Pathology of the neuroendocrine system.

Abstract

Systematic use of immunocytochemistry and radioimmunoassay resulted in an enormous increase in the knowledge of the localization and secretion of peptides and amines. It is now known that many peptides and amines are present in the brain, in peripheral nerves, and in endocrine cells. The original APUD concept (8) had to be extended to include neural elements. At present it is realized that many activities of the body are regulated by this control system (currently called the neuroendocrine system). It’s messengers may act as neurotransmitters, as hormones, or as locally acting substances, the so-called paracrine substances. According to the type of secretion the neuroendocrine system may be considered to contain neurocrine (peptidergic neuron acting upon another neuron), neuroendocrine (neuron secreting its product(s) into the bloodstream), endocrine and paracrine cells. At present we are still at the very beginning of the unraveling of mechanisms resulting in disease of the neuroendocrine system. However, it is safe to predict that pathology of the system will be found to be complicated, and it is already now impossible to cover the subject in one workshop. Therefore, we selected 3 topics which may be of interest to biologists, physiologists, clinicians and pathologists, namely: “pathology of the pituitary;” “the concept and pathology of the disseminated (peripheral) neuroendocrine system;” and “pathology of the endocrine pancreas.” In these fields remarkable progress has been achieved in the understanding of pathophysiology and in accuracy of diagnosis. Immunocytochemistry and radioimmunoassay have significantly contributed to this progress and probably will change concepts of diseases of the neuroendocrine system. Part of this knowledge derived from retrospective analysis of routinely fixed operative samples and autopsy material. Recently, views of the biological behavior of pituitary tumors have dramatically changed. It is now obvious that the histologic classification based on granule staining properties is inadequate because the secretory potentialities of the tumors are far more extensive than is implied by this classification. Using immunocytochemistry it has been shown that so-called chromophobe adenomas often contain hormones (6) and that many pituitary tumors are multihormonal (4). Moreover, functional analysis by radioimmunoassay revealed that tumors often secrete more than one hormone. Hormonal secretion by pituitary tumors and tumor growth may also be stimulated or inhibited by drugs and functional tests and therefore can no longer be considered entirely autonomous (7). Together with the rapidly accumulating knowledge of hypothalamic regulation of pituitary hormone synthesis and secretion, such findings have led to a challenge of the concept of neoplasia (defined as “focal autonomous growth of tissue”). Pituitary “nodules” often behave as a focal hyperplasia (defined as “increase in the number ofcells”). The differentiation ofa tumor from hyperplasia is not merely of academic interest, it is of great importance to the neurosurgeon in prescribing treatment of the patient. The control device of the gastrointestinal tract is part of the disseminated neuroendocrine system. The gastroenteropancreatic peptides are localized in single cells and/or in neuronal cell bodies and their axons. The widespread distribution of these peptides produces an integrated response to diffuse and discontinuous stimuli involved in the intake of food, its transport along the gastrointestinal tract, its digestion and resorption and in the flow of metabolic fuel ( 1). The triple control device of the neuroendocrine system, endocrine, paracrine and neural control (9), can be especially well demonstrated in the gastrointestinal tract. The endocrine pancreas is part of the system of gastroenteropancreatic endocrine cells. The knowledge of its structure and physiology