Real life long-term efficacy and safety of rhGH therapy in children with SHOX deficiency

Objective: This Italian survey aims to evaluate real-life long-term efficacy and safety of rhGH therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3, T4) and at near-final height (nFH) (T5), when available. Results: 117 SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33years (74% prepubertal), 99 completed the 1st year of treatment, and 46 reached nFH. During rhGH therapy, growth velocity (GV) SDS and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14±0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (β -0.31, p = 0.030) and the GV during the first year of rhGH treatment (β 0.45, p = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype

Stories of experiences of care for growth hormone deficiency: the CRESCERE project

AIMS: Growth hormone deficiency therapy is demanding for patients and caregivers. Teams engaged in the clinical management of growth hormone deficiency therapy need to know how families live with this condition, to provide an adequate support and prevent the risk of withdrawal from therapy. METHODS: Using Narrative Medicine, testimonies from patients, their parents and providers of care were collected from 11 Italian centers. Narrations were analyzed throughout an elaboration of recurring words and expressions. RESULTS: Although care management and outcomes were considered satisfying in the 182 collected narratives, recurring signals of intolerance among adolescents and the worry of not being well informed about side effects among parents are open issues. CONCLUSION: Narratives found that communication issues could decrease adherence and influence the physicians' clinical practice

Stories of experiences of care for growth hormone deficiency: the CRESCERE project

Growth hormone deficiency therapy is demanding for patients and caregivers. Teams engaged in the clinical management of growth hormone deficiency therapy need to know how families live with this condition, to provide an adequate support and prevent the risk of withdrawal from therapy. Methods: Using Narrative Medicine, testimonies from patients, their parents and providers of care were collected from 11 Italian centers. Narrations were analyzed throughout an elaboration of recurring words and expressions. Results: Although care management and outcomes were considered satisfying in the 182 collected narratives, recurring signals of intolerance among adolescents and the worry of not being well informed about side effects among parents are open issues. Conclusion: Narratives found that communication issues could decrease adherence and influence the physicians’ clinical practice

Stories of experiences of care for growth hormone deficiency: the CRESCERE project

Aims: Growth hormone deficiency therapy is demanding for patients and caregivers. Teams engaged in the clinical management of growth hormone deficiency therapy need to know how families live with this condition, to provide an adequate support and prevent the risk of withdrawal from therapy. Methods: Using Narrative Medicine, testimonies from patients, their parents and providers of care were collected from 11 Italian centers. Narrations were analyzed throughout an elaboration of recurring words and expressions. Results: Although care management and outcomes were considered satisfying in the 182 collected narratives, recurring signals of intolerance among adolescents and the worry of not being well informed about side effects among parents are open issues. Conclusion: Narratives found that communication issues could decrease adherence and influence the physicians’ clinical practice. Lay abstract: Using Narrative Medicine, testimonies from children and adolescents with growth hormone deficiency, their parents and providers of care were collected in 11 Italian Centers. Although the general high level of satisfaction for the results of the treatment, the analysis of the narrations revealed that adolescents can show recurring signals of intolerance and parents can feel worried and not well informed about side effects. Communication issues could decrease the adherence to therapy, and teams engaged in the clinical management of growth hormone deficiency need to strengthen their communication with all the family members, to provide an adequate support and prevent the risk of withdrawal from therapy

MODELLO DI PREVISIONE DELLA STATURA FINALE IN PAZIENTI PEDIATRICI ITALIANI AFFETTI DA DEFICIT DI GH TRATTATI CON SOMATROPINA

Obiettivi: elaborare un modello di previsione della statura finale in pazienti pediatrici con deficit di GH trattati con somatropina ricombinante, valutando quali siano le variabili più importanti nel determinismo della statura finale. Metodi: 1043 pazienti trattati per deficit di GH (picco di GH <10 ng/dl a 2 test di stimolo) giunti ad altezza finale. Mediana età a inizio trattamento 11 (IQR 8.7/12.8) anni; mediana altezza a inizio trattamento -2.43 (IQR -2.80/-2.01) SDS; mediana altezza bersaglio -1.09 (IQR -1.63/-0.48) SDS; dose iniziale di somatropina mediana altezza finale -1.08 SDS (IQR -1.64/-0.50 SDS, vs altezza a inizio trattamento p <0.001, vs altezza bersaglio p=ns). Analisi statistica con metodica RELIMPO. Risultati: 2 modelli sono risultati migliori rispetto ad altri. Il primo modello (488 pazienti) ha testato l’effetto di genere, altezza bersaglio, età alla pubertà, altezza alla pubertà ed età a fine trattamento sull’altezza finale in cm con r-quadro di 87.2%. Le variabili più importanti nel determinismo dell’altezza finale sono risultate: altezza bersaglio (18.8%), altezza alla pubertà (16.3%) ed età a fine terapia (circa 35% considerando le variabili polinomiali). Il secondo modello ha valutato su 543 pazienti l’effetto di genere, durata della terapia, età a inizio terapia, altezza SDS alla pubertà, altezza bersaglio SDS e altezza dopo 12 mesi di terapia sull’altezza finale SDS con r-quadro di 59%. Altezza a 12 mesi di terapia e altezza SDS alla pubertà sono state le variabili più importanti nel determinismo dell’altezza finale SDS (rispettivamente 23% e 10%). Conclusioni: La metodica RELIMPO (Relative Importance of Regressors in Linear Models) estrae casualmente dal database i pazienti con dataset completo, elabora il modello di previsione e lo valida su altri pazienti estratti sempre casualmente. In questo modo abbiamo ottenuto 2 modelli di previsione staturale, il primo dell’altezza finale in cm e in SDS. La previsione della statura in cm è più precisa. Mostriamo per la prima volta un modello di previsione solo su dati italiani, con una casistica molto ampia e con un r-quadro elevato

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model

Purpose We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. Methods We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. Results We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R-2 87.2%). Conclusion This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies

Management of Childhood-onset Craniopharyngioma in Italy: A Multicenter, 7-Year Follow-up Study of 145 Patients

Context Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results Age at diagnosis was 8.4 +/- 4.1 years. Duration of symptoms was 10.8 +/- 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime

Management of childhood-onset craniopharyngioma in Italy: A multicenter seven year follow-up study of 145 patients

Context: Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective: Identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits and number of patients starting GH treatment. Methods: Retrospective multicenter collection of 145 patients aged 0-18 years underwenting surgery for CP between 2000-2018, followed-up in 17 Italian centers of Pediatric Endocrinology. Results: Age at diagnosis was 8.4±4.1 years. Duration of symptoms was 10.8±12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%) and histology was adamantinomatous in all cases but two. Surgical approach was transcranic (TC) in 67.5% of cases and transphenoidal (TS) in 31.%. TC approach was prevalent in all age groups. Post-surgery complications occurred in 53% of cases with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented at least one hormone pituitary deficiency, with TSH deficit as most frequent (98.3%), followed by ACTH (96.8%), AVP (91.1%) and GH (77.4%). BMI significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years and 54 developed a recurrence or regrowth of the residual lesion. Conclusions: CP is often diagnosed late also in Italy with TC more frequent than TS surgical approach. Post-surgery complications were not rare and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime