Endocrine Sequelae Research Articles

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

Endocrine Complications in Hepatic Glycogen Storage Diseases: A Long-term Perspective.

Patients with hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs. This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (one patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed. The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5 ± 1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR = 36.1; P-value < 0.001). Among 33 patients who reached final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0 ± 1.3 at the L-spine. This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Endocrine sequelae after pediatric craniopharyngioma treatment: a single-center retrospective cohort study.

Craniopharyngiomas (CP) are rare brain tumors with a low mortality rate, but with significant morbidity, in part due to the various long-term endocrine sequelae related to hypothalamic/pituitary deficiencies. Our objective was to assess the prevalence of endocrine dysfunction and outcome after treatment of CP at our institution and to apply the novel diagnostic criteria for hypothalamic syndrome (HS). In addition, we give an overview of treatments already attempted for hypothalamic obesity (HO). This retrospective cohort study included children treated and followed up for CP at the pediatric oncology and endocrinology department at University Hospitals Leuven between January 2000 and December 2023. Clinical and endocrine characteristics were collected during a five-year period following diagnosis of CP. The Müller radiological criteria and the novel diagnostic criteria for HS were applied. A brief literature review regarding treatments already attempted for HO was conducted. 15 patients with pediatric CP were included in the study, all of whom developed endocrine sequelae over time. Seven patients (47 %) presented with at least one hormonal deficit, and eight patients (53 %) developed panhypopituitarism over time. HO was clinically confirmed in nine patients (60 %). 10 patients (67 %) met the diagnostic criteria for HS. Currently, no overall effective treatment strategies are available for HO. Long-term endocrine sequelae and HO are highly prevalent in pediatric CP. Continuing multidisciplinary care to improve the quality of life of these patients is necessary. International cooperation and further long-term prospective trials for the treatment of HO are needed.

Is It Justified to Sacrifice the Pituitary Stalk During Craniopharyngioma Surgery? A Systematic Review and Meta-Analysis.

Pituitary stalk sacrifice is a surgical dilemma in craniopharyngioma surgery that needs a wise decision. To the authors' knowledge, this is the first study to conduct a meta-analysis of the current literature to assess if it is worth preserving the stalk during craniopharyngioma surgery or it is justified to sacrifice it. PubMed, Web of Science, and Embase databases were searched for craniopharyngioma studies till December 2021 that directly compared the endocrine sequelae of stalk sacrifice vs preservation in their patients. Odds ratio (OR) with 95% CI was used through fixed- and random-effects models. Fourteen studies with a total of 2074 patients met our inclusion criteria. The stalk was preserved in 925 patients (44.6%), was sacrificed in 1053 patients (50.8%), and was not identified intraoperatively or partially preserved, or the authors did not mention enough data for 96 patients (4.6%). Our study found that sacrifice of the pituitary stalk was associated with a significantly increased risk of endocrine dysfunction at the last follow-up (OR = 6.69, 95% CI = 3.36-13.35, P < .0001); however, it was not associated with a significant decrease in the risk of recurrence/progression of the disease (OR = 0.80, 95% CI = 0.60-1.06, P = .13). Pituitary stalk sacrifice significantly increased the risk of postoperative endocrine dysfunction without reducing the risk of progression or recurrence of craniopharyngioma. The ability to preserve the pituitary stalk intraoperatively is multifactorial, and stalk preservation is recommended whenever possible. Future prospective studies are recommended to assess the effect of confounding factors on the outcomes of stalk sacrifice/preservation.

Epidemiology of Endocrine Dysfunctions in Pediatric Patients with Previous Central Nervous System Infection: A Scoping Review of the Literature.

Purpose The incidence of endocrine sequelae following central nervous system (CNS) infections in pediatric age is not known. We conducted this scoping review to assess the incidence of endocrinological alterations in patients with prior CNS infections in pediatric age. Methods Our screening process included both randomized and non-randomized controlled trials. All types of observational studies, prospective and retrospective, have been included. Results Ten studies were included in our review. The cumulative number of patients in all of the studies was 211, the mean age of the population study was 4.9 (±5 years). The included papers described the following acute CNS infections: meningitis (nine studies reported eighty-five cases) and encephalitis (three studies described sixty-five cases). Two case reports and one retrospective study reported hypopituitarism as a consequence of Mycobacterium tuberculosis CNS infection. In five studies the patients developed endocrine comorbidities at the time of infection. Another study analyzed 49 young adults who previously had tuberculous meningitis at a mean age of 5.9 ± 5.0 years: seven patients had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia. Conclusion Standardized multidisciplinary follow-up and research of patients with prior CNS infection is crucial. Although pituitary reserve screening is not commonly performed in these patients, clinical and research centers should set up an endocrinological evaluation with monitoring of auxological parameters to detect the signs and symptoms of hypopituitarism early and to initiate the appropriate care in children with previous CNS infections.

RADT-03. IDENTIFYING BRAIN STRUCTURES LINKED TO RADIATION-INDUCED ENDOCRINE AND COGNITIVE SEQUELAE: A MULTI-CENTRE VOXEL-BASED ANALYSIS

Abstract BACKGROUND Radiotherapy (RT) is a common treatment for paediatric brain tumours. Despite advancements in techniques to mitigate RT-induced toxicity, almost two-thirds of patients develop long-lasting endocrine and cognitive sequalae. Image-based data mining (IBDM) is a voxel-based analysis tool that can identify dose-sensitive regions, supporting development of tailored radiation treatments for future patients that avoids these regions. We present the first IBDM study localising endocrine and cognitive effects in paediatric brain tumour patients. METHODS Imaging (MRI and CT) and clinical data were available for 261 children (146 medulloblastoma patients in centre A, 115 patients with mixed diagnoses in centre B). Outcomes were reported as Growth Hormone Deficiency (GHD, presence/absence, both centres) and processing speed (PS, continuous slope derived from a linear mixed-effects model, centre A). IBDM evaluated where dose was associated with outcome (p-value&amp;lt;0.01). Mean dose to this region was included in multivariable analysis adjusting for age, risk status, hydrocephalus status/management, and chemotherapy. RESULTS GHD was associated with dose to a region overlapping the pituitary and brainstem. In centre A, multivariable analysis revealed a 13(2-27)% average increase in GHD odds per 1Gy increase in dose, with an inverse effect for age. Center B showed a 8(4-13)% average increase for every 1Gy, with no other predictors. For PS, a central frontal region from the medial frontal lobes to the hypothalamus was identified (139 patients in centre A). Every 1Gy increase led to a -0.08(-0.20 – 0.04) PS change, with age and hydrocephalus management as contributing factors. CONCLUSION We identified a region (encompassing the pituitary and brainstem) associated with increased risk of GHD, that was consistent in two independent cohort analyses. Furthermore, PS decline was linked to dose to a frontal region. Minimising dose to these regions for future patients could reduce the risk of cognitive and endocrine sequelae.

Endocrine sequelae of adult recipients of hematopoietic stem cell transplantation

Endocrine sequelae of adult recipients of hematopoietic stem cell transplantation

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. To document endocrine sequelae and other late effects of all HSCT recipients. Retrospective review. Royal Children's Hospital Melbourne. 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. None. Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Long-term endocrine sequelae after hematopoietic stem cell transplantation in children and adolescents.

As the survival rate from pediatric cancers has increased significantly with advances in treatment modalities, long-term endocrine complications have also risen. This study investigated the frequencies and risks of endocrine sequelae in childhood cancer survivors who received hematopoietic stem cell transplantation (HSCT). This study included 200 pediatric patients who underwent HSCT. Clinical and endocrinological findings were collected retrospectively. The median follow-up duration after HSCT was 14 years. Endocrine complications occurred in 135 patients (67.5%). Children who underwent HSCT at pubertal age (n=100) were at higher risk of endocrine complications than those who received it at prepubertal age (79% vs. 56%, P=0.001). The most common complication was hypogonadism (40%), followed by dyslipidemia (22%). Short stature and diabetes mellitus were more prevalent in the prepubertal group, whereas hypogonadism and osteoporosis were more common in the pubertal group. Being female, pubertal age at HSCT, and glucocorticoid use were predictors of an increased risk for any complication. Radiation exposure increased the risk of short stature and hypothyroidism. Hypogonadism was significantly associated with being female, pubertal age at HSCT, and high-dose radiation. Pubertal age at HSCT also increased the risks of osteoporosis and dyslipidemia. This study demonstrates that long-term endocrine complications are common after HSCT in children and adolescents. Age at HSCT is a critical factor for endocrine complications after HSCT. These findings suggest that surveillance strategies for endocrine complications in childhood cancer survivors should be specified according to age at HSCT.

Long-term surveillance for endocrine sequelae after bone marrow transplantation

Long-term surveillance for endocrine sequelae after bone marrow transplantation

Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism.

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger post-operative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well.

The late effects of cranial irradiation in childhood on the hypothalamic–pituitary axis: a radiotherapist’s perspective

Brain tumours make up nearly one-third of paediatric malignancies. Over time, advancements in oncological treatments like radiotherapy have helped reduce normal-tissue toxicity when treating cancers in the brain. However, clinicians are still facing a trade-off between treatment efficacy and potential side effects. The aim of this review is to address the late effects of cranial irradiation on the neuroendocrine system and to identify factors that make patients more vulnerable to radiation-induced endocrine sequelae. Radiation damage to the hypothalamic-pituitary axis, which orchestrates hormone release, can lead to endocrinopathy; up to 48.8% of children who have undergone cranial irradiation develop a hormone deficiency. This may lead to further health complications that can appear up to decades after the last treatment, lowering the patients' quality of life and increasing long-term costs as lifelong hormone replacement therapy may be required. Growth hormone deficiency is the most common sequelae, followed by either thyroid or gonadotropic hormone deficiency. Adrenocorticotropic hormone deficiency tends to be the least common. Identified factors that increase the risk of late endocrine deficiency include total radiation dose, age at treatment, and time since last treatment. However, as there are various other factors that may potentiate the damage, a universal solution proven to be most effective in sparing the endocrine tissues is yet to be identified. Until then, accounting for the identified risk factors during treatment planning may in some cases help reduce the development of endocrine sequelae in childhood cancer survivors.

Endocrine Sequelae in 157 Pediatric Survivors of Hematopoietic Stem Cell Transplantation (HSCT).

Successful rates of hematopoietic stem cell transplantation (HSCT) face paralleled escalation of late endocrine and metabolic effects. This work aimed to characterize these sequelae distinguishing between the underlying pathologies and treatments received. A retrospective descriptive study was conducted in 157 children post-HSCT (hematopoietic pathology [N = 106], solid tumors [N = 40], and rare entities [N = 11]) followed at a single endocrine department between 2009 and 2019. Regression analysis was used to ascertain association. Of all patients, 58.7% presented with at least one endocrine abnormality. Endocrinopathies post HSCT were most frequently developed in lymphoblastic leukemia (60.5% of them), whereas myeloid leukemias had the fewest. A total of 64% of patients presented with primary hypogonadism, 52% short stature, and 20% obesity. Endocrinopathy was associated with older age at HSCT (9.78 years [6.25-12.25] vs 6.78 years [4.06-9.75]) (P < .005), pubertal Tanner stage V (P < .001), chronic graft-vs-host disease (GVHD) (P = .022), and direct gonadal therapy (P = .026). The incidence of endocrinopathies was higher in girls (15% more common; P < .02) and in patients who received radiotherapy (18% higher), steroids (17.4% increase), allogenic HSCT (7% higher), thymoglobulin, or cyclophosphamide. Those on busulfan presented with a 27.5% higher rate of primary hypogonadism (P = .003). More than half of children surviving HSCT will develop endocrinopathies. Strikingly, obesity has risen to the third most frequent endocrine disruption, mainly due to steroids, and partly adhering to the general population tendency. Lymphoblastic leukemia was the condition with a higher rate of endocrine abnormalities. Female sex, older age at HSCT, pubertal stage, allogenic transplant, radiotherapy, alkylating drugs, and GVHD pose risk factors for endocrine disturbances.

LINC-04. Optic pathway gliomas in children: an 18-year experience in a middle-income country

Abstract BACKGROUND: Optic pathway gliomas (OPGs) have favorable survival outcomes, but can have significant morbidity, from the tumor or from its treatment. This retrospective study sought to describe the clinical presentation and outcomes of children with OPGs at a tertiary center in a middle-income country. METHODS: Patients younger than 18 years diagnosed with OPGs between 2002-2020 at the Hospital Civil de Guadalajara in Mexico, were included. Survival analyses and logistic regression were used to determine risk factors for progression. RESULTS: Thirty patients were identified with a median age of six years. Common clinical characteristics at presentation included: visual accuracy impairment (40%), headache (23.3%), nystagmus (20%), endocrine disturbances (16.6%), and diencephalic syndrome (13%). Neurofibromatosis-1 was present in 23.3% of the patients. Eight patients underwent resection at diagnosis, 7 of them had secondary complications. One died during surgery due to catecholamine-resistant shock, and the other developed neuro-infection and died due to septic shock after surgery. Five children developed neurological or endocrine sequelae. Fifteen total patients received chemotherapy as their first line treatment. The 5-year progression-free survival was 77.9±10% and overall survival was 89.5±5%. Patients who received chemotherapy or targeted therapy as the first line of treatment had higher PFS compared to those who received other therapies (p=0.03). The patients who received surgery as first-line treatment had a 3.1 times greater risk of achieving a Lansky/Karnofsky score of fewer than 90 points 6 months after diagnosis (p=0.006). Ten patients had pre- and post-treatment ophthalmologic assessment, either visual acuity or visual evoqued potentials. Five had no changes and 5 showed improvement after treatment. CONCLUSIONS: These results show inferior outcomes compared to high-income countries, influenced importantly due to morbidity after surgical resection. These data can be used to prospectively optimize treatment at our institute and other middle-income countries through a multidisciplinary neuro-oncology team.

GCT-01. Pediatric intracranial germ cell tumors and primary polyuria-polydipsia syndrome: a 13-year single institutional experience

Abstract Intracranial germ cell tumors (IGCTs) represent about 4% of all childhood brain tumors. They are common in both the pineal and pituitary regions and sometimes they can be bifocal. Suprasellar and bifocal IGCTs usually present stereotypical symptoms, including primary polyuria-polydipsia syndrome (PPS). Consolidated IGCTs’ therapy is based on the International Society of Pediatric Oncologic (SIOP) CNS GCT II protocol consisting of primary pre-radiation chemotherapy combining etoposide, carboplatin and/or cisplatin and ifosfamide. PPS management in these patients requires monitoring of electrolytes and fluids during chemotherapy, especially for cisplatin and/or ifosfamide-based cycles, for which hyperhydratation is required. We report the results of our single-center cohort of patients with IGCTs treated between 2008 and 2021, focusing on the clinical presentation, treatment and long-term follow-up. Thirty-one patients were analyzed (median age=13 years, 87% male). Twelve children (39%) presented a PPS and needed desmopressin treatment, maintained at long-term follow-up data update in all. Over these PPS patients, 6 had bifocal germinomas, 4 suprasellar germinomas, 1 metastatic germinoma and 1 non-germinomatous IGCT. Eleven PPS children (92%) received cisplatin and/or ifosfamide-based chemotherapy: all of them had optimal biochemical urine and blood investigations before, during and after chemotherapy. None of them presented serious complications during treatment. After a median follow-up of 5 years, two patients (6.5%) died (1 IGCT-related, 1 non-cancer related) and one had a second malignancy (parotid gland mucoepidermoid carcinoma, 6 years after IGCT diagnosis). Childhood IGCTs have an excellent prognosis, but present a significant risk of long-lasting severe endocrine sequelae which may be worsened by the primary oncological strategy, requiring careful management of complications related to fluid and electrolytes disturbances. In order to avoid post-treatment pituitary insufficiency, guidelines for diabetes insipidus management when cisplatin and/or ifosfamide-based protocols are used should be established and all patients should receive meticulous endocrine follow-up.

Endocrine Late Effects in Childhood Cancer Survivors.

Simple SummaryRecent advances in cancer treatment have led to improved survival, with an exponential increase in sequelae among survivors. Around 50% of survivors will experience at least one hormonal disorder, with radiotherapy, hematopoietic stem cell transplantation, and alkylating chemotherapy being the most frequently related. Therefore, lifelong monitoring of childhood cancer survivors at risk is paramount. With this review, we describe in detail the most prevalent endocrine sequelae, considering new approaches such as proton beam therapy and immune-related endocrinopathies with the advent of precision oncology treatment. We hope to encourage oncologists and endocrinologists to develop early detection guidelines that minimize sequelae and have a positive impact on their quality of life.Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. Multiple predisposing factors for endocrine sequelae have been identified, including age at diagnosis, treatment received, radiation, tumor type, and genetic polymorphisms, which could explain the individual predisposition to develop drug toxicity. Novel agents targeting tumor growth and immune checkpoint inhibitors have recently become the cornerstone for the treatment of different cancers, triggering a myriad of immune-related endocrinopathies. Endocrine sequelae of cancer therapy will have an impact on not only childhood but also on the survival and quality of life of these highly complex patients. Therefore, lifelong monitoring of childhood cancer survivors at risk of endocrine diseases is paramount. Encouraging oncologists and endocrinologists to develop new follow-up and early detection guidelines that minimize sequelae among these patients has become a priority, promoting integration between pediatric and adult units since many sequelae may manifest only after years to decades of follow-up.

Diencephalic Syndrome Due to Optic Pathway Gliomas in Pediatric Patients: An Italian Multicenter Study.

Diencephalic syndrome (DS) is a rare pediatric condition associated with optic pathway gliomas (OPGs). Since they are slow-growing tumors, their diagnosis might be delayed, with consequences on long-term outcomes. We present a multicenter case series of nine children with DS associated with OPG, with the aim of providing relevant details about mortality and long-term sequelae. We retrospectively identified nine children (6 M) with DS (median age 14 months, range 3–26 months). Four patients had NF1-related OPGs. Children with NF1 were significantly older than sporadic cases (median (range) age in months: 21.2 (14–26) versus 10 (3–17); p = 0.015). Seven tumors were histologically confirmed as low-grade astrocytomas. All patients received upfront chemotherapy and nutritional support. Although no patient died, all of them experienced tumor progression within 5.67 years since diagnosis and were treated with several lines of chemotherapy and/or surgery. Long-term sequelae included visual, pituitary and neurological dysfunction. Despite an excellent overall survival, PFS rates are poor in OPGs with DS. These patients invariably present visual, neurological or endocrine sequelae. Therefore, functional outcomes and quality-of-life measures should be considered in prospective trials involving patients with OPGs, aiming to identify “high-risk” patients and to better individualize treatment.

Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes

PurposeThe challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population.MethodsRetrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019.ResultsMedian age at diagnosis was 1.81 years [IQR, 0.98–3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74–23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8–86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up.ConclusionYoung children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children.

Exercise as a Moderator of Persistent Neuroendocrine Symptoms of COVID-19.

Precipitated by chronic psychological stress, immune system dysregulation, and a hyperinflammatory state, the sequelae of postacute COVID-19 (long COVID) include depression and new-onset diabetes. We hypothesize that exercise counters the neuropsychiatric and endocrine sequelae of long COVID by inducing the release of circulating factors that mediate the anti-inflammatory response, support brain homeostasis, and increase insulin sensitivity.

The clinical features that contribute to poor bone health in young Australians living with cystic fibrosis: A recommendation for BMD screening

For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Zscore and potential risk factors was conducted using DXA and historical data. The main predictor of future BMD was the previous BMD Zscore (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.