The Endocrine–Gut–Liver Axis in Childhood: Clinical Spectrum, Mechanistic Pathways, and Therapeutic Implications

Background: Gastrointestinal (GI) and hepatic manifestations are increasingly recognized as important clinical components of pediatric endocrine disorders. Because endocrine hormones directly influence gut motility, nutrient absorption, hepatic lipid oxidation, glycogen metabolism, and inflammatory pathways, children may present with GI or hepatic abnormalities before classical endocrine symptoms emerge. Understanding these associations is essential for early diagnosis and targeted management.

Methods: This narrative review synthesized evidence published between 2000 and 2025 from PubMed, Scopus, Web of Science, and major society guidelines. Studies describing GI or hepatic manifestations in children with endocrine disorders were included and appraised using Cochrane risk-of-bias tools (ROB 2 and ROBINS-I). A total of 59 validated, non-duplicated references informed the analysis. GI and hepatic manifestations were categorized as acute or chronic based on pathophysiology and duration.

Results: Across endocrine disorders, distinct and recurring GI and hepatic patterns were identified. Hyperthyroidism produced acute diarrhea and abdominal pain due to increased intestinal motility, while hypothyroidism resulted in chronic constipation and delayed gastric emptying. In type 1 diabetes mellitus (T1DM), autonomic neuropathy and deglycation led to acute and chronic gastroparesis, with glycogenic hepatopathy driving reversible hepatomegaly and transaminase elevations. Type 2 diabetes mellitus (T2DM) and obesity were strongly associated with metabolic dysfunction-associated steatosis liver disease (MASLD/NAFLD), reflecting insulin resistance and increased hepatic lipogenesis.

Chronic hepatic involvement was prominent in growth hormone deficiency, Cushing syndrome, Down syndrome with obesity or thyroid dysfunction, and polycystic ovary syndrome—each linked to hormonal drivers of steatosis. Genetic and metabolic disorders, particularly glycogen storage diseases, presented with persistent hepatomegaly, elevated transaminases, and feeding intolerance. Anorexia nervosa contributed to starvation-related hepatitis and chronic GI dysmotility that resolved with nutritional rehabilitation. During COVID-19 and MIS-C, acute hepatitis and GI symptoms were common due to inflammatory–endocrine interactions.

Across disorders, a consistent pattern emerged: most GI and hepatic manifestations improved significantly when the underlying endocrine abnormality was corrected. Glycemic optimization reversed glycogenic hepatopathy; levothyroxine restored motility and improved steatosis in hypothyroidism; GH therapy improved hepatic fat content in GH deficiency; and cortisol normalization reduced steatosis in Cushing syndrome. Multidisciplinary collaboration enhanced early detection and prevented progression to fibrosis or chronic dysmotility.

Conclusion: GI and hepatic abnormalities are frequent, clinically meaningful, and often early indicators of pediatric endocrine disease. Recognizing these manifestations, guided by evidence from 59 systematically evaluated references, allows earlier diagnosis, targeted treatment, improved metabolic stability, and better long-term outcomes in children and adolescents with endocrine disorders.