Pancreatic Neuroendocrine Tumors Producing GHRH, GH, Ghrelin, PTH, or PTHrP

Neuroendocrine tumors that produce growth hormone-releasing hormone (GHRH), growth hormone (GH), ghrelin, parathyroid hormone-related peptide (PTHrP), or parathyroid hormone (PTH) are rare but fascinating given their inherent ability to secrete biologically active substances, leading to distinct clinical syndromes. These include ectopic acromegaly, a putative ghrelin syndrome, and humoral hypercalcemia of malignancy. Recognition of these paraneoplastic syndromes is critical for early detection. When the diagnosis is delayed, they typically present with metastatic disease and are associated with poor patient outcome. Accurate subtyping is crucial for treatment decision making and requires a thorough integration of pathological features with clinical, biochemical, and imaging findings. Recently, some of the largest series of functioning GHRH- and PTHrP-producing tumors have been reported in the literature, providing crucial insight into the diagnostic and prognostic features of these exceptionally rare neoplasms. This chapter provides an update on the current knowledge of these functioning neuroendocrine tumors which commonly arise in the pancreas, but also in extrapancreatic sites.