Nadia Sawicka-Gutaj

Acromegaly is a chronic disease caused by the hypersecretion of growth hormone (GH), leading to changes in the growth of visceral tissues and glucose impairment. Serum biomarkers that correlate with disease status are still unclear. This study aims to assess the potential of phosphorus and calcium as biomarkers in the clinical evaluation of patients with acromegaly and clarify their relationship with SAGIT and other common biomarkers. We retrospectively analyzed data from 306 medical records of patients with acromegaly hospitalized between 2015 and 2020. Factors such as patient biometrics, duration of disease, SAGIT score, tumor size, GH, insulin-like growth factor 1 (IGF-1), calcium, phosphorus, parathormone, and vitamin D were analyzed concerning current disease status (naïve, non-remission, remission). The results showed that serum phosphorus significantly correlated with IGF-1 and SAGIT scores for patients with active acromegaly. Specifically, the best predictor for the remission of acromegaly was a phosphorus level < 3.98 mg/dL and serum calcium levels < 9.88 mg/dL. Based on logistic regression, the higher the serum phosphorus level, the lower the odds of achieving remission (an increase in one unit leads to a decrease in the chance of about 80%). In conclusion, phosphorus and calcium can be effective biochemical markers for predicting disease status in acromegaly.

Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012–2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.