Towards a Göttingen minipig model of adult onset growth hormone deficiency: evaluation of stereotactic electrocoagulation method

Adult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development. In this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia. Lesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery. Compared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates. The lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs. Neuroscience; Endocrinology; Metabolic disorder; Metabolism; Neurosurgery; Physiology; Surgery; Göttingen minipig; Growth hormone deficiency; Hypophysectomy; Large animal modelling; Stereotaxic surgery; Sus scrofa