Goiter recurrence in patients submitted to thyroid-stimulating hormone suppression: Possible role of insulin-like growth factors and insulin-like growth factor-binding proteins

Background. It is known that factors other than thyroid-stimulating hormone, such as insulin-like growth factor-I (IGF-I) and epidermal growth factor, have a goitrogenic effect. It has been established that insulin-like growth factor-binding proteins (IGFBPs) may play a role as autocrine/paracrine factors in regulating the local actions of IGFs. Both an inhibitory and a stimulatory effect for different IGFBPs have been shown in several cell systems. The aim of this study was to assess the involvement of IGFBPs in the goitrogenic process in patients with goiter recurrence. Methods. The IGFBP-1 and -3 content in normal and nodular tissues obtained at the time of thyroidectomy from 10 patients with recurrent goiters, unresponsive to thyroid-stimulating hormone suppressive therapy, was studied. In all patients, a fragment of normal tissue was also obtained. The IGF-I, IGFBP-1, and -3 content was evaluated by specific immunoassays and/or immunoblotting with anti-IGFBP specific antiserum. Results. The IGF-I content was significantly higher (P < .05) in nodular tissues (8.0 ± 1.6 ng/g of tissue) than what was found in normal tissue (4.8 ± 0.9 ng/g). Radioimmunoassay IGFBP-3 concentration in nodular tissue was 111.5 ± 18.2 ng/g significantly higher (P < .001) than values found in normal tissue (77.5 ± 18.6 ng/g). By immunoblot, IGFBP-1 appeared higher in all but 1 nodular tissue. Conclusions. These data raise the possibility that IGFBPs are important in the proliferative activities entailed in the goitrogenic process. Three mechanisms are potentially involved: (1) reduction of the potency of locally produced IGF peptide to downregulate type I receptors (potentiating effect on the autocrine/paracrine mitogenic action of IGFs); (2) increase of the IGF-I tissue concentration restraining its passage to circulation; and (3) protection of IGF-I from degradation. Further studies are needed to define a more precise link between these factors and the recurrence of goiter.