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Research article - Peer-reviewed, 2019

Development of a Parallel Reaction Monitoring-MS Method To Quantify IGF Proteins in Dogs and a Case of Nonislet Cell Tumor Hypoglycemia

Valdes, Alberto; Lewitt, Moira; Wiss, Erica; Ramstrom, Margareta; Strage, Emma M.


Nonislet-cell tumor hypoglycemia (NICTH) is a rare paraneoplastic phenomenon well described in dogs and humans. Tumors associated with NICTH secrete incompletely processed forms of insulin-like growth factor-II (IGF-II), commonly named big IGF-II. These forms have increased bioavailability and interact with the insulin and IGF-I receptor causing hypoglycemia and growth-promoting effects. Immunoassays designed for human samples have been used to measure canine IGF-I and -II, but they possess some limitations. In addition, there are no validated methods for measurement of big IGF-II in dogs. In the present study, a targeted parallel reaction monitoring MS-based method previously developed for cats has been optimized and applied to simultaneously quantify the serum levels of IGF-I, IGF-II, and IGFBP-3, and for the first time, the levels of big IGF-II in dogs. This method allows the absolute quantification of IGF proteins using a mixture of QPrEST proteins previously designed for humans. The method possesses good linearity and repeatability and has been used to evaluate the IGF-system in a dog with NICTH syndrome. In this dog, the levels of big IGF-II decreased by 80% and the levels of IGF-I and IGFBP-3 increased approximately 20- and 4-times, respectively, after removal of the tumor.


big IGF-II; dog NICTH; IGF system; PRM; targeted proteomics

Published in

Journal of Proteome Research
2019, volume: 18, number: 1, pages: 18-29

Authors' information

Valdes, Alberto
Uppsala University
Lewitt, Moira
University of West Scotland
Wiss, Erica
Albano Anim Hosp
Ramstrom, Margareta
Uppsala University
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Swedish University of Agricultural Sciences, University Animal Hospital

UKÄ Subject classification

Clinical Science

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