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Near-normal linear growth in the setting of markedly reduced growth hormone and IGF-1. A case report
M Murashita1, T Tajima, J Nakae
1Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Insights
Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may not be essential for physical growth. This study found a boy with GH deficiency grew normally, suggesting alternative growth pathways exist.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Axis
- Metabolic Regulation
Background:
- A prepubertal boy with complete growth hormone deficiency (GHd) and tertiary hypothyroidism exhibited growth between -1 and -2 SD despite levothyroxine treatment.
- Investigating the growth mechanism in GHd is crucial for understanding endocrine regulation of physical development.
Observation:
- Serum growth hormone (GH) and bioactivity were low, while growth hormone-binding protein (GHBP) was elevated.
- Insulin-like growth factor-1 (IGF-1), free IGF-1, and insulin-like growth factor-binding protein-3 (IGFBP-3) levels were consistently low.
- The patient's serum demonstrated potent growth-promoting activity on erythroid progenitor cells, exceeding that of healthy controls.
Findings:
- Despite deficient GH and IGF-1, the patient maintained growth within the -1 to -2 SD range.
- Low GH and IGF-1 levels were not absolute prerequisites for normal physical growth in this case.
- Elevated GHBP and potent serum growth-promoting activity suggest compensatory mechanisms for growth.
Implications:
- This case challenges the established understanding of GH and IGF-1 indispensability in human growth.
- Uncharacterized growth pathways or factors may play a significant role in compensating for GH/IGF-1 deficiency.
- Further research into alternative growth mechanisms is warranted to understand pediatric growth regulation.
Abstract:
A 14.2-year-old prepubertal boy diagnosed with complete-type growth hormone deficiency and tertiary hypothyroidism, keeps growing in the height range between -1 and -2 SD. He has been treated with levothyroxine only. To understand the growth mechanism of this boy, we analyzed the serum growth hormone (GH) with a radioimmunoassay (RIA), serum GH bioactivity with Nb2 and erythroid progenitor cell bioassays, and growth hormone-binding protein (GHBP) with a ligand-mediated immunofunctional assay (LIFA). In addition, IGF-1 and free IGF-1 were analyzed by immunoradiometric assay (IRMA) and insulin-like growth factor-binding protein-3 (IGFBP-3) by Western immunoblot. Peak GH-RIA responses to insulin, arginine and GH-releasing factor, and nocturnal GH secretion, were low (0.5-2.3 ng/ml); bioactive GH was low (0.313 ng/ml), and GHBP was elevated (84 ng/ml). The serum levels of IGF-1 and free IGF-1 were continuously low, 17.1-39.3 and 0.17-0.26 ng/ml, respectively. Moreover, serum IGFBP-3 levels were low (1.68- 1.39 mg/l) and IGFBP-3 protease activity was negative. Prolactin and insulin were in the normal range. The result of the assay for growth-promoting activity showed that the patient's serum stimulated normal erythroid progenitor cells twice as potently as did healthy thin adult control serum. These results suggest that GH and IGF-1 are not indispensable for maintaining physical growth in this boy. Thus, it appears that circulating GH and IGF-1 are not mandatory requirements for maintaining normal physical growth, and other, as yet uncharacterized, pathways or growth factors might be sufficiently compensatory under certain conditions.