TY - JOUR

T1 - Towards a Göttingen minipig model of adult onset growth hormone deficiency

T2 - evaluation of stereotactic electrocoagulation method

AU - Ørstrup, Laura Hvidsten

AU - Tvilling, Laura

AU - Orlowski, Dariusz

AU - Zaer, Hamed

AU - Bjarkam, Carsten Reidies

AU - von Voss, Pia

AU - Andersen, Pia Skårup

AU - Christoffersen, Berit

AU - Hedemann Sørensen, Jens Christian

AU - Laursen, Torben

AU - Thygesen, Peter

AU - Lykkesfeldt, Jens

AU - Glud, Andreas Nørgaard

PY - 2019

Y1 - 2019

N2 - Background: 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. New method: 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. Results: 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. Comparison with existing methods: 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. Conclusion: 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

AB - Background: 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. New method: 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. Results: 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. Comparison with existing methods: 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. Conclusion: 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

KW - Endocrinology

KW - Growth hormone deficiency

KW - Göttingen minipig

KW - Hypophysectomy

KW - Large animal modelling

KW - Metabolic disorder

KW - Metabolism

KW - Neuroscience

KW - Neurosurgery

KW - Physiology

KW - Stereotaxic surgery

KW - Surgery

KW - Sus scrofa

U2 - 10.1016/j.heliyon.2019.e02892

DO - 10.1016/j.heliyon.2019.e02892

M3 - Journal article

C2 - 31844758

AN - SCOPUS:85075569962

VL - 5

JO - Heliyon

JF - Heliyon

SN - 2405-8440

IS - 11

M1 - e02892

ER -