MON-317 Prognostic Factors and Mortality According to the Structural and Functional Classification of Acromegaly
Authors: Haro Andrea Rocha , Alonso Juan P Godoy , de la Cruz Germán González , Aguirre Marlon V Vázquez , Cardenas Romina Flores , Gómez-Sámano Miguel A , Domínguez Armando Gamboa , Higuera Calleja Jesús A , Gómez-Pérez Francisco J , Cuevas-Ramos Daniel 
Published: May 2020

Background: acromegaly is a systemic disorder caused by overproduction of growth hormone (GH) where most common cause is a pituitary somatotroph adenoma. Different prognostic factors have been previously reported, such as adenoma granulation, and p21 and somatostatin receptor type 2 (SSTR2) immunohistochemistry expression. Considering these factors, three different acromegaly subtypes were proposed. Type 1 tumors are dense granulated microadenomas with higher expression of p21 and SSTR2, with better prognosis. In contrast, type 3 are sparsely granulated, highly invasive macroadenomas, with less expression of SSTR2 and p21, and worst prognosis with less responsiveness to treatment. Type 2 adenomas showed intermediate prognosis. Objective: to determine independent prognostic factors according to somatotroph adenoma subtypes in patients with acromegaly.

Material and methods: this is a comparative, observational, longitudinal study. We classified patients according to p21, SSTR and tumor granulation as previously reported. Then, bivariate and multivariate using binary logistic and Cox-regression analyses were performed. Results: 222 patients (52% women and 48% men, mean age 40+-13 years old) with confirmed diagnosis of acromegaly were classified in the three acromegaly types. Mean age at diagnosis was significantly different among groups, with 45, 41 and 38 years old, in types 1 to 3, respectively (p 0.010). All patients with type 1 (n=47) showed microadenomas, and type 2 (n=72) and 3 (n=103) macroadenomas (p &lt;0.001). Invasiveness was present in 11% in type 1, 0% in type 2, and 100% in type 3 (p &lt;0.001). GH and the upper limit number IGF-1 index was significantly higher in in type 3 vs. type 1 (p &lt;0.001). Hypertension (43% vs. 34% vs. 23%), cardiovascular/cerebrovascular disease (44% vs. 28% vs. 28%), diabetes (47% vs. 29% vs. 24%), hypertriglyceridemia (54% vs. 24% vs. 22%), and high LDL-c (43% vs. 30% vs. 27%) were significantly higher in type 3 vs. type 2 vs type 1 acromegaly patients, respectively (all p&lt;0.05). Using multivariate Cox regression analysis (adjusted for neurosurgery and radiotherapy) we identified that type 3 acromegaly showed worst prognosis with higher probability of remaining active (2LogR=652.6, chi square=17.7, p=0.001), and higher mortality (2LogR=489, chi square=43, p&lt;0.001) than type 2 vs. type 1 acromegaly patients at last follow-up. Independent parameters related with disease activity were acromegaly types 2 and 3 (OR=2.7; IC95% 1.9-6.7, p=0.005), and radiotherapy (OR=0.36, 0.18-0.70, p=0.003). Conclusions: Type 3 acromegaly patients showed higher frequency of comorbidities, disease activity, and risk of mortality, adjusted for treatment, than type 2 and type 1 patients.

References

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Cuevas-Ramos, D., Carmichael, J. D., Melmed, S. (2015). A Structural and Functional Acromegaly Classification. JCEM, 100(1), 122–131.doi:10.1210/jc.2014-2468