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 fa ctors in regulating the local actions of IGFs. Both an inhibitory and a sti mulatory effect for different IGFBPs have been shown in several cell system s. The aim of this study was to assess the involvement of IGFBPs in the goi trogenic process in patients with goiter recurrence. Methods. The IGFBP-I and -3 content in normal and nodular tissues obtained at the time of thyroidectomy from 10 patients with recurrent goiters, unres ponsive to thyroid-stimulating hormone suppressive therapy, was studied. In all patients, a fragment of normal tissue was also obtained. The IGF-I, IG FBP-I, and -3 content was evaluated by specific immunoassays and/or immunob lotting with anti-IGFBP specific antiserum. Results. The IGF-I content was significantly higher (P < .05) in nodular ti ssues (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 w as 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-I appeared higher in all but I nodular tissue. Conclusions. These data raise the possibility that IGFBPs are important in the proliferative activities entailed in the goitrogenic process. Three mec hanisms are potentially involved: (I) reduction of the potency of locally p roduced IGF peptide to downregulate type I receptors (potentiating effect o n the autocrine/paracrine mitogenic action of IGFs); (2) increase of the IG F-I tissue concentration restraining its passage to circulation; and (3) pr otection of IGF-I from degradation. Further studies are needed to define a mom precise link between these factors and the recurrence of goiter.