Treatment of acromegaly in the era of personalized and predictive medicine

Abstract

Summary Acromegaly is a chronic disorder usually diagnosed late in the disease evolution. Such delayed diagnosis, together with the inability to achieve the treatment goals of normalizing biochemical disease markers and controlling tumour mass may result in substantial morbidity and mortality. Somatostatin analogues (SSA) are accepted as first‐line medical therapy or as second‐line therapy in patients undergoing unsuccessful surgery and are considered a cornerstone in the treatment of acromegaly. However, because a high percentage of patients experience SSA medical treatment failure, the identification of biomarkers associated with a successful or unsuccessful response to all classes of medical therapy would help in the choice of treatment and potentially allow for a quicker normalization of biochemical parameters. The current treatment algorithms for acromegaly are based upon a “trial‐and‐error” approach with additional treatment options provided when disease is not controlled. In many other diseases, therapeutic algorithms have been evolving towards personalized treatment with the medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response. Additionally, a personalized approach to complementary treatment of comorbidities present in the acromegalic patient is also required. This review will discuss the development of a potential treatment algorithm for acromegaly addressing the biochemical control of the disease as well of its associated comorbidities, under a personalized approach based upon markers of prognostic and predictive significance, such as tumour size, MRI adenoma signal, GH value after acute octreotide test, granular adenoma pattern, Ki‐67, somatostatin receptor phenotype, aryl hydrocarbon‐interacting protein expression, gsp mutations, RAF kinase activity, E‐cadherin and beta‐arrestin‐1.

Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

“…In addition, both GH and IGF-1 levels and TVs were assessed in a centralized laboratory to reduce measurement variability. The information yielded may assist in the clinical management of treatment and the potential future personalization of therapeutic decisions, likely in combination with other predictive factors [40].…”

Pegvisomant in acromegaly: an update

“…Some clinical and pathological aspects have been proposed to be effective in predicting the response to SRL. In particular, a better response seems to be associated to female sex, older age, hypo-intensity in T2 at MRI, high SST2R expression, high AIP expression at immunohistochemistry, low Ki67 index, a “densely granulated” pattern at electronic microscopy [125, 126]. A partial to absent response to SRL is also related to particular genetic alterations as observed in patients bearing AIP gene mutations or the newly discovered X-linked acrogigantism [127].…”

Progress in the Diagnosis and Classification of Pituitary Adenomas

“…In the subgroups of patients discussed here, some specific characteristics may predict their clinical behavior and their response to treatment. New techniques may help us to reach a more accurate classification and personalized and precise treatment options for patients harboring pituitary adenomas (53). …”