Impact of adherence on growth response during the first 2 years of growth hormone treatment.

PURPOSE: Adherence to growth hormone (GH) treatment impacts clinical outcomes. The aim of this study is to assess the impact of adherence to rhGH treatment (2 years) on auxological outcomes. METHODS: Multicentric, retrospective observational study in rhGH-naïve GHD/SGA children treated with Saizen® during ≥2 years. Growth response was assessed by evaluating the change in height standard deviation score (ΔH SDS) and the index of responsiveness (IoR). Adherence was monitored using EasyPod™ Connect device. RESULTS: A total of 110 patients (3 Spanish centers) were evaluable (GHD n = 76, SGA n = 34). Adherence was 95.6 and 93.9% (year 1, 2). SGA and GHD children showed an increase of 0.6 cm/year and 1.1 cm/year for each 10% adherence modification. Lower adherence was observed in patients with lower pretreatment height velocity (HV) and in patients whose parents had a lower level of education. A positive correlation between index of responsiveness (IoR) during the first and second years with HV SDS during the second year and between IoR2 and adherence (year 1, 2) was observed. The frequency of patients with HV > 1 SD was higher (p = 0.025) among patients with adherence >90%. The best model to predict the height gain(cm) reaching an adjusted R squared of 0.489 involved percentage of adherence, Tanner stage, pretreatment HV, dose of rhGH, and whether the treatment was initiated before or after puberty. CONCLUSIONS: Adherence during the first 2 years of response was very high >90% and showed a negative association with age, pretreatment HV and treatment duration and a positive correlation with the level of parent education.

Echocardiographic evolution of left ventricular function in childhood leukemia survivors.

BACKGROUND: Cardiac events are the most common nonmalignant cause of death in childhood cancer survivors. This population has an increased risk of morbimortality, probably secondary to the treatment side effects. The objective was to determine the prevalence and determinants of left ventricular dysfunction in a cohort of long term childhood acute leukemia survivors treated with potentially cardiotoxic therapies. METHODS: Retrospective study with at least 10 years of follow-up, diagnosed between 1999 and 2003. The reduction percentage of the fractional shortening and ejection fraction was calculated from the diagnosis to the end of treatment and 10 years after the end of treatment. The factors associated with their decrease were analyzed. RESULTS: The fractional shortening and ejection fraction experienced a significant decrease 10 years after the end of treatment from 38.16 to 32 and 69.08 to 60.79, respectively. Reduction was more pronounced during the evaluation of the first year after treatment (-10.3% and -8.96%, P <0.05). Associated with high tumor risk and adjuvant treatment with hematopoietic stem cell transplantation and total body radiation. No differences were found in the total anthracycline doses received. Patients with the greatest decrease had a lower age at the time of diagnosis (mean 5.7 ± 4.5 years), 62.5% (5/8) less at 5 years, and 75% received radiotherapy and hematopoietic stem cell transplantation. CONCLUSION: There is already a significant decrease in the fractional shortening and ejection fraction during the first year after the end of the treatment, which is maintained 10 years after the end of treatment. Associated with high tumor risk and with total body radiation treatment and hematopoietic stem cell transplantation.

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas.

BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.