing at least 36 months (± 3 months) prior to the date of data collection. A survey also was administered to the treating physicians to assess their perceived safety of using the GEC in patient care. RESULTS: During 36 months (± 3 months) of follow-up, 17 of 98 patients (17.3%) with a 'benign' GEC result underwent surgery. Within the first 2 years after a 'benign' GEC, 88% of surgeries were performed. Regarding safety of the GEC, the treating physicians reported that patient safety was improved by using the GEC compared to not using the GEC in 78 of 91 cases (86%). CONCLUSION: It appears that a 'benign' result on the GEC is associated with a reduction in the rate of thyroid surgeries compared to published data when patients are followed for 36 months after testing. A nonoperative approach to follow-up was felt to be a safe alternative to diagnostic surgery by the majority of responsible physicians in the study. ABBREVIATIONS: AUS = atypia of undetermined significance FLUS = follicular lesion of undetermined significance FN = follicular neoplasm FNA = fine-needle aspiration GEC = gene expression classifier.

Evolution of Growth Hormone Devices: Matching Devices with Patients.

Self-injection of growth hormone (GH) by children with GH deficiency can be problematic. They may have difficulty manipulating injection devices or preparing medication, and injections can be painful and create anxiety. Adherence to daily GH injections optimizes treatment benefit. Studies indicate that injection pens or needle-free devices enable easy self-injection by children, minimize medication reconstitution and storage requirements, and reduce injection pain. Newer GH delivery devices potentially encourage improved patient adherence. Reviewing features of GH devices will help nurses decide which GH device best fits the needs and abilities of pediatric patients. We searched recent medical literature about GH device development, about device-associated patient preferences and treatment adherence, and comparisons among GH devices. We concluded that improved awareness of the strengths and limitations of GH devices will enable nurses to guide families in selecting and using GH devices, improving adherence and outcomes, and helping children reach full growth potential.

Transition care of patients with growth hormone deficiency from pediatric endocrinologists to adult endocrinologists.

OBJECTIVE: To review whether growth hormone (GH) therapy should be continued into young adulthood, beyond achievement of final height, when GH deficiency persists, to summarize the recent evidence of the benefits of GH treatment during the transition period, and to address currently debated issues involving diagnosis, treatment, and transition of care. METHODS: Primary literature was reviewed in the following areas: the benefits and risks of GH therapy during the transition period, the diagnostic criteria for GH deficiency and recommended testing procedures during transition, the optimal dose of GH therapy during transition, and the factors to consider in the transition of care from the pediatric to the adult endocrinologist. RESULTS: Studies support the continuation of GH therapy through the transition period until accrual of peak bone mass, rather than cessation of GH treatment when adult height has been achieved. Continued GH treatment in patients with persistent GH deficiency after achieving final height has been associated with significant additional bone maturation and improved overall metabolic profile. The selection of the most appropriate methods and cutoff values for retesting GH deficiency during the transition period remains a challenge. Reassessment of the optimal GH dose is a key component of transition care. CONCLUSION: For patients with GH deficiency that will likely persist into adulthood, it is important to begin discussing possible continuation of GH treatment early in the management of GH deficiency. Clear communication between pediatric and adult endocrinologists will be needed to determine the timing of the patient-care transition and to minimize the interruption of GH therapy during the transition period.

Sitagliptin treatment of patients with type 2 diabetes does not affect CD4+ T-cell activation.

Dipeptidyl peptidase IV (DPP4) inhibitors have recently become widely used for treating type 2 diabetes, but in meta-analyses are associated with a mildly increased risk of all-cause infections. CD26 is a cell-surface form of DPP4 which can costimulate T-cell proliferation, raising the possibility that DPP4 inhibitors might adversely affect immune function. To address this issue in an observational study, two groups of 20 subjects each were recruited from a private endocrinology practice; one group consisted of type 2 diabetes patients treated for at least 6 months with the DPP4 inhibitor, sitagliptin, whereas patients in the other group had never been treated with this agent. The groups were similar with regard to sex and racial composition, body mass index, hemoglobin A(1c), and use of other medications for diabetes, but the sitagliptin group was slightly older. A blood sample from each patient was analyzed for CD4+ T-cell activation in response to phytohemagglutinin using adenosine triphosphate (ATP)-stimulated bioluminescence. There was not a significant difference in T-cell activation between the treatment groups (median, 419 and 481 ng/ml ATP in the groups that were and were not treated with sitagliptin, respectively). Thus the observed increased rate of infection in diabetic patients treated with sitagliptin cannot be explained by a major effect on T-cell activation. Randomized studies, preferably using several assays of immune function, should be performed to confirm and extend these findings.

Analysis of HSD3B7 knockout mice reveals that a 3alpha-hydroxyl stereochemistry is required for bile acid function.

Primary bile acids are synthesized from cholesterol in the liver and thereafter are secreted into the bile and small intestine. Gut flora modify primary bile acids to produce secondary bile acids leading to a chemically diverse bile acid pool that is circulated between the small intestine and liver. A majority of primary and secondary bile acids in higher vertebrates have a 3alpha-hydroxyl group. Here, we characterize a line of knockout mice that cannot epimerize the 3beta-hydroxyl group of cholesterol and as a consequence synthesize a bile acid pool in which 3beta-hydroxylated bile acids predominate. This alteration causes death in 90% of newborn mice and decreases the absorption of dietary cholesterol in surviving adults. Negative feedback regulation of bile acid synthesis mediated by the farnesoid X receptor (FXR) is disrupted in the mutant mice. We conclude that the correct stereochemistry of a single hydroxyl group at carbon 3 in bile acids is required to maintain their physiologic and regulatory functions in mammals.