Bona G, Rapa A, Boccardo G, Silvestro L, Chiorboli E
Department of Medical Sciences Pediatric Section of Novara, University of Turin, Italy.
Panminerva Med. 1998 Jun;40(2):103-6.
Thyroid hormones are involved in the regulation of the GH/IGF axis. Hypothyroidism is associated with a reduction in GH pulsatility and in GH-response to stimulatory tests. In hypothyroidism, serum levels of IGF-I and IGFBP-3 fall and these changes are reserved after short-term replacement with L-T4. This study was undertaken to determine the effect of long-term replacement therapy with T4 in IGF-1 and IGFBP-3 serum levels.
The study included 12 patients affected with hypothyroidism and in replacement treatment with T4. They were divided into 3 groups according to age at the beginning of treatment. Group A consisted of 4 pre-pubertal subjects with Congenital Hypothyroidism (CH) diagnosed with neonatal screening, where T4 treatment was started within 15 days of life. Group B consisted of 5 young adults where CH was clinically diagnosed at the median age of 6 months and replacement therapy started at this age. Group C consisted of 3 subjects affected with hypothyroidism secondary to thyroiditis where diagnosis and replacement treatment were delayed at age 11, 12 and 14 respectively. All subjects were matched with a control of the same age, sex, weight and pubertal stage.
FT3, FT4 and TSH were in the normal range both in patients and in controls. No correlation was found between FT3 or FT4 and IGF-1 or IGFBP-3 serum levels. IGF-1 serum levels in group A (198 +/- 122 ng/ml) were significantly lower than that in group B (624 +/- 105, p < 0.001) and in group C (649 +/- 98, p=0.003). IGFBP-3 serum levels in group A (1.98 +/- 0.56 microgram/ml) were significantly lower than in group B (3.65 +/- 1.10, p=0.03) and in group C (4.13 +/- 0.49, p=0.003). The increase of IGF-1 and IGFBP-3 levels was seen also in control groups B and C when compared with control group A. IGF-1 and IGFBP-3 were positively correlated with age both in patients and in controls. A linear correlation was found between IGF-1 and IGFBP-3 which was positive for controls (r=0.946, p < 0.001) and patient group A and B (r=0.839, p = 0.005) but tended to be negative for patient group C (r=0.65, n.s.).
: Our data demonstrate that long-term replacement therapy in children with hypothyroidism is associated with a physiological increase in IGF-1 and IGFBP-3. The positive correlation between IGF-1 and IGFBP-3 levels in group A and B confirm the efficacy of long-term replacement treatment on the IGF-1/BP-3 axis in pre- and post-pubertal patients treated for CH. However, this correlation tended to be negative in patients with hypothyroidism secondary to thyroiditis, suggesting that the cause of thyroid insufficiency and/or the age at the beginning of replacement therapy may have a role in the post-pubertal hormonal status in IGF-1 and IGFBP-3 balance.
甲状腺激素参与生长激素/胰岛素样生长因子（GH/IGF）轴的调节。甲状腺功能减退与GH脉冲性降低以及对刺激试验的GH反应降低有关。在甲状腺功能减退症中，血清IGF-I和IGFBP-3水平下降，而在短期补充L-T4后这些变化可恢复。本研究旨在确定长期用T4替代治疗对IGF-1和IGFBP-3血清水平的影响。
该研究纳入了12例接受T4替代治疗的甲状腺功能减退症患者。根据治疗开始时的年龄将他们分为3组。A组由4例青春期前先天性甲状腺功能减退症（CH）患者组成，通过新生儿筛查确诊，在出生后15天内开始T4治疗。B组由5例年轻人组成，CH在6个月龄时临床诊断，并于该年龄开始替代治疗。C组由3例继发于甲状腺炎的甲状腺功能减退症患者组成，诊断和替代治疗分别延迟至11岁、12岁和14岁。所有受试者均与年龄、性别、体重和青春期阶段相同的对照组匹配。
患者和对照组的FT3、FT4和TSH均在正常范围内。未发现FT3或FT4与IGF-1或IGFBP-3血清水平之间存在相关性。A组的IGF-1血清水平（198±122 ng/ml）显著低于B组（624±105，p<0.001）和C组（649±98，p=0.003）。A组的IGFBP-3血清水平（1.98±0.56μg/ml）显著低于B组（3.65±1.10，p=0.03）和C组（4.13±0.49，p=0.003）。与A组对照组相比，B组和C组对照组的IGF-1和IGFBP-3水平也有所升高。患者和对照组中，IGF-1和IGFBP-3均与年龄呈正相关。发现IGF-1和IGFBP-3之间存在线性相关性，对照组（r=0.946，p<0.001）以及患者A组和B组（r=0.839，p = 0.005）呈正相关，但患者C组呈负相关趋势（r=0.65，无统计学意义）。
我们的数据表明，甲状腺功能减退症患儿的长期替代治疗与IGF-1和IGFBP-3的生理性增加有关。A组和B组中IGF-1和IGFBP-3水平之间的正相关证实了长期替代治疗对CH治疗的青春期前和青春期后患者IGF-1/BP-3轴的疗效。然而，继发于甲状腺炎的甲状腺功能减退症患者中这种相关性呈负相关趋势，提示甲状腺功能不全的原因和/或替代治疗开始时的年龄可能对青春期后IGF-1和IGFBP-3平衡的激素状态有影响。
