Growth Without GH: A Case Series and Literature Review

Area of Science:

• Pediatric Endocrinology
• Growth and Development
• Metabolic Disorders

Background:

• Linear growth is primarily linked to the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis.
• However, cases of 'growth without GH' challenge this paradigm, indicating other contributing factors.
• Patients with GH deficiency often present with obesity and metabolic complications.

Purpose of the Study:

• To investigate the mechanisms of linear growth in patients with severe GH deficiency and persistently low IGF-1.
• To explore the role of other factors beyond the GH/IGF-1 axis in achieving normal or tall stature.
• To evaluate the impact of recombinant human GH (rhGH) on growth and metabolic outcomes in this cohort.

Main Methods:

• Case series of five patients with severe GH deficiency (one congenital, four acquired) and low IGF-1.
• Analysis of growth patterns, metabolic parameters (obesity, insulin resistance, dyslipidemia, fatty liver), and response to treatments (sex steroids, rhGH).
• Literature review of published cases of 'growth without GH' to contextualize findings.

Main Results:

• All five patients achieved normal or tall stature despite severe GH deficiency and low IGF-1.
• Growth occurred independently of sex-steroid replacement in most cases; one patient showed prolonged growth with delayed epiphyseal fusion due to hypogonadism.
• rhGH treatment in three patients did not significantly impact growth velocity but showed favorable metabolic outcomes, improving lipid profiles and steatohepatitis.

Conclusions:

• Profound GH deficiency does not preclude normal or accelerated linear growth, highlighting multifactorial growth drivers.
• Factors like insulin signaling, thyroid hormone action, local growth-plate pathways, and genetic modifiers likely contribute.
• Therapeutic focus for 'growth without GH' should prioritize cardiometabolic risk reduction, with rhGH considered for metabolic benefits under close monitoring.