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The Ecuadorian Laron and Brazilian Itabaianinha cohorts with congenital mutations in the GH and GHRH receptors, respectively, both provide a unique and arguably the purest examples to evaluate the effects of chronic severe IGF-I and both severe GH and IGF-I deficiency, respectively, with severe hypoinsulinemia being the common denominator in both cohorts (151, 152) ( Table 1

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In elderly patients, where individual variability is pronounced and comorbidities are frequent, careful evaluation of the risk–benefit balance of pharmacological interventions is particularly critical

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