Growth Hormone Secretion Patterns and Diagnostic Evaluation of Pediatric Growth Hormone Deficiency: A Comprehensive 25-Year Narrative Review (2000–2025)

Background: Growth hormone (GH) plays a central role in childhood growth and metabolic regulation, yet its diagnostic evaluation remains challenging because of its pulsatile secretion and sensitivity to factors such as puberty, sleep, nutrition, and adiposity. Over the past 25 years, advances in assay technology and a deeper understanding of GH–IGF physiology have highlighted major limitations of traditional stimulation tests and IGF-1–based screening, underscoring the need for an updated, integrated diagnostic framework for pediatric GH deficiency (GHD).

Objectives: To synthesize current evidence (2000–2025) on GH secretion physiology, diagnostic performance of GH stimulation tests, IGF-1, and IGFBP-3, and the modifying effects of puberty, BMI, and assay generation; and to propose a modern stepwise diagnostic strategy for accurate early identification of GHD.

Methods: A narrative literature review was performed using PubMed, Scopus, and Google Scholar (2000–2025), including pediatric studies assessing GH secretion, GH stimulation tests, IGF-1/IGFBP-3 performance, and pubertal or BMI influences. Mechanistic and classical physiologic studies were included for context. Findings were synthesized into thematic domains and structured comparative tables.

Results: Across the literature, GH secretion increased two- to three-fold from Tanner I to Tanner III–IV, driven mainly by increased pulse amplitude rather than frequency. Parallel rises in IGF-1 and IGFBP-3 peaked in mid-puberty and declined in late adolescence, creating clearly stage-dependent physiological reference points. Failure of GH or IGF-1 to rise appropriately during mid-puberty strongly differentiated true GHD from constitutional or obesity-related patterns.

GH stimulation tests showed moderate-to-good sensitivity but only modest specificity, with substantial variability across stimuli and assays. Newer chemiluminescent assays produced lower GH peaks, indicating that historical 10 ng/mL cutoffs are no longer valid for many laboratories. Diagnostic accuracy improved when two different stimulation tests were used and when GH values were interpreted alongside Tanner stage and BMI rather than as isolated results.

IGF-1 and IGFBP-3 alone lacked sufficient sensitivity but demonstrated good specificity; combining both biomarkers or using IGF-1/IGFBP-3 ratios improved classification. Obesity consistently suppressed spontaneous GH pulsatility and reduced stimulated GH peaks, while also lowering IGF-1 specificity, confirming the need for BMI-adjusted cutoffs. Tanner III–IV represented the most physiologically informative stage for distinguishing delayed puberty from true GHD. Nocturnal GH sampling and IGF-1 generation tests had limited routine value but remained useful in selecting diagnostic dilemmas.

Conclusion: Accurate diagnosis of pediatric GHD requires an integrated, context-dependent approach that combines auxologic parameters, pubertal staging, BMI, IGF-1/IGFBP-3 interpretation, assay-specific GH cutoffs, and pituitary MRI. Such a strategy reduces misclassification and supports timely, appropriate therapy for children with true GHD.