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Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador

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Abstract

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80’s. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world’s largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.

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Authors and Affiliations

  1. Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

    Jaime Guevara-Aguirre, Camila Bautista, Carlos Torres, Gabriela Peña, Carolina Guevara & Cristina Palacios

  2. Instituto de Endocrinología IEMYR, Quito, Ecuador

    Jaime Guevara-Aguirre, Carolina Guevara & Alexandra Guevara

  3. Maastricht University, Maastricht, The Netherlands

    Jaime Guevara-Aguirre & Antonio W. D. Gavilanes

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  1. Jaime Guevara-Aguirre
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  3. Carlos Torres
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  5. Carolina Guevara
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  8. Antonio W. D. Gavilanes
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Contributions

Camila Bautista: Wrote some draft paragraphs, provided various references;

Carlos Torres: Wrote some draft paragraphs, provided various references;

Gabriela Peña: Wrote some draft paragraphs, provided various references;

Carolina Guevara: Checked concordance of references from previous work;

Cristina Palacios: Wrote some draft paragraphs, provided various references;

Alexandra Guevara: Edited all draft versions; checked concordance with references from previous work, edited final manuscript.

Antonio WD Gavilanes: Commented at various stages, edited final manuscript.

Jaime Guevara-Aguirre: Wrote the manuscript, coordinated the authors.

Corresponding author

Correspondence to Jaime Guevara-Aguirre.

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Guevara-Aguirre, J., Bautista, C., Torres, C. et al. Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador. Rev Endocr Metab Disord 22, 59–70 (2021). https://doi.org/10.1007/s11154-020-09602-4

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