Endocrinological differentiation of primary hypothalamic and pituitary disease

The paper reviews approaches that can be applied to separating the endocrinological central nervous system (CNS) from pituitary components of neuroendocrine disorders. Major reasons which hamper the differentiation of primary hypothalamic from pituitary diseases are considered. Finally, future strategies suitable for a better accomplishment of this task are mentioned. Theoretically, the combined application of CNS-active compounds and hypothalamic regulatory hormones (RHs) should unravel the hypothalamic or pituitary etiology of the disorder. Until now, the most useful diagnostic application of RHs deals with their use in disease states due to isolated or multiple RH deficiency. Thus, the recent isolation of GRF molecules from human pancreatic tumors holds promise of a better functional characterization of GH deficiency states. The differentiation of the hypothalamic or pituitary origin of the disease in states of pituitary hyperfunction, e.g., acromegaly, or prolactinomas, is influenced by factors such as the development or expression of aberrant pituitary receptors for neurotransmitters and neuropeptides, the persistence of the responsiveness of tumorous pituitary cells to the respective RH, the disrupting effect of the excessively produced pituitary or target gland hormone on hypothalamic function. Future strategies of research in this area may include: 1. the development of sensitive and specific assays for RHs, e.g., GRF, CRF, etc. and RH determinations in biological fluids; 2. the search for non-hypophysiotropic peptides in the cerebrospinal fluid and their evaluation after appropriate stimulation; 3. better functional and clinical characterization of ectopic hormone-producing syndromes, or of psychiatric disorders mimicking neuroendocrine abnormalities from an endocrinological viewpoint (e.g., primary affective disorders v. Cushing's disease; 4. use of neuroactive compounds probing selective aspects of neurotransmitter function and, finally, 5. long-term follow-up studies after adenomectomy.