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Somatostatin receptor ligands in the treatment of acromegaly

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Abstract

First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36–75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.

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Fig. 1

Adapted from ref. 16–20,35

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Authors and Affiliations

  1. Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil

    Monica R. Gadelha & Luiz Eduardo Wildemberg

  2. Neuroendocrinology Section and Molecular Genetics Laboratory, Secretaria Estadual de Saúde do Rio de Janeiro, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Monica R. Gadelha & Luiz Eduardo Wildemberg

  3. Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, São Paulo, Brazil

    Marcello D. Bronstein

  4. Endocrinology Unit, Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    Federico Gatto & Diego Ferone

  5. IRCCS AOU San Martino-IST Genoa, Genoa, Italy

    Diego Ferone

Authors
  1. Monica R. Gadelha
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  2. Luiz Eduardo Wildemberg
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  3. Marcello D. Bronstein
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  4. Federico Gatto
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  5. Diego Ferone
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Corresponding author

Correspondence to Monica R. Gadelha.

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Conflict of interest

MRG has received unrestricted research grants and lecture fees from Novartis, Ipsen and Pfizer, has participated on advisory boards of Novartis and Ionis and is PI in clinical trials by Novartis and Ipsen. LEW has no conflicts of interest to declare. MDB is speaker for Ipsen and Novartis; member of Steering Committees of Chiasma, Ipsen and Novartis; PI of clinical trials of Ipsen, Novartis and Pfizer. FG is speaker for Novartis and participated on advisory boards of Novartis, AMCo Ltd. and IONIS Pharmaceuticals. DF is speaker, participated on advisory boards and received research grants from Novartis and Ipsen.

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This article does not contain any studies with human participants performed by any of the authors as it is a review.

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Gadelha, M.R., Wildemberg, L.E., Bronstein, M.D. et al. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary 20, 100–108 (2017). https://doi.org/10.1007/s11102-017-0791-0

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  • DOI: https://doi.org/10.1007/s11102-017-0791-0

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