Context: Somatostatin analogs (SSAs) effectively control growth hormone secretion in first- and second-line treatment of acromegaly. Their effect on glucose metabolism is still debated. Objective: To address the following questions: (1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin, glycosylated hemoglobin (HbA1c), glucose load (glucose levels after 2-hour oral glucose tolerance test), homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of pancreatic β-cell function (HOMA-β), triglycerides, weight, or body mass index? (2) Do lanreotide and octreotide affect metabolism differently? (3) Does their effect depend on disease control? Design: We performed a meta-analysis of prospective interventional trials treating acromegaly with SSAs. Inclusion criteria: all studies reporting glycometabolic outcomes before and after SSAs with a minimum 6-month follow-up. Results: The inclusion criteria were met by 47 studies treating 1297 subjects (631 females). SSA treatment effectively lowered fasting plasma insulin [effect size (ES), −6.67 mU/L; 95% confidence interval (CI), −8.38 to −4.95 mU/L; P < 0.001], HOMA-I (ES, −1.57; CI, −2.42 to −0.72; P < 0.001), HOMA-β (ES, −47.45; CI, −73.15 to −21.76; P < 0.001), and triglycerides (ES, −0.37 mmol/L; CI, −0.47 to −0.27 mmol/L; P < 0.001). SSAs worsened glucose levels after a 2-hour oral glucose tolerance test (ES, 0.59 mmol/L; CI, 0.05 to 1.13 mmol/L; P = 0.032), but not FPG. A mild but significant increase in HbA1c (ES, 0.12%; CI, 0.00% to 0.25%; P = 0.044) was found in subjects treated with octreotide. Conclusions: SSA treatment in acromegaly patients, while improving disease control, reduces insulin levels, increases after-load glucose, and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting postprandial glucose.

The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. Is NETest able to differentiate stable from progressive disease? Increased NETest levels (at least >40%) correlate with disease progression. Is NETest able to predict tumor progression and tumor response to treatment? Some studies demonstrated that the baseline NETest score >33–40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment response also before radiological findings, since the decrease or stability of NETest score predicts tumor response to treatment. Is NETest able to evaluate tumor recurrence risk after surgery? NETest can predict surgical treatment outcome detecting minimal residual disease after radical surgery, which is characterized by a lower but positive NETest score (20–40%), while a higher score (>33–40%) is associated with nonradical surgery. In conclusion, in addition to its demonstrated diagnostic role, this systematic review highlights the efficacy of NETest to assess disease status at the moment of the NETest execution and to predict tumor recurrence after surgery. The efficacy for other applications should be proven by additional studies.

An increased calcitonin serum level is suggestive of a medullary thyroid cancer (MTC), but is not pathognomonic. The possibility of false positives or other calcitonin-secreting neuroendocrine neoplasms (NENs) should be considered. Serum calcitonin levels are generally assessed by immunoradiometric and chemiluminescent assays with high sensitivity and specificity; however, slightly moderately elevated levels could be attributable to various confounding factors. Calcitonin values >100 pg/mL are strongly suspicious of malignancy, whereas in patients with moderately elevated values (10–100 pg/mL) a stimulation test may be applied to improve diagnostic accuracy. Although the standard protocol and the best gender-specific cut-offs for calcium-stimulated calcitonin are still controversial, the fold of the calcitonin increase after stimulation seems to be more reliable. Patients with MTC show stimulated calcitonin values at least three to four times higher than the basal values, whereas calcitonin-secreting NENs can be distinguished from a C-cell disease by the absence of or <two-fold response to stimulation. The measurement of calcitonin in fine-needle aspirate washout (FNA-CT) and calcitonin immunocytochemical staining from thyroid nodules are ancillary methods that may significantly improve MTC diagnosis. The present review examines the gray areas in the interpretation of calcitonin measurement in order to provide a tool to clarify the origin of calcitonin secretion and differentiate the behavior of the two-faced Janus of neuroendocrinology: intra-thyroid (MTC) and extra-th9yroid NENs.