Burden, Mortality, and Follow-Up Gaps in Paediatric Endocrine Care: Five Years of Experience (2020–2025) from a Tertiary Hospital in South-East Nigeria

Burden, Mortality, and Follow-Up Gaps in Paediatric Endocrine Care: Five Years of Experience (2020–2025) from a Tertiary Hospital in South-East Nigeria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Burden, Mortality, and Follow-Up Gaps in Paediatric Endocrine Care: Five Years of Experience (2020–2025) from a Tertiary Hospital in South-East Nigeria Chisom Adaobi Nri-Ezedi, Thomas Obiajulu Ulasi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6646189/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Paediatric endocrine disorders are an emerging concern in sub-Saharan Africa, yet they remain under-recognised due to the predominant focus on infectious diseases. Inadequate specialist services and poor follow-up systems contribute to late presentation and adverse outcomes. This study prospectively reviewed the clinical spectrum, mortality, and follow-up challenges of paediatric endocrine cases managed in the first dedicated endocrinology unit at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nigeria, over a five-year period. Methods: A prospective review was conducted from February 2020 to February 2025, enrolling children aged 0–18 years diagnosed with endocrine or metabolic disorders. Clinical data collected included demographics, diagnoses, and follow-up outcomes, categorised as adherent, lost to follow-up, or deceased. Descriptive statistics were used to summarise patient characteristics, and associations between clinical variables and outcomes were analysed using chi-square or Fisher’s exact tests as appropriate. Results: Fifty-five children were enrolled (median age: 9 years; range: 7 days to 17 years; 56.4% female). The most common diagnoses were type 1 diabetes mellitus (29.1%) and thyrotoxicosis (21.8%), followed by congenital adrenal hyperplasia (10.9%) and precocious puberty (9.1%). Annual case numbers increased progressively, peaking in 2023. Overall mortality was 7.3%, with deaths predominantly due to diabetic ketoacidosis and neonatal endocrine emergencies (Neonatal thyrotoxicosis and hyperinsulinemic hypoglycaemia). Notably, 69.1% of patients were lost to follow-up, while only 25.5% remained in active care by the end of the study period. Conclusion: The establishment of the paediatric endocrinology unit at NAUTH has enhanced case detection and management of childhood endocrine disorders in southeastern Nigeria. However, the high rates of loss to follow-up and preventable deaths highlight persistent systemic barriers, including financial constraints and limited healthcare access. Interventions aimed at strengthening follow-up systems, improving caregiver education, and reducing the cost burden of chronic care are urgently needed to improve long-term outcomes in this resource-limited setting. Paediatric endocrinology type 1 diabetes mellitus thyrotoxicosis follow-up attrition sub-Saharan Africa resource-limited settings Figures Figure 1 Introduction Paediatric endocrine disorders, though less prevalent than infectious diseases, represent a significant but under-recognised cause of morbidity and mortality in low- and middle-income countries (LMICs), including Nigeria [ 1 ]. Historically, the overwhelming burden of communicable diseases and malnutrition in sub-Saharan Africa overshadowed the recognition and management of chronic non-communicable diseases in children [ 2 ]. Consequently, paediatric endocrine disorders often go undiagnosed or are diagnosed late, leading to preventable complications and mortality [ 3 ]. The subspecialty of paediatric endocrinology is still evolving in Nigeria, with fewer than 40 trained specialists serving over 90 million children as of 2022 [ 3 ]. This glaring workforce gap is compounded by the scarcity of diagnostic laboratories, limited access to essential medications, and high out-of-pocket healthcare costs, all of which pose substantial barriers to timely diagnosis and long-term management [ 3 , 4 ]. Despite these challenges, recent data suggest that paediatric endocrine disorders in Nigeria may be more common than previously acknowledged, with studies reporting a wide spectrum of conditions including rickets, type 1 diabetes mellitus (T1DM), and thyroid disorders [ 1 , 2 ]. Emerging evidence indicates a shifting epidemiological pattern, with an increasing burden of autoimmune and hormonal disorders such as Type 1 diabetes mellitus (T1DM) [ 5 , 6 ]. Alarmingly, most children with T1DM in Africa present in diabetic ketoacidosis (DKA), a life-threatening emergency associated with a mortality rate of up to 7%, far exceeding the < 1% reported in high-income countries [ 7 , 8 ]. Similar trends have been noted for other endocrine emergencies, including adrenal crises and severe neonatal thyrotoxicosis [ 1 , 3 , 9 ]. Beyond acute presentations, maintaining long-term follow-up remains a major challenge in Nigeria. Studies have documented follow-up attrition rates as high as 60–70%, driven by poverty, limited health insurance coverage, and lack of caregiver education [ 1 , 3 ]. Poor adherence to treatment, particularly for chronic conditions like T1DM, further compounds the risk of adverse outcomes [ 4 ]. The Global Pediatric Endocrinology and Diabetes (GPED) group has identified these gaps—delayed diagnosis, treatment inaccessibility, and poor follow-up—as critical barriers to optimal care in LMICs [ 9 , 10 ]. While data from southwestern Nigeria have highlighted these trends [ 1 , 2 ], there remains a paucity of published evidence from southeastern Nigeria, where access to specialist services is similarly limited. Understanding the clinical spectrum, outcomes, and system-level challenges in this region is essential for guiding local and national strategies to strengthen paediatric endocrine services. This study, therefore, aimed to review the clinical profile, mortality patterns, and follow-up outcomes of children managed in the first paediatric endocrinology unit established at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, over a five-year period. By contextualising these findings within national and international trends, we sought to provide evidence that could inform future service planning, policy advocacy, and research priorities aimed at improving paediatric endocrine care in resource-limited settings like Nigeria. Methods Study Design and Setting We conducted a prospective descriptive review of paediatric endocrine cases managed at Nnamdi Azikiwe University Teaching Hospital (NAUTH), a tertiary referral centre located in Nnewi, Anambra State, Nigeria. NAUTH serves the southeastern region of Nigeria, providing specialist paediatric services through a multidisciplinary team. The hospital’s dedicated paediatric endocrinology clinic was established in 2019 and began full operations in 2020. This study prospectively followed all eligible patients managed in the unit between February 2020 and February 2025. Study Population and Inclusion Criteria Eligible participants were all children aged 0–18 years who were newly diagnosed with or being managed for endocrine or metabolic disorders in the paediatric endocrinology unit during the study period. Both newly referred and existing follow-up patients attending outpatient clinics or admitted to the paediatric ward under the endocrine team’s care were included. Patients managed for non-endocrine conditions were excluded. Data Collection and Follow-Up Procedures Data for this study were prospectively collected using a structured data collection form specifically designed for the purpose of the review. At the point of first contact, relevant clinical information was documented, including the patient’s demographic details such as age and sex, the clinical diagnosis based on thorough assessment supported by available laboratory and imaging investigations, as well as the year of presentation. All enrolled patients were subsequently followed up throughout the study period during routine clinic visits, hospital admissions, or via telephone contact when necessary. Patient outcomes were prospectively monitored and categorised as either adherent—defined as actively attending scheduled follow-up visits and adhering to treatment recommendations; lost to follow-up—defined as failure to attend clinic for more than six months or being unreachable; or deceased—defined as a confirmed death documented in clinic or hospital records. In cases where patients defaulted on follow-up appointments, efforts were made to contact their families by telephone to clarify their status. These outcomes were continuously updated in the database throughout the five-year review period to ensure that the data reflected the most current follow-up status of each patient. Statistical Analysis All collected data were entered into Microsoft Excel and subsequently analysed using Python (pandas library) to ensure accurate data management and statistical processing. Continuous variables, such as age, were summarised as mean and standard deviation (SD) for normally distributed data, or as median with interquartile range (IQR) for data that were not normally distributed. Categorical variables, including sex, clinical diagnoses, and follow-up outcomes, were presented as frequencies and percentages.To explore relationships between variables, cross-tabulations were conducted. The chi-square test was used to assess associations between categorical variables, such as diagnosis and follow-up status. Where cell counts were small and the assumptions for chi-square were not met, Fisher’s exact test was applied.For continuous variables, such as age comparisons across outcome groups (adherent, lost to follow-up, or deceased), independent samples t-tests were used if the data met normality assumptions. In cases where data were skewed or non-normally distributed, the Kruskal-Wallis test was employed to compare differences across multiple groups. All statistical tests were two-tailed, and a p-value of less than 0.05 was considered statistically significant. This threshold was applied to determine the strength of associations and differences observed in the study. Ethical Considerations We ensured confidentiality by using study codes and aggregating data for publication. This work was carried out in accordance with the Declaration of Helsinki. Results Patient Demographics Over the five-year study period, a total of 55 children with endocrine disorders were enrolled and followed at the paediatric endocrinology unit of NAUTH. The median age at first presentation was 9.0 years (range: 7 days to 17 years), with a bimodal distribution, reflecting peaks in infancy/toddlerhood and early adolescence. Female patients accounted for 56.4% (n = 31), while 43.6% (n = 24) were male, giving a female-to-male ratio of approximately 1.3:1. The distribution of diagnoses varied by sex; for instance, all patients diagnosed with congenital adrenal hyperplasia (CAH) were genotypic females, and the majority of thyrotoxicosis cases (83%) occurred in adolescent girls (Table 1). Trends in Case Presentation An upward trend in the annual number of cases was observed throughout the study period. In 2020, the first full year of clinic operation, only four new cases were documented. This number gradually increased to seven cases in 2021, eleven in 2022, and peaked at seventeen in 2023, representing more than a four-fold increase from the initial year. The numbers slightly declined to nine cases in 2024, and seven cases were recorded in the first month of 2025 (Figure 1). Spectrum of Endocrine Disorders Table 1 summarizes the clinical diagnoses of the 55 patients. A wide range of 17 distinct diagnoses was recorded, reflecting the broad spectrum of paediatric endocrinology. The most common diagnosis was type 1 diabetes mellitus (T1DM), accounting for 16 cases (29.1% of the cohort). Nearly all 14 out of 16 (87.5%) presented with diabetic ketoacidosis (DKA). Thyrotoxicosis (hyperthyroidism) was the second most frequent diagnosis with 12 cases (21.8%), most of whom were adolescent girls (83.3%). Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was diagnosed in 6 children (10.9%); all were phenotypic females who had presented in early infancy with virilized genitalia. Precocious puberty was noted in 5 patients (9.1%), including 3 girls and 2 boys who developed secondary sexual characteristics before age 8 (girls) or 9 (boys). These cases were being evaluated for central precocious puberty and treated with GnRH analogues when feasible. Less common disorders included Cushing syndrome (2 cases, 3.6%), both of which were iatrogenic Cushingoid features from prolonged steroid use for nephrotic syndrome and asthma – these patients were referred for growth failure and obesity. Gynecomastia was the reason for referral in 2 peri-pubertal boys (3.6%); they were evaluated for hormonal causes but considered likely pubertal gynecomastia and were managed conservatively. Rickets (nutritional vitamin D–deficiency rickets and Vitamin D Resistant Rickets Type 1B) was diagnosed in 2 boys (3.6%), both under 5 years old, presenting with delayed motor milestones and leg deformities. A variety of single-case diagnoses (each 1.8% of the total) were recorded namely achondroplasia, micropenis, Turner syndrome, primary hypothyroidism, hypopituitarism, growth hormone deficiency, labial, pseudohypoparathyroidism type 1a, and hyperinsulinemic hypoglycaemia. Table 1. Spectrum of Diagnoses, Sex Distribution, and Follow-Up Outcomes of Paediatric Endocrine Patients Managed at NAUTH, 2020–2025 Diagnosis n (% of total) Female Male Lost to Follow-Up Adherent Deceased Type 1 Diabetes Mellitus (T1DM) 16 (29.1) 8 8 11 3 2 Thyrotoxicosis (Hyperthyroid) 12 (21.8) 10 2 7 4 1 Congenital Adrenal Hyperplasia 6 (10.9) 6 0 3 3 0 Precocious Puberty 5 (9.1) 3 2 4 1 0 Cushing syndrome 2 (3.6) 1 1 2 0 0 Gynecomastia 2 (3.6) 0 2 2 0 0 Rickets (Vitamin D deficiency) 2 (3.6) 0 2 1 1 0 Achondroplasia (dwarfism) 1 (1.8) 0 1 1 0 0 Constitutional delay of growth & puberty (CDGP) 1 (1.8) 0 1 0 1 0 Growth hormone deficiency 1 (1.8) 0 1 1 0 0 Hyperinsulinemic hypoglycaemia 1 (1.8) 0 1 0 0 1 Hypopituitarism 1 (1.8) 1 0 1 0 0 Hypothyroidism 1 (1.8) 0 1 0 1 0 Labial adhesion 1 (1.8) 1 0 1 0 0 Micropenis 1 (1.8%) 0 1 1 0 0 Pseudohypoparathyroidism type 1a 1 (1.8%) 0 1 1 0 0 Turner syndrome 1 (1.8%) 1 0 1 0 0 Outcomes and Follow-Up Status By the end of the five-year review period, patient outcomes were categorised into three groups: adherent (those actively attending follow-up clinics), lost to follow-up (those who defaulted for more than six months and were unreachable), and deceased. Overall, only 14 patients (25.5%) remained in active follow-up and under care at NAUTH by 2025. In contrast, a substantial 38 patients (69.1%) were lost to follow-up at some point after their initial diagnosis. In the majority of these cases, families discontinued clinic visits and could not be reached despite repeated contact attempts, reflecting a concerningly high attrition rate. Additionally, there were four documented deaths (7.3% mortality) within the cohort. Two of these deaths occurred in children with type 1 diabetes mellitus (T1DM): a 6-year-old girl and a 7-year-old boy, both presenting with severe diabetic ketoacidosis (DKA). The remaining two fatalities involved endocrine emergencies in infancy. One was a 3-month-old boy with neonatal thyrotoxicosis (secondary to maternal Graves' disease), who succumbed to heart failure. The other was a 6-month-old boy with hyperinsulinemic hypoglycaemia, who died from hypoglycaemic brain injury. These outcomes underscore the life-threatening nature of delayed or suboptimal management of critical endocrine conditions. The distribution of follow-up outcomes across diagnostic categories is detailed in Table 1. Among the 16 children with T1DM, only 3 (18.8%) remained in care, while 11 (68.8%) were lost to follow-up and 2 (12.5%) had died. Similarly, of the 12 patients with thyrotoxicosis, 4 (33%) remained adherent, 7 (58%) were lost to follow-up, and 1 (8.3%) had died. Children with congenital adrenal hyperplasia (CAH) showed relatively better retention, with 3 out of 6 (50%) still engaged in follow-up and none deceased, although 3 (50%) were lost to follow-up. Conversely, 100% of patients with Cushing syndrome, gynecomastia, Turner syndrome, hypopituitarism, micropenis, labial adhesion, pseudohypoparathyroidism, and achondroplasia defaulted after their initial visits. Among the five cases of precocious puberty, four (80%) were lost to follow-up, with only one patient continuing therapy. Statistical analysis revealed no significant difference in loss to follow-up by sex (67% in females vs 70% in males, p = 0.99) or by diagnostic category, as attrition was consistently high across all groups. Additionally, age did not significantly influence follow-up status, with both adherent and non-adherent patients having a median age of approximately 10 years (p = 0.10). Discussion This five-year review provides valuable insight into the profile and fate of children with endocrine disorders at a tertiary hospital in South-Eastern Nigeria. To our knowledge, it is among the first reports from this region, complementing previous studies from South-Western Nigeria and sub-Saharan Africa. The range of conditions seen at NAUTH reflects both common endocrine diseases and rare disorders. Type 1 diabetes mellitus was the single most common diagnosis (29% of cases), which is consistent with an increasing trend of paediatric diabetes across Africa [3,6]. Our finding aligns with a multi-center Nigerian survey that identified type 1 diabetes as a major component of paediatric endocrine practice nationwide. In earlier Nigerian case series a decade ago, diabetes contributed a smaller share (around 12–15%) [1,2]. The higher proportion in our 2020s data likely reflects both real incidence growth, improved detection and post COVID-19 sequalae [3,6]. Notably, nearly all our diabetic patients presented with DKA, similar to reports that 70–80% of African children initially present in ketoacidosis[5]. Two of these children died, further emphasizing that even with treatment, African paediatric DKA case fatality ~7% remains far above the ~0.5–2% reported in developed countries [8]. This calls for improved DKA management protocols and possibly earlier diagnosis of diabetes (e.g., through awareness campaigns to reduce delay from symptom onset to hospital). Thyroid disorders, particularly hyperthyroidism (Graves’ disease), formed the second largest group (21.8%). This is noteworthy because earlier studies from Nigeria reported thyroid disorders in only ~6–15% of cases [1,2]. The higher proportion at NAUTH might be due to regional differences or a rising incidence of autoimmune thyroid disease [11]. Many of our thyrotoxicosis patients were adolescent girls, a demographic known to be at risk for Graves’ disease. One case was an infant with neonatal thyrotoxicosis, an entity caused by transplacental maternal TSH-receptor antibodies – a reminder of the need for maternal thyroid screening in pregnancy. Unfortunately, that infant succumbed, underscoring that neonatal thyrotoxicosis can be life-threatening if not recognized and aggressively treated. Our data suggest thyroid disorders are an important part of the paediatric endocrine spectrum in this region [11], meriting increased awareness among clinicians and earlier referral for symptoms like goiter, weight loss, or rapid heartbeat in children. Our series had fewer cases of rickets (only 2 cases, 3.6%) compared to the strikingly high rates reported in earlier Nigerian studies (45–56% of cases) [1,2]. Rickets was the leading diagnosis in those studies, reflecting widespread vitamin D deficiency and nutritional calcium deficiency in young children. The lower proportion at NAUTH could be due to differences in study populations or time period. By 2020s, there may be modest improvements in nutrition and vitamin D supplementation in our catchment area, or rickets cases might be managed by general pediatricians without referral to endocrinology, thus underrepresented in our review. Nonetheless, rickets remains a concern; it is a preventable condition and its continued presence indicates ongoing public health needs in nutrition [1]. The observed mortality rate of 7.3% (4 deaths among 55 patients) is higher than the 2.5% reported in Osogbo[2] and the 1% reported in Ibadan [1]. This difference could be due to our smaller sample size or a true difference in case mix. It is possible that our mortality figure underestimates true mortality, as many patients were lost to follow-up – some of those might have died outside the hospital. Unfortunately, without a robust patient tracking system or death registry linkage, we cannot ascertain outcomes for the majority who defaulted. What is clear is that the deaths that did occur were largely preventable with optimal care. Type 1 diabetes, for example, should not be a death sentence for a child; yet in Nigeria and similar contexts, survival is jeopardized by late presentation and inadequate treatment. A study by Umar (2023)[12] noted that African children with T1DM face numerous management challenges, leading to poor outcomes. Improving acute management protocols (DKA treatment per international guidelines and ensuring availability of medications (insulin, anti-thyroid drugs, etc.) could reduce such fatalities. One of the most concerning findings in this study was the nearly 70% loss to follow-up rate, affecting all age groups and diagnoses. This highlights systemic barriers such as financial hardship, limited specialist access, and poor caregiver understanding of chronic disease management. In Nigeria, most families rely on out-of-pocket payments, with low health insurance coverage, making long-term treatment like insulin or hormone therapy financially unsustainable for many [3,4]. Similar high attrition rates have been reported in other centres, including Lagos State University Teaching Hospital and Uniosun Teaching Hospital, where financial constraints and poor health literacy were identified as key drivers of discontinuation [1,2]. Left unchecked, this undermines treatment success and increases the risk of preventable deaths, such as those seen from diabetic ketoacidosis in this and other African studies [7]. Addressing this challenge requires health system reforms to improve access and affordability, such as including endocrine medications in health insurance packages, providing subsidies for essential care, and implementing better patient tracking and education systems [3,9]. Based on our findings, several practical steps could improve paediatric endocrine care at NAUTH and similar centres. First, strengthening follow-up retention is essential. Measures such as SMS reminders, flexible scheduling, and telemedicine could help reduce attrition, especially for families travelling long distances. Reducing financial barriers is equally critical; inclusion of paediatric endocrine medications in national insurance schemes and subsidised drug access—similar to HIV or TB models—could significantly improve adherence. Hospital authorities and NGOs should consider supporting indigent patients with essential medications. Equally important is parent education at diagnosis. Families must clearly understand the chronic nature of these conditions and the consequences of treatment interruption. Peer support groups may also enhance engagement, particularly for families managing conditions like diabetes. Our findings also support the urgent need for newborn screening programmes, particularly for CAH and congenital hypothyroidism[13]. Despite being standard practice in many countries, such screening is largely absent in Nigeria. Pilot programs at tertiary centres could serve as a starting point. Finally, increasing the number of trained specialists and strengthening referral networks will ensure timely diagnosis and care. Continued medical education for general paediatricians and the development of satellite or outreach clinics may decentralise care, reduce delays, and improve long-term outcomes. A key strength of this study is its ability to shed light on paediatric endocrine disorders in an under-reported region of Nigeria. By using real-world clinical data collected over five years, it captures meaningful trends during the formative period of NAUTH’s paediatric endocrine service. The inclusion of all presenting cases, regardless of diagnosis, provides a comprehensive snapshot of the diverse spectrum of endocrine conditions encountered in routine practice—extending beyond the more commonly reported disorders. Additionally, the study quantified the significant follow-up gap, an issue often overlooked in similar reports. However, the study has notable limitations. The high rate of loss to follow-up introduces uncertainty about the true long-term outcomes for many patients. Furthermore, the study did not evaluate key contextual factors such as socioeconomic status, caregiver education, or healthcare access, which likely influenced follow-up adherence and mortality. Finally, the role of unmeasured confounders—such as variations in disease severity, treatment practices, and family support—cannot be fully ruled out. In conclusion, this five-year review demonstrates that paediatric endocrine disorders, once considered rare in Nigeria, are in fact a significant and growing concern. The increasing number of diagnoses at NAUTH over time reflects improved clinical awareness and service development. However, the persistently high mortality in acute cases—particularly diabetic ketoacidosis—and the alarming rate of loss to follow-up expose deep systemic weaknesses in chronic care delivery. Addressing these gaps requires interventions that go beyond diagnosis alone. Ensuring uninterrupted access to essential medications and therapies through healthcare financing reforms, insurance coverage, or targeted support programmes is critical. Strengthening follow-up systems—through patient navigation services, community outreach, or digital health platforms—will also be essential to retain patients in long-term care. Advancing these efforts is key to improving outcomes for children with endocrine disorders in Nigeria and achieving greater health equity for all children living with chronic illnesses. Declarations Authorship Contributions C.A.N. conceptualized the study, designed the methodology, conducted statistical analyses, and drafted the manuscript. T.O.U. provided critical revisions, validated clinical interpretations, and contributed to manuscript editing. All authors reviewed and approved the final version of the manuscript for submission. Human Ethics and Consent to Participate declarations Ethical approval was obtained from the Anambra State Ministry of Health Research Ethics Committee, Awka, Anambra State, Nigeria. Written informed consent was obtained from the parents or legal guardians of all participants. Assent was also obtained from children aged 7 years and above, in accordance with institutional and national ethical guidelines. All procedures involving human participants were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki. Clinical trial number: Not applicable Consent to Publish declaration: Not applicable Conflict of Interest Statement The authors declare that there are no conflicts of interest regarding the publication of this paper. Funding Statement This research was fully funded by the authors without external financial support. No grants or institutional funding were received, and all study-related expenses were covered personally by the authors. References Jarrett O, Ogubosi B, Ayoola O, PAEDIATRIC ENDOCRINE DISORDERS AT THE UNIVERSITY COLLEGE HOSPITAL IBADAN. 2002–2009. 2013 [cited 2025 Mar 1];11:96–101. Available from: https://aipmed.org/?page_id=1400 Oluwayemi IO, Oyedeji OA, Adeniji EO, Afolabi AA, Ayeni TO. Ten-Year Review of Paediatric Endocrine Disorders at Uniosun Teaching Hospital, Osogbo, Nigeria. West Africa Journal of Medicine [Internet] 2021 [cited 2025 Mar 3];38:1114–9. Available from: https://www.researchgate.net/publication/357225658_Ten-Year_Review_of_Paediatric_Endocrine_Disorders_at_Uniosun_Teaching_Hospital_Osogbo_Nigeria Yarhere I, Tamunopriye J. Paediatric endocrinology and diabetes mapping and services in Nigeria: A decade after. African Journal of Diabetes medicine [Internet] 2022 [cited 2025 Mar 3];30:2022. Available from: https://www.africanjournalofdiabetesmedicine.com/articles/paediatric-endocrinology-and-diabetes-mapping-and-services-in-nigeria-a-decade-after-87230.html Eyong M, Nsa E, Etuk I. Pediatric endocrinology practice in Nigeria: Challenges and way forward. Niger J Med. 2020;29:542. Ahmed AM, Khabour OF, Ahmed SM, Alebaid IA, Ibrahim AM. Frequency and severity of ketoacidosis at diagnosis among childhood type 1 diabetes in Khartoum state, Sudan. Afr Health Sci [Internet] 2020 [cited 2025 Mar 3];20:841. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7609092/ Nri-Ezedi CA, Ulasi TO, Okeke KN, Okonkwo IT, Echendu ST, Agu NV, A SURGE OF TYPE 1 DIABETES MELLITUS AMONG NIGERIAN CHILDREN DURING THE COVID-19 PANDEMIC. Ann Ib Postgrad Med [Internet] 2022 [cited 2024 Jul 28];20:58. Available from: /pmc/articles/PMC10061673/. Murunga AN, Owira PMO. Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa? Trop Med Int Health [Internet] 2013 [cited 2025 Mar 3];18:1357–64. Available from: https://pubmed.ncbi.nlm.nih.gov/24112393/ Shimelash RA, Belay GM, Aknaw W, Shibabaw AT, Adebabay AA, Gedefaw GD, et al. Incidence and predictors of mortality in children with diabetic ketoacidosis in the comprehensive specialized referral hospitals of West Amhara Region, Northwest Ethiopia: a retrospective follow-up study. Front Clin Diabetes Healthc. 2023;4:1204133. Zacharin M, Chanoine JP, Cassorla F, Brink S, Hanas R, Fideleff HL et al. Promoting Excellence in the Care of Pediatric Endocrine Diseases in the Developing World. Pediatrics [Internet] 2013 [cited 2025 Mar 3];131:e573–8. Available from: /pediatrics/article/131/2/e573/31882/Promoting-Excellence-in-the-Care-of-Pediatric Home | GPED [Internet]. [cited 2025 May 12];Available from: https://www.globalpedendo.org/ Ndubuisi CA, Ohaegbulam SC, Ejembi GO. Paediatric brain tumours managed in Enugu, Southeast Nigeria: Review of one centre experience. Niger Postgrad Med J. 2018;25:186–90. Umar UI. Spectrum of Pediatric Endocrine Disorders at the Aminu Kano Teaching Hospital, Kano, Northwestern Nigeria: a five-year review. Pyramid Journal of Medicine [Internet] 2023 [cited 2025 Mar 3];6:315. Available from: https://africa.pagepress.net/pjm/article/view/315 Yarhere IE, Jaja T, Briggs D, Iughetti L. Newborn screening in Nigeria: will incorporating congenital hypothyroidism with sickle cell disease improve neonatal screening programme? Acta Bio Medica: Atenei Parmensis [Internet] 2019 [cited 2025 Mar 3];90:316. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6776226/ Additional Declarations No competing interests reported. Supplementary Files working1.csv Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 13 Jun, 2025 Editor invited by journal 23 May, 2025 Editor assigned by journal 23 May, 2025 Submission checks completed at journal 19 May, 2025 First submitted to journal 19 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6646189","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471137693,"identity":"4f0a44a0-5052-4392-9017-65f625233581","order_by":0,"name":"Chisom Adaobi Nri-Ezedi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie3QMUvEMBTA8RcCueVJ1xzI5SukOMgh4leJCLoodCpuVyiky8GtHf0K4hfI8aDTcbd2cKgITg4db1C0OR1bvVEw/yHNkB8vKUAo9GfTX6trARC46PZiT7Is9yffkOPu+wuJCieebxOYqCK/p1P7eKgKYaBNCY6ju14iV2YUrzQcsXmV0I19QZYLx8o1wbRsBl5hxDjTH+e5vNYdIeR8lPEDS6Br10+ixhOYWfWqadoR4cn7T0TupoBBiZpYR5ALx5knm6z/LfWT9SQu8TJZzteEkgvTba5Q1wN/bHFRjbM3UKqgh3ab0plaVHGzTU8metN/MQDWM96fRZBmgAwXDU0JhUKhf9Ynrw1W2tGS3qUAAAAASUVORK5CYII=","orcid":"","institution":"Nnamdi Azikiwe University","correspondingAuthor":true,"prefix":"","firstName":"Chisom","middleName":"Adaobi","lastName":"Nri-Ezedi","suffix":""},{"id":471137694,"identity":"3033cc7a-5607-4609-9fbf-5a5224e57535","order_by":1,"name":"Thomas Obiajulu Ulasi","email":"","orcid":"","institution":"Nnamdi Azikiwe University","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"Obiajulu","lastName":"Ulasi","suffix":""}],"badges":[],"createdAt":"2025-05-12 11:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6646189/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6646189/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84812480,"identity":"9b2a4540-26c8-44e2-8c32-af49aeebb942","added_by":"auto","created_at":"2025-06-17 15:03:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60115,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative number of paediatric endocrine cases seen at NAUTH (2020–2025)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6646189/v1/2c05c78a7d4cebe86c7fbe58.png"},{"id":84813672,"identity":"23977502-6281-4559-892b-a5d95ecb37df","added_by":"auto","created_at":"2025-06-17 15:11:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":931936,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6646189/v1/77b2735e-51ae-45e7-95e9-dfb2e2edd5dd.pdf"},{"id":84811614,"identity":"78bcc671-e9d9-43d3-983d-bf378ab2bc9a","added_by":"auto","created_at":"2025-06-17 14:55:30","extension":"csv","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2062,"visible":true,"origin":"","legend":"","description":"","filename":"working1.csv","url":"https://assets-eu.researchsquare.com/files/rs-6646189/v1/550dcf8b5bb8d76cc746e6ce.csv"}],"financialInterests":"No competing interests reported.","formattedTitle":"Burden, Mortality, and Follow-Up Gaps in Paediatric Endocrine Care: Five Years of Experience (2020–2025) from a Tertiary Hospital in South-East Nigeria","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePaediatric endocrine disorders, though less prevalent than infectious diseases, represent a significant but under-recognised cause of morbidity and mortality in low- and middle-income countries (LMICs), including Nigeria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Historically, the overwhelming burden of communicable diseases and malnutrition in sub-Saharan Africa overshadowed the recognition and management of chronic non-communicable diseases in children [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Consequently, paediatric endocrine disorders often go undiagnosed or are diagnosed late, leading to preventable complications and mortality [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe subspecialty of paediatric endocrinology is still evolving in Nigeria, with fewer than 40 trained specialists serving over 90\u0026nbsp;million children as of 2022 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This glaring workforce gap is compounded by the scarcity of diagnostic laboratories, limited access to essential medications, and high out-of-pocket healthcare costs, all of which pose substantial barriers to timely diagnosis and long-term management [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Despite these challenges, recent data suggest that paediatric endocrine disorders in Nigeria may be more common than previously acknowledged, with studies reporting a wide spectrum of conditions including rickets, type 1 diabetes mellitus (T1DM), and thyroid disorders [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEmerging evidence indicates a shifting epidemiological pattern, with an increasing burden of autoimmune and hormonal disorders such as Type 1 diabetes mellitus (T1DM) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Alarmingly, most children with T1DM in Africa present in diabetic ketoacidosis (DKA), a life-threatening emergency associated with a mortality rate of up to 7%, far exceeding the \u0026lt;\u0026thinsp;1% reported in high-income countries [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Similar trends have been noted for other endocrine emergencies, including adrenal crises and severe neonatal thyrotoxicosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBeyond acute presentations, maintaining long-term follow-up remains a major challenge in Nigeria. Studies have documented follow-up attrition rates as high as 60\u0026ndash;70%, driven by poverty, limited health insurance coverage, and lack of caregiver education [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Poor adherence to treatment, particularly for chronic conditions like T1DM, further compounds the risk of adverse outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The Global Pediatric Endocrinology and Diabetes (GPED) group has identified these gaps\u0026mdash;delayed diagnosis, treatment inaccessibility, and poor follow-up\u0026mdash;as critical barriers to optimal care in LMICs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile data from southwestern Nigeria have highlighted these trends [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], there remains a paucity of published evidence from southeastern Nigeria, where access to specialist services is similarly limited. Understanding the clinical spectrum, outcomes, and system-level challenges in this region is essential for guiding local and national strategies to strengthen paediatric endocrine services.\u003c/p\u003e \u003cp\u003e This study, therefore, aimed to review the clinical profile, mortality patterns, and follow-up outcomes of children managed in the first paediatric endocrinology unit established at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, over a five-year period. By contextualising these findings within national and international trends, we sought to provide evidence that could inform future service planning, policy advocacy, and research priorities aimed at improving paediatric endocrine care in resource-limited settings like Nigeria.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003e We conducted a prospective descriptive review of paediatric endocrine cases managed at Nnamdi Azikiwe University Teaching Hospital (NAUTH), a tertiary referral centre located in Nnewi, Anambra State, Nigeria. NAUTH serves the southeastern region of Nigeria, providing specialist paediatric services through a multidisciplinary team. The hospital\u0026rsquo;s dedicated paediatric endocrinology clinic was established in 2019 and began full operations in 2020. This study prospectively followed all eligible patients managed in the unit between February 2020 and February 2025.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Inclusion Criteria\u003c/h3\u003e\n\u003cp\u003eEligible participants were all children aged 0\u0026ndash;18 years who were newly diagnosed with or being managed for endocrine or metabolic disorders in the paediatric endocrinology unit during the study period. Both newly referred and existing follow-up patients attending outpatient clinics or admitted to the paediatric ward under the endocrine team\u0026rsquo;s care were included. Patients managed for non-endocrine conditions were excluded.\u003c/p\u003e\n\u003ch3\u003eData Collection and Follow-Up Procedures\u003c/h3\u003e\n\u003cp\u003eData for this study were prospectively collected using a structured data collection form specifically designed for the purpose of the review. At the point of first contact, relevant clinical information was documented, including the patient\u0026rsquo;s demographic details such as age and sex, the clinical diagnosis based on thorough assessment supported by available laboratory and imaging investigations, as well as the year of presentation.\u003c/p\u003e \u003cp\u003eAll enrolled patients were subsequently followed up throughout the study period during routine clinic visits, hospital admissions, or via telephone contact when necessary. Patient outcomes were prospectively monitored and categorised as either adherent\u0026mdash;defined as actively attending scheduled follow-up visits and adhering to treatment recommendations; lost to follow-up\u0026mdash;defined as failure to attend clinic for more than six months or being unreachable; or deceased\u0026mdash;defined as a confirmed death documented in clinic or hospital records.\u003c/p\u003e \u003cp\u003eIn cases where patients defaulted on follow-up appointments, efforts were made to contact their families by telephone to clarify their status. These outcomes were continuously updated in the database throughout the five-year review period to ensure that the data reflected the most current follow-up status of each patient.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll collected data were entered into Microsoft Excel and subsequently analysed using Python (pandas library) to ensure accurate data management and statistical processing. Continuous variables, such as age, were summarised as mean and standard deviation (SD) for normally distributed data, or as median with interquartile range (IQR) for data that were not normally distributed. Categorical variables, including sex, clinical diagnoses, and follow-up outcomes, were presented as frequencies and percentages.To explore relationships between variables, cross-tabulations were conducted. The chi-square test was used to assess associations between categorical variables, such as diagnosis and follow-up status. Where cell counts were small and the assumptions for chi-square were not met, Fisher\u0026rsquo;s exact test was applied.For continuous variables, such as age comparisons across outcome groups (adherent, lost to follow-up, or deceased), independent samples t-tests were used if the data met normality assumptions. In cases where data were skewed or non-normally distributed, the Kruskal-Wallis test was employed to compare differences across multiple groups.\u003c/p\u003e \u003cp\u003eAll statistical tests were two-tailed, and a p-value of less than 0.05 was considered statistically significant. This threshold was applied to determine the strength of associations and differences observed in the study.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical Considerations\u003c/strong\u003e \u003cp\u003eWe ensured confidentiality by using study codes and aggregating data for publication. This work was carried out in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient Demographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOver the five-year study period, a total of 55 children with endocrine disorders were enrolled and followed at the paediatric endocrinology unit of NAUTH. The median age at first presentation was 9.0 years (range: 7 days to 17 years), with a bimodal distribution, reflecting peaks in infancy/toddlerhood and early adolescence. Female patients accounted for 56.4% (n = 31), while 43.6% (n = 24) were male, giving a female-to-male ratio of approximately 1.3:1. The distribution of diagnoses varied by sex; for instance, all patients diagnosed with congenital adrenal hyperplasia (CAH) were genotypic females, and the majority of thyrotoxicosis cases (83%) occurred in adolescent girls (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrends in Case Presentation\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn upward trend in the annual number of cases was observed throughout the study period. In 2020, the first full year of clinic operation, only four new cases were documented. This number gradually increased to seven cases in 2021, eleven in 2022, and peaked at seventeen in 2023, representing more than a four-fold increase from the initial year. The numbers slightly declined to nine cases in 2024, and seven cases were recorded in the first month of 2025 (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSpectrum of Endocrine Disorders\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 summarizes the clinical diagnoses of the 55 patients. A wide range of 17 distinct diagnoses was recorded, reflecting the broad spectrum of paediatric endocrinology. The most common diagnosis was type 1 diabetes mellitus (T1DM), accounting for 16 cases (29.1% of the cohort). Nearly all 14 out of 16 (87.5%) presented with diabetic ketoacidosis (DKA). Thyrotoxicosis (hyperthyroidism) was the second most frequent diagnosis with 12 cases (21.8%), most of whom were adolescent girls (83.3%). Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was diagnosed in 6 children (10.9%); all were phenotypic females who had presented in early infancy with virilized genitalia. Precocious puberty was noted in 5 patients (9.1%), including 3 girls and 2 boys who developed secondary sexual characteristics before age 8 (girls) or 9 (boys). These cases were being evaluated for central precocious puberty and treated with GnRH analogues when feasible.\u003c/p\u003e\n\u003cp\u003eLess common disorders included Cushing syndrome (2 cases, 3.6%), both of which were iatrogenic Cushingoid features from prolonged steroid use for nephrotic syndrome and asthma \u0026ndash; these patients were referred for growth failure and obesity. Gynecomastia was the reason for referral in 2 peri-pubertal boys (3.6%); they were evaluated for hormonal causes but considered likely pubertal gynecomastia and were managed conservatively. Rickets (nutritional vitamin D\u0026ndash;deficiency rickets and Vitamin D Resistant Rickets Type 1B) was diagnosed in 2 boys (3.6%), both under 5 years old, presenting with delayed motor milestones and leg deformities. A variety of single-case diagnoses (each 1.8% of the total) were recorded namely achondroplasia, micropenis, Turner syndrome, primary hypothyroidism, hypopituitarism, growth hormone deficiency, labial, pseudohypoparathyroidism type\u0026nbsp;1a, and hyperinsulinemic hypoglycaemia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Spectrum of Diagnoses, Sex Distribution, and Follow-Up Outcomes of Paediatric Endocrine Patients Managed at NAUTH, 2020\u0026ndash;2025\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"116%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (% of total)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLost to Follow-Up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdherent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeceased\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u0026nbsp;1 Diabetes Mellitus (T1DM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e16 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eThyrotoxicosis (Hyperthyroid)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e12 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCongenital Adrenal Hyperplasia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e6 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrecocious Puberty\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e5 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCushing syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e2 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGynecomastia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e2 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRickets (Vitamin D deficiency)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e2 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAchondroplasia (dwarfism)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstitutional delay of growth \u0026amp; puberty (CDGP)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrowth hormone deficiency\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHyperinsulinemic hypoglycaemia\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypopituitarism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypothyroidism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLabial adhesion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMicropenis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePseudohypoparathyroidism type\u0026nbsp;1a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTurner syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.25%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.4583%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes and Follow-Up Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBy the end of the five-year review period, patient outcomes were categorised into three groups: adherent (those actively attending follow-up clinics), lost to follow-up (those who defaulted for more than six months and were unreachable), and deceased. Overall, only 14 patients (25.5%) remained in active follow-up and under care at NAUTH by 2025. In contrast, a substantial 38 patients (69.1%) were lost to follow-up at some point after their initial diagnosis. In the majority of these cases, families discontinued clinic visits and could not be reached despite repeated contact attempts, reflecting a concerningly high attrition rate. Additionally, there were four documented deaths (7.3% mortality) within the cohort.\u003c/p\u003e\n\u003cp\u003eTwo of these deaths occurred in children with type 1 diabetes mellitus (T1DM): a 6-year-old girl and a 7-year-old boy, both presenting with severe diabetic ketoacidosis (DKA). The remaining two fatalities involved endocrine emergencies in infancy. One was a 3-month-old boy with neonatal thyrotoxicosis (secondary to maternal Graves\u0026apos; disease), who succumbed to heart failure. The other was a 6-month-old boy with hyperinsulinemic hypoglycaemia, who died from hypoglycaemic brain injury. These outcomes underscore the life-threatening nature of delayed or suboptimal management of critical endocrine conditions.\u003c/p\u003e\n\u003cp\u003eThe distribution of follow-up outcomes across diagnostic categories is detailed in Table 1. Among the 16 children with T1DM, only 3 (18.8%) remained in care, while 11 (68.8%) were lost to follow-up and 2 (12.5%) had died. Similarly, of the 12 patients with thyrotoxicosis, 4 (33%) remained adherent, 7 (58%) were lost to follow-up, and 1 (8.3%) had died. Children with congenital adrenal hyperplasia (CAH) showed relatively better retention, with 3 out of 6 (50%) still engaged in follow-up and none deceased, although 3 (50%) were lost to follow-up.\u003c/p\u003e\n\u003cp\u003eConversely, 100% of patients with Cushing syndrome, gynecomastia, Turner syndrome, hypopituitarism, micropenis, labial adhesion, pseudohypoparathyroidism, and achondroplasia defaulted after their initial visits. Among the five cases of precocious puberty, four (80%) were lost to follow-up, with only one patient continuing therapy.\u003c/p\u003e\n\u003cp\u003eStatistical analysis revealed no significant difference in loss to follow-up by sex (67% in females vs 70% in males, p = 0.99) or by diagnostic category, as attrition was consistently high across all groups. Additionally, age did not significantly influence follow-up status, with both adherent and non-adherent patients having a median age of approximately 10 years (p = 0.10).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis five-year review provides valuable insight into the profile and fate of children with endocrine disorders at a tertiary hospital in South-Eastern Nigeria. To our knowledge, it is among the first reports from this region, complementing previous studies from South-Western Nigeria and sub-Saharan Africa.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe range of conditions seen at NAUTH reflects both common endocrine diseases and rare disorders. Type 1 diabetes mellitus was the single most common diagnosis (29% of cases), which is consistent with an increasing trend of paediatric diabetes across Africa [3,6]. Our finding aligns with a multi-center Nigerian survey that identified type 1 diabetes as a major component of paediatric endocrine practice nationwide. In earlier Nigerian case series a decade ago, diabetes contributed a smaller share (around 12–15%) [1,2]. The higher proportion in our 2020s data likely reflects both real incidence growth, improved detection and post COVID-19 sequalae [3,6]. Notably, nearly all our diabetic patients presented with DKA, similar to reports that 70–80% of African children initially present in ketoacidosis[5]. Two of these children died, further emphasizing that even with treatment, African paediatric DKA case fatality ~7% remains far above the ~0.5–2% reported in developed countries [8]. This calls for improved DKA management protocols and possibly earlier diagnosis of diabetes (e.g., through awareness campaigns to reduce delay from symptom onset to hospital).\u003c/p\u003e\n\u003cp\u003eThyroid disorders, particularly hyperthyroidism (Graves’ disease), formed the second largest group (21.8%). This is noteworthy because earlier studies from Nigeria reported thyroid disorders in only ~6–15% of cases [1,2]. The higher proportion at NAUTH might be due to regional differences or a rising incidence of autoimmune thyroid disease [11]. Many of our thyrotoxicosis patients were adolescent girls, a demographic known to be at risk for Graves’ disease. One case was an infant with neonatal thyrotoxicosis, an entity caused by transplacental maternal TSH-receptor antibodies – a reminder of the need for maternal thyroid screening in pregnancy. Unfortunately, that infant succumbed, underscoring that neonatal thyrotoxicosis can be life-threatening if not recognized and aggressively treated. Our data suggest thyroid disorders are an important part of the paediatric endocrine spectrum in this region [11], meriting increased awareness among clinicians and earlier referral for symptoms like goiter, weight loss, or rapid heartbeat in children.\u003c/p\u003e\n\u003cp\u003eOur series had fewer cases of rickets (only 2 cases, 3.6%) compared to the strikingly high rates reported in earlier Nigerian studies (45–56% of cases) [1,2].\u0026nbsp;Rickets was the leading diagnosis in those studies, reflecting widespread vitamin D deficiency and nutritional calcium deficiency in young children. The lower proportion at NAUTH could be due to differences in study populations or time period. By 2020s, there may be modest improvements in nutrition and vitamin D supplementation in our catchment area, or rickets cases might be managed by general pediatricians without referral to endocrinology, thus underrepresented in our review. Nonetheless, rickets remains a concern; it is a preventable condition and its continued presence indicates ongoing public health needs in nutrition [1].\u003c/p\u003e\n\u003cp\u003eThe observed mortality rate of 7.3% (4 deaths among 55 patients) is higher than the 2.5% reported in Osogbo[2] and the 1% reported in Ibadan [1]. This difference could be due to our smaller sample size or a true difference in case mix. It is possible that our mortality figure underestimates true mortality, as many patients were lost to follow-up – some of those might have died outside the hospital. Unfortunately, without a robust patient tracking system or death registry linkage, we cannot ascertain outcomes for the majority who defaulted. What is clear is that the deaths that did occur were largely preventable with optimal care. Type\u0026nbsp;1 diabetes, for example, should not be a death sentence for a child; yet in Nigeria and similar contexts, survival is jeopardized by late presentation and inadequate treatment. A study by Umar (2023)[12] noted that African children with T1DM face numerous management challenges, leading to poor outcomes. Improving acute management protocols (DKA treatment per international guidelines and ensuring availability of medications (insulin, anti-thyroid drugs, etc.) could reduce such fatalities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne of the most concerning findings in this study was the nearly 70% loss to follow-up rate, affecting all age groups and diagnoses. This highlights systemic barriers such as financial hardship, limited specialist access, and poor caregiver understanding of chronic disease management. In Nigeria, most families rely on out-of-pocket payments, with low health insurance coverage, making long-term treatment like insulin or hormone therapy financially unsustainable for many [3,4]. Similar high attrition rates have been reported in other centres, including Lagos State University Teaching Hospital and Uniosun Teaching Hospital, where financial constraints and poor health literacy were identified as key drivers of discontinuation [1,2]. Left unchecked, this undermines treatment success and increases the risk of preventable deaths, such as those seen from diabetic ketoacidosis in this and other African studies [7]. Addressing this challenge requires health system reforms to improve access and affordability, such as including endocrine medications in health insurance packages, providing subsidies for essential care, and implementing better patient tracking and education systems [3,9].\u003c/p\u003e\n\u003cp\u003eBased on our findings, several practical steps could improve paediatric endocrine care at NAUTH and similar centres. First, strengthening follow-up retention is essential. Measures such as SMS reminders, flexible scheduling, and telemedicine could help reduce attrition, especially for families travelling long distances. Reducing financial barriers is equally critical; inclusion of paediatric endocrine medications in national insurance schemes and subsidised drug access—similar to HIV or TB models—could significantly improve adherence. Hospital authorities and NGOs should consider supporting indigent patients with essential medications.\u003c/p\u003e\n\u003cp\u003eEqually important is parent education at diagnosis. Families must clearly understand the chronic nature of these conditions and the consequences of treatment interruption. Peer support groups may also enhance engagement, particularly for families managing conditions like diabetes.\u003c/p\u003e\n\u003cp\u003eOur findings also support the urgent need for newborn screening programmes, particularly for CAH and congenital hypothyroidism[13]. Despite being standard practice in many countries, such screening is largely absent in Nigeria. Pilot programs at tertiary centres could serve as a starting point. Finally, increasing the number of trained specialists and strengthening referral networks will ensure timely diagnosis and care. Continued medical education for general paediatricians and the development of satellite or outreach clinics may decentralise care, reduce delays, and improve long-term outcomes.\u003c/p\u003e\n\u003cp\u003eA key strength of this study is its ability to shed light on paediatric endocrine disorders in an under-reported region of Nigeria. By using real-world clinical data collected over five years, it captures meaningful trends during the formative period of NAUTH’s paediatric endocrine service. The inclusion of all presenting cases, regardless of diagnosis, provides a comprehensive snapshot of the diverse spectrum of endocrine conditions encountered in routine practice—extending beyond the more commonly reported disorders. Additionally, the study quantified the significant follow-up gap, an issue often overlooked in similar reports.\u003c/p\u003e\n\u003cp\u003eHowever, the study has notable limitations. The high rate of loss to follow-up introduces uncertainty about the true long-term outcomes for many patients. Furthermore, the study did not evaluate key contextual factors such as socioeconomic status, caregiver education, or healthcare access, which likely influenced follow-up adherence and mortality. Finally, the role of unmeasured confounders—such as variations in disease severity, treatment practices, and family support—cannot be fully ruled out.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this five-year review demonstrates that paediatric endocrine disorders, once considered rare in Nigeria, are in fact a significant and growing concern. The increasing number of diagnoses at NAUTH over time reflects improved clinical awareness and service development. However, the persistently high mortality in acute cases—particularly diabetic ketoacidosis—and the alarming rate of loss to follow-up expose deep systemic weaknesses in chronic care delivery.\u003c/p\u003e\n\u003cp\u003eAddressing these gaps requires interventions that go beyond diagnosis alone. Ensuring uninterrupted access to essential medications and therapies through healthcare financing reforms, insurance coverage, or targeted support programmes is critical. Strengthening follow-up systems—through patient navigation services, community outreach, or digital health platforms—will also be essential to retain patients in long-term care. Advancing these efforts is key to improving outcomes for children with endocrine disorders in Nigeria and achieving greater health equity for all children living with chronic illnesses.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003e\u003cstrong\u003eAuthorship Contributions\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eC.A.N. conceptualized the study, designed the methodology, conducted statistical analyses, and drafted the manuscript. T.O.U. provided critical revisions, validated clinical interpretations, and contributed to manuscript editing. All authors reviewed and approved the final version of the manuscript for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Anambra State Ministry of Health Research Ethics Committee, Awka, Anambra State, Nigeria. Written informed consent was obtained from the parents or legal guardians of all participants. Assent was also obtained from children aged 7 years and above, in accordance with institutional and national ethical guidelines. All procedures involving human participants were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest regarding the publication of this paper.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis research was fully funded by the authors without external financial support. No grants or institutional funding were received, and all study-related expenses were covered personally by the authors.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJarrett O, Ogubosi B, Ayoola O, PAEDIATRIC ENDOCRINE DISORDERS AT THE UNIVERSITY COLLEGE HOSPITAL IBADAN. 2002\u0026ndash;2009. 2013 [cited 2025 Mar 1];11:96\u0026ndash;101. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://aipmed.org/?page_id=1400\u003c/span\u003e\u003cspan address=\"https://aipmed.org/?page_id=1400\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOluwayemi IO, Oyedeji OA, Adeniji EO, Afolabi AA, Ayeni TO. Ten-Year Review of Paediatric Endocrine Disorders at Uniosun Teaching Hospital, Osogbo, Nigeria. West Africa Journal of Medicine [Internet] 2021 [cited 2025 Mar 3];38:1114\u0026ndash;9. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.researchgate.net/publication/357225658_Ten-Year_Review_of_Paediatric_Endocrine_Disorders_at_Uniosun_Teaching_Hospital_Osogbo_Nigeria\u003c/span\u003e\u003cspan address=\"https://www.researchgate.net/publication/357225658_Ten-Year_Review_of_Paediatric_Endocrine_Disorders_at_Uniosun_Teaching_Hospital_Osogbo_Nigeria\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYarhere I, Tamunopriye J. Paediatric endocrinology and diabetes mapping and services in Nigeria: A decade after. African Journal of Diabetes medicine [Internet] 2022 [cited 2025 Mar 3];30:2022. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.africanjournalofdiabetesmedicine.com/articles/paediatric-endocrinology-and-diabetes-mapping-and-services-in-nigeria-a-decade-after-87230.html\u003c/span\u003e\u003cspan address=\"https://www.africanjournalofdiabetesmedicine.com/articles/paediatric-endocrinology-and-diabetes-mapping-and-services-in-nigeria-a-decade-after-87230.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEyong M, Nsa E, Etuk I. Pediatric endocrinology practice in Nigeria: Challenges and way forward. Niger J Med. 2020;29:542.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed AM, Khabour OF, Ahmed SM, Alebaid IA, Ibrahim AM. Frequency and severity of ketoacidosis at diagnosis among childhood type 1 diabetes in Khartoum state, Sudan. Afr Health Sci [Internet] 2020 [cited 2025 Mar 3];20:841. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC7609092/\u003c/span\u003e\u003cspan address=\"https://pmc.ncbi.nlm.nih.gov/articles/PMC7609092/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNri-Ezedi CA, Ulasi TO, Okeke KN, Okonkwo IT, Echendu ST, Agu NV, A SURGE OF TYPE 1 DIABETES MELLITUS AMONG NIGERIAN CHILDREN DURING THE COVID-19 PANDEMIC. Ann Ib Postgrad Med [Internet] 2022 [cited 2024 Jul 28];20:58. Available from: /pmc/articles/PMC10061673/.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurunga AN, Owira PMO. Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa? Trop Med Int Health [Internet] 2013 [cited 2025 Mar 3];18:1357\u0026ndash;64. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/24112393/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/24112393/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShimelash RA, Belay GM, Aknaw W, Shibabaw AT, Adebabay AA, Gedefaw GD, et al. Incidence and predictors of mortality in children with diabetic ketoacidosis in the comprehensive specialized referral hospitals of West Amhara Region, Northwest Ethiopia: a retrospective follow-up study. Front Clin Diabetes Healthc. 2023;4:1204133.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZacharin M, Chanoine JP, Cassorla F, Brink S, Hanas R, Fideleff HL et al. Promoting Excellence in the Care of Pediatric Endocrine Diseases in the Developing World. Pediatrics [Internet] 2013 [cited 2025 Mar 3];131:e573\u0026ndash;8. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e/pediatrics/article/131/2/e573/31882/Promoting-Excellence-in-the-Care-of-Pediatric\u003c/span\u003e\u003cspan address=\"http:///pediatrics/article/131/2/e573/31882/Promoting-Excellence-in-the-Care-of-Pediatric\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHome | GPED [Internet]. [cited 2025 May 12];Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.globalpedendo.org/\u003c/span\u003e\u003cspan address=\"https://www.globalpedendo.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNdubuisi CA, Ohaegbulam SC, Ejembi GO. Paediatric brain tumours managed in Enugu, Southeast Nigeria: Review of one centre experience. Niger Postgrad Med J. 2018;25:186\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUmar UI. Spectrum of Pediatric Endocrine Disorders at the Aminu Kano Teaching Hospital, Kano, Northwestern Nigeria: a five-year review. Pyramid Journal of Medicine [Internet] 2023 [cited 2025 Mar 3];6:315. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://africa.pagepress.net/pjm/article/view/315\u003c/span\u003e\u003cspan address=\"https://africa.pagepress.net/pjm/article/view/315\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYarhere IE, Jaja T, Briggs D, Iughetti L. Newborn screening in Nigeria: will incorporating congenital hypothyroidism with sickle cell disease improve neonatal screening programme? Acta Bio Medica: Atenei Parmensis [Internet] 2019 [cited 2025 Mar 3];90:316. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC6776226/\u003c/span\u003e\u003cspan address=\"https://pmc.ncbi.nlm.nih.gov/articles/PMC6776226/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Paediatric endocrinology, type 1 diabetes mellitus, thyrotoxicosis, follow-up attrition, sub-Saharan Africa, resource-limited settings","lastPublishedDoi":"10.21203/rs.3.rs-6646189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6646189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Paediatric endocrine disorders are an emerging concern in sub-Saharan Africa, yet they remain under-recognised due to the predominant focus on infectious diseases. Inadequate specialist services and poor follow-up systems contribute to late presentation and adverse outcomes. This study prospectively reviewed the clinical spectrum, mortality, and follow-up challenges of paediatric endocrine cases managed in the first dedicated endocrinology unit at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nigeria, over a five-year period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A prospective review was conducted from February 2020 to February 2025, enrolling children aged 0–18 years diagnosed with endocrine or metabolic disorders. Clinical data collected included demographics, diagnoses, and follow-up outcomes, categorised as adherent, lost to follow-up, or deceased. Descriptive statistics were used to summarise patient characteristics, and associations between clinical variables and outcomes were analysed using chi-square or Fisher’s exact tests as appropriate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Fifty-five children were enrolled (median age: 9 years; range: 7 days to 17 years; 56.4% female). The most common diagnoses were type 1 diabetes mellitus (29.1%) and thyrotoxicosis (21.8%), followed by congenital adrenal hyperplasia (10.9%) and precocious puberty (9.1%). Annual case numbers increased progressively, peaking in 2023. Overall mortality was 7.3%, with deaths predominantly due to diabetic ketoacidosis and neonatal endocrine emergencies (Neonatal thyrotoxicosis and hyperinsulinemic hypoglycaemia). Notably, 69.1% of patients were lost to follow-up, while only 25.5% remained in active care by the end of the study period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The establishment of the paediatric endocrinology unit at NAUTH has enhanced case detection and management of childhood endocrine disorders in southeastern Nigeria. However, the high rates of loss to follow-up and preventable deaths highlight persistent systemic barriers, including financial constraints and limited healthcare access. Interventions aimed at strengthening follow-up systems, improving caregiver education, and reducing the cost burden of chronic care are urgently needed to improve long-term outcomes in this resource-limited setting.\u003c/p\u003e","manuscriptTitle":"Burden, Mortality, and Follow-Up Gaps in Paediatric Endocrine Care: Five Years of Experience (2020–2025) from a Tertiary Hospital in South-East Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 14:55:25","doi":"10.21203/rs.3.rs-6646189/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-06-13T06:33:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-23T09:48:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-23T09:45:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-19T17:38:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-05-19T17:37:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7d16ea72-958a-41a5-8c24-ff6137bbb96d","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-17T14:55:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 14:55:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6646189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6646189","identity":"rs-6646189","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}