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Cureus Jul 2023Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually...
Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually presents with gastrointestinal symptoms like bloody diarrhea, fever and loss of weight. The clinical course of CD includes gastrointestinal complications like fistulas, abscesses and perianal disease. Inflammatory bowel diseases (IBD) are usually diagnosed during childhood and adolescence, majority during puberty and pubertal growth spurt. Various extraintestinal manifestations may be a presentation of CD that poses a diagnostic challenge. Growth failure is an important complication of IBD rather than a manifestation. Herein we present a case of a 16-year-old Sri Lankan girl presenting with growth failure and primary amenorrhea. She had minimal gastrointestinal symptoms. She also had microcytic anemia with marginally elevated inflammatory markers and hormonal profile. She underwent colonoscopy and was diagnosed to have Crohn's disease confirmed by ileal biopsy. On initiation of treatment with immunosuppressants, she attained menarche, although no improvement in height was observed.
PubMed: 37593289
DOI: 10.7759/cureus.42020 -
EClinicalMedicine Feb 2020Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with...
BACKGROUND
Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing.
METHODS
Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively.
FINDINGS
All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0·63(0·45,0·89) for GH, 0·48(0·34,0·69) for TSH, 0·55(0·38,0·80) for ACTH, 0·28(0·11,0·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2·27(0·88,5·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80·0% vs 41·6%, p<0·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4·2% (6/144) SOD and 3·2% (1/31) ONH, and only in patients with multisystem phenotypes.
INTERPRETATION
More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions.
FUNDING
M.C., M.G., and N.I. were supported by the European Society of Paediatric Endocrinology (ESPE) through ESPE Clinical Fellowships.
PubMed: 32140665
DOI: 10.1016/j.eclinm.2019.11.017 -
Journal of Clinical Medicine Jan 2023Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are,...
Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the gene have been previously reported in females with premature ovarian insufficiency (POI). is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic subjects has been instigated.
PubMed: 36769638
DOI: 10.3390/jcm12030990 -
JCEM Case Reports Jun 2024OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7...
OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (). Hypogonadism and hypospadias have been described in only a few males. We report a patient with 7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.
PubMed: 38847008
DOI: 10.1210/jcemcr/luae084 -
Kidney International Reports Jun 2024Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is...
INTRODUCTION
Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages.
METHODS
In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed.
RESULTS
Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr ( < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years).
CONCLUSION
The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.
PubMed: 38899199
DOI: 10.1016/j.ekir.2024.03.021 -
Osteoporosis International : a Journal... Feb 2024Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical...
UNLABELLED
Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids.
PURPOSE
Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids.
METHODS
We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF.
RESULTS
The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033).
CONCLUSION
GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.
Topics: Male; Child; Humans; Spinal Fractures; Glucocorticoids; Testosterone; Growth Hormone; Muscular Dystrophy, Duchenne; Zoledronic Acid
PubMed: 37872346
DOI: 10.1007/s00198-023-06951-z -
Transplantation and Cellular Therapy Aug 2021Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve, and patients are thus increasingly faced with the late effects...
Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve, and patients are thus increasingly faced with the late effects of treatment. Infertility is very common for both males and females following HSCT and is one of the most distressing sequelae. Adoption and surrogate egg or sperm donation are possibilities for some patients, but post-HSCT reversal of gonadal failure is not possible. We have recently initiated an oncofertility program with a dedicated practitioner with specific expertise in this area. Our practice is for her to meet with all families and age-appropriate patients during the pre-HSCT evaluation period. This allows patients and families to be accurately informed about the expected treatment-related infertility risk and the available options for fertility preservation. Sperm banking and egg or embryo cryopreservation are established approaches but are not achievable for many children and adolescents. Recently, the harvesting and cryopreservation of ovarian and testicular tissue represents a novel surgical option that allows for the possibility of fertility preservation to be extended to children of all ages. The purpose of this investigation is to evaluate the safety of these procedures proximal to conditioning therapy and HSCT. This is a retrospective report on a consecutive cohort of all patients aged 0 to 25 years who, after discussion with our oncofertility specialist, chose to undergo surgical fertility preservation (laparoscopic unilateral oophorectomy or testicular biopsy) at our institution between March 2018 and April 2020. These procedures occurred under general anesthesia at the time of central line placement prior to the initiation of HSCT conditioning. We assess the safety of the procedures in terms of postoperative complications and impact on HSCT course. Twenty-two patients underwent fertility preservation surgical procedures. Thirteen patients (59%) were female, median age 13 years (1 to 22 years), and 9 (41%) were male, median age 8 years (5 to 12 years). Fourteen (63%) were prepubertal and 8 (36%) pubertal. HSCT indications were hematologic malignancies/solid tumor (40%) and nonmalignant diseases (60%). Most received an allogenic graft (68%) and 81% had myeloablative conditioning. All patients became neutropenic at a median of 10 days (0 to 51 days) from the surgical procedure; 1 was neutropenic at the time of testicular tissue cryopreservation (TTC). The mean duration for the procedures performed, including ovarian tissue cryopreservation (OTC) or TTC, was 98 minutes (49 to 260 minutes) and 97 minutes (56 to 178 minutes), respectively. Estimated blood loss was minimal and no postoperative site infections occurred. One postprocedure, blood culture-negative fever was reported without an identifiable source; the patient completed 48 hours of antibiotics with resolution of fever. Sixty-two percent of females and 56% of males started conditioning within 24 hours of OTC/TTC (15 hours to 113 days; median, 1 day). The median time to engraftment was 22 days (9 to 33 days) in females and 17 days (11 to 67 days) in males, consistent with our institutional benchmarks. One patient with aplastic anemia had primary graft failure, attributed to low cell dose. This patient engrafted after a second transplant from an alternative donor but ultimately died of multiorgan failure. He was neutropenic for over 60 days and never experienced surgical site infection. There were no procedure-related delays to start of conditioning or to discharge. Children of all ages can now be offered the possibility of fertility preservation following HSCT for benign and malignant conditions. Our review suggests that these procedure for both females and males can be performed close to the start of conditioning, which allows for coupling with central access placement. These procedures appear to be safe and do not add to transplant-related morbidity.
Topics: Adolescent; Child; Cryopreservation; Female; Fertility Preservation; Hematopoietic Stem Cell Transplantation; Humans; Male; Retrospective Studies; Transplantation Conditioning
PubMed: 33864966
DOI: 10.1016/j.jtct.2021.04.001 -
JBMR Plus Nov 2020Adults with type 1 diabetes mellitus (T1DM) are at risk of premature osteoporosis and fractures. The onset of T1DM typically starts during childhood and adolescence....
Adults with type 1 diabetes mellitus (T1DM) are at risk of premature osteoporosis and fractures. The onset of T1DM typically starts during childhood and adolescence. Thus, the effects of DM on the skeleton may be established during this period. Studies in children with T1DM primarily use DXA with conflicting results. We present the first study in adolescents assessing the impact of T1DM on skeletal microstructure and strength using HRpQCT. We recruited 22 patients aged 12 to 16 years with T1DM who were matched by age, gender, and pubertal stage with healthy controls. Paired tests were applied to assess differences in cortical and trabecular microarchitecture measurements from HRpQCT, and skeletal strength from HRpQCT-derived microfinite element analysis. Subtotal body, lumbar, and pelvic parameters were assessed using DXA. There was no significant difference in subtotal body, lumbar spine, and pelvic BMD between T1DM and control pairs. However, tibial trabecular thickness was lower (-0.005 mm; 95% CI, -0.01 to -0.001; = 0.029) and trabecular loading was lower at the distal radius (ratio of the load taken by the trabecular bone in relation to the total load at the distal end (Tb.F/TF) distal: -6.2; 95% CI, -12.4 to -0.03; = 0.049), and distal and proximal tibia (Tb.F/TF distal: -5.2, 95% CI, -9.2 to -1.2; = 0.013; and Tb.F/TF proximal: -5.0, 95% CI, -9.8 to -0.1; = 0.047) in T1DM patients. A subanalysis of radial data of participants with duration of T1DM of at least 2 years and their matched controls demonstrated a reduced trabecular bone number (-0.15, 95% CI, -0.26 to -0.04; = 0.012), increased trabecular separation (0.041 mm, 95% CI, 0.009-0.072; = 0.015), an increased trabecular inhomogeneity (0.018, 95% CI, 0.003-0.034; = 0.021). Regression models demonstrated a reduction in tibial stiffness (-0.877 kN/mm; = 0.03) and tibial failure load (-0.044 kN; = 0.03) with higher HbA1C. Thus, in adolescents with T1DM, detrimental changes are seen in tibial and radial microarchitecture and tibial and radial strength before changes in DXA occur and may result from poor diabetic control. © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 33210068
DOI: 10.1002/jbm4.10422 -
Endocrine Journal Jan 2021SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic... (Review)
Review
SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic effect, GH therapy has been regarded as a contraindication. We observed a Brazilian girl with SHORT syndrome who received GH therapy from 4 6/12 years of age for SGA short stature. GH dosage was increased from 0.23 to 0.36 mg/kg/week, but statural response to GH therapy remained poor. Her blood HbA1c level, though it remained 5.5-6.0% in childhood, began to elevate with puberty and increased to 9.2% at 10 6/12 years of age, despite the discontinuation of GH therapy at 9 11/12 years of age. Laboratory studies indicated antibody-negative IRDM. She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Whole exome sequencing revealed a de novo heterozygous pathogenic variant (c.1945C>T:p.(Arg649Trp)) in PIK3R1 known as the sole causative gene for SHORT syndrome. Subsequent literature review for patients with molecularly confirmed SHORT syndrome revealed the development of IRDM in 10 of 15 GH-untreated patients aged ≥12 years but in none of three GH-treated and six GH-untreated patients aged ≤10 years. These findings imply a critical role of pubertal development and/or advanced age rather than GH therapy in the development of IRDM, and a usefulness of SGLT2 inhibitor in the treatment of IRDM.
Topics: Brazil; Canagliflozin; Child; Diabetes Complications; Diabetes Mellitus; Drug Therapy, Combination; Female; Growth Disorders; Human Growth Hormone; Humans; Hypercalcemia; Insulin Resistance; Metabolic Diseases; Metformin; Nephrocalcinosis; Puberty; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 32879144
DOI: 10.1507/endocrj.EJ20-0291 -
BMC Medical Ethics Apr 2020Chemotherapy and/or radiotherapy treatments may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now...
BACKGROUND
Chemotherapy and/or radiotherapy treatments may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of therapies on future reproductive autonomy are a major concern. While a few options are open to post-pubertal patients, the only immediate option currently open to pre-pubertal girls is cryopreservation of ovarian tissue and subsequent transplantation. The aim of the study was to address a current gap in knowledge regarding the offer of fertility preservation by Ovarian Tissue Cryopreservation (OTC) for prepubescent girls with cancer, and to explore current practices and attitudes of Canadian, French and Moroccan pediatric heme oncologists. The comparative perspective is relevant since legal frameworks surrounding fertility preservation and funding offered by the healthcare system vary greatly.
METHODS
An online survey was sent to the 45 pediatric oncology centers in Canada, France and Morocco.
RESULTS
A total of 39 centers responded (86.6%). OTC is offered by almost all pediatric heme oncologists in France (98%), very few in Canada (5%), and none in Morocco (0%). For pediatric hematologists/oncologists who do not propose fertility preservation in Canada, the reasons are: the technique is still experimental (54%), it is not available locally (26%) and cost of the technique for the family (14%). 97% of Canadian and 100% of Moroccan pediatric hematologists/oncologists think OTC should be funded by the healthcare system as it is in France and in the province of Quebec in Canada.
CONCLUSIONS
The results of this study show tremendous diversity in the provision of OTC across countries, whereby its offer is correlated with legislation and funding. We argue that the current reality, in which this technology is often not offered to families, raises ethical issues related to justice and equity of access, as well as informed consent and future reproductive autonomy.
Topics: Canada; Child; Female; Fertility Preservation; France; Humans; Legislation as Topic; Male; Neoplasms; Oncologists; Quebec
PubMed: 32245465
DOI: 10.1186/s12910-020-00466-6