No abstract

Background Childhood cancer survivors are at high risk for reduced bone mineral density (BMD). Our objective was to determine whether post-pubertal adolescent survivors of brain tumors, whose tumor or treatments placed them at risk for pituitary hormone deficiencies, have low BMD near time of peak bone mass accrual, and to assess risk factors for decreased BMD. Procedure Chart review of 36 post-pubertal adolescents with history of tumor or radiation therapy (RT) of the hypothalamic-pituitary area who had undergone BMD screening via dual-energy x-ray absorptiometry (DXA). Results Age at DXA was 16.9 ±1.9 years (mean ± SD). Time since diagnosis was 8.5 ±3.6 years. Median BMD Z-scores were −0.95 (range −2.7 to 1.7) at the femoral neck, −1.20 (−3.6 to 1.8) at the hip, and −0.90 (−3.7 to 1.8) at the spine. Bone mineral apparent density (BMAD) Z-scores were −0.23 (−2.7 to 1.9) at the femoral neck and −0.45 (−3.0 to 2.3) at the spine. Those with history of ≥1 fracture had lower BMD Z-scores of the femoral neck, total hip and spine (P<0.05). Those with treated GH deficiency had a higher BMD Z-score at the femoral neck, total hip and spine (P<0.05) than those not treated. There was no difference in BMD with respect to treatment with chemotherapy, cranial or spinal RT, or hypogonadism. Spontaneous menarche and regular periods did not correlate with BMD. Conclusions In post-pubertal adolescent survivors of childhood brain tumors, fracture history and untreated GH deficiency are risk factors for decreased BMD.

Proprotein convertase 1/3 (PC1/3), encoded by the PCSK1 gene, is expressed in neuronal and (entero)endocrine cell types, where it cleaves and hence activates a number of protein precursors that play a key role in energy homeostasis. Loss-of-function mutations in PCSK1 cause a recessive complex endocrinopathy characterized by malabsorptive diarrhea and early-onset obesity. Despite the fact that neonatal malabsorptive diarrhea is observed in all patients, it has remained understudied. The aim of this study was to investigate the enteroendocrine pathologies in a male patient with congenital PCSK1 deficiency carrying the novel homozygous c.1034A>C (p.E345A) mutation. This patient developed malabsorptive diarrhea and metabolic acidosis within the first week of life, but rapid weight gain was observed after total parenteral nutrition, and he displayed high proinsulin levels and low adrenocorticotropin. In vitro analysis showed that the p.E345A mutation in PC1/3 resulted in a (near) normal autocatalytic proPC1/3 processing and only partially impaired PC1/3 secretion, but the processing of a substrate in trans was completely blocked. Immunohistochemical staining did not reveal changes in the proGIP/GIP and proglucagon/GLP-1 ratio in colonic tissue. Hence, we report a novel PCSK1 deficient patient who, despite neonatal malabsorptive diarrhea, showed a normal morphology in the small intestine.

Fat intake increased with treatment, possibly due to the recommendation to take ivacaftor with high fat meals. Increased energy and fat intake correlated with weight gain. Regional dietary patterns differed.

Objectives: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study. Subjects/methods: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively. Results: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy. Conclusions: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.