Metabolic and Growth Outcome of Two-year Growth Hormone Treatment in Children Born Small for Gestational Age: A Retrospective Study.

BACKGROUND: Children born Small for Gestational Age (SGA) without early catch-up growth may show impaired growth rate, adult height, and metabolic profile [1]. Growth Hormone (GH) is recommended for their treatment, and it has been shown to have positive effects on growth and metabolic profile and good tolerability [2]. OBJECTIVE: The study aimed to evaluate the auxological and metabolic effects and safety of GH treatment in SGA children. METHODS: 34 SGA children (15 F, 19 M; mean age: 8.72 ± 2.48 yrs) treated with GH (starting dosage: 32.24 ± 2.88 mcg/kg/die) were evaluated every six months for 24 months with growth and metabolic parameters. RESULTS: After two years, SGA children showed a significant improvement in height, weight, and growth rate, already evident after six months (p < 0.001), with a constant, significant improvement in height throughout the treatment (p ≤ 0.03 T0 vs. T12, T12 vs. T24). Conversely, although significantly higher than baseline at each visit (p < 0.001), the growth rate significantly decreased from 6 to 18 months (p ≤ 0.015 T6 vs. T12, T12 vs. T18). During the follow-up, an increase in glycemia (p ≤ 0.042 vs. T12, T18) and urycemia (p ≤ 0.01 vs. T12, T18, and T24) and a decrease in AST (p ≤ 0.021 vs. T12, T18, and T24) and LDL cholesterol (p = 0.03 vs. T24) were observed. Overall, treatment was found to be well tolerated, with poor compliance being the most frequent adverse event (11.8%) and no reported hyperglycemia. CONCLUSION: In conclusion, GH can be considered an effective, safe treatment in SGA children, improving height and growth rate, although proper metabolic follow-up is required.

Auxological and metabolic effects of long-term treatment with recombinant growth hormone in children born small for gestational age: a retrospective study.

RATIONALE: Children born small for gestational age (SGA) not showing catch-up during the first two years of life reportedly show an impaired growth rate and adult height, as well as a worse metabolic outcome, mainly in terms of glycemic and lipid profile, compared to general population. In SGA children with short stature, treatment with recombinant growth hormone (GH) is currently recommended until adolescence; therefore, it may last long-term. STUDY METHODS: The aim of the current study was to evaluate the auxological and metabolic effects and the safety of long-term recombinant GH treatment in SGA children. The study included 15 SGA children (5 F, 10 M; mean age: 6.78 yrs) treated with GH for at least 48 months. Growth and metabolic parameters, including glycemic and lipid profile, transaminases, and urycemia, were collected every six months. RESULTS: Compared to baseline, SGA children showed a significant improvement in height, weight, and growth rate after four yaers of treatment with GH (p ≤ 0.002), being already evident after six months of treatment (p < 0.001). Noteworthy, patients showed a constant, significant improvement in height throughout the treatment, as it was significantly higher at each follow-up compared to the previous one, until 42 months of treatment, except at 30 months of treatment (p < 0.001 T6VST12; p < 0.01 T12VST18, T18VST24; p < 0.05 T30VST36, T36VST42). Considering metabolic parameters, compared to baseline, a recurring increase in glycemia (p ≤ 0.028 vs T30, T36, and T48) and decrease in AST (p ≤ 0.035 vs T36, T42, and T48) and an occasional decrease in LDL cholesterol (p ≤ 0.04 vs T24 and T42) and triglycerides (p = 0.008 vs T18) and increase in urycemia (p = 0.034 vs T42). Considering safety profile, treatment was well tolerated, as the most frequently reported adverse event was poor compliance (20%); no hyperglycemia, hypercholesterolemia or hyperstransaminasemia occurred throughout the treatment, CONCLUSIONS: Long-term GH treatment showed to be effective in improving height and growth rate in SGA children, with a positive impact of metabolic profile and a safety profile, although glycemia should be carefully monitored over time.

Co-occurrence of Beckwith-Wiedemann syndrome and pseudohypoparathyroidism type 1B: coincidence or common molecular mechanism?

Imprinting disorders are congenital diseases caused by dysregulation of genomic imprinting, affecting growth, neurocognitive development, metabolism and cancer predisposition. Overlapping clinical features are often observed among this group of diseases. In rare cases, two fully expressed imprinting disorders may coexist in the same patient. A dozen cases of this type have been reported so far. Most of them are represented by individuals affected by Beckwith-Wiedemann spectrum (BWSp) and Transient Neonatal Diabetes Mellitus (TNDM) or BWSp and Pseudo-hypoparathyroidism type 1B (PHP1B). All these patients displayed Multilocus imprinting disturbances (MLID). Here, we report the first case of co-occurrence of BWS and PHP1B in the same individual in absence of MLID. Genome-wide methylation and SNP-array analyses demonstrated loss of methylation of the KCNQ1OT1:TSS-DMR on chromosome 11p15.5 as molecular cause of BWSp, and upd(20)pat as cause of PHP1B. The absence of MLID and the heterodisomy of chromosome 20 suggests that BWSp and PHP1B arose through distinct and independent mechanism in our patient. However, we cannot exclude that the rare combination of the epigenetic defect on chromosome 11 and the UPD on chromosome 20 may originate from a common so far undetermined predisposing molecular lesion. A better comprehension of the molecular mechanisms underlying the co-occurrence of two imprinting disorders will improve genetic counselling and estimate of familial recurrence risk of these rare cases. Furthermore, our study also supports the importance of multilocus molecular testing for revealing MLID as well as complex cases of imprinting disorders.

Growth alterations in rare forms of primary adrenal insufficiency: a neglected issue in paediatric endocrinology.

Primary adrenal insufficiency (PAI) is an endocrine disorder characterized by direct adrenal failure, with consequent glucocorticoid, and eventually mineralocorticoid, deficiency. In children, the main cause of PAI is congenital adrenal hyperplasia (CAH), due to a loss of function of adrenal steroidogenic enzymes, but also rarer forms, including autoimmune polyglandular syndrome, adrenoleucodistrophy, adrenal hypoplasia congenita, familial glucocorticoid deficiency, and Allgrove's Syndrome, may be observed. In PAI children, growth alterations represent a major issue, as both inadequate and excessive glucocorticoid replacement treatment may lead to reduced growth rate and adult height impairment. However, growth abnormalities are poorly studied in rare forms of paediatric PAI, and specific studies on growth rate in these children are currently lacking. In the present review, the currently available evidence on growth alterations in children with rare PAI forms will be summarized, with a major focus on comorbidities with a potential impact on patients' growth rate.

Recurrent abdominal pain in children: underlying pathologies in the absence of "alarm" symptoms.

BACKGROUND: Recurrent abdominal pain (RAP) is a common disorder in childhood. However, it is not clear what the incidence of organic disease is, in the absence of "alarm" symptoms or signs. The aim of this study was to clarify if the performance of diagnostic tests can be useful in revealing underlying organic disorders. METHODS: The participants were 4- to 16-year-old children, who had been referred to our tertiary care pediatric center. A total of 98 children (48 males, 50 females) with RAP but without any alarm symptoms or signs were selected. In the 98 selected children, the performance of diagnostic tests for suspected organic diseases was recommended. RESULTS: Fourteen children refused diagnostic tests. Forty-eight out of 84 children with RAP without any alarm symptoms and signs received a diagnosis of organic disease. Nineteen (22.6%) patients resulted positive for lactose intolerance. Seventeen patients (20.2%) were affected by celiac disease. Two (2.4%) patients were positive for cow milk allergy. Nine (10.7%) patients resulted positive for ureteral calculosis. One (1.2%) was affected by teniasis. Thirty-three children of the 38 children tested positive for lactose intolerance, celiac disease or cow-milk allergy were completely symptom-free at the 6 months follow-up and the remaining five patients reported a significant lower mean level of pain severity overall. Seven of 9 children with calculosis improved symptomatology. At the next follow-up six children were again suffering from RAP. CONCLUSIONS: Children with RAP should be referred to pediatric gastroenterologists if symptoms persist; testing should be performed even in the absence of alarm signs because of the high prevalence of underlying organic pathologies.

Evaluation of Helicobacter Pylori eradication in pediatric patients by triple therapy plus lactoferrin and probiotics compared to triple therapy alone.

BACKGROUND: To evaluate whether the addition of a probiotic could improve Helicobacter pylori (H.P.) eradication rates and reduce the side effects of treatment in children. METHODS: Between July 2008 and July 2011 all patients with a clinical, laboratory and endoscopic diagnosis of H.P. positive gastritis referred to our Unit were included in the study. Patients suffering from allergy to any of drugs used in the study, with previous attempts to eradicate H.P. and those who received antibiotics, PPIs or probiotics within 4 weeks were excluded from the present study. Patients were randomized into two therapy regimens (group A and B): both groups received standard triple treatment (omeprazole, amoxicillin and clarithromycin) while only group B patients were also given a probiotic (Probinul - Cadigroup). Patients compliance was evaluated at the end of the treatment. Successful eradication was defined as a negative 13 C-urea breath test (C13-ubt) result four weeks after therapy discontinuation. RESULTS: A total of 68 histopathologically proven H.P.-infection children (32 male and 36 females) were included in the study. All of the patients in both groups used more than 90% of the therapies and no patients were lost at follow up. All side effects were selflimiting and disappeared once the therapy was terminated. Epigastric pain was observed in 6 (17.6%) group A vs 2 (5.8%) group B patients (P<0.05), nausea in 3 (8.8%) group A vs 1 (2.9%) group B patients (P<0.05); vomiting and diarrhea were observed in 2(5.8%) and 8 (23.5%) group A patients, respectively and never in group B (P<0.05). There was no significant difference between the two groups in terms of constipation (5.8% in group A and B). Four weeks after the completion of therapy, 56/68 patients (82.3%) tested negative for H.P. on C13-ubt. H.P. was eradicated in 26 patients (76.4%) in group A and in 30 patients (88.2%) in group B. There was no significantly difference in the rate of H.P. eradication between group A and group B (p=0.1), although the success rate for H.P. eradication was higher in group B than in group A. CONCLUSION: The addition of a probiotic formula to triple therapy significantly decreased the frequency of epigastric pain, nausea, vomiting and diarrhea.