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Low growth hormone-binding protein in infants with congenital hypothyroidism
A Cassio1, E Cacciari, A Balsamo
1Department of Pediatrics, University of Bologna, Italy.
Insights
Congenital hypothyroidism (CH) in infants is linked to altered growth hormone-binding protein (GHBP) levels, which may persist even after treatment. Intrauterine insulin-like growth factor I (IGF-I) production is influenced by fetal thyroid function.
Area of Science:
- Pediatric Endocrinology
- Neonatal Screening
- Hormone Regulation
Background:
- Congenital hypothyroidism (CH) is a condition diagnosed in newborns, requiring timely treatment with levothyroxine (L-T4).
- Growth hormone (GH) and insulin-like growth factor I (IGF-I) are crucial for growth and development, and their regulation may be affected by thyroid status.
- Understanding the impact of CH on the GH-IGF-I axis is important for optimizing treatment strategies.
Purpose of the Study:
- To investigate circulating levels of GH, IGF-I, GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) in infants with CH before and during L-T4 therapy.
- To compare these levels with age- and sex-matched healthy controls.
- To explore the relationship between CH, GHBP, and IGF-I production.
Main Methods:
- Serum GHBP was measured using high-performance liquid chromatography-gel filtration.
- Serum GH, IGF-I, and IGFBP-3 levels were determined using commercial kits.
- Measurements were taken before L-T4 therapy and at several time points during treatment in 19 infants with CH and in a control group.
Main Results:
- Infants with CH had significantly lower GHBP levels before treatment compared to controls; these levels increased with treatment but remained lower after 6 months.
- Pretreatment GH levels were similar to controls, but GH levels were significantly higher during treatment due to a lack of decrease observed in controls.
- Pretreatment IGF-I levels were not significantly different from controls but were lower in severe CH; IGF-I levels decreased over time and became significantly lower than controls by 7 months of age.
Conclusions:
- Congenital hypothyroidism may induce changes in GHBP expression, potentially starting in fetal life.
- Intrauterine IGF-I production appears to be independent of GHBP levels but partially influenced by fetal thyroid function.
- These findings suggest a complex interplay between thyroid status, GHBP, and IGF-I in neonatal development.
Abstract:
We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I), GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4 therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days, diagnosed by neonatal screening and in a group of age- and sex-matched control infants. The same parameters were reevaluated after several months of treatment. Serum GHBP was measured by the high performance liquid chromatography-gel filtration method; serum GH, IGF-I, and IGFBP-3 levels were determined by commercial kits. The hypothyroid patients, before beginning therapy, presented significantly lower GHBP values than controls (P < 0.0001); during treatment, these values increased significantly; however, after 6 months they were still significantly lower than control values (P < 0.01). The pretreatment levels of GH were not significantly different from control values; after 1 month of treatment, GH did not show the decrease observed in controls and, therefore, was significantly higher (P < 0.01). The pretreatment levels of IGF-I were not significantly different from control values, but were lower in patients with severe than in those with mild hypothyroidism. They decreased at about 4 months of life and became significantly lower than control values at about 7 months of age (P < 0.05). In conclusion, it may be hypothesized that the condition of CH induces a change in GHBP expression, perhaps beginning in fetal life. The intrauterine production of IGF-I seems to be independent of the levels of GHBP and partially affected by fetal thyroid function.