Effect of insulin-like growth factor I on the thyroid axis in patients with Laron-type dwarfism and healthy subjects

Abstract

Z. Effect of insulin-like growth factor I on the thyroid axis in patients withLaron-typedwarfism and healthy subjects.We have evaluated the effect of exogenous administration of IGF-I on the thyroid axis in four separate studies: (1) iv bolus injection; (2) single sc injection; (3) seven days' sc treatment, and (4) four months' treatment. Thirteen patients with Laron-type dwarfism (LTD) participated in the investigations. In studies 1 and 2,10 healthy subjects were also included. Before and during long-term treatment (study 4) six LTD patients underwent a TRH test. IGF-I was administered in a dose of 75 \ g=m\ g\ m=. \ kg\ m=-\ 1 iv or 120\p=n-\ 150 \ g=m\ g\ m= . \ kg\m=-\ 1 sc. Single injections of IGF-I caused significant decreases of serum TSH in LTD patients (iv: 1.7\m=+-\0.2 to 1 . 1 \ m = + -\ 0 . 1 mU/l; sc: from 2.1\m=+-\0.4to 1.1 \m=+-\0.2;p<0.0005). In controls the decrease was for iv from 1.2\m=+-\0.2to 0.8\m=+-\0.2mU/l (p<0.02) and for sc from 2.0\m=+-\0.5to 0.8\m=+-\0.2mU/l (p<0.05). Long-term administration of IGF-I induces a transitory decrease of both serum TSH and fT4, followed by a spontaneous rise to pretreatment or even higher values. No changes in T3 were observed. TSH stimulation by TRH was significantly augmented after four months of IGF-I treatment (p<0.005). The effects of IGF-I can be explained by an early stimulation of somatostatin release causing a decrease in TSH and followed by the development of compensatory mechanisms. All changes were within the normal ranges, not causing abnormal thyroid function. As the clinical use of recombinant IGF-I extends for longer periods than those described, it is recommended that thyroid function is followed. Z Laron, Recent reports have documented that exogenously administered growth hormone (GH) affects thyroid function in both normal individuals ( 1 ) and GH deficient adults (2), as well as in children with either GH deficiency (3) or hypothyroidism (4). All the reports describe suppression of the thyroid function during GH administration, but the expression of the results varied.Thus, some reported a lowering of serum T4 and an increase of serum T3 (2-4), decrease in 151I thyroidal uptake (5), or decrease in serum TSH (6). The avail¬ ability of recombinant IGF-I, the effector hormone of hGH and its introduction into clinical use made it possible to test whether the GH effect on the thyroid function is a direct one or is mediated by IGF-I.We report the effect on thyroid function of a single intravenous or subcutaneous injection of IGF-I and short and long-treatment of IGF-I in Laron-type dwarfism (LTD) patients. Subjects and methodsThe effect of rIGF-I on the thyroid function was investi¬ gated during four separate studies. Study 1 comprised 10 patinets with LTD (5M, 5F) aged 8 to 35 years and a control group of 8 healthy subjects (5M, 3F)aged8 to 39 years. Thyroid function was studied before and after an iv bolus of rIGF-I (75 jUg.kg-1). The study was performed after an overnight fast and blood samples for TSH determinations were drawn at 0, 2, ...

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

“…Our current data indicate that this might also reflect an increase in T4-to-T3 conversion during the rhIGF-I infusion. In contrast to our results, Klinger et al (44) found no increase in T3 during rhIGF-I treatment, despite TSH suppression similar to what we observed. Of interest, an increase in T3 has also been found during GH treatment (45).…”

Insulin-like growth factor I reduces thyroid hormone receptors in the rat liver. Evidence for a feed-back loop regulating the peripheral thyroid hormone action

“…The doses of rhIGF-I that we used in this study were substantially greater than the sustitutive doses used in growth disorders in children (Klinger et al 1992). However, serum IGF-I concentration in adult normal rats is about eightfold greater than that in human beings (Yamamoto et al 1991, Nanto-Salonen et al 1993.…”

“…The reduction in FT 4 concentrations with a concomitant increase in TT 3 induced by IGF-I treatment, suggests an enhanced conversion of T 4 to T 3 . However, short-term administration of IGF-I to normal adults and Laron-type dwarfs resulted in a reduction in FT 4 but failed to augment TT 3 concentrations (Klinger et al 1992). Nevertheless, the changes in serum thyroid hormone concentrations induced by IGF-I Table 2.…”

“…The impact of administration of GH to normal and GH-deficient patients on thyroid function has yielded conflicting results. Diverse reports have described a decrease in thyroid uptake of iodine-125, serum thyrotrophin (TSH) and serum thyroxine (T 4 ) and an increase in serum T 3 after administration of GH (Grunfeld et al 1988, Jorgensen et al 1989, whereas IGF-I administered to Laron-type dwarfs and healthy individuals induces a decrease in TSH and free T 4 , with no change in the T 3 serum concentration (Klinger et al 1992).…”

Impacto do tratamento com GH sobre as funções tireoidiana e adrenal

“…Em pacientes com DGH, apesar de o tratamento com IGF-1 ser capaz de induzir o aumento dos níveis de T 3 séricos, efeito mais pronunciado é observado após a reposição de GH (42), sugerindo que este induz a tais mudanças além do mecanismo via IGF-1. Em um outro estudo nenhum efeito nos níveis séricos de T 3 foi observado após a administração de IGF-1 em pacientes com insensibilidade ao GH em razão de mutações no receptor de GH (69). Em conjunto, esses resultados sugerem que os efeitos da reposição de GH nos níveis circulantes de HT parecem ser mediados predominantemente pelo efeito direto do GH.…”