Endocrinopathies in Paediatric Iron Deficiency Anaemia: Spectrum, Mechanisms, and Reversibility with Treatment
Ashraf T. Soliman *
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Fawzia Alyafei
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Nada Mwafak Al Aaraj
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Noor Sadeq Abdullah Hamed
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Shayma Ahmed
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Nada Soliman
Directorate of Health Affairs in Alexandria, Ministry of Health, Alexandria, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Background: Iron deficiency anaemia (IDA) is a prevalent micronutrient disorder in childhood, with well-recognised haematological effects and increasingly reported endocrine consequences.
Objectives: This review synthesised evidence on the spectrum, risk factors and reversibility of endocrine dysfunction associated with paediatric IDA.
Methods: PubMed/MEDLINE literature published from January 1999 to December 2024 was reviewed using predefined MeSH and free-text search strategies. Eligible studies included children and adolescents aged 0-18 years with biochemically confirmed IDA and at least one endocrine, growth, pubertal, adrenal or neurodevelopmental outcome. The review followed a systematic-style narrative approach guided by SANRA and PRISMA-ScR principles. Methodological quality was assessed using the Newcastle-Ottawa Scale for observational studies and AMSTAR-2 for systematic reviews. No independent meta-analysis was performed.
Results: The search identified more than 480 records; 47 studies met the inclusion criteria and were supplemented by five foundational studies. The evidence base comprised 12 systematic reviews or meta-analyses, 18 cohort or case-control studies, nine cross-sectional studies, five randomised controlled trials and three narrative reviews. Reported endocrine manifestations included impaired growth with reduced growth velocity and suppressed IGF-1, subclinical hypothyroidism related to impaired thyroid peroxidase activity, delayed pubertal progression linked to gonadotrophin-axis suppression, attenuated adrenal reserve in severe IDA, and neurodevelopmental deficits after early-life deficiency. Duration of deficiency, delayed treatment, nutritional co-deficiencies, age at exposure, environmental stressors and genetic susceptibility were identified as relevant modifying factors. Iron supplementation, commonly in the range of 3-6 mg/kg/day for 3-6 months, was associated with improvements in growth, thyroid function, somatotropic-axis activity, adrenal reserve and pubertal parameters. Neurodevelopmental recovery appeared less complete when IDA occurred during infancy.
Conclusion: Paediatric IDA is associated with multi-axis endocrine dysfunction, much of which may improve following timely iron repletion. Early diagnosis, appropriate treatment and targeted endocrine assessment are important for reducing potentially persistent sequelae.
Keywords: Iron deficiency anaemia, paediatric endocrinology, growth hormone, insulin-like growth factor-1, thyroid function, puberty, adrenal reserve, neurodevelopment, hepcidin, iron supplementation