Publications by authors named "Margaret Boguszewski"

55 Publications

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Pituitary 2021 Oct 25;24(5):810-827. Epub 2021 Jul 25.

Barrow Pituitary Center, Barrow Neurological Institute, Departments of Neuroendocrinology and Neurosurgery, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USA.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11102-021-01173-0DOI Listing
October 2021

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

J Endocr Soc 2021 Mar 9;5(3):bvaa205. Epub 2021 Feb 9.

Royal Veterinary College, University of London, London, UK.

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jendso/bvaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874572PMC
March 2021

Growth hormone deficiency and replacement in children.

Rev Endocr Metab Disord 2021 03 8;22(1):101-108. Epub 2020 Oct 8.

Department of Pediatrics, Endocrine Division (SEMPR), University Hospital, Federal University of Parana, Curitiba, Brazil.

Growth hormone deficiency (GHD) is a rare but treatable cause of short stature. The diagnosis requires a careful evaluation of clinical history, physical examination and appropriate interpretation of longitudinal growth, with specific features for each period of life. Other clinical findings, in addition to growth failure, may be present and can be related to the etiology and to associated hormone deficiencies. Despite more than 50 years since the first reports of provocative tests of growth hormone (GH) secretion for the diagnosis of GHD, the interpretation of the results remains a matter of debate. When GHD is confirmed, GH treatment is recommended. Treatment is effective and safe, but requires daily injections during many years, which can affect adherence. At the end of longitudinal growth, during the transition phase, it might be necessary to re-evaluate GH secretion. This review summarizes and updates the recent information related to GHD in children, as well the recommendations for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11154-020-09604-2DOI Listing
March 2021

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

J Clin Endocrinol Metab 2020 07;105(7)

Erasmus University Medical Center / Sophia Children's Hospital, Rotterdam, The Netherlands.

Context: Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described.

Objective: To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment.

Design: KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH.

Setting: KIGS database.

Patients: A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH.

Intervention: GH treatment.

Main Outcome Measure: NAH.

Results: Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated.

Conclusion: GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa203DOI Listing
July 2020

The challenge of long-term follow-up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource-limited countries: A single-center report from Brazil.

Pediatr Transplant 2020 06 4;24(4):e13691. Epub 2020 Apr 4.

Bone Marrow Transplantation Unit, Federal University of Paraná, Curitiba, Brazil.

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9 years (2.0-29.0); median age at follow-up was 17.5 years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13691DOI Listing
June 2020

What's in a name? What we call growth hormone is much more than just a growth-related peptide.

Arch Endocrinol Metab 2019 Nov-Dec;63(6):546-548

Departamento de Pediatria, Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná (SEMPR), Curitiba, PR, Brasil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20945/2359-3997000000183DOI Listing
March 2020

From dwarves to giants: South American's contribution to the history of growth hormone and related disorders.

Growth Horm IGF Res 2020 02 2;50:48-56. Epub 2019 Dec 2.

Department of Internal Medicine, Sector of Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address:

The aim of this article is to present a historical review on giants and dwarves living in South America and the contribution of South America's researchers to scientific advances on growth hormone (GH) and human disorders related to GH excess and GH deficiency (GHD). We went back in time to investigate facts and myths stemming from countless reports of giants who lived in the Patagonia region, focusing on what is currently known about gigantism in South America. Additionally, we have reviewed the exceptional work carried out in two of the world's largest cohorts of dwarfism related to GH-IGF axis: one living in Itabaianinha, Brazil, suffering from severe GHD due to a mutation in the GHRH receptor (GHRHR) gene, and the other living in El Oro and Loja provinces of Ecuador, who are carriers of GH receptor gene mutation that causes total GH insensitivity (Laron syndrome). Importantly, we present an overview of the outstanding medical contribution of Jose Dantas de Souza Leite, a Brazilian physician that described the first cases of acromegaly, and Bernardo Alberto Houssay, an Argentine researcher graced with the Nobel Prize, who was one the first scientists to establish a link between GH and glucose metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ghir.2019.11.004DOI Listing
February 2020

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective.

Horm Res Paediatr 2019 12;92(1):1-14. Epub 2019 Sep 12.

University Children´s Hospital, Tübingen, Germany.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000502231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979443PMC
April 2020

Growth hormone therapy in children; research and practice - A review.

Growth Horm IGF Res 2019 02 26;44:20-32. Epub 2018 Dec 26.

New York University Winthrop Hospital, 101 Mineola Boulevard, Mineola, NY 11201, USA. Electronic address:

Short stature remains the most common reason for referral to a pediatric Endocrinologist and its management remains a challenge. One of the main controversies is the diagnosis of idiopathic short stature and the role of new technologies for genetic investigation of children with inadequate growth. Complexities in management of children with short stature includes selection of who should receive interventions such as recombinant human growth hormone, and how should this agent dose be adjusted during treatment. Should anthropometrical data be the primary determinant or should biochemical and genetic data be used to improve growth response and safety? Furthermore, what is considered a suboptimal response to growth hormone therapy and how should this be managed? Treatment of children with short stature remains a "hot" topic and more data is needed in several areas. These issues are reviewed in this paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ghir.2018.12.004DOI Listing
February 2019

Postnatal management of growth failure in children born small for gestational age.

J Pediatr (Rio J) 2019 Mar - Apr;95 Suppl 1:23-29. Epub 2018 Dec 11.

Universidade Federal da Bahia, Faculdade de Medicina, Departamento de Pediatria, Salvador, BA, Brazil.

Objectives: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age.

Source Of Data: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors.

Data Synthesis: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period.

Conclusions: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jped.2018.10.015DOI Listing
April 2020

Growth Hormone's Links to Cancer.

Endocr Rev 2019 04;40(2):558-574

Department of Pediatrics, Endocrine Division (SEMPR), University Hospital, Federal University of Parana, Curitiba, Brazil.

Several components of the GH axis are involved in tumor progression, and GH-induced intracellular signaling has been strongly associated with breast cancer susceptibility in genome-wide association studies. In the general population, high IGF-I levels and low IGF-binding protein-3 levels within the normal range are associated with the development of common malignancies, and components of the GH-IGF signaling system exhibit correlations with clinical, histopathological, and therapeutic parameters in cancer patients. Despite promising findings in preclinical studies, anticancer therapies targeting the GH-IGF signaling system have led to disappointing results in clinical trials. There is substantial evidence for some degree of protection against tumor development in several animal models and in patients with genetic defects associated with GH deficiency or resistance. In contrast, the link between GH excess and cancer risk in acromegaly patients is much less clear, and cancer screening in acromegaly has been a highly controversial issue. Recent studies have shown that increased life expectancy in acromegaly patients who attain normal GH and IGF-I levels is associated with more deaths due to age-related cancers. Replacement GH therapy in GH deficiency hypopituitary adults and short children has been shown to be safe when no other risk factors for malignancy are present. Nevertheless, the use of GH in cancer survivors and in short children with RASopathies, chromosomal breakage syndromes, or DNA-repair disorders should be carefully evaluated owing to an increased risk of recurrence, primary cancer, or second neoplasia in these individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/er.2018-00166DOI Listing
April 2019

Novel SUZ12 mutations in Weaver-like syndrome.

Clin Genet 2018 11 6;94(5):461-466. Epub 2018 Aug 6.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

SUZ12 is a core component of polycomb repressive complex 2 (PRC2) along with EZH2 and EED. Recently, germline mutations in the SUZ12, EZH2 and EED genes have been reported in Weaver syndrome (WS) or Weaver-like syndrome, suggesting a functional link between PRC2 deficits and WS. However, only one case of a SUZ12 mutation presenting with Weaver-like syndrome has been reported. Here, we report a missense and a frameshift mutation in SUZ12 (c.1797A>C; p.Gln599His and c.844_845del; p.Ala282Glnfs*7), both of which are novel, in two individuals. Their clinical features included postnatal overgrowth, increased bifrontal diameter, large ears, round face, horizontal chin crease and skeletal anomalies, but did not fulfill the WS diagnostic criteria. These data provide strong evidence that SUZ12 mutations cause Weaver-like syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cge.13415DOI Listing
November 2018

Biomarkers of GH action in children and adults.

Growth Horm IGF Res 2018 06 20;40:1-8. Epub 2018 Mar 20.

Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ghir.2018.03.005DOI Listing
June 2018

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults.

Endocr Connect 2018 Mar 26;7(3):R126-R134. Epub 2018 Feb 26.

Aarhus University HospitalAarhus, Denmark

Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly.

Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry.

Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs.

Consensus Process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process.

Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-18-0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868631PMC
March 2018

MANAGEMENT OF ENDOCRINE DISEASE: Growth and growth hormone therapy in short children born preterm.

Eur J Endocrinol 2017 Mar 1;176(3):R111-R122. Epub 2016 Nov 1.

Department of PediatricsEndocrine Division (SEMPR), Federal University of Paraná, Curitiba, Brazil.

Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-16-0482DOI Listing
March 2017

Growth hormone, insulin-like growth factor system and carcinogenesis.

Endokrynol Pol 2016 8;67(4):414-26. Epub 2016 Jul 8.

Department of Internal Medicine, Endocrine Division (SEMPR), Federal University of Paraná, Curitiba, Brazil.

The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414-426).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/EP.a2016.0053DOI Listing
April 2017

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations.

Eur J Endocrinol 2016 Jun 23;174(6):C1-8. Epub 2016 Mar 23.

Cedars-Sinai Medical Center Los Angeles, California, USA.

Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH).

Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry.

Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues.

Consensus Process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors.

Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-16-0111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081743PMC
June 2016

The influence of glycemic control on the oral health of children and adolescents with diabetes mellitus type 1.

Arch Endocrinol Metab 2015 Dec;59(6):535-40

Departamento de Pediatria, UFPR, Curitiba, PR, Brasil.

Objective: To evaluate the influence of disease control, expressed by the mean values of glycated hemoglobin (HbA1c), in the oral health of children and adolescents with diabetes mellitus type 1 (T1DM).

Subjects And Methods: A cross sectional study involving 87 children and adolescents (59 girls), 10 ± 2.6 years old. The participants were divided into three groups: HbA1c ≤ 8%, 8% < HbA1c ≤ 10% and HbA1c > 10%. The duration of the disease, age and average HbA1c were obtained from their medical records. Oral health was evaluated according to the following indexes: Simplified Oral Hygiene Index (OHI-S); Community Periodontal Index (CPI); Decayed, Missing or Filled Teeth Index (DMFT/dmft) for permanent and deciduous teeth; and the stimulated salivary flow rate (SSFR).

Results: The median SSFR was 1.1 mL/min in the group with HbA1c ≤ 8%, 0.7 mL/min in the intermediary group and 0.6 mL/min in the HbA1c > 10% group. A significant decrease in salivary flow was observed with an increase in HbA1c (p = 0.007). The DMFT/dmft and CPI indexes were higher in individuals with higher HbA1c values. More caries-free individuals were found in the group with HbA1c ≤ 8% compared to those with HbA1c > 10%. The group with HbA1c > 10% exhibited more caries and bleeding gums than the other groups. HbA1c values in girls were higher than in boys.

Conclusion: Children and adolescents with unsatisfactory glycemic control, represented by higher HbA1c concentrations, exhibited a higher frequency of caries and gingivitis, and a reduction in salivary flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/2359-3997000000117DOI Listing
December 2015

Short Children with CHARGE Syndrome: Do They Benefit from Growth Hormone Therapy?

Horm Res Paediatr 2015 29;84(1):49-53. Epub 2015 May 29.

Division of Pediatric Endocrinology, Department of Pediatrics, University of Erlangen, Erlangen, Germany.

Aim: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome.

Patients: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years.

Results: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged.

Conclusions: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000382017DOI Listing
May 2016

Metabolic risk and television time in adolescent females.

Int J Public Health 2015 Feb 10;60(2):157-65. Epub 2014 Dec 10.

Faculdade de Ciências do Desporto e Educação Física, Universidade de Coimbra, Coimbra, Portugal,

Objectives: A sedentary lifestyle is increasingly implicated in a negative metabolic health profile among youth. The present study examined relationships between clustered metabolic risk factors and TV viewing in female adolescents.

Methods: The sample comprised 262 girls 14-17 years. Height, weight, fasting glucose, insulin, HDL cholesterol, triglycerides, and blood pressure were measured. Body mass index (BMI) was calculated. TV viewing time and moderate-to-vigorous physical activity (MVPA) were estimated from a 3-day diary. Outcome variables were normalized and expressed as Z scores which were summed into a metabolic risk score. Multiple linear regression analysis was used.

Results: TV viewing was independently associated with increased prevalence of clustered metabolic risk in girls after adjustment for several confounders (i.e., chronological age, BMI, MVPA, and parental education). The final model also indicated that lower levels of MVPA, higher BMI, and lower mother education were associated with higher metabolic risk.

Conclusions: Increased TV viewing had an adverse effect on metabolic health of adolescent girls. The findings highlight the potential importance of preventive actions to ameliorate metabolic risk in youth which target both sedentary and physically active behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00038-014-0625-zDOI Listing
February 2015

Whole exome sequencing of extreme morbid obesity patients: translational implications for obesity and related disorders.

Genes (Basel) 2014 Aug 25;5(3):709-25. Epub 2014 Aug 25.

Mind and Brain Theme, South Australian Health and Medical Research Institute, and Department of Psychiatry, School of Medicine, Flinders University, PO Box 11060 Adelaide SA 5001, Adelaide, Australia.

Whole-exome sequencing (WES) is a new tool that allows the rapid, inexpensive and accurate exploration of Mendelian and complex diseases, such as obesity. To identify sequence variants associated with obesity, we performed WES of family trios of one male teenager and one female child with severe early-onset obesity. Additionally, the teenager patient had hypopituitarism and hyperprolactinaemia. A comprehensive bioinformatics analysis found de novo and compound heterozygote sequence variants with a damaging effect on genes previously associated with obesity in mice (LRP2) and humans (UCP2), among other intriguing mutations affecting ciliary function (DNAAF1). A gene ontology and pathway analysis of genes harbouring mutations resulted in the significant identification of overrepresented pathways related to ATP/ITP (adenosine/inosine triphosphate) metabolism and, in general, to the regulation of lipid metabolism. We discuss the clinical and physiological consequences of these mutations and the importance of these findings for either the clinical assessment or eventual treatment of morbid obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes5030709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198926PMC
August 2014

Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys.

J Pediatr Endocrinol Metab 2015 Jan;28(1-2):125-31

Background: Evaluation of lipid profile in children and adolescents is important for early diagnosis of dyslipidemias. Physiological changes might be observed in the concentration of the lipid profile components, according to the stage of sexual maturation.

Objective: To evaluate the variation in lipid and lipoprotein concentrations in boys during puberty.

Methods: The sample consisted of 570 male adolescents with ages between 10 and 17 years. Weight, height, and body mass index (BMI) were assessed. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were determined by the enzymatic method, and low-density lipoprotein cholesterol (LDL-C) was calculated. Puberty was classified according to Tanner references. The percentile criterion was adopted for the distribution and identification of lipoprotein levels. The analysis of variance and description tests with p<0.05 was applied.

Results: Participants had similar BMI z-score and physical activity habits in all groups. A significant reduction in TC and HDL-C concentrations between the start and end of puberty was observed. LDL-C levels rose during stage 3 of development, decreasing at the end of the pubertal process. TG levels did not change significantly with pubertal status.

Conclusion: Lipid and lipoprotein concentrations tend to undergo changes during puberty in boys. The use of percentile values can be very useful to track variations in lipid and lipoprotein levels during the maturation process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2013-0450DOI Listing
January 2015

Three-year growth response to growth hormone treatment in very young children born small for gestational age-data from KIGS.

J Clin Endocrinol Metab 2014 Aug 23;99(8):2683-8. Epub 2014 Apr 23.

Department of Pediatrics (M.C.S.B.), Federal University of Paraná, Curitiba PR 80060-900, Brazil; Pfizer Inc (A.L.), Endocrine Care, SE-190 91 Sollentuna, Sweden; and Pfizer Inc (H.A.W.), Endocrine Care, 10117 Berlin, Germany.

Context: Children born small for gestational age (SGA) with poor growth during the first years of life may remain short in stature during childhood and as adults.

Objective: To evaluate the 3-year growth response to GH treatment in very young short children born SGA, and to test the existing predictions models for growth response developed for older SGA children.

Setting: KIGS (The Pfizer International Growth Database).

Patients: A total of 620 SGA children (birth length and/or weight below -2 SD score [SDS]) on GH treatment, 156 in the 2- to 4-year-old group (100 boys; median age, 3.3 y), and 464 in the 4- to 6-year-old group (284 boys; median age, 4.9 y).

Results: Median values and 10th-90th percentiles are presented. Both groups presented a significant increase in height velocity during GH treatment. Median height SDS increased from -3.9 (-5.4 to -2.9) at the start to -2.2 (-3.8 to -1.0) at 3 years in the 2- to 4-year-old group (P < .01) and from -3.4 (-4.5 to -2.6) to -2.0 (-3.3 to -0.9) in the 4- to 6-year-old group (P < .01). Median weight SDS increased from -3.8 (-5.9 to -2.4) to -2.1 (-4.1 to -0.5) in the 2- to 4-year-old group (P < .01). Respective values for the 4- to 6-year-old group were -3.1 (-4.8 to -1.8) to -1.6 (-3.1 to -0.1) SDS (P < .01). First- and second-year growth response could be estimated by the SGA model.

Conclusion: Very young children born SGA without spontaneous catch-up growth presented a significant improvement in height and weight during the 3 years of GH treatment. Growth response could be estimated by the SGA model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2013-4117DOI Listing
August 2014

Relationship between metabolic syndrome and moderate-to-vigorous physical activity in youth.

J Phys Act Health 2015 Jan 11;12(1):13-9. Epub 2014 Apr 11.

Faculty of Sport Sciences and Physical Education, University of Coimbra, Coimbra, Portugal.

Background: Associations of metabolic syndrome (MetS) with lifestyle behaviors in youth is potentially important for identifying subgroups at risk and encourage interventions. This study evaluates the associations among the clustering of metabolic risk factors and moderate-to-vigorous physical activity (MVPA) in youth.

Methods: The sample comprised 522 girls and 402 boys (N = 924) aged 11 to 17 years. Height, weight, waist circumference (WC), fasting glucose, high-density lipoprotein cholesterol, triglycerides, and blood pressures were measured. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. MVPA was estimated with a 3-day diary. Outcome variables were statistically normalized and expressed as z scores. A clustered metabolic risk score was computed as the mean of z scores. Multiple linear regression was used to test associations between metabolic risk and MVPA by sex, adjusted for age, WC, and CRF.

Results: After adjustment for potential confounders, MVPA was inversely associated with the clustering of metabolic risk factors in girls, but not in boys; in addition, after adjusting for WC, the statistical model of that relationship was substantially improved in girls.

Conclusion: MVPA was independently associated with increased risk of MetS in girls. Additional efforts are needed to encourage research with different analytical approach and standardization of criteria for MetS in youth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1123/jpah.2013-0053DOI Listing
January 2015

Independent association of clustered metabolic risk factors with cardiorespiratory fitness in youth aged 11-17 years.

Ann Hum Biol 2014 May-Jun;41(3):271-6

Research Centre for Anthropology and Health .

Background: Although the prevalence of metabolic syndrome (MetS) has increased in youth, the potential independent contribution of cardiorespiratory fitness (CRF) to the clustering of metabolic risk factors has received relatively little attention.

Aim: This study evaluated associations between the clustering of metabolic risk factors and CRF in a sample of youth.

Subjects And Methods: Height, weight, BMI, fasting glucose, insulin, HDL-cholesterol, triglycerides and blood pressures were measured in a cross-sectional sample of 924 youth (402 males, 522 females) of 11-17 years. CRF was assessed using the 20-metre shuttle run test. Physical activity (PA) was measured with a 3-day diary. Outcome variables were statistically normalized and expressed as Z-scores. A MetS risk score was computed as the mean of the Z-scores. Multiple linear regression was used to test associations between CRF and metabolic risk, adjusted for age, sex, BMI, PA and parental education.

Results: CRF was inversely associated with MetS after adjustment for potential confounders. After adjusting for BMI, the relationship between CRF and metabolic risk has substantially improved.

Conclusion: CRF was independently associated with the clustering of metabolic risk factors in youth of 11-17 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/03014460.2013.856471DOI Listing
February 2015

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period.

Arq Bras Endocrinol Metabol 2013 Dec;57(9):709-16

Objective: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase.

Subjects And Methods: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30).

Results: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies.

Conclusion: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/s0004-27302013000900006DOI Listing
December 2013

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age.

Clinics (Sao Paulo) 2013 Jun;68(6):785-91

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormonios e Genetica Molecular LIM/42, São Paulo/SP, Brazil.

Objective: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth.

Patients And Methods: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients.

Results: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables.

Conclusion: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6061/clinics/2013(06)10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674288PMC
June 2013

Variations in the vitamin D-binding protein (DBP) gene are related to lower 25-hydroxyvitamin D levels in healthy girls: a cross-sectional study.

Horm Res Paediatr 2013 20;79:162-8. Epub 2013 Mar 20.

Gynecologic Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

Background/aims: Vitamin D deficiency has been recognized as a worldwide epidemic affecting several pediatric and adolescent populations. We determined the genotype and haplotype distribution of the rs4588 and rs7041 polymorphisms of the GC gene encoding vitamin D-binding protein (DBP) and investigated the associations between these gene variants and their haplotypes with 25-hydroxyvitamin D [25(OH)D] levels in girls from South Brazil.

Methods: Cross-sectional study including 198 apparently healthy girls aged 10-18 years. Plasma levels of 25(OH)D were assessed by radioimmunoassay. Participants were genotyped for rs4588 and rs7041 by real-time PCR, with allelic discrimination assays.

Results: Mean chronological age and BMI percentile were 13.17 ± 1.74 years and 57.81 ± 29.03, respectively. Sufficient circulating 25(OH)D levels (≥30 ng/ml) were found in 9.1% of the overall group, insufficient levels (20-29.9 ng/ml) in 59.6%, and deficient levels (<20 ng/ml) in 31.3%. The AA genotype of rs4588, TT genotype of rs7041 and CT-AT/AT-AT (GC 1f-2/2-2) diplotypes were significantly associated with lower 25(OH)D levels, even after adjustment for age and season at the time of blood collection.

Conclusions: The GC gene genotype may be related to the susceptibility to low 25(OH)D levels in female children and adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000348847DOI Listing
November 2013

GH-releasing hormone receptor gene: a novel splice-disrupting mutation and study of founder effects.

Horm Res Paediatr 2012 10;78(3):165-72. Epub 2012 Oct 10.

Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, São Paulo, Brazil.

Background: Mutations in GH-releasing hormone receptor gene (GHRHR) are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD).

Objective: To search for GHRHR mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations.

Methods: The coding region of GHRHR was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking GHRHR were analyzed in patients with c.57+1G>A (IVS1+1G>A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G>A (p.E382E) mutation.

Results: A novel homozygous intronic GHRHR c.752-1G>A (IVS7-1G>A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G>A];[1146G>A] and a heterozygous c.527C>T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G>A mutation and independent recurrence for the c.1146G>A mutation.

Conclusion: We report a novel splice-disrupting mutation in GHRHR in 2 siblings and provide evidence that all c.57+1G>A (IVS1+1G>A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000342760DOI Listing
May 2013

Chiari I malformation with neurogenic hypertension: case report.

Childs Nerv Syst 2012 Nov 14;28(11):1985-7. Epub 2012 Aug 14.

Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00381-012-1880-zDOI Listing
November 2012
-->