Giulia Maida¹, Alessandro Brunetti¹, Giacomo Cristofolini¹, Andrea Saladino² and Renato Cozzi^3
1Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
²Division of Neurosurgery (NCH 1), IRCCS Foundation Neurological Institute “Carlo Besta,” Milan, Italy
³SC Endocrinology Great Metropolitan Hospital Niguarda Milan, Milan, Italy

Part of the book: Advances in Health and Disease. Volume 62

Abstract

The first-generation somatostatin analogues (SSA) Octreotide and Lanreotide are renowned as a cornerstone for medical therapy in acromegaly. Both drugs act as receptor ligands of somatostatin, a neuro-hormone exerting a wide variety of effects on different tissues, including inhibition of GH secretion from normal and adenomatous pituitary somatotroph cells. Somatostatin interacts with different receptor subtypes (SSTR), classified from number 1 to 5. Octreotide and Lanreotide specifically show a high affinity for SSTR2, the prevalent receptor subtype expressed in GH-secreting pituitary adenoma, and to minor extent for SSTR5. Octreotide was first released in 1980’s and completely revolutioned medical therapy in acromegaly. Indeed, the only available treatment until then was limited to dopamine-agonists, only partially effective in a minority of patients with a burden of adverse events that limited their use in most of them. Octreotide has clearly shown a significant lowering effect of GH/IGF-1 levels in most patients, normalizing hormonal values in many of them, and tumour size shrinkage, improving both overall survival and quality of life of acromegalic patients. Therapy proved also a good profile of tolerability, with mostly minor adverse drug reactions (ADRs), such as mild and transient gastro-intestinal symptoms and colelithiasis, without any significant impairment in glucose metabolism. The first formulations of octreotide and lanreotide were limited by the need for frequent parenteral administration, but this inconvenience has been overcome by the development of longer acting formulations, octreotide long-acting release (LAR) and lanreotide autogel, that maintain their efficacy up to 28 days and longer in more sensitive patients. Several years after their release, study on first-generation SSAs is still ongoing; a new oral formulation of Octreotide has been approved in 2020 by FDA and EMA and predictors of response to therapy are of increasing interest in the current scientific scenario. The purpose of this review is to retrace the history of first-generation SRLs and to depict the changes in the therapeutic strategy in acromegaly, heading towards a more personalized therapeutic approach for the disease.

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