Resistance to Somatostatin Analogs in Acromegaly

Abstract

Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA.

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

“…In isolated cases the shrinkage effect can be spectacular (Espinosa de los Monteros et al 2014). Tumor decrease is more frequent and significant in primary-treated patients and in large macroadenomas (Mazziotti & Giustina 2010, Colao et al 2011.…”

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy)

“…Treatment throughout the study was as follows: primary radiotherapy nZ20 patients, of whom seven were additionally treated with DAs; primary DAs, nZ12 patients; one surgical intervention, nZ126 patients; one surgeryCradiotherapy, nZ7 patients, one surgeryCDAs, nZ68 patients; one surgeryCradiotherapyCDAs, nZ21 patients; two or more surgical interventions, nZ16 patients; two or more surgeriesCradiotherapy, nZ11 patients; two surgeriesC DAs, nZ32 patients; and two or more surgeriesC radiotherapyCDAs, nZ49 patients. In Italy, a number of recent papers have described the treatment protocols (10,11,12,13). During the study, 190 of the Bulgarian and 27 of the Italian patients were lost to follow-up and all of them had data relating to life/death status obtained from the civil registration and administrative services of both countries.…”

“…Treatment options currently available include surgery, medical therapy such as dopamine agonists (DAs), somatostatin analogs (SSAs), and GH receptor antagonists (GHRAs), and irradiation (8). While surgery and irradiation are used worldwide, modern medical therapies (i.e.…”

Ocena efektów leczenia analogami somatostatyny nieczynnych hormonalnie gruczolaków przysadki w porównaniu z akromegalią

“…Criteria for disease control are defined as an age-normalised serum IGF-1 value and a random GH level < 1.0 ng/mL in oral glucose tolerance test [13]. Full response to somatostatin analogues is also understood as a ≥ 20% decrease in tumour volume in primary as well as in secondary therapy or at least stabilisation of tumour remnant in the case of second-line treatment [14]. Some authors suggest the importance of somatotropinomas pretreatment with somatostatin analogues prior to planned neurosurgery, which can be beneficial, especially in the aspect of tumour debulking [15].…”